Targeting STT3A-oligosaccharyltransferase with NGI-1 causes herpes simplex virus 1 dysfunction.
Herpes simplex virus 1 (HSV-1) is a contagious neurotropic herpesvirus responsible for oral lesions and herpesviral encephalitis. The HSV-1 envelope contains N-glycosylated proteins involved in infection and that are candidate drug targets. NGI-1 is a small-molecule inhibitor of oligosaccharyltransferase (OST) complexes STT3A-OST and STT3B-OST, which catalyze cotranslational and post-translational N-glycosylation, respectively. Because host OSTs attach HSV-1 glycans, NGI-1 might have anti-HSV-1 activity. We evaluated HSV-1 function using NGI-1 and human embryonic kidney 293 knockout lines for OST isoform-specific catalytic and accessory subunits. N-glycosylation of 2 representative envelope proteins (gC and gD) was primarily dependent upon STT3A-OST, but to a large extent replaceable by STT3B-OST. Knockouts impairing STT3A- or STT3B-OST activity, by themselves, did not appreciably affect HSV-1 function (plaque-forming units, normalized to viral particles measured by unglycosylated capsid protein VP5 content). However, with cells lacking STT3B-OST activity (missing the catalytic subunit STT3B or the oxidoreductase subunits magnesium transporter 1/tumor suppressor candidate 3) and thus solely dependent upon STT3A-OST for N-glycosylation, NGI-1 treatment resulted in HSV-1 having cell type-dependent dysfunction (affecting infectivity with Vero cells much more than with the 293 lines). Ablation of post-translational N-glycosylation can therefore make HSV-1 infectivity, and possibly masking of immunogenic peptide epitopes by glycans, highly sensitive to pharmacological inhibition of cotranslational N-glycosylation.-Lu, H., Cherepanova, N. A., Gilmore, R., Contessa, J. N., Lehrman, M. A. Targeting STT3A-oligosaccharyltransferase with NGI-1 causes herpes simplex virus 1 dysfunction.


Ultrafast separations via pulse flow valve modulation to enable high peak capacity multidimensional gas chromatography.
Ultrafast modulation with a modulation period PM ≥ 50ms via a pulse flow valve is demonstrated for comprehensive two-dimensional gas chromatography (GC×GC) and comprehensive three-dimensional (3D) gas chromatography (GC3). Significant increases in peak capacity and peak capacity production are achieved for GC×GC and GC3 relative to previous studies due to using pulse flow valve modulation. Due to the nature of the "partial" modulation process, the separation dimension following pulse flow valve modulation is not a traditional chromatogram, rather requires data processing to convert the data to expose the encoded chromatographic information, producing "apparent" chromatographic peaks. In the GC×GC mode, a 115-component test mixture was evaluated using a PM of 500ms, creating an apparent 2D peak width-at-base 2W with an average of 25ms, producing a 2nc of 20. Based on the average 1W of 1.0s for the 6min first dimension 1D separation, an ideal peak capacity nc,2D of 7200 is achieved (1,200/min peak production). For a high-speed GC×GC separation (30s run), a PM of 75ms produced apparent 2W of 8ms, ideal for the third dimension of a GC3 instrument. Using the knowledge gained from this high-speed GC×GC experiment, the pulse flow valve was implemented as the second modulator in GC3. Three samples were evaluated in the GC3 mode: a simple mixture containing 18 compounds (to illustrate basic concepts), the 115-component test mixture (to determine peak capacity figures-of-merit), and a diesel spiked with 8 polar compounds (to illustrate chemical selectivity benefits of GC3). For the 115-component test mixture with a 1PM of 1.2s and a 2PM of 60ms, average 1W of 3.2s, 2W of 130ms, and apparent 3W of 13ms were produced, resulting in a 1nc of 210, 2nc of 9.2, and 3nc of 5, respectively. Hence, an ideal peak capacity, nc,3D of ∼10,000 for GC3 was achieved for the 11min 1D separation window of the 115-component test mixture.


Efficacy of a synthetic mesh sling in keeping the small bowel in the upper abdomen to prevent radiation enteropathy in gynecologic malignancies.
Radiation therapy in gynecological malignancies is limited by the frequent occurrence of radiation enteropathy at effective dose levels of 45 Gy and higher. Elevation of the small bowel out of the true pelvis should enable doses of up to 60-70 Gy to be given without damaging the small bowel. We report a feasibility study concerning elevation of the small bowel out of the true pelvis, by creating an intra-abdominal sling with a synthetic mesh. Twelve patients with pelvic gynecological malignancies were included since 1986. In all patients peroperative application of the mesh was possible. In ten patients adequate elevation of the small bowel was achieved. Two patients showed a right-sided herniation of a small bowel loop on a control barium opacification, performed 1 week postoperatively. In one of these a fistula occurred after resecuring the mesh. The most important problem in this study, as has also been reported elsewhere, was a herniation of a small bowel loop. The incidence is probably inversely correlated with the skill of the surgeon and will therefore be reduced with increasing experience. Future long-term studies should address the issue whether or not radiation enteropathy can be prevented by this method.


Single-incision laparoscopic-assisted appendectomy in children: exteriorization of the appendix is a key component of a simple and cost-effective surgical technique.
Single-incision laparoscopic appendectomy was recently introduced as a less-invasive surgical technique than existing methods, and is increasingly being performed worldwide. We have started to perform transumbilical laparoscopic-assisted appendectomy (TULAA) in children. In this study, we assessed its feasibility, efficacy, and cost-effectiveness compared with conventional multiport laparoscopic appendectomy (MLA). We retrospectively reviewed all of the patients who underwent MLA or TULAA between August 2009 and December 2012. Patient characteristics, operative time, length of hospital stay, postoperative complications, cost-effectiveness, and cosmetic results were analyzed. A total of 88 patients underwent laparoscopic appendectomy, with MLA in 48 patients and TULAA in 40 patients. TULAA was successful in 36/40 patients. There were no significant differences in mean operative time or mean length of stay between the two groups of patients. There were no postoperative complications in the TULAA group. The cost of TULAA was much lower than that of MLA. TULAA also provided nearly scarless surgery. TULAA, in which the appendix is exteriorized via a combination of open and laparoscopic techniques, is a safe and effective procedure for treating appendicitis in children. TULAA is a cost-effective treatment that provides excellent cosmetic results.


A Single-Cell-Type Real-Time PCR Method Based on a Modified Patch-Pipette Cell Harvesting System.
Real-time PCR is a powerful tool for quantifying nucleic acid expression. Real-time PCR is conventionally performed at the tissue level to guarantee an abundance of nucleic acid for detection. The precision and reliability of this method, however, is limited by usually being composed of a mixture of different cell types. Single-cell PCR, in contrast, eliminates the purity problem of the cell source. However, use of this method is usually impeded by difficulties in cell harvesting and stringent requirements for processing of very small quantities of nucleic acids. In this study, we combined the advantages of the high purity of selected cells in single-cell PCR with the greater nucleic acid quantities and thus greater ease of tissue-level PCR. The key aspect of our method is to use a modified patch-clamp pipette to harvest several selected cells of the same type. This method is therefore especially useful for cells that can be morphologically or histologically identified such as primary sensory neurons, striated muscle fibers and cells labeled with fluorescent makers.


Characterisation of epidermal lipid composition and skin morphology of animal skin ex vivo.
Epidermal lipids and skin morphology are assumed to substantially influence skin permeability. Although these parameters have been studied extensively, available data are hard to interpret as data have been gathered at different experimental conditions. Therefore, the aim of this study was to provide detailed information on these parameters for four different mammalian skin types. Lipids were extracted from heat separated epidermis, the total epidermal lipid content was measured and the epidermal lipid composition was quantitatively determined by high-performance thin-layer chromatography. Furthermore, vertical and horizontal cryostate skin slices were analysed by light microscopy for thickness of the horny layer, epidermal thickness, density, depth of anchorage and diameter of the hair follicles. The highest total epidermal lipid content was detected in rat epidermis, followed by bovine udder, dog and pig epidermis. Considering the amount of single lipid fractions, cholesterol, cholesteryl ester and free fatty acids were found to be the major constituents of epidermal lipids in all the examined species. However, as confirmed by hierarchical cluster analysis the epidermal lipid profile and morphology showed marked differences between all the examined species.


CT evaluation of shock viscera: a pictorial review.
The purpose of this article is to review both the pathophysiology and the computed tomography features of the hypoperfusion complex and shock viscera. The main findings include dilated fluid-filled loops of bowel with hyperenhancing mucosa, intensely enhancing kidneys and mesenteric vasculature, and small caliber, dense aorta and collapsed, slit-like inferior vena cava. Variable features include increased enhancement of the adrenals, decreased enhancement of the spleen, and altered enhancement of the pancreas with both hypo- and hyperenhancement described. This complex of findings indicates a tenuous hemodynamic status and has been associated with a poor prognosis. In addition, it is important to discern this collection of findings from direct injury to the viscera to aid in appropriate triage and management of the patients' injuries.


Changes in visual field defects during 10-year follow-up for indocyanine green-assisted macular hole surgery.
To determine whether the visual field defects detected within 3 months of indocyanine green (ICG)-assisted inner-limiting membrane (ILM) peeling continue to worsen over longer periods. This was a retrospective observational case series. Four eyes with visual field defects that developed within 3 years of ICG-assisted ILM peeling for a macular hole (MH) were examined yearly for 10 years. The main outcome measures were the degree of mean deviation (MD) determined by Humphrey perimetry with the 30-2 SITA-Fast program and the best-corrected visual acuity (BCVA). Four patients were examined yearly for more than 10 years, with a mean duration of follow-up of 139.5 months (11.6 years) and a range of follow-up of 137-156 months (11.4-13 years). The mean (±standard deviation) preoperative MD value was -4.99 ± 3.26 dB, and the mean postoperative MD values were -12.9 ± 1.29 dB after 1 year, -14.1 ± 0.75 dB after 3 years, and -12.73 ± 2.65 dB after 10 years. The mean preoperative BCVA was 0.65 ± 0.26 logarithm of the minimal angle of resolution (logMAR) units, and the postoperative BCVA was 0.21 ± 0.07 logMAR units at 1 year, 0.28 ± 0.21 logMAR units at 3 years, and 0.14 ± 0.06 dB logMAR units at 10 years. The visual field defects detected soon after ICG-assisted ILM peeling continued to worsen for 3 years, but not thereafter.


