Usefulness of Procalcitonin in Diagnosing Diabetic Foot Osteomyelitis: A Pilot Study.
Infected diabetic foot is the leading cause of hospital admissions for people with diabetes mellitus. Diabetic foot osteomyelitis (DFO) causes high morbidity and significant mortality. Current diagnostic tests for DFO are either expensive, invasive, or of low diagnostic yield. The objective of the study was to determine whether serum levels of procalcitonin (PCT), an inflammatory marker, differ between DFO and diabetic foot ulcers without osteomyelitis (ie, cellulitis) as controls. The authors also aimed to assess the usefulness of PCT in diagnosing DFO. A case-control study was designed comparing DFO with diabetic foot cellulitis as the control. Patients were classified as having osteomyelitis and cellulitis based on the International Working Group on the Diabetic Foot diagnostic criteria. Serum inflammatory markers PCT, adiponectin, C-reactive protein-1, osteoprotegerin (OPG), osteopontin (OPN), and interleukin 6 (IL-6) were analyzed in patients with DFO and controls. The median serum procalcitonin was significantly higher in the DFO group 108.5 pg/mL (range, 65.0-124.0 pg/mL) compared with 57.0 pg/mL (range, 37.2-77.0 pg/mL) controls (P = .02). Procalcitonin had a sensitivity of 79% compared with 50%, 63%, 66%, and 75% for adiponectin, OPG, OPN, and IL-6, respectively. Procalcitonin had a specificity of 70% compared with 50%, 71%, 70%, and 64%. Receiver operator characteristic curves showed a value of area under the curve of 0.73 and 0.77 for PCT and IL-6 compared with 0.4, 0.6, and 0.6 for adiponectin, OPG, and OPN, respectively. In this study, procalcitonin was a useful diagnostic test for DFOs and provided distinct diagnostic discrimination between DFO from cellulitis. It may serve as a useful marker for diagnosing DFO. Further studies in a larger population are needed to verify the findings.


[Community acquired pneumonia in the elderly].
Pneumonia, more frequent in the elderly, results in higher morbidity and mortality, and is a frequent cause of hospitalisation. Although the incidence of pneumonia increases with age, mainly after 70-75 years, life in institution, comorbid medical illness (heart disease, chronic obstructive pulmonary disease, dementia), malnutrition and defence impairments are independent risk factors. Older patients with pneumonia complain of significantly fewer symptoms than younger patients. Streptococcus pneumonia is the most common cause of pneumonia, atypical pathogen are rare. There is a shift toward gram-negative bacteria and opportunistic flora with increasing age and severity of concomitant medical illness. Anaerobic bacteria are frequent in aspiration pneumonia. To hospitalize or not is the first decision to take, based on clinical criteria and risks factors. Use of the guidelines for empirical treatment of pneumonia is recommended. Old patients often recover slowly. Pneumococcal and influenza vaccinations are effective and warranted.


Reovirus type 3 clone 9 increases interleukin-1alpha level in the brain of neonatal, but not adult, mice.
Reovirus Type 3 clone 9 (T3C9)-induced lethal encephalitis is age dependent. We examined the effects of T3C9 inoculated into neonatal and adult mice by intracerebral, intramuscular, or peroral routes and the effect of lipopolysaccharide (LPS) on IL-1alpha levels in the blood and the brain. In parallel, we measured mice survival to T3C9 challenge, primary replication, and growth in and spread to the brain. The results show that T3C9 infection increased IL-1alpha only in the brain of neonatal mice, whereas LPS enhanced IL-1alpha in the brain and in the blood in both neonatal and adult mice. In neonatal mice, a T3C9-induced IL-1alpha increase coincided with viral replication-induced nervous tissue injury and preceded death. Anti-IL-1alpha antibody partially protected neonatal mice against T3C9 peroral challenge, further suggesting that this cytokine is involved in the mechanisms leading to lethal encephalitis. In adult mice, T3C9 was not lethal and did not modify IL-1alpha levels although it slowly replicated in nervous tissues when inoculated directly into the brain. Together, these results suggest that differences in nervous tissue response to T3C9 replication between newborn and adult mice could account in part for the age-dependent susceptibility to T3C9-induced lethal encephalitis.


Reduction of Eu(3+) due to a change of the topological structure of the BO3 unit in borate glass.
Adjusting and controlling an ion's chemical state has always been a focus of researchers' attention. Herein, an intense long-lasting phosphorescence of Eu(2+) is obtained without any sacrificial reductant. The remarkable self-reducing process and the unique luminescence properties stem from a variation of the topological structure of the BO3 triangle.


Warfarin prophylaxis to prevent mortality from pulmonary embolism after total hip replacement.
Between 1970 and 1987, 3000 total hip replacements were performed at the University of California at Los Angeles, and all patients were given warfarin prophylactically, in conjunction with early postoperative elevation of the lower limb in balanced suspension and the application of elastic hose. Since 1973, the first dose of warfarin has been given on the night of the operation, and the prothrombin time has been maintained between sixteen and eighteen seconds. A pulmonary embolism occurred after fourteen (0.5 per cent) of the 3000 operations. It was never fatal. Bleeding occurred after forty-four operations (1.5 per cent). The effectiveness of the protocol of the University of California at Los Angeles was demonstrated in a large number of patients over a seventeen-year period. Since 1974, the protocol has included closer monitoring of the prothrombin time. After 2595 hip replacements that were done between 1974 and 1987, the rate of pulmonary embolism was 0.2 per cent and the rate of bleeding complications was 1.0 per cent. However, recently a higher incidence of bleeding complications (2.3 per cent) has been noted after non-cemented total hip (stem-type) replacement.


Yin and yang in cytokine regulation of corneal wound healing: roles of TNF-alpha.
During wound healing, corneal tissue has to restore its transparency for proper vision. Various cytokines and growth factors are believed to orchestrate cellular behavior in a healing cornea. This review summarizes the roles of 1 such factor, the proinflammatory cytokine tumor necrosis factor (TNF)-alpha, in the process of wound healing in the cornea. Many studies have shown the anti-transforming growth factor-beta activity of TNF-alpha in cultured cell types. However, it remains unknown whether endogenous TNF-alpha has such an effect in the in vivo healing cornea. Recently, experiments that used TNF-alpha-deficient mice clearly showed that loss of TNF-alpha results in excess inflammation and fibrogenic reaction in response to external stimuli in lung and joint tissue. In the cornea, my group's experiments reveal that the lack of TNF-alpha potentiates pathogenic excess inflammation, fibrogenic response, and neovascularization in an alkali-burned mouse cornea. We uncovered the principal role of the lack of TNF-alpha in invaded macrophages, but not in corneal cells, in the development of this phenomenon by using Smad7 gene transfer, bone marrow transplantation, and cell culture experiments. These findings provide additional information for understanding the role of the cytokine network in corneal wound healing. Further studies are needed to determine if anti-TNF-alpha strategies might be effective in the treatment of ocular surface inflammatory or allergic disorders.


[Correlation of sperm DNA fragmentation index and high DNA stainability with teratospermia severity and the patient's age: A study of 1 393 infertile males].
To investigate the correlation of the severity of teratospermia and the age of the patient with sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) in male infertility patients. We collected semen samples from 1 393 infertile males from July to December 2021. Based on the WHO Laboratory Manual for the Examination and Processing of Human Semen (5th Ed), we performed sperm morphology analysis, examined perm DFI and HDS by flow cytometry, and analyzed the impacts of the severity of teratospermia and the age of the patients on sperm DFI and HDS. Among the 1 393 male infertility patients, 124 (8.90%) were found with extremely severe, 214 (15.36%) with severe, 235 (16.87%) with moderate, 163 (11.70%) with mild teratospermia, and 657 (47.16%) with morphologically normal sperm (MNS), with statistically significant differences in sperm DFI and HDS among the five groups, and 822 (59.00%) were aged <35 years, 306 (21.97%) 35-<40 years, 223 (16.01%) 40-<45 years and 42 (3.02%) ≥45 years, with statistically significant differences in sperm DFI and HDS among different age groups (P < 0.05). Sperm DFI and HDS were correlated negatively with the percentage of MNS (P > 0.05), but positively with the age of the patients (P < 0.05). Increased severity of teratospermia and age of the patient can increase sperm DFI and HDS, and sperm nuclear chromatin integrity and maturity are important indicators of male fertility.


The investigation of antibacterial activity of selected native plants from North of Iran.
Plant derived products have been used for medicinal purposes during centuries. Bacterial resistance to currently used antibiotics has become a concern to public health. The development of bacterial super resistant strains has resulted in the currently used antibiotic agents failing to end many bacterial infections. For this reason, the search is ongoing for new antimicrobial agents, both by the design and by the synthesis of new agents, or through the search of natural sources for yet undiscovered antimicrobial agents. Herbal medications in particular have seen a revival of interest due to a perception that there is a lower incidence of adverse reactions to plant preparations compared to synthetic pharmaceuticals. Coupled with the reduced costs of plant preparations, this makes the search for natural therapeutics an attractive option. This research was carried out to assess the antibacterial activity aqueous and ethanolic extracts of six Azadshahr township Native plants in north of Iran against six species of pathogen bacteria by using three methods of Disk diffusion, Well method and MBC. The results of this research indicated that the effect of ethanol extracts were more than aqueous extract and among six plants, Lippia citriodora and Plantago major ethanol extract had the most antibacterial activity in any of the three methods. Gram-positive bacteria were more sensitive than gram-negative bacteria. Staphylococcus epidermidis and Staphylococcus aureus were the most susceptible Gram-positive bacteria.


