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: Thrombocytopenia has been closely associated with small-for-gestational-age neonates (SGA; birthweight less than tenth percentile) admitted to the special care nursery or neonatal ICU. It is unclear if 'well' SGA neonates experience the same incidence of thrombocytopenia in the SGA population as compared to sick neonates. We conducted a retrospective cohort study from a health network in Melbourne, Australia, between 2012 and 2015 to identify SGA neonates (? 35 weeks' gestation at birth) that were otherwise well. Neonates with at least one platelet count within 7 days of life were matched to appropriate-for-gestational-age (AGA) neonates from the same birth centre, with the same sex, and closest gestational age and birth date, who were also considered otherwise well. 16.7% of matched neonates had thrombocytopenia (303/1814) and of these, a larger proportion of SGA neonates were thrombocytopenic, 21.7% (197/907), than AGA neonates, 11.7% (106/907, P < 0.01). The incidence of thrombocytopenia was greater in the SGA cohort regardless of admission destination (special care nursery/neonatal ICU 26.8 vs. 13.9%, P < 0.01; Postnatal Ward 16.5 vs. 9.4%, P < 0.01). Thrombocytopenia is more prevalent amongst constitutionally well SGA neonates than AGA neonates. SGA alone increases the risk of thrombocytopenia. | [
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] |
: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the development of autoantibodies against clotting factor VIII. Although the cause of this disorder remains obscure, it is often linked to malignancies, drug administration, autoimmune diseases and pregnancy. In pregnancy-associated AHA, hemorrhagic symptoms usually present 1-4 months peripartum, however they may occur up to 1-year postpartum. Compartment syndrome of the forearm is also very uncommon complication of AHA but can have devastating consequences. We report a rare case of a compartment syndrome of the forearm in a 30-year-old woman 2.5 months postpartum as the presentation of pregnancy-associated AHA. | [
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BACKGROUND: Intravenous dexamethasone or dexmedetomidine is reported to prolong the duration of analgesia after single-shot interscalene brachial plexus block (ISBPB). However, the effect of co-administration of these agents on the duration of analgesia has not been evaluated.OBJECTIVES: We evaluated the difference in time to first rescue analgesic request between patients receiving co-administered intravenous dexamethasone and dexmedetomidine and patients receiving intravenous dexamethasone alone after single-shot ISBPB for arthroscopic shoulder surgery.DESIGN: A randomised controlled study.SETTING: A single tertiary care centre, study period from August 2017 to January 2018.PATIENTS: Sixty-six patients undergoing arthroscopic shoulder surgery with ISBPB with 15 ml of 0.5% ropivacaine with 1 : 200 000 epinephrine.INTERVENTIONS: We randomly assigned the patients to one of three groups: intravenous 0.9% saline (control), intravenous dexamethasone 0.11 mg kg (D1 group), or co-administered intravenous dexamethasone 0.11 mg kg and intravenous dexmedetomidine 1.0 g kg (D2 group).MAIN OUTCOME MEASURES: The primary outcome was the time to first rescue analgesic request.RESULTS: The median [interquartile range] time to first rescue analgesic request was significantly longer for the D2 group (66.3 h [23.3 to 72]) than the D1 (17.4 h [14.9 to 36], P = 0.002) and control (10.9 h [10.1 to 12.2], P < 0.001) groups. The D1 and D2 groups both had reduced pain scores, reduced postoperative opioid consumption, less sleep disruption and improved patient satisfaction compared with the control group. There were no significant elevations in blood glucose concentrations in patients receiving dexamethasone (D1 and D2 groups) compared with the control group at postoperative day 1.CONCLUSION: Co-administration of intravenous dexamethasone (0.11 mg kg) with dexmedetomidine (1.0 g kg) significantly prolonged the time to first rescue analgesic request after single-shot ISBPB in patients undergoing arthroscopic shoulder surgery.TRIAL REGISTRATION: Clinical Trial Registry of Korea; https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0002569. | [
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BACKGROUND: Postoperative nausea and vomiting (PONV) is an extremely distressing side effect for patients. Despite PONV prophylaxis guided by well established scoring systems, the incidence of PONV is still high.OBJECTIVE: The aim of the current study was to investigate the predictive value of anxiety sensitivity as an additional independent risk factor for PONV in patients with an increased risk of PONV.DESIGN: A noninterventional, observational study.SETTING: A tertiary care university hospital.PATIENTS: Patients with an increased risk of PONV (i.e. female, nonsmoking) undergoing elective surgery (general, gynaecological, urological, musculoskeletal or neurosurgical) under general anaesthesia.MAIN OUTCOME MEASURES: The number of patients with anxiety sensitivity assessed pre-operatively with the Anxiety Sensitivity Index-3 questionnaire, the number of patients experiencing PONV, predictive value of anxiety sensitivity compared with other established risk factors for PONV.RESULTS: Some 41.5% of the patients experienced PONV within the first 24 h after surgery. In these patients increased anxiety sensitivity (Anxiety Sensitivity Index-3 score higher than seven points) was associated with a five-fold increase in the odds ratio (OR) for PONV. From the regression model, the risk of PONV was increased by lack of PONV prophylaxis (OR, 3.68), the postoperative administration of opioids (OR, 3.60) and patient age (OR, 1.03), but laparoscopic surgery did not increase the risk.CONCLUSION: In addition to the well established risk factors, anxiety sensitivity can help to predict the risk of PONV. It seems justifiable to add psychological factors such as anxiety sensitivity to PONV risk-scores. PONV prophylaxis should be considered when anxiety sensitivity is high.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01875120. | [
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] |
PURPOSE: Brittle cornea syndrome (BCS) is a rare recessive disorder affecting connective tissues, most prominently in the eye. Pathogenic mutations causing BCS have been identified in PRDM5 and ZNF469 genes. This study investigates the genetic cause of BCS in a large, consanguineous Pakistani family with 4 affected and 3 unaffected individuals.METHODS: The coding region and exon-intron splice junctions of PRDM5 and ZNF469 genes were amplified by polymerase chain reaction, and bidirectional Sanger sequencing was performed to find the pathogenic change responsible for causing the disease in the family.RESULTS: A novel homozygous duplication c.9831dupC (p.Arg3278GlnfsX197) in the ZNF469 gene was identified, which was found to be co-segregating with the disease in the family.CONCLUSIONS: This is the first report of a ZNF469 homozygous mutation causing a BCS phenotype in a consanguineous Pakistani family. Our data extend the mutation spectrum of ZNF469 variants implicated in BCS. | [
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] |
PURPOSE: To characterize posterior corneal surface features in patients with keratoconus and healthy controls and correlate them with the severity of the disease according to visual limitation.METHODS: Retrospective, comparative, clinical study including 477 cases, 374 keratoconic eyes and 103 healthy corneas. Patients were classified according to the degree of visual limitation. The corneal posterior surface including shape indices and keratoconus screening indices was evaluated using the rotating Scheimpflug camera and Placido disc topographer.RESULTS: Dioptric power of the posterior corneal surface increases linearly as corrected distance visual acuity deteriorates (r > 0.700; P < 0.001). A significant correlation was also observed between shape indices root mean square per unit of area (RMS/A) (posterior surface irregularity) and corrected distance visual acuity (r = -0.750; P < 0.001). In addition, keratoconus screening indices such as posterior corneal aberrations and posterior ectasia vertex (KVb) also showed significant correlation with the degree of visual limitation (r = -0.687; P < 0.001 and r = -0.789; P < 0.001, respectively). Receiver operating characteristic curves demonstrate that RMS/A and KVb showed highest discriminating capabilities between normal and mild keratoconus cases with an area under the curve of 0.96 and 0.97, respectively, with a sensitivity and specificity of more than 93% for the RMS/A and 89% and 84% for the KVb.CONCLUSIONS: Posterior corneal surface characteristics correlate with the degree of visual impairment and can be used for classifying patients with keratoconus. RMS/A, KVb, and posterior corneal aberrations are the most representative variables of visual function deterioration and are also useful to differentiate normal from mild keratoconus cases. | [
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] |
PURPOSE: To report a novel clinical presentation of corneal biofilms, consisting of formation of superficial and recurrent corneal plaques.METHODS: Interventional case report. A 9-year-old boy presented with subepithelial, whitish, avascular, and recurrent corneal plaques without any clinical manifestations of active corneal inflammation and/or infection. He had a history of minor ocular trauma; otherwise, his medical history was unremarkable.RESULTS: An excisional biopsy was performed under topical anesthesia. Histological analysis identified these plaques as clusters of gram-negative bacilli surrounded by an extracellular matrix. Samples were further evaluated with special stains (calcofluor white, Flamingo fluorescent dye, propidium iodide, and Gomori-Grocott) that demonstrated biofilm structures.CONCLUSIONS: Corneal plaques are a very rare clinical presentation of corneal biofilms that allow prolonged survival of microorganisms even in the absence of prosthetic material and clinical signs or symptoms of corneal active inflammation and/or infection. | [
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PURPOSE: To report the outcomes of cyanoacrylate tissue adhesive (CTA) application in corneal thinning and perforation.METHODS: A retrospective interventional case series of 137 patients receiving CTA for corneal thinning and perforation in 140 eyes between 2001 and 2018 at a single center was reviewed. Success rate and factors associated with glue failure were analyzed.RESULTS: Median age of the cohort was 63 years and 69 (50%) were women. One hundred fifteen patients (84%) had at least 1 systemic condition, 46 (34%) had autoimmune diseases. Eighty-nine eyes (64%) presented with perforation and 51 (36%) with thinning. The perforation/thinning was central/paracentral in 82 eyes (59%) and peripheral in 57 eyes (41%). Median size of perforation was 3.1 mm. Causes of perforation and thinning were microbial infection in 75 (55%), sterile melt in 49 (35%), laceration in 10, and keratoprosthesis melt in 8 eyes. Median glue retention was 58 days. Success rate of glue application (defined as intact globe without surgical intervention) was 72%, 61%, and 46% at 10, 30, and 90 days after glue application, respectively. Larger size of perforation/thinning, perforation (vs. thinning), and single glue application (vs. multiple) were correlated with higher failure rate. Systemic conditions, use of topical corticosteroid, etiologies, and location of perforation/thinning were not significantly correlated with glue failure.CONCLUSIONS: CTA application was moderately effective in stabilizing corneal perforation and thinning in the very short-term. Multiple applications are often required. Maintenance of globe integrity after glue application decreases with time and the need for surgical intervention remains high. | [
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Our study aimed to investigate the effects of different intubation devices on middle ear pressure (MEP) dynamics by evaluating MEP during stages of anesthesia.Sixty-one consecutive patients were randomly assigned to 2 groups: the classical endotracheal intubation group and the Baska Mask (a new laryngeal mask [LMA]) group. All patients received the same anesthesia protocol. The right and left MEP values of the patients were measured and recorded preoperatively, during the induction of anesthesia, at the time of intubation and at 5th minute of anesthesia.In group 1, the pressure values measured in the right ear during anesthesia induction, at the time of intubation and at 5th minute of anesthesia were 10.97 27.06, 16.77 29.40, and 21.64 90.31, respectively, compared to left ear values of 8.61 26.39, 18.77 37.84, and 38.61 56.96 daPa, respectively. In group 2, MEP values measured in the right ear during anesthesia induction, at the time of intubation, and at 5th minute of anesthesia were 9.53 20.43, 22.30 41.50, and 20.60 46.85 daPa, respectively, compared to left ear values of -4.26 25.17, 6.20 26.56, and 30.30 65.17 daPa, respectively. MEP was statistically significantly increased in the classical endotracheal intubation group compared to the LMA group.We found that the increase in pressure is lower in patients receiving LMA compared to classical endotracheal intubation. The Baska Mask LMA is recommended in selected patients to prevent complications of MEP elevation. | [
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Primary pediatric orbital tumors requiring surgery are uncommon and often require multidisciplinary management. Commonly used surgical approaches to the orbit include transconjunctival, transcutaneous (eyelid), transcranial, or extracranial osteotomies. This paper reviews a 10-year experience of cases that required a transcranial or extracranial surgical approach at the Birmingham Children's Hospital. A total of 9 patients were identified between the years 2008 to 2017. Pathologies included rhabdomyosarcoma, juvenile ossifying fibroma, optic nerve glioma, and retinoblastoma. Surgical approaches to the orbit included supraorbital bar osteotomy (transcranial) or lateral orbitotomy (extracranial). Surgical team members included neurosurgery, craniofacial surgery, and ophthalmology. This study aims to review the role of surgery in management as well as the specific indications for performing transcranial or extracranial osteotomies. It also highlights the excellent access achieved with the use of these osteotomies in certain cases, especially when compared with transconjunctival or transcutaneous approaches. | [
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Static facial sling techniques are useful rehabilitation modalities where dynamic rehabilitation methods are not feasible in the management of facial paralysis. The authors present their technique as an alternative static sling method, which may give the patient a more natural nasolabial sulcus restoration in addition to suspension of the oral commisure. | [
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BACKGROUND: The prevalence of secretory otitis media is very high among the nonoperated cleft palate patients.METHODS: Ninety-one cleft palate operations were performed on late presented cases in Sudan, Africa. The surgeries were performed according to the Veau-Wardill-Kilner push-back technique. A laptop connected pen-type endoscopic camera was used to evaluate the tympanic membrane and address middle ear disease in all patients simultaneously. The procedure was performed after removing wax from the external auditory canal. A small incision was made with a myringotomy knife through the layers of the tympanic membrane if any sign of fluid collection was observed, after which the middle ear effusion was evacuated and the ventilation tube was inserted.RESULTS: This procedure was undertaken in 182 ears; 41 ears (22.5%) were healthy, 19 ears (10.5%) had chronic perforations, 122 ears (67%) underwent myringotomy procedures, and 54 (44.2%) were treated by inserting a ventilation tube. Despite the challenging work environment, standard monitoring facilities were available and all operations were completed with no early complications.CONCLUSION: The pen-type camera instead of an operating microscope was a tremendous contribution, as it was easy to handle and contributed to the good outcomes. The use of this technique is strongly recommended in surgical camps.LEVEL OF EVIDENCE: III. | [
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BACKGROUND: Repair of long-span mandibular defects with vascularized free fibular grafts is now a routine procedure. Vertical discrepancy between a graft segment and the occlusal plane can be resolved through several options, including delayed onlay bone graft, iliac bone reconstruction, fibula distraction, and double-barrel fibula flap grafts. The present study (level of evidence: level IV, case series) introduces a new method for mandibular augmentation, wherein a vascularized fibular segment was used to simulate the superior alveolar ridge of the neomandible, whereas a nonvascularized fibular segment was used to reconstruct the inferior border.METHODS: Patients who underwent mandibular reconstruction with this technique between January 2014 and May 2017 were retrospectively reviewed for complications, vertical height, bone resorption rates, and crown to implant (C/I) ratios.RESULTS: The study included 10 patients. Flap loss occurred in 1 patient. A sufficiently long vascular pedicle could be maintained when the average fibular length was up to 15.3 cm to reconstruct long-span mandibular defects. Mean height of the neomandible at 2 weeks and 1 year after surgery was 34.1 and 29.4 mm, respectively. Mean resorption rates of vascularized and nonvascularized fibulas were 10.3% and 3.4%, respectively, at 1 year after surgery. Dental implants were placed in 4 patients with a mean C/I ratio of 1:1.15.CONCLUSION: The present method to reconstruct the alveolar ridge and basal portion of the mandible with vascularized and nonvascularized fibular flaps was safe and effective. It provided sufficient vertical height for lip support and implantation as well as adequate length for long-span mandibular reconstruction. | [
