Antarctic sponges from the Terra Nova Bay (Ross Sea) host a diversified bacterial community.
Sponges represent important habitats for a community of associated (micro)organisms. Even if sponges dominate vast areas of the Antarctic shelves, few investigations have been performed on Antarctic sponge-associated bacteria. Using a culture-dependent approach, the composition of the bacterial communities associated with 14 Antarctic sponge species from different sites within the Terra Nova Bay (Ross Sea) area was analyzed. Overall, isolates were mainly affiliated to Gammaproteobacteria, followed by Actinobacteria and CF group of Bacteroidetes, being the genera Pseudoalteromonas, Arthrobacter and Gillisia predominant, respectively. Alphaproteobacteria and Firmicutes were less represented. Cluster analyses highlighted similarities/differences among the sponge-associated bacterial communities, also in relation to the sampling site. The gammaproteobacterial Pseudoalteromonas sp. SER45, Psychrobacter sp. SER48, and Shewanella sp. SER50, and the actinobacterial Arthrobacter sp. SER44 phylotypes occurred in association with almost all the analyzed sponge species. However, except for SER50, these phylotypes were retrieved also in seawater, indicating that they may be transient within the sponge body. The differences encountered within the bacterial communities may depend on the different sites of origin, highlighting the importance of the habitat in structuring the composition of the associated bacterial assemblages. Our data support the hypothesis of specific ecological interactions between bacteria and Porifera.


Pernicious anaemia and granulomatous skin lesions in a case of common variable hypogammaglobulinaemia.
A 45-year-old woman is reported with a history of recurrent bacterial infections since childhood; at the age of 37 years she developed recurrent ulcerated lesions around her mouth, in the groins and buttocks, which histologically contained small, non-caseating granulomas. A year latter when being treated for empyema, she was found to have common variable hypogammaglobulinaemia. Three years after this she developed a megaloblastic anaemia of vitamin B12-deficiency type.


ΔNp63α promotes Bortezomib resistance via the CYGB-ROS axis in head and neck squamous cell carcinoma.
Bortezomib, a proteasome inhibitor, proved potent in the treatment of recurrent multiple myeloma or mantle cell lymphoma. However, slow progress was made when it was applied to treat solid tumors. We discovered that different head and neck squamous cell carcinoma (HNSCC) cell lines had significantly different sensitivities to bortezomib, and also demonstrated that individual relatively sensitive HNSCC cell lines had fewer ΔNp63α expressions. Based on these findings, we speculated that ΔNp63α may be a key factor in the resistance of HNSCC cells to bortezomib. ΔNp63α knockdown made HNSCC more sensitive to bortezomib, while ΔNp63α overexpression made it more resistant. RNA sequencing (RNA-seq) analysis of ΔNp63α-knockdown cells revealed clear alterations in the subset of genes that were associated with oxidative stress and antioxidant defense. The gene CYGB was downregulated significantly. CHIP-seq detection showed that CYGB was the transcriptional regulatory site of ΔNp63α. CHIP-PCR showed evidence of ΔNp63α binding. The detection of the dual-luciferase reporter gene demonstrated that ΔNp63α significantly enhanced the CYGB promoter activity. Furthermore, we confirmed that CYGB plays a role in clearing excess ROS induced by bortezomib to inhibit HNSCC apoptosis. Consequently, ΔNp63α regulated the expression of CYGB in HNSCC. CYGB was the target of transcription regulation of ΔNp63α. It reduced apoptosis by clearing excess ROS produced by bortezomib, and thus exerted drug resistance.


REACH exposure assessment of anticorrosive paint products--determination of exposure from application and service life to the aquatic environment.
The European Community Regulation on the registration, evaluation, authorisation and restriction of chemicals (REACH) introduced exposure scenarios describing safe use quantitatively, and enhancing the importance of scientific based exposure assessments. This paper presents methods to determine exposure from the airless spray application of anti-corrosive paint and leaching of painted articles submerged in seawater, to establish whether it is possible to test these exposures in a reproducible and feasible way. The paper also presents results from using the methods in order to assess how well the default values recommended under REACH coincide with the tested values and corresponding values available in literature. The methods used were feasible under laboratory conditions. The reproducibility of the application study was shown to be good and all analyses of the leaching showed concentrations below detection limit. More replicates will be required to validate the reproducibility of the growth inhibition tests. Measured values for the present overspray scenario were between, and the leaching values below, values from REACH guidelines and emission scenario documents. Further development of the methods is recommended.


U.K. parents' decision-making about measles-mumps-rubella (MMR) vaccine 10 years after the MMR-autism controversy: a qualitative analysis.
Public concern about an unsubstantiated link between MMR vaccine and autism stemmed from a 1998 paper by Dr Andrew Wakefield and colleagues, and the substantial media coverage which that work attracted. Though the Wakefield paper is now discredited and an MMR-autism link has never been demonstrated empirically, this concern has manifested in over a decade of suboptimal MMR uptake. Few qualitative studies have explored parents' MMR decision-making since uptake began to improve in 2004. This study updates and adds methodological rigour to the evidence base. 24 mothers planning to accept, postpone or decline the first MMR dose (MMR1) for their 11-36 month-old children, described their decision-making in semi-structured interviews. Mothers were recruited via General Practice, parents' groups/online forums, and chain referral. MMR1 status was obtained from General Practice records 6 months post-interview. Interview transcripts were coded and interpreted using a modified Grounded Theory approach. Five themes were identified: MMR vaccine and controversy; Social and personal consequences of MMR decision; Health professionals and policy; Severity and prevalence of measles, mumps and rubella infections; Information about MMR and alternatives. Results indicated that MMR1 acceptors were sympathetic toward Wakefield as a person, but universally rejected his study which sparked the controversy; parents opting for single vaccines expressed the sense that immune overload is not a consideration but that not all three components of MMR are warranted by disease severity; and MMR1 rejectors openly criticised other parents' MMR decisions and decision-making. This study corroborated some previous qualitative work but indicated that the shrinking group of parents now rejecting MMR comprises mainly those with more extreme and complex anti-immunisation views, whilst parents opting for single vaccines may use second-hand information about the controversy. In response, policymakers and practitioners should revise their expectations of today's MMR decision-makers, and their methods for supporting them.


Primary health care roles of community pharmacists in low- and middle-income countries: A protocol for a mixed methods systematic review.
The roles of community pharmacists in primary health care cannot be overemphasized, these professionals have evolved from the traditional dispensing to providing health promotion, vaccination services, and medication therapy management as well as other areas of patient care needs. The objectives of this review are to explore evidence of the provision of primary health care services by community pharmacists in low- and middle-income countries (LMICs) and identify barriers to these services and how these barriers can be mitigated. A systematic search will be conducted in Medline, CINAHL, Google scholar, Global Index Medicus, LILACS, and CENTRAL to identify potentially relevant primary literature for inclusion. Also, ProQuest Dissertations and Theses will be search to identify relevant gray literature. The review will be guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist for systematic reviews. All primary research articles regardless of study design exploring or reporting on community pharmacists' involvement in primary health care in LMICs will be considered for possible inclusion. A summary of the included studies will be provided and a quality assessment will be conducted using the 2018 version of the mixed methods analytical tool. Findings from this review will add to the evidence in the literature and cause the need for policy change to empower the community pharmacy practice by providing a friendlier legal framework for delivering services in tandem with international best practices. PROSPERO registration ID: CRD42023357312.


Indirect continuous automatic determination of pharmaceuticals by atomic absorption spectroscopy.
The implementation of continuous separation techniques such as precipitation, liquid-liquid and solid-liquid extraction in FIA manifolds coupled on-line with an atomic absorption spectrometer for the determination of active components (sulphonamides, local anaesthetics, amphetamines, benzodiazepines, chloramphenicol and methadone) in pharmaceuticals and biological fluids is systematically described. The basic features of the analytical methodologies described (sensitivity, selectivity, precision and rapidity) are also discussed and critically compared.


Spontaneous bleeding in pancreatitis treated by transcatheter arterial coil embolization: a retrospective study.
A rare, but life-threatening complication in pancreatitis is a spontaneous bleeding from intestinal vessels with or without previous formation of (pseudo-) aneurysms. And yet, the optimal diagnostic and therapeutic strategies remain unclear. We performed a retrospective analysis of all patients with pancreatitis and intraabdominal bleeding at a German tertiary referral center between January 2002 and December 2012. Bleeding occurred in <1% (14/3,421) of patients with pancreatitis. Most involved vessels were arteria lienalis, arteria gastroduodenalis, and arteria pancreaticoduodenalis. All bleedings could be stopped by transcatheter arterial coil embolization. Recurrent bleeding after coil embolization occurred in 2/14 (14%) patients. In cases of intraabdominal hemorrhage in patients with pancreatitis, transcatheter arterial coil embolization should be considered as the first interventional procedure.


Acceptability of Behavioral Activation for Depression Among Latinas: A Mixed Methods Study.
Latinxs represent the largest ethnoracial minority population in the United States. Despite having significant rates of depression, Latinxs underutilize behavioral health services. This, combined with the association between gender and depression (women have higher rates of depression than men), underscores the importance of developing an improved understanding of how Latinas view behavioral activation (BA), an empirically supported treatment for depression. In this mixed methods study, participants consisted of 77 Latinas; participants were provided with a vignette depicting a fictional character that underwent BA for depression. Participants in the quantitative study completed a measure of treatment acceptability of BA (n = 60); participants in the qualitative study completed a semistructured interview assessing their views on BA (n = 17). Latinas had generally positive attitudes about BA, although they also identified some elements that they perceived might act as barriers to treatment success. Because we were interested in the interplay of cultural factors and treatment acceptability, we also examined enculturation and acculturation as predictors of treatment acceptability-enculturation only was a significant predictor treatment acceptability. Our sample was relatively small, social desirability may have influenced our responses, and it is not known to what extent our results generalize to Latinx men. Latina women find BA to be an acceptable treatment for depression, which suggests promise with regard to clinical outcomes for depressed Latinas receiving BA. Addressing potential barriers to treatment engagement may improve outcomes for depressed Latinas receiving BA.


Ethical Issues for Public Health Approaches to Obesity.
Obesity is a major public health concern worldwide. Because individual-level interventions have been unsuccessful at curbing obesity rates, there is an emphasis on public health approaches. In addition to testing the effectiveness of any public health interventions, it is important to consider the ethical implications of these interventions in order to protect the public's rights and promote overall well-being. In this paper, we review public health approaches to obesity in three broad domains (changes to the socio-communicative environment, changes to the economic environment, and changes to the physical environment/access) and consider the potential ethical issues that arise in each of those domains. We suggest that interventions that target the physical environment/access (making it easier for people to engage in healthy behaviors), that target the entire population (rather than just individuals with obesity), and that focus on health behaviors (rather than on weight) have the least potential for ethical concerns.