Alzheimer's disease risk factor complement receptor 1 is associated with depression.
Variation in the complement receptor 1 gene (CR1) has been identified in recent genome-wide association studies as a risk factor for Alzheimer's disease. Here, we show that two Alzheimer's disease-associated CR1 variants, rs6656401 and rs3818361, are associated with major recurrent depression in females in a population-based cohort using individuals from the Generation Scotland: Scottish Family Health Study.


Percutaneous reanastomosis of transplant kidney.
A successful percutaneous reanastomosis of a transplanted kidney is reported. The kidney already had been operated on several times. The kidney-ureter anastomosis was occluded. Using a combination of ureteroscopy and the percutaneous technique, the old anastomosis was bypassed, and a new one was made.


Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia's southern province: a simulation study.
Malaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. To achieve this goal in Southern province, Zambia a mass test and treat (MTAT) campaign was conducted from 2011-2013 to complement high coverage of long-lasting insecticide-treated nets (LLIN). To identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operational strategies for parasite clearance in southern province. OpenMalaria, a discrete-time, individual-based stochastic model of malaria, was parameterized for the study area to simulate anti-malarial drug administration for interruption of transmission. Simulations were run for scenarios with a range of artemisinin-combination therapies, proportion of the population reached by the campaign, targeted age groups, time between campaign rounds, Plasmodium falciparum test protocols, and the addition of drugs aimed at preventing onward transmission. A sensitivity analysis was conducted to assess uncertainty of simulation results. Scenarios were evaluated based on the reduction in all-age parasite prevalence during the peak transmission month one year following the campaign, compared to the currently-implemented strategy of MTAT 19 % population coverage at pilot and 40 % coverage during the first year of implementation in the presence of 56 % LLIN use and 18 % indoor residual spray coverage. Simulation results suggest the most important determinant of success in reducing prevalence is the population coverage achieved in the campaign, which would require more than 1 year of campaign implementation for elimination. The inclusion of single low-dose primaquine, which acts as a gametocytocide, or ivermectin, which acts as an endectocide, to the drug regimen did not further reduce parasite prevalence one year following the campaign compared to the currently-implemented strategy. Simulation results indicate a high proportion of low-density infections were missed by rapid diagnostic tests that would be treated and cleared with mass drug administration (MDA). The optimal implementation strategy for MTAT or MDA will vary by background level of prevalence, by rate of infections imported to the area, and by ability to operationally achieve high population coverage. Overall success with new parasite clearance strategies depends on continued coverage of vector control interventions to ensure sustained gains in reduction of disease burden.


Improving outcomes for retroperitoneal sarcomas: a work in progress.
This article presents the current understanding of prognostic factors and outcomes for retroperitoneal sarcoma. The discussion focuses on the literature published since 2000, including studies with cohorts of at least 30 patients. An interpretation of factors that have contributed to an improvement in outcomes has been performed. With demonstration of the potential for good long-term outcomes and a better appreciation for the importance of minimizing treatment-related morbidity, the international sarcoma community has increasingly recognized and emphasized the importance of expert multidisciplinary assessment and care for this rare malignancy.


Barriers and facilitators to access mental health services among refugee women in high-income countries: a systematic review.
Based on the Global Trends report from the United Nations High Commissioner for Refugee, in high-income countries, there are 2.7 refuges per 1000 national population, girls and women account for nearly 50% of this refuge population. In these high-income countries, compared with the general population refuge women have higher prevalence of mental illness. Thus, this review was conducted to examine the barriers to and facilitators of access to mental health services for refugee women in high-income countries for refugee resettlement. We searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for research articles written in English with qualitative component. The last search date was on March 14, 2020. A narrative synthesis was conducted to gather key synthesis evidence. Refugee women (aged 18 and older) that could receive mental health services were included. Men and women under non-refugee migrant legal status were excluded. Studies were evaluated studies using the Critical Appraisal Skills Programme (CASP) qualitative checklist. Of the four databases searched, 1258 studies were identified with 12 meeting the inclusion criteria. Three studies were cross-sectional by design, eight studies used a qualitative approach and one studies used mixed approach. The major barriers identified were language barriers, stigmatization, and the need for culturally sensitive practices to encourage accessing mental health care within a religious and cultural context. There were several studies that indicated how gender roles and biological factors played a role in challenges relating to accessing mental health services. The major facilitators identified were service availability and awareness in resettlement countries, social support, and the resilience of refugee women to gain access to mental health services. This review revealed that socio-economic factors contributed to barriers and facilitators to accessing mental health among women refugees and asylum seekers. Addressing those social determinants of health can reduce barriers and enhance facilitators of access to mental health care for vulnerable populations like refugee women. A key limitation of the evidence in this review is that some data may be underreported or misreported due to the sensitive and highly stigmatizing nature of mental health issues among refugee populations. PROSPERO CRD42020180369.


Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status.
Immunosuppression is a risk factor for poor prognosis of critically ill patients, but current monitoring of the immune status in clinical practice is still inadequate. Absolute lymphocyte count (ALC) is not only a convenient biomarker for immune status monitoring but is also suitable for clinical application. In this study, we aimed to explore different trajectories of ALC, and evaluate their relationship with prognosis in critically ill patients. We retrospectively enrolled 10,619 critically ill patients admitted to a general intensive care unit (ICU) with 56 beds from February 2016 to May 2020. Dynamic ALC was defined as continuous ALC from before ICU admission to 5 days after ICU admission. Initial ALC was defined as the minimum ALC within 48 h after ICU admission. Group-based trajectory modeling (GBTM) was used to group critically ill patients according to dynamic ALC. Multivariate cox regression model was used to determine the independent association of trajectory endotypes with death and persistent inflammation, immunosuppression, catabolism syndrome (PICS). A total of 2022 critically ill patients were unsupervisedly divided into four endotypes based on dynamic ALC, including persistent lymphopenia endotype (n = 1,211; 58.5%), slowly rising endotype (n = 443; 22.6%), rapidly decreasing endotype (n = 281; 14.5%) and normal fluctuation endotype (n = 87; 4.4%). Among the four trajectory endotypes, the persistent lymphopenia endotype had the highest incidence of PICS (24.9%), hospital mortality (14.5%) and 28-day mortality (10.8%). In multivariate cox regression model, persistent lymphopenia was associated with increased risk of 28-day mortality (HR: 1.54; 95% CI: 1.06-2.23), hospital mortality (HR: 1.66; 95% CI: 1.20-2.29) and PICS (HR: 1.79; 95% CI: 1.09-2.94), respectively. Sensitivity analysis further confirmed that the ALC trajectory model of non-infected patients and non-elderly patients can accurately distinguished 91 and 90% of critically ill patients into the same endotypes as the original model, respectively. The ALC trajectory model is helpful for grouping critically ill patients, and early persistent lymphopenia is associated with poor prognosis. Notably, persistent lymphopenia may be a robust signal of immunosuppression in critically ill patients.


Post-thoracotomy intercostal artery pseudoaneurysm manifesting as a chest wall metastasis.
Intercostal artery pseudoaneurysm (IAP) represents an extremely rare vascular abnormality developing after an insult to the vascular wall with blood collection within the vascular wall layers and subsequent dilatation. Treatment options, apart from observation, include embolization, endovascular stenting, and surgical correction. We describe the case of a 73-year-old male patient with colonic adenocarcinoma pulmonary metastasis. Repetitive wedge resections and a right lower lobectomy were performed to remove multiple metastatic lesions. At follow-up assessment, the patient reported localized thoracotomy site pain progressing with time and unresponsive to oral analgesics. Chest computed tomography (CT) revealed a pseudoaneurysm of 4-cm diameter of the right 5th intercostal artery. The patient underwent embolization of the lumen and was discharged from the hospital after 24 h. Successive CT re-assessment checks were unremarkable.


Association between circulating oxidized OxLDL/LDL-C ratio and the severity of coronary atherosclerosis, along with other emerging biomarkers of cardiovascular disease in patients with type 2 diabetes.
The aim of this study was to evaluate the association between circulating oxLDL/LDL-C ratio and the severity of coronary atherosclerosis, along with other emerging biomarkers of cardiovascular disease (CVD) in patients with type 2 diabetes. We recruited 152 patients with type 2 diabetes for our study. ELISA measured the plasma levels of oxLDL and other biomarkers. The severity of coronary lesions was evaluated using Gensini scores, which were calculated based on results of coronary computed tomographic angiography (CCTA). All patients were allocated into four groups according to CCTA findings and Gensini score: normal group (score = 0), mild coronary atherosclerosis group (0 < scores ≤ 3), moderate coronary atherosclerosis group (3.01 ≤ scores ≤ 32.67) and severe coronary atherosclerosis group (32.68 ≤ scores ≤ 180). Association between the oxLDL/LDL-C ratio and the severity of coronary atherosclerosis were evaluated using logistic regression models. Multivariate logistic regression analysis showed that the oxLDL/LDL-C ratio was positively associated with severity of coronary atherosclerosis (OR 2.03, 95% CI 1.31-3.14, p < 0.01). Interleukin 33 (IL33) correlated positively with oxLDL/LDL-C ratio (r = 0.274, p < 0.01). However, vascular cell adhesion molecular-1 (VCAM-1) had similar trends with oxLDL/LDL-C ratio in these 4 groups. OxLDL/LDL-C ratio is considered as a potential biomarker in patients with diabetes for early recognition and intervention of severe coronary atherosclerosis, and will be more effective if tested IL33 and VCAM-1 at the same time.


Isolation and culture of neural progenitor cells from rat postnatal cerebellum.
The mammalian brain contains undifferentiated, mitotically active, and multipotent neural stem/progenitor cells that in vivo contribute new neurons and glia to specific areas of the mature brain. When isolated under the appropriate conditions, these cells maintain in vitro the ability to proliferate and differentiate into cells that express neuronal and glial markers. Neural stem/progenitor cells have been identified and isolated from many regions of the embryonic, postnatal, and adult central nervous system, including cerebellum. This chapter details techniques to isolate and culture neural progenitor cells from rat postnatal cerebellum, which can be used as an in vitro model to study the molecular mechanisms underlying proliferation and differentiation into mature neural cells induced by various stimuli including pharmacological agents.


