Fusarium infection causes genotoxic disorders and antioxidant-based damages in Orobanche spp.

Abstract: This study aims to evaluate the toxic effects of Fusarium oxysporum on root parasitic weed, Orobanche spp. Comparative genetic and gene expression studies were conducted on uninfected and fungus-infected orobanches. In genetic studies, isolated total DNA was amplified by RAPD PCR. Fragment properties were analysed by GTS test. According to the results, the fragment properties of control and Fusarium infected (experimental) groups varied widely; and it has been observed that Fusarium has genotoxic effects on the DNA of orobanches. In gene expression studies, the expression levels of genes encoding enzymes or proteins were associated with ROS damage and toxic effects, therefore, gene expressions of Mn-superoxide dismutase (SOD), Zn-superoxide dismutase (=SOD2, mitochondrial), glutamine synthetase (GS), heat shock protein gene (HSP70), BAX, Caspase-3 and BCL2 were significantly higher in the experimental group. In the light of obtained data, it was concluded that F. oxysporum (1) caused heavy ROS damage in Orobanche (2) induced significant irrevocable genotoxic effects on the DNA of Orobanche, (3) degraded protein metabolism and synthesis, and finally (4) triggered apoptosis. The results of this study can be a ground for further research on reducing the toxic effects of Fusarium on agricultural products, so that advancements in bio-herbicide technology may provide a sustainable agricultural production.

D018506:Gene Expression Regulation, Plant

D019105:Random Amplified Polymorphic DNA Technique

Biocontrol
Broomrape
Mycoherbicide
Parasitic plant


Rapid analgesia for prehospital hip disruption (RAPID): protocol for feasibility study of randomised controlled trial.

Abstract:
BACKGROUND
Adequate pain relief at the point of injury and during transport to hospital is a major challenge in all acute traumas, especially for those with hip fractures, whose injuries are difficult to immobilise and whose long-term outcomes may be adversely affected by administration of opiate analgesics. Fascia iliaca compartment block (FICB) is a procedure routinely undertaken by doctors and nurses in the emergency department for patients with hip fracture but not yet evaluated for use by paramedics at the scene of emergency calls. In this feasibility study, we aim to test whether FICB administered by paramedics at the scene of participants' hip fractures is feasible, safe and acceptable. This will enable us to decide whether to proceed to a fully powered, multi-centre pragmatic randomised trial to evaluate whether the procedure is effective for patients and worthwhile for the NHS.

METHODS/DESIGN
In this study, we propose to recruit ten paramedics in an urban area of South Wales. We will train them to carry out FICB when they attend patients with hip fracture. We will randomly allocate eligible patients to FICB or usual care using audited scratch cards. We will follow up participants to assess measurability of key outcomes including quality of life, pain scores, adverse events, length of stay in hospital, acceptability to patients and compliance of paramedics. We will assess whether the findings meet specified feasibility criteria and, if so, plan a full trial.

DISCUSSION
This study will enable us to recommend whether to undertake a definitive trial of FICB by paramedics for hip fracture.

TRIAL REGISTRATION
ISRCTN60065373.

Bulger|Jenna K|JK|
Brown|Alan|A|
Evans|Bridie A|BA|
Fegan|Greg|G|
Ford|Simon|S|
Guy|Katy|K|
Jones|Sian|S|
Keen|Leigh|L|
Khanom|Ashrafunnesa|A|
Pallister|Ian|I|
Rees|Nigel|N|
Russell|Ian T|IT|
Seagrove|Anne C|AC|
Snooks|Helen A|HA|

Analgesia
Prehospital
Pain
Hip fracture
Paramedic
Fractured neck of femur


Cross-Cultural Adaptation and Psychometric Properties of the Malay Version of the Communication Skills Attitude Scale (CSAS) among Medical Students in Malaysia.

Abstract: Communication is one of the fundamental skills in the medical profession. The Communication Skills Attitude Scale (CSAS) is a widely used questionnaire to measure the attitudes of medical students toward learning communication skills. It has been adapted and translated into many languages. The objective of this study was to adapt and translate the CSAS into the Malay language and determine its psychometric properties in medical students. This is a cross-sectional study involving 218 first-year Universiti Teknologi MARA students. Content validation, cross-cultural adaptation, translation, and face validation of the 26-item CSAS were performed according to established guidelines. Principal component analysis with direct oblimin rotation was used to determine the underlying structure of the CSAS-Malay. The reliability was assessed using Cronbach's α coefficient for internal consistency and using the intraclass correlation coefficient for the test-retest reliability. Although the contents of the CSAS-Malay and the original version were conceptually equivalent, item 11 was removed during the content validation stage due to a low item content validity index (I-CVI < 1.00). Two subscales were derived from the remaining 25 items, which were the Positive Attitude Scale and the Negative Attitude Scale. Items 1 and 15 were removed due to poor factor loadings. The total variance explained by the final two-factor solution with three items removed was 30.8%. Cronbach's α coefficients for both the Positive and Negative Attitude Scales in the final questionnaire were 0.815 and 0.614, respectively. It also showed a good reproducibility with intraclass correlation coefficient (ICC) values of 0.725-0.950 for all the items. This study provided preliminary information about the psychometric properties of the CSAS-Malay. The final 23-item questionnaire had a good construct validity, an acceptable internal consistency, and at least a moderate test-retest reproducibility. It can be used to assess the attitudes of medical students toward learning communication skills. Future research to improve the generalizability of the questionnaire should include medical students from other universities with diverse backgrounds.

cross-cultural adaptation
Malay version
communication skill attitude scale
communication skills
attitude
medical student
medical education
validation study


An exploration of interpersonal violence among Holocene foragers of Southern Africa.

Abstract: A common assertion that humans are inherently aggressive toward one another is based in part on interpretation of anthropological evidence, including observational reports of Khoesan immediate-return hunter-gatherers of southern Africa. Bioarchaeological evidence from 446 dated South African Cape Holocene skeletons representing Khoesan ancestors provides an opportunity to review approaches to interpersonal conflict over thousands of years. A synthesis of paleodemographic and skeletal information suggests a complex picture. The pattern noted among descendant Khoesan groups of male killings via poison arrows is not discernable in ancestral demography. Published reports of healed cranial trauma are not geographically localized; most are adult men, and some can be parsimoniously explained as the outcomes of accidents. Skeletons with unhealed perimortem lesions are limited to the southwestern region, at dates around 2500 years ago; most are women and children. The perimortem skeletal trauma is contemporaneous with a period during which a transitory decline in adult stature occurs throughout the Cape but not in the region with the apparent violence. This suggests a novel, transient social pattern in that community. In sum, the disparate patterns of antemortem and perimortem trauma among these Holocene foragers support a narrative that emphasizes the situational nature, and the general rarity, of interpersonal violence.

Hunter-gatherers
Trauma
Bone healing
Coastal adaptations
Fractures
Murder


VEGF promotes cardiac stem cells differentiation into vascular endothelial cells via the PI3K/Akt signaling pathway.

Abstract: Recent research suggested that cardiac stem cells (CSCs) may have the clinical application for cardiac repair. However, their characteristics and the regulatory mechanisms of their growth and differentiation have not been fully investigated. Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of physiological and pathological angiogenesis. But the homing role of VEGF for CSCs is unclear. In this report, CSCs were isolated, purified, and expanded in vitro from rat heart. VEGF, SU5416 (VEGF receptor blocker), and Wortmannin (PI3K/Akt signaling pathway inhibitor) were used for differentiation into vascular endothelial cells (VECs). Real-time qPCR was selected to confirm the role of PI3K/Akt signaling pathway in VECs differentiation from rat CSCs. The result of real-time qPCR demonstrated that PI3K/Akt signaling pathway plays an important role in rat CSCs differentiated into VECs. So, our research provides a theoretical basis and experimental evidence for therapeutic application of rat CSCs to treat cardiac repair.

Xiao|Nuan|N| Qi|Xiao-Yong|XY| Tang|Lu-Ning|LN| Tan|Li-Li|LL| Chen|Ya-Qing|YQ| Zhao|Hong-Mei|HM|

D040262:Receptors, Vascular Endothelial Growth Factor

D042461:Vascular Endothelial Growth Factor A

cardiac stem cells
vascular endothelial cells
PI3K/Akt signaling pathway
rat


Electrical muscle stimulation: Application and potential role in aging society.

Abstract: Neurodegenerative diseases and sarcopenia become more prevalent as individuals age and, therefore, represent a serious issue for the healthcare system. Several studies have reported the relationship between physical activity and reduced incidence of dementia or cognitive deterioration. Thus, exercise and strength training are most recommended treatments, but it is proving difficult to engage individuals to initiate exercise and strength training. Electrical muscle stimulation (EMS) may provide an alternative and more efficient solution. Although EMS has undergone a decline in use, mainly because of stimulation discomfort, new technologies allow painless application of strong contractions. Such activation can be applied in higher exercise dosages and more efficiently than people are likely to achieve with exercise. Unlike orderly recruitment of motor units (MUs) during low intensity voluntary exercise, EMS activates large fast-twitch MUs with glycolytic fibers preferentially and this could have benefit for prevention and treatment of diabetes and chronic diseases associated with muscle atrophy that ultimately lead to bed-ridden conditions. Recent evidence highlights the potential for EMS to make a major impact on these and other lifestyle related diseases and its role as a useful modality for orthopedic and cardiac rehabilitation. This paper will discuss the potential for EMS to break new ground in effective interventions in these frontiers of medical science.

Electrical Muscle Stimulation
Aging
Sarcopenia
Muscle Hypertrophy
Muscle Training


Enzymatic synthesis of 2'-O-methylribonucleosides with a nucleoside hydrolase family enzyme from Lactobacillus buchneri LBK78.

Abstract: 2'-O-Methylribonucleosides (2'-OMe-NRs) are promising raw materials for the production of nucleic acid drugs. We previously reported that LbNH, a nucleoside hydrolase from Lactobacillus buchneri LBK78 (NITE P-01581), was the first enzyme found to act on 2'-OMe-NRs. In the present study, we determined that LbNH also has the transribosylation activity between 2'-OMe-NRs and nucleobases, in addition to the hydrolyzing activity towards 2'-OMe-NRs. When 2'-O-methyluridine (2'-OMe-UR) and adenine were reacted with LbNH, 2'-O-methyladenosine (2'-OMe-AR) was produced. LbNH preferred purine nucleobases as its acceptor substrates for the transribosylation with 2'-OMe-UR as a donor substrate. Kinetic analysis of LbNH revealed that adenine behaved as a mixed inhibitor of the hydrolysis of 2'-OMe-UR. Under the optimal reaction conditions, the maximum molar yield of enzymatic 2'-OMe-AR produced reached 0.97% towards 2'-OMe-UR, corresponding to 0.16 g/L.