Increased expression of insulin-like growth factor-1 receptor predicts poor prognosis in patients with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a lethal disease worldwide. In this study, we sought to explore the expression of insulin-like growth factor-1 receptor (IGF-1R) and its prognostic value in HCC.The expressions of IGF-1R mRNA and protein were estimated using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The association between IGF-1R expression and clinicopathologic characteristic of patients with HCC was analyzed through Chi-squared test. Kaplan-Meier analysis and multivariate Cox analysis were performed to analyze prognostic value of IGF-1R in HCC.The IGF-1R was significantly upregulated in HCC tissues at both mRNA and protein levels compared with adjacent normal ones (P < .01). Its expression was associated with tumor node metastasis stage (P = .037) and lymph node metastasis (P = .027) of patients with HCC. Patients with HCC with high expression of IGF-1R had worse overall survival than those with low expression. IGF-1R might be a potential prognostic biomarker for HCC (hazard ratio [HR] = 1.912, 95% confidence interval [CI]: 1.023-3.572, P = .042).The IGF-1R expression level is upregulated in HCC tissues and may act as a prognostic biomarker for the disease.


Effects of exopolysaccharide production on liquid vegetative growth, stress survival, and stationary phase recovery in Myxococcus xanthus.
Exopolysaccharide (EPS) of Myxococcus xanthus is a well-regulated cell surface component. In addition to its known functions for social motility and fruiting body formation on solid surfaces, EPS has also been proposed to play a role in multi-cellular clumping in liquid medium, though this phenomenon has not been well studied. In this report, we confirmed that M. xanthus clumps formed in liquid were correlated with EPS levels and demonstrated that the EPS encased cell clumps exhibited biofilm-like structures. The clumps protected the cells at physiologically relevant EPS concentrations, while cells lacking EPS exhibited significant reduction in long-term viability and resistance to stressful conditions. However, excess EPS production was counterproductive to vegetative growth and viable cell recovery declined in extended late stationary phase as cells became trapped in the matrix of clumps. Therefore, optimal EPS production by M. xanthus is important for normal physiological functions in liquid.


Behavioral management in the inpatient geriatric population.
Urinary incontinence is a reversible problem in many nursing home patients. The types of patients that respond to nursing management procedures have been identified in this article. Specific diagnostic and rehabilitative assessments, as well as treatment procedures, have been described in a fashion that makes them usable by most nursing professionals in long-term care facilities. Two key issues remain to be addressed. The foremost issue is that, once patients are taught to request toileting assistance, the challenge remains to motivate staff to render that assistance over long periods of time. Second, a number of patients with urologic conditions (most notably, high residual urine volumes and low bladder capacities) do not respond well to nursing management. The type of medical or nursing treatment best suited for these patients has not yet been resolved. Nevertheless, this article has detailed techniques that positively affect incontinence in nursing home patients. Nursing implementation of prompted voiding can dramatically improve continence within the geriatric inpatient population.


Anemia in pregnancy: it's effect on oxidative stress and cardiac parameters.
We aimed to evaluate the changes in cardiac functions by echocardiography and oxidative stress markers in pregnant women with iron deficiency anemia. A total of 100 patients (pregnant women with IDA n = 34, healthy pregnant women n = 33, non-pregnant control group n = 33) were enrolled. Demographic data, serum thiol-disulfide and ischemia modified albumin levels, and echocardiographic parameters were compared. Native thiol (NT) (p < .001) and Total Thiol (TT) (p < .001) levels as antioxidant markers; left ventricular ejection fraction (LVEF) (p < .001), tricuspid annular plane systolic excursion (TAPSE) (p < .001) were significantly decreased in the IDA group compared to healthy pregnant women and non-pregnant controls. Adjusted IMA ratios were significantly increased in the IDA group (p =.001). A significant negative correlation was determined between adjusted IMA and LVEF (r = -0,4226; p =.016), a significant positive correlation was determined between thiol levels and TAPSE (r = 0.361; p =.041) in IDA group, no correlation was observed in healthy pregnant women and healthy non-pregnant control group. Anemia in pregnanc may trigger oxidative stress and increased OS may be related to changes in cardiac functions. The possible cardiovascular impact should be considered in pregnant women with anemia and clinicians should not neglect to refer these patients to cardiology in clinical practise.


Retinoic acid leads to cytoskeletal rearrangement through AMPK-Rac1 and stimulates glucose uptake through AMPK-p38 MAPK in skeletal muscle cells.
Retinoic acid (RA) is one of the major components of vitamin A. In the present study, we found that retinoic acid activated AMP-activated protein kinase (AMPK). RA induced Rac1-GTP formation and phosphorylation of its downstream target, p21-activated kinase (PAK), whereas the inhibition of AMPK blocked RA-induced Rac1 activation. Moreover, cofilin, an actin polymerization regulator, was activated when incubated with RA. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPK alpha1 blocked RA-induced cofilin phosphorylation. Additionally, we found that retinoic acid-stimulated glucose uptake in differentiated C2C12 myoblast cells and activated p38 mitogen-activated protein kinase (MAPK). Finally, the inhibition of AMPK and p38 MAPK blocked retinoic acid-induced glucose uptake. In summary, our results suggest that retinoic acid may have cytoskeletal roles in skeletal muscle cells via stimulation of the AMPK-Rac1-PAK-cofillin pathway and may also have beneficial roles in glucose metabolism via stimulation of the AMPK-p38 MAPK pathway.


Uteroglobin mRNA from the lung of the hare (Lepus capensis): cell-free translation and properties.
Poly(A)-containing RNA was obtained from the lung of hares (Lepus capensis) and uteroglobin mRNA was characterized by cell-free translation and molecular hybridization to a rabbit uteroglobin cDNA probe. In the cell-free system, hare uteroglobin mRNA was preferentially translated as compared to the whole lung mRNA and it directed the synthesis of a precursor, preuteroglobin, containing about twenty additional amino acids. Hare uteroglobin mRNA was about 40 nucleotides larger than the homologous rabbit one, as analyzed by electrophoresis on agarose gel. Thermal stability of the hybrids formed between rabbit or hare uteroglobin mRNAs and the rabbit cDNA probe indicated differences in the nucleotide sequence of both mRNAs. The levels of uteroglobin mRNA and uteroglobin synthesis in lung are about two-fold higher in hare than in rabbit lung.


Feasibility of repeated testing for learning ability in juvenile primates for pediatric safety assessment.
Assessment of learning ability in nonhuman primate (NHP) models is sometimes requested by regulatory authorities. The double choice object discrimination task using a Wisconsin General Testing Apparatus (WGTA) approach is typically being applied. In this study, the WGTA approach was performed on 66 juvenile cynomolgus monkeys aged 8-9 months in the predose phase of juvenile toxicity assessment. In addition, reversal learning data of seven control animals/gender were obtained for the weeks 25 and 52 of dosing. Gender differences in the number of days required to pass the habituation, learning or reversal learning phases were statistically comparable, males and females may be combined for statistical analysis. At first instance, the habituation phase was passed on average after 6.4 days, and the learning test on average after 8.6 days with improvement to 2.0-2.6 days for habituation and 6.4-6.7 days for learning in weeks 52. Power analysis (α = 0.05, one-sided t-test) revealed a sample size of 8 and 41 to predict a 50% and 20% difference, respectively. In conclusion, examination for learning ability, but not for memory ability (during repeated testing) is feasible in juvenile NHPs using the WGTA approach.


Germination and ROS detoxification in bell pepper (Capsicum annuum L.) under NaCl stress and treatment with microalgae extracts.
We evaluated the salt tolerance of hybrids of pepper (Capsicum annuum L.) during germination. Treatments were applied at 0, 25, and 50 mM NaCl with preparations of supplemental extracts of the microalgae Dunaliella salina and Phaeodactylum tricornutum to determine the percentage germination rate as well as measured indicators of oxidative stress caused by the salt treatments during seed germination. We found that root growth was favorably influenced by the microalgae leading to increased germination rate. Tissues were analyzed in terms of superoxide radical production, lipid peroxidation, and activity of antioxidant enzymes viz. superoxide dismutase, catalase, and glutathione peroxidase. Our results suggest that application of microalgae extracts significantly reduced (p < 0.05) superoxide radical production, as well as lower lipid peroxidation in comparison to plants without extracts of microalgae. The antioxidant enzymes increased in the presence of microalgae showing a significant difference (p < 0.05). The results suggest differences in oxidative metabolism in response to the magnitude of salt stress and concentrations of microalgae help mitigate salt stress in plants during the germination process.


Effect of addition of Ca2+ to titanium by a hydrothermal method on soft tissue sealing.
The long-term stability of implants requires good peri-implant soft tissue sealing. Calcium ion (Ca2+ ) was loaded onto titanium surface by a hydrothermal method. In vitro, the morphology and composition of titanium surfaces were determined by scanning electron microscopy and energy-dispersive spectroscopy; proliferation of hGF-1 cells was measured by the CCK-8 assay; immunofluorescence staining was done to detect adherent proteins on titanium surface. In vivo, the degree of attachment between the implant and the surrounding soft tissue was measured by horseradish peroxidase (HRP). The percentage of hGF-1 cells adhering in the Ca group was significantly higher (p < .01); the fluorescence of integrin-β1 and F-actin in the Ca group was stronger; Ca group had the shorter length of HRP (p < .01). Ca2+ can be added to the surface of titanium by a hydrothermal method and it will be more beneficial for soft tissue early sealing. HIGHLIGHTS: A simple method to form micron crystals on titanium surface. The micron crystal promotes the attachment of human gingival fibroblasts. Facilitates early and rapid formation of soft-tissue sealing around implants.


Controversies in the management of pancreatic pseudocysts.
Review of the diagnosis and treatment of patients with pancreatic pseudocysts over the past 8 years has led us to three conclusions regarding controversial aspects of their treatment. We found that patients who present with chronic pseudocysts can be identified with the help of computerized axial tomography and promptly undergo successful internal drainage, whereas patients with acute peripancreatic fluid secondary to pancreatitis can be observed expectantly with a 43 percent frequency of spontaneous resolution. Patients with infected pancreatic pseudocysts can be safely drained internally. The most common cause of extrahepatic biliary obstruction in this group of patients with pancreatic pseudocysts was stricture due to pancreatitis and fibrosis, not extrinsic compression.


Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system.
The cerebrospinal fluid (CSF)/serum concentration quotients of albumin and the immunoglobulins G, A and M have been determined for 396 patients with a normal blood CSF barrier function or a pure barrier impairment without a humoral immune response within the central nervous system. The ratios between the concentration quotients of the three immunoglobulins and that of albumin increase in a nonlinear fashion with progressive impairments of the blood CSF barrier, i.e. the molecular size dependent discrimination of the protein transfer ('selectivity') decreases. The upper reference values of the concentration quotients for the whole range of passive transfer comply with the hyperbolic function: Q(IgX) = a/b square root Q(Alb)2 + b2 - c with different constants a/b, b2, c for IgG (0.8, 15 X 10(-6), 1.8 X 10(-3), IgA (0.72, 80 X 10(-6), 5.1 X 10(-3) and IgM (0.65, 150 X 10(-6), 7.5 X 10(-3). With these discriminatory functions the locally synthesized fractions IgX(loc) of IgG, IgA and IgM in CSF can be calculated by the general formula: IgX(loc) = [Q(IgX) - a/b square root Q(Alb)2 + b2 + c] X IgX(Ser).


Weight gain in women of normal weight before pregnancy: complications in pregnancy or delivery and birth outcome.
To investigate the relation between gestational weight gain in women of normal prepregnant weight and complications during pregnancy and delivery in a population with high gestational weight gain and birth weight. Healthy women (n = 615) of normal weight before pregnancy (body mass index 19.5-25.5 kg/m(2)) were randomly selected. Maternity records gave information on age, height, prepregnant weight, gestational weight gain, parity, smoking, gestational hypertension and diabetes, preeclampsia, delivery complications, and infants' birth size and health. The mean weight gain in pregnancy was 16.8 +/- 4.9 kg (mean +/- standard deviation). A total of 26.4% of the women had complications, either in pregnancy (9.1%) or delivery (17.3%). Women gaining weight according to the recommendation of the Institute of Medicine (11.5-16.0 kg) had lower frequency of pregnancy-delivery complications than women gaining more than 20.0 kg (P =.017), but did not differ significantly from those gaining 16-20 kg (P >.05). When dividing weight gain in pregnancy into quintiles, a relative risk of 2.69 (95% confidence interval 1.01, 7.18, P =.048) was found for complications in pregnancy in the fourth quintile (17.9-20.8 kg), using the second quintile as reference (12.5-15.5 kg). The mean birth weight was 3778 +/- 496 g. A low weight gain in pregnancy (less than 11.5 kg) was associated with an increased frequency of infants weighing less than 3500 g at birth (P <.01). A gestational weight gain of 11.5-16.0 kg (Institute of Medicine recommendation) for women of normal prepregnant weight is related to the lowest risk for pregnancy-delivery complications. In the population studied, the upper limit might be higher (up to 18 kg), and low weight gain should be avoided to optimize birth outcome.


Body composition changes in patients with anorexia nervosa after complete weight recovery.
To assess body composition changes occurring in female anorectic patients after complete weight recovery. Longitudinal study. : Ten female patients with anorexia nervosa (age at baseline: 19.7+/-5.8 y) were studied both when undernourished (body mass index, BMI 14.8+/-1.3 kg/ m(2)) and after the achievement of a BMI >18.5 kg/m(2). The control group comprised 18 well-nourished women (age 20.1+/-4.4 y; BMI 19.0-23.0 kg/ m(2)). Fat mass and fat-free mass were determined by dual-energy X-ray absorptiometry. Skinfold thicknesses and circumferences were also measured. Arm muscle area and arm fat area were calculated by standard formulas. The undernourished patients had lower fat-free mass, fat mass, skinfold thicknesses and circumferences. After refeeding, fat mass represented 25-71% (mean 56%) of the mass regained, this percentage being directly related to the extent of weight gain. The increases in skinfolds and circumferences depended upon the site considered and were correlated to a various extent with those in weight or BMI. Skinfolds at biceps and abdominal sites and the waist-to-hip ratio remained significantly higher, whereas arm muscle circumference was significantly lower, in the refed group than in the control one. The percentage of fat in the weight regained by refed female anorectic patients was directly related to the extent of body mass increase. Refed anorectic patients appear to preferentially regain fat in the abdominal and triceps regions. Abnormalities in skinfolds (at biceps and abdominal sites), arm muscle area and waist-to-hip ratio still persist in refed anorectic patients in comparison to control healthy controls.


Filtering for the best policy: An economic evaluation of policy options for kidney replacement coverage in the Philippines.
Kidney failure patients in the Philippines have free choice on their kidney replacement therapy (KRT), with a majority choosing haemodialysis (HD) over peritoneal dialysis (PD) and transplantation despite the inadequate coverage of HD. Although national health insurance coverage is limited, KRT remains to be one of the top benefits pay-outs in the country. The study aims to identify the most cost-effective policy strategy for financing KRT in the Philippines, in the context of a universal healthcare policy. A Markov model was developed to estimate and compare the costs and benefits of different policy options with the comparator being partial HD coverage. Direct medical, non-medical and indirect costs were measured, while outcomes were reported through quality-adjusted life years (QALYs). Parameters were derived from the kidney disease registry, hospital statistics from a tertiary hospital and a patient survey. The results of the cost-effectiveness analysis showed that shifting to a PD-First policy provides better value-for-money with an incremental cost-effectiveness ratio (ICER) of 570 029 Philippine Pesos (PHP) per QALY gained, compared with the ICER of the PD-First combined with pre-emptive transplant option of 577 989 PHP per QALY gained. Expanding existing HD coverage to 156 sessions was the least cost-effective policy (1 522 437 PHP per QALY gained). Government should consider shifting to a PD-First strategy and support policies that promote kidney transplants among existing PD and HD patients. This study also highlights the need for proper evaluation of partial coverage policies to ensure that government investments represent good value-for-money and patients receive optimal care.


Primary leiomyosarcoma of the adrenal; a case report.
Primary adrenal leiomyosarcoma (PAL) is an extremely rare neoplasm that usually arises from the smooth muscle cells of the adrenal or adjacent vascular structures. The tumor is asymptomatic until it grows up and develops a mass effect in the retroperitoneal region. Although there are about 50 reported valid cases, surgical intervention is mandatory in the majority of patients. Herein, we report the case of a 32-year-old healthy woman with a chief complaint of vague abdominal pain. After initial clinical and radiological examinations, we found a large retroperitoneal mass located around the right adrenal gland. Due to the patient's pain, a laparotomy was performed, and a large mass was resected with free margins. Immunohistochemical examination was positive for vimentin, smooth muscle actin (SMA), and desmin. Therefore, the diagnosis of PAL was confirmed. Although PAL is an uncommon malignancy, its diagnostic and therapeutic approaches are almost straightforward. A computed tomography scan can show the characteristics of the tumor and direct the management. Surgical resection is the mainstay of treatment, and the effects of adjuvant therapies have not been apparent yet.


A 5% Glucose Solution for the Liquid Formulation Gemcitabine Solvent Decreases Gemcitabine-induced Vascular Pain.
Gemcitabine (GEM)-induced vascular pain often occurs in patients. A 5% glucose solution for the lyophilized formulation of GEM solvent is known to decrease the frequency of GEM-induced vascular pain compared with saline. In this study, we aimed to examine the availability of glucose for a liquid formulation GEM solvent for the prevention of GEM-induced vascular pain. In total, 214 patients with bile tract or pancreatic cancer, who received GEM-containing regimens, were enrolled in this retrospective study. The patients were divided into a glucose group, which was administered the liquid formation GEM diluted with glucose, and a saline group. The frequency of GEM-induced vascular pain was compared between them. Glucose significantly decreased the frequency of GEM-induced vascular pain during the first GEM administration (36% vs. 55%, p=0.005). Switching the solution for liquid formulation GEM from saline to glucose significantly decreased the frequency of vascular pain.


Management of Challenging Urethro-ileal Anastomosis During Robotic Assisted Radical Cystectomy with Intracorporeal Neobladder Formation.
Robotic assisted radical cystectomy (RARC) is increasingly being adopted, but intracorporeal neobladder formation remains a challenging procedure limited to selected centers. Common challenges with intracorporeal neobladder formation relate to fashioning a tension-free urethro-ileal anastomosis. In this paper, we describe a series of maneuvers to overcome these challenges that we believe will be of great utility to surgeons performing intracorporeal neobladder. To describe maneuvers to overcome challenges during intracorporeal urethro-ileal anastomosis formation and to report postoperative outcomes for patients in whom these maneuvers were used. A retrospective review of medical records of patients who underwent RARC with intracorporeal neobladder performed by one surgeon (G.-P.H.) at our tertiary center from January 2012 to February 2015 in which at least one additional maneuver was required beyond preservation of urethral length, removal of the sigmoid colon from the pelvis, and careful ileal loop selection. The primary end point was 90-d complications. Follow-up ranged from 6 to 36 mo, and 16 patients had at least 1-yr follow-up. RARC with intracorporeal neobladder formation. Clinical and operative data collected from a prospectively maintained, institutional review board-approved database. Maneuvers used during intracorporeal urethro-ileal anastomosis were recorded. Descriptive statistics were used to evaluate postoperative outcomes. Nineteen patients met the inclusion criteria. Mean operative time was 486 min (standard deviation: 112 min) with median hospitalization of 7 d (interquartile range: 7-9 d). Seven patients (36.8%) experienced a complication, with one (5.3%) major complication thought to be unrelated to surgery. No open conversions were required. There was no 90-d mortality. Our stepwise approach can help overcome challenges of urethro-ileal anastomosis during intracorporeal neobladder formation. When performing intracorporeal neobladder formation, challenges are often encountered in fashioning the urethro-ileal anastomosis. We describe a series of maneuvers that, when used in a stepwise manner, help overcome these challenges.


Continent cutaneous urinary diversion in patients with spinal cord injury.
Retrospective study. To examine the functional results and effect on quality of life of continent cutaneous urinary diversion in spinal cord injured patients. Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden. A total of 10 patients with spinal cord injury (SCI). The patients were operated on with an ileal reservoir (Kock reservoir or T-pouch), Cr-EDTA clearance was determined preoperatively and at follow-up. The patients answered a questionnaire concerning reservoir function, various activities and quality of life. The patient charts were reviewed. One patient died of pulmonary embolism 3 years after surgery. Two patients were reoperated on for reservoir perforation. All patients were satisfied/very satisfied with their reservoirs. Half of them reported improved ability to perform various activities. Eight out of nine patients reported improved quality of life. For a selected group of patients with SCI, continent cutaneous urinary diversion provides successful outcome with improved quality of life.