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] |
An external jugular vein (EJV) aneurysm is an extremely rare disease. Ultrasonography with color doppler methods is considered the criterion standard for diagnosis of a venous aneurysm. The treatment of choice for an EJV aneurysm is surgical excision. Herein, we report an unusual case of an EJV aneurysm in a child with hemophilia A. Because the incidence of an EJV aneurysm is low, it is important to distinguish it from other neck lesions, including congenital disease. In addition, it should be noted that in hemophilia patients, an EJV aneurysm may occur in a spontaneous or small trauma. | [
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OBJECTIVE: This study aimed to evaluate the relationships between ocular protrusion and other craniofacial structures.METHODS: The lateral cephalograms of 124 nonsyndromic white adults were assessed. Two orbital and 13 craniofacial parameters were measured. Subgroups were constructed according to sex, anteroposterior position of maxilla, and mandibular plane angle values.Anatomical parameters and their relationships were statistically analyzed by analysis of variance and multivariate stepwise regression analysis.RESULTS: There were no significant differences in ocular protrusion distances between sexes, and between individuals with different maxillary anteroposterior position and mandibular plane angle values. Ocular protrusion distances, the distance between the eyeball apex and the lateral orbital margin (Eyeball apex-LOr: OP1) and inferior orbital margin (Eyeball apex-IOr: OP2), were found to be 20.6 2.8 and 16.5 3.1, respectively. However, regression analysis showed that the ocular protrusion distances had weak correlation with a few craniofacial structures. The OP1 had a low negative relationship with the maxillary anteroposterior position (N-Aperp) (r: -0.289) (P < 0.05). The OP2 had a low negative relationship with the palatal plane angle (FH/PP) (r: -0.291) (P < 0.01) but had a positive relationship with the cranial base angle (BSN) (r: 0.304) (P < 0.01) and posterior facial height (SGo) (r: 0.299) (P < 0.01).CONCLUSIONS: Ocular protrusion distances did not differ by sex, maxillary anteroposterior position, and amount of mandibular plane angle and showed weak correlation with a few craniofacial structures. Ocular protrusion amounts can be used for diagnosis and treatment plan in craniofacial syndromic or nonsyndromic anomalies. | [
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Submental mass secondary to toxoplasmosis is a rare condition and physicians rarely consider its diagnosis. The presented case reports a 43-year-old woman referred with a constant, painless, edema located in the submental area for 2 weeks. Diagnosis of toxoplasmosis was established by the positive serological finding after an accurate medical history of the infectious disease specialist (the patient had eaten raw meat). The patient underwent antimicrobial therapy with resolution of lymphadenopathy. According to review of literature, the article aims to remind clinicians, maxillofacial surgeons, and otolaryngologists that a neck mass can be related to the infectious cause with involving of lymph node like as toxoplasmosis. Therefore, a serological diagnosis should be considered before moving to needle biopsy or excisional biopsy of neck mass. | [
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Merkel cell carcinoma (MCC) is a rare malignant tumor with a neuroendocrine phenotype. The authors report a case of MCC of the left cheek region in an 85-year-old Caucasian woman who also received sentinel node biopsy using both Technectium-99m-labeled (99mTc) lymphoscintigraphy and indocyanine green lymphography. | [
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] |
BACKGROUND: B-thalassemia carrier state or thalassemia minor confers cardiovascular protection through favorable lipidemic and blood pressure profile. However, its impact on inflammatory status-a common denominator of the above conditions-has not been addressed.METHODS: We investigated a wide range of inflammatory markers [white blood cell (WBC) count, homocysteine, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, plasminogen, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and uric acid] in a large cohort of 15 805 newly diagnosed hypertensive patients (8299 men, 7506 women); 626 of them (4.0%) had thalassemia minor.RESULTS: The levels of WBC, homocysteine, CRP, SAA, fibrinogen, and PAI-1 were significantly lower in thalassemia minor patients, but not of plasminogen, fibronectin, and uric acid. In multivariate linear regression analyses, the lower values of WBC (<0.001), CRP (<0.001), homocysteine (<0.001), fibrinogen (<0.001), and PAI-1 (0.008), but not of SAA, were independently associated with thalassemia minor. The interaction between thalassemia minor and body mass index had a significant impact only on WBC and CRP (P for the interaction 0.010 and 0.005, respectively), whereas the interaction between thalassemia minor and sex had a significant impact only on fibrinogen (P for the interaction 0.007).CONCLUSION: Thalassemia minor is followed by a favorable inflammatory profile that may contribute to the overall better cardiovascular health of the carriers. | [
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: Acetylsalicylic acid (ASA) represents one of the most widely used pharmacological treatments for the prevention of atherothrombotic events. However, its use in low-risk patients is still debated, due to the complex balance between benefits and bleeding complications, therefore requiring new tools for the assessment of cardiovascular risk. Immature platelet count (IPC) has been suggested as a marker of platelet reactivity and turnover, thus potentially reflecting the progression of the chronic atherothrombotic vascular damage, which could be prevented by ASA. However, no study has evaluated, so far, the impact of long-term therapy with ASA on the IPC among patients undergoing coronary angiography, which was the aim of the present study. We included patients from a single centre. Significant coronary artery disease (CAD) was defined as at least one-vessel stenosis more than 50%. Immature platelet fraction (IPF) levels were measured by routine blood cells count (a Sysmex XE-2100) in patients naive or chronically treated with ASA at admission. Among 1475 patients, 464 (31.5%) were ASA-naive. Patients on long-term antiplatelet therapy were more often men (P < 0.001), with a higher prevalence of cardiovascular risk factors and CAD. The mean levels of IPC did not differ between ASA-naive and treated patents (8 5.3 vs. 7.8 4.9, P = 0.48). Similar results were obtained when considering IPC distribution across tertiles, as ASA therapy did not result as an independent predictor of IPC levels above the third tertile (?8.6 ? 10/ml) [adjusted odds ratio (95% confidence interval) = 0.96 (0.63-1.48), P = 0.87]. Results were confirmed in major higher risk subgroups of patients. The present study shows that among high-risk patients undergoing coronary angiography, the long-term therapy with ASA does not affect the levels of IPC. | [
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] |
AIMS: Objective data on epidemiology, management and outcome of patients with acute cardiac illness are still scarce, and producing evidence-based guidelines remains an issue. In order to define the clinical characteristics and the potential predictors of in-hospital and long-term mortality, we performed a retrospective, observational study, in a tertiary cardiac centre in Italy.METHODS: One thousand one hundred and sixty-five consecutive patients, admitted to our intensive cardiac care unit (ICCU) during the year 2016, were included in the study. The data were collected from the hospital discharge summary and the electronic chart records.RESULTS: Global in-hospital mortality was 7.2%. Predictors of in-hospital mortality were age [odds ratio (OR): 2.0; P = 0.011], female sex (OR: 2.18; P = 0.003), cardiac arrest (OR: 12.21; P = 0.000), heart failure/cardiogenic shock (OR: 9.99; P = 0.000), sepsis/septic shock (OR: 5.54; P = 0.000), acute kidney injury (OR: 3.25; P = 0.021) and a primary diagnosis of acute heart failure or a condition other than acute heart failure and acute coronary syndrome. During a mean follow-up period of 17.4 4.8 months, 96 all-cause deaths occurred in patients who were still alive at discharge. One-year mortality rate was 8.2%. Predictors of long-term mortality were age (hazard ratio: 1.08; P = 0.000), female sex (hazard ratio: 0.59; P = 0.022), comorbidity at least 3 (hazard ratio: 1,60; P = 0.047), acute kidney injury (hazard ratio: 3.15; P = 0.001), inotropic treatment (hazard ratio: 2.54; P = 0.002) and a primary diagnosis of acute heart failure.CONCLUSION: In our Level-2 ICCU, predictors of in-hospital and long-term mortality are similar to those commonly found in a Level-3 ICU. These data strongly suggest that ICUs dealing with acute cardiovascular patients should be reorganized with a necessary upgrading of competences and resources for medical and nursing staff. | [
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] |
PURPOSE: To assess the clinical utility of 5 physical therapy (PT) outcome measures in quantifying functional changes in pediatric lower extremity chronic pain treated at a hospital-based interdisciplinary rehabilitation center.DESIGN: This was a cross-sectional study with retrospective review of 173 individuals, 8 to 18 years old, treated from June 2008 to 2013.METHODS: The measures used were the Timed Up and Go, Timed Up and Down Stairs, Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, 6-minute walk test, and Lower Extremity Functional Scale. Participant performance was correlated with demographic characteristics, the Functional Disability Index, Multidimensional Anxiety Scale for Children, Child Depression Inventory, and Canadian Occupational Performance Measure.RESULTS: Scores from all 5 PT measures showed significant improvement following treatment. Functional Disability Index correlated to every PT measure except the 6-minute walk test.CONCLUSIONS: This study supports the clinical use of these PT measures to track functional progress after rehabilitative treatment of lower extremity chronic pain-related disability. | [
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PURPOSE: To assess effects of adaptive bungee trampoline training for children with cerebral palsy.METHODS: This was a single-subject intervention study, A-B-A, with 4 children aged 6 to 11 years. Measurements included muscle strength, balance, functional muscle strength, functional mobility, selected Gross Motor Function Measure items, heart rate, enjoyment, and for adverse effects-range of motion and spasticity. Goals were measured using the Canadian Occupational Performance Measure.RESULTS: Lower limb muscle strength improved in 3 children, and balance and functional strength in 2 children. The child who was not walking increased sitting and supported standing times. All participants had clinically significant increases on the Canadian Occupational Performance Measure. Adherence and enjoyment were high, with no adverse effects.CONCLUSION: Adaptive bungee trampoline training can improve strength, balance, and functional mobility in children with cerebral palsy. | [
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] |
PURPOSE: To investigate postural effects of the family-centered program, COPing with and CAring for infants with special needs (COPCA), applied at 3 to 6 months' corrected age in infants at high risk of cerebral palsy. Previously, we reported postural differences between the infants at risk of CP in the control group of the current study and a group of infants developing typically. Now we focus on differences between 2 intervention groups.METHODS: We explored postural adjustments during reaching in seated infants at 4, 6, and 18 months using surface electromyography of arm, neck, and trunk muscles. Infants randomly received the family-centered program or another infant physical therapy. Using videotaped intervention sessions, we investigated correlations between time spent on specific physical therapeutic actions and direction specificity, recruitment order, and anticipatory activation at 18 months.RESULTS: Postural adjustments in both groups were similar, but development of direction specificity and anticipatory activation in COPCA infants better mimicked typical development. These 2 parameters were associated with COPCA-type physical therapeutic actions.CONCLUSIONS: Postural control was similar after both interventions. Positive outcomes were associated with fewer intervening actions of the therapist and greater allowance of spontaneous movements. | [
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PURPOSE: Although pediatric physical therapists may evaluate and treat infants with both congenital muscular torticollis (CMT) and gastroesophageal reflux disorder (GERD), a literature review found only 1 article suggesting a connection between these diagnoses. This study investigates a correlation between CMT and GERD.METHODS: A retrospective chart review spanning 5 years including 2519 infants younger than 12 months examined the correlation between CMT, GERD, and other comorbidities including developmental dysplasia of the hip, oligohydramnios, multiparity, and breech positioning.RESULTS: The CMT cohort had a significantly higher rate of GERD versus the general population. For all age groups, the GERD rate was significantly higher in the CMT population than in the reference population. The rate of developmental dysplasia of the hip, oligohydramnios, and breech positioning was higher in infants with both CMT and GERD.CONCLUSIONS: The increased likelihood of infants with CMT also having GERD has clinical implications for the pediatric physical therapist. | [
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] |
PURPOSE: Reduced propulsive capability can impact negatively on mobility activities of many children with spastic unilateral cerebral palsy (SUCP). This study investigated the effect of a task-oriented training program combined with functional electrical stimulation (FES) on the motor capacity of children with SUCP.METHODS: Single-case A-B design with follow-up. Gross motor function and biomechanical walking data of 4 children with SUCP were measured repeatedly across the baseline, intervention, and follow-up phases. Intervention was a task-oriented training program combined with FES applied on the gastrocnemius. Outcome variables included gait speed, impulsive torque, and ankle/hip power generation ratio. The 2-SD band and celeration line methods compared outcomes among the baseline, intervention, and follow-up periods.RESULTS: One child improved walking speed. All children improved impulsive torque and ankle/hip power ratio of the affected leg. All children improved gross motor function.CONCLUSION: The intervention improved children's propulsive capability and positively influenced their mobility. | [
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] |
PURPOSE: To evaluate parent satisfaction of patients attending a novel advanced practice physical therapy clinic in pediatric orthopedics.METHODS: A cross-sectional survey collected data using 2 approaches: a modified version of the VSQ-9 and open-ended responses. The component structure of the Visit Specific Satisfaction Questionnaire (VSQ) was explored and the Cronbach alpha assessed internal consistency. Responses were summarized as mean (95% CI). An inductive content analysis was performed for open-ended responses.RESULTS: Satisfaction ratings were excellent. A 2-component structure for the VSQ was confirmed. The Cronbach alpha coefficient was 0.85, indicating high internal consistency. Emergent themes were mostly positive in relation to Time, Communication, Professionalism, and Service Delivery, with Physical Resources receiving negative comments.CONCLUSIONS: This study evaluated parent satisfaction with a novel advanced practice in pediatric orthopedics, demonstrating high levels of satisfaction and identifying positive and negative themes that impact parent perceptions of quality of care. | [
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] |
PURPOSE: This study aimed to describe Early Activity Scale for Endurance (EASE) scores and 6-minute walk test (6MWT) distances of children with cerebral palsy (CP) by functional ability level, sex, and age and to examine the convergent validity of the 2 tests.METHODS: A total of 708 participants with CP, Gross Motor Function Classification System (GMFCS) levels I to V, completed the EASE, and 376 of the study participants (3-12years), GMFCS levels I to III, completed the 6MWT.RESULTS: Children with CP vary in EASE scores and 6MWT distances based on GMFCS level and, to a lesser extent, age. The EASE and the 6MWT demonstrate a statistically significant but low, positive correlation.CONCLUSIONS: Understanding the relationship between these outcomes and GMFCS levels and age assists clinicians in establishing plans of care targeted at improving endurance for activity and functional walking capacity for children with CP. | [
