Treatment of high fracture risk patients in routine clinical practice.
A retrospective cohort study determined the high incidence of recurrent fractures in osteoporotic patients with high fracture risk during the observation. The strategy of starting treatment with more potent regimens (zoledronic acid, denosumab and/or teriparatide) seems to have the best secondary fracture prevention efficacy. This paper describes the various medical therapy regimens prescribed to osteoporotic patients with high fracture risk and the result of treatment. We carried out a retrospective cohort study in selected Osteoporosis Centers. Patients were considered to have high fracture risk in case of a history of a low-energy hip fracture or two or more vertebral or other site fractures. A total of 812 subjects (768 women and 44 men) aged 36-95 years were included. The observation period was 2285.1 patient-years. Demographic data, clinical findings, and BMD data obtained by DXA, as well as a history of fractures that had occurred during the follow-up, were included in the analysis. Overall, at baseline, there were 637 non-vertebral fractures including 104 hip fractures. A total of 590 patients had vertebral fractures; of these, 69% suffered multiple fractures. Being on treatment, 119 (14.7%) patients developed new vertebral and non-vertebral fractures. The incidence of new non-vertebral fractures and hip fractures was 39.4 and 13.1 per 1000 patient-years. The total number of vertebral fractures increased by 24.8% from 1353 to 1689. The best results of the treatment were achieved in patients who were started on zoledronic acid, denosumab, or teriparatide and had an adequate duration of treatment. Although these patients had significantly lower BMD values at the time of diagnosis compared with other patients, they showed a lower incidence of new vertebral and hip fractures, during the follow-up. Therapy of patients at high risk of fractures started with more potent treatment regimens (zoledronic acid, denosumab and/or teriparatide) of adequate duration was more effective in terms of prevention of new vertebral and hip fractures as compared with other treatment options. However, treatment appears to be challenging given the number of recurrent fractures in patients on treatment and the frequency of drug withdrawal or replacement.


[Toxic action of kanamycin on the internal ear of the frog Rana temporaria].
It has been demonstrated that administration of kanamycin (0.25 and 0.5 g/ml) to the inner ear in the frog results into a rapid decrease in the microphonic response to clicks.


Migration of lymphoid cells to the bone marrow of rat following eradication of cells in DNA synthesis and in mitosis.
Eradication of replicating bone marrow cells of rat by means of combined administration of single doses of hydroxyurea and vinblastin is followed within 9--10 h by an inflow of lymphoid cells of extramedullary origin in the range of 13,200,000/femur. The rat bone marrow with a high content of lymphoid cells was previously shown to be concentrated in stem cells. The factor(s) which convey the 'information' of decrease of replicating marrow cells to extramedullary sites is at present unknown.


Orbital measurements in 63 hyperteloric patients. Differences between the anthropometric and cephalometric findings.
Anthropometric and cephalometric orbital measurements were compared in 63 North American Caucasian patients (24 males, 39 females) aged 3 to 29 years who had 13 craniofacial syndromes involving hypertelorism. The hypertelorism, which was diagnosed anthropometrically, was mild in 11 patients, moderate in 25 and severe in 27. The surface intercanthal width was larger than the bony interorbital distance in all patients (mean 12.2 mm). The differences were smaller in mild cases and larger in severe cases. The soft-tissue binocular width was shorter than the bony lateral orbital distance in 53 patients, by a mean of 4.4 mm; in the other 10 patients the two measurements were identical. The hypertelorism was confirmed by cephalometry in 8 of the 11 cases identified as mild by anthropometry (72.7%), 24 of the 25 moderate cases (96.0%) and 25 of the 27 severe cases (92.6%). The abnormally wide surface intercanthal distance was matched by an abnormally wide bony interorbital distance in 57 of the 63 patients (90.5%). In the other six patients (3 with the mild form, 1 with the moderate form and 2 with the severe form) the bony widths were near the upper limit of the normal range (mean + 2 standard deviations).


Chemotherapy of cerebral metastases from solid tumors.
With proper staging, patients with parenchymal brain metastases from solid tumors are usually found to have widespread extracranial disease. Systemic chemotherapy offers the potential advantage of simultaneous therapy of both intracranial and extracranial tumor. Limited data is available on the efficacy of drug therapy alone in this patient population for selected patients with chemosensitive malignancies and brain metastases, systemic chemotherapy administration represents a useful treatment modality when given at presentation or following recurrence after surgery or radiation therapy.


Sexual disparities in the incidence and course of MS.
Multiple sclerosis (MS) affects three times more women than men and this ratio appears to be increasing. However male patients experience increased disease progression, brain atrophy, and cognitive impairment. Gonadal hormones may modulate these sex differences. For example, female puberty heralds an increased risk of MS, and during pregnancy disease activity is milder, with an increased risk of postpartum relapses. Gonadal hormones likely have complex and inflammatory and neuroprotective effects, and may interact with other disease modulators, such as vitamin D. Sex differences in the heritability of disease susceptibility genes implicate a role for epigenetic modification. Many questions remain, including the impact of sex on treatment response and epigenetic changes, and the modulatory potential of hormonal treatments. This article summarizes what is known about sexual dimorphism in MS onset and course, as well as potential interactions between sex and other factors influencing MS pathogenesis, incidence and severity.