Design and synthesis of D₁ agonist/D₂ antagonist for treatment of schizophrenia.
A series of tetrahydroisoquinolines were designed, synthesized and evaluated as the first non-natural product type of compounds with dual D(1) receptor (D(1)R) agonism and D(2) receptor (D(2)R) antagonism properties for treatment of schizophrenia. The initial SAR of the series was explored. The lead in the series, 3g, exhibited high affinity and good potency. Compound 3g displayed 95% of D(1)R occupancy (10 mg/kg, sc) and 75% of D(2)R occupancy (10 mg/kg, sc) in the striatum of male CD-1 mice. The series exhibited unique pharmacology and merit as tool compounds for target validation and future optimizations.


Stenting the nasopharyngeal isthmus by nasopharyngeal airway after correction of acquired total nasopharyngeal obstruction: surgical procedure and results.
The objective of this study is to describe a simple surgical procedure for management of acquired total nasopharyngeal obstruction in adults. Five patients were diagnosed as having complete nasopharyngeal obstruction over a 3-year period. Three patients previously underwent uvulopalatoplasty, while for the remaining two it was due to pharyngoscleroma. In all the patients, nasopharyngeal obstruction was at the level of the inferior edge of the soft palate. Two of the post-uvulopalatoplasty patients had recurrent obstruction after scar excision and topical application of mitomycin-C without stenting. All the patients were treated surgically by creation of a new anatomical nasopharyngeal isthmus and stenting it by nasopharyngeal airway for 6 months. All the patients experienced satisfactory results and good tolerability to airway placement. The nasopharyngeal airway can counteract the inevitable scar contraction of the new nasopharyngeal isthmus after surgical correction and maintain its patency.


The Breast Surgeon's Role in Risk-Reducing Medication Uptake.
The role of the breast surgeon continues to evolve in an era of improved precision pharmacological agents combating breast cancer and de-escalation of locoregional treatments. Surgical breast oncologists should lead the effort to create preventive strategies and help to improve the uptake of risk-reducing medications (RRMEDS) for women at higher risk of developing breast cancer. Helping women to understand their risk of developing breast cancer will help the initiation of RRMEDS. Fear of side effects caused by these RRMEDS remains a significant obstacle for uptake. Low-dose tamoxifen has shown to help mitigate side effects and reduce attrition rate of women who initiated therapy and should be considered as part of the surgeon's armamentarium for RRMEDS.


[Technology-enhanced learning in anesthesiology and emergency medicine : A new approach to medical school teaching in the wake of the pandemic].
Coronavirus disease 2019 (COVID-19) has brought about unprecedented challenges to medical schools. Physical distancing as the most effective means of infection prevention renders traditional classroom teaching nearly impossible and new teaching methods are required to contain the infection risk whilst ensuring high-level education. In order to minimize the need for classroom teaching we have created an interactive multimedia eLearning environment using the open-source learning management system "Moodle". This article describes the development of the eLearning environment and aims to establish the acceptance of technology-enhanced learning (TEL) among medical students and the evaluation of TEL as an alternative to classroom teaching. We have built a multimedia eLearning environment for fourth year medical students covering the medical school curriculum "anesthesiology and emergency medicine", which is based on the recommendations of the German Society for Anesthesiology and Intensive Care Medicine (DGAI). We have chosen the open-source learning management system "Moodle" as a platform. "Moodle" is widely used by Anglo-American educational institutions to support and conduct academic and nonacademic teaching. In order to assess the students' experience, we have carried out an anonymized post-course survey consisting of multiple-choice and free-answer questions. Of the 157 participants 85.4% rated the course as "very good", 12.1% as "good" and 1.9% as "OK". Lower ratings were not given, 54.8% rated the course content as "very relevant", 43.3% as "relevant" and 1.9% as "neutral", 94.3% felt that more comparable online courses should be offered. The free-text answers revealed that accessibility and multimedia self-controlled learning were highly valued; however, it was felt that hands-on training cannot be replaced by eLearning. Technology Enhanced Learning was highly valued by our students and helped to reduce the need for classroom teaching; however, for teaching practical skills classroom teaching remains indispensable.


Efficacy of long scleral tunnel technique in preventing Ahmed glaucoma valve tube exposure through conjunctiva.
To evaluate the efficacy of long scleral tunnel technique used in Ahmed glaucoma valve (AGV) implantation in preventing tube exposure through conjunctiva. Patients of adult age, who were unresponsive to maximum medical treatment and underwent AGV implantation, were divided into two groups and investigated retrospectively. Group 1 consisted of 40 eyes of 38 patients that underwent surgery by long scleral tunnel technique and Group 2 consisted of 38 eyes of 35 patients that underwent implantation by processed pericardium patch graft method. The mean age was 54.8 ± 14.6 years (range 26-68 years) and the mean follow-up duration was 46.7 ± 19.4 months (range 18-76 months) for the patients in Group 1, whereas the mean age was 58.6 ± 16.7 years (range 32-74 years) and mean follow-up period was 43.6 ± 15.7 months (range 20-72 months) for the patients in Group 2 (p > 0.05). In the course of follow-up, tube exposure was detected in one (2.5%) eye in Group 1 and in three (7.9%) eyes in Group 2 (p = 0.042). Long scleral tunnel technique is beneficial in preventing conjunctival tube exposure in AGV implantation surgery.


[Multiple coronary fistulas to the left ventricle. An unusual cause of myocardial ischemia].
Diffuse communications between the left coronary artery and the left ventricular cavity were found in a 54-years-old man presenting with angina pectoris and reversible ischemia documented on stress Thallium scintigraphy. During atrial pacing the patient experienced chest pain which was accompanied by lactate production. Atenolol, but not nifedipine, did ameliorate the symptoms. The anatomical types and the embriogenesis of coronary microfistulas along with possible mechanisms of ischemia are discussed.


Characterization of the glass-to-vitroceramic transition in yttrium aluminum borate laser glasses using solid state NMR.
The crystallization of laser glasses in the system (Y(2)O(3))(0.2){((Al(2)O(3))(x))(B(2)O(3))(0.8-x)} (0.15 ≤ x ≤ 0.40) doped with 0.5 mol% of ytterbium oxide has been investigated by x-ray powder diffraction, and various solid state NMR techniques. The crystallization process has been analyzed in a quantitative fashion by high-resolution solid state (11)B, (27)Al, and (89)Y NMR spectroscopy as well as (11)B{(27)Al} and (27)Al{(11)B} rotational echo double resonance (REDOR) experiments. The homogeneous glasses undergo major phase segregation processes resulting in crystalline Al(5)BO(9) (historically denoted as Al(18)B(4)O(33)), YBO(3), crystalline YAl(3)(BO(3))(4), residual glassy B(2)O(3), and an additional yet not identified crystalline phase ("X-phase").


The Unfulfilled Promise of the N170 as a Social Biomarker.
Greater affordability and accessibility of noninvasive brain imaging techniques have led to an increased interest in identifying biomarkers of various cognitive processes, particularly in the field of neurodevelopmental disabilities. Autism spectrum disorder (ASD) is one area of research in which strong claims in support of brain-based biomarkers, such as the face-sensitive N170 event-related potential response, are currently emerging. This study systematically examined the possibility of the N170 amplitude and latency measures serving as a biomarker of social information processing in ASD. The N170 response to faces and houses was recorded during passive picture viewing in 77 children with ASD, 7 to 16 years of age, at 2 time points (before and after a social skills intervention) 3 months apart. Social functioning was assessed using standardized behavioral tests, caregiver reports, and observational measures of naturalistic social interactions. The results replicated prior findings of larger N170 amplitudes in response to faces than to houses, but the associations with the behavioral measures of social functioning were modest and not consistently present across the 2 assessment time points. Neither the amplitude nor the latency of the N170 response to faces was sensitive to the effects of a social skills intervention that produced behavioral improvements. The N170 is a reliable event-related potential response reflecting the sensory-perceptual stage of face processing, but it does not fit the definition of a biomarker of social deficits in ASD because it is not sufficiently informative about heterogeneity of social functioning and is not sensitive to treatment effects.


Vascular disease in scleroderma: mechanisms of vascular injury.
Vascular endothelial injury in systemic sclerosis (SSc) includes a spectrum of changes that involve predominantly the microcirculation and arterioles. The pathologic changes in the blood vessels adversely impact the physiology of many organ systems, with a reduction in the size of microvascular beds leading to decreased organ blood flow and ultimately to a state of chronic ischemia. Current hypotheses in SSc vascular disease suggest a possible chemical or infectious trigger.


Discovery and mechanism of action of Thonzonium bromide from an FDA-approved drug library with potent and broad-spectrum inhibitory activity against main proteases of human coronaviruses.
Although the effective drugs or vaccines have been developed to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their efficacy may be limited for the viral evolution and immune escape. Thus, it is urgently needed to develop the novel broad-spectrum antiviral agents to control the coronavirus disease 2019 (COVID-19) global pandemic. The 3C-like protease (3CLpro) is a highly conserved cysteine proteinase that plays a pivotal role in processing the viral polyprotein to create non-structural proteins (nsps) for replication and transcription of SARS-CoV-2, making it an attractive antiviral target for developing broad-spectrum antiviral agents against SARS-CoV-2. In this study, we identified Thonzonium bromide as an inhibitor of SARS-CoV-2 3CLpro with an IC50 value of 2.04 ± 0.25 μM by fluorescence resonance energy transfer (FRET)-based enzymatic inhibition assay from the FDA-approved drug library. Next, we determined the inhibitory activity of Thonzonium bromide analogues against SARS-CoV-2 3CLpro and analyzed their structure-activity relationship (SAR). Interestingly, Thonzonium bromide showed better inhibitory activity than other analogues. Further fluorescence quenching assay, enzyme kinetics analysis, circular dichroism (CD) analysis and molecular docking studies showed that Thonzonium bromide inhibited SARS-CoV-2 3CLpro activity by firmly occupying the catalytic site and inducing conformational changes of the protease. In addition, Thonzonium bromide didn't exhibit inhibitory activity on human chymotrypsin C (CTRC) and Dipeptidyl peptidase IV (DPP-IV), indicating that it had a certain selectivity. Finally, we measured the inhibitory activities of Thonzonium bromide against 3CLpro of SARS-CoV, MERS-CoV and HCoV-229E and found that it had the broad-spectrum inhibitory activity against the proteases of human coronaviruses. These results provide the possible mechanism of action of Thonzonium bromide, highlighting its potential efficacy against multiple human coronaviruses.