Mitsukawa|Yuuki|Y| Hibi|Makoto|M| Matsutani|Narihiro|N| Horinouchi|Nobuyuki|N| Takahashi|Satomi|S| Ogawa|Jun|J|

Nucleoside hydrolase
Lactobacillus buchneri
Nucleic acid drugs
Transribosylation
2′-O-Methylribonucleosides


Thermal conduction of titanium implants under CO2 laser irradiation in vitro.

Abstract:
OBJECTIVE
The surgical exposure of dental implants can be performed by means of scalpel, punch, or, with less bleeding, by means of CO2 laser. Possible overheating of the peri-implant bone tissue should be avoided. The goal of this study was to examine the temperature changes on implants under CO2 laser irradiation (Luxar CO2 20 SP laser from POLYMED, Glattbrugg, Switzerland).

STUDY DESIGN
Straumann(®) implants were irradiated with continuous wave (cw), continuous wave with super-pulse (cw/sp), and pulsed wave (pw). The irradiation power was 4, 5, 6, 7, 8, 9, and 10 W and the irradiation times were 10, 20, 30, and 60 s. Similar temperature changes occurred in cw/sp mode and cw mode, but substantially higher temperatures appeared in pulsed wave mode.

RESULTS
The quickest temperature changes were observed with cw/sp irradiation (+0.5°C to +41.1°C, depending on the irradiation parameters). Beyond 20 s and 8 W irradiation, a rise exceeding 10°C on the implant surface was found.

CONCLUSIONS
Implant diameter and length as well as the setting parameters of the CO2 laser (irradiation power, irradiation time, and irradiation mode) are important factors to consider so that risk-free implant exposure can be accomplished. Ignoring these factors causes a risk of pathological heating of the irradiated implants and thus the surrounding tissue, which can result in the loss of an implant.

Lambrecht|J Thomas|JT|
Nyffeler|Tino|T|
Linder|Manuela|M|

thermal conduction
CO2 laser
titanium dental implant


Dopamine and uric acid electrochemical sensor based on a glassy carbon electrode modified with cubic Pd and reduced graphene oxide nanocomposite.

Abstract: A cubic Pd and reduced graphene oxide modified glassy carbon electrode (Pd/RGO/GCE) was fabricated to simultaneously detect dopamine (DA) and uric acid (UA) by cyclic voltammetry (CV) and different pulse voltammetry (DPV) methods. Compared with Pd/GCE and RGO/GCE, the Pd/RGO/GCE exhibited excellent electrochemical activity in electrocatalytic behaviors. Performing the Pd/RGO/GCE in CV measurement, the well-defined oxidation peak potentials separation between DA and UA reached to 145mV. By using the differential pulse voltammetry (DPV) technique, the calibration curves for DA and UA were found linear with the concentration range of 0.45-421μM and 6-469.5μM and the detection limit (S/N =3) were calculated to be 0.18μM and 1.6μM, respectively. Furthermore, the Pd/RGO/GCE displayed high selectivity when it was applied into the determination of DA and UA even though in presence of high concentration of interferents. Additionally, the prepared electrochemical sensor of Pd/RGO/GCE demonstrated a practical feasibility in rat urine and serum samples determination.

Wang|Jin|J| Yang|Beibei|B| Zhong|Jiatai|J| Yan|Bo|B| Zhang|Ke|K| Zhai|Chunyang|C| Shiraishi|Yukihide|Y| Du|Yukou|Y| Yang|Ping|P|

Dopamine
Uric acid
Graphene
Electrochemical detection
Pd nanocubes


Surface conditioning of additively manufactured titanium implants and its influence on materials properties and in vitro biocompatibility.

Abstract: Customized osteosynthesis materials of titanium alloy can be generated by additive manufacturing replacing the complex adaptation to the patient individual anatomy, especially to the lower jaw bone which shows a highly individual surface area. After printing further conditioning is necessary to adjust surface roughness. The aim of the present study was to analyse the effect of different grinding and polishing procedures on sample surface and composition and in vitro biocompatibility. Ti-6Al-4V ELI samples printed by laser powder bed fusion (LPBF) were post-treated by multi-level procedures to adjust surface roughness using the surface conditioning technologies sandblasting, vibratory finishing, electro polishing or plasma polishing. Topography and chemical composition of the surfaces was analysed. Furthermore, the release of metal ions in contact to cell culture medium was quantified. Human osteoblasts as well as primary human gingiva cells (fibroblasts and epithelial cells) were cultivated in extracts or directly on the surfaces to analyse cytotoxicity, cell adhesion and cell proliferation. Surface roughness of the different materials after final polishing was in between 0.2 and 0.5 μm, which is in the same range as usually found for conventional titanium materials used in maxillofacial surgery. Furthermore, the wettability was comparable for all post-processing techniques. The chemical compositions of the finished surfaces showed a remarkable impact by the applied finishing technique. Extracts of the samples showed low cytotoxicity with exception of the plasma polished samples, which were shown to release significantly higher amounts of vanadium ions. Accordingly, cells showed good adhesion and proliferation on all samples except plasma polished specimens. Customized devices for midline osseodistraction were exemplarily printed with LPBF starting with patient's 3D data. Those devices can be considered for clinical use, since the printed and finished material meets the requirements of ISO 10993-5 for medical devices.

Bernhardt|Anne|A| Schneider|Jakob|J| Schroeder|Andreas|A| Papadopoulous|Kiriaki|K| Lopez|Elena|E| Brückner|Frank|F| Botzenhart|Ute|U|

Ti-6Al-4V
Laser powder bed fusion
Electro polishing
Plasma polishing
Vanadium
Vibratory polishing


Laparoscopic resection of a gastrointestinal stromal tumor that recurred more than 15 years after surgery using lighted ureteral catheters: A case report.

Abstract: A 69-year-old woman underwent abdominoperineal resection for a gastrointestinal stromal tumor (GIST) of the rectum 15 years ago. She received adjuvant chemotherapy for 8 years. Seven years later, abdominal computed tomography revealed a soft-tissue shadow in the left lower abdomen, and fluorodeoxyglucose uptake was observed at the same site on positron emission tomography. The recurrence of GIST was suspected, and laparoscopic resection was performed. Laparoscopy showed that the tumor was located at the retroperitoneum near to the descending colon and invaded the left ovarian vessels. It also made contact with the left ureter; however, lighted ureteral catheters enabled us to identify and preserve the left ureter. An immunohistochemical examination revealed the recurrence of GIST. Recurrence may become apparent 15 years or more after GIST surgery, and, thus, a long-term follow-up is required. Lighted ureteral catheters were useful for identifying the ureter and preventing ureteral injury in a recurrent case suspected of invading the ureter.

gastrointestinal stromal tumor
laparoscopic surgery
neoplasm recurrence


Diagnosis and Treatment of Aplastic Anemia.

Abstract: Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of early hematopoietic cells. Diagnosis of AA requires a comprehensive approach with prompt evaluation for inherited and secondary causes of bone marrow aplasia, while providing aggressive supportive care. The choice of frontline therapy is determined by a number of factors including AA severity, age of the patient, donor availability, and access to optimal therapies. For newly diagnosed severe aplastic anemia, bone marrow transplant should be pursued in all pediatric patients and in younger adult patients when a matched sibling donor is available. Frontline therapy in older adult patients and in all patients lacking a matched sibling donor involves immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporine A. Recent improvements in upfront therapy include encouraging results with closely matched unrelated donor transplants in younger patients and the emerging benefits of eltrombopag combined with initial IST, with randomized studies underway. In the refractory setting, several therapeutic options exist, with improving outcomes of matched unrelated donor and haploidentical bone marrow transplantation as well as the addition of eltrombopag to the non-transplant AA armamentarium. With the recent appreciation of frequent clonal hematopoiesis in AA patients and with the growing use of next-generation sequencing in the clinic, utmost caution should be exercised in interpreting the significance of somatic mutations in AA. Future longitudinal studies of large numbers of patients are needed to determine the prognostic significance of somatic mutations and to guide optimal surveillance and treatment approaches to prevent long-term clonal complications.

Peslak|Scott A|SA|
Olson|Timothy|T|
Babushok|Daria V|DV|

D018380:Hematopoietic Stem Cell Transplantation

Aplastic anemia
Bone marrow failure
Bone marrow transplant
Immunosuppressive therapy
Antithymocyte globulin
Eltrombopag
Clonal hematopoiesis
Cyclosporine A


Establishment of a risk assessment tool for pregnancy-associated venous thromboembolism and its clinical application: protocol for a prospective observational study in Beijing.

Abstract:
BACKGROUND
The risk of venous thromboembolism (VTE) during pregnancy and puerperal periods is significantly higher than during the non-pregnant period and is one of the major causes of maternal mortality. Developed countries have promulgated guidelines for risk assessment and prevention of maternal VTE, and standardized management has led to a significant reduction in maternal mortality. However, there is a paucity of relevant research related to pregnancy and puerperal VTE in China.

METHODS/DESIGN
We will perform a prospective cohort study and recruit 13,000 pregnant women from 2018 to 2020 in Beijing, China. VTE risk assessment will be conducted using the Royal College of Obstetricians and Gynaecologists (RCOG) pregnancy and puerperal VTE risk-assessment-scoring tool during early and late pregnancy, as well as during the puerperal period. Venous ultrasonography of lower extremities, routine blood tests, and coagulation parameters will be examined. These VTE risk assessments will be performed again if patients have VTE-related symptoms during their pregnancies, or if any of the following occur: (1) patients are hospitalized over 7 days due to any pregnancy complications; (2) patients are placed under strict bed rest for ≥ 3 days to prevent miscarriage. For patients with a confirmed diagnosis of VTE, treatment and follow-up plans will be decided jointly by the obstetricians, vascular surgeons, and pulmonologists. All patients in the study will be followed up by dedicated healthcare providers for up to 42 days postpartum. Statistical analyses will be performed to test the feasibility of the RCOG scoring tool for the Chinese population. The RCOG scoring tool will then be revised based upon the characteristics of the Chinese population, and the revised assessment scoring tool will then be tested in the cohort to evaluate its efficacy. Finally, a pregnancy and puerperal VTE risk-assessment tool will be proposed based on our study results.

DISCUSSION
This study will establish a preliminary VTE risk-assessment tool that is applicable to pregnant and puerperal women in China and provide guidelines for further thrombophylactic interventions. Furthermore, we wish to draw increased attention to pregnancy-associated VTE to reduce VTE-related mortality.

TRIAL REGISTRATION
Chi CTR1800015848 (04/24/2018).