[Safety of liposomal amphotericin B in patients with high risk of nephrotoxicity].
Amphotericin B is the medication of choice in systemic or invasive fungal infections, but its use often is limited by nephrotoxicity. Lipid formulations of amphotericin B have reduced this risk, but it is not known if these medications also prevent the deterioration of kidney function in patients with previous kidney failure or at risk of kidney failure, such as newborns and patients treated with cyclosporine A. A retrospective analysis was made of epidemiological, clinical and analytic data collected from the clinical histories of patients with previous renal failure or at high risk of nephrotoxicity who were treated with liposomal amphotericin B at our hospital between January 1991 and January 1997. An analysis was made of 23 patients (15 men and 8 women, mean age 38 years) who met established criteria. All had severe immunosuppression. Twelve patients had been treated previously with conventional amphotericin B, but treatment was interrupted for kidney failure. The other 11 patients in the group received cyclosporine A (9 cases) or were at risk of nephrotoxicity because of their underlying disease or situation (2 cases). No deterioration of kidney function due to liposomal amphotericin B was observed in any patient. In 5 of the 12 patients who had deterioration of kidney function as a result of previous use of conventional amphotericin B and lived more than one week after changing treatment, it was observed that kidney function recovered and baseline creatinine levels were reached. Our findings suggest that liposomal amphotericin B can be used safely in immunocompromised patients with fungal infection who have failure or high risk of kidney failure.


Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy.
Autoimmunity to antigens of the central nervous system is usually considered detrimental. T cells specific to a central nervous system self antigen, such as myelin basic protein, can indeed induce experimental autoimmune encephalomyelitis, but such T cells may nevertheless appear in the blood of healthy individuals. We show here that autoimmune T cells specific to myelin basic protein can protect injured central nervous system neurons from secondary degeneration. After a partial crush injury of the optic nerve, rats injected with activated anti-myelin basic protein T cells retained approximately 300% more retinal ganglion cells with functionally intact axons than did rats injected with activated T cells specific for other antigens. Electrophysiological analysis confirmed this finding and suggested that the neuroprotection could result from a transient reduction in energy requirements owing to a transient reduction in nerve activity. These findings indicate that T-cell autoimmunity in the central nervous system, under certain circumstances, can exert a beneficial effect by protecting injured neurons from the spread of damage.


Natural biomarocmolecule-based antimicrobial hydrogel for rapid wound healing: A review.
Antibacterial hydrogels are a type of hydrogel that is designed to inhibit the growth of bacteria and prevent infections. These hydrogels typically contain antibacterial agents that are either integrated into the polymer network or coated onto the surface of the hydrogel. The antibacterial agents in these hydrogels can work through a variety of mechanisms, such as disrupting bacterial cell walls or inhibiting bacterial enzyme activity. Some examples of antibacterial agents that are commonly used in hydrogels include silver nanoparticles, chitosan, and quaternary ammonium compounds. Antibacterial hydrogels have a wide range of applications, including wound dressings, catheters, and medical implants. They can help to prevent infections, reduce inflammation, and promote tissue healing. In addition, they can be designed with specific properties to suit different applications, such as high mechanical strength or controlled release of antibacterial agents over time. Hydrogel wound dressings have come a long way in recent years, and the future looks very promising for these innovative wound care products. Overall, the future of hydrogel wound dressings is very promising, and we can expect to see continued innovation and advancement in this field in the years to come.


Quality measures for palliative care in patients living with cancer in low- and middle-income countries: a scoping review protocol.
Quality assessment is a critical component of determining the value of medical services, including palliative care. The utilisation of palliative care quality measures could assist in assessing the degree to which patients living with cancer conform to best practice of palliative care, identifying gaps and monitoring changes in cancer care delivery models in different setting. This scoping review aims to map the available data on the usage of palliative care quality indicators that are relevant to cancer patients in low- and middle-income countries (LMICs). To structure this study, we will use the framework developed by Arksey and O'Malley, the Levac et al. recommendations and the Joanna Briggs Institute recommendations. We will search EBSCOHost, Web of Science, ProQuest One Academic, MEDLINE and Google Scholar for evidence on palliative care quality measures applicable for patients living with cancer published from inception till 2022. We will search grey literature in the form of dissertations, conference proceedings and websites of international organisations such as the World Health Organisation (WHO) reporting palliative care quality measures applicable to patients living with cancer in LMICs. The purpose of this study is to establish the extent of existing research on the palliative care quality measures in LMICs. Although palliative care is still a new phenomenon, understanding of the palliative care quality measures applicable for cancer patients will assist to improve care across all components of health systems. No ethical approval is required for the study as the data collection and results of the proposed scoping review will be conducted and disseminated electronically using peer-reviewed journals, print and presentations at scientific conferences and stakeholder presentations.


Tumor cells induced by the v-src oncogene are heterogeneous for expression of markers of mesenchyme differentiation.
The observation that v-src-induced tumors contain tumor cells of differing morphology, notably fibroblastoid or polygonal, raised the question as to whether the tumor cells are also heterogeneous with respect to expression of markers of cellular differentiation. Of the markers tested here, consistent reactivity for tumor tissue was noted only for antibody probes reactive to muscle actin (HHF35, alpha sm-1) or to procollagen type I (SP1. D8); for any given tumor, whether induced by v-src DNA or by Rous sarcoma virus, each of these markers was found only in a subpopulation of tumor cells. The observation of marker heterogeneity in the one v-src DNA-induced tumor examined here that typed as monoclonal suggests that v-src-induced transformation is consonant with a degree of plasticity in the phenotypes of the clonal progeny of a single transformant.


Visceral representation within the nucleus of the tractus solitarius in the pigeon, Columba livia.
This study describes the distribution of organ-specific populations of vagal afferent fibers within the nucleus of the solitary tract (nTS) in the pigeon. The central projections of vagal sensory neurons were visualized by the centripetal and trans-ganglionic transport of horseradish peroxidase from either the central cut ends of peripheral vagal branches or from HRP injection sites in peripheral vagal target tissues. This paper also includes a detailed description of the cytoarchitectural organization of the nTS in the pigeon based on studies of Nissl-stained material. Vagal afferent fibers that innervate different peripheral target organs are partially segregated within cytoarchitecturally distinct subnuclei of the nTS. Gastrointestinal afferents, for example, project primarily to medial subnuclei. On the other hand, pulmonary, and on the basis of earlier studies, cardiovascular afferents, project primarily to lateral subnuclei. Moreover, the rostral to caudal distribution of gastrointestinal afferents corresponds to the rostrocaudal topography of the gastrointestinal tract. In addition, our data demonstrate a projection of gastrointestinal afferents to the lateral descending tract of the trigeminal nerve that appears to terminate in the external cuneate nucleus. The cytoarchitectural organization of visceral representations within the pigeon nTS corresponds closely to recent descriptions of this cell group in mammals. Comparison of our results with studies of the central connections of nTS neurons suggests that the subnuclear distribution of organ-specific vagal afferents within nTS plays a critical role in the organization of ascending and descending visceral afferent pathways.


Study on web pillar failure mechanism during auger mining and its associated risk assessment.
To safely and efficiently recover trapped coal under final endwalls in open cut mines, theoretical analysis and numerical calculation were used to study the stability of web pillar during auger mining. The partial ordered set (poset) evaluation model was used to develop a risk assessment methodology, and auger mining at Pingshuo Antaibao open cut coal mine was used as a field example for validation. Based on the catastrophe theory, the failure criterion of web pillar was established. From the limit equilibrium theory, the maximum allowable plastic yield zone width and minimum web pillar width were proposed under various Factor of Safety (FoS) thresholds. This in turn provides a new method for web pillar design. Based on the poset theory and combining with the risk evaluation and proposed hazard levels, input data were standardized and weighted. Subsequently, the comparison matrix, HASSE matrix and HASSE diagram were established. The study shows that: when the width of the plastic zone of web pillar exceeds 88% of the total width, web pillar may be unstable. Based on the calculation formula for the required width of web pillar, the required pillar width was 4.93 m and it was deemed as "mostly stable". This was consistent with the field condition on site. Such that this method was validated.


Cytochromes P-450 in the intestinal mucosa of man.
With monoclonal antibodies against cytochrome P-450(5) and P-450(4,5,6), 52 and 54 kDa bands are visualized in microsomes from proximal as well as distal human small intestine. These bands most probably correspond to cytochrome P-450(5) and P-450(4), respectively. This and several other cytochrome P-450 related proteins are present in hepatic microsomes from the same patient. In both hepatic and intestinal microsomes from this patient cytochrome P-450(8) is hardly detectable. In contrast to the small intestine and liver, large intestinal tissue from several other patients does not contain cytochrome P-450(5). Here the 54 kDa isoenzyme, possibly cytochrome P-450(4), is most prominent. Earlier we found a higher content of total cytochrome P-450 in the proximal as compared to the distal small intestine. A similar distribution is now found with regard to aldrin epoxidase activity.


Bone marrow-derived mesenchymal stem cells alleviate severe acute pancreatitis-induced multiple-organ injury in rats via suppression of autophagy.
Patients with severe acute pancreatitis (SAP) represent a substantial challenge to medical practitioners due to the high associated rates of morbidity and mortality and a lack of satisfactory therapeutic outcomes. In a previous study, our group demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate SAP; however, the mechanisms of action remain to be fully understood. BMSCs were intravenously injected into SAP rats 12 h after experimental induction of SAP using sodium taurocholate (NaT). Histopathological changes and the levels of pro-inflammatory mediators were assessed by hematoxylin and eosin (H&E) staining and ELISA, respectively. Autophagy levels were assessed using qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, and transmission electron microscopy. AR42J cells and human umbilical vein endothelial cells (HUVECs) were administered BMSC-conditioned media (BMSC-CM) after NaT treatment, and cell viability was measured using a Cell Counting Kit-8 (CCK-8) and flow cytometry. In vivo, BMSCs effectively reduced multiple systematic inflammatory responses, suppressed the activation of autophagy, and improved intestinal dysfunction. In vitro, BMSC-CM significantly improved the viability of injured cells, promoted angiogenesis, and decreased autophagy. We therefore propose that the administration of BMSCs alleviates SAP-induced multiple organ injury by inhibiting autophagy.