Comparison of gastric mucosal blood flow as determined by aminopyrine clearance and gamma-labeled microspheres.
Gastric mucosal blood flow was simultaneously determined by aminopyrine clearance and gamma-labeled microspheres (15 +/- 5 mu in diameter) in anesthetized dogs prepared with a chambered segment of stomach greater curvature. Paired flow measurements were made in 11 dogs (n = 28) secreting in response to intravenous histamine (1mug per kg per min), in 11 (n = 21) nonsecreting dogs given intravenous isoproterenol (0.5 or 1.0 mug per kg per min), and in 9 (n = 10) dogs given no drugs to stimulate secretion or blood flow (resting dogs). Eight additional injections were done in dogs receiving various combinations of isoproterenol and histamine. Isotonic HCl was maintained on the mucosal surface during all experiments. Regression analysis demonstrated a highly significant linear correlation between clearance and microsphere-measured flow in the histamine (P less than 0.001, r = 0.96) and isoproterenol (P less than 0.001, r = 0.78) experiments, with clearance averaging 83% of microsphere flow during histamine stimulation but only 25% during isoproterenol. The relationship between clearance and microsphere flow was not significantly different for the resting and isoproterenol experiments. Mucosal perfusion measured by microspheres was about 5 times the resting value for both histamine and isoproterenol-stimulated dogs. Perfusion calculated from aminopyrine clearance averaged 46, 38, and 90% of the microsphere value in the resting, isoproterenol, and histamine experiments, respectively. Pooled data from secreting dogs demonstrated a fairly constant ratio of microsphere-measured flow to clearance (1.25 +/- 0.06 mean +/- SEM), regardless of the secretory rate. Our results indicate that aminopyrine clearance reflects only a small fraction of mucosal blood flow in the nonsecreting stomach, even in the presence of exogenous acid.


Dobutamine in the treatment of depressed cardiac function: a study in patients with ischaemic heart disease during the early post-operative period.
Dobutamine was administered by intravenous infusion to 10 patients with ischaemic heart disease who had a low cardiac output syndrome following abdominal surgery. The dosage of dobutamine started from 2.5 mcg kg-1 min-1 and was increased stepwise to 5, 7.5, 10, 12.5 and 15 mcg kg-1 min-1. Cardiac index increased significantly from 2.05 +/- 0.32 to 3.03 +/- 0.61. min-1 min-2 with 15 mcg kg-1 min-1. Heart rate was unchanged with 7.5 mcg kg-1 min-1 but increased significantly from 97.7 +/- 18.5 to 126.1 +/- 21.5 beats. min-1 with 15 mcg kg-1. min-1. Stroke index increased significantly from 21 +/- 4.4 to 25.4 +/- 5.1 ml m-2. beat-1 with 7.5 mcg kg-1 min-1. Pulmonary wedge pressure fell significantly from 14 +/- 2.9 to 9.1 +/- 2.4 mmHg with 2.5 mcg kg-1 min-1. Mean arterial pressure showed no significant change. No side effects were observed in these patients. We conclude that in patients with depressed cardiac function dobutamine at low doses of 2.5 mcg kg-1 min-1 decreases afterload and filling pressures. At the average doses of 5 - 7.5 mcg kg-1 min-1 stroke index and cardiac index are increased. At higher doses of 10 - 15 mcg kg-1 min-1 heart rate and cardiac index increase while stroke index fails to increase further.


Predictors of Mental Health Services Use Across the Life Course among Racially-Ethnically Diverse Adults.
Little is known about key factors associated with use of mental health services across the life course. This study determined key socioeconomic, social support, psychiatric, and medical predictors of services use in younger, middle, and older age. The sample included 3,708 adults with DSM-IV-based mood, anxiety, and substance use disorders in the Collaborative Psychiatric Epidemiology Surveys. Key predictors of mental health services use for each age group were systematically determined by multivariable models, and exploratory analyses examining potential effect modification by race-ethnicity and sex were assessed by interaction terms. Statistical analyses included complex design-corrected and weighted logistic regression analyses that provide results generalizable to the United States. Psychiatric and medical issues such as prior suicidal behavior, comorbid psychiatric disorders, and perceived cognitive impairment increased odds of mental health services use in younger, middle, and older age. Chronic medical conditions also influenced services use in younger and older age, with their impact on use across age potentially modified by racial-ethnic disparities (p interaction = 0.01). Moreover, socioeconomic factors like marital status influenced use in middle and older age, where being divorced, separated, widowed, or never married encouraged use. The effect of marital status on use across age was also potentially modified by racial-ethnic disparities (p interaction = 0.02). Key socioeconomic, social support, psychiatric, and medical predictors uniquely influence use of mental health services across the life course. These findings will help inform efforts to encourage greater services use by adults across the life course in need of care.


Changing motor patterns of the 3rd axillary muscle activities associated with longitudinal control in freely flying hawkmoths.
The 3rd axillary muscles (3AXMs) in the mesothorax in hawkmoths are direct flight muscles and pull forewings back along to the body axis. The 3AXMs are regarded as steering muscles because of their changeable activities during turning flight under tethered conditions. We investigated activities of the upper unit of the 3AXMs during free flight with a micro-telemetry device and captured body and wing movements by high-speed cameras. The 3AXM was activated with 1 to 3 spikes per each wingbeat cycle but sometimes ceased to fire. The phase of the onset of the activities was, even though it was variable, close to the phase of the elevator muscle activities. Therefore the upper unit of the 3AXM activities would affect upstroke properties phasically including wing retractions. We focused on longitudinal flight control and identified a correlation between the phase of the 3AXM and body pitch angle, which is important kinematical parameter for longitudinal control in insect flight. The phasic changes of the 3AXM activities would support quick changes in longitudinal control.


Limited susceptibility and lack of systemic infection by an H3N2 swine influenza virus in intranasally inoculated chickens.
Chickens were intranasally inoculated with the swine influenza virus (SIV) A/swine/NC/307408/04 (H3N2) (NC/04 SIV) to determine the infectivity of a North American SIV for chickens, as well as the possibility of chicken meat serving as a transmission vehicle for SIV. White leghorn (WL) layer-type chickens were used for initial pathotyping and infectivity tests, and a more comprehensive intranasal pathogenesis study was done with white Plymouth rock (WPR) broiler-type chickens. None of the NC/04 SIV-inoculated WL or WPR chickens displayed clinical signs. Serologic tests showed that the virus was able to infect both intranasally inoculated WL and WPR chickens, but the antibody titers were low, suggesting inefficient replication. Some of the NC/04 SIV-inoculated WL chickens shed low levels of virus, mostly from the alimentary tract, but viral shedding was not detected in NC/04 SIV-inoculated WPR chickens. The comprehensive pathogenesis study demonstrated that the virus did not cause systemic infections in WPR chickens, and feeding breast and thigh meat from the NC/04 SIV-inoculated WPR to WL chickens did not transmit NC/04 SIV.


The Second Heart Program-A multidisciplinary team supporting people who inject drugs with infective endocarditis: Protocol of a feasibility study.
Infective endocarditis (IE) is a severe and highly prevalent infection among people who inject drugs (PWID). While short-term (30-day) outcomes are similar between PWID and non-PWID, the long-term outcomes among PWID after IE are poor, with 1-year mortality rates in excess of 25%. Novel clinical interventions are needed to address the unique needs of PWID with IE, including increasing access to substance use treatment and addressing structural barriers and social determinants of health. PWID with IE will be connected to a multidisciplinary team that will transition with them from hospital to the community. The six components of the Second Heart Team are: (1) peer support worker with lived experience, (2) systems navigator, (3) addiction medicine physician, (4) primary care physician, (5) infectious diseases specialist, (6) cardiovascular surgeon. A convergent mixed-methods study design will be used to test the feasibility of this intervention. We will concurrently collect quantitative and qualitative data and 'mix' at the interpretation stage of the study to answer our research questions. This study has been approved by the Hamilton Integrated Research Ethics Board (Project No. 7012). Results will be presented at national and international conferences and submitted for publication in a scientific journal. Trial registration number: ISRCTN14968657 https://www.isrctn.com/ISRCTN14968657.


A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease.
Hypofunction of brain N-methyl-d-aspartate (NMDA) receptors has been implicated in psychiatric disorders such as schizophrenia and Alzheimer's disease. Inhibition of glycine transporter-1 (GlyT1) is expected to increase glycine, a co-agonist of the NMDA receptor and, consequently, to facilitate NMDA receptor function. We have identified ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole) as a novel GlyT1 inhibitor, and here describe our in vitro and in vivo characterization of this compound. ASP2535 potently inhibited rat GlyT1 (IC(50)=92 nM) with 50-fold selectivity over rat glycine transporter-2 (GlyT2). It showed minimal affinity for many other receptors except for μ-opioid receptors (IC(50)=1.83 μM). Oral administration of ASP2535 dose-dependently inhibited ex vivo [(3)H]-glycine uptake in mouse cortical homogenate, suggesting good brain permeability. This profile was confirmed by pharmacokinetic analysis. We then evaluated the effect of ASP2535 on animal models of cognitive impairment in schizophrenia and Alzheimer's disease. Working memory deficit in MK-801-treated mice and visual learning deficit in neonatally phencyclidine (PCP)-treated mice were both attenuated by ASP2535 (0.3-3mg/kg, p.o. and 0.3-1mg/kg, p.o., respectively). ASP2535 (1-3mg/kg, p.o.) also improved the PCP-induced deficit in prepulse inhibition in rats. Moreover, the working memory deficit in scopolamine-treated mice and the spatial learning deficit in aged rats were both attenuated by ASP2535 (0.1-3mg/kg, p.o. and 0.1mg/kg, p.o., respectively). These studies provide compelling evidence that ASP2535 is a novel and centrally-active GlyT1 inhibitor that can improve cognitive impairment in animal models of schizophrenia and Alzheimer's disease, suggesting that ASP2535 may satisfy currently unmet medical needs for the treatment of these diseases.