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] |
PURPOSE: The proposed project tests the principle that frequency of rehabilitation is an important regulator of therapeutic response in infants.METHODS: We will randomize 75 infants with cerebral palsy, 6 to 24 months of age and/or Gross Motor Function Classification System levels III to V (higher severity), to determine the short-term and long-term effects of 3 dosing protocols consisting of an identical number of 2-hour sessions of the same motor learning-based therapy applied over a different total number of calendar weeks.RESULTS AND CONCLUSIONS: The results will inform clinicians, families, and scientists about dosing and will provide needed recommendations for frequency of rehabilitation to optimize motor function and development of young children with cerebral palsy. | [
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A mitochondria-responsive and -activatable photosensitizer (PS), MPS, composed of a pyridinium cation as a mitochondria targeting group and a dibenzylideneacetone derivative with environment-sensitive emission properties as the ROS generator and self-efficacy tracer, is reported. This multifunctional PS offers a new strategy for traceable photodynamic ablation of cancer cells. | [
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A supramolecular hybrid hydrogel displaying a wide array of dynamic physical properties along with enhanced in vivo stem cell retention has been developed. The key strategy is facilely polymerizing bioactive gelatin methacrylate (GelMA) with 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and 2-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (UPyMA) to generate one hybrid branched copolymer. Rapid gelation occurs upon increasing the temperature above the lower critical solution temperature (LCST) of this supramolecular copolymer, where PMEO2MA segments dehydrate and assemble into clusters, providing a hydrophobic microenvironment facilitating UPy dimerization to connect polymer chains, thus forming quadruple hydrogen bond reinforced crosslinking networks. The biodegradable, self-healing, thermo-reversible and injectable properties of the supramolecular hydrogel are finely tunable by changing the hydrogel formulation. Mesenchymal stem cells encapsulated in the hydrogel show high viability and proliferation. The subcutaneous study shows that the stem cells delivered within the in situ formed hydrogel are well protected from mechanical damage and have significantly enhanced in vivo cell retention for three weeks. These results suggest that the dynamic supramolecular hydrogel can be utilized to regulate stem cells for tissue regeneration applications. | [
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Controlling the interactions between cells and viruses is critical for treating infected patients, preventing viral infections, and improving virus-based therapeutics. Chemical methods using small molecules and biological methods using proteins and nucleic acids are employed for achieving this control, albeit with limitations. We found, for the first time, that retroviral DNA integration patterns in the human genome, the result of complicated interactions between cells and viruses, can be engineered by adapting cells to the defined nanotopography of silica bead monolayers. Compared with cells on a flat glass surface, cells on beads with the highest curvature harbored retroviral DNAs at genomic sites near transcriptional start sites and CpG islands during infections at more than 50% higher frequencies. Furthermore, cells on the same type of bead layers contained retroviral DNAs in the genomic regions near cis-regulatory elements at frequencies that were 2.6-fold higher than that of cells on flat glass surfaces. Systems-level genetic network analysis showed that for cells on nanobeads with the highest curvature, the genes that would be affected by cis-regulatory elements near the retroviral integration sites perform biological functions related to chromatin structure and antiviral activities. Our unexpected observations suggest that novel engineering approaches based on materials with specific nanotopography can improve control over viral events. | [
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Computational particokinetics models become essential in the design and interpretation of in vitro nanoparticle toxicology assays involving submerged adherent cell cultures. Yet, none of the current models offers the possibility of addressing the delivered dose of high-aspect ratio nanoparticles, including nanorods, nanotubes, and nanofibers. Here we present a straightforward method that lends this ability to any of the models used currently. | [
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] |
Males and females of Artemia franciscana, a crustacean commonly used in the aquarium trade, are highly dimorphic. Sex is determined by a pair of ZW chromosomes, but the nature and extent of differentiation of these chromosomes is unknown. Here, we characterize the Z chromosome by detecting genomic regions that show lower genomic coverage in female than in male samples, and regions that harbor an excess of female-specific SNPs. We detect many Z-specific genes, which no longer have homologs on the W, but also Z-linked genes that appear to have diverged very recently from their existing W-linked homolog. We assess patterns of male and female expression in two tissues with extensive morphological dimorphism, gonads, and heads. In agreement with their morphology, sex-biased expression is common in both tissues. Interestingly, the Z chromosome is not enriched for sex-biased genes, and seems to in fact have a mechanism of dosage compensation that leads to equal expression in males and in females. Both of these patterns are contrary to most ZW systems studied so far, making A. franciscana an excellent model for investigating the interplay between the evolution of sexual dimorphism and dosage compensation, as well as Z chromosome evolution in general. | [
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The importance of climate in determining biodiversity patterns has been well documented. However, the relationship between climate and rates of genetic evolution remains controversial. Latitude and elevation have been associated with rates of change in genetic markers such as cytochrome b. What is not known, however, is the strength of such associations and whether patterns found among these genes apply across entire genomes. Here, using bumblebee genetic data from seven subgenera of Bombus, we demonstrate that all species occupying warmer elevations have undergone faster genome-wide evolution than those in the same subgenera occupying cooler elevations. Our findings point to a critical biogeographic role in the relative rates of whole species evolution, potentially influencing global biodiversity patterns. | [
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BACKGROUND: Infantile colic is typically defined as full-force crying for at least three hours per day, on at least three days per week, for at least three weeks. Infantile colic affects a large number of infants and their families worldwide. Its symptoms are broad and general, and while not indicative of disease, may represent a serious underlying condition in a small percentage of infants who may need a medical assessment. Probiotics are live microorganisms that alter the microflora of the host and provide beneficial health effects. The most common probiotics used are of Lactobacillus, Bifidobacterium and Streptococcus. There is growing evidence to suggest that intestinal flora in colicky infants differ from those in healthy infants, and it is suggested that probiotics can redress this balance and provide a healthier intestinal microbiota landscape. The low cost and easy availability of probiotics makes them a potential prophylactic solution to reduce the incidence and prevalence of infantile colic.OBJECTIVES: To evaluate the efficacy and safety of prophylactic probiotics in preventing or reducing severity of infantile colic.SEARCH METHODS: In January 2018 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 10 other databases and two trials registers. In addition, we handsearched the abstracts of relevant meetings, searched reference lists, ran citation searches of included studies, and contacted authors and experts in the field, including the manufacturers of probiotics, to identify unpublished trials.SELECTION CRITERIA: Randomised control trials (RCTs) of newborn infants less than one month of age without the diagnosis of infantile colic at recruitment. We included any probiotic, alone or in combination with a prebiotic (also known as synbiotics), versus no intervention, another intervention(s) or placebo, where the focus of the study was the effect of the intervention on infantile colic.DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of Cochrane.MAIN RESULTS: Our search yielded 3284 records, and of these, we selected 21 reports for full-text review. Six studies with 1886 participants met our inclusion criteria, comparing probiotics with placebo. Two studies examined Lactobacillus reuteri DSM, two examined multi-strain probiotics, one examined Lactobacillus rhamnosus, and one examined Lactobacillus paracasei and Bifidobacterium animalis. Two studies began probiotics during pregnancy and continued administering them to the baby after birth.We considered the risk of bias for randomisation as low for all six trials; for allocation concealment as low in two studies and unclear in four others. All studies were blinded, and at low risk of attrition and reporting bias.A random-effects meta-analysis of three studies (1148 participants) found no difference between the groups in relation to occurrence of new cases of colic: risk ratio (RR) 0.46, 95% confidence interval (CI) 0.18 to 1.19; low-certainty evidence; I2 = 72%.A random-effects meta-analysis of all six studies (1851 participants) found no difference between the groups in relation to serious adverse effects (RR 1.02, 95% CI 0.14 to 7.21; low-certainty evidence; I2 not calculable (only four serious events for one comparison, two in each group: meconium plug obstruction, patent ductus arteriosus and neonatal hepatitis).A random-effects meta-analysis of three studies (707 participants) found a mean difference (MD) of -32.57 minutes per day (95% CI -55.60 to -9.54; low-certainty evidence; I2 = 93%) in crying time at study end in favour of probiotics.A subgroup analysis of the most studied agent, Lactobacillus reuteri, showed a reduction of 44.26 minutes in daily crying with a random-effects model (95% CI -66.6 to -21.9; I2 = 92%), in favour of probiotics.AUTHORS' CONCLUSIONS: There is no clear evidence that probiotics are more effective than placebo at preventing infantile colic; however, daily crying time appeared to reduce with probiotic use compared to placebo. There were no clear differences in adverse effects.We are limited in our ability to draw conclusions by the certainty of the evidence, which we assessed as being low across all three outcomes, meaning that we are not confident that these results would not change with the addition of further research. | [
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BACKGROUND: Patients who undergo lower extremity amputation secondary to the complications of diabetes or peripheral artery disease have poor long-term survival. Providing patients and surgeons with individual-patient, rather than population, survival estimates provides them with important information to make individualized treatment decisions.METHODS: Patients with peripheral artery disease and/or diabetes undergoing their first unilateral transmetatarsal, transtibial or transfemoral amputation were identified in the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database. Stepdown logistic regression was used to develop a 1-year mortality risk prediction model from a list of 33 candidate predictors using data from three of five Department of Veterans Affairs national geographical regions. External geographical validation was performed using data from the remaining two regions. Calibration and discrimination were assessed in the development and validation samples.RESULTS: The development sample included 5028 patients and the validation sample 2140. The final mortality prediction model (AMPREDICT-Mortality) included amputation level, age, BMI, race, functional status, congestive heart failure, dialysis, blood urea nitrogen level, and white blood cell and platelet counts. The model fit in the validation sample was good. The area under the receiver operating characteristic (ROC) curve for the validation sample was 076 and Cox calibration regression indicated excellent calibration (slope 096, 95 per cent c.i. 085 to 106; intercept 002, 95 per cent c.i. -012 to 017). Given the external validation characteristics, the development and validation samples were combined, giving a total sample of 7168.CONCLUSION: The AMPREDICT-Mortality prediction model is a validated parsimonious model that can be used to inform the 1-year mortality risk following non-traumatic lower extremity amputation of patients with peripheral artery disease or diabetes. | [
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] |
AIM: To assess progressive learning of root canal shaping in order to define the number of simulated canals in resin blocks needed to reach a level of learning beyond which no further improvement in performance is observed.METHODOLOGY: A total of 216 simulated canals in resin blocks were instrumented by 18 operators without experience in Endodontics and by 18 Endodontists. The R25 file of the Reciproc system (VDW, Munich, Germany) was used to prepare the canals. The blocks were photographed before and after instrumentation. An analysis was made of the variations in the dimensions of the canals at 6 locations and of the instrumentation time. A Student's t-test was used to analyse the data (P<0.05).RESULTS: The group without experience were associated with significant differences in instrumentation time between the first canal and the subsequent canals (P<0.05) but differences in canal dimensions were not significant (P>0.05). In the group with experience, the instrumentation time did not differ significantly after the fifth canal, and no significant variations in canal dimensions were observed (P>0.05).CONCLUSIONS: When conducting studies on root canal shaping or educating students with new instruments, a simulated canal sample size of 6 was appropriate to achieve competence. | [
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BACKGROUND: Cell blocks and immunohistochemistry (IHC) are increasingly recognized as being complementary tools for cytologic diagnostics, especially for neoplastic diseases.OBJECTIVES: The study aimed to evaluate the utility of cell tube block (CTB) IHC for refining the diagnosis of effusions in dogs and cats.METHODS: Cavitary effusions (n=25) from dogs and cats classified by cytology as reactive, neoplastic, borderline (suspicious of neoplasia), and chylous were studied. CTB sections were stained with H&E, and immunostained with PAX-5, CD3, pancytokeratin (CK), vimentin, and Wilms tumor 1 protein (WT1) antibodies, according to the cytologic diagnoses. A histologic case series of confirmed normal, reactive, and neoplastic mesothelium and several different carcinomas were included to test the utility of WT1 as a marker of mesothelial cells.RESULTS: CTBs had a layered appearance with reduced background staining. CD3 and PAX5 immunolabeling allowed immunophenotype assessment in all of the lymphoma cases. In carcinomatous effusions, neoplastic cells were CK-positive, WT1-negative, and vimentin-negative (except for two cases). Wilms tumor 1 protein was positive in the nuclei of normal, reactive, and neoplastic mesothelial cells, and ovarian carcinomatous cells. Other carcinomas and lymphomas were negative.CONCLUSIONS: CTBs are valuable tools to assist in making a diagnosis of cavitary effusions in dogs and cats, and WT1 is a promising marker to differentiate mesothelial from carcinomatous cells. | [
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BACKGROUND: Lowering the dose of desoxycorticosterone pivalate (DOCP) for the treatment of dogs with primary hypoadrenocorticism (PH) decreases costs and could lead to increased owner motivation to treat their affected dogs.OBJECTIVE: To evaluate the efficacy of a low-dose DOCP treatment protocol in dogs with PH.ANIMALS: Prospective study, 17 client-owned dogs with naturally occurring PH (12 newly diagnosed, 5 previously treated with fludrocortisone acetate [FC]).METHODS: Dogs with newly diagnosed PH were started on 1.5 mg/kg DOCP SC; dogs previously treated with FC were started on 1.0-1.8 mg/kg DOCP SC. Reevaluations took place at regular intervals for a minimum of 3 months and included clinical examination and determination of serum sodium and potassium concentrations. The DOCP dosage was adjusted to obtain an injection interval of 28-30 days and to keep serum electrolyte concentrations within the reference interval.RESULTS: Median (range) follow-up was 16.2 months (4.5-32.3 months). The starting dosage was sufficient in all but 2 dogs and had to be significantly decreased after 2-3 months to a median dosage (range) of 1.1 mg/kg (0.7-1.8). Dogs 3 years of age or younger needed significantly higher dosages compared to older dogs. None of them, however, needed the 2.2 mg/kg DOCP dosage, recommended by the manufacturer.CONCLUSIONS AND CLINICAL IMPORTANCE: A starting dosage of 1.5 mg/kg DOCP is effective in controlling clinical signs and serum electrolyte concentrations in the majority of dogs with PH. An additional dose reduction often is needed to maintain an injection interval of 28-30 days. Young and growing animals seem to need higher dosages. | [