Echocardiographic findings in a contemporary Afro-Caribbean population referred for evaluation of atrial fibrillation or flutter.
Atrial fibrillation and/or flutter is the most common and the most significant cardiac arrhythmia in the Caribbean. This study is an attempt to determine the echocardiographic findings in a current, consecutive series of Afro-Caribbean patients referred for evaluation of atrial fibrillation and flutter. Between May 1998 and June 2000, 50 patients (mean age 67 years, 58% male) had echocardiograms done. Measurements included left atrial dimension (LA), left ventricular end-systolic dimension (LVESD), LV end-diastolic dimension (LVEDD), LV posterior wall thickness (LVPWT) and ventricular septal thickness (VST). Left ventricular ejection fraction (EF) was calculated. LA > 4 cm, LVPWT or VST > 13 mm, and LVEF < 50% were considered abnormal. Atrial fibrillation was seen in 92%, atrial flutter in 8%; 60% were chronic, 40% paroxysmal; 56% had congestive heart failure. The most frequent echocardiographic finding was LV hypertrophy (19/50, 38%). Left ventricular systolic dysfunction was present in 12/50, 24% (25% with LV hypertrophy also). Valvular disease (abnormal appearing valve, no Doppler study), was seen in 9/50, 18%. Normal findings ("lone atrial fibrillation") were seen in 10/50, 20%. Increased LA dimension was seen in 39/50, 78%. Patients with lone atrial fibrillation were younger (mean 56 years) than those with valvular disease (mean 64 years), LV systolic dysfunction (mean 69 years) and those with LV hypertrophy (mean 72 years). Thus, LV hypertrophy, probably secondary to hypertension, is the most frequent echocardiographic finding, with LV dysfunction (such as seen in coronary artery disease) seen less often. Valvular disease and lone atrial fibrillation rates are similar to rates in developed countries.


Beam orientation optimization for IMRT by a hybrid method of the genetic algorithm and the simulated dynamics.
We have developed a new method for beam orientation optimization in intensity-modulated radiation therapy (IMRT). The problem of beam orientation optimization in IMRT is solved by a decoupled two-step iterative process: (1) optimization of the intensity profiles for given beam configurations; (2) selection of optimal beam configurations based on the ranking by an objective function score for the results of the intensity profile optimization. The simulated dynamics algorithm is used for the intensity profile optimization. This algorithm enforces both the hard constraints and dose-volume constraints. A genetic algorithm is used to select beam orientation configurations. The method has been tested for both a simulated and clinical case, and the results show that beam orientation optimization significantly improved IMRT plans within a time period that is clinically acceptable. The results also show the dependence of the optimal orientation configurations on the prescribed constraints. In addition, beam orientation optimization by the method described here can provide multiple plans with similar dose distributions. This degeneracy characteristic can be exploited to our advantage in introducing additional planning objectives, e.g., the smoothness of intensity profiles, for the selection of the optimal plan among the degenerate configurations for treatment delivery.


Teachers' in-flight thinking in inclusive classrooms.
This article explores the thinking of five junior high school teachers as they teach students with learning difficulties in inclusive classrooms. Insights into the ways these teachers think about students in these inclusive secondary school contexts were obtained through triangulating data from semistructured interviews, stimulated recall of in-flight thinking, and researcher field notes. Exploration of teachers' in-flight thinking (i.e., the thinking of teachers as they engaged in classroom teaching) revealed a knowledge of individual students that was not related to categorical notions of learning difficulties. This research has implications for the practice of teaching in inclusive settings as well as for teacher preparation. Specifically, it suggests that attention to student differences should be replaced by the development of teachers' knowledge about individual students as a rich source of practical knowledge and the basis for developing effective instructional techniques.


Intravascular ultrasound-guided bedside placement of inferior vena cava filters.
Pulmonary emboli in a critically ill patient population is an occurrence that may be reduced with appropriate utilization of inferior vena cava (IVC) filters. Complications both during transfer or transport of critically ill patients who are dependent upon multiple intravenous drips, ventilators and intensive monitoring may be reduced with bedside placement of inferior vena cava filters. Over the last decade, investigators have been developing techniques for bedside IVC filter placement based on intravascular ultrasound techniques. We discuss and detail a single venous access technique of IVC filter placement using intravascular ultrasound.


[Effect of hydrogen-rich saline on the CD4(+) CD25(+) Foxp3(+) Treg cells of allergic rhinitis guinea pigs model].
Objective: To explore the effect of hydrogen-rich saline on the CD4(+) CD25(+) Foxp3(+) Treg cells in a guinea pig model of allergic rhinitis (AR) and investigate the underling anti-inflammatory mechanism. Methods: Using random number table, eighteen guinea pigs were divided into three groups (control group/AR group/HRS group, n=6 of each group). AR guinea pig model was built with ovalbumin and aluminum. The guinea pigs were injected with hydrogen-rich saline (HRS group) for ten days after sensitation. And control group was injected with equal normal saline at the same time. Number of sneezes, degree of runny nose and nasal rubbing movements were scored. Peripheral blood eosinophil count was recorded. The content of interleukin 10(IL-10) and transforming growth factor β (TGF-β) in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical method was taken to detect IL-10 and TGF-β in nasal mucosa. The proportion of CD4(+) CD25(+) Foxp3(+) T cells in the CD4(+) T cells of spleen and peripheral blood were determined with flow cytometry. SPSS 17.0 software was used to analyze the data. Results: There was significant difference in symptom scores among them. The scores of AR group preceded control group, and HRS could decrease the scores of AR ((6.29±1.79) vs (1.01±0.71), (4.50±0.84) vs (6.29±1.79), F=24.725, all P<0.05). The highest number of eosinophils in the peripheral blood belonged to control group, and the number of eosinophils were dramatically reduced after HRS administration ((0.41±0.05)×10(9)/L vs (0.25±0.03 )×10(9)/L, (0.32±0.03)×10(9)/L vs (0.41±0.05)×10(9)/L, F=70.05, all P<0.05). The content of IL-10 and TGF-β in control group is peak ((86.88±17.17) pg/ml, (598.28±72.70) pg/ml, respectively), and compared with AR group, HRS also increased the expression of IL-10 and TGF-β of peripheral blood ((72.54±11.75) pg/ml vs (53.49±10.07) pg/ml, (530.23±57.15) pg/ml vs (482.69±65.96) pg/ml, F value was 28.357, 14.128, respectively, all P<0.05). The proportion of CD4(+) CD25(+) Foxp3(+) Treg cells in controls exceeded HRS group and AR group (1.81%±0.10%, 1.29%±0.74%, respectively), and HRS treatment increased the ratio of CD4(+) CD25(+) Foxp3(+) Treg cells than AR group of peripheral blood ((1.50%±0.11%) vs (1.15%±0.11%), F=168.96, P<0.05). But there was no significant diferences in splene tissue ((1.01%±0.08%) vs (0.98%±0.09%), F=97.381, P>0.05). Conclusion: Both the number and the cytokine secretion of CD4(+) CD25(+) Foxp3(+) Treg cells are decreased in AR group, HRS may inhibit inflammatory response and ameliorate AR via improving the number and the cytokine secretion.


Association of Vitamin K and Non-Vitamin K Oral Anticoagulant Use and Cancer Incidence in Atrial Fibrillation Patients.
The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants (DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person-year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), and breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real-world cohort of patients with NVAF followed for up to 5 years.


[Research progress of Chinese herbs inhibiting NADPH oxidase].
Oxidative damage mediated by the abnormal activation of NADPH oxidase and the resulting excessive ROS generation is the pathogenesis for various diseases. Chinese herbs can play a role in the antioxidant treatment by inhibiting NADPH oxidase, which is meaningful for the treatment of pathological conditions such as injury of tissues, blood vessels and nerves, atherosclerosis, ischemia reperfusion, hypertension and hyperglycemia. In this paper, different forms of Chinese herbs including monomers, compounds and Chinese patent medicines with the inhibitory effect against NADPH oxidase would be reviewed, in order to explain and generalize their possible functions and the target mechanism for inhibition.


Comparative genomics on ROR1 and ROR2 orthologs.
Transmembrane proteins with extracellular Frizzled domain, such as ROR1, ROR2, MUSK, MFRP, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9 and FZD10, are key molecules for WNT signaling network. Here, comparative integromics analyses on ROR1 and ROR2 orthologs were performed by using bioinformatics. Zebrafish ror2 gene, consisting of nine exons, was identified within CR-450684.3 genome sequence. CV490605.1 EST corresponded to the 5'-end of zebrafish ror2 mRNA, and BM533602.1 EST corresponded to the 3'-end. Zebrafish ror2 gene was found to encode a 939-aa transmembrane protein, showing 71.7% and 56.2% total amino-acid identity with human ROR2 and ROR1, respectively. Immunoglobulin-like domain, Frizzled domain, Kringle domain within the extracellular region, tyrosine kinase domain, Ror homology C-terminal (RORHC) domain and juxta-C-terminal LLGD motif within the cytoplasmic region were conserved among vertebrate ROR1 and ROR2 orthologs. SH2 binding site within the RORHC domain was conserved among vertebrate ROR2 orthologs, but not among vertebrate ROR1 orthologs. ROR1 mRNA was expressed in embryonic stem (ES) cells, infant brain, renal cancer, and colon cancer. ROR2 mRNA was expressed in parathyroid, testis, uterus, and also in diffuse type gastric cancer with signet ring cell features. ROR2 promoter rather than ROR1 promoter was more evolutionarily conserved. WNT5A and ROR family receptors, co-expressed in ES cells and gastric cancer, are implicated in the planar cell polarity (PCP) pathway. ROR1 and ROR2 are the pharmacogenomics targets in the fields of stem cell biology and oncology.


Malnutrition in Hospitals: It Was, Is Now, and Must Not Remain a Problem!
Malnutrition is an under-recognized problem in hospitalized patients. Despite systematic screening, the prevalence of malnutrition in the hospital did not decrease in the last few decades. The aim of our study was to evaluate the prevalence of malnutrition and to determine the explicit daily calorie intake of hospitalized patients, to identify the risk factors of developing malnutrition during hospitalization and the effect on the financial reimbursement according to the German DRG-system. 815 hospitalized patients were included in this study. The detection of malnutrition was based on the nutritional-risk-screening (NRS) and subjective-global-assessment (SGA) scores. A trained investigator recorded the daily calorie and fluid intake of each patient. Furthermore, clinical parameters, and the financial reimbursement were evaluated. The prevalence of malnutrition was 53.6% according to the SGA and 44.6% according the NRS. During hospitalization, patients received on average 759.9±546.8 kcal/day. The prevalence of malnutrition was increased in patients with hepatic and gastrointestinal disease and with depression or dementia. The most important risk factors for malnutrition were bed rest and immobility (OR=5.88, 95% CI 2.25-15.4). In 84.5% of patient records, malnutrition was not correctly coded, leading to increased financial losses according to the DRG-system (94.908 Euros). Hospitalized patients suffer from inadequate nutritional therapy and the risk for developing malnutrition rises during the hospital stay. The early screening of patients for malnutrition would not only improve management of nutritional therapy but also, with adequate coding, improve financial reimbursement according to the DRG-system.