Survival and predictors of outcome in patients with acute leukemia admitted to the intensive care unit.
Predictors of outcome and rates of successful discharge have not been defined for patients with acute leukemia admitted to intensive care units (ICUs) in the US. This is a retrospective analysis of 90 patients with acute leukemia (no history of bone marrow transplant) admitted to an ICU from 2001-2004. The primary endpoints were improvement and subsequent discharge from the ICU, discharge from the hospital, and 2-month survival after hospital discharge. Secondary endpoints were 6- and 12-month survival. Univariate and multivariate logistic regression analyses were performed to identify factors predicting outcome. The median age of patients was 54 years and 48 (53%) were male. The most common reason for ICU transfer for all patients was respiratory compromise. The majority of all patients (68%) were eventually placed on ventilator support and approximately half required pressors. During the ICU course, 29 patients (32%) improved and subsequently resumed aggressive leukemia management, and 24 patients (27%) survived to be discharged from the hospital. The 2-, 6-, and 12-month overall survival was 24 (27%), 16 (18%), and 14 (16%), respectively. Higher APACHE II score, use of pressors, undergoing bone marrow transplantation preparative regimen, and adverse cytogenetics predicted worse outcome. Newly diagnosed leukemia, type of leukemia, or age did not. One of 4 patients with acute leukemia survived an ICU admission to be discharged from the hospital and were alive 2 months later. A diagnosis of acute leukemia should not disqualify patients from an ICU admission.


Pulmonary blastoma: a rare case of childhood malignancy.
A case of pulmonary blastoma is presented with review of the radiographic, ultrasonographic and CT appearances of this rare malignant tumor of children. Pulmonary blastoma arises from primitive lung mesenchyma and histologically resembles fetal lung. The clinical presentation is usually respiratory distress. The prognosis of the disease is poor even if surgical resection, supplemental chemotherapy and radiation therapy are performed. We present a case of pulmonary blastoma who died two days after surgical resection.


Does receiving high or low breast cancer risk estimates produce a reduction in subsequent breast cancer screening attendance? Cohort study.
Risk-stratified breast cancer screening may improve the balance of screening benefits to harms. We assess a potential new harm: reduced screening attendance in women receiving below average-risk (false reassurance) or higher-risk results (screening avoidance). Following initial screening, 26,668 women in the PROCAS study received breast cancer risk estimates, with attendance recorded for two subsequent screening rounds. First-screen attendance was slightly reduced in below-average (85.6%) but not higher-risk women, compared to other women (86.4%). Second-screen attendance increased for women at higher-risk (89.2%) but not below-average, compared to other women (78.8%). Concerns about this potential harm of risk-stratified screening therefore appear unfounded.


Modified intrapleural cisplatin treatment for lung cancer with positive pleural lavage cytology or malignant effusion.
We evaluate the efficacy and safety of the modified intrapleural cisplatin treatment for lung cancer patients with positive pleural lavage cytology or malignant effusion. The treatment was performed for seven patients with malignant effusion and 18 patents with positive pleural lavage cytology. After pulmonary resection, the pleural cavity was filled with cisplatin with a normal saline solution for 30 min. Complications and survival of the patients were evaluated. The chest tube duration were significantly prolonged in the treatment (CDDP) group (5.7 +/- 3.6 vs. 2.8 +/- 2.6 days). We had one operative death that developed a bronchial fistula; however, the other complications were not severe. The mortality rate was 4% and the morbidity rate was 60%. We experienced two carcinomatous pleuritis in the CDDP group. The median survival time of the CDDP group was 47.0 +/- 11.1 months and the 3- and 5-year survival rate was 52.6% and 11.3%, respectively. We were able to perform this treatment for these advanced lung cancer patients, which had the preventive effect of carcinomatous pleuritis. This therapy shows the possibility of a treatment that might lead to an improvement in the prognosis of these patients, without causing severe complications.


Detection of metabolite induction in fungal co-cultures on solid media by high-throughput differential ultra-high pressure liquid chromatography-time-of-flight mass spectrometry fingerprinting.
Access to new biological sources is a key element of natural product research. A particularly large number of biologically active molecules have been found to originate from microorganisms. Very recently, the use of fungal co-culture to activate the silent genes involved in metabolite biosynthesis was found to be a successful method for the induction of new compounds. However, the detection and identification of the induced metabolites in the confrontation zone where fungi interact remain very challenging. To tackle this issue, a high-throughput UHPLC-TOF-MS-based metabolomic approach has been developed for the screening of fungal co-cultures in solid media at the petri dish level. The metabolites that were overexpressed because of fungal interactions were highlighted by comparing the LC-MS data obtained from the co-cultures and their corresponding mono-cultures. This comparison was achieved by subjecting automatically generated peak lists to statistical treatments. This strategy has been applied to more than 600 co-culture experiments that mainly involved fungal strains from the Fusarium genera, although experiments were also completed with a selection of several other filamentous fungi. This strategy was found to provide satisfactory repeatability and was used to detect the biomarkers of fungal induction in a large panel of filamentous fungi. This study demonstrates that co-culture results in consistent induction of potentially new metabolites.


Recent developments in the way forward for alternative methods: formation of national consensus platforms in Europe.
Ecopa, the European Consensus Platform on 3R-Alternatives, is an international not-for-profit organization that wants to stimulate the development of 3R-alternatives, increase awareness among the public, scientists and regulatory bodies, and help their implementation into the different national legislations. This is done by networking and bringing together National Consensus Platforms on 3R-alternatives. Consensus means that all parties concerned are represented, namely, animal welfare, industry, academia, and governmental institutions. Actually, 14 Member State Platforms exist. Fully complying with the criteria, set by ecopa, are the platforms of Austria, Belgium, the Czech Republic, Finland, Germany, Italy, the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom. Under development are the platforms of Denmark, Norway, and Poland. To reach its goals, ecopa uses conventional scientific tools such as workshops and meetings but it also makes scientific-political statements. A recent realization in particular is the involvement of ecopa in several European projects of the Sixth Framework Programme, either as coordinator, research partner, or board member.


A novel biclustering algorithm of binary microarray data: BiBinCons and BiBinAlter.
The biclustering of microarray data has been the subject of a large research. No one of the existing biclustering algorithms is perfect. The construction of biologically significant groups of biclusters for large microarray data is still a problem that requires a continuous work. Biological validation of biclusters of microarray data is one of the most important open issues. So far, there are no general guidelines in the literature on how to validate biologically extracted biclusters. In this paper, we develop two biclustering algorithms of binary microarray data, adopting the Iterative Row and Column Clustering Combination (IRCCC) approach, called BiBinCons and BiBinAlter. However, the BiBinAlter algorithm is an improvement of BiBinCons. On the other hand, BiBinAlter differs from BiBinCons by the use of the EvalStab and IndHomog evaluation functions in addition to the CroBin one (Bioinformatics 20:1993-2003, 2004). BiBinAlter can extracts biclusters of good quality with better p-values.


Evaluation of a novel repetitive gas-enhanced permeation test for restoration leakage determination after thermo-mechanical loading.
To assess leakage of class-I restorations using a gas-enhanced permeation test (GEPT) as compared with conventional SEM or dye analysis. Pressure differences over time and penetrating water volumes were measured simultaneously in a two-chamber system (GEPT) before and after class I cavity preparation in 30 molars. Ten teeth were restored with a composite restoration without bonding (A1), a composite restoration with bonding (A2) or a ceramic indirect restoration (B). Five intact teeth served as controls (C). Another GEPT measurement was performed and impressions were taken. Teeth were subjected to thermodynamic loading (1 200 000 cycles) and final GEPT measurements and impressions were made. SEM evaluation of the marginal continuity was performed and teeth were subjected to a Fuchsin dye penetration test. Spearman's rank test was used to compare results from different tests. The GEPT and SEM values did not correlate before loading (0.359, p = 0.051), but significantly correlated afterwards (0.662, p < 0.0001). The correlations between the Fuchsin dye penetration test and GEPT and SEM surface marginal analysis were significant (0.777 and 0.534, p-values < 0.0001 and 0.002, respectively). SEM marginal analysis was mainly limited in reflecting the surface restoration integrity. GEPT evaluation may, therefore, serve as a tool to non-destructively assess restoration sub-surface integrity over time. The current study provided proof that restoration margin quality does not necessarily reflect its leakage behaviour.


[Effect of RU38486 on fibronectin expression in cultured human trabecular cells].
To study the effect of RU38486 on fibronectin expression in human trabecular cells (HTCs) in vitro. The trabecular specimens from human donors were primarily cultured and subcultured. Cultured cells were observed by light and electron microscopes. Fibronectin (FN), laminin (LN) and neuron-specific enolase (NSE) in extracellular matrix (ECM) of the cells were immunohistochemically stained with LSAB method. The quantities of FN [optical density (A) means] affected by different concentrations of dexamethasone (Dex) and RU38486 were measured through indirect immunochemical method associated with computer image analysis. According to the growing characteristics and morphological features, the cultured cells were identified as HTCs. Comparison of A means of FN induced by Dex and RU38486 was 10(-6) mol/L dex (12 days) > 10(-7) mol/L Dex (12 d) > 10(-7) mol/L Dex (5 d) > Control group = 10(-7) mol/L Dex (5 d) + 10(-8) mol/L RU38486 (7 d). Dex can stimulate HTCs in vitro to secrete more FN. Bit RU38486 can reverse this high level of FN expression induced by Dex on receptor level. The efficacy of RU 38486 [glucocorticoid receptor (GR)-antagonist] in reducing intraocular pressure in vivo should be confirmed by further studies.


Imidacloprid: Comparative toxicity, DNA damage, ROS production and risk assessment for aquatic non-target organisms.
Imidacloprid is a neonicotinoid systemic insecticide used worldwide. Despite its hazardous impact on non-target organisms, few studies have been conducted concerning the potential eco-genotoxic effects in invertebrates of surface waters where this pesticide is detected from units of ng/L to tens of μg/L. The aim of the present work was to determine the acute, the sub-chronic and the chronic toxicity of imidacloprid in producers and primary consumers of the freshwater trophic chain. The organisms under investigation were the green alga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus, the cladoceran crustacean Ceriodaphnia dubia and the benthic ostracod Heterocypris incongruens. In addition, potential DNA damage and ROS production were evaluated in C. dubia. Furthermore, in accordance with European guidelines, toxicological risk assessment of imidacloprid was performed for all continents considering its global occurrence in surface waters. In addition, we assessed the genotoxicological risk and median inhibition of reproduction was observed at units of mg/L for rotifers and daphnids. Algae showed the lowest level of sensitivity to the pesticide with effective concentrations from units to hundreds of mg/L. DNA lesions were marked from 7 μg/L with a significant increase in damage as concentrations increased. Chronic toxicity risk quotient values were generally below to a threshold value of 1, with no consequential environmental concern other than for the Canadian areas. On the contrary, the genotoxicological risk quotient values were found higher than the threshold value in all continents.