Pregnancy-associated
Venous thromboembolism
Pregnancy and puerperal


Sesquiterpene Synthase-3-Hydroxy-3-Methylglutaryl Coenzyme A Synthase Fusion Protein Responsible for Hirsutene Biosynthesis in Stereum hirsutum.

Abstract: The wood-rotting mushroom Stereum hirsutum is a known producer of a large number of namesake hirsutenoids, many with important bioactivities. Hirsutenoids form a structurally diverse and distinct class of sesquiterpenoids. No genes involved in hirsutenoid biosynthesis have yet been identified or their enzymes characterized. Here, we describe the cloning and functional characterization of a hirsutene synthase as an unexpected fusion protein of a sesquiterpene synthase (STS) with a C-terminal 3-hydroxy-3-methylglutaryl-coenzyme A (3-hydroxy-3-methylglutaryl-CoA) synthase (HMGS) domain. Both the full-length fusion protein and truncated STS domain are highly product-specific 1,11-cyclizing STS enzymes with kinetic properties typical of STSs. Complementation studies in Saccharomyces cerevisiae confirmed that the HMGS domain is also functional in vivo Phylogenetic analysis shows that the hirsutene synthase domain does not form a clade with other previously characterized sesquiterpene synthases from Basidiomycota. Comparative gene structure analysis of this hirsutene synthase with characterized fungal enzymes reveals a significantly higher intron density, suggesting that this enzyme may be acquired by horizontal gene transfer. In contrast, the HMGS domain is clearly related to other fungal homologs. This STS-HMGS fusion protein is part of a biosynthetic gene cluster that includes P450s and oxidases that are expressed and could be cloned from cDNA. Finally, this unusual fusion of a terpene synthase to an HMGS domain, which is not generally recognized as a key regulatory enzyme of the mevalonate isoprenoid precursor pathway, led to the identification of additional HMGS duplications in many fungal genomes, including the localization of HMGSs in other predicted sesquiterpenoid biosynthetic gene clusters.IMPORTANCE Hirsutenoids represent a structurally diverse class of bioactive sesquiterpenoids isolated from fungi. Identification of their biosynthetic pathways will provide access to this chemodiversity for the discovery and synthesis of molecules with new bioactivities. The identification and successful cloning of the previously elusive hirsutene synthase from the S. hirsutum provide important insights and strategies for biosynthetic gene discovery in Basidiomycota. The finding of a terpene synthase-HMGS fusion, the discovery of other sesquiterpenoid biosynthetic gene clusters with dedicated HMGS genes, and HMGS gene duplications in fungal genomes give new importance to the role of HMGS as a key regulatory enzyme in isoprenoid and sterol biosynthesis that should be exploited for metabolic engineering.

D015971:Gene Expression Regulation, Enzymologic


A Time to Reflect and a Time to Move Forward.

Abstract: The winter solstice marks the astronomical moment when the sun is aligned over the Tropic of Capricorn. On December 21, those who live in the Northern Hemisphere had the shortest day and longest night of the year. This was accompanied in 2020 by a rare alignment of Jupiter and Saturn, which appeared as a singular bright point of light in the night sky for the first time since the Middle Ages. Although many cultures celebrate the winter solstice, the solstice is mostly overlooked in the United States, largely because of the multitude of other holidays around this time of the year. However, the shortest day and longest night seems like a metaphor of sorts for a year like no other in the memory of most-a fitting end and a pause. From the stillness, we can reflect in the space between the past and the future, reviewing the year behind us while appreciating the challenges to be faced in 2021.

COVID-19
health disparities
nurse education
oncology nursing
pandemic
personal protective equipment


Regenerative Endodontic Treatment with Orthodontic Treatment in a Tooth with Dens Evaginatus: A Case Report with a 4-year Follow-up.

Abstract: Dens evaginatus is a developmental tooth anomaly in which an extra cusp or tubercle protrudes on the occlusal surface of the tooth along with some pulpal tissue. Because of the fragile nature of the protrusion, these teeth are often at risk of pulpal exposure. When this occurs in an immature tooth, regenerative endodontic treatment may be a good treatment approach to promote root formation. There is limited literature that documents the occurrence of orthodontic treatment in teeth that have undergone regenerative endodontic therapy using triple antibiotic paste. Here we present a case of an immature premolar tooth with dens evaginatus that was diagnosed with pulp necrosis and chronic apical abscess. The tooth was treated with regenerative endodontic treatment; after which, the patient received orthodontic treatment with fixed appliances for 2 years. The tooth responded favorably to the regenerative endodontic treatment and orthodontic tooth movement. Clinically and radiographically, all the follow-up examinations revealed an asymptomatic tooth with evidence of periapical healing with stunted root development. The tooth remained asymptomatic even after 4 years. The regenerative endodontic procedure (REP) was successful in treating an immature permanent premolar with pulp necrosis and apical periodontitis with dens evaginatus. In this case, the tooth treated with an REP responded to orthodontic treatment similar to the nonendodontically treated teeth. Further studies are recommended to clarify the precise effects of orthodontic treatment on teeth treated with an REP.

orthodontic treatment
Dens evaginatus
root formation
regenerative endodontic therapy
repair


Eusocial wasp fauna of Sulawesi Island, the central island of Wallacea (Hymenoptera: Vespidae; Polistinae, Vespinae).

Abstract: Taxonomy of eusocial wasps (Polistinae and Vespinae) occurring in Sulawesi Island, the central island of Wallacea, is reviewed. Sixteen (12 polistine and four vespine) species are recognized. Polistes (Polistella) stigma, known to be widely distributed in southern Asia and Australasia, is newly recorded for Sulawesi Island. A key to the Sulawesian eusocial wasp species is provided. Their biogeographical characteristics are discussed to show that the Sulawesian eusocial wasp fauna is composed of Oriental elements.

Handru|Alan|A| Nugroho|Hari|H| Saito-Morooka|Fuki|F| Ubaidillah|Rosichon|R| Kojima|Jun-Ichi|JI|

Hymenoptera, Oriental elements, Malay Archipelago, endemism, new record


Teaching Diagnostic Reasoning: A Review of Evidence-Based Interventions.

Abstract:
Problem/Background: The ability to accurately diagnose patients based on symptom profiles is a vital yet challenging skill that Nurse Practitioners (NPs) undertake frequently.

PURPOSE
This integrative literature review highlights a variety of evidence based, practical educational strategies that foster the development of diagnostic reasoning.

METHODS
An integrative literature review was conducted in order to identify original research focusing on diagnostic reasoning educational interventions.

RESULTS
Eighteen primary sources met inclusion and exclusion criteria. Results are synthesized in terms of sample and setting, methodological features, interventions, and outcomes. Interventions broadly fit into five educational themes: testing strategies, cognitive biases, simulation programs, course formats, and instructional approaches.

DISCUSSION
Interventions are simple and can be implemented in multiple educational settings. Future research should occur in populations of NP students. Validated, easy-to-use measurement tools as well as more precise diagnostic reasoning concept development should occur.

D002983:Clinical Competence
D004506:Education, Nursing
D006801:Humans
D009722:Nurse Practitioners
D009733:Nursing Diagnosis
D011340:Problem Solving
D013338:Students, Nursing

diagnostic reasoning
nurse practitioner
educational interventions
evidence based education


A Clinical Case of Insulinoma Presenting with Postprandial Hypoglycemia in a Patient with a History of Gastric Bypass Surgery.

Abstract: A 61-year-old man with a history of total gastrectomy for cancer with Roux-en-Y reconstruction showed severe postprandial hypoglycemia accompanied by endogenous hyperinsulinemia. Abdominal ultrasonography and contrast-enhanced computed tomography showed no abnormal findings in the pancreas. A selective arterial secretagogue injection test showed the marked induction of serum immunoreactive insulin when calcium was injected into the splenic artery. A pathological analysis following distal pancreatectomy with splenectomy revealed a pancreatic neuroendocrine microadenoma containing insulin-producing cells in the resected pancreas. This case highlights the importance of carefully evaluating refractory and severe hypoglycemia in patients with a history of gastric surgery to exclude insulinoma.

Hayashida|Ryosuke|R| Tsuchiya|Kyoichiro|K| Sekine|Tetsuo|T| Momose|Takashi|T| Sato|Fuminori|F| Sakurada|Maya|M| Nishida|Kenji|K| Hayashi|Tatsuya|T| Morita|Yasuhiro|Y| Okada|Haruka|H| Fukushima|Noriyoshi|N| Yamada|Tetsuya|T| Tsujino|Motoyoshi|M|


Mortality Risk Associated With Truncating Founder Mutations in Titin.

Abstract: Background Truncating titin variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy, found in ≤25% of familial cases. Moreover, TTNtv associated with dilated cardiomyopathy are estimated to be present in 0.5% of the general population. The prognosis of asymptomatic carriers of TTNtv is poorly understood because TTNtv are associated with a highly variable phenotype. We aim to assess the natural history and clinical relevance of TTNtv by analyzing standardized mortality ratios (SMR) in multigenerational pedigrees and in close relatives of present-day patients. Methods Haplotype and genealogical analyses were performed on 3 recurrent TTNtv. Subsequently, the family tree mortality ratio method was used to compare all-cause mortality of subjects at an a priori 50% risk of carrying TTNtv to the general Dutch population. SMRs were stratified for sex, age, and calendar period. Subgroups were compared with Poisson regression. Similarly, SMRs were calculated in parents of 128 present-day dilated cardiomyopathy probands with TTNtv using the reverse parent-offspring method. Results The TTNtv were established as founder mutations and traced to 18th century ancestors. In 20 522 person-years, overall mortality was not significantly increased (SMR, 1.06; 95% CI, 0.95-1.18; P=0.162). However, mortality was significantly increased in subjects living after 1965 (SMR, 1.27; 95% CI, 1.04-1.53; P=0.009) and aged ≥60 years (SMR, 1.17; 95% CI, 1.01-1.35; P=0.02). The reverse parent-offspring analysis showed overall excess mortality (SMR, 1.26; 95% CI, 1.07-1.48; P=0.003), driven by subjects aged ≥60 years. Conclusions The natural history of the analyzed TTNtv shows a relatively mild disease course with significant excess mortality in elderly patients. With increasing life expectancy, TTNtv-associated morbidity and mortality will likely become more prevalent.

Helderman-van den Enden|Paula J T M|PJTM|

mortality
mutation
titin
natural history
cardiomyopathy, dilated


Effect of Bonding and Rebonding on the Shear Bond Strength of Two-Piece Implant Restorations.

Abstract:
PURPOSE
To evaluate the rebonding strength of ceramics to titanium alloy after disassembling by heat treatment.

