Unique miRNAs and their targets in tomato leaf responding to combined drought and heat stress.
Both drought and heat stress are serious global problems, leading to agricultural production loss. MicroRNAs (miRNAs) play important roles in plant species responding to individual drought and heat stress. However, the miRNAs and mRNAs in association with combined drought and heat in crops like tomato remains unclear. We studied the crosstalk of miRNAs and their target genes in tomato plants grown under simultaneous drought and heat stress that frequently happen in field conditions. In total, 335 known miRNAs representing 55 miRNA families and 430 potential novel miRNAs were identified in Solanum lycopersicum L. using small RNA deep sequencing. Through expression analysis, miRNAs in association with drought, heat and the combination of these were investigated. In total, 61, 74 and 37 miRNAs were differentially regulated for combination (of both stresses) vs control, combination vs drought and combination vs heat, respectively. Target genes with different expression levels were found using degradome sequencing, which were mainly involved in transcription factor activity, sequence-specific DNA binding, transcription, regulation of transcription, nucleus, DNA binding etc. The quantitative real-time polymerase chain reaction (qRT-PCR) results confirmed the accuracy of sequencing. Our study serves as valuable knowledge on how crop adapted to combined drought and heat stress by regulating miRNAs and mRNAs, which provide information for crop improvement to deal with future climate changes.


Assessment of the stability of N-terminal pro-brain natriuretic peptide in vitro: implications for assessment of left ventricular dysfunction.
Plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are raised in patients with left ventricular dysfunction. Measurement of this peptide has a potential diagnostic role in the identification and assessment of patients with heart failure. The stability of this peptide over time periods and conditions pertaining to routine clinical practice has not been reported previously. Blood samples were obtained from 15 subjects. One aliquot was processed immediately, and the remaining portions of the blood samples were stored for 24 h or 48 h at room temperature or on ice prior to processing. Plasma concentrations of NT-proBNP were measured with a novel immunoluminometric assay developed within our laboratory. Mean plasma concentrations of NT-proBNP were not significantly different whether blood samples were centrifuged immediately and stored at -70 degrees C or kept at room temperature or on ice for 24 h or 48 h. The mean percentage differences from baseline (reference standard) were +5.2% (95% confidence interval +18.2 to -7.8%) and +0.8% (+15.2 to -13.7%) after storage for 24 h at room temperature or on ice respectively, and +8.9% (+24.2 to -6. 5%) and +3.2% (+15.1 to -0.9%) for storage for 48 h at room temperature or on ice respectively. Pearson correlation coefficients for baseline NT-proBNP concentrations compared with levels at 48 h at room temperature or on ice were r=0.89 and r=0.83 respectively (both P<0.0001). Thus NT-proBNP extracted from plasma samples treated with EDTA and aprotinin is stable under conditions relevant to clinical practice.


[Experience with newer psoriasis therapies (author's transl)].
The following treatments for psoriasis are compared with each other: PUVA, UVB, retinoid 10-9359 alone and in combination with 4 mg triamcinolone or UVB. The best results were obtained with UVB alone and with the combination of UVB and retinoid. Based on a survey of various psoriasis therapies during the last 40 years, it is concluded that a final assessment of the value of a new therapy is only possible after some time.


E-cadherin immunohistochemical analysis of histiocytoid carcinoma of the breast.
Histiocytoid carcinoma is a rare type of invasive breast carcinoma. It has been considered to be a variant of lobular carcinoma, a variant of apocrine ductal carcinoma, and an apocrine variant of lobular carcinoma and to resemble lipid-rich carcinoma. In attempts to elucidate its histogenesis, investigators have used mucin and oil red O histochemical analysis and GCDFP-15 immunostaining. E-cadherin is a relatively recent addition to the armamentarium of immunohistochemical markers used for cell differentiation and is a member of a family of transmembrane glycoproteins that has been shown to have a strong correlation with the histologic phenotypes of breast carcinoma. Most ductal carcinomas show diffuse membrane expression of E-cadherin, and lobular carcinomas are characterized by complete lack of membrane staining of E-cadherin. The object of this study was to use E-cadherin immunohistochemical analysis to help clarify the histogenesis of histiocytoid carcinoma. Fourteen cases containing the diagnosis of histiocytoid carcinoma of the breast were identified at M. D. Anderson Cancer Center (Houston, TX) from 1988 to 2001. All cases were rereviewed, histologic features were evaluated, and immunohistochemical staining with E-cadherin and GCDFP-15 was performed. Clinical information was extracted from the patients' medical records. Eleven cases met published histologic criteria for histiocytoid carcinoma. The remaining three cases were apocrine carcinoma. The pattern of tumor infiltration was solid, without secondary lumen formation in all cases of histiocytoid carcinoma. Lobular carcinoma in situ was identified in eight cases, but was absent in three. There was no E-cadherin immunohistochemical staining in eight of the 11 cases of histiocytoid carcinoma (72.7%). GCDFP-15 was immunoreactive in all 10 cases of histiocytoid carcinoma where it was performed. Follow-up data was available for nine of the 11 cases of histiocytoid carcinoma: six patients were alive with disease at 1.5 to 48 months, one patient had died of disease at 60 months, and two patients had no evidence of disease at 32 and 45 months. We conclude that histiocytoid carcinoma has an immunophenotypical profile consistent with both ductal and lobular differentiation. Moreover, the lack of consistent morphologic features, a specific clinical profile, and a distinct immunohistochemical pattern lead us to hypothesize that histiocytoid carcinoma is not a special type of breast cancer.


Screening for obesity in reproductive-aged women.
Although obesity screening and treatment are recommended by the US Preventive Services Task Force, 1 in 5 women are obese when they conceive. Women are at risk for complications of untreated obesity particularly during the reproductive years and may benefit from targeted screening. Risks of obesity and potential benefits of intervention in this population are well characterized. Rates of adverse pregnancy outcomes including gestational diabetes, preeclampsia, cesarean delivery, and stillbirth increase as maternal body mass index increases. Offspring risks include higher rates of congenital anomalies, abnormal intrauterine growth, and childhood obesity. Observational data suggest that weight loss may reduce risks of obesity-related pregnancy complications. Although obesity screening has not been studied in women of reproductive age, the effect of obesity and the potential for significant maternal and fetal benefits make screening of women during the childbearing years an essential part of the effort to reduce the impact of the obesity epidemic.


Distribution of C-peptide and its determinants in North American children at risk for type 1 diabetes.
To determine basal and stimulated C-peptide percentiles in North American children and adolescents at risk for type 1 diabetes (T1D) and to examine factors associated with this distribution in the Diabetes Prevention Trial-Type 1 (DPT-1). We included 582 subjects aged 4-18 years at randomization in the DPT-1 trials. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and every 6 months during the 5-year follow-up period. The percentile values of C-peptide after baseline OGTT were estimated according to age, BMI Z score (BMIZ), and/or sex categories. Conditional quantile regression was used to examine the relationship between C-peptide percentiles and various independent variables. The basal and stimulated C-peptide levels increased significantly as age and BMIZ increased (P < 0.05). Both age and BMIZ had a stronger impact on the upper quartile of C-peptide distributions than the lower quartile. Sex was only significantly associated with stimulated C-peptide. Higher stimulated C-peptide levels were generally observed in girls compared with boys at the same age and BMIZ (P < 0.05). HLA type and number of positive antibodies and antibody titers (islet cell antibody [ICA], insulin autoantibody, GAD65A, and ICA512A) were not significantly associated with C-peptide distribution after adjustment for age, BMIZ, and sex. Age-, sex-, and BMIZ-specific C-peptide percentiles can be estimated for North American children and adolescents at risk for T1D. They can be used as an assessment tool that could impact the recommendations in T1D prevention trials.


Clinical presentation and outcomes of peripartum cardiomyopathy in the Middle East: a cohort from seven Arab countries.
Published data on the clinical presentation of peripartum cardiomyopathy (PPCM) are very limited particularly from the Middle East. The aim of this study was to examine the clinical presentation, management, and outcomes of patients with PPCM using data from a large multicentre heart failure (HF) registry from the Middle East. From February to November 2012, a total of 5005 consecutive patients with HF were enrolled from 47 hospitals in 7 Middle East countries. From this cohort, patients with PPCM were identified and included in this study. Clinical features, in-hospital, and 12 months outcomes were examined. During the study period, 64 patients with PPCM were enrolled with a mean age of 32.5 ± 5.8 years. Family history was identified in 11 patients (17.2%) and hypertension in 7 patients (10.9%). The predominant presenting symptom was dyspnoea New York Heart Association class IV in 51.6%, class III in 31.3%, and class II in 17.2%. Basal lung crepitations and peripheral oedema were the predominant signs on clinical examination (98.2% and 84.4%, respectively). Most patients received evidence-based HF therapies. Inotropic support and mechanical ventilation were required in 16% and 5% of patients, respectively. There was one in-hospital death (1.6%), and after 1 year of follow-up, nine patients were rehospitalized with HF (15%), and one patient died (1.6%). A high index of suspicion of PPCM is required to make the diagnosis especially in the presence of family history of HF or cardiomyopathy. Further studies are warranted on the genetic basis of PPCM.