Validation of the adaptive scan method in the quest for time-efficient methods of testing auditory processes.
A major barrier to the clinical application of psychophysical testing of central auditory processes is the time required to obtain precise estimates of different listening abilities. In this study, we validate a novel adaptive scan (AS) method of threshold estimation that is designed to adapt on a range of values around threshold rather than on a single threshold value. This method has the advantage of providing the listener with greater familiarity with the stimulus characteristics near threshold while maintaining precise measurement and increasing time-efficiency. Additionally, we explore the time-efficiency of AS through comparison with two more conventional adaptive algorithms and the method of constant stimuli in two common psychophysical tasks: the detection of a gap in noise and the detection of a tone in noise. Seventy undergraduates without hearing complaints were tested using all four methods. The AS method provided similar threshold estimates with similar precision to those from the other adaptive methods and, thus, it is a valid adaptive method of psychophysical testing. We also provide an analysis of the AS method based on precision metrics to propose a shortened version of the algorithm that maximizes the time/precision tradeoff and can achieve similar thresholds to the adaptive methods tested in the validation. This work lays the foundation for using AS across a wide variety of psychophysical assessments and experimental situations where different levels of precision and/or time-efficiency may be required.


The metabolic effects of two different lipid emulsions used in parenterally fed premature infants--a randomized comparative study.
To compare the effects of two different lipid emulsions, based on soybean oil and olive oil respectively on plasma lipid concentrations and acylcarnitine profile of very low birth weight infants. Randomized comparative study. Forty very low birth weight infants, ≤32 weeks of gestational age and receiving at least 40% of the calorie taken by parenteral nutrition from lipid solution at 14th day of life were evaluated. Group I (n=20) received soybean oil based lipid emulsion (Intralipid®) and Group II (n=20) received olive oil based lipid emulsion (Clinoleic®). Plasma lipid concentrations and acylcarnitine profile were assessed. Triglyceride, cholesterol, high and low density lipoprotein levels, liver function tests were similar between two groups whereas very low density lipoprotein level was statistically lower in Group I (p<0.05). Free carnitine levels were 15.73±10.67 in Group I and 34.25±22.18 μM in Group II (p=0.012) and hexanoyl carnitine levels 2.18±2.10 in Group I and 0.38±0.12 μM in Group II, respectively (p=0.005). Plasma medium chain acylcarnitine levels were significantly higher in Group I. Low levels of very low density lipoprotein in Group I may be a way of hemostasis to keep the serum triglyceride within normal levels. Lower free carnitine levels in soybean oil-based group is the result of carnitine need during the mitochondrial transport of long chain fatty acids. In Group I, due to the inefficient transport of medium chain fatty acids into the mitochondria, medium chain acylcarnitines accumulate in plasma. This may be the reason of lower carnitine levels in Group I. We suggest that higher levels of hexanoyl carnitine, reflecting defective mitochondrial transport of hexanoyl which leads immunsupression, may be the cause of higher sepsis risk in Group I.


The ability of feline spermatozoa in different epididymal regions to undergo capacitation and acrosome reaction.
The sperm maturation process that occurs in the epididymis is a necessary process for spermatozoa to acquire motility and the ability to undergo capacitation, which is an important key for fertilization. The aim of this study was to evaluate the ability of feline spermatozoa from different regions of the epididymis to undergo capacitation and acrosome reaction. Experiment I: epididymal spermatozoa from caput, corpus and cauda regions were placed in phosphate buffered saline (control medium) and in vitro fertilization medium (capacitating conditions). Sperm motility, motility patterns, plasma membrane integrity and tyrosine phosphorylation were evaluated at time 0 and 60min after incubation. Experiment II: spermatozoa were treated with 2μM of calcium ionophore (A23187) to induce the acrosome reaction and acrosome reaction was evaluated. The results showed a significant effect of region with a higher percentage of tyrosine phosphorylation in spermatozoa from the cauda than in the caput or corpus regions (P=0.0061; P=0.0088). Spermatozoa from corpus and cauda showed higher values in the majority of the measured motility parameters than spermatozoa from the caput (P<0.0001). Spermatozoa from all epididymal regions can undergo the acrosome reaction in vitro in response to induction by calcium ionophore with no difference between regions (P>0.05). Spermatozoa from all epididymal regions were able to undergo capacitation. Higher percentage of tyrosine phosphorylation in spermatozoa from the cauda reflect that they more easily underwent capacitation compared to spermatozoa from caput and corpus which required more time of incubation for capacitation. In conclusion feline epididymal spermatozoa from all regions can undergo capacitation and acrosome reaction in vitro and do not require incubation under capacitating conditions.


YihE is a novel binding partner of Rho and regulates Rho-dependent transcription termination in the Cpx stress response.
The conjugative pilus expression (Cpx) stress response system can sense cell envelope stressors, such as misfolded proteins, and upregulate proteases to modify or degrade damaged proteins. YihE is a protein kinase implicated in the Cpx system, and Rho is a transcription termination factor in prokaryotes, but no functional connection between YihE and Rho has been reported. Here, we found that YihE can interact with Rho to form a binary complex with a stoichiometric ratio of 6:1 (Rho:YihE). A low resolution of Rho crystal structure in the presence of YihE was determined. YihE overexpression helped lessen the aberrant effects caused by Rho overexpression, including long cell morphology and other Rho-mediated phenotypes. Overall, YihE is a Rho binding partner that acts as a Rho antagonist in the Cpx stress. YihE binding to Rho would compete RNA from binding to Rho, thereby helping bacteria cope with stress through the regulation of Rho-dependent transcription termination.


Early diagnosis of retinal neurovascular injury in diabetic patients without retinopathy by quantitative analysis of OCT and OCTA.
To quantitatively analyze and compare the differences in retinal neurovascular units (NVUs) between healthy individuals and patients with type 2 diabetes mellitus (DM) by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) techniques and to determine the value of this technique for the early diagnosis of retinal neurovascular damage in patients with diabetes mellitus without retinopathy (NDR). This observational case‒control study was conducted from July 1, 2022, to November 30, 2022, at the outpatient ophthalmology clinic of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All subjects underwent baseline data entry and mean thickness of the peripapillary retinal nerve fiber layer (pRNFL), the thickness of each retinal layer in the macula 3 × 3 mm, and vascular density (VD) examination. The study included 35 healthy individuals and 48 patients with DM. The retinal VD as well as partial pRNFL, macular nerve fiber layer (NFL), and macular ganglion cell layer (GCL) thickness in DM patients exhibited significantly lower VD in the DM group than in the control group (p < 0.05). Age and disease duration of DM patients showed a negative trend with pRNFL thickness, macular NFL thickness, macular GCL thickness, and VD. However, a positive trend was observed between DM duration and partial inner nuclear layer (INL) thickness. Moreover, there was a positive correlation between macular NFL and GCL thickness and VD for the most part, while a negative correlation was shown between INL temporal thickness and DVC-VD. pRNFL-TI and GCL-superior thickness were screened as two variables in the analysis of the predictors of retinal damage in DM according to the presence or absence of DM. The AUCs were 0.765 and 0.673, respectively. By combining the two indicators for diagnosis, the model predicted prognosis with an AUC of 0.831. In the analysis of retinal damage indicators associated with the duration of DM, after regression logistic analysis according to the duration of DM within 5 years and more than 5 years, the model incorporated two indicators, DVC-VD and pRNFL-N thickness, and the AUCs were 0.764 and 0.852, respectively. Combining the two indicators for diagnosis, the AUC reached 0.925. Retinal NVU may have been compromised in patients with DM without retinopathy. Basic clinical information and rapid noninvasive OCT and OCTA techniques are useful for the quantitative assessment of retinal NVU prognosis in patients with DM without retinopathy.


Effects of mirabegron on JJ stent-related symptoms: A multicentric study.
To investigate the effect of mirabegron 50 mg/daily for JJ stent-related symptoms after ureteroscopic stone surgery. Medical records of 145 patients who were given a single daily oral dose of 50 mg of mirabegron for relieving stent-related symptoms were retrospectively analysed. Demographic and clinical data and stone parameters were recorded. All participants completed the Turkish version of the Ureter Symptom Score Questionnaire (USSQ-T) on the postoperative 7th day, and again after at least 3 weeks, before JJ stent removal. The severity of stent-related symptoms was statistically compared before and after the mirabegron treatment. The mean urinary symptoms score decreased significantly from 30.87 ± 9.43 to 22.61 ± 6.78 (P < .0001), mean body pain score decreased significantly from 21.82 ± 11.22 to 14.03 ± 7.52 (P < .0001), mean work performance score decreased from 10.50 ± 8.61 to 7.02 ± 6.51 (P < .0001) and mean general health score decreased significantly from 15.43 ± 6.50 to 11.12 ± 3.70 (P < .0001). The mean sexual matters score significantly decreased from 3.88 ± 3.40 to 2.48 ± 2.03 (P < .0001), the additional problem score decreased from 9.31 ± 4.61 to 6.51 ± 2.83 (P < .0001) and the overall quality of life (QoL) score decreased from 5.18 ± 1.94 to 4.23 ± 1.71 after mirabegron use (P < .0001). Daily use of 50 g of mirabegron significantly improved stent-related symptoms, sexual matters and quality of life.


Characterization of a tight-binding MMP-3 inhibitor using improved fluorescence spectroscopy techniques.
Accurate kinetic characterization of stromelysin (MMP-3) inhibitors is critical in the design of potent inhibitors of this enzyme. We have successfully modified a previously described assay [1] which used an internally quenched peptide substrate (Dnp-PYAYWMR) that, upon cleavage by MMP-3, produces the products, Dnp-PYA (quiet) and YWMR (a fluorophore at 360 nm). This improved assay uses purified human MMP-3 in the presence of either 5% methanol or 5% DMSO. Fluorescence intensities associated with total hydrolysis of substrate by enzyme have been successfully mimicked using a combination of the product peptides as a standard. We have determined a Km of 39.2 microM and Kcat/Km of 4.6 microM/h for MMP-3 (in 5% MeOH) using this peptide substrate. This assay was used successfully to characterize Ro 31-4724 ((N-[(N-[2-[(N-hydroxycarbamoyl)methyl]-4-methyl-valeryl]-L-leucyl ] - L-alanine ethyl ester) as a reversible, tightly binding, inhibitor with a Ki of 26 nm.