Buprenorphine 5, 10 and 20 μg/h transdermal patch: a guide to its use in chronic non-malignant pain.
Buprenorphine lower-dose (5, 10 and 20 μg/h) transdermal patches, which are administered once every 7 days, are indicated in the management of chronic non-malignant pain. This review focuses on the labelling of this formulation (BuTrans®) in the EU. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol and generally superior to a matching transdermal placebo patch. When used together with regularly scheduled oral paracetamol (acetaminophen), transdermal buprenorphine was noninferior to codeine plus paracetamol. Transdermal buprenorphine has also shown analgesic efficacy in patients with chronic non-malignant pain of various causes.


Survival Time to Modern Contraceptive Uses from the Resumption of Sexual Intercourse Among Postpartum Women in Ethiopia.
The timing of contraceptive use is important for a woman who intends to avoid pregnancy during the postpartum period and it has key implications for reproductive health outcomes. Therefore, this study aimed to determine the time it takes to start modern contraceptive uses from the resumption of sexual intercourse among postpartum women in Ethiopia and to identify its predictors. A cross-sectional study using the 2016 Ethiopia Demographic and Health Survey (EDHS) was applied. The data were analyzed with SPSS version 20. Kaplan-Meier estimates were performed to explain time-to- modern contraceptive use. Cox-proportional hazard regression analysis was conducted to identify predictors. The adjusted hazard ratio (AHR) with a 95% confidence interval was considered to declare a statistically significant association. The total weighted sample comprised 1178 women. The median survival time to modern contraceptive use after birth was 4 months. In this study, the risk of modern contraceptive use was 1.29 times (AHR: 1.29; 95% CI: 1.04-1.61) higher among urban resident, 1.26 times (AHR: 1.26; 95% CI: 1.09-1.47) higher among women's attended primary education and 1.19 times (AHR: 1.19; 95% CI: 1.02-1.38) higher among women's accessed media. But, the risk of modern contraceptive use was lower among breastfeeding women by 17% (AHR: 0.83; 95% CI: 0.74-0.95). The median survival timing of modern contraceptive use from the resumption of sexual intercourse was four months. Women residing in urban area, who attended primary education and accessed to media shorten the time to use contraceptives after birth, whereas women breastfed their infant lengthen the time to use a modern contraceptive. Therefore, the health-care provider should enhance modern contraceptive use through health education and promotion to curb down the four months lag period identified by considering the spotted factors.


Imaging of the spine at 3 tesla.
Magnetic resonance (MR) imaging at 3 T has proved superior to 1.5 T in the brain for detecting numerous pathologic entities including hemosiderin, tiny metastases, subtle demyelinating plaques, active demyelinating plaques, and some epileptogenic foci, as well as small aneurysms with MR angiography. 3 T is superior to most advanced imaging techniques including diffusion, diffusion tensor imaging, perfusion, spectroscopy and functional MR imaging. The increased signal/noise ratio at 3 T permits higher spatial resolution. Initially spine imaging at 3 T proved more difficult with less successful results. During the past 7 years, technological advances in magnet and surface coil design as well as improved radio frequency transmitters and pulse sequence design in combination with the large body of knowledge accrued by radiologists and physicists during a nine year experience with clinical imaging of the spine with the doubled B0, has resulted in 3 T MRI of the spine achieving a reputation similar to that for brain imaging.


Comparison of the disinfection efficacy of chlorine-based products for inactivation of viral indicators and pathogenic bacteria in produce wash water.
Outbreaks of pathogenic bacteria infections associated with the consumption of fresh produce has occurred with increased frequency in recent years. This study was undertaken to determine the efficacy of three commonly used disinfectants in packing-houses of Culiacan, Mexico (sodium hypochlorite [NaOCl], trichlor-s-triazinetrione [TST] and thrichlormelamine [TCM]) for inactivation of viral indicators and pathogenic bacteria inoculated onto produce wash water. Each microbial challenge consisted of 2 L of water containing approximately 8 log10 bacterial CFU ml(-1), and 8 log10 viral PFU ml(-1) treated with 100 and 300 mg l(-1) of total chlorine with modified turbidity. Water samples were taken after 2 min of contact with chlorine-based products and assayed for the particular microorganisms. TST and NaOCl were found to effectively reduce for bacterial pathogens and viral indicators 8 log10 and 7 log10, respectively (alpha=0.05). The highest inactivation rate was observed when the turbidity was low and the disinfectant was applied at 300 mg l(-1). TCM did not show effective results when compared with the TST and NaOCl (P<0.05). These findings suggest that turbidity created by the organic and inorganic material present in the water tanks carried by the fresh produce may affect the efficacy of the chlorine-based products.