Trends in scale and structure of Korea's health expenditure over last three decades (1980-2009): financing, functions and providers.
This paper introduces statistics related to the size and composition of Korea's total health expenditure. The figures produced were tailored to the OECD's system of health accounts. Korea's total health expenditure in 2009 was estimated at 73.7 trillion won (US$ 57.7 billion). The annual per capita health expenditure was equivalent to US$ PPP 1,879. Korea's total health expenditure as a share of gross domestic product was 6.9% in 2009, far below the OECD average of 9.5%. Korea's public financing share of total health expenditure increased rapidly from less than 50% before 2000 to 58.2% in 2009. However, despite this growth, Korea's share remained the fourth lowest among OECD countries that had an average public share of 71.5%. Inpatient, outpatient, and pharmaceutical care accounted for 32.1%, 33.0%, and 23.7% of current health expenditure in 2009, respectively. A total of 41.1% of current health expenditure went to hospitals, 28.1% to providers of ambulatory healthcare (15.9% on doctor's clinics), and 17.9% to pharmacies. More investment in the translation of national health account data into policy-relevant information is suggested for future progress.


Is fluoroquinolone monotherapy a useful alternative treatment for Pseudomonas aeruginosa bacteraemia?
Pseudomonas aeruginosa bacteraemia is associated with high mortality, and most monotherapies are beta-lactam-based. We aimed to investigate clinical outcomes of definitive fluoroquinolone monotherapy versus beta-lactam monotherapy for P. aeruginosa bacteraemia. This retrospective study enrolled adult patients receiving definitive monotherapy with beta-lactam or fluoroquinolone between November 2013 and November 2014 at Taipei Veterans General Hospital. The independent risk factors for 28-day mortality were analyzed by logistic regression and propensity score-adjusted analysis. Among the 105 patients enrolled, 78 patients received beta-lactams and 27 received fluoroquinolones (20 with ciprofloxacin and 7 with levofloxacin). Primary bacteraemia (39.0%) and urinary tract infections (37.1%) were the most common sources of bacteraemia. The 28-day mortality rate was 11.1% for those receiving fluoroquinolones and 32.1% for those receiving beta-lactams (P = 0.062). The 28-day mortality rate between the two groups stratified by APACHE II and Pitt bacteraemia scores showed no significant differences in each category. Propensity score-adjusted multivariate analysis revealed that definitive therapy with a fluoroquinolone was not associated with 28-day mortality (OR 0.42; 95% CI 0.08-2.23; P = 0.305). Fluoroquinolone might be an alternative to beta-lactam as a definitive monotherapy for P. aeruginosa bacteraemia provided they are active in vitro. Our results could be a basis for further studies and provide a possible target for antibiotic stewardship interventions in P. aeruginosa bacteraemia.


Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders.
C-reactive protein (CRP) tends to be elevated in individuals with psychiatric disorders. Recent findings have suggested a protective effect of the genetic liability to elevated CRP on schizophrenia risk and a causative effect on depression despite weak genetic correlations, while causal relationships with bipolar disorder were inconclusive. We investigated the shared genetic underpinnings of psychiatric disorders and variation in CRP levels. Genome-wide association studies for CRP (n = 575,531), bipolar disorder (n = 413,466), depression (n = 480,359), and schizophrenia (n = 130,644) were used in causal mixture models to compare CRP with psychiatric disorders based on polygenicity, discoverability, and genome-wide genetic overlap. The conjunctional false discovery rate method was used to identify specific shared genetic loci. Shared variants were mapped to putative causal genes, which were tested for overrepresentation among gene ontology gene-sets. CRP was six to ten times less polygenic (n = 1400 vs 8600-14,500 variants) and had a discoverability one to two orders of magnitude higher than psychiatric disorders. Most CRP-associated variants were overlapping with psychiatric disorders. We identified 401 genetic loci jointly associated with CRP and psychiatric disorders with mixed effect directions. Gene-set enrichment analyses identified predominantly CNS-related gene sets for CRP and each of depression and schizophrenia, and basic cellular processes for CRP and bipolar disorder. In conclusion, CRP has a markedly different genetic architecture to psychiatric disorders, but the majority of CRP associated variants are also implicated in psychiatric disorders. Shared genetic loci implicated CNS-related processes to a greater extent than immune processes, which may have implications for how we conceptualise causal relationships between CRP and psychiatric disorders.


STM imaging, spectroscopy and manipulation of a self-assembled PTCDI monolayer on epitaxial graphene.
Scanning Tunneling Microscopy (STM), Scanning Tunneling Spectroscopy (STS), and manipulation studies were performed on an ordered self-assembled monolayer (SAM) of N,N'-bis(1-hexylheptyl)perylene-3,4:9,10-bis(dicarboximide) molecules on epitaxial graphene on hexagonal silicon carbide - SiC(0001). Four novel aspects of the molecular SAM on graphene are presented. Molecules adsorb in both armchair and zig-zag configurations, giving rise to six orientations of the molecular layer with respect to the underlying substrate. The interaction between the molecules and the graphene surface shifts the LUMO towards the Fermi level, inducing a charge transfer and the opening of a band gap in the graphene, with the LUMO inside. This decouples the LUMO from the surface rendering it invisible in the dI/dV spectroscopy. The HOMO only becomes visible at short tip-surface distances, as its energy lies within the band gap of the SiC substrate. Finally, the observed molecular defects are very particular, being composed exclusively of molecular dimers. These molecular dimers have a stronger interaction with the graphene than other molecules.


Good surgeon: A search for meaning.
The art and philosophy of surgery are not as often discussed as scientific discoveries and technological advances in the modern era of surgery. Although these are difficult to teach and pass on to the next generations of surgeons they are no less important for training good surgeons and maintaining their high standards. The authors of this review and opinion article tried to define what being a good surgeon really means and to look into the subject by analysing the essential conditions for being a good surgeon and the qualities that such a specialist should possess. In addition to a strong theoretic knowledge and practical skills and among the several described professional and personal characteristics, a good surgeon is expected to have common sense. It enables a surgeon to make a sound practical judgment independent of specialized medical knowledge and training. The possible ways of developing and/or enhancing common sense during surgical training and subsequent practice require separate analysis.


Computed Tomography of Thoracolumbar Spine Trauma.
Thoracolumbar spine trauma typically occurs when high-energy forces damage bony and ligamentous spinal structures and, in severe cases, the spinal cord. These injuries often cause considerable neurological deficits as a result of the damage. Computed tomography (CT) is the imaging method of choice for determining injury severity in most victims of multiple trauma. In addition to describing various types of thoracolumbar trauma, this article discusses the role of CT in emergency diagnosis and management of thoracolumbar injuries.


Electrothermal Transistor Effect and Cyclic Electronic Currents in Multithermal Charge Transfer Networks.
A theory is developed to describe the coupled transport of energy and charge in networks of electron donor-acceptor sites which are seated in a thermally heterogeneous environment, where the transfer kinetics are dominated by Marcus-type hopping rates. It is found that the coupling of heat and charge transfer in such systems gives rise to exotic transport phenomena which are absent in thermally homogeneous systems and cannot be described by standard thermoelectric relations. Specifically, the directionality and extent of thermal transistor amplification and cyclical electronic currents in a given network can be controlled by tuning the underlying temperature gradient in the system. The application of these findings toward the optimal control of multithermal currents is illustrated on a paradigmatic nanostructure.


Uncovering hidden abilities for participation in research through photo-elicitation interviews: a view on participatory research with people living in residential care facilities.
Participatory research has been described to improve the relevance of research findings for the society in terms of quality of healthcare services and other public benefits. Nevertheless, there is limited guidance on how to conduct participatory research, and especially in relation to persons living in residential care facilities. To make the voices of this group heard, we therefore take a stance in the democratic approach to participatory research, and we have applied the theoretical framework Model of Human Occupation (MoHO) on participation to evaluate photo-elicitation interviews as a participatory research method with this group. A total of 13 persons living in two residential care facilities were involved in the study and asked to take photographs of their everyday life over one week. They were then invited to an individual interview to narrate the meaning of the photographs and to describe how they experienced the photo-elicitation method. The interviews were analysed in the six steps of theoretically driven reflexive thematic analysis. The findings are described in the theme 'Uncovering hidden abilities for participation in research' that describes how photo elicitation interviews facilitated the older persons' participation in research. This is illustrated by four sub-themes: 'Bridging the ageing body', 'Altering habituation to everyday life', 'Empowering storytelling', and 'Negotiating the institutional culture'. Our study findings support further application and evaluation of photo-elicitation interviews as a method for participatory research in residential care facilities. The major finding is how photo-elicitation interviews were used to reduce the impact of the institutional culture on the older persons' participation in research. The method is, however, not without limitations and we encourage researchers to study the dynamic relationship between physical, social, and cultural aspects of residential care facilities in relation to the use of photo-elicitation interviews with the persons living there.


Senescence-induced alterations of laminin chain expression modulate tumorigenicity of prostate cancer cells.
Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs) are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM alpha4 and beta2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM alpha4 or beta2 chain or both chains. Increased expression of either the LM alpha4 or beta2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer.