Neuropilin (NRPs) Related Pathological Conditions and Their Modulators.
Neuropilin 1 (NRP1) represents one of the two homologous neuropilins (NRP, splice variants of neuropilin 2 are the other) found in all vertebrates. It forms a transmembrane glycoprotein distributed in many human body tissues as a (co)receptor for a variety of different ligands. In addition to its physiological role, it is also associated with various pathological conditions. Recently, NRP1 has been discovered as a coreceptor for the SARS-CoV-2 viral entry, along with ACE2, and has thus become one of the COVID-19 research foci. However, in addition to COVID-19, the current review also summarises its other pathological roles and its involvement in clinical diseases like cancer and neuropathic pain. We also discuss the diversity of native NRP ligands and perform a joint analysis. Last but not least, we review the therapeutic roles of NRP1 and introduce a series of NRP1 modulators, which are typical peptidomimetics or other small molecule antagonists, to provide the medicinal chemistry community with a state-of-the-art overview of neuropilin modulator design and NRP1 druggability assessment.


Biochemical Characterization and 16S rRNA Sequencing of Few Lipase-Producing Thermophilic Bacteria from Taptapani Hot Water Spring, Orissa, India.
Three lipase-producing thermophilic bacteria (AK-P1, AK-P2, and AK-P3) were isolated from the Taptapani hot water spring in Orissa, India. The crude extra cellular lipases from cell-free culture supernatant were reacted in an olive oil mixture, and their lipolytic activities were compared. Identification of the bacteria was carried out using biochemical tests, 16SrRNA sequencing and sequences submitted to NCBI GenBank. Strain AK-P3, exhibited the highest lipolytic activity of 5.5 U/mL was identified as Porphyrobacter sp. The lipolytic activities of strains AK-P1 and AK-P 2 were 4.5 U/mL and 3.5 U/mL, respectively. Strains AK-P1 and AK-P2 were identified as Acinetobacter sp. and Brevibacillus spp. The GenBank accession numbers of the 16S rRNA gene sequences determined in this study for the strains AK-P1, AK-P2, and AK-P3 are HM359120, HM359119, and HM359118, respectively.


Purification and cloning of the salivary peroxidase/catechol oxidase of the mosquito Anopheles albimanus.
Salivary homogenates of the adult female mosquito Anopheles albimanus have been shown previously to contain a vasodilatory activity associated with a catechol oxidase/peroxidase activity. We have now purified the salivary peroxidase using high-performance liquid chromatography. The pure enzyme is able to relax rabbit aortic rings pre-constricted with norepinephrine. The peroxidase has a relative molecular mass of 66 907 as estimated by mass spectrometry. Amino-terminal sequencing allowed us to design oligonucleotide probes for isolation of cDNA clones derived from the salivary gland mRNA from female mosquitoes. The full sequence of the cDNA demonstrated homology between A. albimanus salivary peroxidase and several members of the myeloperoxidase gene family. A close comparison of A. albimanus salivary peroxidase with canine myeloperoxidase, for which the crystal structure is known, showed that all six disulfide bridges were conserved and demonstrated identity for all five residues associated with a Ca2+-binding site. In addition, 16 of 26 residues shown to be in close proximity to the heme moiety in the canine myeloperoxidase were identical. We conclude that the salivary peroxidase of A. albimanus belongs to the myeloperoxidase gene family. Other possible functions for this molecule in blood feeding are discussed.


Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria.
Serious systemic infections may occur during cancer chemotherapy due to disturbances in the oropharyngeal and gastrointestinal microflora, impaired mucosal barrier functions and immunosuppression. Bacteria may spread from the gastrointestinal tract to the regional lymph nodes. The routes for bacterial spread from the oral cavity are less well known. In the present study we investigated changes in the oral and intestinal microfloras in rats given 50 mg/kg 5-fluorouracil (5-FU) i.v. for 6 days. Bacterial dissemination to the lymph nodes draining the oral cavity and the lymph nodes draining the gastrointestinal tract was examined. Effects of adding the probiotic strain Lactobacillus plantarum 299v in the drinking water to the rats were measured. 5-FU treatment caused an increase in the number of facultative and strictly anaerobic bacteria in biopsies from the oral cavity and an increase in the number of facultative anaerobes in the large intestine. The proportion of facultative gram-negative rods increased in both the oral cavity and intestine. Bacteria translocated to both the cervical and mesenteric lymph nodes in untreated animals and increased in numbers after 5-FU treatment due to an increase in the number of facultative gram-negative rods. Treatment with L. plantarum 299v improved food intake and body weight in 5-FU-treated rats. It also reduced the 5-FU-induced raise in the total numbers of facultative anaerobes in the intestine, but did not reduce translocation and did not prevent diarrhea. This study reinforces the oral cavity, along with the gastrointestinal tract, as a source for bacterial dissemination. The use of probiotic bacteria may reduce some side effects of 5-FU treatment.


MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration.
Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA-mRNA network of inflamed motor neurons by leveraging cell type-specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE). We found robust induction of miR-92a in inflamed spinal cord neurons and identified cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) as a key target of miR-92a-mediated posttranscriptional silencing. We detected CPEB3 repression in inflamed neurons in murine EAE and human MS. Moreover, both miR-92a delivery and Cpeb3 deletion protected neuronal cultures against excitotoxicity. Supporting a detrimental effect of Cpeb3 in vivo, neuron-specific deletion in conditional Cpeb3 knockout animals led to reduced inflammation-induced clinical disability in EAE. Together, we identified a neuroprotective miR-92a-Cpeb3 axis in neuroinflammation that might serve as potential treatment target to limit inflammation-induced neuronal damage.


Gastroretentive drug delivery system of metoclopramide hydrochloride: formulation and in vitro evaluation.
The present investigation concerns the development of floating matrix tablets of metoclopramide hydrochloride (MHCl) for improving its bioavailability by prolonging gastric residence time. Floating matrix tablets (FMT) of MHCl were prepared using the polymers guar gum (GG), karaya gum (KG), HPMC E15 (HE) alone and in combination with HPMC K15M (HK) and gas generating agents such as calcium carbonate and citric acid. The fabricated tablets were evaluated for their physical characteristics such as hardness, drug content, buoyancy, swelling properties and in vitro release studies in 0.1N HCl. The tablets without gas generating agents and HK did not float at all whereas tablets with gas generating agents and without HK floated for 2.33-5.48 h then eroded completely and exhibited faster drug release. Tablets with gas generating agents and HK floated for 24 h without complete erosion and showed slower drug release. This indicates that gas generating agents contributes towards the initial floating of tablets and faster drug release and HK for maintaining the integrity of the FMT and sustaining the drug release. The increase in the concentration of HK in FMT from 10 mg to 40 mg resulted in decrease in release rate of drug. The possibility of drug polymer interaction was determined by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) spectrometer, and confirmed no interaction between drug and polymers. The release pattern of prepared tablets followed Higuchi kinetics which confirms release mechanism by diffusion.


Israel's long-term care insurance law after a decade of implementation.
Israel's Long-Term Care Insurance (LTCI) law has been in effect for a decade. It is timely to review the effects of this legislation with a view to identifying possible directions for reform and lessons for other countries considering the introduction of a similar social insurance scheme. The paper considers the law's effects in terms of the size and characteristics of the beneficiary population, the coverage of the scheme, its financial standing, the rate of institutionalization of the elderly, the caregiving burden, the service delivery system, and the overall scope of long-term care services for the aged. Israel's experience has lessons for financing arrangements, target efficiency, service delivery arrangements, and the construction of the burden of care.


Donor-to-donor variability in the expansion potential of human bone marrow cells is reduced by accessory cells but not by soluble growth factors.
Clinical trials assessing the utility of cultured hematopoietic cells for the support of patients receiving high-dose chemotherapy are beginning. Although many reports have described these cultures, little is known about the donor-to-donor variability that might be expected to occur in widespread use. Therefore, this study was undertaken to assess variables which might predict and reduce the donor-to-donor variability in cell expansion potential. CD34-enriched cell cultures, plated to contain 3000 CD34+lin- cells per well, exhibited a wide range of cell output (0.02 to 5.07 x 10(6)) with a high coefficient of variation (CV = 0.69, n = 52). The range in CFU-GM output was even greater (12 to 9455, CV = 0.90). Addition of preformed stroma had a significant positive effect, and resulted in narrower ranges of cell (0.19 to 8.27 x 10(6), CV = 0.41) and CFU-GM (218 to 17586, CV = 0.54) output. A wide range of stromal-dependency was exhibited by CD34-enriched cells from different donors, with stroma augmenting cell output by 1.2- to 14-fold (mean 3.5), and CFU-GM output by 1.7- to 24-fold (mean 6.5). In contrast, changes in the soluble growth factor combination affected cells from different donors in a similar fashion, thereby altering the mean level of performance without reducing donor-to-donor variability. Experiments were next performed to assess the relative contribution of CD34+lin- cells and stromal cells to culture variability by culturing CD34+lin- cells from three donors on preformed stroma from three donors in parallel. Variability in culture output was attributed to the CD34+lin- cell donor, whereas stroma from different autologous or allogeneic donors gave similar performance. Therefore, both expansion potential and stromal-dependency were inherent characteristics of CD34+lin- cells from different donors. Donor characteristics (i.e., sex, age, weight, and height) and flow cytometric assays (i.e., CD34+lin- cell purity, and CD38-, Thy-1+, and c-kit+ subsets thereof) were not well correlated with expansion potential. In contrast, many of the different biological characteristics (i.e., inoculum CFU-GM, cell and CFU-GM output, and stromal-dependency) were strongly correlated with each other. Mononuclear cell (MNC) cultures, which provide an accessory cell environment (including endogenous stroma) in which CD34+lin- cells grow, were compared with CD34-enriched cell cultures. MNC cultures (containing 3000 CD34+lin- cells) were found to give the greatest and most consistent cell (2.51 to 5.20 x 10(6), CV = 0.17) and CFU-GM (2618 to 14,745, CV = 0.46) output. These results have significant implications for the design of clinical trials of cultured hematopoietic cells, as well as for the understanding of diversity in human stem cell behavior. Furthermore, the results demonstrate the importance of a large sample size in scientific studies of primary human hematopoietic cell behavior.