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BACKGROUND: Data on bloodstream infection (BSI) due to enteric organisms are scarce.METHODS: This retrospective study (1/2009-5/2017) was aimed to evaluate the incidence of BSI episodes due to enteric organisms during the first 6months after intestinal transplant (ITx). Differences between the first (2009-2012) and second period (2013-2017) were evaluated as they differed from each other in the perioperative fungal prophylaxis and immunosuppressive regimen.RESULTS: Fifty-five adult patients were analyzed. Twenty-eight (51%) patients developed a total of 51 episodes of BSI. Mean time from transplant to BSI was 85.558.8days. The most common organisms were Klebsiella pneumoniae (33%), Enterococcus spp (31%), and Candida spp (18%). Twenty-three (45%) were multidrug resistant. The most common sources were gut translocation (35%), central line infection (20%), and intra-abdominal abscess (14%). Biopsy-proven rejection was associated with 16 (31%) of the BSI episodes. Patients during the first period were more likely to develop BSI (79% vs 41%, P=0.03). There were more episodes of rejection associated with BSI in the first period (45% vs 14%, P=0.03). The rate of reoperation into the abdominal cavity within 2weeks after ITx was higher and the transplant hospital stay was longer among those who developed BSI (P=0.04 for both).CONCLUSIONS: Half of our patients developed BSI (typically during the first 3months). Gut translocation was the most common source of BSI. Patients with rejection and/or enteritis should be monitored closely for BSI. | [
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In this commentary on the special issue, it is argued that the studies presented illustrate three pivotal characteristics of a new, evolving paradigm to study the consequences of prolonged intercultural encounters, such as globalization. The first refers to the topics studied and involves the need to delineate more distal, universal, and more proximal, culture-specific elements in intercultural encounters in these topics. The second is the need to deal with variation in intensity and focus of intercultural contact, ranging from casual contact to immersion. The third involves the need to delineate the psychological mechanisms involved in intercultural contact (and their consequences). The studies in the special issue illustrate the importance of including contextual features in the study of globalization. Challenges of the evolving paradigm are described. | [
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] |
Most studies have investigated brain activation changes after the course of arithmetic learning, and the question remains whether these changes are detectable during the course of learning, i.e., before memory consolidation. Twenty-four fifth graders solved multiplication problems while ongoing electroencephalography (EEG) was recorded. The arithmetic training revealed reduced errors together with a power increase in theta (4-7Hz) but not in lower alpha (8-10Hz) or upper alpha (10-13Hz) bands. We conclude that increases in theta power subserved a shift from slow, procedural strategies to more efficient, automated procedural and retrieval strategies, which led to more efficient performance. | [
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Diving optimality models predict air breathers to routinely dive within aerobic limits, but predator avoidance dives may be an exception. Lengthening submergence times during a predation threat may enhance survival probability, and we therefore hypothesized that predator avoidance dives in juvenile estuarine crocodiles (Crocodylus porosus) would be partially anaerobically fueled. We also predicted that reliance on anaerobic metabolism would increase at elevated temperatures to offset the faster depletion of body oxygen stores. Crocodiles were maintained at 28 and 34C for 60 d and subsequently underwent simulated predator avoidance dive trials at two test temperatures (28 and 34C). Blood was sampled immediately on surfacing to measure plasma lactate concentrations relative to nondiving (control) values. Aerobic dive limits (cADL; min) were also calculated using known body mass and oxygen storage relationships and rates of diving oxygen consumption and compared with observed dive durations. Postdive plasma lactate levels were elevated beyond resting levels at both test temperatures, indicating that aerobic thresholds were surpassed during simulated predator avoidance dives. Similarly, ?90% of dive durations exceeded cADLs at both test temperatures. Postdive plasma lactate concentrations were independent of water temperature and thermal acclimation treatment. Together, these findings suggest that reliance on anaerobiosis during simulated predator avoidance dives is important regardless of temperature. | [
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BACKGROUND: Among the neuropsychiatric complications commonly induced by traumatic brain injury (TBI), behavioral disorders, such as agitation and aggression, can hinder neurological recovery and deteriorate rehabilitation outcomes. Pharmacological treatment for behavioral disorders might be beneficial but could lead to drug-induced parkinsonism. We report a case of a patient with drug-induced parkinsonism manifested as freezing of gait after TBI, which improved with the cessation of the offending drugs and comprehensive rehabilitation.CASE PRESENTATION: A 35-year-old male patient left with a TBI after a car accident was referred to our hospital. He had been on many neuropsychiatric medications, including atypical antipsychotics, for his agitated behaviors. He could walk independently but showed freezing of gait at the initiation of his gait, when turning to the side, when reaching his destination, and passing through narrow corridors. Under the impression of drug-induced parkinsonism, we gradually tapered the patient off his neuropsychiatric medications. He also underwent comprehensive rehabilitation, including gait training under visual and auditory cues and balance training. Five weeks after admission to the hospital, the patient's freezing of gait improved, with disappearance of his hesitation at gait initiation and a decreased freezing duration while turning around.CONCLUSIONS: This is a rare report of drug-induced parkinsonism manifested as freezing of gait, which showed improvement after discontinuation of the causative drugs and subsequent rehabilitation. | [
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Amenorrhea is one of the clinical consequences of hyperprolactinemia. Although symptomatic hyperprolactinemia is among the well-described adverse reactions of antipsychotic agents, it may also be reported with the use of selective serotonin reuptake inhibitors. Hereby, we present a case of sertraline-related hyperprolactinemic amenorrhea in an adolescent. Amenorrhea occurred 2 months after starting sertraline, and menstrual cycle restored after stopping the treatment. | [
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Nurse transition programs have predominantly used internal evaluations to evaluate quality outcomes, and thus, there appears to be a lack of current literature on external evaluation of these programs. External evaluation provides an objective and valuable tool for the nursing professional development practitioner to demonstrate return on investment. The results support the use of the innovative and groundbreaking Clinical Nurse Transition Program Evaluation Tool to externally evaluate the nurse transition program. | [
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Opioids are commonly prescribed in orthopaedics for acute or chronic pain for a variety of conditions, including injury, trauma, degenerative processes, and postsurgical. Patients who are taking opioids because of a substance use disorder (SUD) are also seen in orthopaedics. Patients who are prescribed opioids are at risk of developing an opioid use disorder (OUD). Ten percent of Americans will develop an SUD, which is considered a chronic medical condition that develops due to an imbalance in brain chemistry. In studies, orthopaedic surgeons have a high rate of prescribing opioids, but this rate is decreasing along with national average due to public and provider awareness of the opioid epidemic and professional recommendations. Despite the evidence of a neurobiological cause for SUDs, stigma toward patients with SUDs and a knowledge deficit are common among healthcare professionals, including orthopaedic nurses. A harm reduction approach when working with orthopaedic patients taking opioids either prescribed or used because of an OUD can be applied to reduce the problematic effects of opioids. Harm reduction strategies are supportive to the patient and include education and prevention, adopting evidence-based treatment and communication strategies, and the use of naloxone to prevent opioid overdose. | [
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Individuals and food-insecure households who rely on food banks have a higher likelihood of chronic health conditions. A study of the Action Family Program at a faith-based community center demonstrated how nurses can impact food bank recipients' health measures through health promotion interventions. Providing healthier food options with the weekly food distribution box, cooking demonstrations, health screenings, and health education resulted in reduced weight, and decreased systolic and diastolic blood pressure measurements. | [
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Ukraine has been an independent country since the fall of Communism in 1991. Its history has been and continues to be marked by war. Through the story of one patient, this article describes the ministry of faith community nursing in the capital city, Kiev. Through an ongoing partnership, the Association for Christian Nurses and Volunteers-Welfare Organization (BLAGO) teaches nurses and volunteers the principles of faith community nursing, with the goal of establishing faith community nursing practice in each state/oblast. | [
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Depression among homebound older adults is a significant problem. This pilot project examined the effect of a faith community nurse (FCN) educational intervention based on the CREATION Health Model, on depression in older homebound adults. Results showed a downward trend in depression scores on the Geriatric Depression Scale: Short Form, suggesting that FCN interventions and the CREATION Health Model may be helpful for decreasing depression in this group. | [
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Confronting incivility in the online classroom can significantly benefit from spiritual approaches that address behaviors on a continuum of mild to aggressive. This may include the need to intervene when covert or overt threats occur. Electronic communications can lead to misperceptions and misunderstandings between students and faculty. Lack of understanding of diverse cultures, life experiences, and professional and spiritual histories can lead to behaviors that are perceived as intentionally hostile when, in fact, they are not. It is important in the online classroom to differentiate between the two and establish expected virtual classroom behaviors. | [
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This qualitative study utilized a phenomenological approach to better understand nurse, chaplain, and family member experiences with the delivery of spiritual services at the end of life in an inpatient intensive care unit. Triadic semistructured interviews (six with the patient's family members, six with nurses, and six with chaplains) were conducted. Family members perceived that the nurses' role was to care for the physical needs of their loved one, whereas chaplains were there to care for the emotional needs of those involved. | [
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Nurses employed in a caustic work environment can find their ability to give quality patient care impeded. Situations in which there is incivility, high stress, jealousy, or harassment, exemplify work environments that can be discouraging, especially for Christian nurses who may have pursued the profession in response to a spiritual calling. There are biblical passages that nurses may use to help them cope, including six focus points to guide and encourage nurses in caustic work situations. | [
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Service-learning is an experiential process of action and reflection that allows students to expand their knowledge through real-world activities that benefit others. Service-learning opportunities for baccalaureate nursing students in Kenya have provided many ongoing examples of learning from our Kenyan collaborators. Receiving ministry from those we came to serve, allows allows us, in turn, to demonstrate Christ's humility. In this article, we share specific stories of how various community partners ministered in unexpected ways to our teams of students and faculty, as we served in Kenya through healthcare and education. | [
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Using an ethnographical case study method, faculty members examined senior nursing students' experiences and learning during a cultural immersion service-learning trip in Haiti. Pediatric care was emphasized, as well as cultural awareness and competency. Following thematic analysis, students' guided reflections revealed common themes: knowledge and skills, culture, healthcare, and challenges and opportunities. Students also reported improved cultural understanding and self-perception. | [
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This study investigates the applicability of adipose mesenchymal stem cells (mADSCs) and hyaluronic acid (HA) as a cellular compound for bone tissue engineering. A critical bone defect was created on each femur of 25 rats in vivo, receiving the following 5 graft treatments: I-Control-defect; II-HA; III-mADSCs; IV-mADSCs+HA; and V-previously osteoinduced mADSCs+HA. Evaluation using microcomputed tomography, histomorphometry, and RT-PCR analysis was performed 23 days after implantation. Microcomputed tomography analysis indicated higher means of bone contact surface (BCS) and bone surface density (BSD) for the mADSCs+HA group compared with Control and the HA groups (P < 0.05). Histomorphometric findings showed higher means of bone regeneration in the mADSCs+HA compared with HA and Control groups (P < 0.05). The RT-PCR ratios showed no difference in type 1 collagen (Col1A) gene expression or osteopontin (OP) gene expression, whereas for the osteonectin gene (ON) higher means were found in the HA and mADSCs osteoin+HA groups (P < 0.05). These results suggest that a combination of HA and mADSCs without prior osteoinduction might be applicable for bone tissue regeneration. | [
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Cartilage created by tissue engineering is a promising new development in facial reconstructive surgery. The purpose of this study was to evaluate the histological results of implantation of synthetic polymer scaffold with chondrocytes differentiated from adipose-derived mesenchymal stem cells. Adipose tissue obtained from Wistar albino rats was dissociated, incubated and placed in culture medium. After a sufficient level of stem cell proliferation, the differentiation phase was started. Cells were collected on the 7th and 21st day of culture for chondrogenic characterization. After the 21st day of the differentiation phase of chondrocytes, they were transferred onto poly(dl-lactide-epsilon-caprolactone) synthetic polymer and culture continued for 24 hours. The scaffold with chondrocytes was then implanted into a subcutaneous area of skin on the back of the neck of the rat. Six weeks after implantation, all rats were sacrificed and the implantation areas were analyzed. Chondrocytes derived from adipogenic mesenchymal stem cells were stained positively with collagen II, aggrecan and Sox-9 after the differentiation stages. Histological examination of the excised material showed that chondrocytes were present, and the scaffold had been completely absorbed. The results of this study indicate that the differentiation method from mesenchymal stem cells to chondrogenic lineage was straightforward and scaffold with cells was easily accessible. This technique may be a good option for cartilage tissue engineering. | [