A novel form of hereditary sideroblastic anaemia with macrocytosis.
We describe a pedigree with maternally inherited sideroblastic anaemia in which the red cells are dimorphic with a raised MCV. To our knowledge, this form of hereditary sideroblastic anaemia (HSA) has not been reported previously. 16 members of the family were investigated, revealing eight affected members. Two further family members were not tested but were presumed affected on the histories available. The proband, born in 1967, presented during pregnancy with a macrocytic anaemia (Hb 7.0 g/dl, MCV 106 fl) and a dimorphic red cell picture. Post partum, a bone marrow biopsy showed hypercellularity, mild dyserythropoiesis and ring sideroblasts. Cytogenetics were normal. Other causes of macrocytosis were excluded. Six other family members (three female, three male) have similar findings. There is no evidence of paternal transmission. An additional female relative who presented in 1992 with refractory anaemia with excess blasts in transformation and a dimorphic blood film, died from progression to AML. Affected members show a raised metal-free red cell protoporphyrin level suggestive of a defect at the level of Fe2+ incorporation into protoporphyrin. We propose that this form of HSA is due to a mitochondrial mutation. A search for deletions or point mutations in the mitochondrial DNA is currently underway.


scHiCDiff: detecting differential chromatin interactions in single-cell Hi-C data.
Here, we presented the scHiCDiff software tool that provides both nonparametric tests and parametirc models to detect differential chromatin interactions (DCIs) from single-cell Hi-C data. We thoroughly evaluated the scHiCDiff methods on both simulated and real data. Our results demonstrated that scHiCDiff, especially the zero-inflated negative binomial model option, can effectively detect reliable and consistent single-cell DCIs between two conditions, thereby facilitating the study of cell type-specific variations of chromatin structures at the single-cell level. scHiCDiff is implemented in R and freely available at GitHub (https://github.com/wmalab/scHiCDiff).


COST OF GLANDULAR TRICHOMES, A "RESISTANCE" CHARACTER IN DATURA WRIGHTII REGEL (SOLANACEAE).
Models regarding the evolution of plant resistance to herbivory often assume that the primary mechanism maintaining resistance polymorphisms is the balance between benefits of increased resistance to herbivores and costs associated with the production of a resistance character. However, rarely has it been demonstrated that genetically based resistance traits are costly. Here, we document costs associated with the production of glandular trichomes, a resistance character in Datura wrightii that is predominantly under the control of a single gene of large effect. In the absence of herbivores, plants with glandular trichomes (sticky) produced 45% fewer viable seeds than plants with nonglandular trichomes (velvety). Although both plant types flowered with similar frequency, sticky plants matured fewer capsules and fewer of their seeds germinated. The fitness difference between the types in herbivore-free conditions was not mitigated by the addition of water, a potentially limiting resource for sticky plants. Under herbivore pressure, there was no significant fitness difference between the types, although the fitness of velvety plants was still higher than that of sticky plants. This occurred even though velvety plants sustained more herbivore damage than sticky plants and were more likely to be attacked by most herbivore species present. The fitness difference between the plant types was especially reduced when herbivore-attacked plants were watered, which indicates that sticky plants may have higher tolerance for damage than velvety plants when supplied with a potentially limiting resource. Yet, the maintenance of a fitness deficit (albeit small and nonsignificant) for sticky plants when attacked by herbivores indicates no net benefit associated with the production of glandular trichomes in this first year of our study. These results add to our current understanding that herbivore resistance characters can be costly and raise the question of how this genetic polymorphism is maintained in wild populations.


Immunomodulatory Activity of Mesenchymal Stem Cells in Lupus Nephritis: Advances and Applications.
Lupus nephritis (LN) is a significant cause of various acute and chronic renal diseases, which can eventually lead to end-stage renal disease. The pathogenic mechanisms of LN are characterized by abnormal activation of the immune responses, increased cytokine production, and dysregulation of inflammatory signaling pathways. LN treatment is an important issue in the prevention and treatment of systemic lupus erythematosus. Mesenchymal stem cells (MSCs) have the advantages of immunomodulation, anti-inflammation, and anti-proliferation. These unique properties make MSCs a strong candidate for cell therapy of autoimmune diseases. MSCs can suppress the proliferation of innate and adaptive immune cells, such as natural killer cells (NKs), dendritic cells (DCs), T cells, and B cells. Furthermore, MSCs suppress the functions of various immune cells, such as the cytotoxicity of T cells and NKs, maturation and antibody secretion of B cells, maturation and antigen presentation of DCs, and inhibition of cytokine secretion, such as interleukins (ILs), tumor necrosis factor (TNF), and interferons (IFNs) by a variety of immune cells. MSCs can exert immunomodulatory effects in LN through these immune functions to suppress autoimmunity, improve renal pathology, and restore kidney function in lupus mice and LN patients. Herein, we review the role of immune cells and cytokines in the pathogenesis of LN and the mechanisms involved, as well as the progress of research on the immunomodulatory role of MSCs in LN.


[What is the athlete's heart?].
The different components of the cardiovascular system adapt to the stress related to physical training. These adaptations, mainly functional and partly morphological, concern both the heart and the vessels. They play a key role in physical performance improvement, especially in case of endurance sports.


A Study of the Effectiveness of Mobile Health Application in A Self-management Intervention for Kidney Transplant Patients.
With the development of information technology in medical treatment, mobile medical treatment has become a new way to seek treatment, follow-up, extended care, popular science, disease prevention and access to disease expertise. The application of mobile medical treatment is relatively mature in the management of chronic diseases. Currently, mobile medical intervention is also introduced in the self-management of patients after Renal Transplantation. Compared with traditional intervention methods, mobile medical treatment has the advantages of convenience, speed, low cost and no geographical restriction, and it is easy to be used by KT recipients in self-management and has good feasibility. Therefore, we conducted self-management intervention for patients after Renal Transplantation based on mobile medical procedures, so as to improve patients' satisfaction, medication compliance, follow-up rate, and ease patients' anxiety about the disease. A total of 160 discharged patients with stable recovery of transplanted Renal function who underwent renal transplantation surgery in our hospital from January 2021 to January 2023 were selected for retrospective analysis. According to the different intervention plan, the patients were divided into the intervention group and the comparison group, 80 cases each. Among them, the intervention group used the mobile medical application selfmanagement behavior intervention, and the comparison group used the conventional self-management behavior intervention. The differences of self-management behavior score, quality of life score, Basel score and anxiety score between the two groups of patients after Renal Transplantation were analyzed and compared. After intervention, there were statistically significant differences in the scores of self-management behavior scale, Quality of life related rating scale, Basel Assessment scale and Self-rating Anxiety Scale between the intervention group and the control group (P < .05). Mobile health intervention tools can provide efficient, comprehensive and accurate remote health intervention and professional support for patients, optimize the medical service system, and meet the social medical needs of high-quality nursing services. DOI: 10.52547/ijkd.7693.


Methamphetamine and emerging drugs of concern: A training needs analysis of Australian alcohol and other drug helplines.
Fielding greater than 100,000 calls annually, telephone helplines are an important point of entry to alcohol and other drug (AOD) support and services in Australia. Methamphetamine and emerging drugs can present a particular challenge for this workforce. We sought to identify training needs for these services, so that appropriate targeted resources can be developed. We distributed an anonymous, online, cross-sectional survey to helpline staff from New South Wales, Queensland, South Australia, Victoria and Western Australia. Based on the WHO Hennessy-Hicks training needs analysis tool, participants were asked: to rate on a 7-point likert scale the importance of a topic to their practice and how well they perform in relation to the topic; open-ended questions specifying their own self-perceived training needs; and demographic data. Of 50 participants, 29 completed the full survey (median age 49 [IQR 30-57.5]; median time working in AOD sector 6 years [IQR 1-20]). The results identified a need for: practical community-informed population relevant information for culturally and linguistically diverse populations and Aboriginal and Torres Strait Islander peoples for calls relating to methamphetamine and emerging drugs of concern; training and resources with a particular focus on families and friends of people who use methamphetamine and emerging drugs; and readily accessible up-to-date information on new and emerging drugs and treatment of related disorders. This training needs analysis provides a structured approach to supporting the first-line AOD counsellors to provide up-to-date and accurate information to assist Australians seeking information, support and advice.


Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization.
Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.


A technology evaluation of the atypical use of a CPP-containing peptide in the formulation and performance of a clinical botulinum toxin product.
Cell-penetrating peptides (CPPs), are small peptides that facilitate cytosolic access and, thus, transport of therapeutic macromolecules to intracellular sites when conjugated to cargo proteins. As with all new delivery platforms, clinical development of CPP-containing therapeutics has faced considerable challenges. RTP004 is a novel, 35-amino acid, bi-CPP-containing excipient that binds noncovalently with its cargo (botulinum toxin type A) rather than conjugated as a fusion protein. An RTP004-containing neurotoxin formulation, daxibotulinumtoxinA-lanm for injection (DAXI), has recently been approved by the FDA. The formulation and pharmacological characteristics of RTP004 and the efficacy and safety of the RTP004-neurotoxin formulation are discussed. RTP004 is a highly positively charged lysine- and arginine-rich structure that provides formulation stability, preventing self-aggregation of the cargo protein and adsorption to container surfaces. The presence of RTP004 in the formulation also appears to increase presynaptic binding of the neurotoxin, reduces post-injection diffusion, and thus facilitates an increase in the cleavage of the intracellular substrate for the botulinum toxin, likely through enhanced cellular uptake. The RTP004-neurotoxin formulation is the first CPP-containing product approved for clinical use. The potential for RTP004 to facilitate other therapeutic cargo molecules requires further research.