Hypohydration adversely affects lactate threshold in endurance athletes.
The purpose of this investigation was to observe the effect of hypohydration (-4% body mass) on lactate threshold (LAT) in 14 collegiate athletes (8 men and 6 women; age, 20.9 +/- 0.5 years; height, 171.1 +/- 2.4 cm; weight, 64.8 +/- 2.3 kg; V(O)2 max, 62.8 +/- 1.9 ml x kg(-1) x min(-1); percentage of fat, 11.4 +/- 1.5%). Subjects performed 2 randomized, discontinuous treadmill bouts at a dry bulb temperature (T(db)) of 22 degrees C to volitional exhaustion in 2 states of hydration, euhydrated and hypohydrated. The hypohydrated condition was achieved in a thermally neutral environment (T(db), 22 degrees C; humidity, 45%), with exercise conducted at a moderate intensity as defined by rating of perceived exertion (RPE, approximately 12) 12-16 hours before testing. On average, subjects decreased 3.9% of their body mass before the hypohydration test. Blood lactate, hematocrit, V(O)2, minute ventilation (VE), R value, heart rate (HR), and RPE were measured during each 4-minute stage of testing. In the hypohydrated condition, LAT occurred significantly earlier during exercise and at a lower absolute V(O)2, VE, respiratory exchange ratio, RPE, and blood lactate concentration. Also, the blood lactate concentration was significantly lower in the hypohydrated condition (6.7 +/- 0.8 mmol) compared with the euhydrated condition (10.2 +/- 0.9 mmol) at peak exercise. There were no differences in HR or percentage of maximum HR at LAT nor did plots of V(CO2):V(O)2 reveal differences in bicarbonate buffering during exercise between the 2 conditions. From these results, we speculate that hypohydration did not significantly alter cardiovascular function or buffering capacity but did cause LAT to occur at a lower absolute exercise intensity.


Memory of social defeat is facilitated by cAMP response element-binding protein overexpression in the amygdala.
The cAMP-responsive element binding protein (CREB) is a transcription factor that regulates synaptic plasticity and memory formation. Studies that have used conditioned fear models have established that CREB is important for the acquisition and consolidation of fear learning. The authors demonstrate that overexpression of CREB within the basolateral amygdala (BLA) of animals that are exposed to social defeat enhances subsequent defeat-induced changes in social behavior. This effect is specific to the acquisition of defeat-induced behaviors; overexpression of CREB has no effect on the expression of these behaviors if the overexpression occurs after the initial defeat. These data demonstrate that CREB is important for regulating learning not only to explicit cues but also for mediating behavioral plasticity in ethologically relevant social contexts.


Measurement of intracellular Ca2+ mobilization to study GPCR signal transduction.
Understanding G protein-coupled receptor (GPCR) structure-function relationship and its activation mechanism has been broadly explored using mutational strategy due to problems in GPCR crystallization. Probing into GPCR: effector (G protein/β-arrestin) interactions and downstream signaling are important aspects of GPCR research. Among the G proteins, though there are some approaches to investigate Gq-mediated signaling, they involve the use of radioactivity and are qualitative in nature. Our method described here makes use of the cell permeable nature of fluorescent Ca2+ indicator dye, fura2AM, that binds with the Ca2+ released in response to GPCR: Gq interaction on ligand treatment. Using this spectrophotometric method, EC50 values of the GPCR: ligand binding can be calculated and the binding affinity can be analyzed.


Synthesis, spectroscopic, thermal and DFT calculations of 2-(3-amino-2-hydrazono-4-oxothiazolidin-5-yl) acetic acid binuclear metal complexes.
The binuclear complexes of 2-(3-amino-2-hydrazono-4-oxothiazolidin-5-yl) acetic acid ligand (HL) with Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) ions were prepared and their stoichiometry was determined by elemental analysis. The stereochemistry of the studied series of metal complexes was established by analyzing their infrared, (1)H NMR spectra and the magnetic moment measurements. According to the elemental analysis data, the complexes were found to have the formulae [Fe2L(H2O)8]Cl5 and [M2L(H2O)8]Cl3 (M=Co(II), Ni(II), Cu(II) and Zn(II)). The present analyses demonstrate that all metal ions coordinated to the ligand via O(9), O(11), N(16) and N(18) atoms. Thermal decomposition studies of the ligand-metal complexes have been performed to verify the status of water molecules present in these metal complexes and their general decomposition pattern. Density Functional Theory (DFT) calculations at the B3LYP/6-31G(*) level of theory have been carried out to investigate the equilibrium geometry of the ligand and complexes. Moreover, charge density distribution, extent of distortion from regular geometry, dipole moment and orientation have been performed and discussed.


Down-regulation of cardiac bradykinin B2 receptors and eNOs mRNA in rats with remnant kidneys.
The changes in the expression of cardiac bradykinin B2 receptors (BKB2Rs) and endogenous nitrix oxide synthase (eNOs) mRNA were studied in rats with remnant kidneys. Thirty-two rats were divided into sham-operated and experimental groups randomly (n = 16 in each group). The remnant kidney model was established by 2-stage 5/6 nephrectomy. Blood pressure and serum Cr were measured before operation and 15, 30, 60, 120 days after 5/6 nephrectomy. Eight animals in each group were killed at the first month and 4th month after the operation. The expression of BKB2Rs and eNOs mRNAs was detected by using RT-real time PCR from isolated left ventricle, and their correlation was also analyzed. The results showed that blood pressure and serum Cr were increased significantly 15 days after 5/6 nephrectomy (both P<0.01), and the hypertension and azomia existed constantly till 120 days but had no significant fluctuation. Cardiac BKB2Rs and eNOs mRNA was declined time-dependently (both P<0.05). And there was a close positive correlation between cardiac BKB2Rs and eNOs mRNA (r= 0.82, P< 0.01). It was suggested that a significant chronic renal failure can be produced at least 15 days after 5/6 nephrotomy and can sustain more than 4 months. The expression of BKB2Rs and eNOs was down-regulated time-dependently in this model, and there was a significant correlation between them.


Emergency cervical cerclage using a metreurynter in patients with bulging membranes.
Emergency cervical cerclage was performed in 26 women between 18 and 32 weeks of gestation who had fetal membranes bulging through a widely dilated cervix. A bulging bag was pushed into the uterine cavity by a new method, using a metreurynter. The average prolongation of pregnancy after the operation in the 26 women was 41 days (ranging from 2 to 115 days). All pregnancies resulted in the live birth of altogether 28 babies. The neonatal survival rates at gestational ages of less than or equal to 26 (including two sets of twins), 27-29, and greater than or equal to 30 weeks at the time of cervical cerclage were 80.0 (12/15), 85.7 (6/7), and 100% (6/6), respectively. Ten (83.3%) of the 12 infants who survived from patients receiving cerclage at a gestational age of less than or equal to 26 weeks are alive and well. The average duration of pregnancy after cerclage was 60 days when cervical dilation was less than or equal to 5 cm at operation, in contrast to 5.4 days in patients with cervical dilation of greater than or equal to 6 cm, suggesting that emergency cervical cerclage could be suitable in the presence of a cervical dilation of 5 cm or less.


High-level gene transfer to the cornea using electroporation.
Methods for gene transfer to the cornea that yield high-level expression without inflammation or trauma are currently lacking. Because electroporation has proven effective for gene transfer in other tissues in terms of expression levels and safety, this study quantitatively evaluated its use in the cornea. To evaluate the use of electroporation in the mouse cornea, plasmids expressing either luciferase or green fluorescent protein were injected intracorneally or subconjunctivally and square-wave electric pulses were immediately applied to the eyes. Gene expression was quantified at later times and trauma and inflammation were monitored visually and by measuring interleukin-6 (IL-6) production. The application of electric pulses to eyes injected with plasmid resulted in nanogram levels of gene product expression. At an optimal field strength of 200 V/cm, no trauma, corneal edema or inflammation was observed. However, at higher field strengths, corneal damage was detected. Compared with injection of DNA alone, up to 1000-fold more gene product was produced using electroporation. Expression was detected as early as 6 h post-electroporation, remained high for 3 days, and decreased by 7 days. Gene expression was detected over the entire surface of the cornea in both epithelial and stromal layers. These results demonstrate that electroporation is an excellent method for delivering genes to multiple cell layers within the mouse cornea and that it results in extremely high levels of gene expression with little, if any, inflammatory response or tissue damage, making this a very useful technique for corneal gene transfer.


The Tinel sign has no diagnostic value for nerve entrapment or neuropathy in the legs.
The presence of a Tinel sign in leg nerves has been proposed as a criterion for decompressive surgery in polyneuropathy. We investigated the diagnostic yield of the Tinel sign for nerve entrapment and for distal symmetrical peripheral neuropathy (DSPN). We prospectively tested for the Tinel sign at 3 sites of possible nerve entrapment per leg in 91 patients. Entrapment was defined using nerve conduction data. We also investigated whether the number of sites at which the Tinel sign was present identified patients with DSPN. Sensitivity of the Tinel sign for nerve entrapment was low (29%, 44%, and 17%) for the 3 sites, and specificity was moderate (86%, 75%, and 81%). In the subgroup with DSPN, sensitivity was extremely low (0%, 20%, and 8%), and specificity was moderate (91%, 79%, and 73%). The number of sites with a Tinel sign did not identify patients with DSPN. The Tinel sign does not reliably indicate nerve entrapment or DSPN. Muscle Nerve 54: 25-30, 2016.


Autoimmune pancreatitis and inflammatory bowel disease: Case series and review of the literature.
An association between autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) has been documented, but its clinical significance remains unclear. Characterize the particular phenotypes of IBD and AIP in patients with both diseases (IBD-AIP). Retrospective study of patients with IBD-AIP followed at our IBD referral centre and literature search to identify previous reports of IBD-AIP patients. We found 5 cases of IBD-AIP in our records and 5 prior studies reporting 47 additional IBD-AIP patients. A combined analysis showed that most IBD-AIP patients were young males with ulcerative colitis, usually extensive, and that in all Crohn's disease cases, the colon was involved. IBD severity was heterogeneous across studies, ranging from mild disease to severe disease requiring colectomy. The most frequent type of AIP was idiopathic duct-centric pancreatitis (type 2) and it most often occurred after the diagnosis of IBD. AIP presentation and treatment were similar to those in the general population. AIP occurs rarely with IBD; in the other way around, up to 1/3 of AIP patients, especially type 2, may have concomitant IBD. IBD-AIP patients are usually males presenting extensive colitis. More data are needed on the impact of AIP, if any, in IBD course.