[Management of diabetic ketoacidosis in diabetic patients: clinical practice nursing recommendations].
Diabetic ketoacidosis is a severe and acute condition in Type 1 Diabetes mellitus that is prompted by relative or absolute insulin deficiency. It is frequently related to stressful situations, in which stress hormones are elevated. It is considered a clinical emergency that requires immediate and effective intervention. This article, based on the physiopathology and the clinical manifestations, aims at providing clinical practice nursing recommendations for the management of diabetic ketoacidosis


Learning through reinforcement for N-person repeated constrained games.
The design and analysis of an adaptive strategy for N-person averaged constrained stochastic repeated game are addressed. Each player is modeled by a stochastic variable-structure learning automaton. Some constraints are imposed on some functions of the probabilities governing the selection of the player's actions. After each stage, the payoff to each player as well as the constraints are random variables. No information concerning the parameters of the game is a priori available. The "diagonal concavity" conditions are assumed to be fulfilled to guarantee the existence and uniqueness of the Nash equilibrium. The suggested adaptive strategy which uses only the current realizations (outcomes and constraints) of the game is based on the Bush-Mosteller reinforcement scheme in connection with a normalization procedure. The Lagrange multipliers approach with a regularization is used. The asymptotic properties of this algorithm are analyzed. Simulation results illustrate the feasibility and the performance of this adaptive strategy.


[Mini-invasive interventions for cystic formations of the spleen].
The data of complex clinical examination and surgical treatment of 89 patients, having splenic cysts (SC), are analyzed. Indications and contraindications for miniinvasive methods of treatment (laparoscopic and puncture-draining procedures under ultrasonographic control) application are substantiated, taking into account their size, localization, pathogenesis and presence of SC complications. Diagnostic efficacy of abdominal ultrasonography, computer tomography for SC was estimated, the significance of these methods, while choosing a rational tactics of treatment, was determined. There were elaborated and introduced into clinical practice the stages of endosurgical procedures, including performance of organpreserving operations for SC. Introduction of the elaborated diagnostic algorithm and tactics of treatment of SC have permitted to reduce postoperative complications rate and the patients stay in hospital, improving their quality of life as well.


Treatment practice and research issues in improving opioid treatment outcomes.
Providers of treatment for opioid addiction have entered a new era of accountability, as Federal and State regulators increasingly demand objective evidence of treatment effectiveness. Since the length of treatment is associated with success of treatment, opioid treatment programs that demonstrate an ability to retain patients can make a strong case that they are effective. The challenge to opioid treatment providers is to examine their practices and begin organizational change to incorporate scientifically proven practices to improve patient retention. The challenge to the research community is to partner more effectively with community-based providers to help them through the transition.


Previous loss of chromosome 11 containing a suppressor locus increases radiosensitivity, neoplastic transformation frequency and delayed death in HeLa x fibroblast human hybrid cells.
CGL1 (HeLa x fibroblast) hybrid cells have been utilized to study mechanisms of radiation-induced neoplastic transformation of human cells in vitro. Previous analysis has shown that loss of active tumor suppressor alleles on fibroblast chromosomes 11 and 14 may be required for radiation-induced neoplastic transformation of CGL1 cells. Loss of chromosome 11 alone was, therefore, found to be necessary but not sufficient for neoplastic transformation. We postulated that the loss of chromosome 11 may make the hybrid cells more susceptible to radiation-induced neoplastic transformation, since these cells have already undergone one of the required tumor suppressor loss events. Hybrid cells which have lost one copy of chromosome 11 were designated CON104(-11). CON104(-11) hybrid cells were found to have increased X-ray sensitivity and susceptibility to radiation-induced neoplastic transformation when compared with the parental CGL1 cells. In addition, the neoplastically transformed foci appear to arise earlier after radiation exposure in CON104(-11) versus CGL1 cells. Furthermore, the plating efficiency (PE) of the progeny of the irradiated CON104(-11) cells, growing in transformation flasks, is persistently lower than parental CGL1 cells during the 21 day assay period. The lower PE of the progeny of irradiated cells was attributed to the expression of delayed death/lethal mutations post-irradiation, a reflection of genomic instability. Taken together, the data indicate that previous loss of chromosome 11 may increase the radiation-induced genomic instability of the hybrid cells, leading to increased radiation sensitivity and neoplastic transformation potential. The data suggest that one possible function of the chromosome 11 tumor suppressor gene may be to help maintain genome stability after radiation damage.


Teaching psychiatry residents to teach: a national survey.
Because there have been no previously published national surveys on teaching psychiatry residents about how to teach, the authors surveyed United States psychiatry program directors on what and how residents are taught about teaching. All psychiatry training programs across the United States were mailed a semistructured questionnaire; 95 responded (response rate: 53%). The survey included questions on what, if anything, was provided in the way of formal instruction; the number of seminars offered each year; texts and other materials that were used for teaching; and how seminars were evaluated. The majority (N=69, 73%) of all responding programs provided formal instruction to residents about how to teach. Topics most commonly taught included evaluation and feedback (N=57; 60%), lecturing skills (N=43; 45%), small-group skills (N=40; 42%), learning theory (N=37; 39%), and problem-based learning (N=36; 38%). Instructional methods used were predominantly group discussion (N=62; 65%), lecturing (N=59; 62%), reading of relevant literature (N=35; 37%), role-playing (N=33; 35%), and audiovisual instruction (N=32; 34%). There was a heterogeneity of texts and materials used for teaching. Few of the programs utilized formal validated and reliable tools for evaluating their teaching. Although most programs provided formal teaching, there remains a need to further develop teaching programs and to create model ones.


Evaluation of a fluidised positioner to reduce occipital pressure injuries in intensive care patients: A pilot study.
This pilot study aimed to evaluate the clinical efficacy and feasibility of a fluidised positioning device to reduce occipital pressure injuries (PIs). A post-test design with a historical control group was used in a 54-bed intensive care unit between September 2017 and August 2018. Patients who were receiving either extracorporeal membrane oxygenation, were mechanically ventilated, or had raised intracranial pressure (≥20) were recruited. The intervention consisted of a fluidised positioning device under the patient's head, and a skin assessment every 8 h. Outcome measures included the occurrence of occipital PIs and registered nurses (RNs)' perspectives of the intervention. Data collected from patients in the intervention group were compared with data obtained from the historical control group between May 2016 and April 2017. Sixty-four patients were recruited in the intervention phase and 63 were in the historical control group. Results showed a statistically significant reduction in occipital PIs by 87.7% (16/63; 25.4% historical control vs 2/64; 3.13% interventional group). Bedside RNs provided positive evaluation of the fluidised positioning device. The findings demonstrate that the fluidised positioning device is a feasible and effective intervention in reducing the risk of occipital PIs in intensive care patients, which merits the continuation of use and further evaluation through a larger-scale study.


Young people with chronic illness: the approach to transition.
As increasing numbers of young people with chronic illness reach adulthood, their ongoing medical care must evolve to be delivered in an adult rather than paediatric setting, a process known as transition. Towards this goal, increasing numbers of paediatric and adult hospitals are engaging in processes to promote the continuity of care for young people with chronic illness. Increasing evidence shows that adverse health consequences occur when inadequate transition arrangements are in place. This article draws from the experience of a transition programme emanating from the Royal Children's Hospital, Melbourne and describes the preparation that can ensure effective transition of young people with chronic illness to adult institutions. In paediatric settings, this includes opportunities for young people to be seen medically on their own to encourage independence with health-care goals and ensuring that adequate health information is transferred to the adult service. In adult institutions, understanding the concept of adolescent development will encourage young people's engagement with the new health-care providers to improve health outcomes. Joint clinics between paediatric and adult health-care teams can improve the transfer of individual patient knowledge, promote a collaborative approach to patient care, facilitate continuity of care and build confidence from both medical and patient perspectives. Including patients in decision-making processes around transition services will encourage youth-focused service developments that will help achieve optimal outcomes in young people with chronic illness.


Atopic eczema and the allergist.
Several decades ago, the skin was considered to be little more than a simple barrier to dehydration, environmental toxins, and extrinsic bacteria; however, we now recognize that the skin is a complex immune organ that is fully integrated with the immune functions of the bone marrow, lymph nodes, liver, and spleen. Lymphocytes possess a surface glycoprotein, referred to as the cutaneous lymphocyte-associate antigen (CLA), which specifically binds to the skin. The Langerhans cell is the primary antigen processing cell in skin, and they have been shown to traverse to regional lymph nodes where they then have an opportunity to network with lymphocytes that traffic to and from the skin. This paints the picture of the skin as being a very dynamic immune organ that is totally integrated with the other immune organs and effector cells of the body. This discussion will review clinical complexities of atopic dermatitis as a prototype of allergic skin disease.