Health Care Quality: It's Motherhood and Apple Pie. Until You Start To Measure It.
The pay-for-value movement could justify rewarding-and punishing-doctors based on quality scores. Hardly anyone likes the current ways quality is measured, especially physicians. Few believe that Medicare's Merit-based Incentive Payment System (MIPS) will clear things up. In fact, it might cause more confusion.


Long-term Safety of Synthetic Midurethral Sling Implantation for the Treatment of Stress Urinary Incontinence in Adult Women: A Systematic Review.
Midurethral slings (MUSs) are the most used therapy for the treatment of stress urinary incontinence (SUI). While warning signals about potential complications have been raised worldwide, there is a lack of safety data especially in the long term. Our objective was to evaluate synthetic MUS safety outcomes at long term in adult women. We included all studies evaluating MUSs in adult women with SUI. All synthetic MUSs have been considered: tension-free vaginal tape (TVT), transobturator tape (TOT), and mini-slings. The primary outcome was the reoperation rate at 5 yr. Of 5586 references screened after duplicate removal, 44 studies (8218 patients) were included. Among these, nine were randomized controlled trials and 35 were cohort studies. The overall reoperation rates at 5 yr varied between 0% and 19% for TOT (11 studies), 0% and 13% for TVT (17 studies), and 0% and 19% for mini-slings (two studies). The overall reoperation rates at 10 yr varied between 5% and 15% for TOT (four studies) and between 2% and 17% for TVT (four studies). There were few safety data beyond 5 yr: 22.7% of the articles reported a follow-up at ≥10 yr and 2.3% at ≥15 yr. The incidence rates of reoperations and complications are heterogeneous, and data beyond 5 yr are rare. There is an urgent need to improve safety monitoring of mesh as our review highlights that available safety data are heterogeneous and of insufficient quality to guide the decision.


Recessive Retinopathy Consequent on Mutant G-Protein β Subunit 3 (GNB3).
Mutations in phototransduction and retinal signaling genes are implicated in many retinopathies. To our knowledge, GNB3 encoding the G-protein β subunit 3 (Gβ3) has not previously been implicated in human disease. In this brief report, whole-exome sequencing was conducted on a patient with distinct inherited retinal disease presenting in childhood, with a phenotype characterized by nystagmus, normal retinal examination, and mild disturbance of the central macula on detailed retinal imaging. This sequencing revealed a homozygous GNB3 nonsense mutation (c.124C>T; p.Arg42Ter). Whole-exome sequencing was conducted from April 2015 to July 2015. Expressed in cone photoreceptors and ON-bipolar cells, Gβ3 is essential in phototransduction and ON-bipolar cell signaling. Knockout of Gnb3 in mice results in dysfunction of cone photoreceptors and ON-bipolar cells and a naturally occurring chicken mutation leads to retinal degeneration. Identification of further affected patients may allow description of the phenotypic and genotypic spectrum of disease associated with GNB3 retinopathy.


Knowledge, attitude, and determinants of exclusive breastfeeding during COVID-19 pandemic among lactating mothers in Mekelle, Tigrai: a cross sectional study.
Due to the nutritive and immunologic benefits of breastmilk, children should be exclusively breastfed for the first 6 months of life, even during the corona virus pandemic. However, fear of transmission risk and pandemic-related restrictions could undermine the practice of breastfeeding. This study aimed to assess the knowledge, attitude, and determinants of exclusive breastfeeding (EBF) during COVID-19 among lactating mothers in Mekelle, Tigrai, Ethiopia. A community based cross-sectional study was conducted among 621 lactating mothers living in Mekelle city, Tigrai, from April to June, 2021. Data were collected using an adapted form of a standard KAP questionnaire. Binary logistic regression was used to determine the independent determinants of EBF at a statistical significance of p < 0.05. The strength of the association was measured by odds ratio and 95% confidence interval. Four hundred (64.4%) mothers exclusively breastfed their children. Infants from female-headed households had twice (AOR 2.21; 95% CI 1.31, 3.71) higher odds of EBF. Higher educational status was associated with higher odds of EBF practice. A unit increase in parity was associated with a 23% increase in the odds of EBF. Mothers who received breastfeeding information had a 73% (AOR 1.73; 95% CI 1.17, 2.56) higher odds of EBF. Moreover, mothers with high knowledge score and positive attitude showed a 74% higher (AOR 1.74; 95% CI 1.20, 2.51) and more than double (AOR 2.35; 95% CI 1.50, 3.70) odds of EBF, respectively. About two-thirds of the mothers practiced EBF. Household head, maternal educational, parity, breastfeeding information, knowledge of breastfeeding, and attitude towards EBF were significant determinants of EBF. Our study findings highlighted that programs that enhance women's participation in education and decision-making could improve EBF practice. Besides, during the COVID-19 pandemic, providing lactating mothers with adequate and up-to-date breastfeeding information could be significant in improving EBF practice.


The effects of sponsorship in 12-step treatment of injection drug users.
What contributes to sustained abstinence from injection drug use by those who participate in community-based Narcotics Anonymous (NA) and Alcoholics Anonymous (AA) is not well understood. We know that sponsorship is a central element in these programs. To investigate the relationship between sponsorship and abstinence, we evaluated NA/AA sponsorship over a 1-year period in a longitudinal study of 500 former and current injection drug users in inner-city Baltimore recruited from the community-at-large, independent of treatment center affiliation. The findings indicated that having a sponsor in NA/AA for this population was not associated with any improvement in 1-year sustained abstinence rates than a non-sponsored group. However, being a sponsor over the same time period was strongly associated with substantial improvements in sustained abstinence rates for the sponsors, controlling for involvement with community organizations, NA/AA meeting attendance, marital status, employment, participation in drug and alcohol treatment centers and HIV status. Involvement in community organizations was also strongly associated with successful abstinence, controlling for the same variables. Of those participants involved with community organizations, more than half reported involvement in church activities. Our investigation suggests that, for NA/AA sponsors in this study population, providing direction and support to other addicts is associated with improved success in sustained abstinence for the sponsors but does little to improve the short-term success of the persons being sponsored.


[Tuberculous meningitis: value of neuro-imaging for early diagnosis].
The authors report a case of tuberculous meningoencephalitis diagnosed in a 20-month-old boy with severe neurological sequelae. Most cases of the tuberculous meningitis occur in children less than 3 years old. The mortality rate and incidence of sequelae are greater without early treatment. Imaging has a great impact in the early diagnosis of this disease. In Europe, the increasing incidence of tuberculosis underscores the need to diagnose tuberculous meningitis without delay in children in order to provide a prompt and appropriate treatment.


Measuring ulnar variance: a comparison of techniques.
This study compared three commonly used methods of measuring ulnar variance. The comparison included the project- a-line technique (A), the method of concentric circles (B), and the method of perpendiculars (C). Specific features studied were variations in results generated by each technique as well as the interobserver and intraobserver reliability for each technique. The only significant difference among techniques was between techniques A and B (p = 0.0224), where mean A values were more positive than mean B values. Observers were found to differ significantly (p = 0.0092) independent of technique. All methods studied were highly reliable, although the method of perpendiculars was most reliable for both interobserver (reliability = 0.9801) and intraobserver (reliability = 0.9719) reliability. This study shows that the clinician may choose whichever technique he prefers when measuring ulnar variance.


Effect of Previous Abdominal Surgery on Laparoscopic Roux-en-Y Gastric Bypass Surgery.
Previous abdominal surgery (PAS) is a relative contraindication of laparoscopic surgery. In this study, we aimed to investigate the effect of PAS on the feasibility and safety of laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in patients with obesity and type 2 diabetes mellitus (T2DM). A retrospective analysis was conducted for a total of 235 consecutive patients with obesity and T2DM from Shanghai Tongren Hospital from February 2011 to December 2015. The patients were classified into two groups: no previous abdominal surgery group (NPAS group, n = 179) and previous abdominal surgery group (PAS group, n = 56). The patients underwent LRYGB, and the data of basic information, presence of adhesions, adhesiolysis requirement, operative time, blood loss, hospital stay, and perioperative and postoperative complications were collected and compared between the groups. Adhesion was found in 14 patients in the NPAS group and in 43 patients in the PAS group, with adhesiolysis requirement in 4 (2.23%) and 37 (66.07%) patients, respectively (P < 0.05). There were no complications directly associated with adhesiolysis. No patients were converted to open surgery. There were no significant differences in gender (P = 0.30), T2DM duration (P = 0.58), body mass index (P = 0.06), blood loss (P = 0.36), or perioperative or postoperative complications (P = 0.41) between the groups. Significant differences were observed in the mean age, ASA score, operative time, and hospital stay between the groups (P < 0.001). PAS is relatively safe and feasible for LRYGB in Chinese patients with obesity and T2DM.


Electric Field-Assisted Uptake of Hexavalent Chromium Ions with In Situ Regeneration of Carbon Monolith Adsorbents.
The uptake of hexavalent chromium (Cr(VI)) ions from wastewater is of great significance for environmental remediation and resource utilization. In this study, a self-designed instrument equipped with an oxidized mesoporous carbon monolith (o-MCM) as an electro-adsorbent is developed. o-MCM with a super hydrophilic surface displayed a high specific surface area (up to 686.5 m2 g-1 ). With the assistance of an electric field (0.5 V), the removal capacity of Cr(VI) ions is as high as 126.6 mg g-1 , much higher than that without an electric field (49.5 mg g-1 ). During this process, no reduction reaction of Cr(VI) to Cr(III) ions is observed. After adsorption, the reverse electrode with 10 V is used to efficiently desorb the ions on the carbon surface. Meanwhile, the in situ regeneration of carbon adsorbents can be obtained even after ten recycles. On this basis, the enrichment of Cr(VI) ions in a special solution is achieved with the assistance of an electric field. This work lays a foundation for the uptake of heavy metal ions from wastewater with the assistance of the electric field.


MR imaging of the glenohumeral ligaments.
The glenohumeral ligaments, particularly the inferior one, are the major passive stabilizers of the joint, and the labrum functions as a site of ligamentous attachment. The strong union between the collagen fibers of the glenohumeral ligaments and the glenoid labrum is more resistant to injury than the union between the glenoid rim and the labrum. Labral tears associated with glenohumeral instability are therefore usually secondary to avulsion rather than impaction. This article reviews the normal MR imaging anatomy, variants and pitfalls of the glenohumeral ligaments, and the basic biomechanics of the glenohumeral ligaments. Examples of injuries involving these structures are provided.