MATERIALS AND METHODS
A total of 40 titanium alloy (titanium-6 aluminum-4 vanadium) disks (4.0 × 6.6 mm) and 20 zirconia (Lava Plus) disks were manufactured using computer-aided design and computer-aided manufacturing (CAD/CAM) technology. Twenty heat-pressed lithium disilicate glass-ceramic (IPS e.max Press LT) disks were fabricated and used as controls. Bonding protocol for each specimen surface was performed according to manufacturer's instructions. Specimens (n = 10) of zirconia/titanium alloy (ZR) and lithium disilicate/titanium alloy (LD) were bonded using adhesive resin cement (RelyX Ultimate) and then subjected to a heat treatment (HT, 320°C, 2 minutes) to disassemble the bonding complex, cleaned with aluminum oxide airborne-particle abrasion, and rebonded following the initial protocol, group ZRHT and group LDHT, respectively. After 5000 cycles of thermal cycling, a shear bond test was conducted. A universal testing machine was used at a 5 mm/min crosshead speed. Failed specimens were examined with stereomicroscopy at 10× magnification to identify the mode of failure. One-way ANOVA and Tukey HSD tests were applied for statistical analysis of the shear bond strength data, with statistical significance at α = 0.05.

RESULTS
The mean ± SD bond strength values ranged from 28.3 ± 7.2 to 45.9 ± 9.7 MPa. Statistically significant lower shear bond strength values were obtained from the LD group (p = 0.002, F = 5.89), while no statistically significant differences in bond strength were observed between the ZR and ZRHT groups (p > 0.05). Failure mode was predominantly mixed-type failure pattern for all specimens.

CONCLUSIONS
Heat and abrasion surface treatment increased the bond strength of lithium disilicate glass-ceramics cemented to titanium alloy, but no effect was observed on zirconia/titanium alloy bonding.

Putra|Armand|A|
Chung|Kwok-Hung|KH|
Guilherme|Nuno Marques|NM|
Cagna|David R|DR|

D000537:Aluminum Oxide
D002516:Ceramics
D001840:Dental Bonding
D003776:Dental Porcelain
D003799:Dental Stress Analysis
D008422:Materials Testing
D019279:Resin Cements
D033081:Shear Strength
D013499:Surface Properties

Bonding strength
titanium alloy
heat treatment
zirconia
lithium disilicate
fracture resistance


Functional assessment for elimination of mismatches in nuclear and whole cell extracts obtained from mouse and human blastocysts.

Abstract: Preimplantation embryos may have an increased risk of having mismatches due to the rates of cell proliferation and DNA replication. Elimination of mismatches in human gametes and embryos has not been investigated. In this study we developed a sensitive functional assay to examine the repair or elimination of mismatches in both commercially available cell extracts and extracts obtained from preimplantation embryos. Heteroduplex molecules were constructed using synthetic oligonucleotides. Efficiency of the repair of mismatches was semi-quantitatively analysed by exposure to nuclear/whole cell extracts (as little as 2.5 µg) and extracts obtained from pooled mouse and human blastocysts to investigate the repair capacity in human embryos. A cell free in vitro assay was successfully developed to analyze the repair of mismatches using heteroduplex complexes. The assay was further optimized to analyze repair of mismatches in cell extracts obtained from oocytes and blastocysts using minute amounts of protein. The efficiency of mismatch repair was examined in both mouse and human blastocysts (2.5 µg). The blastocysts were observed to have a lower repair efficiency compared to commercially available nuclear and whole cell extracts. In conclusion, a sensitive, easy, and fast in vitro technique was developed to detect the repair of mismatch efficiency in embryos.

Tulay|Pinar|P|
Jaroudi|Souraya|S|
Doshi|Alpesh|A|
SenGupta|Sioban B|SB|

elimination of mismatches
human
embryo
functional assay
DNA repair


Leaf transcriptomic signatures for somatic embryogenesis potential of Elaeis guineensis.

Abstract: Potentially embryogenic oil palms can be identified through leaf transcriptomic signatures. Differential expression of genes involved in flowering time, and stress and light responses may associate with somatic embryogenesis potential. Clonal propagation is an attractive approach for the mass propagation of high yielding oil palms. A major issue hampering the effectiveness of oil palm tissue culture is the low somatic embryogenesis rate. Previous studies have identified numerous genes involved in oil palm somatic embryogenesis, but their association with embryogenic potential has not been determined. In this study, differential expression analysis of leaf transcriptomes from embryogenic and non-embryogenic mother palms revealed that transcriptome profiles from non- and poor embryogenic mother palms were more similar than highly embryogenic palms. A total of 171 genes exhibiting differential expression in non- and low embryogenesis groups could also discriminate high from poor embryogenesis groups of another tissue culture agency. Genes related to flowering time or transition such as FTIP, FRIGIDA-LIKE, and NF-YA were up-regulated in embryogenic ortets, suggesting that reproduction timing of the plant may associate with somatic embryogenesis potential. Several light response or photosynthesis-related genes were down-regulated in embryogenic ortets, suggesting a link between photosynthesis activity and embryogenic potential. As expression profiles of the differentially expressed genes are very similar between non- and low embryogenic groups, machine learning approaches with several candidate genes may generate a more sensitive model to better discriminate non-embryogenic from embryogenic ortets.

D058439:Plant Somatic Embryogenesis Techniques

Flowering time
Stress
Light
Embryogenic potential
Transcriptome profiling
Cloning


Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

Abstract:
BACKGROUND AND OBJECTIVES
Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy.

METHODS
A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin.

RESULTS
The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls.

CONCLUSIONS
Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

esophagectomy
preconditioning
anastomosis
esophageal cancer


The benefits of being self-determined in promoting physical activity and affective well-being among women recently treated for breast cancer.

Abstract:
PURPOSE
In this study, changes in motivational regulations in women following treatment for breast cancer were described. Changes in motivational regulations as predictors of subsequent change in light and moderate-to-vigorous physical activity (PA) and affect were also examined.

METHODS
Women [n = 150; M(age) = 54.41 (SD = 10.87) years] completed self-report questionnaires and wore an accelerometer for 7 days at Time 1 [M = 3.94 (SD = 3.08) months following primary treatment], as well as 3 (Time 2) and 6 (Time 3) months later. Data were analyzed using repeated-measures analysis of variance and path analysis using residual change scores.

RESULTS
Identified regulation and self-determined motivation (i.e., combined intrinsic motivation and identified regulation) scores decreased over time (p < 0.05). In the path model [χ(2)(4) = 5.66, p = 0.22, root mean square error of approximation = 0.05 (90% CI: 0.0; 0.15), comparative fit index = 0.99, standardized root mean square of the residuals = 0.03], ΔTime(1-2) in external regulation was associated with ΔTime(2-3) in positive affect (β = -0.16), ΔTime(1-2) in introjected (β = 0.25) and amotivation (β = 0.19) were related to ΔTime(2-3) in negative affect, and ΔTime(1-2) in self-determined motivation was related to ΔTime(2-3) in positive affect (β = 0.40) and moderate-to-vigorous PA (β = 0.21).

CONCLUSIONS
Changes in motivational regulations were related to changes in PA and affect in the aftermath of breast cancer. Given the benefits of self-determined motivation, additional research is needed to develop and test interventions aimed at enhancing this type of motivation.

Brunet|Jennifer|J|
Burke|Shaunna M|SM|
Sabiston|Catherine M|CM|

physical activity
breast cancer
motivation
longitudinal study
oncology
survivorship
well‐being


Cornus officinalis var. koreana Kitam polyphenol extract decreases pro-inflammatory markers in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages by reducing Akt phosphorylation.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Cornus officinalis var. koreana Kitam (CO) is found predominantly in China but also in Korea and Japan and has been used in Eastern medicine for over 2000 years to treat several conditions including diabetes, cardiovascular disease and kidney disease. Chronic inflammation underlies the pathogenesis of these diseases. The mechanisms by which CO may exert its anti-inflammatory effects have not been well defined.

AIM OF THE STUDY
We aimed to determine whether Cornus officinalis var. koreana Kitam extract (COE) attenuate the inflammatory response induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and to elucidate the mechanisms which contribute to these anti-inflammatory effects.

MATERIALS AND METHODS
COE was prepared using ethanolic extraction, followed by solvent evaporation and freeze-drying. RAW 264.7 macrophages were treated with 0, 50, 100, 200 and 400 μg/ml of COE. After 2 h, cells were treated with 100 ng/ml of LPS for 6 h. Cells were then collected for whole cell protein expression analysis of signaling and inflammatory molecules via western blot.

RESULTS
Pre-treatment with 100, 200 and 400 μg/ml of COE significantly reduced Akt phosphorylation in LPS stimulated macrophages compared to LPS alone (P ≤ 0.003). NF-κB expression was significantly attenuated with 400 μg/ml of COE compared to LPS treatment alone (P = 0.01). LPS induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression, which was significantly decreased by treatment with 400 μg/ml COE (P = 0.0001 and 0.02, respectively). COE dose-dependently decreased LPS-induced expression of interleukin (IL)-1β (P ≤ 0.0008) and IL-6 (P = 0.01).

CONCLUSION
In summary, COE attenuated the inflammatory response induced by LPS in RAW 264.7 macrophages, likely due to Akt inhibition.

Najjar|Rami S|RS|
Akhavan|Neda S|NS|
Pourafshar|Shirin|S|
Arjmandi|Bahram H|BH|
Feresin|Rafaela G|RG|

Cornus Polyphenols Macrophages Akt Inflammation LPS Berries


Treatment of volumetric muscle loss in mice using nanofibrillar scaffolds enhances vascular organization and integration.

Abstract: Traumatic skeletal muscle injuries cause irreversible tissue damage and impaired revascularization. Engineered muscle is promising for enhancing tissue revascularization and regeneration in injured muscle. Here we fabricated engineered skeletal muscle composed of myotubes interspersed with vascular endothelial cells using spatially patterned scaffolds that induce aligned cellular organization, and then assessed their therapeutic benefit for treatment of murine volumetric muscle loss. Murine skeletal myoblasts co-cultured with endothelial cells in aligned nanofibrillar scaffolds form endothelialized and aligned muscle with longer myotubes, more synchronized contractility, and more abundant secretion of angiogenic cytokines, compared to endothelialized engineered muscle formed from randomly-oriented scaffolds. Treatment of traumatically injured muscle with endothelialized and aligned skeletal muscle promotes the formation of highly organized myofibers and microvasculature, along with greater vascular perfusion, compared to treatment of muscle derived from randomly-oriented scaffolds. This work demonstrates the potential of endothelialized and aligned engineered skeletal muscle to promote vascular regeneration following transplantation.