Stomatal behaviour under terminal drought affects post-anthesis water use in wheat.
Post-anthesis water use is important for grain yield in wheat under drought because this water is immediately used for grain filling. The aim of this study was to determine whether root capacity for water uptake from deeper layers in the soil profile differed between two genotypes with contrasting stomatal behaviour under terminal drought. The wheat cultivar Drysdale and the breeding line IGW-3262 were grown in 1m deep pots in a glasshouse under well-watered conditions until anthesis, when three watering treatments were imposed: (i) watering maintained at 90% pot soil water capacity (WW), (ii) watering withheld but supplementary watering supplied to the bottom 30cm of the pot to keep this layer of the soil profile wet until physiological maturity (WB) and (iii) watering completely withheld (WS). Stomatal conductance, post-anthesis water use and water use efficiency, and grain yield were measured. Post-anthesis water use in Drysdale was similar in the WB and WW treatments, while in IGW-3262 it was 30% less in the WB treatment than in the WW treatment. In the WB treatment as the top soil dried, stomatal closure was faster in IGW-3262 than in Drysdale, which may have affected the capacity of roots to uptake available water at depth. The reduction in post-anthesis water use in IGW-3262 resulted in a decline in grain yield.


Optical label switching of DRZ/DPSK orthogonal signal generated by photonic-crystal fiber.
We demonstrate orthogonal label switching by using a dark-return-to-zero (DRZ) payload and differential phase-shift keying (DPSK) label generated by a dispersion-flattened photonic-crystal fiber. The high extinction ratio of both the payload and label improves the receiver margin. The DRZ payload introduces little cross talk to the DPSK label due to the RZ-like output of the demodulated DPSK. Simulations are performed to study the eye-closure penalty of the payload and label at different DRZ pulse widths. We compare the DRZ/DPSK with the RZ and DPSK signals numerically at the same data rate and show that the DRZ/DPSK has a strong tolerance to the polarization-mode dispersion. The DRZ/DPSK has a more compact spectrum suitable for the strong filtering requirements in WDM systems.


Individual differences in anxiety trait are related to spatial learning abilities and hippocampal expression of mineralocorticoid receptors.
Although high levels of anxiety might be expected to negatively influence learning and memory, it remains to be shown whether individual differences in anxiety may influence spatial learning and memory in outbred rat populations. We have studied this possibility in male Wistar rats whose levels of anxiety were first characterized as either high (HA) or low (LA) according to their behavior in the elevated plus maze or in the open field test. Subsequently, their performance in the Morris water maze was studied, a task dependent on hippocampal activity. Interestingly, LA rats showed a faster acquisition and better memory in the water maze when compared to HA rats. Indeed, this difference in performance could mainly be attributed to the increase in thigmotactic behavior (swimming in circles close to the maze walls) displayed by HA rats during spatial navigation. Glucocorticoids are known to affect the state of anxiety and the hippocampus is the main target of glucocorticoids in the brain. Hence, we investigated whether the hippocampal expression of the two classical corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) differed in the two groups of rats. We found that LA rats displayed higher hippocampal expression of MR but not GR than HA rats. Indeed, the expression levels for these receptors were positively correlated with the amount of time spent by the animals in the open arms of the elevated plus maze. Moreover, we present evidence that the levels of anxiety quantified in the first stages of our study constitute a trait rather than a state. Taken together, this study has generated evidence of a close interaction between the anxiety trait, hippocampal MR expression and the learning abilities of individuals in stressful spatial orientation tasks.


Effect of temporal fine structure on speech intelligibility modeling.
Temporal fine structure (TFS) carries important information for the speech perception of hearing-impaired listeners and for the design of novel prosthetic hearing devices. This study assessed the performance of present intelligibility indices for predicting the intelligibility of speech containing different amount of TFS information. Speech intelligibility data was collected from vocoded and wideband Mandarin sentences containing little/partial and intact TFS information, respectively, and was then subjected to the correlation analysis with existing intelligibility indices. It was found that, though performing well in predicting the intelligibility of vocoded or wideband speech separately, present intelligibility indices were not highly correlated with the intelligibility scores when a general function was used to map all intelligibility measures to intelligibility scores. Analysis further showed that the intelligibility prediction power could be significantly improved when multiple condition-dependent functions were used for mapping intelligibility measures to intelligibility scores.


Panax notoginseng saponins administration modulates pro- /anti-inflammatory factor expression and improves neurologic outcome following permanent MCAO in rats.
Ischemic stroke, particularly permanent occlusion, accounts for the overwhelming majority of all strokes. In addition to the occlusion of arteries, the inflammatory response plays a pivotal role in the severity of the cerebral injury and its clinical prognosis. Here, panax notoginseng saponins (PNS) extracted from a traditional Chinese herbal medicine was administered following permanent middle cerebral artery occlusion (MCAO) in rats to explore the neuroprotective mechanisms against ischemic injury. The results showed that MCAO surgery was successful in producing an infarct and that PNS and nimodipine could ameliorate the neurological deficits. The expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased, while the level of interleukin-10 (IL-10) was reduced in the infarct cortex 7 days after MCAO, as assessed by immunohistochemistry, western blotting and quantitative real-time PCR (qRT-PCR). PNS was able to markedly reduce the overexpression of IL-1β and TNF-α while significantly promoting the expression of IL-10, but did not affect the elevated expression of TGF-β1. Meanwhile, nimodipine was able to significantly reduce the expression of IL-1β and TNF-α, but had no obvious effect on IL-10 or TGF-β1. In addition, the serum levels of TNF-α, IL-10 and TGF-β1 were basically consistent with cerebral tissue results; however, the IL-1β levels did not differ. We conclude that PNS can directly down-regulate the overexpression of proinflammatory factors IL-1β and TNF-α while up-regulating the expression of anti-inflammatory factor IL-10 in the core region of the cerebral infarct, thereby preventing neurological damage in rats after permanent MCAO.


Coronal plane Calcaneal-Talar Orientation in Varus Ankle Osteoarthritis.
We do not yet fully understand how the subtalar joint position is related to the varus osteoarthritic ankle joint. The purposes of this study were (1) to investigate the coronal orientation of the calcaneus relative to the talus according to the ankle osteoarthritis stage, talar tilt (TT), and (2) to determine if there is TT threshold at which apparent subtalar compensation begins to fade. We retrospectively reviewed 132 ankles that underwent weightbearing computed tomography (WBCT) for varus ankle osteoarthritis. The TT, subtalar inclination angle (SIA), and calcaneal inclination angle (CIA) were measured using WBCT. Ankles were divided into 5 groups according to Takakura stage and 2 groups according to the apparent compensation status of the subtalar joint and compared the index of the inclination of the subtalar joint relative to the ankle (SIA) or the index of the inclination of the calcaneus relative to the ankle (CIA). Additionally, we explored the relationship between SIA or CIA and the TT. Apparent subtalar compensation (SIA and CIA) was significantly lower in Takakura stages 3b and 4. The SIA and CIA significantly differed according to the apparent compensation status (P < .001 and P = .030, respectively). The CIA of the noncompensated group varied widely, whereas the SIA was relatively constant. Furthermore, TT was greater than 9.5, which indicated a high probability of a noncompensated heel (sensitivity, 92.6%; specificity, 89.7%). The position of the calcaneus appears compensatory with coronal plane orientation in varus ankle osteoarthritis when the TT is ≤9.5 degrees. Level IV, case series.


What Social Workers Need to Know about Muslims: An Analysis of the Contemporary Social Work Scholarship.
This article analyzes peer-reviewed English-language social work scholarship on Islam and Muslims published between 2011 and 2021. Of these 127 articles, 70 journal venues are represented, and first authors are primarily American (44 percent), followed by British (15 percent) and Canadian (11 percent). A total of 70 journals published studies analyzing data related to Muslims/Islam and social work, with 46 consisting of only one publication between 2011 and 2021. A total of 13 of these journals had a SCImago Journal Rank indicator of over 0.5, and three with rankings over 1.0. The volume of publications was high in 2015 and 2020, in particular. Major themes include faith-aligned and strengths-based approaches, the importance of mosques in the lives of Muslims, the relevance of the hijab in the lives of Muslim women, and the prevalence and impact of sociopolitical stereotypes. The conclusion calls for still greater culturally respectful approaches to the profession that include Islam and Muslim individuals/communities and ensuring that ethics and practice/research continue to evolve in ways that are culturally relevant to diverse communities.


Identification and purification of a peroxisomal branched chain fatty acyl-CoA oxidase.
Isoprenoid (branched) fatty acids such as pristanic acid can be degraded via beta-oxidation in peroxisomes. We synthesized 2-methylpalmitoyl-CoA as a model substrate in order to study the first step of the peroxisomal beta-oxidation of branched fatty acids, catalyzed by an acyl-CoA oxidase. 2-Methylpalmitoyl-CoA oxidase activity was found in rat liver homogenates. Subcellular fractionation demonstrated that the oxidase was confined to peroxisomes. 2-Methylpalmitoyl-CoA oxidase was also present in kidney and intestine. It was not induced in liver or in the extrahepatic tissues by treatment of rats with peroxisome proliferators or by feeding diets containing excess isoprenoids. The enzyme was partially purified together with palmitoyl-CoA oxidase and trihydroxycoprostanoyl-CoA oxidase by heat treatment and ammonium sulfate fractionation of liver extracts. The partially purified preparation was chromatographed on various columns. 2-Methylpalmitoyl-CoA oxidase could be separated from the inducible (by peroxisome proliferators) palmitoyl-CoA oxidase and from trihydroxycoprostanoyl-CoA oxidase, but it always coeluted with the noninducible palmitoyl-CoA oxidase, recently described by us (Schepers, L., Van Veldhoven, P. P., Casteels, M., Eyssen, H. J., and Mannaerts, G. P. (1990) J. Biol. Chem. 265, 5242-5246). 2-Methylpalmitoyl-CoA oxidase was purified to near homogeneity in three chromatographic steps (anion exchange, hydroxylapatite, and gel filtration). Its apparent molecular mass is approximately 415 kDa, and it consists of identical subunits of approximately 70 kDa. The enzyme oxidized 2-methylpalmitoyl-CoA twice as rapidly as palmitoyl-CoA and pristanoyl-CoA as rapidly as palmitoyl-CoA, so that it can be considered as a branched fatty acyl-CoA oxidase. Since pristanoyl-CoA is one of its naturally occurring substrates we propose to name this enzyme pristanoyl-CoA oxidase.