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BACKGROUND AND OBJECTIVES: Large scars formed after burns injury can seriously hamper appearance and function in children. Surgical resection of scars and secondary skin or flap grafting often brings severe damages to donor sites, which may lead to physiological and psychological development disorders in children. Here, we introduce the use of artificial dermis and skin grafts from scalps to treat large scars in children to minimize the donor site morbidity.METHODS: A retrospective char review was performed including 7 children with large scars between January 2016 and December 2017. First, the scars were resected, and artificial dermis was applied to the secondary wounds. Twelve days later, outer silicone membrane was removed. Another 2 days later, scalp skin grafts of 0.3 mm were transplanted to the wounds. Manchester Scar Scale and Visual Analog Scale were used to evaluate scar appearance before and after the treatment respectively. One special patient with extensive scars was treated twice at an interval of 1 year. The first therapy was performed with both conventional method of resection and skin grafting and the new method described above. In the second therapy, 4 samples were taken from 4 different sites-the normal skin, scars, the skin where artificial dermis and scalp skin grafting were performed, and the skin where only scalp skin grafting was performed. H-E staining, Masson staining, Aldehyde fuchsin staining, and scanning electron microscopy were used for histological observation.RESULTS: All skin grafts survived well. The Manchester Scar Scale score of the graft area was significantly reduced (P < 0.01) after the treatment. Histological examination showed obviously better dermis arrangement where artificial dermis and scalp grafting was performed.CONCLUSION: The therapy achieves better appearances and minimizes donor site morbidity. It is beneficial to physical and psychological development of children and provides an alternative to treat children with large scars. | [
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Intensity-modulated radiation therapy is being increasingly used to treat cervical esophageal cancer (CEC); however, delineating the gross tumor volume (GTV) accurately is essential for its successful treatment. The use of computed tomography (CT) images to determine the GTV produces a large degree of interobserver variation. In this study, we evaluated whether the use of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/CT fused images reduced interobserver variation, compared with CT images alone, to determine the GTV in patients with CEC. FDG-PET/CT scans were obtained for 10 patients with CEC, imaged positioned on a flat tabletop with a pillow. Five radiation oncologists independently defined the GTV for the primary tumors using routine clinical data; they contoured the GTV based on CT images (GTVCT), followed by contouring based on FDG-PET/CT fused images (GTVPET/CT). To determine the geometric observer variation, we calculated the conformality index (CI) from the ratio of the intersection of the GTVs to their union. The interobserver CI was compared using Wilcoxon's signed rank test. The mean (SD) interobserver CIs of GTVCT and GTVPET/CT were 0.39 0.15 and 0.58 0.10, respectively (P = 0.005). Our results suggested that FDG-PET/CT images reduced interobserver variation when determining the GTV in patients with CEC. FDG-PET/CT may increase the consistency of the radiographically determined GTV in patients with CEC. | [
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] |
HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order genomic structural features are largely unknown. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line's genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments at high resolution, SNVs and Indels (corrected for aneuploidy), regions with loss of heterozygosity, phased haplotypes extending to entire chromosome arms, retrotransposon insertions and structural variants (SVs) including complex and somatic genomic rearrangements. A large number of SVs were phased, sequence assembled and experimentally validated. We re-analyzed published HepG2 datasets for allele-specific expression and DNA methylation and assembled an allele-specific CRISPR/Cas9 targeting map. We demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework. | [
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The aim of this study was to evaluate the effect of SERPINB2 on cell proliferation, cell cycle, epithelial-mesenchymal transition (EMT), invasion, migration, and radiosensitivity in nasopharyngeal carcinoma cells. Both CNE2R and CNE2 cells were transfected with pEGFP-N1-SERPINB2. Cell proliferation was measured by MTT assay, cell cycle by flow cytometry, and SERpINB2 expression by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was carried out to detect the protein expression. In addition, SERPINB2 and -catenin were located intracellularly using an immunofluorescent assay, and cell migration and invasion were measured by wound healing and Transwell assays, respectively. Radiosensitivity was assessed using colony formation and MTT assays. SERPINB2 expression was downregulated in CNE2R cells. After transfection with pEGFP-N1-SERPINB2, the OD values were decreased, and there was an increased fraction in the G2/M phase. Moreover, SERPINB2 overexpression could inhibit the invasion and migration capabilities of CNE2R and CNE2 cells, with downregulation of vimentin, N-cadherin, nuclear -catenin, matrix metalloproteinase (MMP)-2 and MMP-9, and upregulation of E-cadherin. Moreover, transfection with the SERPINB2 plasmid reduced the growth rate of CNE2R cells at doses of 2, 4 and 6 Gy, and also decreased the surviving fractions. Overexpression of SERPINB2 could reduce the proliferation, invasion and migration capabilities of CNE2R and CNE2 cells, and led to G2/M arrest via EMT inhibition, and this may be a potential strategy for enhancing the radiation sensitivity of nasopharyngeal carcinoma cells. | [
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Mitochondrial genome (mitogenome) plays important roles in evolutionary and ecological studies. It becomes routine to utilize multiple genes on mitogenome or the entire mitogenomes to investigate phylogeny and biodiversity of focal groups with the onset of High Throughput Sequencing(HTS)technologies. We developed a mitogenome toolkit MitoZ, consisting of independent modules of de novo assembly, findMitoScaf (find Mitochondrial Scaffolds), annotation and visualization, that can generate mitogenome assembly together with annotation and visualization results from HTS raw reads. We evaluated its performance using a total of 50 samples of which mitogenomes are publicly available. The results showed that MitoZ can recover more full-length mitogenomes with higher accuracy compared to the other available mitogenome assemblers. Overall, MitoZ provides a one-click solution to construct the annotated mitogenome from HTS raw data and will facilitate large scale ecological and evolutionary studies. MitoZ is free open source software distributed under GPLv3 license and available at https://github.com/linzhi2013/MitoZ. | [
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] |
Eukaryotic cells contain sub-cellular compartments that are not membrane bound. Some structures are always present, such as nuclear speckles that contain RNA-binding proteins (RBPs) and poly(A)+ RNAs. Others, like cytoplasmic stress granules (SGs) that harbor mRNAs and RBPs, are induced upon stress. When we examined the formation and composition of nuclear speckles during stress induction with tubercidin, an adenosine analogue previously shown to affect nuclear speckle composition, we unexpectedly found that it also led to the formation of SGs and to the inhibition of several crucial steps of RNA metabolism in cells, thereby serving as a potent inhibitor of the gene expression pathway. Although transcription and splicing persisted under this stress, RBPs and mRNAs were mislocalized in the nucleus and cytoplasm. Specifically, lncRNA and RBP localization to nuclear speckles was disrupted, exon junction complex (EJC) recruitment to mRNA was reduced, mRNA export was obstructed, and cytoplasmic poly(A)+ RNAs localized in SGs. Furthermore, nuclear proteins that participate in mRNA export, such as nucleoporins and mRNA export adaptors, were mislocalized to SGs. This study reveals structural aspects of granule assembly in cells, and describes how the flow of RNA from the nucleus to the cytoplasm is severed under stress. | [
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IGF2mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets. | [
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Single-cell RNA sequencing (scRNA-seq) is able to give an insight into the gene-gene associations or transcriptional networks among cell populations based on the sequencing of a large number of cells. However, traditional network methods are limited to the grouped cells instead of each single cell, and thus the heterogeneity of single cells will be erased. We present a new method to construct a cell-specific network (CSN) for each single cell from scRNA-seq data (i.e. one network for one cell), which transforms the data from 'unstable' gene expression form to 'stable' gene association form on a single-cell basis. In particular, it is for the first time that we can identify the gene associations/network at a single-cell resolution level. By CSN method, scRNA-seq data can be analyzed for clustering and pseudo-trajectory from network perspective by any existing method, which opens a new way to scRNA-seq data analyses. In addition, CSN is able to find differential gene associations for each single cell, and even 'dark' genes that play important roles at the network level but are generally ignored by traditional differential gene expression analyses. In addition, CSN can be applied to construct individual network of each sample bulk RNA-seq data. Experiments on various scRNA-seq datasets validated the effectiveness of CSN in terms of accuracy and robustness. | [
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The general transcription factor P-TEFb, a master regulator of RNA polymerase (Pol) II elongation, phosphorylates the C-terminal domain (CTD) of Pol II and negative elongation factors to release Pol II from promoter-proximal pausing. We show here that P-TEFb surprisingly inhibits the myoblast differentiation into myotubes, and that P-TEFb and its two positive complexes are eliminated in this process. In contrast, DYRK1A, another CTD kinase known to control transcription of a subset of genes important for development and tissue homeostasis, is found to activate transcription of key myogenic genes. We show that active DYRK1A exists in a complex with the WD40-repeat protein DCAF7 that stabilizes and tethers DYRK1A to Pol II, so that DYRK1A-DCAF7 can co-migrate with and phosphorylate Pol II along the myogenic gene loci. Thus, DCAF7 modulates the kinase signaling output of DYRK1A on Pol II to stimulate myogenic transcription after active P-TEFb function is shut off. | [
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] |
Hair follicles (HFs) are a well‑characterized niche for adult stem cells (SCs), and include epithelial and melanocytic SCs. HF cells are an accessible source of multipotent adult SCs for the generation of the interfollicular epidermis, HF structures and sebaceous glands in addition to the reconstitution of novel HFs in vivo. In the present study, it was demonstrated that HF cells are able to be induced to differentiate into cardiomyocyte‑like cells in vitro under specific conditions. It was determined that HF cells cultured on OP9 feeder cells in KnockOut‑Dulbecco's modified Eagle's medium/B27 in the presence of vascular endothelial growth factors differentiated into cardiomyocyte‑like cells that express markers specific to cardiac lineage, but do not express non‑cardiac lineage markers including neural stem/progenitor cell, HF bulge cells or undifferentiated spermatogonia markers. These cardiomyocyte‑like cells exhibited a spindle‑ and filament‑shaped morphology similar to that presented by cardiac muscles and exhibited spontaneous beating that persisted for over 3 months. These results demonstrate that SC reprogramming and differentiation may be induced without resulting in any genetic modification, which is important for the clinical applications of SCs including tissue and organ regeneration. | [
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Hepatoblastoma (HB) is the most common liver tumor in children under the age of 3years worldwide. While many patients achieve good outcomes with surgical resection and conventional chemotherapy, there is still a high‑risk population that exhibits a poor treatment response and unfavorable prognosis, which warrants the search for novel treatment options. In recent years, it has become clear that genetic events alone are not sufficient to explain the aggressive phenotype of this embryonal malignancy. Instead, epigenetic modifications and aberrant gene expression seem to be key drivers of HB. In the present study, expression analyses such as reverse transcription‑quantitative polymerase chain reaction revealed that the oncogene, MYCN proto‑oncogene basic‑helix‑loop‑helix transcription factor (MYCN) was upregulated in HB and other pediatric liver tumors, due to the transcriptional activity of its antisense transcript MYCN opposite strand (MYCNOS). Pyrosequencing demonstrated the hypomethylated regions in the promoter of MYCN and MYCNOS, suggesting that an epigenetic mechanism may underlie the induction of aberrant expression. Transient MYCN knockdown in HB cells resulted in growth inhibition over time. In addition, treating HB cells with the MYCN inhibitors JQ1 and MLN8237 led to the significant downregulation of MYCN either at the mRNA or protein levels, respectively. The underlying mechanism of action of the two inhibitors was revealed to be associated with the induction of dose‑dependent growth arrest, by arresting cells at either the G1/G0 or G2 phase. Furthermore, MLN8237 and JQ1 were able to cause spindle disturbances and/or apoptosis in HB cells. The present results suggest that MYCN may be a promising biomarker for HB and a potential therapeutic target in patients with tumors overexpressing MYCN. | [
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Reversine, a 2,6‑diamino‑substituted purine analogue, has been reported to be effective in tumor suppression via induction of cell growth arrest and apoptosis of cancer cells. However, it remains unclear whether reversine exerts anticancer effects on human colorectal cancer cells. In the present study, invitro experiments were conducted to investigate the anticancer properties of reversine in human colorectal cancer cells. The effect of reversine on human colorectal cancer cell lines, SW480 and HCT‑116, was examined using a WST‑1 cell viability assay, fluorescence microscopy, flow cytometry, DNA fragmentation, small interfering RNA(siRNA) and western blotting. Reversine treatment demonstrated cytotoxic activity in human colorectal cancer cells. It also induced apoptosis by activating poly(ADP‑ribose) polymerase, caspase‑3, ‑7 and ‑8, and increasing the levels of the pro‑apoptotic protein second mitochondria‑derived activator of caspase/direct inhibitor of apoptosis‑binding protein with low pI. The pan‑caspase inhibitor Z‑VAD‑FMK attenuated these reversine‑induced apoptotic effects on human colorectal cancer cells. Additionally, reversine treatment induced cell cycle arrest in the subG1 and G2/Mphases via increase in levels of p21, p27 and p57, and decrease in cyclinD1 levels. The expression of Fas and death receptor5(DR5) signaling proteins in SW480 and HCT116 cells was upregulated by reversine treatment. Reversine‑induced apoptosis and cell cycle arrest were suppressed by inhibition of Fas and DR5 expression via siRNA. In conclusion, Reversine treatment suppressed tumor progression by the inhibition of cell proliferation, induction of cell cycle arrest and induction of apoptosis via upregulation of the Fas and DR5 signaling pathways in human colorectal cancer cells. The present study indicated that reversine may be used as a novel anticancer agent in human colorectal cancer. | [
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Autophagy and apoptosis are associated with cardiovascular diseases. Emerging evidence shows that microRNAs (miRs) are critical in the development of pathological processes underlying cardiovascular diseases by regulating the induction of apoptosis and autophagy. The present study aimed to investigate the role of miR‑103a‑3p in cardiomyocyte injury through autophagy and apoptosis. H9c2 cells were cultured under hypoxia and reoxygenation (H/R) conditions and were used to mimic cells under ischemia. The transfection of cells with miR‑103a‑3p (mimics and inhibitors) was performed to examine its function in cardiomyocytes. The expression levels of miR‑103a‑3p were evaluated by reverse transcription‑quantitative polymerase chain reaction analysis. Cell viability was determined using an MTT assay, and the lactate dehydrogenase assay (LDH) was used to investigate cell injury. The expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein, Beclin‑1, autophagy‑related 5 (Atg5), cleaved caspase‑3 and cleaved caspase‑9 were detected using western blotting. Immunofluorescence assays were performed to detect the expression of LC3 as a marker of autophagy. The target gene of miR‑103a‑3p was identified using dual‑luciferase reporter assays. The results revealed that the expression levels of miR‑103a‑3p were significantly downregulated in cardiomyocytes under H/R conditions. Injury of the cardiomyocytes was evaluated under H/R conditions. Following transfection of the cells with miR‑103a‑3p inhibitors, cell injury was increased, as determined by LDH and MTT assays. The expression levels of apoptotic proteins were consistent with the results obtained in the LDH and cell viability assays. The induction of autophagy was increased in cells under H/R conditions and cells with miR‑103a‑3p inhibitor transfection, whereas the induction of autophagy was decreased in cells transfected with miR‑103a‑3p mimics. In addition, the data indicated that miR‑103a‑3p directly targeted Atg5, which regulated the induction of autophagy and apoptosis. Taken together, these findings indicate that, following the inhibition of miR‑103a‑3p, Atg5 promotes autophagy and apoptosis in cardiomyocytes by directly targeting Atg5. Therefore, miR‑103a‑3p can be considered a potential therapeutic target for myocardial ischemia. | [