Evidence for heterogenous glycine domains but conserved multiple states of the excitatory amino acid recognition site of the NMDA receptor: regional binding studies with [3H]glycine and [3H]L-glutamate.
The possible heterogeneity of the agonist and glycine sites of the N-methyl-D-aspartate (NMDA) receptor-complex was examined using receptor binding techniques. Binding of [3H]L-glutamate [( 3H]GLU) and [3H]glycine to synaptic membranes of cerebral and cerebellar cortices, and membranes of a granule cell preparation of rat cerebellum, was characterized. [3H]Glycine always labelled a single population of sites; densities of binding sites (Bmax) in cortical, cerebellar and "granule" membranes were 3.1, 0.87 and 3.6 pmol/mg protein, respectively. Dissociation constants (Kd) in the same three preparations were 0.13, 0.31 and 1.9 microM, respectively. In competition studies, D-cycloserine, but not D-serine and 7-chlorokynurenate, showed varying potency between the membrane preparations, and analysis of variance (ANOVA) revealed a significant interaction between ligands and membrane fractions. Binding of [3H]GLU was saturable and to a single population of sites: Kd 0.5-0.9 microM and Bmax 3.2-3.6 pmol/mg protein. In all three membrane preparations the rank order of potency of NMDA agonists as inhibitors of the binding of [3H]GLU was always L-aspartate greater than L-cysteate greater than L-cysteinesulphinate greater than L-serine-O-sulphate greater than ibotenate greater than L-homocysteate. NMDA, quinolinate and competitive NMDA antagonists were only weak inhibitors of the binding of [3H]GLU and never fully inhibited specific binding. Other subtype-selective excitatory amino acids were very weak or ineffective inhibitors of binding. Binding of NMDA agonists was better described by a two site model whereby the proportion of high affinity sites did not vary significantly across the three membrane preparations.(ABSTRACT TRUNCATED AT 250 WORDS)


Enzymatic identification of the load-bearing boundary lubricant in the joint.
Bovine articular cartilage and synovial fluid (SF) were co-incubated with one of three enzymes selected to destroy each of the three major contenders for the active ingredient imparting such remarkable load-bearing lubrication to the normal joint. Destroying hyaluronic acid (HA), alias hyaluronan, with hyaluronidase, both frictional and wear tests displayed no significant change in accordance with most previous studies of SF alone. Destroying surface-active phospholipid (SAPL) with phospholipase A2, there was a highly significant dose-dependent compromise of lubrication as recorded on both tests. Trypsin produced a somewhat surprising result in that lubrication of the cartilage actually improved. This result can be interpreted as indicating that lubricin is not the lubricant per se, but, as a water-soluble, macromolecular, proteinaceous carrier for phospholipid, its destruction caused more SAPL to be deposited as the true load-bearing lubricant. These results are discussed in the context that SAPL, lubricin and HA each have specific roles in a comprehensive lubrication system.


Elasticity of smectic liquid crystals with in-plane orientational order and dispiration asymmetry.
The Nelson-Peliti formulation of the elasticity theory of isolated fluid membranes with orientational order emphasizes the interplay between geometry, topology, and thermal fluctuations. Fluid layers of lamellar liquid crystals such as smectic-C, hexatic smectics, and smectic-C^{*} are endowed with in-plane orientational order. We extend the Nelson-Peliti formulation so as to bring these smectics within its ambit. Using the elasticity theory of smectics-C^{*}, we show that positive and negative dispirations (topological defects in Smectic-C^{*} liquid crystals) with strengths of equal magnitude have disparate energies-a result that is amenable to experimental tests.


Laboratory assessment of the anticoagulant activity of dabigatran.
Our aim was to identify laboratory assays in order to assess the anticoagulant effects of dabigatran etexilate (DE). Twenty patients with nonvalvular atrial fibrillation treated on DE (110 mg per os twice daily) and 20 on acenocoumarol were studied. Conventional coagulation tests, endogenous thrombin potential (ETP), thromboelastometry (ROTEM), epinephrine-induced light transmission aggregometry (LTA), and Hemoclot Thrombin Inhibitors (HTI) were performed in all patients. In ROTEM analysis, the lysis index at 60 minutes was significantly lower in patients receiving DE (P = .011). In LTA, patients on DE showed decreased aggregation compared to those on acenocoumarol, marginally insignificant (P = .068). Regarding ETP, acenocoumarol affected thrombin generation more than dabigatran (area under the curve [AUC], P < .001), while statistically significant associations were detected between dabigatran levels, as determined by the HTI assay, and almost all parameters of ETP assay (AUC, P < .001). The role of ETP in estimating anticoagulant activity of dabigatran possibly requires further research.


A morphometric study of the amygdala in the guinea pig.
The characteristic features of guinea pig amygdala (CA), as shown by volumetric comparisons of the individual nuclei, are the poor development of the basolateral (BL) and lateral olfactory tract (NLOT) nuclei as well as the strong formation of the lateral (LA) and basomedial (BM) nuclei. The central (CE), cortical (CO) and medial (ME) nuclei also appear to be well represented in this species. All these features are even more pronounced when the total number of neurons in the nuclei referred to was taken into consideration. A comparison of the densities of neurons in the individual nuclei with the mean numerical density of cells in the guinea pig CA indicates that the densities of neurons in LA, BL, BM, CE and CO are significantly lower than the mean (p < 0.05), whereas in the ME and NLOT these values are significantly higher than the mean (p < 0.05). It is noteworthy, that the densities of the neurons in CE and CO do not differ statistically from each other (p > 0.05) and are significantly higher than the respective values in LA, BL and BM (p < 0.05). Furthermore, a similar division of the guinea pig CA may to some extent be made using the size parameters of the amygdaloid neurons as a marker. Interestingly, the large neurons populate organised CA areas like LA, BL and BM less densely, whereas the small cells create ME and NLOT, where the neurons are densely arranged. CE and CO occupy intermediate positions, with the neurons similar in size to the mean for the guinea pig CA.


Azo complexes of osmium(II): preparation and reactivity of organic azide and hydrazine derivatives.
Mixed-ligand hydride complexes OsHCl(CO)(PPh3)2L (2) [L = P(OMe)3, P(OEt)3] were prepared by allowing OsHCl(CO)(PPh3)3 (1) to react with an excess of phosphite P(OR)3 in refluxing toluene. Dichloro compounds OsCl2(CO)(PPh3)2L (3, 4) were also prepared by reacting 1, 2 with HCl. Treatment of hydrides OsHCl(CO)(PPh3)2L (2), first with triflic acid and then with an excess of RN3 afforded organic azide complexes [OsCl(η(1)-N3R)(CO)(PPh3)2L]BPh4 (5-7) [R = 4-CH3C6H4CH2, C6H5CH2, C6H5; L = P(OEt)3]. Benzylazide complexes react in CH2Cl2/ethanol solution, leading to the imine derivative [OsCl(CO){η(1)-NH═C(H)C6H4-4-CH3}(PPh3)2{P(OEt)3}]BPh4 (8b). Hydrazine complexes [OsCl(CO)(RNHNH2)(PPh3)2L]BPh4 (9-11) [R = H, CH3, C6H5; L = P(OMe)3, P(OEt)3] were prepared by allowing hydride species OsHCl(CO)(PPh3)2L (2) to react first with triflic acid and then with an excess of hydrazine. Aryldiazene derivatives [OsCl(CO)(ArN═NH)(PPh3)2L]BPh4 (12, 13) were also prepared following two different methods: (i) by oxidizing arylhydrazine [OsCl(C6H5NHNH2)(CO)(PPh3)2L]BPh4 (11) with Pb(OAc)4 in CH2Cl2 at -30 °C; (ii) by allowing hydride species OsHCl(CO)(PPh3)2L (2) to react with aryldiazonium cations ArN2(+) (Ar = C6H5, 4-CH3C6H4) in CH2Cl2. The complexes were characterized spectroscopically and by X-ray crystal structure determination of OsHCl(CO)(PPh3)2[P(OEt)3] (2b) and [OsCl{η(1)-NH═C(H)C6H4-4-CH3}(CO)(PPh3)2{P(OEt)3}]BPh4 (8b).


AN EXAMINATION OF THE GLUTEAL MUSCLE ACTIVITY ASSOCIATED WITH DYNAMIC HIP ABDUCTION AND HIP EXTERNAL ROTATION EXERCISE: A SYSTEMATIC REVIEW.
A wide variety of hip abduction and hip external rotation exercises are used for training, both in athletic performance and in rehabilitation programming. Though several different exercises exist, a comprehensive understanding of which exercises best target the gluteus maximus (Gmax) and gluteus medius (Gmed) and the magnitude of muscular activation associated with each exercise is yet to be established. The purpose of this systematic review was to quantify the electromyographic (EMG) activity of exercises that utilize the Gmax and Gmed muscles during hip abduction and hip external rotation. Pubmed, Sports Discuss, Web of Science and Science Direct were searched using the Boolean phrases (gluteus medius OR gluteus maximus) AND (activity OR activation) AND (electromyography OR EMG) AND (hip abduction OR hip external rotation). A systematic approach was used to evaluate 575 articles. Articles that examined injury-free participants of any age, gender or activity level were included. No restrictions were imposed on publication date or publication status. Articles were excluded when not available in English, where studies did not normalize EMG activity to maximum voluntary isometric contraction (MVIC), where no hip abduction or external rotation motion occurred or where the motion was performed with high acceleration. Twenty-three studies met the inclusion criteria and were retained for analysis. The highest Gmax activity was elicited during the lateral step up, cross over step up and rotational single leg squat (ranging from 79 to 113 % MVIC). Gmed activity was highest during the side bridge with hip abduction, standing hip abduction with elastic resistance at the ankle and side lying hip abduction (ranging from 81 to 103 % MVIC). The methodological approaches varied between studies, notably in the different positions used for obtaining MVIC, which could have dramatically impacted normalized levels of gluteal activation, while variation also occurred in exercise technique and/or equipment. The findings from this review provide an indication for the amount of muscle activity generated by basic strengthening and rehabilitation exercises, which may assist practitioners in making decisions for Gmax and Gmed strengthening and injury rehabilitation programs.