Nakayama|Karina H|KH|
Quarta|Marco|M|
Paine|Patrick|P|
Alcazar|Cynthia|C|
Karakikes|Ioannis|I|
Garcia|Victor|V|
Abilez|Oscar J|OJ|0000-0002-9991-400X
Calvo|Nicholas S|NS|
Simmons|Chelsey S|CS|
Rando|Thomas A|TA|
Huang|Ngan F|NF|0000-0003-2298-6790

Tissues
Regeneration
Cell therapies
Musculoskeletal models
Tissue engineering


Changes in Blood Lymphocyte Subpopulations and Expression of MHC-II Molecules in Wild Mares Before and After Parturition.

Abstract:
Introduction
Pregnancy is a physiological state in which the immune system undergoes certain changes. On the one hand, by depleting cell defence mechanisms, it favours development and maintenance of the pregnancy. At the same time cells of the immune system ensure resistance to many risk factors, including infectious agents.

Material and Methods
The study was carried out on 24 Polish Konik breed mares which were divided into two equal groups. The first group (group I) included mares living in the reserve. The second group (group II) comprised mares maintained under conventional conditions in the stables. The blood samples were collected for the first time in the perinatal period, i.e. 2 weeks before parturition (trial 0), then within the first 24 h after delivery, and then on 7th and 21st day after foaling. Flow cytometric analysis of lymphocyte expressing TCD4+, TCD8+, CD2+, and MHC class II antigens was performed.

Results
Before the delivery, in group I there was a significantly higher CD4:CD8 ratio compared to group II (P ≤ 0.05). Similarly, significantly increased CD4:CD8 ratio in group I was noted within 24 h after parturition (P ≤ 0.001) and it was also observed on 7th day (P ≤ 0.03) and 21st day after foaling (P ≤ 0.02). In the first 24 h after parturition, a significant decline of lymphocytes CD8+ (P ≤ 0.02) was noted. No significant differences in terms of lymphocytes CD2+ and CD3+ were observed. Expression of MHC-II molecules before and after the parturition was higher in group I compared to group II; however, the difference between the groups was not significant.

Conclusion
The results obtained indicate that mares living in the reserve display higher activity of cell defence mechanisms.

Krakowski|Leszek|L| Bartoszek|Przemysław|P| Krakowska|Izabela|I| Stachurska|Anna|A| Piech|Tomasz|T| Brodzki|Piotr|P| Wrona|Zygmunt|Z|

lymphocytes
mares
pregnancy
immunity
major histocompatibility complex


Early Childhood Caries in 3 to 5 Year Old Children in Trinidad and Tobago.

Abstract:
BACKGROUND
This study was done to evaluate the prevalence and contributory factors of early childhood caries (ECC) and severe ECC (S-ECC) among preschool children of Kindergartens and Early Childhood Centres in Trinidad and Tobago.

METHODS
A cross-sectional study was carried out involving 342 preschool children aged 3 to 5 years. The school staff distributed a structured questionnaire to the children to be completed by the mother. Clinical examinations were conducted by calibrated examiners. Statistical significance was set at p < 0.05 in all analyses.

RESULTS
The prevalence of ECC and S-ECC was 50.3% and 52.3%, respectively. Dietary and oral hygiene factors particularly with bottle feeding and high plaque levels were major contributors to dental caries in this population.

CONCLUSION
ECC and S-ECC are significant issues that occur in preschool children in Trinidad and Tobago. The development of ECC and S-ECC can be attributed to certain environmental factors like dietary habits and oral hygiene practices. Early dental assessment, broad-based oral health education programmes, increased parental/guardian engagement during oral hygiene practices and greater access to facilities for early childhood caries prevention and management can help alleviate the problems of ECC and S-ECC in this population.

Percival|Tricia|T|
Edwards|Julien|J|
Barclay|Salvacion|S|
Sa|Bidyadhar|B|
Majumder|Md Anwarul Azim|MAA|

early childhood caries
Trinidad and Tobago
preschool children
oral health


Can Total Knee Arthroplasty Be Performed Safely as an Outpatient in the Medicare Population?

Abstract:
BACKGROUND
The Centers for Medicare and Medicaid Services has solicited public comments for the 2017 Proposed Rule to consider removing total knee arthroplasty (TKA) from the Inpatient Only List. The purpose of this study is to compare the complication rates between outpatient (same-day discharge), short-stay (discharge within 1 day), and inpatient TKA and to identify the ideal candidates for a short-stay or outpatient procedure.

METHODS
We queried the American College of Surgeons-National Surgical Quality Improvement Program database for patients over age 65 years who underwent TKA from 2014 to 2015. Demographics, comorbidities, 30-day complications, and readmission rates were compared between patients after outpatient, short-stay, and inpatient procedures. A multivariate regression analysis was then performed to identify at-risk patients who should not be candidates for outpatient or short-stay TKA.

RESULTS
Of the 49,136 Medicare-aged TKA patients, 365 (0.7%) were outpatient, 3033 (6%) were short-stay and 45,738 (93%) were inpatient. Short-stay patients had a lower complication rate than both the outpatient and inpatient groups (2% vs. 8% vs. 8%, P < .001). Independent risk factors (all P < .05) for experiencing a complication or requiring an inpatient stay include female gender (odds ratio [OR] 1.655), general anesthesia (OR 1.282), diabetes mellitus (OR 1.171), chronic obstructive pulmonary disease (OR 1.579, P < .001), hypertension (OR 1.144), kidney disease (OR 1.425), American Society of Anesthesiologists Score 4 (OR 1.748), body mass index >35 kg/m2 (OR 1.265), and age >75 years (OR 1.429).

CONCLUSION
TKA can be performed safely as an outpatient in a subset of healthy Medicare patients with a complication rate similar to an inpatient stay. A 23-hour stay, however, may be the "sweet spot" that minimizes complications in this population.

Courtney|P Maxwell|PM|
Froimson|Mark I|MI|
Meneghini|R Michael|RM|
Lee|Gwo-Chin|GC|
Della Valle|Craig J|CJ|

total knee arthroplasty
outpatient
Inpatient Only List
complications
health policy


Impact of Progerin Expression on Adipogenesis in Hutchinson-Gilford Progeria Skin-Derived Precursor Cells.

Abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS and normal fibroblast cultures, with senescence of 5 and 30%. We observed that the presence of high numbers of senescent cells reduced SKPs' adipogenic differentiation potential. Treatment with baricitinib, a JAK-STAT inhibitor, ameliorated the ability of HGPS SKPs to differentiate into adipocytes. Our findings suggest that the development of lipodystrophy in patients with HGPS may be associated with an increased rate of cellular senescence and chronic inflammation.

D019941:Cyclin-Dependent Kinase Inhibitor p16

progerin
adipogenesis
skin-derived precursor cells
senescence
adipocyte


A New Suite of Allelic-Exchange Vectors for the Scarless Modification of Proteobacterial Genomes.

Abstract: Despite the advent of new techniques for genetic engineering of bacteria, allelic exchange through homologous recombination remains an important tool for genetic analysis. Currently, sacB-based vector systems are often used for allelic exchange, but counterselection escape, which prevents isolation of cells with the desired mutation, occasionally limits their utility. To circumvent this, we engineered a series of "pTOX" allelic-exchange vectors. Each plasmid encodes one of a set of inducible toxins, chosen for their potential utility in a wide range of medically important proteobacteria. A codon-optimized rhaS transcriptional activator with a strong synthetic ribosome-binding site enables tight toxin induction even in organisms lacking an endogenous rhamnose regulon. Expression of the gene encoding blue AmilCP or magenta TsPurple nonfluorescent chromoprotein facilitates monitoring of successful single- and double-crossover events using these vectors. The versatility of these vectors was demonstrated by deleting genes in Serratia marcescens, Escherichia coli O157:H7, Enterobacter cloacae, and Shigella flexneri Finally, pTOX was used to characterize the impact of disruption of all combinations of the 3 paralogous S. marcescens peptidoglycan amidohydrolases on chromosomal ampC β-lactamase activity and the corresponding β-lactam antibiotic resistance. Mutation of multiple amidohydrolases was necessary for high-level ampC derepression and β-lactam resistance. These data suggest why β-lactam resistance may emerge during treatment less frequently in S. marcescens than in other AmpC-producing pathogens, like E. cloacae Collectively, our findings suggest that the pTOX vectors should be broadly useful for genetic engineering of Gram-negative bacteria.IMPORTANCE Targeted modification of bacterial genomes is critical for genetic analysis of microorganisms. Allelic exchange is a technique that relies on homologous recombination to replace native loci with engineered sequences. However, current allelic-exchange vectors often enable only weak selection for successful homologous recombination. We developed a suite of new allelic-exchange vectors, pTOX, which were validated in several medically important proteobacteria. They encode visible nonfluorescent chromoproteins that enable easy identification of colonies bearing integrated vectors and permit stringent selection for the second step of homologous recombination. We demonstrate the utility of these vectors by using them to investigate the effect of inactivation of Serratia marcescens peptidoglycan amidohydrolases on β-lactam antibiotic resistance.

Lazarus|Jacob E|JE|
Warr|Alyson R|AR|
Kuehl|Carole J|CJ|
Giorgio|Rachel T|RT|
Davis|Brigid M|BM|
Waldor|Matthew K|MK|

allelic exchange
Serratia marcescens
ampC
antibiotic resistance
AmilCP gene
ampD
beta-lactamase
sacB
toxin-antitoxin
type VI toxin


Randomized controlled trial comparing the efficacy of pectoral nerve block with general anesthesia alone in patients undergoing unilateral mastectomy.

Abstract: This study was conducted to evaluate the efficacy of pectoral nerve block for post-operative analgesia in breast surgery patients. This double blinded, randomized controlled trial was conducted after Clinical Trials Registry-India registration. Sixty ASA grade I-II female patients undergoing unilateral modified radical mastectomy under general anesthesia, were recruited pre-operatively in two groups. PECS group (n  =  29) was given ipsilateral pectoral nerve block I & II while the CONTROL group (n  =  29) directly proceeded to surgery. Our primary outcome was comparison of immediate post-operative pain scores at rest and movement. The secondary outcomes were post-operative pain scores at 2, 4, 6, 12, 18, and 24 h, total intraoperative fentanyl consumption, time to rescue analgesia, post-operative nausea vomiting, and complications, if any. Categorical data was analyzed by using the chi-squared test or Fishers Exact test. Comparison of pain scores was analyzed by using the Independent sample t test. The immediate post-operative pain scores in two groups were comparable. The pain scores were also comparable at 4, 6, 12, and 24 h; but statistically significantly lower in PECS group at 2 and 18 h. The total intraoperative fentanyl consumption was also reduced in PECS group (P = 0.009). Only 9 patients in PECS group (796.5 min) as compared to 22 patients in CONTROL group (387.7 min) required rescue analgesia (P  =  0.001). Pectoral nerve block benefits patients undergoing mastectomy by achieving similar post-operative pain scores with decreased consumption of intraoperative and post-operative opioids. Registration. Clinical Trials Registry of India, (CTRI/2017/04/008289). ctri.nic.in.