Desaturation of eicosa-11,14-dienoic acid in human testes.
The metabolism of [1-14C]eicosa-11,14-dienoic acid was investigated in human testes using whole tissue minces and microsomal preparations. Both types of preparations catalyzed the desaturation of the labeled diene to eicosa-8,11,14-trienoic as well as eicosa-5,11,14-trienoic acid. The reported results, therefore, indicate that human testicular tissue, as well as rat testicular tissue (reported previously), is capable of utilizing eicosa-11,14-dienoic acid as a precursor of arachidonic acid. Since it is known that there is no delta 8 desaturase activity in rat liver and brain, these studies support the concept that there is a tissue variation in this enzymatic pathway.


Different epidermal growth factor growth responses and receptor levels in human colon carcinoma cell lines.
The growth response to epidermal growth factor (EGF) and the numbers and types of EGF receptors were studied in three human colon tumor cell lines from each of two groups of cell lines that differ markedly in their growth properties and extent of differentiation. Aggressively growing and poorly differentiated colon cells (group I) did not respond to EGF alone, while less aggressively growing and more differentiated cells (group III) responded with increased growth when EGF was added to their chemically defined, serum-free medium. The average number of EGF receptors (EGF-R) measured at the surface of group III cell lines by radioligand binding assays, was eight-fold higher than that measured for group I cell lines. These observations provide evidence for possible autocrine mechanisms that maintain available EGF-R levels in more differentiated group III colon tumor cells and down-regulate EGF-R levels in group I colon tumor cells.


Too hot! Preventing, recognizing and managing heat injury in children.
Climate change-related extreme heat events leading to public health emergencies are increasing in Canada and expected to affect more regions, more frequently and for longer time periods. Children, city dwellers and marginalized populations are amongst the most vulnerable to morbidity and mortality related to extreme heat. Paediatricians can provide caregivers and families with advice to minimize risks as well as advocate for safer city planning and harm mitigation strategies.


Sensitive LC MS quantitative analysis of carbohydrates by Cs+ attachment.
The development of a sensitive assay for the quantitative analysis of carbohydrates from human plasma using LC/MS/MS is described in this paper. After sample preparation, carbohydrates were cationized by Cs(+) after their separation by normal phase liquid chromatography on an amino based column. Cesium is capable of forming a quasi-molecular ion [M + Cs](+) with neutral carbohydrate molecules in the positive ion mode of electrospray ionization mass spectrometry. The mass spectrometer was operated in multiple reaction monitoring mode, and transitions [M + 133] --> 133 were monitored (M, carbohydrate molecular weight). The new method is robust, highly sensitive, rapid, and does not require postcolumn addition or derivatization. It is useful in clinical research for measurement of carbohydrate molecules by isotope dilution assay.


Odor-taste pairings lead to the acquisition of negative hedonic qualities by the odor in aversion learning.
Three experiments examined the affective responses conditioned to an odorous stimulus in the taste-mediated odor aversion learning paradigm. Experiment 1 analyzed the microstructure of licking behavior during voluntary consumption. Before conditioning, water-deprived rats had access to a bottle containing either a tasteless odor (0.01% amyl acetate) diluted in water or mixed with 0.05% saccharin. Next, the rats were injected with either LiCl or saline immediately after drinking saccharin. At test, they received the odor and taste solutions on separate days. Lick cluster size was used as a direct measure of the hedonic response to the odor cue. Rats receiving odor-taste pairings prior to the saccharin devaluation showed both lower consumption and lick cluster size, reflecting a reduced hedonic evaluation of the odor. Experiments 2a and 2b used the orofacial reactivity method. After pretraining in the drinking boxes with the odor alone or mixed with saccharin, the rats were intraorally infused with saccharin before injection with LiCl or saline. At test, they were infused in separate sessions with the odor and taste and their orofacial reactions video recorded. There were increased aversive orofacial responses to the odor in rats that had prior odor-taste experience, a result indicating a negative hedonic evaluation of the odor. These results provide evidence of conditioned changes in affective value of odor cues through taste-mediated learning and are consistent with the idea that odor-taste pairings lead to the acquisition of taste qualities by the odor.


The microbial diversity, distribution, and ecology of permafrost in China: a review.
Permafrost in China mainly located in high-altitude areas. It represents a unique and suitable ecological niche that can be colonized by abundant microbes. Permafrost microbial community varies across geographically separated locations in China, and some lineages are novel and possible endemic. Besides, Chinese permafrost is a reservoir of functional microbial groups involved in key biogeochemical cycling processes. In future, more work is necessary to determine if these phylogenetic groups detected by DNA-based methods are part of the viable microbial community, and their functional roles and how they potentially respond to climate change. This review summaries recent studies describing microbial biodiversity found in permafrost and associated environments in China, and provides a framework for better understanding the microbial ecology of permafrost.


Adverse effects associated with extra doses of bupropion.
To determine the frequency of adverse effects, clinical outcomes, and possible dose-response relationships associated with inadvertent extra doses of bupropion. Retrospective review. Toxic Exposure Surveillance System of the American Association of Poison Control Centers. Four hundred seventy-six patients who inadvertently took extra doses of bupropion. Cases in the surveillance database were evaluated based on documented doses, treatment sites, symptoms, and clinical outcomes by using standard data-field definitions. Over a 4-year period from 2000-2003, more women than men unintentionally took extra doses of bupropion (354 [74.4%] vs 122 [25.6%]). Ingested doses ranged from 75-1500 mg with a median and mode of 300 mg. Of the 476 patients, only 127 (26.7%) had to be evaluated in an emergency department. Seizures were reported in four patients (0.8%), and one developed status epilepticus. Other prominent adverse effects were agitation (39 patients [8.2%]), dizziness (35 [7.4%]), tremor (34 [7.1%]), nausea and/or vomiting (32 [6.7%]), drowsiness (29 [6.1%]), tachycardia (26 [5.5%]), and hallucination (2 [0.4%]). Clinical outcomes were no effect (293 patients [61.6%]), minor effect (132 [27.7%]), moderate effect (49 [10.3%]), or major effect (2 [0.4%]). Overall, 183 patients (38.4%) had at least one adverse effect. Doses were higher in patients with adverse effects than in those with no effect (p = 0.045). Doses were slightly higher in those with moderate or major outcomes than in others, but the difference was not significant (p = 0.083). Adverse effects were common with extra doses of bupropion, and clinically significant effects occurred in approximately 10% of patients. Seizures were present twice as often as reported with therapeutic dosing. Extra doses of bupropion appear to increase the risk of adverse effects. Patients should be educated about these risks to minimize them.


Time course of changes in baroreceptor reflex control of heart rate in conscious SHR and WKY: contribution of the cardiac vagus and sympathetic nerves.
1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine- and nitroprusside-induced steady-state changes in blood pressure. 2. MAP increased with age in both strains but was 17-23% higher in SHR. 3. By contrast baroreflex parameters (HR range: difference between upper and lower HR plateaus, and gain: average slope between inflection points of the logistic MAP-HR relationship) decreased with age in SHR but increased in WKY. 4. After methylatropine, no differences in the cardiac sympathetic baroreflex range or gain parameters were observed between strains or ages. 5. It was concluded that older SHR have normal sympathetic but reduced vagal capacity to control HR in response to changes in MAP, but that this deficit was not dependent on the absolute level of blood pressure. 6. Because the differences were confined to one effector, SHR may have different central rather than arterial baroreceptor afferent mechanisms.


Comprehensive analysis of hub biomarkers associated with immune and oxidative stress in Hashimoto's thyroiditis.
Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.


Functional properties of the anaerobic responsive element of the maize Adh1 gene.
The functional properties of the anaerobic responsive element (ARE) of the maize Adh1 gene have been analysed using a transient expression assay in electroporated maize protoplasts. The ARE functions in both orientations although inversion of the ARE sequence relative to the TATA box element produces slightly weaker promoter activity under anaerobic conditions and elevated expression under aerobic conditions. Promoter activity under anaerobic conditions is proportional to the number of complete ARE sequences in the Adh1 promoter. The ARE contains two sub-regions and dimers of sub-region II are as efficient as the wild-type sequence in activating gene expression under anaerobic conditions. However, sub-region I dimers do not appear capable of inducing gene expression in response to anaerobic stress. We conclude that sub-region II is essential for anaerobic induction of gene expression. Reporter gene expression remains constant when the spacing between sub-regions of the ARE is increased up to at least 64 bp, but increased spacing of 136 bp or greater abolishes expression in both aerobic and anaerobic conditions, indicating that a close association of the two sub-regions is required both for anaerobic responsiveness and for maximal levels of aerobic gene expression. When the ARE is placed upstream of position -90 of the CaMV 35S promoter, the ARE produces a high level of expression in both aerobic and anaerobic conditions. The general enhancement of gene expression driven by the hybrid ARE/35S promoter in aerobic conditions requires an intact sub-region II motif since mutation or deletion of sub-region II from the hybrid promoter reduces the level of expression to that observed for the truncated 35S promoter alone. In addition, mutation of the sub-region I sequences in the ARE/35S hybrid promoter does not significantly reduce expression in aerobic conditions, relative to pARE/delta 35S(-90), suggesting that sub-region I does not contribute to this general enhancer function.


Neurodevelopmental outcome and electronic fetal heart rate monitoring in a neonatal intensive care population.
In a one-year population, 1977, of newborn infants admitted to the Neonatal Intensive Care Unit (NICU) the incidence of persistent neurodevelopmental handicaps was 3%, i.e. 13 of 427 survivors at 2 years of age. Transient abnormalities during the first 6 months of life were found in 63 infants, but after 6 months of age they were all normal at follow-up examinations. Most mothers with infants showing transient abnormalities or persistent handicaps had a high-risk pregnancy but one-third (35.5%) had a low-risk pregnancy and in this group 4 out of 7 cases with persistent major neurodevelopmental handicaps were found. In the total one-year population, 6% showed ominous fetal heart rate patterns (FHR) in labor compared with 31% of infants with later abnormalities and handicaps. Furthermore, all 13 infants with persistent handicaps had a normal Apgar score at 5 min, indicating that Apgar scoring was less predictive than FHR for neurodevelopmental outcome. Altogether 54 infants born in 1977 were small for gestational age (SGA): 33 NICU-treated and 21 not NICU-treated. Seven (6 NICU-treated, 1 not NICU-treated) had transient abnormalities (12.9%). No SGA infant developed persistent handicaps. The results suggest an improved obstetric and neonatal care of these infants.