Sulphated polysaccharides from Ulva clathrata and Cladosiphon okamuranus seaweeds both inhibit viral attachment/entry and cell-cell fusion, in NDV infection.
Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC50 of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage.


Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch.
A clear relationship exists between visceral obesity and type 2 diabetes, whereas subcutaneous obesity is comparatively benign. Here, we show that adipocyte-specific deletion of the coregulatory protein PRDM16 caused minimal effects on classical brown fat but markedly inhibited beige adipocyte function in subcutaneous fat following cold exposure or β3-agonist treatment. These animals developed obesity on a high-fat diet, with severe insulin resistance and hepatic steatosis. They also showed altered fat distribution with markedly increased subcutaneous adiposity. Subcutaneous adipose tissue in mutant mice acquired many key properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation. Transplantation of subcutaneous fat into mice with diet-induced obesity showed a loss of metabolic benefit when tissues were derived from PRDM16 mutant animals. These findings indicate that PRDM16 and beige adipocytes are required for the "browning" of white fat and the healthful effects of subcutaneous adipose tissue.


A combined micromagnetic-microfluidic device for rapid capture and culture of rare circulating tumor cells.
Here we describe a combined microfluidic-micromagnetic cell separation device that has been developed to isolate, detect and culture circulating tumor cells (CTCs) from whole blood, and demonstrate its utility using blood from mammary cancer-bearing mice. The device was fabricated from polydimethylsiloxane and contains a microfluidic architecture with a main channel and redundant 'double collection' channel lined by two rows of dead-end side chambers for tumor cell collection. The microdevice design was optimized using computational simulation to determine dimensions, magnetic forces and flow rates for cell isolation using epithelial cell adhesion molecule (EpCAM) antibody-coated magnetic microbeads (2.8 μm diameter). Using this device, isolation efficiencies increased in a linear manner and reached efficiencies close to 90% when only 2 to 80 breast cancer cells were spiked into a small volume (1.0 mL) of blood taken from wild type mice. The high sensitivity visualization capabilities of the device also allowed detection of a single cell within one of its dead-end side chambers. When blood was removed from FVB C3(1)-SV40 T-antigen mammary tumor-bearing transgenic mice at different stages of tumor progression, cells isolated in the device using anti-EpCAM-beads and magnetically collected within the dead-end side chambers, also stained positive for pan-cytokeratin-FITC and DAPI, negative for CD45-PerCP, and expressed SV40 large T antigen, thus confirming their identity as CTCs. Using this isolation approach, we detected a time-dependent rise in the number of CTCs in blood of female transgenic mice, with a dramatic increase in the numbers of metastatic tumor cells appearing in the blood after 20 weeks when tumors transition to invasive carcinoma and exhibit increased growth of metastases in this model. Importantly, in contrast to previously described CTC isolation methods, breast tumor cells collected from a small volume of blood removed from a breast tumor-bearing animal remain viable and they can be easily removed from these devices and expanded in culture for additional analytical studies or potential drug sensitivity testing.


Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant.
Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. We found that BA.2.86 does not have significantly more escape relative to Omicron XBB.1.5 from neutralizing immunity elicited by either Omicron XBB-family subvariant infection or from residual neutralizing immunity of recently collected sera from the South African population. BA.2.86 does have extensive escape relative to ancestral virus with the D614G substitution (B.1 lineage) when neutralized by sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 when neutralized by sera from Omicron BA.1 infected individuals. BA.2.86 and XBB.1.5 show similar viral infection dynamics in the VeroE6-TMPRSS2 and H1299-ACE2 cell lines. We also investigate the relationship of BA.2.86 to BA.2 sequences. The closest BA.2 sequences are BA.2 samples from Southern Africa circulating in early 2022. Similarly, many basal BA.2.86 sequences were sampled in Southern Africa. This suggests that BA.2.86 potentially evolved in this region, and that unobserved evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.


Physiological regulation of hypothalamic IL-1beta gene expression by leptin and glucocorticoids: implications for energy homeostasis.
Interleukin-1beta (IL-1beta) is synthesized in a variety of tissues, including the hypothalamus, where it is implicated in the control of food intake. The current studies were undertaken to investigate whether hypothalamic IL-1beta gene expression is subject to physiological regulation by leptin and glucocorticoids (GCs), key hormones involved in energy homeostasis. Adrenalectomy (ADX) increased hypothalamic IL-1beta mRNA levels twofold, measured by real-time PCR (P < 0.05 vs. sham-operated controls), and this effect was blocked by subcutaneous infusion of a physiological dose of corticosterone. Conversely, hypothalamic IL-1beta mRNA levels were reduced by 30% in fa/fa (Zucker) rats, a model of genetic obesity caused by leptin receptor mutation (P = 0.01 vs. lean littermates), and the effect of ADX to increase hypothalamic IL-1beta mRNA levels in fa/fa rats (P = 0.02) is similar to that seen in normal animals. Moreover, fasting for 48 h (which lowers leptin and raises corticosterone levels) reduced hypothalamic IL-1beta mRNA levels by 30% (P = 0.02), and this decrease was fully reversed by refeeding for 12 h. Thus leptin and GCs exert opposing effects on hypothalamic IL-1beta gene expression, and corticosterone plays a physiological role to limit expression of this cytokine in both the presence and absence of intact leptin signaling. Consistent with this hypothesis, systemic leptin administration to normal rats (2 mg/kg ip) increased hypothalamic IL-1beta mRNA levels twofold (P < 0.05 vs. vehicle), an effect similar to that of ADX. These data support a model in which expression of hypothalamic IL-1beta is subject to opposing physiological regulation by corticosterone and leptin.


Omega-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women.
Omega-3 (n-3) fatty acid supplementation enhances muscle protein synthesis and muscle size. Whether n-3 fatty acid supplementation attenuates human muscle disuse atrophy is unknown. We determined the influence of n-3 fatty acid supplementation on muscle size, mass, and integrated rates of myofibrillar protein synthesis (MyoPS) following 2 wk of muscle disuse and recovery in women. Twenty women (BMI = 23.0 ± 2.3 kg/m2, age = 22 ± 3 yr) underwent 2 wk of unilateral limb immobilization followed by 2 wk of return to normal activity. Starting 4 wk prior to immobilization, participants consumed either 5 g/d of n-3 fatty acid or an isoenergetic quantity of sunflower oil (control). Muscle size and mass were measured pre- and postimmobilization, and after recovery. Serial muscle biopsies were obtained to measure integrated (daily) MyoPS. Following immobilization, the decline in muscle volume was greater in the control group compared to the n-3 fatty acid group (14 vs. 8%, P < 0.05) and was not different from preimmobilization at recovery in the n-3 fatty acid group; however, it was still lower in the control group ( P < 0.05). Muscle mass was reduced in the control group only ( P < 0.05). MyoPS was higher in the n-3 group compared with the control group at all times ( P < 0.05). We conclude that n-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy in young women, which may be mediated by higher rates of MyoPS.-McGlory, C., Gorissen, S. H. M., Kamal, M., Bahniwal, R., Hector, A. J., Baker, S. K., Chabowski, A., Phillips, S. M. Omega-3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women.


Human opsonins induced during meningococcal disease recognize transferrin binding protein complexes.
Patient serum opsonins against transferrin binding protein A+B (TbpA+B) complexes from two Neisseria meningitidis strains (K454 and B16B6, with 85- and 68-kDa TbpB, respectively) were quantified by a functional phagocytosis and oxidative burst assay. TbpA+B complexes adsorbed to fluorescent beads were opsonized with individual acute and convalescent sera from 40 patients infected by a variety of meningococcal strains. Flow cytometric quantitation of leukocyte phagocytosis products (PP) demonstrated that disease-induced serum opsonins recognized TbpA+B, and the highest anti-TbpA+B serum opsonic activities were found between admission to hospital and 6 weeks later. The PP values obtained with TbpA+B from strain B16B6 (PP(B16B6)) were higher than those obtained with TbpA+B from strain K454 (PP(K454)), with both acute and convalescent sera (P < 0.0001), and correlated positively with higher immunoglobulin G enzyme-linked immunosorbent assay titers against TbpA+B from strain B16B6 than from strain K454 (P < 0.001). In spite of considerable variations between individuals, significant correlations were found between the PP(B16B6) and PP(K454) values, and the PP values did not depend on the variability of the TbpB proteins of the disease-causing strains. Simultaneously measured oxidative burst activity correlated closely with the PP values. We conclude that highly cross-reactive anti-TbpA+B serum opsonins are produced during meningococcal disease. The anti-TbpA+B opsonic activities were not affected by the variability of the TbpB proteins of the disease-causing strains, which further adds to the evidence for the vaccine potential of meningococcal TbpA+B complexes.