Sharma|Sudivya|S|0000-0003-0608-8819 Tiwari|Shashank|S| Sharma|Kailash|K| Nair|Nita|N|

Pectoral nerve block
General anesthesia
Mastectomy
Analgesia
Post-operative pain


8q24 and 17q prostate cancer susceptibility loci in a multiethnic Asian cohort.

Abstract:
OBJECTIVES
Recently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men.

MATERIALS AND METHODS
We performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP.

RESULTS
In the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04-2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥ 7 (OR = 1.76, 95% CI = 1.14-2.73) and prostate-specific antigen (PSA) levels of ≥ 10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01-2.63), as well as for rs6983267 GG with stage 3-4 CaPs (OR = 1.91, 95% CI = 1.01-3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10-4.32).

CONCLUSIONS
This exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.

Chan|Jason Yongsheng|JY|
Li|Huihua|H|
Singh|Onkar|O|
Mahajan|Anupama|A|
Ramasamy|Saminathan|S|
Subramaniyan|Koilan|K|
Kanesvaran|Ravindran|R|
Sim|Hong Gee|HG|
Chong|Tsung Wen|TW|
Teo|Yik-Ying|YY|
Chia|Sin Eng|SE|
Tan|Min-Han|MH|
Chowbay|Balram|B|

D020022:Genetic Predisposition to Disease

Prostate Cancer Polymorphism Gleason Ethnicity Pharmacogenetics


Delusion of pregnancy: an unusual symptom in the context of dementia.

Abstract:
BACKGROUND
Delusions can complicate practically all brain disorders. They may be dramatic and bizarre. An example is the so-called delusion of pregnancy.

OBJECTIVE
To identify the characteristic of a psychotic symptom, the phenomenon of delusion of pregnancy, in the context of dementia.

METHOD
MEDLINE and Google Scholar searches were conducted for relevant articles, chapters, and books published before 2014. Search terms used included delusion of pregnancy, uncommon presentation, behavioral and psychological symptoms, dementia, Alzheimer's disease, and frontotemporal dementia (FTD). Publications found through this indexed search were reviewed for further relevant references. We included case reports that highlight the relationship and overlap between dementia presenting as schizophrenia-like psychosis and schizophrenia.

RESULTS
Literature on delusion of pregnancy in the course of dementia consists mostly of case reports and small samples of patients.

CONCLUSION
Psychotic phenomena such as delusion of pregnancy may be a feature in some cases of dementia. If this bizarre features of dementia appears as early presentation of FTD whose usual onset is in the presenium, it may be mistaken for schizophrenia.

delusion of pregnancy
dementia
uncommon presentation
behavioral and psychological symptoms
Alzheimer's disease
frontotemporal dementia


Effect of corticosterone on larval growth, antipredator behaviour and metamorphosis of Hylarana indica.

Abstract: Corticosterone (CORT), a principal glucocorticoid in amphibians, is known to regulate diverse physiological processes including growth and metamorphosis of anuran tadpoles. Environmental stressors activate the neuroendocrine stress axis (hypothalamus-pituitary-interrenal axis, HPI) leading to an acute increase in CORT, which in turn, helps in coping with particular stress. However, chronic increase in CORT can negatively affect other physiological processes such as growth and metamorphosis. Herein, we studied the effect of exogenous CORT on larval growth, antipredator behaviour and metamorphic traits of Hylarana indica. Embryonic exposure to 5 or 20μg/L CORT did not affect their development, hatching duration as well as larval growth and metamorphosis. Exposure of tadpoles to 10 or 20μg/L CORT throughout larval development caused slower growth and development leading to increased body mass at stage 37. However, body and tail morphology of tadpoles was not affected. Interestingly, larval exposure to 5, 10 or 20μg/L CORT enhanced their antipredator response against kairomones in a concentration-dependent manner. Further, larval exposure to increasing concentrations of CORT resulted in the emergence of heavier froglets at 10 and 20μg/L while, delaying metamorphosis at all concentrations. Interestingly, the heavier froglets had shorter hindlimbs and consequently shorter jump distances. Tadpoles exposed to 20μg/L CORT during early, mid or late larval stages grew and developed slowly but tadpole morphology was not altered. Interestingly, exposure during early or mid-larval stages resulted in an enhanced antipredator response. These individuals metamorphosed later but at higher body mass while SVL was unaffected.

Corticosterone
Antipredator behaviour
Metamorphosis
Hylarana indica
Stress response


Comparing the performance of four macrophytes in bacterial assisted floating treatment wetlands for the removal of trace metals (Fe, Mn, Ni, Pb, and Cr) from polluted river water.

Abstract: Here we compared the performance of four macrophytes namely Brachia mutica, Typha domingensis, Phragmites australis and Leptochala fusca, in bacterially assisted floating treatment wetlands (FTWs) for the clean-up of five trace metals (Fe, Mn, Ni, Pb, and Cr) from polluted river water. The river water was artificially spiked with reagent grade chemicals to increase the trace metal pollution. The macrophytes were planted in a polystyrene sheet to prepare FTWs, which were placed over the metal-contaminated river water. The consortium of five rhizospheric and endophytic bacterial strains, i.e., Aeromonas salmonicida, Pseudomonas indoloxydans, Bacillus cerus, Pseudomonas gessardii, and Rhodococcus sp., was inoculated support the natural remediation ability. We found a significant reduction in the metal content by all four macrophytes and the removal was significantly enhanced when bacterial inoculum was applied. The maximum removal was observed in FTWs planted with P. australis and inoculated with bacteria. In this treatment (T6) the Fe, Mn, Ni, Pb and Cr contents were reduced to 0.53, 0.20, 0.09, 1.04 and 0.07 mg L-1 after five weeks retention time. The bacterial inoculation sufficiently increased the plant biomass. All macrophytes depicted potential to uptake and translocate trace metals in the roots instead of shoots. The bacterial inoculation acclimatize the plants roots followed by shoots and enhanced the uptake of metals by macrophytes. This study emphasized the usefulness of macrophytes-bacteria mutualism in FTWs system for the remediation of trace metals. The similar systems may provide practical solutions for the remediation of trace metals of polluted river water.

Shahid|Munazzam Jawad|MJ|
Ali|Shafaqat|S|
Shabir|Ghulam|G|
Siddique|Muhammad|M|
Rizwan|Muhammad|M|
Seleiman|Mahmoud F|MF|
Afzal|Muhammad|M|

Macrophytes
Trace metals
Floating wetlands
Phyto-remediation
Plant-bacteria partnership


Emotional granularity and social functioning in individuals with schizophrenia: an experience sampling study.

Abstract: Previous research has shown that healthy individuals who fail to differentiate among emotional states (i.e., those with low emotional granularity; EG) have poorer social functioning (SF) than those with high EG. It is unknown, however, whether these associations extend to clinical disorders characterized by impaired SF, such as schizophrenia. In the present study, we compared SF and EG in individuals with schizophrenia and healthy controls, and then, within the schizophrenia group, we examined the links between EG and SF. Employing an Experience Sampling Method approach, 77 individuals with schizophrenia and 27 healthy controls rated their momentary emotions (sadness, anxiety, anger, and happiness) up to 10 times/day over a two-day period using mobile electronic devices. For each participant, we then calculated the within-subject average correlations among the momentary emotion ratings, producing two EG indices - EGIall for all emotions and EGIneg for negative ones. A subsample of participants with schizophrenia also completed self-report, interview, and ability-based measures of SF. Compared to healthy controls, individuals with schizophrenia displayed significantly poorer SF and lower EGIall, but comparable EGIneg. Within the schizophrenia group, hierarchical multiple regression analyses indicated that EGIall, but not EGIneg, significantly predicted social dysfunction after controlling for emotional awareness, symptoms, and emotional intensity and variability. Our findings indicate that individuals with schizophrenia have a relatively intact ability to differentiate among negative emotions in everyday life. However, they experience significant difficulties differentiating between positive and negative emotions, and this may contribute to their social difficulties.

Kimhy|David|D|
Vakhrusheva|Julia|J|
Khan|Samira|S|
Chang|Rachel W|RW|
Hansen|Marie C|MC|
Ballon|Jacob S|JS|
Malaspina|Dolores|D|
Gross|James J|JJ|

D011569:Psychiatric Status Rating Scales

Emotional granularity
Emotions
Social functioning
Schizophrenia
Experience Sampling Method
Emotional awareness
Ambulatory assessment
Ecological momentary assessment
Emotion processing
Emotion regulation
Social cognition
Social support


Expression pattern and prognostic implication of SALL4 gene in myeloid leukemias: a case-control study.

Abstract: SALL4 is a transcription factor that retains stem cells in an undifferentiated state and promotes its self-renewal. In addition, it is implicated in leukemogenesis via its effect on leukemic stem cells. This study aimed to characterize the expression pattern of SALL4 gene in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) at different progression phases of the leukemic process and to assess its prognostic significance. Real-time PCR was used in 106 patients: 54 AML patients; 43 de novo and 11 in complete remission (CR), 52 CML patients; 31 in chronic phase (CP), 11 in deep molecular response (MR4) and 10 in accelerated/blastic phase (AP/BP); and in 21 nonmalignant bone marrow samples. SALL4 gene expression was elevated in AML, AML-CR and CML-CP (median = 5.180, 4.604 and 14.125 fold changes, respectively). Elevated SALL4 gene expression among AML de novo patient was associated with poor disease-free survival (DFS) rates (p = .022). Among CML patients, the highest percentage of patients with a high SALL4 (p = .033) was among CML-CP. SALL4 has a role in leukemogenesis; high SALL4 expression was associated with poor DFS among AML patients.

Farawela|Hala M|HM|
Zawam|Hamdy M|HM|
Al-Wakeel|Hanan A|HA|
El-Nagdy|Mona H|MH|
El-Refaey|Fatma A|FA|
Abdel-Rahman|Hala A|HA|

D000971:Antineoplastic Combined Chemotherapy Protocols

D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive

SALL4
leukemic stem cell
Acute myeloid leukemia
chronic myeloid leukemia
gene expression
real time PCR


Investigation of Hot Spot Region in XIAP Inhibitor Binding Site by Fragment Molecular Orbital Method.