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von Willebrand factor C and EGF domain‑containing protein (URG11), a cell growth regulator, is involved in the progression of a variety of types of cancer, including prostate cancer (Pca). However, the functions of the URG11 gene in Pca cells require in‑depth investigation. The mRNA and protein levels of URG11 were measured by reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. Cell Counting kit‑8 (CCK‑8), wound‑healing and Transwell assays were used to detect cell viability, migration and invasion, respectively. Apoptosis and cell cycle analyses were performed using flow cytometry. The mRNA and protein expression levels of epithelial (E)‑cadherin, vimentin, ‑smooth muscle actin (‑SMA), cyclin D1 and MYC proto‑oncogene protein (c‑Myc) were analyzed by RT‑qPCR and western blot analysis. In the present study, the mRNA and protein levels of URG11 were markedly upregulated in Pca cell lines compared with those in the normal prostate epithelial cell line. With functional experiments, the cell viability, migration and invasion of Pca cells were markedly promoted by URG11 overexpression. The cell cycle was effectively induced by URG11 and apoptosis was inhibited by the overexpression of URG11. Concomitantly, the epithelial marker E‑cadherin was downregulated, and the mesenchymal markers vimentin and ‑SMA were upregulated following URG11 overexpression. By contrast, genetic knockout of URG11 elicited the opposite effects. The present study also identified that the downstream effector genes of the Wnt/‑catenin signal pathway, cyclin D1 and c‑Myc, were increased following the overexpression of endogenous URG11, which are known to regulate cell proliferation. In addition, the Wnt/‑catenin inhibitor FH535 ameliorated the promotive effects of URG11 on LNCaP cells viability, migration and invasion, and the Wnt/‑catenin agonist LiCl reversed the inhibitory effects of siURG11 in LNCaP cells on cell viability, migration and invasion. The present study demonstrated that URG11 served an oncogenic role in the development of Pca cells and provided evidence that URG11 has potential as a novel therapeutic target in Pca. | [
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The purpose of the present study was to investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified by CXC‑chemokine receptor type 3 (CXCR3) and heme oxygenase‑1 (HO‑1) genes can repair damaged intestinal epithelial cells in vitro, and the role of the p38 mitogen‑activated protein kinase (p38‑MAPK) pathway in this process. A model of intestinal epithelial crypt cell line‑6 (IEC‑6) damage was created, and BMMSCs were transfected with either the CXCR3 and/or HO‑1 gene in vitro. There were nine experimental groups in which the damaged IEC‑6 cells were co‑cultured with differentially‑treated BMMSCs and lymphocytes for 24 h. Reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemistry and a western blot analysis were performed to detect stem cell transfection, the repair of damaged intestinal epithelial cells and the expression of related molecules in the P38‑MAPK pathway, respectively. Crystal violet staining and live cell imaging were used to detect the chemotaxis of BMMSCs. Flow cytometry was used to detect T lymphocyte activity and the surface markers expressed on BMMSCs. An ELISA was used to quantify cytokine production. The adenovirus (Ad)‑CXCR3/MSCs exhibited the characteristics of stem cells and exhibited chemotaxis. The Ad‑CXCR3/MSCs and Ad‑(CXCR3 + HO)/MSCs exhibited increased expression of tight junction protein zonula occludens‑1 (ZO‑1) and anti‑proliferating cell nuclear antigen in the damaged IEC‑6 cells, and apoptosis of the damaged IEC‑6 cells was decreased. BMMSCs inhibited the phosphorylation of p38, in addition to downstream molecules of the p38MAPK signaling pathway. The Ad‑CXCR3/MSCs and Ad‑(CXCR3 + HO)/MSCs exhibited significantly decreased expression levels of downstream molecules, including phosphorylated (p)‑p38, p‑activated transcription factor 2, p‑C/EBP homologous protein‑10, and p‑myocyte enhancer factor 2C, and target molecules (e.g., apoptotic bodies). The effects of Ad‑(CXCR3 + HO)/MSCs on the repair of the damaged intestinal tract and inhibition of the p38‑MAPK pathway was more marked than those in other groups on day 7 post‑surgery in the rejection model for small bowel transplantation. BMMSCs modified by the CXCR3 and HO‑1 genes exhibited superior ability to repair damaged intestinal epithelial cells and served this role via the p38‑MAPK pathway. | [
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Honokiol, a natural biphenolic compound, exerts anticancer effects through a variety of mechanisms on multiple types of cancer with relatively low toxicity. Adenosine 5'‑phosphate‑activated protein kinase (AMPK), an essential regulator of cellular homeostasis, may control cancer progression. The present study aimed to investigate whether the anticancer activities of honokiol in ovarian cancer cells were mediated through the activation of AMPK. Honokiol decreased cell viability of 2 ovarian cancer cell lines, with an half‑maximal inhibitory concentration value of 48.7111.31M for SKOV3 cells and 46.425.37M for Caov‑3 cells. Honokiol induced apoptosis via activation of caspase‑3, caspase‑7 and caspase‑9, and cleavage of poly‑(adenosine 5'‑diphosphate‑ribose) polymerase. Apoptosis induced by honokiol was weakened by compound C, an AMPK inhibitor, suggesting that honokiol‑induced apoptosis was dependent on the AMPK/mechanistic target of rapamycin signaling pathway. Additionally, honokiol inhibited the migration and invasion of ovarian cancer cells. The combined treatment of honokiol with compound C reversed the activities of honokiol in wound healing and Matrigel invasion assays. These results indicated that honokiol may have therapeutic potential in ovarian cancer by targeting AMPK activation. | [
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] |
Barbaloin (Bar) has a myocardial protective effect, but its mechanism of action is uncertain. The endoplasmic reticulum stress (ERS)‑mediated apoptosis pathway serves an important role in the pathogenesis of myocardial ischemia‑reperfusion injury (MIRI). Inhibiting ERS may significantly improve the progression of MIRI and serve a role in its prevention. Therefore, based on current knowledge of ERS‑mediated cardiomyocyte apoptosis and the cardioprotective effect of Bar, the purpose of the present study was to further evaluate the myocardial protective effect and potential mechanisms of Bar pretreatment in MIRI. The present study established a MIR rat model and randomly divided these rats into four groups. Prior to myocardial ischemia, Bar (20 mg/kg) was administered to rats once daily for 1 week. Myocardial blood serum lactate dehydrogenase and creatine kinase were subsequently measured. A terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay was used to evaluate the myocardial protective effect of Bar pretreatment on MIRI. To assess whether the ERS signaling pathway was involved in the myocardial protection mechanism of Bar pretreatment, the expression levels of ERS‑associated proteins, protein canopy homolog 2 (CNPY2), glucose regulatory protein 78, transcriptional activator 4, C/EBP‑homologous protein (CHOP), PKR endoplasmic reticulum kinase (PERK), caspase‑12 and caspase‑3 were detected by western blot analysis, immunohistochemistry or reverse transcription‑quantitative polymerase chain reaction. The results confirmed that Bar pretreatment significantly reduced the damage and the level of apoptosis caused by MIR. Bar pretreatment significantly inhibited the expression of ERS‑associated proteins in cardiomyocytes. In addition, the immunohistochemistry results demonstrated that Bar pretreatment significantly inhibited the CNPY2‑positive cell apoptosis ratio of cardiomyocytes. Therefore, the results of the current study suggested that CNPY2 is present in cardiomyocytes and participates in the development of MIRI by initiating the PERK‑CHOP signaling pathway. Bar pretreatment may attenuate MIRI by inhibiting the CNPY2‑PERK apoptotic pathway. | [
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Although treatment of chronic myeloid leukemia (CML) has improved with the development of tyrosine kinase inhibitors (TKIs), patients develop fatal blast crisis(BC) whilst receiving TKI treatment. Alternative treatments for cases resistant to TKIs are required. A serine/threonine protein kinase, T‑lymphokine‑activated killer cell‑originated protein kinase(TOPK), is highly expressed in various malignant tumors. Binding of peptides to human leukocyte antigen was assessed via mass spectrometry in K562 CML cells. TOPK expression was assessed in various CML cell lines and in clinical samples obtained from patients with CML using reverse transcription‑quantitative polymerase chain reaction and western blot assays. It was observed that TOPK was expressed abundantly in BCR/ABL‑positive cell lines and at significantly higher levels in CML clinical samples compared with healthy donor samples. Overexpression of BCR/ABL or the presence of its inhibitor imatinib upregulated and downregulated TOPK expression, respectively, indicating that TOPK may be a target of BCR/ABL. TOPK inhibitor OTS514 suppressed proliferation of BCR/ABL‑positive cell lines and colony formation of CD34‑positive cells from patients with CML compared with lymphoma patients without bone marrow involvement. Furthermore, phosphorylation of TOPK was increased by protein phosphatase2A(PP2A) inhibitor okadaic acid and was decreased in the presence of PP2A activator FTY720 compared with untreated samples. As constitutive BCR/ABL activity and inhibition of PP2A are key mechanisms of CML development, TOPK may be a crucial signaling molecule for this disease. Inhibition of TOPK may control disease status of CML, even in cases resistant to TKIs. | [
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] |
Lung adenocarcinoma (LA) is the most commonly occurring histological type of non‑small cell lung cancer. Diagnosis and treatment of LA remain a major clinical challenge. In the present study, to identify early LA biomarkers, extracellular vesicles (EVs) were separated from the plasma samples from 153patients with LA and 75healthy controls. microRNA (miRNA) expression profiling was performed at the screening stage (5patients with LA vs.5controls), followed by verification at the validation stage (40patients with LA vs.20controls) using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The four disordered miRNAs (miR‑505‑5p, miR‑486‑3p, miR‑486‑3p and miR‑382‑3p) identified in the plasma EVs were further evaluated at the testing stage (108patients with LA vs.50controls) by RT‑qPCR. It was revealed that miR‑505‑5p was upregulated, whereas miR‑382‑3p was downregulated, in the EVs from patients with LA. Furthermore, miR‑505‑5p was also upregulated in tumor tissues, compared with adjacent non‑tumor control tissues. Subsequently, the direct targets of miR‑505‑5p were predicted using bioinformatics analyses, and verified by luciferase assay and immunoblotting. The present study determined that miR‑505‑5p functions as an oncogene, promoting lung cancer cell proliferation and inhibiting cancer cell apoptosis via the targeting of tumor protein P53‑regulated apoptosis‑inducing protein1 (TP53AIP1). Finally, it was confirmed that miR‑505‑5p in plasma EVs could be delivered to lung cancer cells, inhibiting cell apoptosis and promoting cell proliferation by targeting TP53AIP1. In conclusion, the present study indicated that miRNA‑505‑5p functions as an oncogene that may be used as a novel biomarker for the diagnosis and treatment of LA. | [
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Preeclampsia (PE) is a pathological condition that manifests during pregnancy as the occurrence of an abnormal urine protein level and increased blood pressure due to inadequate cytotrophoblast invasion. To elucidate the mechanism underlying PE, the present study primarily focused on the regulatory effects and mechanism of the G protein 7 (GNG7) on placental cytotrophoblasts in a rat PE model. Initially, the PE model was established with 45 specific pathogen‑free Sprague‑Dawley rats (30 females and 15 males). The expression patterns of GNG7, 4E‑binding protein 1 (4E‑BP1), phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) and mammalian target of rapamycin (mTOR) were examined in the PE rats. Placental cytotrophoblasts isolated from normal and PE rats were treated with a small interfering RNA against GNG7, mTOR signaling pathway activator (HIV‑1 Tat) or inhibitor (rapamycin). Following treatment, cell proliferation, differentiation and apoptosis were evaluated, and mTOR signaling pathway‑related factors (4E‑BP1, p70S6K and mTOR), cell proliferation‑related factors (vascular endothelial growth factor and transforming growth factor‑1), differentiation‑related factors [activator protein‑2 (AP‑2) and AP‑2], and apoptosis‑related factors [B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein] were determined. Finally, soluble fms‑like tyrosine kinase 1 (sFlt‑1) and soluble endoglin (sEng) levels were measured via enzyme‑linked immunosorbent assay. Initially, the mTOR signaling pathway was inactivated in the placental tissues and cytotrophoblasts in the PE rats. Silencing GNG7 reduced the levels of sFlt‑1 and sEng and activated the mTOR signaling pathway. Silencing of GNG7 or activation of the mTOR signaling pathway enhanced cell proliferation and differentiation, but inhibited the apoptosis of placental cytotrophoblasts in the PE rats. Taken together, the results showed that GNG7 silencing repressed apoptosis and enhanced the proliferation and differentiation of placental cytotrophoblasts in PE rats through activation of the mTOR signaling pathway. | [
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Solamargine, a derivative from the steroidal solasodine in Solanum species, has exhibited anticancer activities in numerous types of cancer; however, its role in gastric cancer (GC) remains unknown. In the present study, it was demonstrated that Solamargine suppressed the viability of five gastric cancer cell lines in a dose‑dependent manner and induced notable alterations in morphology. Treatment with Solamargine promoted cell apoptosis (P<0.01). Solamargine increased the expression of long noncoding RNA (lnc) p53 induced transcript and lnc nuclear paraspeckle assembly transcript1 (NEAT1)_2 (P<0.01) in GC by reducing the phosphorylation of extracellular signal‑regulated kinase (Erk)1/2 mitogen‑activated protein kinase (MAPK). To gain insight into the potential mechanism, an Erk1/2 inhibitor (U0126) was applied. The results revealed that lncNEAT1_2 expression levels increased, which was consistent with the effects of Solamargine. Downregulation of lncNEAT1_2 in GC cells revealed no effect on the expression levels of total Erk1/2 and, and counteracted the effect of Solamargine. Solamargine was observed to increase the expression of lncNEAT1_2 via the Erk1/2 MAPK signaling pathway. Of note, the knockdown of lncNEAT1_2 reduced the inhibitory effect of Solamargine (P<0.05). Additionally, experiments invivo and in primary GC cells from patients demonstrated that Solamargine significantly suppressed tumor growth (P<0.05). Invivo analysis of a xenograft mouse model further supported that Solamargine could induce the apoptosis of cancer cells in tumor tissue as observed by a terminal deoxynucleotidyl transferase‑mediated dUTP‑biotin nick end labeling and H&E staining (P<0.05). Experiments in primary GC cells from patients verified the anti‑tumor effect of Solamargine. In summary, the findings of the present study indicated that Solamargine inhibited the progression of GC by regulating lncNeat1_2 via the MAPK pathway. | [
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Type 2 diabetes mellitus (T2DM) is a disease associated with a number of metabolic disturbances, including protein metabolism. In the present study, blood samples were obtained from Bahraini subjects, including 6 patients with T2DM and 6 age‑ and sex‑matched, non‑diabetic, healthy controls. Depleted and non‑depleted sera were prepared from the collected blood, and the global protein expression changes were evaluated by liquid chromatography tandem mass spectrometry. Only significantly and markedly differentially‑expressed proteins (P<0.05, analysis of variance; maximum fold change ?1.5) were considered as candidate proteins for informatics analysis. Accordingly, a total of 62 proteins were identified to be differentially expressed in T2DM, compared with control subjects, and they were grouped functionally into 16 classes of proteins. The largest class was that of the immune‑associated proteins. Additionally, ~25 of these proteins (40%) had previously been associated with DM; however, the association of the other 37 proteins with T2DM was a novel observation. The majority of the identified proteins were upregulated in T2DM. The identified proteins could be involved in the pathogenesis of the disease or serve as disease biomarkers. Further validation of the identified proteins in a large study cohort is required, in order to fully access their potential clinical usefulness. | [