Ashwagandha (Withania somnifera) supercritical CO2 extract derived withanolides mitigates Bisphenol A induced mitochondrial toxicity in HepG2 cells.
Bisphenol A (BPA) safety aspects on human health are debated extensively for long time. In the present study, we have studied the toxicity induced by BPA at no observed adverse effect level (NOAEL) using HepG2 cells. We report that BPA at 100 nM induced cytotoxicity to HepG2 cells as determined by MTT assay at 0-72 h. The toxicity was result of reduced oxygen consumption and reduced mitochondrial membrane potential associated with decreased ATP production. The BPA treatment resulted in increase of malondialdehyde (MDA) content with decreased glutathione and other antioxidant enzymes. BPA derived toxicity is a concern to human health and alternative non-toxic natural products/derivatives or adjuvants that serve as antidote will be relevant. In this context, Ashwagandha (Withania somnifera) a widely used herb to treat arthritis, rheumatism and to improve longevity for time immemorial is investigated for its antidote effect. Ashwagandha supercritical CO2 extract derived Withanolides (ADW) at 100 μg/ml protect HepG2 cells from BPA induced toxicity by suppressing mitochondrial damage and increased ATP production. Further, cellular MDA content was significantly suppressed with increased non-enzymic and antioxidant enzyme activities. These findings derived from the present study suggest the beneficial effect of ADW in mitigating BPA induced mitochondrial toxicity in HepG2 cells.


Following a Surgical Paradigm Shift Through the Adoption of Nerve Transfers Among Board-Eligible and Practicing Plastic Surgeons.
Nerve transfers represent a new paradigm in the treatment of nerve injuries. Their current level of adoption among surgeons is unknown. This study evaluates the incidence of nerve transfers on case logs of board-eligible plastic surgeons over the past 14 years and surveys practicing nerve surgeons regarding their use of this technique. We queried the American Board of Plastic Surgery case log database for all nerve reconstruction Current Procedural Terminology codes from 2008 to 2021 and assessed trends and relationships between geographic region, examination year, and nerve transfer use. We surveyed nerve surgery professional societies to assess trends in practice, compared with a 2017 survey. A total of 1959 nerve reconstruction cases were logged by 738 candidates from 2008 to 2021. Twelve percent of cases included nerve transfers. The proportion of nerve transfer codes (Z = -11.57; P < .0001) and the proportion of candidates performing nerve transfers (Z = -9.21, P < .0001) increased over the study period. Nerve transfers were associated with geographic region (χ2 = 25.826, P = .0002), with most cases performed in the Midwest (26.4%). A higher proportion of practicing nerve surgeons reported performing nerve transfers in this survey than in our 2017 survey (χ2 = 16.7, P < .001). There has been an increase in nerve transfers logged in the past 14 years by board-eligible plastic surgeons, as well as increased use among currently practicing nerve surgeons. Although nerve transfer use is increasing among both plastic and orthopedic surgeons, a greater proportion of nerve reconstructions include nerve transfers in the plastic surgery cohort.


Waveform analysis of differential graphs of reconstructed impedance cardiography from healthy individuals.
The aim is to measure and analyze the wave amplitudes and time intervals of differential graphs of reconstructed impedance cardiography (RICG). 180 adults with normal cardiac function between the ages of 18-78 were included in the study. Six mingled impedance changes on chest surface were simultaneously detected for each subject. The differential graphs of five impedance change components of RICG were obtained through waveform separation and software differentiation. The amplitudes of C, X, O, b waves and time intervals of Q-b and Q-C were measured and statistically analyzed. The amplitudes of C and X waves in PL, PR, AO, and that of C, O, b waves in LV and RV, all decrease as age increases. Wave amplitudes of the female group were bigger than those of the male group (p < .01), while the Q-C intervals of the female group were shorter than that of the male group (p < .01). Among five impedance change components, the wave amplitude of AO was larger than those of PL and PR (p < .01), and wave amplitudes of PL and PR were bigger than those of LV and RV (p < .01). Q-C intervals of LV and RV were longer than those of AO, PL and PR (p < .01), while the Q-b intervals of LV and RV were shorter than the Q-C intervals of AO, PL, and PR. The differential graphs of RICG could reflect indirectly the physiological activities and pathological changes of the heart and of the large blood vessels in thorax.


Mini Pig Nutrition and Weight Management.
Mini pigs are engaging, intelligent animals that require different management than other pet species. Published nutrient requirements for production pigs are a good reference, but they must be critically evaluated in the context of pet mini pigs' needs to prioritize longevity and healthy weight. A balanced diet includes a pelleted feed, vegetables, and roughage, with minimal fruit or other treats. Mini pigs easily gain weight, and a balanced, high-fiber diet helps maintain healthy body condition to reduce the risk of metabolic and joint diseases.


Somatic cell genetic analysis of HLA-A, B, C and human beta 2-microglobulin expression.
We have examined the cell surface expression of the human histocompatibility antigens HLA-A, B, C and beta 2-microglobulin (beta 2m) on a human-mouse somatic cell hybrid line. Using specific antibodies and the fluorescence-activated cell sorter (FACS), we viably fractionated and characterized four separate hybrid subpopulations (HLA+,beta 2m+; HLA+,beta 2m-; HLA-,beta 2m+; HLA-,beta 2m-). Hybrid selection based on surface antigen expression resulted in corresponding genetic selection for and against human chromosomes 6 and 15. Studies of the homogeneous hybrid sublines revealed that the presence of human beta 2m in a hybrid cell dramatically increased the surface expression of human HLA-A, B, C and mouse H-2Kk antigens. The results demonstrate the importance of human chromosome-specific surface markers and the fluorescence-activated cell sorter in somatic cell genetic analysis.


Measuring autonomy support in special needs teachers from a self-determination theory perspective: validation of the Italian version of the learning climate questionnaire.
Self-determination construct is a motivation theory used in professional and educational context to foster special needs teachers' development of metacognition, and psychological wellbeing. The Learning Climate Questionnaire (LCQ) is a validate questionnaire used to underly teachers' professional and personal competence, and improving social, emotional and career outcomes. The present paper aims to evaluate the degree of reliability (R1) and the adherence of construct validity to the construct of self-determination (R2) of the Italian adaptation of the LCQ. A confirmatory factorial analysis was conducted to evaluate the factorial structure of the LCQ in a sample of Italian special needs teachers (N = 953). Teachers was asked to complete an online version of the LCQ. Construct validity was conducted by relating the learning climate with the basic psychological needs satisfaction, measured with PBNSF, and with academic motivation scale, measured with AMS. The analysis showed a good reliability (R1) and construct validity of the Italian adaptation of the questionnaire, with a high internal consistency compared to those obtained in other studies (R2). Teachers' autonomy support and teacher-student relation can positively impact the students' psychological factors and enhance students' learning motivation and academic achievement. Findings reveal that higher levels of learning climate could also be a key factor in reducing teachers' negative stress and mental health consequences. This study may facilitate further research about the autonomy-supportive learning climate in educational settings in Italy.


The emerging spectrum of allelic variation in schizophrenia: current evidence and strategies for the identification and functional characterization of common and rare variants.
After decades of halting progress, recent large genome-wide association studies (GWAS) are finally shining light on the genetic architecture of schizophrenia. The picture emerging is one of sobering complexity, involving large numbers of risk alleles across the entire allelic spectrum. The aims of this article are to summarize the key genetic findings to date and to compare and contrast methods for identifying additional risk alleles, including GWAS, targeted genotyping and sequencing. A further aim is to consider the challenges and opportunities involved in determining the functional basis of genetic associations, for instance using functional genomics, cellular models, animal models and imaging genetics. We conclude that diverse approaches will be required to identify and functionally characterize the full spectrum of risk variants for schizophrenia. These efforts should adhere to the stringent standards of statistical association developed for GWAS and are likely to entail very large sample sizes. Nonetheless, now more than any previous time, there are reasons for optimism and the ultimate goal of personalized interventions and therapeutics, although still distant, no longer seems unattainable.


A new strong inhibitor of beta-mannosidase.
N-phenyl-carbamate of D-mannonohydroxymolactone (I) was synthesized from mannose and was shown to be the best competitive inhibitor of beta-mannosidase so far reported (Ki = 25 nM).


[The progesterone releasing I.U.D. Its indications in function of the menstrual disorders (author's transl)].
Progesterone releasing I.U.D. improves dysmenorrhea and hypermenorrhea. This type of I.U.D. may be used whereas other I.U.D. are contra indicated. But over all it is a new kind of drug delivery system which could be used with other medications, for other purposes than contraception.


Therapy of symptomatic pyelonephritis in women.
A prospective randomized controlled study was performed on 44 women with community-acquired, uncomplicated pyelonephritis requiring hospitalization. The study was designed to determine if an extended course of therapy (21 days) would be more effective than the conventional 10-day course of therapy. All patients initially received either gentamicin or tobramycin parenterally for 48 to 72 hours, and then were prescribed an oral agent that possessed in vitro inhibitory activity for the urinary pathogen to complete the course of therapy. Duration of medication was assigned according to a table of random digits. Of the 22 women receiving the 10-day treatment 17 were cured, 4 experienced a reinfection and none had a relapse, compared to 12, 5 and 3, respectively, of 22 receiving the 21-day treatment. Analysis of the therapeutic failures did not demonstrate any superior response for either treatment program (p less than 0.75 and greater than 0.50). No statistically increased incidence of adverse drug reactions occurred in patients receiving the extended course of therapy. Our data do not support an extended course of therapy in women with acute symptomatic pyelonephritis uncomplicated by structural abnormalities.