Selective Capture of Transcribed Sequences: A Promising Approach for Investigating Bacterium-Insect Interactions.
Bacterial interactions with eukaryotic hosts are complex processes which vary from pathogenic to mutualistic. Identification of bacterial genes differentially expressed in the host, promises to unravel molecular mechanisms driving and maintaining such interactions. Several techniques have been developed in the past 20 years to investigate bacterial gene expression within their hosts. The most commonly used techniques include in-vivo expression technology, signature-tagged mutagenesis, differential fluorescence induction, and cDNA microarrays. However, the limitations of these techniques in analyzing bacterial in-vivo gene expression indicate the need to develop alternative tools. With many advantages over the other methods for analyzing bacterial in-vivo gene expression, selective capture of transcribed sequences (SCOTS) technique has the prospect of becoming an elegant tool for discovery of genes involved in the bacterium-host interaction. Here, we summarize the advances in SCOTS technique, including its current and potential applications in bacterial gene expression studies under a variety of conditions from in-vitro to in-vivo and from mammals to insects.


Prevalence and Incidence of Multiple Sclerosis in Tehran, Iran.
Tehran is the capital of Iran with an increasing Multiple Sclerosis (MS) incidence. A retrospective population-based study was conducted to evaluate the status of MS prevalence and MS incidence trends in Tehran Province, Iran. A population-based study was conducted from 1991 to 2014 in Tehran Province, the capital city of Iran based on Iranian MS Society (IMSS) registry system. A structured questionnaire design to cover the important epidemiological variables, related at the individual level for MS. A Monte Carlo Permutation method was utilized to test whether the apparent change in MS trends during 1991-2014 was statistically significant. MS incidence was significantly increased during our study period. The annual percent change (APC) was 12.8% in women during 1991 to 2004 and 12.5% in men during the same period. The point prevalence of MS was 101.39 per 100000 populations in 2014. The age-adjusted prevalence rates were 134.03 and for male patients were 42.45 per 100000. MS prevalence and incidence in Tehran are markedly rising, it is crucial to elucidate the causes of the increasing trends and implement efficient policies lowering disease burden.


The construction of community participation: village family planning groups and the Indonesian state.
Indonesia's family planning program has been one of the most effective in the developing world in promoting contraceptive use and contributing to fertility transition. In evaluating why the program has worked, analysts have given much credit to a network of village family planning groups that developed from the 1970s to the 1990s and that blanketed the archipelago. These groups, composed primarily of female volunteers, made contraception available to women in even the most remote parts of the country, and acted as agents of family planning motivation. They have been labeled by the Indonesian state family planning agency as an example of effective community participation on a national scale. In this paper, I investigate this claim and find it to be simplistic. I provide extensive evidence that the creation of this network was orchestrated by the Indonesian state. On the other hand, I show that these groups are not fully state entities, as they have several characteristics that mark them as socially embedded institutions. They are best labeled as unusual state-society hybrids. In my investigation I draw on one of the newest paradigms in the discipline of political science--the state-society approach--to uncover the odd nature of this family planning network. More deeply, I argue that the state-society approach ought to be adopted in family planning analysis on a comprehensive basis. The traditional organizational and social-demographic approaches that have dominated the field offer only limited understanding of the nature of family planning programs in developing countries. The state-society approach is ideally suited to identifying how family planning programs are institutions of a political nature, embedded in states and societies, and transformed by and transformative of each.


Characterization of the novel In1059 harbouring VIM gene cassette.
VIM-type enzyme encodes the most widely acquired metallo-β-lactamases in Gram- negative bacteria. To obtain current epidemiological data for integrons from enterobacteriae in hospital, the study characterizes the genetic structure in In1059 by comparison with In846 integrons harbouring VIM gene and other class 1 integrons including In37, In62, In843 and In1021 with the aim of identifying the putative mechanisms involved integron mobilization and infer evolution of relevant integrons. Six of 69 recombinant plasmids from clinical strains were found to be class 1 integrons by digestion with BamHI, drug susceptibility testing, conjugation experiments, PCR amplification, integron cloning and sequencing, genome comparison, and detection of carbapenemase activity. The sequences of the six recombinant plasmids encoding In1021, In843, In846, In37, In62, and the novel In1059 integron had approximate lengths of ~4.8-, 4.1-, 5.1-, 5.3-, 5.3- and 6.6- kb, respectively. The genetic structures of these integrons were mapped and characterized, and the carbapenemase activities of their parental strains were assessed. Our results suggest that the six variable integron structures and regular variations that exist in the gene cassettes provide a putative mechanism for the integron changes. Our study has also shown that the genetic features in the integrons named above fall within a scheme involving the stepwise and parallel evolution of class 1 integron variation likely under antibiotic selection pressure in clinical settings.


DeepMiceTL: a deep transfer learning based prediction of mice cardiac conduction diseases using early electrocardiograms.
Cardiac conduction disease is a major cause of morbidity and mortality worldwide. There is considerable clinical significance and an emerging need of early detection of these diseases for preventive treatment success before more severe arrhythmias occur. However, developing such early screening tools is challenging due to the lack of early electrocardiograms (ECGs) before symptoms occur in patients. Mouse models are widely used in cardiac arrhythmia research. The goal of this paper is to develop deep learning models to predict cardiac conduction diseases in mice using their early ECGs. We hypothesize that mutant mice present subtle abnormalities in their early ECGs before severe arrhythmias present. These subtle patterns can be detected by deep learning though they are hard to be identified by human eyes. We propose a deep transfer learning model, DeepMiceTL, which leverages knowledge from human ECGs to learn mouse ECG patterns. We further apply the Bayesian optimization and $k$-fold cross validation methods to tune the hyperparameters of the DeepMiceTL. Our results show that DeepMiceTL achieves a promising performance (F1-score: 83.8%, accuracy: 84.8%) in predicting the occurrence of cardiac conduction diseases using early mouse ECGs. This study is among the first efforts that use state-of-the-art deep transfer learning to identify ECG patterns during the early course of cardiac conduction disease in mice. Our approach not only could help in cardiac conduction disease research in mice, but also suggest a feasibility for early clinical diagnosis of human cardiac conduction diseases and other types of cardiac arrythmias using deep transfer learning in the future.


Assessment of Knowledge, Attitude, and Practice Regarding Diabetic Retinopathy in an Urban Population in Northeast China.
This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic subjects with diabetic retinopathy (DR) and those without DR (NDR) in an urban community in Northeast China, as well as their risk factors in subjects with DR and NDR. A community-based survey involving 1,662 subjects was conducted in Fushun, China, between July 2012 and May 2013. The subjects included diabetics with DR (n = 783) and those NDR (n = 879), and questionnaires were completed to collect information about their sociodemographic and healthcare characteristics. A Chi-square test and multiple logistic analyses were performed to analyze the data. Among the DR group, 21.88% had a good knowledge of DR, 94.15% had a positive attitude, and 68.07% followed good practice, whereas 20.98% of the NDR group had a good knowledge of DR, 94.18% had a positive attitude, and 66.92% followed good practice. There was no significant difference in the KAP of the two groups of subjects. In the NDR group, a good level of knowledge was associated with a high-level of education (OR = 0.1, 0.2; p < 0.05), a good attitude was associated with retirement (OR = 0.2; p < 0.05), and good practice was associated with being female, having a high-level of education, and the type of treatment (OR = 0.5, 0.4, 2.3, 3.1; p < 0.05). In the DR group, good practice was associated with older age and retirement (OR = 0.6, 0.4; p < 0.05). There was no significant difference between the DR and NDR subjects in the overall levels of KAP, but both groups showed a poor level of knowledge. Age, gender, education, occupation, and type of treatment were the main factors associated with the KAP scores, more risk factors in the NDR group than in the DR group. There is an urgent need for coordinated educational campaigns with a prioritized focus on the northeast region of China, especially NDR group.


Crohn's disease and gastrocnemius vasculitis: two new cases.
We report two cases of gastrocnemius muscle vasculitis revealing Crohn's disease. Gastrocnemius muscle biopsy evidenced a necrotizing vasculitis resembling panarteritis nodosa in one case; a nonnecrotizing vasculitis was found in the other case. Neither of the patients had systemic vasculitic involvement, and the muscle disease resembled calf muscle-located panarteritis nodosa. Our literature review shows five cases of calf-located myalgia occurring during Crohn's disease characterized by heterogenous histopathological findings including vasculitic and myositic lesions. Thus, faced with calf-located myalgia with vasculitis or myositis, a search for Crohn's disease is probably necessary to determine precisely the frequency and the etiopathogenic mechanisms of this association.


Characteristics and composition of the vitamin K-dependent gamma-glutamyl carboxylase-binding domain on osteocalcin.
Two different sites on vitamin K-dependent gamma-glutamyl carboxylase (VKC) are involved in enzyme-substrate interaction: the propeptide-binding site required for high-affinity substrate binding and the active site for glutamate carboxylation. Synthetic descarboxy osteocalcin (d-OC) is a low-K(m) substrate for the VKC, but unique since it possesses a high-affinity recognition site for the VKC, distinct from the propeptide which is essential as a binding site for VKC. However, the exact location and composition of this VKC-recognition domain on d-OC has remained unclear until now. Using a stereospecific substrate analogue [t-butyloxycarbonyl-(2S,4S)-4-methylglutamic acid-Glu-Val (S-MeTPT)] we demonstrate in this paper that the high affinity of d-OC for VKC cannot be explained by a direct interaction with either the active site or with the propeptide-binding site on VKC. It is shown using various synthetic peptides derived from d-OC that there are two domains on d-OC necessary for recognition: one located between residues 1 and 12 and a second between residues 26 and 39, i.e. at the C-terminal side of the gamma-carboxyglutamate (Gla) domain. Both internal sequences contribute substantially to the efficiency of carboxylation. On the basis of these data we postulate the presence of a second high-affinity substrate-binding site on VKC capable of specifically binding d-OC, which is the first vitamin K-dependent substrate of which the VKC binding domain is interrupted by the Gla domain.