A hybrid multi-scale model of COVID-19 transmission dynamics to assess the potential of non-pharmaceutical interventions.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in Wuhan, China in December 2019. It has caused a global outbreak which represents a major threat to global health. Public health resorted to non-pharmaceutical interventions such as social distancing and lockdown to slow down the spread of the pandemic. However, the effect of each of these measures remains hard to quantify. We design a multi-scale model that simulates the transmission dynamics of COVID-19. We describe the motion of individual agents using a social force model. Each agent can be either susceptible, infected, quarantined, immunized or deceased. The model considers both mechanisms of direct and indirect transmission. We parameterize the model to reproduce the early dynamics of disease spread in Italy. We show that panic situations increase the risk of infection transmission in crowds despite social distancing measures. Next, we reveal that pre-symptomatic transmission accelerates the onset of the exponential growth of cases. After that, we demonstrate that the persistence of SARS-CoV-2 on hard surfaces determines the number of cases reached during the peak of the epidemic. Then, we show that the restricted movement of the individuals flattens the epidemic curve. Finally, model predictions suggest that measures stricter than social distancing and lockdown were used to control the epidemic in Wuhan, China.


[Accelerated surgical stay programs. A professional and administrative challenge].
Accelerated surgical stay programs represent a multi-modal, multi-disciplinary concept to reduce postoperative morbidity, hospitalisation and convalescence based upon recent advantages in surgical pathophysiology and pain treatment. Preliminary data from a variety of surgical procedures suggest major improvements in quality of surgical care and cost reduction and call for further controlled or large-size multi-center studies.


Nanodot-doped peptide hydrogels for antibacterial phototherapy and wound healing.
Bacterial infection of wounds delays the healing process, increases the risk of chronic trauma associated with pain and complications, and offers a breeding ground for drug-resistant bacteria. A rapid and effective eradication of the bacterial species in the wound area is thus important. Herein, we designed a phototherapeutic antibacterial platform based on peptides and copper sulfide nanodots (CuS NDs) for multi-mechanistic eradication of bacteria colonized on the wound surface. The antimicrobial peptide weaves into a network in the form of a hydrogel, which supports CuS NDs to generate heat and produce reactive oxygen species (ROS) under the irradiation of near-infrared light (NIR). The heat and ROS generated in situ act as non-contact-based antibacterial factors and together with contact-based antimicrobial peptides cause irreversible membrane destruction, cell content damage, and thermal ablation of the bacteria. Lastly, nanodot-doped peptide hydrogels combined with collagen showed complete bacterial elimination and significantly accelerated wound healing in a splint-fixed mouse infection model.


Ectopic thyroid gland: description of a case and review of the literature.
The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from a developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.


Intragenic suppressor mutations of the COQ8 protein kinase homolog restore coenzyme Q biosynthesis and function in Saccharomyces cerevisiae.
Saccharomyces cerevisiae Coq8 is a member of the ancient UbiB atypical protein kinase family. Coq8, and its orthologs UbiB, ABC1, ADCK3, and ADCK4, are required for the biosynthesis of coenzyme Q in yeast, E. coli, A. thaliana, and humans. Each Coq8 ortholog retains nine highly conserved protein kinase-like motifs, yet its functional role in coenzyme Q biosynthesis remains mysterious. Coq8 may function as an ATPase whose activity is stimulated by coenzyme Q intermediates and phospholipids. A key yeast point mutant expressing Coq8-A197V was previously shown to result in a coenzyme Q-less, respiratory deficient phenotype. The A197V substitution occurs in the crucial Ala-rich protein kinase-like motif I of yeast Coq8. Here we show that long-term cultures of mutants expressing Coq8-A197V produce spontaneous revertants with the ability to grow on medium containing a non-fermentable carbon source. Each revertant is shown to harbor a secondary intragenic suppressor mutation within the COQ8 gene. The intragenic suppressors restore the synthesis of coenzyme Q. One class of the suppressors fully restores the levels of coenzyme Q and key Coq polypeptides necessary for the maintenance and integrity of the high-molecular mass CoQ synthome (also termed complex Q), while the other class provides only a partial rescue. Mutants harboring the first class of suppressors grow robustly under respiratory conditions, while mutants containing the second class grow more slowly under these conditions. Our work provides insight into the function of this important yet still enigmatic Coq8 family.


Trajectories of Insomnia in Adults After Traumatic Brain Injury.
Insomnia is common after traumatic brain injury (TBI) and contributes to morbidity and long-term sequelae. To identify unique trajectories of insomnia in the 12 months after TBI. In this prospective cohort study, latent class mixed models (LCMMs) were used to model insomnia trajectories over time and to classify participants into distinct profile groups. Data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a longitudinal, multisite, observational study, were uploaded to the Federal Interagency Traumatic Brain Injury Repository (FITBIR) database. Participants were enrolled at 1 of 18 participating level I trauma centers and enrolled within 24 hours of TBI injury. Additional data were obtained directly from the TRACK-TBI investigators that will be uploaded to FITBIR in the future. Data were collected from February 26, 2014, to August 8, 2018, and analyzed from July 1, 2020, to November 15, 2021. Traumatic brain injury. Insomnia Severity Index assessed serially at 2 weeks and 3, 6, and 12 months thereafter. The final sample included 2022 participants (1377 [68.1%] men; mean [SD] age, 40.1 [17.2] years) from the FITBIR database and the TRACK-TBI study. The data were best fit by a 5-class LCMM. Of these participants, 1245 (61.6%) reported persistent mild insomnia symptoms (class 1); 627 (31.0%) initially reported mild insomnia symptoms that resolved over time (class 2); 91 (4.5%) reported persistent severe insomnia symptoms (class 3); 44 (2.2%) initially reported severe insomnia symptoms that resolved by 12 months (class 4); and 15 (0.7%) initially reported no insomnia symptoms but had severe symptoms by 12 months (class 5). In a multinomial logistic regression model, several factors significantly associated with insomnia trajectory class membership were identified, including female sex (odds ratio [OR], 1.65 [95% CI, 1.02-2.66]), Black race (OR, 2.36 [95% CI, 1.39-4.01]), history of psychiatric illness (OR, 2.21 [95% CI, 1.35-3.60]), and findings consistent with intracranial injury on computed tomography (OR, 0.36 [95% CI, 0.20-0.65]) when comparing class 3 with class 1. These results suggest important heterogeneity in the course of insomnia after TBI in adults. More work is needed to identify outcomes associated with these insomnia trajectory class subgroups and to identify optimal subgroup-specific treatment approaches.


Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids.
A clinical study to investigate the pharmacokinetics and pharmacodynamics of oral tetrahydrocannabinol was performed. This randomized, double-blind, placebo-controlled, within-subject, inpatient study compared the effects of THC-containing hemp oils in liquid and capsule form to dronabinol (synthetic THC) in doses used for appetite stimulation. The National Institute on Drug Abuse Institutional Review Board approved the protocol and each participant provided informed consent. Detection times and concentrations of THC, 11-hydroxy-Delta-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Delta-tetrahydrocannabinol (THCCOOH) in plasma were determined by gas chromatography-mass spectrometry [limits of quantification (LOQ)=0.5, 0.5, and 1.0 ng/mL, respectively] after oral THC administration. Six volunteers ingested liquid hemp oil (0.39 and 14.8 mg THC/d), hemp oil in capsules (0.47 mg THC/d), dronabinol capsules (7.5 mg THC/d), and placebo. Plasma specimens were collected during and after each dosing condition. THC and 11-OH-THC concentrations were low and never exceeded 6.1 ng/mL. Analytes were detectable 1.5 hour after initiating dosing with the 7.5 mg THC/d regimen and 4.5 hour after starting the 14.8 mg THC/d sessions. THCCOOH was detected 1.5 hour after the first dose, except for the 0.47 mg THC/d session, which required 4.5 hour for concentrations to reach the LOQ. THCCOOH concentrations peaked at 3.1 ng/mL during dosing with the low-dose hemp oils. Plasma THC and 11-OH-THC concentrations were negative for all participants at all doses within 15.5 hours after the last THC dose. Plasma THCCOOH persisted for at least 39.5 hours after the end of dosing and at much higher concentrations (up to 43.0 ng/mL). This study demonstrated that subjects who used high THC content hemp oil (347 mug/mL) as a dietary supplement had THC and metabolites in plasma in quantities comparable to those of patients using dronabinol for appetite stimulation. There was a significant correlation between body mass index and Cmax and body mass index and number of specimens positive for THC and 11-OH-THC.


Discovery of the rare genus Blacometeorus Tobias, 1976 (Hymenoptera, Braconidae, Blacinae) in the Oriental part of China, with description of a new species.
The rare genus Blacometeorus Tobias, 1976 (Hymenoptera: Braconidae: Blacinae)is discovered in Yunnan, China, and a new species, Blacometeorus sinicus Chai & Chen, sp. n. is described and illustrated. It represents the first record of this genus both for China and Oriental region. A key to genus Blacometeorus is updated.