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Family with sequence similarity 20‑memberC (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands. Fam20cf/f; Mmtv‑Cre mice were created in which Fam20c was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross‑sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of nerve growth factor, ‑amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na+, Cl- and K+ concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore, Fam20c deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia. | [
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Ovarian cancer remains the most lethal type of cancer among all gynecological malignancies. The majority of patients are diagnosed with ovarian cancer at the late stages of the disease. Therefore, there exists an imperative need for the development of early ovarian cancer diagnostic techniques. Exosomes, secreted by various cell types, play pivotal roles in intercellular communication, which emerge as promising diagnostic and prognostic biomarkers for ovarian cancer. In this study, we present for the first time, at least to the best of our knowledge, the proteomics profiling of exosomes derived from the plasma of patients with ovarian cancer via liquid chromatography tandem mass spectrometry(LC‑MS/MS) with tandem mass tagging(TMT). The exosomes enriched from patient plasma samples were characterized by nanoparticle tracking analysis(NTA), dynamic light scattering (DLS), transmission electron microscopy(TEM) and western blot analysis. The size of the plasma exosomes fell into the range of 30to100nm in diameter. The exosomal marker proteins, CD81 and TSG101, were clearly stained in the exosome samples; however, there was no staining for the endoplasmic reticulum protein, calnexin. A total of 294proteins were identified with all exosome samples. Among these, 225proteins were detected in both the cancerous and non‑cancerous samples. Apart from universal exosomal proteins, exosomes derived from ovarian cancer patient plasma also contained tumor‑specific proteins relevant to tumorigenesis and metastasis, particularly in epithelial ovarian carcinoma(EOC). Patients with EOC often suffer from coagulation dysfunction. The function of exosomes in coagulation was also examined. Several genes relevant to the coagulation cascade were screened out as promising diagnostic and prognostic factors that may play important roles in ovarian cancer progression and metastasis. On the whole, in this study, we successfully isolated and purified exosomes from plasma of patients with EOC, and identified a potential role of these exosomes in the coagulation cascade, as well as in the diagnosis and prognosis of patients. | [
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] |
MicroRNAs (miRNAs/miRs) are a class of endogenous and non‑coding RNAs that are present in eukaryotes. In previous studies, miRNAs have been revealed to have an important role in cell growth and apoptosis. In the present study, the function of a novel and rarely studied miRNA, miR‑4530, was investigated in human umbilical vein endothelial cells(HUVECs). The expression level of miR‑4530 in HUVECs was investigated using reverse transcription‑quantitative polymerase chain reaction following transfection with miR‑4530 precursor plasmids, anti‑miR‑4530 plasmids and empty vector plasmids. Following this, it was revealed that overexpression of miR‑4530 can suppress cell proliferation and enhance cell apoptosis. TargetScan analysis suggested that Ras p21 protein activator1(RASA1) is a target gene of miR‑4530. The results of a dual‑luciferase reporter assay also suggested that miR‑4530 targets RASA1. Furthermore, the results of dual‑luciferase reporter assay suggested that miR‑4530 enhanced luciferase activity of the wild-type reporter, but not the mutant RASA1 reporter activity, thus suggesting that miR‑4530 enhances the expression of RASA1. In addition, western blot analysis demonstrated that the protein expression level of RASA1 was enhanced following upregulation of miR‑4530. The exact mechanism underlying this process has not yet been determined and requires further investigation. In addition, a RASA1 overexpression plasmid vector was transfected into HUVECs. The results suggest that overexpression of RASA1 suppresses cell growth and promotes apoptosis, which was in agreement with the results regarding the overexpression of miR‑4530. To investigate how miRNA‑4530 affects cellular function, numerous proteins associated with the extracellular signal‑regulated kinase(ERK)/mitogen‑activated protein kinase (MAPK) and phosphoinositide3‑kinase(PI3K)/AKT serine/threonine kinase pathways were investigated via western blot analysis. The results suggested that miRNA‑4530 suppresses cell proliferation and enhances apoptosis by targeting RASA1 via the ERK/MAPK and PI3K/AKT signaling pathways. | [
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Previously, we demonstrated that RhizomaParidis saponins (RPS), the major active component of RhizomaParidis, may exhibit hepatoprotective effects. The present study aimed to identify the potential mechanism of RPS on hepatic injury and improvement in hepatic fibrosis (HF). A HF model was created in Sprague‑Dawley rats by administration of carbon tetrachloride. RPS was administered for treatment following creation of the HF model. The protein and mRNA expression of vascular endothelial growth factor (VEGF), platelet‑derived growth factor (PDGF), extracellular signal‑regulated kinase (ERK)1/2 and ‑smooth muscle actin (SMA) was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. RPS was demonstrated to improve hepatic inflammation and decrease HF severity according to hematoxylin and eosin and Masson trichrome staining. Following RPS treatment, the level of alanine aminotransferase, aspartate aminotransferase and malondialdehyde, and expression levels of the mRNA and protein of VEGF, ERK1/2, PDGF and ‑SMA in the model group was decreased. By contrast, the content of glutathione‑PX and superoxide dismutase was increased. These data suggest that RPS may treat HF primarily through downregulation of the expression levels of the mRNA and phosphorylated VEGF, ERK1/2, PDGF and ‑SMA proteins. | [
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The thoracic ossification of the posterior longitudinal ligament (T‑OPLL) can cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. Our previous whole‑genome sequencing study first reported rs199772854 in the interleukin 17 receptor C (IL17RC) gene as a potentially pathogenic loci for T‑OPLL. The aim of the present study was to examine the effects of the IL17RC gene rs199772854A site mutation on osteogenesis by establishing a model of osteogenic differentiation. IL17RC gene mutation site and wild‑type site mouse embryonic osteoblast (3T3‑E1) models were constructed in order to induce the differentiation of the cells into osteoblasts. Whether the mutation site causes the abnormal expression of the IL17RC gene and osteogenic markers was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The IL17RC gene rs199772854A site mutation was demonstrated to play a biological role through the overexpression of its own gene, and also to significantly increase the expression levels of osteogenic markers. Furthermore, the mutation upregulated the expression of the key proteins, tumor necrosis factor receptor (TNFR)‑associated factor 6 (TRAF6) and nuclear factor (NF)‑B, in the interleukin (IL)‑17 signaling axis. On the whole, the findings of this study suggest that the IL17RC gene rs199772854A loci mutation propels mouse embryonic osteoblasts towards osteogenic differentiation and may play an important role in the pathogenesis of T‑OPLL. The IL17RC gene may promote osteogenesis through the IL‑17 signaling pathway and may thus be involved in the process of ectopic osteogenesis in T‑OPLL. | [
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Myrica rubra is well known for its delicious taste and high nutritional value. The present study investigated the potential protective effects and mechanisms of M. rubra flavonoids (MRF) extract on isoproterenol (ISO)‑induced myocardial injury in rats and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. An in vivo study revealed that MRF decreased serum cardiac enzyme levels, ameliorated pathological heart alterations and increased the antioxidant potential. The in vitro investigation demonstrated that MRF inhibited cell death, reactive oxygen species (ROS) accumulation, mitochondrial membrane depolarization, apoptosis rate and caspase‑3 activation and enhanced the Bcl‑2/Bax ratio during H/R injury. These effects were accompanied by the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase (GSK)‑3. Further mechanism studies demonstrated that LY294002, a specific inhibitor of phosphoinositide 3‑kinase (PI3K), abolished the MRF‑mediated cardioprotection against H/R‑induced apoptosis and ROS overproduction. Collectively, these results suggested that MRF exerts cardioprotective effects by attenuating oxidative damage and cardiomyocyte apoptosis most likely via a PI3K/Akt/GSK3‑dependent mechanism. | [
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] |
The present study evaluated the association between single nucleotide polymorphism (SNP) rs3746444 and the risk of non‑small cell lung carcinoma (NSCLC) in a Chinese population. Computational analyses and luciferase assays were performed to investigate the regulatory relationship between miR‑499a and CD200. In addition, reverse transcription‑quantitative polymerase chain reaction and western blot assays were performed to examine the effect of rs3746444 on the expression of miR‑499a and CD200. The results demonstrated a significant difference in the smoking history of patients carrying malignant pulmonary nodules and those carrying benign pulmonary nodules. Furthermore, CD200 was demonstrated to be a direct target of miR‑499a, and a miR‑499a binding site was located in the 3'UTR of CD200. Notably, the levels of miR‑499a in malignant pulmonary nodules were higher compared with benign pulmonary nodules, while the levels of CD200 were higher in benign pulmonary nodules compared with malignant pulmonary nodules. In addition, the subjects carrying the AA genotype of SNP rs3746444 exhibited upregulated miR‑499a expression and reduced CD200 expression, compared with the subjects carrying AG and GG genotypes. These findings indicate that the SNP rs3746444 in miR‑499a could affect the prognosis of NSCLC patients by regulating the expression of CD200. | [
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Malignant melanoma is a highly aggressive skin cancer that is highly resistant to chemotherapy. Adjuvant therapy is administered to patients with melanoma that possess no microscopic metastases or have a high risk of developing microscopic metastases. Methylating agents, including dacarbazine(DTIC) and temozolomide(TMZ), pegylated interferon(IFN)‑2b and interleukin‑2 have been approved for adjuvant immuno‑chemotherapy; however, unsatisfactory results have been reported following the administration of methylating agents. IFN‑ has been considered to be a signaling molecule with an important therapeutic potential in cancer. The aim of the present study was to elucidate whether antitumor effects could be augmented by the combination of TMZ and IFN‑ in malignant melanoma. We evaluated the efficacy of TMZ and IFN‑ by comparing O6‑methylguanine‑DNA transferase(MGMT)‑proficient and ‑deficient cells, as MGMT has been reported to be associated with the resistance to methylating agents. Cell viability was determined by counting living cells with a Coulter counter, and apoptosis was analyzed by dual staining with AnnexinV AlexaFluor488 and propidium iodide. The expression of proteins involved in the cell cycle, apoptosis and autophagy was evaluated by western blot analysis. The combined treatment with TMZ and IFN‑ suppressed cell proliferation and induced cell cycle arrest. We also demonstrated that a combination of TMZ and IFN‑ enhanced apoptosis and autophagy more efficiently compared with TMZ treatment alone. These findings suggest that antitumor activity may be potentiated by IFN‑ in combination with TMZ. | [
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Y‑box‑binding protein1 (YB‑1) is a DNA/RNA‑-binding protein and an important transcription and translation factor in carcinogenesis. However, the biological function and molecular correlation of YB‑1 in colorectal cancer are not fully understood. The aim of the present study was to determine the significance of YB‑1 expression and its biological role in colorectal cancer. Cell proliferation, migration and apoptosis were examined upon knockdown of YB‑1 expression in different colon cancer cell lines that had different genetic backgrounds. Since the properties of different colon cancer cell lines with specific RAS/RAF gene mutations downstream epidermal growth factor receptor (EGFR) may differ from wild‑type colorectal cancer, it is critical to study the role of YB‑1 with respect to the mutational status of RAS. The results indicated that the suppression of YB‑1 decreased cell proliferation (P<0.05) and migration (P<0.05) regardless of the status of RAS/RAF in the HT29, HCT116 and CaCo2 cell lines. In contrast, YB‑1 knockdown altered the expression of apoptosis‑related genes and the expression of EGFR was detected in the cell lines expressing wild‑type RAS/RAF but not in those expressing mutated RAS/RAF. These results indicated that YB‑1 plays an important role in cell proliferation, migration, apoptosis and EGFR expression in colorectal cancer. Furthermore, apoptosis and EGFR expression may be affected by the mutational status of RAS/RAF and controlled through YB‑1. | [
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] |
The aim of the present study was to further define the role of microRNA (miR)‑590in osteoarthritis (OA) and to investigate the underlying mechanism. In brief, reverse transcription‑quantitative polymerase chain reaction was used to analyze miR‑590 expression in bone tissue samples from rats with OA. Results indicated the expression of miR‑590 was increased. miR‑590 upregulation induced apoptosis in bone cells, whereas miR‑590 downregulation reduced apoptosis of bone cells. Furthermore, miR‑590 upregulation suppressed the protein expression levels of transforming growth factor (TGF)‑1, phosphoinositide3‑kinase (PI3K) and phosphorylated (p)‑Akt in bone cells. However, downregulation of miR‑590 induced the protein expression levels of TGF‑1, PI3K and p‑Akt in bone cells. In addition, TGF‑1 attenuated the effects of miR‑590 upregulation on bone cell apoptosis and the inactivation of PI3K inhibited the effects of miR‑590 downregulation on bone cell apoptosis. Taken together, the present data suggested that miR‑590promoted apoptosis in bone cells from rats with OA by regulating the TGF‑1/PI3K signaling pathway. | [
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Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor and is highly resistant to therapy. The median survival time for patients with GBM is 15 months. GBM resistance to treatment is associated with cancer stem cells (CSCs). CD133 membrane glycoprotein is the best‑known marker of GBM CSCs. The Wnt signaling pathway plays an important role in the proliferation of all stem cells. To the best of our knowledge, the present study was the first to examine the expression levels of proteins associated with the Wnt signaling pathway in ?D133+ CSCs of human GBM. Furthermore, potential targets that may regulate ?D133+ CSCs in human GBM were investigated. The human GBM U‑87MG cell line was cultured in neurobasal medium supplemented with B27, fibroblast growth factor, epidermal growth factor and no serum. Immunohistochemical characteristics of glioma spheres were investigated based on the expression of key markers of CSCs. CD133+ cells were extracted from glioma spheres by cell sorting and then lysed. High‑performance liquid chromatography‑mass spectrometry was used for proteome analysis. Lysates of CD133‑ cells in GBM were used for comparison. The present study was the first to describe the conceptual proteome differences between GBM and CD133+ CSCs of the common pool. Major differences were identified in the glycolysis/gluconeogenesis, focal adhesion, tight junction and Wnt signaling pathways. This study aimed to analyze the crucial role that proteins of the Wnt signaling pathway play in stem cell proliferation. The identified proteins were analyzed for their association with the Wnt signaling pathway using the international open databases PubMed, Protein Analysis Through Evolutionary Relationships, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Search Tool for the Retrieval of Interacting Genes/Proteins. An increased expression of 12 proteins associated with the Wnt signaling pathway were identified in GBM CD133+ CSCs, which included catenin ‑1, disheveled associated activator of morphogenesis 1, RAC family small GTPase 2 and RAS homolog gene family member A, a number of which are also associated with adherens junctions. The Wnt signaling pathway is not upregulated in CSCs; however, the high expression levels of adenomatous polyposis coli, ‑catenin, C‑terminal binding protein (CtBP) and RuvB‑like AAA ATPase 1 (RUVBL1 or Pontin52) proteins suggest the possibility of alternative activation of specific genes in the nuclei of these cells. Calcyclin‑binding protein, casein kinase II , casein kinase II , CtBP1, CtBP2, CUL1 and RUVBL1 proteins may be used as targets for the pharmaceutical regulation of CSCs in complex GBM treatment. | [