Comparison of four surgical methods for pediatric forearm double diaphyseal fractures: a retrospective analysis.
One of the most frequent fractures in children is a double forearm fracture. They make up 26% of children's long bone fractures in the upper extremities and their incidence has increased in recent years. In this study, pediatric patients with double forearm fractures were treated using plate screw, intramedullary K-wire (I-KW), intramedullary titanium elastic nails (TENs), and hybrid fixation (HF) to compare the radiographic and functional results. The printed and digital medical records were retrospectively examined from our hospital's archives after receiving consent from the regional ethics committee. Legal guardians of the patients, who were under the age of 18, gave their informed consent. Based on the surgical procedure used, the patients were split into 4 groups. Double plating was the D-P group, hybrid fixation method was the HF group, intramedullary elastic titanium nail was the TEN group, and intramedullary K-wire was the I-KW group. The study comprised 78 patients in total, with 19 patients in the HF group, 21 patients in the TEN group, 20 patients in the I-KW group, and 18 patients in the D-P group. When the mean operating times of the four approaches were compared, a substantial difference was found. The D-P group's mean operating time (65.2±4.9 minutes) was noticeably longer than those of the other groups (p<0.001). The HF group's mean operating time was 55.93.4 min longer than that of the TENs and I-KW groups, which was statistically significant (p<0.001). In comparison to the other groups, the D-P group's mean intraoperative fluoroscopy time was considerably shorter (6±3 sec) (p<0.001). When compared to the D-P group, it was considerably higher in the HF group (12±2 sec) (p<0.001). In comparison to the TENs (20±4 sec) and I-KW groups (19±5 sec), it was significantly lower in the HF group (p<0.001). In comparison to the HF group, the D-P group's tourniquet use lasted much longer (p<0.001). The TENs and I-KW groups did not use a tourniquet because a mini-incision was made. The D-P group's mean blood loss (110±10 ml) was substantially larger than that of the other groups (p<0.001) in the mean blood loss data. In comparison to the TENs (40±5 ml) and I-KW (40±5 ml) groups, the mean blood loss in the HF group (90±10 ml) was considerably larger (p<0.001). All patients received an above-elbow postoperative cast. The HF group (2 weeks) and the D-P group (2 weeks) experienced significantly less postoperative immobility than the TENs and I-KW groups (4.4 weeks, p<0.001). The four fixation techniques used in the current study for juvenile diaphyseal double forearm fractures produced positive clinical and functional outcomes. The hybrid fixation technique was discovered to be comparable to the other techniques and even beneficial in some ways. So, a safe and efficient treatment option for juvenile diaphyseal double forearm fractures is hybrid fixation.


Primary adenocarcinoma of the appendix.
A case of primary adenocarcinoma of the appendix in which the patient had the usual symptoms of acute appendicitis is presented. A review of the literature showed the potential for early extension and nodal metastasis in this lesion and led to the recommendation of right hemicolectomy as the treatment of choice. The operation should be done either primarily or secondarily after an appendectomy and should lead to a five-year survival of approximately 45%. Every effort should be made to make the diagnosis and provide definitive treatment at the primary operation by examining the appendix grossly and obtaining frozen section microscopic study of any suspicious tumor or ulceration.


The functional form of the erythropoietin receptor is a 78-kDa protein: correlation with cell surface expression, endocytosis, and phosphorylation.
An abundant 70- to 78-kDa form of the erythropoietin receptor (EPOR) was observed in HC-D57 murine erythroleukemia cells deprived of erythropoietin (EPO). In contrast to the 64- and 66-kDa EPOR proteins, these high molecular mass forms of EPOR (hmm-EPOR) correlated well with the number of binding sites and endocytosis of EPO. The hypothesis that hmm-EPOR are more highly glycosylated forms of the EPOR, appear on the cell surface, and represent at least one component of the biologically active EPOR was tested. Consistent findings were as follows. (i) Only hmm-EPOR increased following withdrawal of EPO from HC-D57 cells, correlating with a 10-fold increase in binding of 125I-labeled EPO. In addition, the EPO-dependent downregulation of 125I-EPO binding and disappearance of hmm-EPOR occurred in parallel while the amount of 66-kDa EPOR did not change. (ii) The 78-kDa EPOR was detected in COS cells expressing EPOR cDNA. (iii) Probing of the intact surface of these cells with anti-NH2-terminal antibody recovered only the 78-kDa EPOR. (iv) Enzymatic deglycosylation and dephosphorylation showed that hmm-EPOR apparently resulted from additional N-linked glycosylation of a 62-kDa EPOR. (v) The hmm-EPOR turnover in HC-D57 cells was accelerated 12-fold in the presence of EPO (half-life changed from 3 hr to 15 min). (vi) Anti-phosphotyrosine antiserum detected an EPO-dependent phosphorylation of the 78-kDa EPOR. The kinetics of tyrosine phosphorylation of a 97-kDa protein correlated with the occupancy and internalization of hmm-EPOR. In summary, we suggest that the 78-kDa EPOR is directly involved in the initial biological actions of EPO.


Localized reactive angioendotheliomatosis.
We present a unique case of a woman with multiple painful dermal lesions localized to the left upper quadrant of the body. Histological investigation revealed microvascular thrombosis with capillary-wall proliferation. Further investigation revealed a very high anticardiolipin IgG titre and a left subclavian stenosis, presumably providing the reduced blood flow and relative hypoxia to allow microthromboses to occur in the presence of a thrombophilic tendency. Similar clinical and histological features have been reported in patients with the antiphospholipid syndrome and cases of reactive angioendotheliomatosis (RAE). This case represents a unique variant of RAE.


[Basic study on the chemosensitivity test by miniaturized improved nucleic acid precursor incorporation assay (MINI assay)].
Miniaturized improved nucleic acid precursor incorporation assay (MINI assay) has been developed by Kern D. H. and Tanigawa N. et al since 1985. We investigated in vitro effects of mitomycin C (MMC), cisplatin (CDDP) and bleomycin (BLM) against A 549 lung cancer cells and HeLa cells by MINI assay. 3H-thymidine (3H-TdR) uptake in the positive control was 734.2 cpm +/- 10 cpm. The cut-off level for in vitro sensitivity was defined as more than 80% inhibition of 3H-TdR uptake in the drug treated cells compared to the positive controls. A 549 cells were sensitive to MMC (81.6%), CDDP (78.6%), but not to BLM (-57%). HeLa cells were sensitive to MMC (91%), CDDP (79.4%), but not to BLM (43%). MINI assay could be done with fewer cells than other methods and the results were obtained within 5 days. This method was considered to be useful for the chemosensitivity test with human tumors.


Human tumor xenografts in athymic (nude) mice: chemotherapy trials in serially transplanted tumors.
In a total of 38 consecutive attempts at transplanting freshly excised malignant human neoplasms in athymic nu/nu mice during the past year, 12 resulted in successful xenografts. To date, all of these have been subsequently transplanted for two or more generations. These successful xenografts include two squamous cell carcinomas of the head and neck, three squamous cell carcinomas and one undifferentiated large cell carcinoma of the lung, three adenocarcinomas of ovarian or endometrial origin, and one carcinoma of each of the following sites: urinary bladder, stomach, and colon. Chemotherapy trials on three different squamous cell carcinomas serially transplanted in nude mice revealed three different degrees of sensitivity to bleomycin. One tumor which was markedly sensitive to bleomycin showed only a slight response to cis-diamminedichloroplatinum (II). These chemotherapy trials will be expanded to wider panel of transplantable human squamous cells cacinomas of different origins with anti-tumor agents used singly or in combination.


[Life-threatening malnutrition after a laparoscopic gastric bypass operation reverting the gastrointestinal tract into normal anatomy].
We present a case report of a woman who had repeating episodes of severe life-threatening malnutrition four years after a laparoscopic gastric bypass operation for severe overweight. Despite several normal examinations her condition remained unstable. She was offered a laparoscopic operation reverting the stomach and small intestine into normal anatomy and it was performed without complications so the condition resolved. The malnutrition was probably caused by a mixture of an eating disorder and the effects of the operation influencing gut hormones. It is important to handle this category of patients in a competent multidisciplinary team.


Total synthesis and determination of the absolute configuration of rakicidin A.
Rakicidin A is a cyclic depsipeptide that has exhibited unique growth inhibitory activity against chronic myelogenous leukemia stem cells. Furthermore, rakicidin A has five chiral centers with unknown stereochemical assignment, and thus, can be represented by one of 32 possible stereoisomers. To predict the most probable stereochemistry of rakicidin A, calculations and structural comparison with natural cyclic depsipeptides were applied. A total synthesis of the proposed structure was subsequently completed and highlighted by the creation of a sterically hindered ester bond (C1-C15) through trans-acylation from an easily established isomer (C1-C13). The analytic data of the synthetic target were consistent with that of natural rakicidin A, and then the absolute configuration of rakicidin A was assigned as 2S, 3S, 14S, 15S, 16R. This work suggests strategies for the determination of unknown chiral centers in other cyclic depsipeptides, such as rakicidin B, C, D, BE-43547, and vinylamycin, and facilitates the investigations of rakicidin A as an anticancer stem cell agent.


Effects of the Combination of β-Hydroxy-β-Methyl Butyrate and R(+) Lipoic Acid in a Cellular Model of Sarcopenia.
: Sarcopenia is a clinical problem associated with several pathological and non-pathological conditions. The aim of the present research is the evaluation of the pharmacological profile of the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) associated with the natural R(+) stereoisomer of lipoic acid (R(+)LA) in a cellular model of muscle wasting. The C2C12 cell line is used as myoblasts or is differentiated in myotubes, sarcopenia is induced by dexamethasone (DEX). A Bonferroni significant difference procedure is used for a post hoc comparison. DEX toxicity (0.01-300 µM concentration range) is evaluated in myoblasts to measure cell viability and caspase 3 activation after 24 h and 48 h; cell incubation with 1 µM DEX for 48 h is chosen as optimal treatment for decreasing cell viability and increasing caspase 3 activity. R(+)LA or HMB significantly prevents DEX-induced cell mortality; the efficacy is improved when 100 µM R(+)LA is combined with 1 mM HMB. Regarding myoblasts, this combination significantly reduces DEX-evoked O2- production and protein oxidative damage. During the early phase of myotube formation, the mixture preserves the number of myogenin-positive cells, whereas it completely prevents the DEX-dependent damage in a later phase of myotube differentiation (7 days), as evaluated by cell diameter and percentage of multinucleated cells. R(+)LA in association with HMB is suggested for sarcopenia therapy.