Cytokine modulation of human blood viscosity from vivax malaria patients.
Malaria is a major infectious disease in several countries and is caused by protozoa of the genus Plasmodium. In vivax malaria patients, inflammatory processes occur, as well as changes in cytokines and blood flow. The present study analyzed the cytokine modulation of blood viscosity from patients infected with Plasmodium vivax (P. vivax). Blood samples were collected from 42 non-infected individuals (control group) and 37 individuals infected with P. vivax. The IL-2, IL-4, IL-6, IL-10, TNFα, TGF-β and IL-17 cytokine concentrations in the serum were assessed, and the blood rheological properties were determined. The analysis of blood viscosity for shear rates revealed that the blood viscosity of the infected patients was significantly greater than that of the non-infected individuals. The viscosity of the blood was greater in the infected individuals than in the non-infected subjects. The serum from individuals with P. vivax infections exhibited higher IFN-γ and IL-17 concentrations and lower TGF-β levels. Incubation of the blood from infected individuals with IL-17 or IL-17 associated with IFN-γ reduced the viscosity to rates equivalent to the blood from non-infected individuals. Independently of cytokine modulation, no correlation was found between the parasitemia and blood viscosity of the infected patients. These data suggest that the alterations of blood viscosity are relevant as an auxiliary tool for the clinical diagnosis of disease. In malaria, erythrocytes are more sensitive to osmotic shock, and the reduction of viscosity by IL-17 may be related to a possible immunomodulator agent during infection.


A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis.
CD40/CD40 ligand (CD40L) signaling is a potent activator of endothelial cells (ECs) and promoter of atherosclerosis. In this study, we investigate whether A20 (a gene we have shown to be antiinflammatory and antiapoptotic in ECs) can protect from CD40/CD40L-mediated EC activation. Overexpression of CD40, in a transient transfection system, activates the transcription factor NF-kappaB and upregulates IkappaBalpha, E-selectin, and tissue factor (TF) reporter activity. Coexpression of A20 inhibits NF-kappaB and upregulation of IkappaBalpha and E-Selectin but not TF, suggesting that CD40 induces TF in a non-NF-kappaB-dependent manner. In human coronary artery ECs (HCAECs), adenovirus-mediated overexpression of A20 blocks physiological, CD40-induced activation of NF-kappaB, upstream of IkappaBalpha degradation (Western blot) and subsequently upregulation of ICAM-1, VCAM-1, and E-selectin (flow cytometry). Although A20 does not block TF transcription its expression in HCAECs inhibits TF induction (colorimetric assay and RT-PCR) by blunting CD40 upregulation. We demonstrate that CD40 signaling induces apoptosis in a proinflammatory microenvironment. A20 overexpression protects from CD40-mediated EC apoptosis (DNA content analysis and trypan blue exclusion). We also demonstrate that signaling through CD40L activates NF-kappaB and induces apoptosis in ECs, both of which are inhibited by A20 overexpression. A20 works at multiple levels to protect ECs from CD40/CD40L mediated activation and apoptosis. A20-based therapy could be beneficial for the treatment of vascular diseases such as atherosclerosis and transplant-associated vasculopathy.


Association of the hOGG1 Ser326Cys polymorphism with gynecologic cancer susceptibility: a meta-analysis.
The association between the hOGG1 Ser326Cys polymorphism and gynecologic cancer susceptibility is inconclusive. We performed a comprehensive meta-analysis to precisely estimate of the impact of the hOGG1 Ser326Cys polymorphism on gynecologic cancer susceptibility. Electronic databases including PubMed, Embase, WanFang, and the China National Knowledge Infrastructure were searched for relevant studies. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were determined to assess the strength of the association. Fourteen studies with 2712 cases and 3638 controls were included in the final meta-analysis. The pooled analysis yielded a significant association between the hOGG1 Ser326Cys polymorphism and overall gynecologic cancer susceptibility (dominant model: OR = 1.16, 95% CI = 1.03-1.30, P=0.017). A significantly higher gynecologic cancer risk was found for the European population (homozygous model: OR = 2.17, 95% CI = 1.80-2.61, P<0.001; recessive model: OR = 2.11, 95% CI = 1.41-3.17, P<0.001; dominant model: OR = 1.29, 95% CI = 1.12-1.48, P<0.001; and allele model: OR = 1.40, 95% CI = 1.13-1.74, P=0.002), but not in the Asian population. The stratified analysis by cancer type revealed endometrial cancer was significantly associated with the hOGG1 Ser326Cys polymorphism (dominant model: OR = 1.29, 95% CI = 1.09-1.54, P=0.003; and allele model: OR = 1.28, 95% CI = 1.02-1.60, P=0.031). In conclusion, the hOGG1 Ser326Cys polymorphism was associated with higher overall gynecologic cancer susceptibility, especially for endometrial cancer in the European population.


Impact of adjusted kidney volume measured in the bench surgery on one-year renal function in kidney transplantation.
Kidney transplantation is the treatment of choice in patient with end stage chronic kidney disease, offering the best long term survival and greater Quality of Life in this group of patients. Graft volume was correlated with improved renal function in living donor transplantations. The primary aim of this study was to correlate renal volume adjusted to body surface area with renal function one year (estimated glomerular filtration rate; eGFR) after kidney transplantation. This single-center, prospective cohort study included 256 patients who underwent kidney transplantation from January 2011 through December 2015 at Hospital das Clínicas de Botucatu-UNESP. We evaluated three kidney measurements during the bench surgery; the final graft volume was calculated using the ellipsoid formula and adjusted to body surface area. In the living donors there was positive correlation between adjusted graft volume and eGFR (r = 0.311, p = 0.008). Multivariate analysis revealed that low rejection rate and increased adjusted graft volume were independent factors correlated with eGFR. In deceased donors, there was no correlation between adjusted kidney volume and eGFR (r = 0.08, p = 0.279) in univariate analysis, but a multivariate analysis indicated that lower kidney donor profile index (KDPI), absence of rejection and high adjusted kidney volume were independent factors for better eGFR. Adjusted kidney volume was positively correlated with a satisfactory eGFR at one year after living donor and deceased donor transplantations.


CDA deficiency as a possible culprit for life-threatening toxicities after cytarabine plus 6-mercaptopurine therapy: pharmacogenetic investigations.
We describe here the case of a 7-year old girl with lymphoma who developed life-threatening toxicities upon cytarabine plus mercaptopurine. Surprisingly, initial investigations on canonical thiopurine methyltransferase genetic polymorphism proved to be negative. We focused next on deregulations affecting the CDA gene implicated in the liver disposition of cytarabine. This patient was homozygous for both the 79A>C and the -31delC polymorphisms on the CDA gene and promoter, two genotypes with reported opposite effects on CDA phenotype. To determine the CDA status of this patient, additional functional testing was performed and eventually demonstrated that this patient was a poor metabolizer. This case demonstrates that besides affecting thiopurine methyltransferase, dysregulations with CDA should be screened to anticipate toxicities with the cytarabine plus mercaptopurine combination.


F-18 fluorodeoxyglucose uptake in lymph nodes and sonographic features on endobronchial ultrasonography predict lymph node metastasis in lung cancer patients.
Sonographic findings of lymph nodes on endobronchial ultrasonography (EBUS) images have been reported to be useful to predict lymph node metastasis (LNM) in lung cancer patients. F-18 fluorodeoxyglucose (FDG) uptake in lymph nodes was also found to be useful. In this study, we aimed to clarify whether a combination of sonographic features and maximum standardized uptake values of lymph nodes (LN-SUVmax) is useful for predicting LNM in lung cancer patients. From January 2014 to December 2019, a total of 147 lymph nodes from 104 patients with lung cancer, who underwent preoperative EBUS and FDG-positron emission tomography (PET)/computed tomography (CT) followed by surgery were retrospectively assesses. The characteristics of the patients, LN-SUVmax, and sonographic findings of lymph nodes were reviewed. Predictive factors associated with LNM were identified using the logistic regression model. The average size of the lymph nodes was 8.55 (range, 3-22) mm and the average LN-SUVmax was 5.36 (range, 1.79-31.19). The prevalence of nodal metastasis was 26/147 (17.4%), including 22 in mediastinal lymph nodes and 4 in hilar lymph nodes. Multivariate analysis demonstrated four independent predictive factors for LNM; size, round or oval shape, absence of a central hilar structure, and LN-SUVmax. The optimal cutoff value for lymph node size and LN-SUVmax were 10 mm and 6.00, respectively. By combinating of the two modalities, we obtained the results with sensitivity of 76.9%, specificity of 95.1% and accuracy of 93.2%. A combination of sonographic findings and LN-SUVmax showed a higher diagnostic rate of LNM than either modality alone in lung cancer patients.


Increased Expression of Neuregulin 1 and erbB2 Tyrosine Kinase in the Bladder of Rats With Cyclophosphamide-Induced Interstitial Cystitis.
The aim of this study was to evaluate changes in expressions of neuregulin (NRG)1 and erbB2 tyrosine kinase (ErbB2) in bladders of rats with cyclophosphamide (CYP)-induced interstitial cystitis (IC). Twenty-four Sprague-Dawley rats were divided into the IC group (n=16) and the control group (n=8). After inducing IC with intraperitoneal CYP injection, expressions of NRG1 and ErbB2 were analyzed using western blotting and reverse transcriptase-polymerase chain reaction. In Western blotting, relative intensities and distributions of both NRG1 and ErbB2 were approximately 1.5- and 3.2-fold higher, respectively, in the IC group than in the control group (mean±standard deviation: 1.42±0.09 vs. 0.93±0.15 and 0.93±0.16 vs. 0.29±0.08, P<0.05). In the rat bladder samples, mRNA expression levels of NRG1 and ErbB2 were higher in the IC group than in the control group (P<0.05). Our study has demonstrated significant changes in mRNA expression and immunoreactivity of NRG1 and ErbB2 receptors in the urinary bladder after CYP-induced IC. These results suggest that the up-regulated NRG1 may play a role in inducing an overactive bladder and promoting regeneration in the inflammatory bladder with CYP-induced IC.


Glucose diffusivity in cell-seeded tissue engineering scaffolds.
To determine the effective glucose diffusion coefficient in cell-seeded porous scaffolds to understand the importance of nutrient diffusion in tissue engineering bioreactors. Cell growth changed the morphological structure of the scaffolds decreasing the effective pore space and, inevitably, decreasing the effective glucose diffusivity in the chosen scaffolds, namely, collagen, poly(L-lactide) and poly(caprolactone) scaffolds from 3.7 × 10(-9) to 3.2 × 10(-9) m(2)/s, 1.4 × 10(-10) to 9.1 × 10(-11) m(2)/s and 1.8 × 10(-10) to 1.3 × 10(-10) m(2)/s, respectively. The presence of cells over time during cell culture reduces the mobility of glucose. The results can predict the glucose concentration profiles in thick engineered tissues.