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Cyclin‑dependent kinase 5 regulatory subunit‑associated protein 3 (CDK5RAP3 or C53) is involved in the development of various types of tumor, and alternative splicing of C53 results in numerous transcription variants that encode different isoforms. The present study aimed to clone human C53 isoform d (IC53d) and explore its role in the proliferation of gastric cancer cells. Reverse transcription‑quantitative polymerase chain reaction was used to detect the expression levels of IC53d in 80 primary gastric adenocarcinoma tissues and adjacent normal tissues. In addition, the association between IC53d and clinicopathological parameters was determined. Gastric cancer cell lines stably overexpressing IC53d were established to observe its effects on cell proliferation, invasion and migration, and on in vivo tumorigenicity, and the mechanism of action was explored. The results of the presen study demonstrated that IC53d was upregulated in gastric cancer tissues and was associated with tumor T‑stage. Furthermore, overexpression of IC53d promoted the proliferation, colony formation and G1/S phase transition of gastric cancer cells, leading to enhancement of tumorigenesis in vitro and in vivo. Overexpression of IC53d also promoted phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3 (GSK3), which increased the expression of cyclin D1. In addition, high cyclin D1 expression was associated with a significantly worse prognosis for patients compared with in patients with low cyclin D1 expression. These results indicated that IC53d may promote the phosphorylation of AKT and GSK3, which in turn may increase cyclin D1 expression, enhancing G1/S phase transition, accelerating cell cycle progression, promoting the proliferation of gastric cancer cells, and inducing a poor prognosis in patients with gastric cancer. | [
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Prostate cancer is a common type of malignancy. Given the complexity of prostate cancer and the pressing challenge of chemoresistance, the current study was conducted to investigate the effect of docetaxel (Doc) on androgen receptor (AR)‑dependent and AR‑independent prostate cancers cells. Subsequent experiments were designed to explore the mechanism underlying the Doc‑induced apoptosis. Three different human prostate cancer cell lines, namely PC‑3, LNCaP and DU‑145, were exposed to various concentrations of Doc. The cytotoxic effects of Doc were evaluated by an MTT assay, while apoptosis and cell cycle distribution were determined by flow cytometric analysis of cells stained with Annexin V‑FITC and propidium iodide. Western blot assay was also used to measure the protein levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated death promoter (Bad), total protein kinase B (Akt), phospho‑Akt and caspase‑3/9. Doc induced cytotoxicity in all three cell lines in a dose‑dependent manner. The half maximal inhibitory concentration values for the effect of Doc on PC‑3, DU‑145 and LNCaP cells were 3.72, 4.46 and 1.13nM, respectively. Furthermore, the results indicated a significant difference in Doc sensitivity between AR‑dependent and AR‑independent prostate cancer cells. Evaluation of key gene expression at protein levels revealed a notable decrease in antiapoptotic Bcl‑2 and p‑Akt levels, along with a significant increase in pro‑apoptotic Bad, caspase‑3 and caspase‑9 levels. Therefore, Doc may induce cell apoptosis in prostate cancer via various pathways. | [
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Mesenchymal stem cells (MSCs) have been demonstrated to be involved in tumor progression and the modulation of the tumor microenvironment, partly through their secretome. Extracellular vesicles(EVs) are membranous nanovesicles secreted by multiple types of cells and have been demonstrated to mediate intercellular communication in both physiological and pathological conditions. However, numerous questions still remain regarding the underlying mechanisms and functional consequences of these interactions. The purpose of this study was to investigate the effects of human umbilical cord mesenchymal stem cell‑derived EVs(hUC‑MSC‑EVs) on the proliferation, migration and invasion of human breast cancer cells. We successfully generated and identified hUC‑MSCs and hUC‑MSC‑EVs which were used in this study. The results revealed that treatment of the MDA‑MB‑231 and MCF‑7 human breast cancer cells with medium containing hUC‑MSC‑EVs significantly enhanced the proliferation, migration and invasion of the cells invitro. Treatment of the cells with medium containing hUC‑MSC‑EVs also reduced E‑cadherin expression and increased N‑cadherin expression, thus promoting the epithelial‑mesenchymal transition(EMT) of the breast cancer cells. Treatment of the breast cancer cells with extracellular signal‑regulated kinase(ERK) inhibitor prior to the interaction with hUC‑MSC‑EVs significantly reversed the enhanced proliferation, migration and invasion, as well as the EMT of the breast cancer cells induced by the hUC‑MSC‑EVs. On the whole, these data indicate that hUC‑MSC‑EVs promote the invasive and migratory potential of breast cancer cells through the induction of EMT via the ERK pathway, leading to malignant tumor progression and metastasis. Taken together, the findings of this study suggest that targeting pathways to reverse EMT may lead to the development of novel therapeutic approaches with which to combat breast cancer. | [
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Glioblastoma or gradeIV astrocytoma is the most common and lethal form of glioma. Current glioblastoma treatment strategies use surgery followed by chemotherapy with temozolomide. Despite this, numerous glioblastoma cases develop resistance to temozolomide treatments, resulting in a poor prognosis for the patients. Novel approaches are being investigated, including the inhibition of histone deacetylase6 (HDAC6), an enzyme that deacetylates ‑tubulin, and whose overexpression in glioblastoma is associated with the loss of primary cilia. The aim of the present study was to treat glioblastoma cells with a selective HDAC6 inhibitor, tubastatinA, to determine if the malignant phenotype may be reverted. The results demonstrated a notable increase in acetylated ‑tubulin levels in treated cells, which associated with downregulation of the sonic hedgehog pathway, and may hypothetically promote ciliogenesis in those cells. Treatment with tubastatinA also reduced glioblastoma clonogenicity and migration capacities, and accelerated temozolomide‑induced apoptosis. Finally, HDAC6 inhibition decreased the expression of mesenchymal markers, contributing to reverse epithelial‑mesenchymal transition in glioblastoma cells. | [
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Gastric cancer is one of the most common malignant tumors in the world. Due to the lack of early diagnosis and effective treatment, the outcome of treatment and prognosis is poor. MicroRNA‑145 (miR‑145) is downregulated in various cancer types. In the present study, miR‑145 expression was detected by reverse transcription‑quantitative polymerase chain reaction in gastric cancer cell lines and normal gastric epithelial cells. The function of miR‑145 in the gastric cancer cell line SGC‑7901 was investigated. The present results demonstrated that the expression of miR‑145 was downregulated in gastric cancer cells. Further analysis identified that upregulation of miR‑145 significantly suppressed SGC‑7901 cell proliferation, increased cellular apoptosis and blocked the cell cycle in the G1 phase. Additionally, overexpression of miR‑145 reduced SGC‑7901 cell invasion and metastasis invitro. Western blot analysis demonstrated that overexpression of miR‑145 downregulated Myc proto‑oncogene protein, phosphoinositide 3‑kinase/protein kinase B and matrix metalloproteinase 2/9, and upregulated p21 in SGC‑7901 cells. The present results revealed potential signaling pathways that miR‑145 may use to regulate gastric cancer cell proliferation, apoptosis and metastasis. Collectively, the present results suggest that miR‑145 is a tumor suppressor for gastric cancer and it may be a potential therapeutic target for gastric cancer treatment. | [
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] |
MicroRNAs (miRNAs) serve important roles in drug‑resistance; however, exosomal miRNAs associated with drug‑resistance in ovarian cancer (OC) have not been reported to date. The current study aimed to analyze the drug resistance‑associated exosomal miRNAs in original OC cells and their derived exosomes using microarray data downloaded from the Gene Expression Omnibus database (series GSE76449). The chemosensitive OC cell lines SKOV3_ip1, A2780_PAR and HEYA8, as well as the chemoresistant cell lines SKOV3_TR, A2780_CP20 and HEYA8_MDR, were investigated. Differentially expressed miRNAs (DE‑miRNAs) were identified using the limma method, and their mRNA targets were predicted using the miRWalk and LinkedOmics database. Functions of target genes were analyzed with DAVID tool, while TCGA data were used to explore the survival association of identified miRNAs. According to the results, 28DE‑miRNAs were found to be common in exosomal and original samples of A2780_CP20 cells, among which the functions of 5 miRNAs were predicted (including miR‑146b‑5p, miR‑509‑5p, miR‑574‑3p, miR‑574‑5p and miR‑760). In addition, 16and 35DE‑miRNAs were detected for HEYA8_MDR and SKOV3_TR, respectively, with the functions of 4 of these miRNAs predicted for each cell line (HEYA8_MDR: miR‑30a‑3p, miR‑30a‑5p, miR‑612 and miR‑617; SKOV3_TR: miR‑193a‑5p, miR‑423‑3p, miR‑769‑5p and miR‑922). It was also reported that miR‑183‑5p was the only one common miRNA among the three cell lines. Furthermore, miR‑574‑3p, miR‑30a‑5p and miR‑922 may regulate CUL2 to mediate HIF‑1 cancer signaling pathway, while miR‑183‑5p may modulate MECP2, similar to miR‑760, miR‑30a‑5p and miR‑922, to influence cell proliferation. Finally, the downregulated miR‑612 may promote the expression of TEAD3 via the Hippo signaling pathway, and this miRNA was associated with poor prognosis. In conclusion, the findings of the present study suggested several underlying miRNA targets for improving the chemotherapy sensitivity of OC. | [
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Chronic lymphocytic leukemia (CLL) treatment is improving; however, some patients do not respond to therapy. Due to the high heterogeneity in disease development, there is an urgent need for personalization of therapy. In the present study, the response of leukemic mononuclear cells to anticancer drugs used for CLL treatment (cladribine+mafosfamide; CM or CM combined with rituximab; RCM) was compared with the response to new cyclin‑dependent kinase(CDK) inhibitors: BP14 and BP30. Viable apoptotic and necrotic cells were quantified by flow cytometry using propidium iodide and Yo‑Pro stains. CDK inhibitors were studied in several doses to determine the reduction of necrosis and simultaneous increase of apoptosis in leukemic cell incubations with anticancer agents. The distinct cell response to applied doses/anticancer agents was observed. Results obtained in the current manuscript confirmed that modulation of doses is important. This was particularly indicated in results obtained at 24h of cells incubation with anticancer agent. While an important time for analysis of anticancer response efficacy (monitoring of apoptosis induction potential) seems to be 48h of cells exposition to anticancer agents. High variability in response to the drugs revealed that both the nature and the dose of the anticancer agents could be important in the final effect of the therapy. The present findings support the thesis that personalized medicine, before drug administration in the clinic, could be important to avoid the application of ineffective therapy. | [
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Myocardial edema is divided into cellular edema and interstitial edema; however, the dynamic change of cardiomyocyte edema has not been described in detail. Pigment epithelium‑derived factor (PEDF) is known for its protective effects on ischemic cardiomyocytes; however, the association between PEDF and cardiomyocyte edema remains to be fully elucidated. In the present study, rat neonatal left ventricular cardiomyocytes were isolated and treated with oxygen‑glucose deprivation (OGD) and recovery. During OGD and recovery, the cardiomyocytes exhibited significant edema following 30 min of OGD (OGD 30 min) and OGD 30 min with recovery for 6 h. PEDF significantly decreased the lactate content and extracellular acidification rate of the OGD‑treated cardiomyocytes, thereby reducing cellular osmotic gradients and preventing the occurrence of cell edema. In addition, the glycolytic agonist, fructose‑1, 6‑diphosphate, eliminated the effect of PEDF on inhibiting edema in the OGD‑treated cardiomyocytes. Furthermore, PEDF reduced the protein and mRNA expression of aquaporin 1 (AQP1), and thus downregulated cardiomyocyte edema during the OGD/recovery period. The addition of AQP1 agonist, arginine vasopressin, inhibited the inhibitory effect of PEDF on cardiomyocyte edema during OGD/recovery. In conclusion, the present study revealed a novel mechanism for the regulation of cardiomyocyte edema by PEDF involving lactate levels and the expression of AQP1 during OGD/recovery. The reduction of lactate content during OGD was associated with a decrease in the protein level of AQP1 during OGD/recovery; therefore, PEDF decreased cardiomyocyte edema and cellular apoptosis, prolonging the viability of the cells. | [
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Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder of the central nervous system that causes severe cognitive impairment. One of the most significant pathological features of AD is the accumulation of ‑amyloid (A) peptide in the brain. Resveratrol (Res) is a polyphenol derived from peanuts, red grapes and other plants, which has received increasing attention due to its neuroprotective features. Tg6799 mice are transgenic mice with five familial AD (FAD) mutations that are also known as 5XFAD mice. The present study aimed to investigate the effects of Res on Tg6799 mice. The transgenic mice were randomly divided into the Res treatment group and the vehicle control group, and were treated with 0.5% Res solution (60mg/kg) or volume‑matched normal saline, respectively. Treatment was administered by oral gavage daily for 60 consecutive days. Res reduced amyloid plaque formation and the levels of A42, and ‑secretase 1 levels were also significantly decreased. Furthermore, Res was able to reduce the expression of amyloid precursor protein and its cleavage products. The administration of Res to Tg6799 mice also improved their spatial working memory, as measured by the Y‑maze test, and rescued spatial memory deficits, as measured using the Morris water maze test; however, Res did not affect their motor function. In conclusion, this study suggested that Res may reduce A‑induced neuronal damage, thus preventing memory loss. | [
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Butyrate, a histone deacetylase inhibitor, is a typical short chain fatty acid produced by gut microbiota, the dysmetabolism of which has been consistently associated with colorectal diseases. However, its role in tumorigenesis and progression of colorectal cancer cells remains under‑investigated. The present study examined the antitumor function of butyrate in the colorectal cancer cell line HCT116 and investigated the underlying molecular mechanism. MTT assay was used to measure cell proliferation and ELISA assay was used to determine cell apoptosis by measuring histone release and caspase‑3 activation. The results demonstrated that butyrate treatment significantly inhibited proliferation and induced apoptosis in HCT116 cells with an increased B‑cell lymphoma-2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio. Western blotting demonstrated that the phosphorylation of mammalian target of rapamycin (mTOR) at Ser2448, ribosomal protein S6 kinase‑1 (S6K1) at Thr389, S6 at Ser235/236 and expression of silent mating type information regulation2 homolog(SIRT)1 were decreased following butyrate treatment, while the acetylation of S6K1 was indicated to be increased. Silencing of SIRT1 by small interfering RNA technology demonstrated a similar inhibition on growth, induction of apoptosis, elevation of S6K1 acetylation and deactivation of mTOR/S6K1 signaling. Butyrate treatment also enhanced the inhibition of SIRT1 silencing on cell proliferation and activity of mTOR/S6K1. The activation of mTOR/S6K1 signaling and upregulation of cell proliferation mediated by overexpression of SIRT1 were blocked by butyrate. These data suggested that butyrate inhibited proliferation and induced apoptosis in HCT116 cells by deactivating mTOR/S6K1 signaling, possibly through its inhibition of SIRT1. | [
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