Abstract: X-linked inhibitor of apoptosis protein (XIAP) is an important regulator of cancer cell survival whose BIR3 domain (XIAP-BIR3) recognizes the Smac N-terminal tetrapeptide sequence (AVPI), making it an attractive protein-protein interaction (PPI) target for cancer therapies. We used the fragment molecular orbital (FMO) method to study the binding modes and affinities between XIAP-BIR3 and a series of its inhibitors (1-8) that mimic the AVPI binding motif; the inhibitors had common interactions with key residues in a hot spot region of XIAP-BIR3 (P1-P4 subpockets) with increased binding affinity mainly attributed to specific interactions with the P1 and P4 subpockets. Based on the structural information from FMO results, we proposed a novel XIAP natural product inhibitor, neoeriocitrin 10, which was derived from our preciously reported XIAP-BIR3 inhibitor 9, can be used as a highly potent candidate for XIAP-BIR3 inhibition. We also performed pair interaction energy decomposition analysis to investigate the binding energies between specific binding residues and individual ligands, showing that the novel natural product neoeriocitrin 10 had a higher binding affinity than epicatechin gallate 9. Molecular docking and dynamics simulations were performed to explore the mode of binding between 10 and XIAP-BIR3, demonstrating that 10 binds more strongly to the P1 and P4 pockets than 9. Overall, we present a novel natural product, neoeriocitrin 10, and demonstrate that the FMO method can be used to identify hot spots in PPIs and design new compounds for XIAP inhibition.

Lim|Hocheol|H|
Jin|Xuemei|X|
Kim|Jongwan|J|
Hwang|Sungbo|S|
Shin|Ki Beom|KB|
Choi|Jiwon|J|
Nam|Ky-Youb|KY|
No|Kyoung Tai|KT|

Fragment molecular orbital method
X-linked inhibitor of apoptosis protein
Protein-protein interaction
Natural product
XIAP-BIR3 inhibitor
Molecular docking
Drug discovery
MD simulation


Spheno-Orbital Meningiomas: When the Endoscopic Approach Is Better.

Abstract: Spheno-orbital meningiomas were historically treated by traditional craniotomies. However, in the past few years new endoscopic treatments have been successfully performed. In this study, we analyzed different indications for craniotomy and endoscopy, and the advantages and disadvantages of these procedures.Thirty patients with spheno-orbital meningiomas were operated on over 2 years, between 2013 and 2014. Computed tomography (CT) and magnetic resonance imaging (MRI) were performed in all patients preoperatively. Navigated surgical removal and histological confirmation, as well as follow-up examinations, including CT scan at 24 h and MRI at 3, 6, and 12 months after surgery, were performed. Twenty-three patients were treated by traditional fronto-temporal, fronto-temporo-orbital, and supraorbital craniotomies; in six cases the tumor was removed via endoscopic endonasal and lateral transorbital resection. Only one case required a combined supraorbital and endoscopic endonasal approach.We analyzed the results of the different surgical techniques, in particular those of the endoscopic approaches.In selected cases, the endoscopic approach to spheno-orbital meningiomas, compared with traditional approaches, may be more effective in removing tumors completely. The surgical technique is easy and the rate of complications is low.

Peron|Stefano|S| Cividini|Andrea|A| Santi|Laura|L| Galante|Nicola|N| Castelnuovo|Paolo|P| Locatelli|Davide|D|

Spheno-orbital meningiomas
Endonasal approach
Orbital tumors
Transorbital approach


Epigenetic regulation of intestinal stem cell differentiation.

Abstract: To fulfill the lifelong need to supply diverse epithelial cells, intestinal stem cells (ISCs) rely on executing accurate transcriptional programs. This review addresses the mechanisms that control those programs. Genes that define cell behaviors and identities are regulated principally through thousands of dispersed enhancers, each individually <1 kb long and positioned from a few to hundreds of kilobases away from transcription start sites, upstream or downstream from coding genes or within introns. Wnt, Notch, and other epithelial control signals feed into these cis-regulatory DNA elements, which are also common loci of polymorphisms and mutations that confer disease risk. Cell-specific gene activity requires promoters to interact with the correct combination of signal-responsive enhancers. We review the current state of knowledge in ISCs regarding active enhancers, the nucleosome modifications that may enable appropriate and hinder inappropriate enhancer-promoter contacts, and the roles of lineage-restricted transcription factors.

stem cells
differentiation
transcription factors
epigenetic control
transcriptional regulation


Testing the efficacy and efficiency of a single "universal warming protocol" for vitrified human embryos: prospective randomized controlled trial and retrospective longitudinal cohort study.

Abstract:
PURPOSE
To study the efficacy and efficiency of a "universal warming protocol" for vitrified human embryos, based on subsequent steps with 1 and 0.5 M concentration of extracellular cryoprotectant (ECCP).

METHOD
Two studies on patients undergoing fertility treatments via ICSI: a prospective randomized controlled trial (RCT) and a retrospective cohort study (CS).

SETTING
Private assisted reproductive (AR) center. RCT: duration 01/03/2017-01/10/2017; 315 embryos at blastocyst stage obtained from 169 patients. Each patient's embryos were first randomized for vitrification with two different kits: Vitrification Kit (Kitazato, Japan) and Sage Vitrification Kit (Origio, Denmark). The embryos were randomly warmed with either Kitazato (K) or Sage (S) warming kits, specifically: group A (KK), group B (KS), group C (SK), and group D (SS).

PRIMARY OUTCOME MEASURE
survival rate (number of embryos surviving per number of embryos warmed). Secondary: implantation rate (number of embryos implanted per number of embryos transferred). CS: duration 01/01/2013-31/12/2015 embryos from patients' own oocytes; 10/04/2015-31/07/2017 embryos from donors' oocytes. A total of 1055 embryos vitrified at cleavage stage obtained from 631 warming cycles: 847 of these obtained from patients' own oocytes, 208 egg-donation-derived embryos. Each patient's embryos were vitrified and warmed in various combinations of three different vitrification/warming kits: Kitazato (K), Sage (S), or made in-house in our laboratory (H). Vitrification/warming kits from different manufacturers are routinely used in our AR center, and the warming procedures are randomly performed with any available kit on a "first-in-first-out" basis, irrespective of the kit used for vitrification. Group names: KK, KS, SK, SS, SH, HK, HS, HH (embryos from patients' own oocytes); eKK, eKS, eSK, eSS (egg-donation-derived embryos).

RESULTS
Cryo-survival rates were comparable in all study groups. RCT. Group A 99.0% (96/97), group B 98.8% (83/84), group C 98.4% (61/62), and group D 98.6% (71/72). CS. Embryos from patients' own oocytes: KK 96.4% (54/56), KS 100.0% (13/13), SK 98.8% (80/81), SS 97.2% (174/179), SH 97.6% (40/41), HK 95.2% (20/21), HS 99.5% (187/188), and HH 97.4% (261/268). Egg-donation-derived embryos: eKK 100.0% (91/91), eKS 98.4% (60/61), eSK 100.0% (26/26), and eSS 96.7 (29/30). Implantation was generally comparable in all study groups-exceptions were in CS: KS vs. SK (P = 0.049), SS (P = 0.012), HS (P = 0.010), HH (P = 0.025); and SH vs. SS (P = 0.042), HS (P = 0.035).

CONCLUSION
Worldwide, millions of embryos have been cryopreserved using different vitrification kits; these studies establish that it is possible to combine different kits for vitrification and warming using a universal warming protocol. This can optimize costs, simplify lab routines, and favor embryo exchange between IVF centers.

RCT REGISTRATION NUMBER
ISRCTN12342851.

Warming
Vitrification
Sage Vitrification Kit
Embryo cryopreservation
Kitazato Vitrification Kit
Universal warming procedure


Goblet Cell Hyperplasia is not Epithelial-Autonomous in the Cftr Knockout Intestine.

Abstract: Goblet cell hyperplasia is an important manifestation of cystic fibrosis (CF) disease in epithelial-lined organs. Explants of CF airway epithelium show normalization of goblet cell numbers; therefore we hypothesized that small intestinal enteroids from Cftr knockout (KO) mice would not exhibit goblet cell hyperplasia. Toll-like receptors 2 and 4 (Tlr2, Tlr4) were investigated as markers of inflammation and influence on goblet cell differentiation. Ex vivo studies found goblet cell hyperplasia in Cftr KO jejunum as compared to wild-type (WT). IL-13, SAM pointed domain-containing ETS transcription factor (Spdef), Tlr2 and Tlr4 protein expression was increased in Cftr KO intestine relative to WT. In contrast, WT and Cftr KO enteroids did not exhibit differences in basal or IL-13-stimulated goblet cell numbers, or differences in expression of Tlr2, Tlr4 and Spdef. Ileal goblet cell numbers in Cftr KO/Tlr4 KO and Cftr KO/Tlr2 KO mice were not different from Cftr KO mice, but enumeration was confounded by altered mucosal morphology. Treatment with Tlr4 agonist LPS did not affect goblet cell numbers in WT or Cftr KO enteroids, whereas the Tlr2 agonist Pam3Csk4 stimulated goblet cell hyperplasia in both genotypes. Pam3Csk4 stimulation of goblet cell numbers was associated with suppression of Notch1 and Neurog3 expression and upregulated determinants of goblet cell differentiation. We conclude that goblet cell hyperplasia and inflammation of the Cftr KO small intestine are not exhibited by enteroids, indicating that this manifestation of CF intestinal disease is not epithelial-automatous but secondary to the altered CF intestinal environment.

Walker|Nancy M|NM|
Liu|Jinghua|J|
Young|Sarah M|SM|
Woode|Rowena A|RA|
Clarke|Lane L|LL|

goblet cell
Cystic fibrosis
small intestine
enteroid
toll-like receptor


German Society of Biomechanics (DGfB) Young Investigator Award 2019: Proof-of-Concept of a Novel Knee Joint Simulator Allowing Rapid Motions at Physiological Muscle and Ground Reaction Forces.

Abstract: The in vitro determination of realistic loads acting in knee ligaments, articular cartilage, menisci and their attachments during daily activities require the creation of physiological muscle forces, ground reaction force and unconstrained kinematics. However, no in vitro test setup is currently available that is able to simulate such physiological loads during squatting and jump landing exercises. Therefore, a novel knee joint simulator allowing such physiological loads in combination with realistic, rapid movements is presented. To gain realistic joint positions and muscle forces serving as input parameters for the simulator, a combined in vivo motion analysis and inverse dynamics (MAID) study was undertaken with 11 volunteers performing squatting and jump landing exercises. Subsequently, an in vitro study using nine human knee joint specimens was conducted to prove the functionality of the simulator. To do so, slow squatting without muscle force simulation representing quasi-static loading conditions and slow squatting and jump landing with physiological muscle force simulation were carried out. During all tests ground reaction force, tibiofemoral contact pressure, and tibial rotation characteristics were simultaneously recorded. The simulated muscle forces obtained were in good correlation (0.48 ≤ R ≤ 0.92) with those from the in vivo MAID study. The resulting vertical ground reaction force showed a correlation of R = 0.93. On the basis of the target parameters of ground reaction force, tibiofemoral contact pressure and tibial rotation, it could be concluded that the knee joint load was loaded physiologically. Therefore, this is the first in vitro knee joint simulator allowing squatting and jump landing exercises in combination with physiological muscle forces that finally result in realistic ground reaction forces and physiological joint loading conditions.