Preliminary study on ultrasound-guided high-intensity focused ultrasound ablation for treatment of broad ligament uterine fibroids.
To investigate the feasibility, efficacy and safety of ultrasound-guided high-intensity focused ultrasound (HIFU) ablation for treating the broad ligament uterine fibroid (BLUF). A total of 236 patients with symptomatic uterine fibroids were enrolled and treated with JC-200 extracorporeal ultrasound-guided HIFU under conscious sedation between January 2017 and December 2018. Of them, data of 12 patients with 13 broad ligament fibroids were retrospectively analyzed. The patients' mean age was 38.6 ± 6.3 years. The focused ultrasound target was deployed and moved from the deeper layer to the superficial layer of BLUFs. All patients underwent contrast-enhanced MRI (CE-MRI) before, immediate post-operation, and six months after the HIFU ablation procedure. The fibroid size, non-perfusion volume (NPV) ratio, the reduction of fibroid volumes, adverse events, symptom changes, and abnormal MRI findings associated with the HIFU treatment were analyzed. Ultrasound-guided HIFU ablation in the twelve patients was technically successful with one session treatment. The mean longest diameter of BLUFs was 6.2 ± 2.3 cm. The mean NPV ratio of fibroids was 84.08%± 9.4%. After HIFU ablation, lower abdominal pain occurred in 7 cases, sacrococcygeal pain in 3 cases, and mild skin pain in 6 cases. There were no severe adverse events and complications associated with the treatment. At 6 months post-treatment follow-up, the mean fibroid volume decreased by 56.2%± 9.0% (p < 0.05), and the symptoms related to broad ligament fibroids were improved or disappeared. Ultrasound-guided high-intensity focused ultrasound ablation is feasible, effective, and safe for treating broad ligament fibroids.


The Association of Serum Vitamin D Deficiency and Metabolic Risk Factors in Chinese Adults with Prediabetes: A Cross-Sectional Study.
The association of serum vitamin D deficiency and metabolic risk factors in Chinese adults with prediabetes (PreDM) has not been investigated. The present study aimed to investigate the association of serum vitamin D deficiency and metabolic risk factors in Chinese adults with PreDM. In this cross-sectional study, we stratified 412 PreDM patients into vitamin D sufficient, vitamin D insufficient and vitamin D deficient subgroups. The physical examination data was collected. Serum 25-hydroxyvitamin D3 [25(OH)D3] were measured by high performance liquid chromatography. The prevalence of vitamin D deficiency and insufficiency in PreDM patients were 30.58% and 26.70%, respectively. Compared with the vitamin D deficient group, the prevalence of metabolic syndrome, central obesity, hyperglycemia and hypertension were higher than those in the vitamin D insufficient or sufficient group (p<0.05). Moreover, the prevalence of dyslipidemia in the vitamin D deficient group was higher than those in the vitamin D sufficient group (p<0.05). We observed an inverse relationship between 25(OH)D3 levels and waist circumference, triglyceride, and serum uric acid (β=-0.315; β=-0.134; β=-0.239), a positive relationship between 25(OH)D3 levels and high-density lipoprotein cholesterol (β=0.197) after adjusting for age, sex and body mass index. Vitamin D deficiency is very common among PreDM patients in China and this deficiency is related to metabolic risk factors.


Pterostilbene, a novel natural plant conduct, inhibits high fat-induced atherosclerosis inflammation via NF-κB signaling pathway in Toll-like receptor 5 (TLR5) deficient mice.
Atherosclerosis is a specific form of an artery wall thickens, a syndrome affecting arterial blood vessels due to a chronic inflammatory response in the walls of arteries, which is promoted by fat accumulation. Toll-like receptors (TLRs) play prominent roles in inflammatory responses. And TLR5 is overexpressed in several diseases. Here in our study, we investigated the effect of TLR5 in high fat-induced atherosclerosis via NF-κB signaling pathway modulating pro-inflammatory cytokines releasing. Our results found that high fat induced atherosclerosis in wild type mice with fat accumulation and inflammatory response through NF-κB activation. Contrastly, TLR5 knockout mice displayed lower fat accumulation and ameliorated inflammation after high fat feeding with NF-κB inactivation. In addition, pterostilbene, as a natural dimethyl ether derivative of resveratrol mainly from blueberries, has diverse pharmacological activities, especially anti-inflammation. Our study also found that pterostilbene displayed inhibited role in suppressing inflammatory response through inactivating NF-κB signaling pathway regulated by TLR5 down-regulation in high fat-induced mice. Moreover, in vitro experiments of vascular smooth muscle cells (VSMCs) challenged with LPS or TNF-α, further indicated that NF-κB was involved in atherosclerosis progression, leading to high secretion of pro-inflammatory cytokines. However, VSMCs from TLR5 deficient mice inhibited phosphorylated levels of NF-κB signalilng pathway, finally resulting in down-regulation of inflammatory cytokines. Notably, pterostilbene also displayed suppressed role in inflammatory response via NF-κB inactivity in LPS or TNF-α-induced VSMCs by decreasing TLR5 expression. The results above indicated a novel therapeutic strategy of pterostilbene to protect against atherosclerosis via TLR5 regulation for clinic treatment in the future.


The majority of males with subnormal hypoosmotic test scores have normal vitality.
To determine if males with low hypoosmotic swelling (HOS) test scores may have normal vitality tests. Retrospective nine-year review of initial semen analyses evaluating vitality and HOS tests. Only 12.5% (45/361) of males with low HOS test scores have low vitality. WHO seems to treat vitality and HOS as equal tests. We disagree and find that structural defects of the sperm membrane are much less common than functional impairment of the sperm membrane. Since a male with an HOS test score < 50% will rarely achieve a pregnancy with intercourse, intrauterine insemination, or IVF with conventional insemination it is important to check for the HOS test not viability because the HOS test can be easily corrected with ICSI.


Regional expression of NAD(P)H oxidase and superoxide dismutase in the brain of rats with neurogenic hypertension.
Single injection of small quantities of phenol into the kidney cortex causes hypertension which is mediated by renal afferent sympathetic pathway activation. This phenomenon can be prevented by superoxide dismutase (SOD) infusion in the lateral ventricle, suggesting the role of superoxide (O(2)(-).) in noradrenergic control of arterial pressure. Since NAD(P)H oxidase is a major source of O(2)(-)., we tested the hypothesis that hypertension in this model may be associated with upregulation of NAD(P)H oxidase in relevant regions of brain. NAD(P)H oxidase subunits, mitochondrial (MnSOD) and cytoplasmic (CuZnSOD) SOD were measured in rats 4 weeks after injection of phenol or saline in the left kidney cortex. Phenol-injected rats exhibited hypertension, upregulation of gp91(phox), p22(phox), p47(phox) and p67(phox) in the medulla, gp91(phox) and p22(phox) in pons and gp91(phox) in hypothalamus. This was associated with upregulation of MnSOD with little change in CuZnSOD. Chronic hypertension in phenol-injected rats is associated with upregulation of NAD(P)H oxidase and hence increased O(2)(-). production capacity in the key regions of the brain involved in regulation of blood pressure. Since reactive oxygen species can intensify central noradrenergic activity, the observed maladaptive changes may contribute to the genesis and maintenance of the associated hypertension.


Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia.
This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state.


[Analyses of clinicopathologic factors affecting neck control after postoperative radiation as adjuvant treatment for lymph node metastasis in head and neck squamous cell carcinoma].
To investigate the clinicopathologic factors associated with neck control and distant metastasis in patients with neck metastases in head and neck squamous cell carcinoma (HNSCC) after postoperative radiation as adjuvant treatment. Clinicopathologic data of 208 pathologic N+ (pN+ ) patients with HNSCC initially treated with neck dissection and postoperative radiation in Bethune International Peace Hospital of China from January 2004 to December 2009 were reviewed. The clinicopathologic factors, includeding age, sex, primary tumor site, pathologic T and N stage, tumor growth pattern, histological grade, tumor resection margin, size and number of positive lymph node, number of levels with positive lymph node, and extracapsular nodal spread (ECS), were evaluated for their association with neck control and distant metastasis in patients with HNSCC after postoperative radiation. Univariate χ(2) test and multiple stepwise logistic regression model were used for the analysis. Overall 5-year neck control rate after postoperative radiotherapy was 72.6% (151/208), with 84.0% (63/75) for SND, 72.9% (78/107) for MRND, and 38.5% (10/26) for RND, respectively. Univariate analysis showed that neck control after postoperative radiation was related with following factors: primary tumor site, pathologic N stage, size of positive node, number of levels with positive node, number of positive node, and ECS. Pathologic N stage and number of levels with positive lymph node were associated with distant metastasis. Multivariate analysis indicated that ECS was the most significant risk factor for neck metastasis after surgery and postoperative radiotherapy and the number of levels with positive node was the most significant risk factor for distant metastasis. ECS is the most important pathologic factor in planning postoperative adjuvant treatment for pN+ patients with HNSCC, therefore ECS should be evaluated routinely after neck dissection. The value of postoperative radiotherapy in controlling the ECS-related recurrence after surgery is limited. Postoperative concurrent chemoradiotherapy and targeted therapy can be considered in HNSCC patients with ECS.


Modelling recurrent events: a tutorial for analysis in epidemiology.
In many biomedical studies, the event of interest can occur more than once in a participant. These events are termed recurrent events. However, the majority of analyses focus only on time to the first event, ignoring the subsequent events. Several statistical models have been proposed for analysing multiple events. In this paper we explore and illustrate several modelling techniques for analysis of recurrent time-to-event data, including conditional models for multivariate survival data (AG, PWP-TT and PWP-GT), marginal means/rates models, frailty and multi-state models. We also provide a tutorial for analysing such type of data, with three widely used statistical software programmes. Different approaches and software are illustrated using data from a bladder cancer project and from a study on lower respiratory tract infection in children in Brazil. Finally, we make recommendations for modelling strategy selection for analysis of recurrent event data.