Development of microsatellite markers in Byrsonima crassifolia (Malpighiaceae).
We developed and characterized microsatellite markers for Byrsonima crassifolia (Malpighiaceae), a widely distributed neotropical fruit tree. Eight polymorphic and two monomorphic microsatellite loci were identified and screened in 60 samples from four geographically disparate populations (Bolivia, Brazil, Mexico, and Panama). Each locus exhibited between two and 11 alleles. Expected heterozygosity ranged from 0 to 0.839. All loci amplify in the congeners B. variabilis and B. basiloba, four amplify in B. bucidaefolia, and seven amplify in B. variabilis, although levels of polymorphism have not been assessed. These loci will provide novel tools for comparing genetic diversity present in cultivated and noncultivated populations of B. crassifolia throughout its range, and may prove valuable in related species.


Development of a one-step microwave-assisted extraction method for simultaneous determination of organophosphorus pesticides and fungicides in soils by gas chromatography-mass spectrometry.
A one-step microwave-assisted extraction (MAE) procedure was developed for the simultaneous extraction of organophosphorus pesticide and fungicide residues in soil which have been greatly used in agriculture. Parameters that could influence the MAE efficiency such as irradiation power, temperature, time and solvent were investigated, and extraction efficiencies in the range of 92.6-103.7% were obtained using 400 W (100% output) at 160 °C for 10 min with only 12 mL of acetone-hexane (2:1, v/v). The analytes in extracts were analyzed directly by gas chromatography-mass spectrometry (GC-MS) without any further cleanup. At 5 and 50 ng g(-1) fortification levels for each analyte, the average recoveries obtained were ranged from 70.0% to 120.0% with relative standard deviation (RSD) between 0.2% and 14%. The method was linear over 1-250 ng g(-1) with a correlation coefficient (r(2)) between 0.9916 and 0.9966. The detection limits (S/N=3) were between 0.10 and 0.12 ng g(-1). The applicability of the method was demonstrated by analyzing field soil samples collected from six intensive horticultural sites in Ethiopia.


Comparison of vision-related quality of life between wearing Orthokeratology lenses and spectacles in myopic children living in Kuala Lumpur.
There are limited reports available on the impact of wearing Orthokeratology (ortho-K) lenses on the quality of life of Asian children. This study evaluated and compared vision-related quality of life (VRQoL) between myopic children wearing ortho-K lenses and single-vision spectacles (SVSs), living in Kuala Lumpur, using Paediatric Refractive Error Profile (PREP) questionnaires. This is a cross sectional study. Myopic children who had been wearing ortho-K and SVSs for 12 months were recruited, and the questionnaires were distributed online. The PREP scores were obtained using a summary scoring method. The Shapiro-Wilk test was used to determine data normality. Unpaired t-test was performed for normally distributed data, and the Mann-Whitney test for non-normally distributed data. P < 0.05 was considered significant. A total of 70 subjects participated in this study (45 ortho-K and 25 SVSs), with a mean age of 10.86 ± 0.73 years. The mean scores for all the items were higher in ortho-K than SVS wearers (p < 0.05). With regard to symptoms during ortho-K lens wear at night, <10 % of the subjects reported difficulty falling asleep, itch/burning/dry eyes and foreign body sensation after lens insertion. Ortho-K improves the vision-related quality of life of myopic school children in Kuala Lumpur. Thus, it should be considered by more local optometrists when managing myopic children.


A case report of Lemierre's Syndrome associated with dental sepsis.
Lemierre's syndrome is a potentially fatal condition characterised by spread of an oropharyngeal infection, resulting in thrombosis of the internal jugular vein. This leads to septicaemia and possible metastatic abscesses. We discuss the case of a previously healthy 17-year-old male who developed Lemierre's syndrome following dental sepsis. He presented with bilateral submandibular and submental swelling extending into the neck and chest. His management included a tracheostomy; incision and drainage of the abscesses; drainage of a pleural effusion and prolonged anticoagulant therapy. The incidence of Lemierre's disease appears to be increasing and early diagnosis is essential. A high index of suspicion is needed in cases of oropharyngeal infection followed by fever, tender swelling of the neck and dysphagia - especially in young patients.


A novel dual-emission fluorescent probe for the simultaneous detection of H2S and GSH.
A novel chlorinated coumarin-malononitrile fluorescent probe with three potential reaction sites, which exhibited highly selective, rapid response, low detection limit, and was capable of the simultaneous detection of H2S (λex/em = 515/564 nm) and GSH (λex/em = 430/517 nm), was first proposed. The probe was successfully applied to dual-channel imaging H2S and GSH in MCF-7 cells.


Food-based ingredients to modulate blood glucose.
Maintenance of normal blood glucose levels is important for avoiding chronic diseases such as type 2 diabetes, cardiovascular problems, and obesity. Type 2 diabetes is one of the major health problems affecting the world population and this condition can be exacerbated by poor diet, low physical activity, and genetic abnormalities. Food plays an important role in the management of blood glucose and associated complications in diabetes. This is attributed to the ability of food-based ingredients to modulate blood glucose without causing any adverse health consequences. This chapter focuses on four important food groups such as cereals, legumes, fruits, and spices that have active ingredients such as soluble dietary fiber, polyphenols, and antinutrients with the ability to reduce glycemic and insulin response in humans. Other food ingredients such as simple sugars, sugar alcohols, and some proteins are also discussed in moderation.


Physical fitness and cognitive function in an 85-year-old community-dwelling population.
Little is known about the association between physical fitness and cognitive function in very elderly people (over 80 years of age). To evaluate that relationship in 85-year-old community-dwelling individuals. Out of 207 participants (90 males, 117 females) who were 85 years old and community-dwelling, 205 completed the Mini-Mental State Examination (MMSE) for evaluating cognitive function. The numbers of subjects who completed physical fitness measurements such as hand-grip strength, isometric leg extensor strength, one-leg standing time, stepping rate, and walking speed were 198, 159, 169, 168, and 151, respectively. There were significant associations in MMSE with hand-grip strength (right or left hand), isometric leg extensor strength, stepping rate, and walking speed by simple regression analysis. MMSE was still significantly associated with hand-grip strength (beta = 0.305, p = 0.005 for right side; beta = 0.309, p = 0.004 for left side), stepping rate (beta = 0.183, p = 0.046), and walking speed (beta = -0.222, p = 0.014) by multiple regression analysis after adjustments for the amount of education, gender, smoking, drinking, complication of stroke, body weight, body height, regular medical care, serum albumin, blood HbA1c, and marital status. By logistic regression analysis, the prevalence of a normal MMSE score (MMSE >or=24) was increased by 9% with each 1-kg increase in hand-grip strength of the left hand (OR 1.087, 95% CI 1.003-1.179, p = 0.042), and was increased by 6% with each step per 10 s in stepping rate (OR 1.060, 95% CI 1.000-1.122, p = 0.048). In a very elderly population of 85-year-olds, cognitive function was associated with some physical fitness measurements, independent of confounding factors.


Immunomodulatory activity of methanolic fruit extract of Aegle marmelos in experimental animals.
The aim of the present study was to investigate the immunomodulatory action of methanolic extract of Aegle marmelos fruit (FEAM) in experimental model of immunity. Cellular immunity was carried out by neutrophil adhesion test and carbon clearance assay, whereas, humoral immunity was analyzed by mice lethality test and indirect haemagglutination assay. FEAM dose was selected by Stair case method (up and down) and administered at 100 and 500 mg/kg orally. The Ocimum sanctum (OSE, 100 mg/kg, p.o) was used as standard. FEAM at 100 and 500 mg/kg produced significant increases in adhesion of neutrophils and an increase in phagocytic index in carbon clearance assay. Both high and low doses of FEAM significantly prevented the mortality induced by bovine Pasteurella multocida in mice. Treatment of animals with FEAM and OSE significantly increased the circulating antibody titre in indirect haemagglunation test. Among the different doses, low one was more effective in cellular immunity models than the high. However, all the doses exhibited similar protection in humoral immunity procedures. From the above findings, it is concluded that FEAM possesses potential for augmenting immune activity by cellular and humoral mediated mechanisms more at low dose (100 mg/kg) than high dose (500 mg/kg).


Ascorbic acid attenuates antineoplastic drug 5-fluorouracil induced gastrointestinal toxicity in rats by modulating the expression of inflammatory mediators.
Damage to the mucous membrane is a serious issue associated with chemotherapy. Gastrointestinal (GI) toxicity is complex and multistep process and unregulated production of reactive oxygen species (ROS) and inflammatory mediators play vital role in the development of GI toxicity. In the present study we have investigated the attenuating potential of vitamin C (vit. C) on 5 fluorouracil (5-FU) induced GI toxicity by targeting oxidative stress and inflammatory markers in Sprague Dawley (SD) rats. Rats were gavaged with vit. C (500 mg/kg b. wt.) or vehicle daily (day 1-10) and were given intraperitoneal injection of 5-FU (150 mg/kg b. wt.) or saline (control) on day 8 to induce mucositis. We found that vit. C supplementation attenuated 5-FU induced lipid peroxidation, myeloperoxidase (MPO) activity, activation of NF-kB and expression of COX-2. Histological observations further supported the protective potential of vit. C against 5-FU induced intestinal anomalies such as neutrophil infiltration, loss of cellular integrity, villus and crypt deformities. Thus the biochemical, molecular and histological findings of the present study demonstrate that oxidative stress and inflammation play vital role in 5-FU induced GI toxicity and the inhibitory potential of vit. C is may be due to the modulation of oxidative stress, activation of redox sensitive transcription factor and also its downstream target molecules.


Immunostaining of germline stem cells and the niche in Drosophila ovaries.
Stem cells have the ability to switch between proliferative (self-renewal) and differentiation modes. The Drosophila germarium is a well-established in vivo model for the study of communication between stem cells and their niche. One commonly used technique for such study is immunostaining that allows examination of protein localization at a fixed time point. This chapter provides a detailed protocol for immunofluorescence staining of Drosophila ovaries. This protocol has been optimized to enable explicit visualization of the niche structure, as well as to maximize the degree of multiplexing for protein labeling and detection.