Schall|Florian|F|
Seitz|Andreas M|AM|
Hacker|Steffen|S|
van Drongelen|Stefan|S|
Wolf|Sebastian I|SI|
Ignatius|Anita|A|
Dürselen|Lutz|L|

biomechanics
knee
simulator
in vitro
muscle forces
rapid movement
contact pressure


Advances in motion and electromyography based wearable technology for upper extremity function rehabilitation: A review.

Abstract:
STUDY DESIGN
Scoping review.

INTRODUCTION
With the recent advances in technologies, interactive wearable technologies including inertial motion sensors and e-textiles are emerging in the field of rehabilitation to monitor and provide feedback and therapy remotely.

PURPOSE OF THE STUDY
This review article focuses on inertial measurement unit motion sensor and e-textiles-based technologies and proposes approaches to augment these interactive wearable technologies.

METHODS
We conducted a comprehensive search of relevant electronic databases (eg, PubMed, the Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, The Cochrane Central Register of Controlled Trial, and the Physiotherapy Evidence Database). The scoping review included all study designs.

RESULTS
Currently, there are a numerous research groups and companies investigating inertial motion sensors and e-textiles-based interactive wearable technologies. However, translation of these technologies to the clinic would need further research to increase ease of use and improve clinical validity of the outcomes of these technologies.

DISCUSSION
The current review discusses the limitations of the interactive wearable technologies such as, limited clinical utility, bulky equipment, difficulty in setting up equipment inertial motion sensors and e-textiles.

CONCLUSION
There is tremendous potential for interactive wearable technologies in rehabilitation. With the evolution of cloud computing, interactive wearable systems can remotely provide intervention and monitor patient progress using models of telerehabilitation. This will revolutionize the delivery of rehabilitation and make rehabilitation more accessible and affordable to millions of individuals.

Sethi|Amit|A| Ting|Jordyn|J| Allen|Marcus|M| Clark|William|W| Weber|Douglas|D|

Electromyography
Wearable technology
Upper extremity
Rehabilitation
Inertial measurment unit sensors


Genomic Variations in the Structural Proteins of SARS-CoV-2 and Their Deleterious Impact on Pathogenesis: A Comparative Genomics Approach.

Abstract: A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis.

Mohammad|Taj|T|
Choudhury|Arunabh|A|
Habib|Insan|I|
Asrani|Purva|P|
Mathur|Yash|Y|
Umair|Mohd|M|
Anjum|Farah|F|
Shafie|Alaa|A|
Yadav|Dharmendra Kumar|DK|
Hassan|Md Imtaiyaz|MI|


Effects of Growth Factors on Establishment and Propagation of Embryonic Stem Cells from Very Early Stage IVF Embryos and Their Characterization in Buffalo.

Abstract:
BACKGROUND AND OBJECTIVES
Although ES cells have been derived from very early stage embryos in different species, but, so far ES cell line could be derived from early stage IVF embryos in buffalo. The present experiment was carried out to study the effects of different growth factors on attachment, formation of ES cell colonies, their extent of passaging and relative expression of pluripotency marker in these colonies in buffalo.

METHODS AND RESULTS
For this, 8~16 cell stages zona free IVF embryos were cultured with different culture condition viz. Control, Media-I: (Control+SCF), Media-II: (Control+SCF+bFGF) and Media-III: (Control+SCF+bFGF+IGF1). A total of 25 number of embryos were cultured in each medium. The efficiency (%) of blastomere attachment, % stem cell colony formation were recorded and number of passaging were evaluated in each culture condition. The results indicated that the efficiency of embryonic blastomere attachment, % stem cell colonies formation and propagation were significantly higher when medium was supplemented with growth factors viz. SCF, bFGF and IGF-1 (Media-III) than when supplemented with either SCF or SCF+bFGF. The expression of pluripotent genes viz Oct4, Nanog, FoxD3 and KLF4 were significantly higher (p<0.005) when medium was supplemented with three growth factors.

CONCLUSIONS
It can be concluded that when 8~16 cell stages zona free IVF embryos of buffalo was cultured on feeder,the %of blastomere attachment, % of ES cell colony formation and their further propagation were higher in ES cell medium supplemented with SCF+bFGF+IGF1 which may be due to high expression of pluripotent stem cell markers.

Puri|G|G|
Kumar|Kuldeep|K|
Singh|Renu|R|
Singh|R K|RK|
Yasotha|T|T|
Ranjan|R|R|
Kumar|Manish|M|
Das|B C|BC|
Singh|G|G|
Sarkar|M|M|
Bag|Sadhan|S|

Growth factors
Buffalo
Embryonic stem cell like cells


Human-Based Advanced in vitro Approaches to Investigate Lung Fibrosis and Pulmonary Effects of COVID-19.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has caused considerable socio-economic burden, which fueled the development of treatment strategies and vaccines at an unprecedented speed. However, our knowledge on disease recovery is sparse and concerns about long-term pulmonary impairments are increasing. Causing a broad spectrum of symptoms, COVID-19 can manifest as acute respiratory distress syndrome (ARDS) in the most severely affected patients. Notably, pulmonary infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the causing agent of COVID-19, induces diffuse alveolar damage (DAD) followed by fibrotic remodeling and persistent reduced oxygenation in some patients. It is currently not known whether tissue scaring fully resolves or progresses to interstitial pulmonary fibrosis. The most aggressive form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF). IPF is a fatal disease that progressively destroys alveolar architecture by uncontrolled fibroblast proliferation and the deposition of collagen and extracellular matrix (ECM) proteins. It is assumed that micro-injuries to the alveolar epithelium may be induced by inhalation of micro-particles, pathophysiological mechanical stress or viral infections, which can result in abnormal wound healing response. However, the exact underlying causes and molecular mechanisms of lung fibrosis are poorly understood due to the limited availability of clinically relevant models. Recently, the emergence of SARS-CoV-2 with the urgent need to investigate its pathogenesis and address drug options, has led to the broad application of in vivo and in vitro models to study lung diseases. In particular, advanced in vitro models including precision-cut lung slices (PCLS), lung organoids, 3D in vitro tissues and lung-on-chip (LOC) models have been successfully employed for drug screens. In order to gain a deeper understanding of SARS-CoV-2 infection and ultimately alveolar tissue regeneration, it will be crucial to optimize the available models for SARS-CoV-2 infection in multicellular systems that recapitulate tissue regeneration and fibrotic remodeling. Current evidence for SARS-CoV-2 mediated pulmonary fibrosis and a selection of classical and novel lung models will be discussed in this review.

Kiener|Mirjam|M|
Roldan|Nuria|N|
Machahua|Carlos|C|
Sengupta|Arunima|A|
Geiser|Thomas|T|
Guenat|Olivier Thierry|OT|
Funke-Chambour|Manuela|M|
Hobi|Nina|N|
Kruithof-de Julio|Marianna|M|

COVID-19
SARS-CoV-2
interstitial pulmonary fibrosis
precision-cut lung slices
organoids
lung-on-chip
alveolar regeneration
in vitro lung models


Spawning in a cold bath: reproduction of polar and deep-sea fish family Psychrolutidae.

Abstract: This study describes the spawning of the fatheads Psychrolutes marmoratus and Cottunculus granulosus, two psychrolutid species that inhabit the shelf edge and continental slope of the south-west Atlantic. Females lay large eggs of c. 2·5 mm (P. marmoratus) and 4·5-5·0 mm (C. granulosus); fecundity is from the hundreds (C. granulosus) to a few thousand eggs (P. marmoratus). Egg maturation is synchronous in P. marmoratus with an autumn-winter peak of spawning and group-synchronous in C. granulosus, which reproduces all year round. In the fishery, females predominate among adult fish in both species, possibly indicating male nest guarding on hard grounds inaccessible to fishing vessels. The reproductive strategy of representatives of the Psychrolutidae is similar to that of other sculpins of the superfamily Cottoidea.

Psychrolutes marmoratus
Cottunculus granulosus
fecundity
maturation
Cottoidea
South Atlantic


Internet-based treatment for panic disorder: A three-arm randomized controlled trial comparing guided (via real-time video sessions) with unguided self-help treatment and a waitlist control. PAXPD study results.

Abstract: A growing body of evidence suggests that Internet-based cognitive behavioral treatments (ICBT) are effective to treat anxiety disorders. However, the effect of therapist guidance in ICBT is still under debate and guided ICBT offered in a real-time audio-video communication format has not yet been systematically investigated. This three-arm RCT compared the efficacy of guided with unguided ICBT (12 weeks intervention) and a waitlist (WL). A total of 111 individuals meeting the diagnostic criteria for panic disorder (PD) were randomly assigned to one of three conditions. Primary outcomes were the severity of self-report panic symptoms and diagnostic status. Secondary outcomes were symptoms of depression, functional impairment, catastrophic cognitions, fear of sensations and body vigilance. At post-treatment, both active conditions showed superior outcomes regarding PD and associated symptoms (guided ICBT vs. WL: d = 1.04-1.36; unguided ICBT vs. WL: d = 0.70-1.06). At post-treatment, the two active conditions did not differ significantly in self-reported symptom reduction (d = 0.21-0.54, all ps > 0.05), but the guided treatment was superior to the unguided treatment in terms of diagnostic status (χ2 (1) = 13.15, p < 0.01). Treatment gains were maintained at successive follow-ups and the guided treatment became superior to the unguided treatment at 6 months follow-up (d = 0.72-1.05, all ps < 0.05).

Ciuca|Amalia M|AM|
Berger|Thomas|T|
Crişan|Liviu G|LG|
Miclea|Mircea|M|

Internet-based cognitive-behavioral treatment (ICBT)


Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration.

Abstract: In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent-non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions.

Basile|Maria Assunta|MA|
d'Ayala|Giovanna Gomez|GG|
Malinconico|Mario|M|
Laurienzo|Paola|P|
Coudane|Jean|J|
Nottelet|Benjamin|B|
Ragione|Fulvio Della|FD|
Oliva|Adriana|A|

Nanocomposites
Membranes
Poly(ε-caprolactone)
Guided tissue regeneration
Biocompatibility
Functionalization of polymers