Modeling the Effect of Polymer Chain Stiffness on the Behavior of Polymer Nanocomposites.
Due to their central role in industrial formulations spanning from food packaging to smart coatings, polymer nanocomposites have been the object of remarkable attention over the last two decades. Incorporating nanoparticles (NPs) into a polymer matrix modifies the conformation and mobility of the polymer chains at the NP-polymer interface and can potentially provide materials with enhanced properties as compared to pristine polymers. To this end, it is crucial to predict and control the ability of NPs to diffuse and achieve a good dispersion in the polymer matrix. Understanding how to control the NPs' dispersion is a challenging task controlled by the delicate balance between enthalpic and entropic contributions, such as NP-polymer interaction, NP size and shape, and polymer chain conformation. By performing molecular dynamics (MD) simulations, we investigate the effect of polymer chains' stiffness on the mobility of spherical NPs that establish weak or strong interactions with the polymer. Our results show a sound dependence of the NPs' diffusivity on the long-range order of the polymer melt, which undergoes an isotropic-to-nematic phase transition upon increasing chain stiffness. This phase transition induces a dynamical anisotropy in the nematic phase, with the NPs preferentially diffusing along the nematic director rather than in the directions perpendicular to it. Not only does this tendency determine the NPs' mobility and degree of dispersion in the polymer matrix, but it also influences the resistance to flow of the polymer nanocomposite when a shear is applied. In particular, to assess the role of the chains' conformation on the macroscopic response of our model PNC, we employ reverse nonequilibrium MD to calculate the zero-shear viscosity in both the isotropic and nematic phases, and unveil a plasticizing effect at increasing chain stiffness when the shear is applied along the nematic axis.


The Influence of the COVID-19 Pandemic on the Clinical Application of Evidence-Based Practice in Health Science Professionals.
(1) Background: Evidence-based practice (EBP) informs daily clinical interventions with the purpose of seeking changes to traditional practice through scientific evidence that justifies the reasons for our actions. The objectives were to describe the barriers, beliefs, and attitudes in the application of EBP among university health professionals (not doctors) and to evaluate the influence of the COVID-19 pandemic among them. (2) Methods: This prospective study is both descriptive and observational. The individuals under study were university health professionals (not doctors) from various autonomous regions within Spain, in both public and private spheres. Sociodemographic and labor-related variables linked to the research and its completion were studied. Likewise, the survey instrument Health Sciences Evidence-Based Practice questionnaire (HS-EBP) was administered to evaluate the barriers to, beliefs in, and attitudes towards evidence-based practice. (3) Results: A total of 716 responses were gathered, of which 387 were collected during the period of confinement, and 343 in the COVID-19 post-confinement period. Possible associations that might help respond to the objectives were explored through a correlational study between the sociodemographic variables and each sub-scale of the HS-EBP 30 questionnaire (n = 716). (4) Conclusions: Barriers to, beliefs in, and attitudes towards evidence-based practice are described. There is a leadership gap where line management provides insufficient motivation to follow work routines. The COVID-19 pandemic has caused immense stress among health professionals. The post-confinement group showed a significant change in the variables "beliefs and attitudes", and likewise in the "evaluation" block, justified by the need to update knowledge and to apply evidence.


Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT.
Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.


Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice.
Catch-up growth after insults to growing organs is paramount to achieving robust body proportions. In fly larvae, injury to individual tissues is followed by local and systemic compensatory mechanisms that allow the damaged tissue to regain normal proportions with other tissues. In vertebrates, local catch-up growth has been described after transient reduction of bone growth, but the underlying cellular responses are controversial. We developed an approach to study catch-up growth in foetal mice in which mosaic expression of the cell cycle suppressor p21 is induced in the cartilage cells (chondrocytes) that drive long-bone elongation. By specifically targeting p21 expression to left hindlimb chondrocytes, the right limb serves as an internal control. Unexpectedly, left-right limb symmetry remained normal, revealing deployment of compensatory mechanisms. Above a certain threshold of insult, an orchestrated response was triggered involving local enhancement of bone growth and systemic growth reduction that ensured that body proportions were maintained. The local response entailed hyperproliferation of spared left limb chondrocytes that was associated with reduced chondrocyte density. The systemic effect involved impaired placental function and IGF signalling, revealing bone-placenta communication. Therefore, vertebrates, like invertebrates, can mount coordinated local and systemic responses to developmental insults that ensure that normal body proportions are maintained.


Interactions of lymphotoxin alpha (TNF-beta), angiotensin-converting enzyme (ACE), and endothelin-1 (ET-1) gene polymorphisms in adult periodontitis.
Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. To investigate whether the genes encoded within the HLA class III region may confer susceptibility to periodontitis, polymorphisms in the ET-1 and TNF-beta genes were analyzed together with the I/D polymorphism of the ACE gene. We determined allele and genotype frequencies of the NcoI bi-allelic polymorphism of the TNF-beta gene, the I/D (insertion/deletion) polymorphism of the ACE gene, and the TaqI polymorphism of the ET-1 gene in 63 Caucasian patients with adult periodontitis and 95 orally healthy controls. We found a significant difference in a 3 locus combination of genotypes between patients and controls (P<0.05). In the next analyses, no significant differences were found in allele frequencies of single genes, but we did find a significant difference in the genotype distribution between cases and controls for TNF-beta (P<0.03). Differences were also observed for 2 locus combinations of ACE and TNF-beta genotypes (P<0.03), and the ET-1 and TNF-beta (P<0.05) genes. Evidence of deviation from Hardy-Weinberg equilibrium was observed in the periodontitis group for TNF-beta, with an absence of the B1B1 homozygotes in patients. This study is of an exploratory nature. Considering the number of significant results, however, at least a part of the observed associations may obviously be real and our findings suggest that interactions of the TNF-beta, ET-1, and ACE genes may be involved in susceptibility to adult periodontitis.


Molecular tracers for the PET and SPECT imaging of disease.
The development of positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging continues to grow due to the ability of these techniques to allow the non-invasive in vivo visualisation of biological processes at the molecular and cellular levels. As well as finding application for the diagnosis of disease, these techniques have also been used in the drug discovery process. Crucial to the growth of these techniques is the continued development of molecular probes that can bind to the target biological receptor with high selectivity. This tutorial review describes the use of PET and SPECT for molecular imaging and highlights key strategies for the development of molecular probes for the imaging of both cancer and neurological diseases.


Socio-economic inequalities in smoking and drinking in adolescence: Assessment of social network dynamics.
We investigated whether (1) adolescents selected friends with a similar socio-economic status (SES), (2) smoking and alcohol consumption spread in networks and (3) the exclusion of non-smokers or non-drinkers differed between SES groups. This was a longitudinal study using stochastic actor-oriented models to analyze complete social network data over three waves. Eight Hungarian secondary schools with socio-economically diverse classes took part. This study comprised 232 adolescents aged between 14 and 15 years in the first wave. Self-reported smoking behavior, alcohol consumption behavior and friendship ties were measured. SES was measured based upon entitlement to an income-tested regular child protection benefit. Non-low-SES adolescents were most likely to form friendships with peers from their own SES group [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.02-1.11]. Adolescents adjusted their smoking behavior (OR = 24.05, 95% CI = 1.27-454.86) but not their alcohol consumption (OR = 1.65, 95% CI = 0.62-4.39) to follow the behavior of their friends. Smokers did not differ from non-smokers in the likelihood of receiving a friendship nomination (OR = 0.98, 95% CI = 0.87-1.10), regardless of their SES. Alcohol consumers received significantly more friendship nominations than non-consumers (OR = 1.16, 95% CI = 1.01-1.33), but this association was not significantly different according to SES. Hungarian adolescents appear to prefer friendships within their own socio-economic status group, and smoking and alcohol consumption spread within those friendship networks. Socio-economic groups do not differ in the extent to which they encourage smoking or alcohol consumption.


Cuba's National Medical Genetics Program.
Since first emerging in the late 1970s, the field of human genetics has advanced with extraordinary speed. In just thirteen years (1990 to 2003), the human genome project deciphered the code of life. Today, by detecting genetic predisposition to certain diseases, we can anticipate their appearance even before the onset of symptoms, and progress is being made toward creating so-called "personalized drugs" designed to fit an individual's genetic profile. Yet, these developments are far beyond the reach of the vast majority of people. Few countries have transformed the giant steps in human genetics into national policies, programs and services accessible to the general population.


Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion?
Conversion between duplicated genes limits their independent evolution. Models in which conversion frequencies decrease as genes diverge are examined to determine conditions under which genes can "escape" further conversion and hence escape from a gene family. A review of results from various recombination systems suggests two classes of sequence-dependence models: (1) the "k-hit" model in which conversion is completely inactivated by a few (k) mutational events, such as the insertion of a mobile element, and (2) more general models where conversion frequency gradually declines as genes diverge through the accumulation of point mutants. Exact analysis of the k-hit model is given and an approximate analysis of a more general sequence-dependent model is developed and verified by computer simulation. If mu is the per nucleotide mutation rate, then neutral duplicated genes diverging through point mutants are likely to escape conversion provided 2 mu/lambda much greater than 0.1, where lambda is the conversion rate between identical genes. If 2 mu/lambda much less than 0.1, the expected number of conversions before escape increases exponentially so that, for biological purposes, the genes never escape conversion. For single mutational events sufficient to block further conversions, occurring at rate nu per copy per generation, many conversions are expected if 2 nu/lambda much less than 1, while the genes essentially evolve independently if 2 nu/lambda much greater than 1. Implications of these results for both models of concerted evolution and the evolution of new gene functions via gene duplication are discussed.


Role of Platelet-Rich Plasma Gel in Promoting Wound Healing Based on Medical Images of Wounds.
A wound is the pathological change of soft tissue under normal skin caused by various factors, such as collision, contusion, hot crush, avulsion, corrosive chemicals, operations, excessive wound tension after operations, local pressure that cannot be relieved for a long time, liquid immersion, local infection, and rejection reactions caused by allogeneic substances. The skin itself or its underlying soft tissue loses its integrity and continuity, thus losing its normal physiological function. Medical image analysis is a medical term that refers to the interdisciplinary fields of integrated medical imaging, artificial intelligence, digital image processing and analysis, mathematical modeling, and numerical algorithms. According to the time of wound formation, they can be divided into acute and chronic wounds. The common acute wounds include lacerations caused by trauma, surgical incisions, burns, and donor sites formed after skin graft operations. This article mainly studies the role of platelet-rich plasma gel nanocomposites in promoting wound healing. It is proven that ptt-rich plasma gel can significantly promote tissue repair and regeneration and accelerate wound healing in patients with severe burns. The atomic number of the nanocomposite has a better treatment effect on the nanoparticle approach. In this paper, chitosan nanocomposite membrane, nanocomposite algorithm, and the calculation method of enthalpy of formation of high alloy nanomaterials were used to study the role of ptt-rich plasma gel combined chitosan nanocomposite membrane loaded bone marrow stromal cells in promoting wound healing, and its effects were applied to the repair of special site burns, special burns, and different age burns. Good wound repair benefits from the correct treatment of the wound, which directly affects the stability and development of the internal environment. The difference in healing time between the two groups was statistically significant, and the recovery time of the PRP group was 0.001 less than that of the control group. The results showed that the wound healing time of the PRP group was significantly shorter than that of the control group (P < 0.05); after treatment, the content of VEGF in the wound tissue of the two groups increased, especially in the PRP group; the effective rate of the PRP group was 75.0%, which was higher than 68.8% of the control group. It can play an important role in the regulation of expression and the pathophysiological process of wound healing.


The in vitro uptake of 14C-praziquantel by cestodes, trematodes, and a nematode.
14C-praziquantel was rapidly taken up by Schistosoma mansoni, Fasciola hepatica, Hymenolepis nana, and isolated strobilocerci of Taenia taeniaeformis. Schistosoma mansoni lost praziquantel rapidly to drug-free medium. Chromatography of extracts prepared after incubation of S. mansoni and H. nana yielded no indication that praziquantel was metabolized. Autoradiography revealed a uniform distribution of praziquantel throughout the tissues of S. mansoni and H. nana. Uptake was considerably slower in the nematode Heterakis spumosa and apparently via the oral route.


Exploring behavioral markers of long-term physical activity maintenance: a case study of system identification modeling within a behavioral intervention.
Efficacious interventions to promote long-term maintenance of physical activity are not well understood. Engineers have developed methods to create dynamical system models for modeling idiographic (i.e., within-person) relationships within systems. In behavioral research, dynamical systems modeling may assist in decomposing intervention effects and identifying key behavioral patterns that may foster behavioral maintenance. The Active Adult Mentoring Program was a 16-week randomized controlled trial of a group-based, peer-delivered physical activity intervention targeting older adults. Time-intensive (i.e., daily) physical activity reports were collected throughout the intervention. We explored differential patterns of behavior among participants who received the active intervention (N = 34; 88% women, 64.1 ± 8.3 years of age) and either maintained 150 minutes/week of moderate to vigorous intensity physical activity (MVPA; n = 10) or did not (n = 24) at 18 months following the intervention period. We used dynamical systems modeling to explore whether key intervention components (i.e., self-monitoring, access to an exercise facility, behavioral initiation training, behavioral maintenance training) and theoretically plausible behavioral covariates (i.e., indoor vs. outdoor activity) predicted differential patterns of behavior among maintainers and nonmaintainers. We found that maintainers took longer to reach a steady-state of MVPA. At week 10 of the intervention, nonmaintainers began to drop whereas maintainers increased MVPA. Self-monitoring, behavioral initiation training, percentage of outdoor activity, and behavioral maintenance training, but not access to an exercise facility, were key variables that explained patterns of change among maintainers. Future studies should be conducted to systematically explore these concepts within a priori idiographic (i.e., N-of-1) experimental designs.


Free-electron laser induced processes in thin molecular ice.
Intermolecular reactions in and on icy films on silicate and carbonaceous grains constitute a major route for the formation of new molecular constituents in interstellar molecular clouds. In more diffuse regions and in protoplanetary discs, energetic radiation can trigger reaction routes far from thermal equilibrium. As an analog of interstellar ice-covered dust grains, highly-oriented pyrolytic graphite (HOPG) covered with D2O, NO, and H atoms is irradiated by ultrashort XUV pulses and the desorbing ionic and neutral products are analysed. The yields of several products show a nonlinear intensity dependence and thus enable the elucidation of reaction dynamics by two-pulse correlated desorption.


Genetic diversity and epidemiology of Genogroup II noroviruses in children with acute sporadic gastroenteritis in Shanghai, China, 2012-2017.
Noroviruses (NoVs) are considered an important cause of acute gastroenteritis (AGE) across all age groups, especially in children under 5 years of age. We investigated the epidemiology of noroviruses in outpatient children from the Children's Hospital of Fudan University in Shanghai, China. Stool specimens were collected between January 2012 and December 2017 from 1433 children under 5 years of age with acute gastroenteritis. All samples were analysed by conventional reverse transcription-polymerase chain reaction (RT-PCR) for genogroup II NoVs amplifying both the RNA-dependent RNA polymerase (RdRp) and partial capsid genes. The Norovirus Genotyping Tool v.2.0 ( https://www.rivm.nl/mpf/typingtool/norovirus/ ) was used for genotyping the strains, and phylogenetic analyses were conducted by MEGA 6.0. From 2012 to 2017, GII NoVs were detected in 15.4% (220/1433) of the samples, with the highest detection rate in children aged 7-12 months (19.2%, 143/746). The seasons with the highest prevalence of GII NoVs infection were autumn and winter. Based on genetic analysis of RdRp, GII.Pe (74.5%%, 137/184) was the most predominant RdRp genotype from 2013 to 2017, while GII.P4 played a dominant role in 2012 (55.6%, 21/36). Among the capsid genotypes, the most prevalent NoV genotype from 2012 to 2017 was GII.4 (74.1%, 163/220). On the basis of genetic analysis of RdRp and capsid sequences, the strains were clustered into - 19 RdRp/capsid genotypes, and 12 of them were discordant, such as GII.Pe/GII.4-Sydney_2012, GII.P12/GII.3, GII.P7/GII.6, GII.Pe/GII.3, and GII.P16/GII.2. Starting with 2013, GII.Pe/GII.4-Sydney_2012 had completely replaced the pandemic GII.P4-2006b/GII.4-2006b subtype and was detected in children across all age groups. The present study shows high detection rates and the genetic diversity of circulating NoV GII genotypes in paediatric AGE samples from Shanghai. The findings emphasize the importance of continuous molecular surveillance of emerging NoV strains.


Revealing Complex Functional Topology Brain Network Correspondences Between Humans and Marmosets.
Functional correspondences are known to exist within the brains of both human and non-human primates; however, our understanding of this phenomenon remains largely incomplete. The examination of the topological characteristics inherent in whole-brain functional connectivity bears immense promise in elucidating shared as well as distinctive patterns across different species. In this investigation, we applied topological graph analysis to brain networks and scrutinized the congruencies and disparities within the connectomes of human and marmoset monkey brains. The findings brought to light noteworthy similarities in functional connectivity patterns distributed across the entire brain, with a particular emphasis on the dorsal attention network, default mode network and visual network. Moreover, we discerned unique neural connections between humans and marmosets during both resting and task-oriented states. In essence, our study reveals a combination of shared and divergent functional brain connections underlying spontaneous and specific cognitive functions across these two species.


Thyroid cancer in patients with hyperthyroidism.
The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves' disease. Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves' disease had thyroid cancer. During the follow-up of 74 months (range 4-154), there were no deaths or any recurrences. Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a 'cold' nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.


Boosting Graph Neural Networks with Molecular Mechanics: A Case Study of Sigma Profile Prediction.
Sigma profiles are quantum-chemistry-derived molecular descriptors that encode the polarity of molecules. They have shown great performance when used as a feature in machine learning applications. To accelerate the development of these models and the construction of large sigma profile databases, this work proposes a graph convolutional network (GCN) architecture to predict sigma profiles from molecule structures. To do so, the usage of molecular mechanics (force field atom types) is explored as a computationally inexpensive node-level featurization technique to encode the local and global chemical environments of atoms in molecules. The GCN models developed in this work accurately predict the sigma profiles of assorted organic and inorganic compounds. The best GCN model here reported, obtained using Merck molecular force field (MMFF) atom types, displayed training and testing set coefficients of determination of 0.98 and 0.96, respectively, which are superior to previous methodologies reported in the literature. This performance boost is shown to be due to both the usage of a convolutional architecture and node-level features based on force field atom types. Finally, to demonstrate their practical applicability, we used GCN-predicted sigma profiles as the input to machine learning models previously developed in the literature that predict boiling temperatures and aqueous solubilities. Using the predicted sigma profiles as input, these models were able to compute both physicochemical properties using significantly less computational resources and displayed only a slight decrease in performance when compared with sigma profiles obtained from quantum chemistry methods.