Chemoprevention of chemically-induced mammary and colon carcinogenesis by 1alpha-hydroxyvitamin D5.
Epidemiological data as well as experimental models yield evidence for a protective effect of vitamin D against the genesis of several types of cancers. Given its toxic properties at effective concentrations, numerous analogs of vitamin D have been developed. We synthesized an analog of vitamin D(5), 1alpha-hydroxy-24-ethylcholechalciferol (1alpha(OH)D(5)) and previously reported on its anti-proliferative activities against several cancer cell lines. To further examine its chemopreventive potential, experiments were conducted to investigate the in vivo effects of 1alpha(OH)D(5) using the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model. Results showed that 1alpha(OH)D(5) (25 and 50microg/kg diet) decreased the incidence and multiplicity of mammary tumors in female Sprague-Dawley rats. In a subsequent study, the stage specific inhibition was investigated using the 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis model. While supplementation with of 1alpha(OH)D(5) (40microg/kg diet) showed no significant effects during the initiation phase, tumor incidence during the promotional stage was significantly (p<0.05) decreased by 37.5%. In the colon, 1alpha(OH)D(5) (25microg/kg diet) was highly effective (p<0.001) in inhibiting the development of azoxymethane (AOM)-induced Aberrant crypt foci (ACF) in CF-1 mice. Studies on the stage specific inhibitory effects of 1alpha(OH)D(5) in the colon demonstrated that animals receiving 1alpha(OH)D(5) (25microg/kg diet) during the initiation, promotion, and entire period had a reduction in ACF number of 71, 80 and 82%, respectively. Immunohistochemistry studies comparing the colons of animals receiving control versus 1alpha(OH)D(5) supplemented diets showed that 1alpha(OH)D(5) partly mediates its effects by regulating members of the oncogenic beta-catenin pathway. 1Alpha(OH)D(5) inhibited expression of beta-catenin and peroxisome proliferator-activated receptor beta, a beta-catenin-TCF-4 responsive gene, whereas it induced expression of VDR. Cumulatively, these studies support the chemopreventive properties of 1alpha(OH)D(5) against the development of breast and colon cancers.


Living with tics: Nursing care of pediatric tourette syndrome.
Tourette syndrome (TS) is a neurodevelopmental movement characterized by abrupt, rapid, repetitive, and non-rhythmic tics. While TS is not life-threatening, such tics and comorbidities affect a children's physical and mental health and social interactions. Treatment is necessary when the children experience physical discomfort, functional dysfunction, and poor interpersonal interaction and mental health. Common management strategies for TS include psychological interventions and pharmacological treatment. Additionally, it is important to consider the individual needs of youths with TS and reassess the treatment outcomes and the need to receive continuous treatment regularly. This review summarizes the symptom management and nursing care measures for youths with TS. Understanding and listening to the healthcare problems of youths with TS can help providers develop healthcare interventions tailored to the youths' needs. Providing the youths with strategies to reduce the tics' interference with their learning outcomes and helping them develop strategies to cope with diverse interpersonal interactions at school are also important. Further, enhancing acceptance given by parents, teachers, and peers, as well as improving the general public's understanding of TS are important measures that promote the youths' social adjustment as well as their ability to coexist with TS.


BCR-ABL promotes hematopoietic stem and progenitor cell formation in embryonic stem cells.
Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous leukemia (CML), in embryonic stem cells (ESCs)-derived hematopoietic cells is sufficient to confer long-term in vivo repopulating potential. To precisely uncover the molecular events regulated by the tyrosine kinase activity of BCR-ABL1 (p210) during the course of hematopoietic differentiation, we engineered a Tet-ON inducible system to modulate its expression in murine ESCs (mESCs). We showed in unique site-directed knock-in ESC model that BCR-ABL expression tightly regulated by doxycycline (dox) controls the formation and the maintenance of immature hematopoietic progenitors. Interestingly, these progenitors can be expanded in vitro for several passages in the presence of dox. Our analysis of cell surface markers and transcriptome compared with wild-type fetal and adult HSCs unraveled a similar molecular signature. Long-term culture initiating cell (LTC-IC) assay confirmed their self-renewal capacities albeit with a differentiation bias toward erythroid and myeloid cells. Collectively, our novel Tet-ON system represents a unique in vitro model to shed lights on ESC-derived hematopoiesis, CML initiation, and maintenance.


Effects of multiple stresses on radish growth and resource allocation : I. Responses of wild radish plants to a combination of SO2 exposure and decreasing nitrate availability.
Acclimation of wild radish plants to a simultaneous combination of SO2 fumigation and decreasing nitrate availability was investigated. Plants were grown for 24 d under continuous daytime (10h) exposure to 0 or 0.4 ppm SO2 and were grown in a nutrient solution with stable nitrate concentrations of 100 μM for the first 15 d, 50 μM from day 15 to day 19, and 25 μM from day 19 to day 24. Analysis of relative growth rates (RGR) showed that radish plants responded rapidly to changes in nitrate availability and that SO2 treatment affected those responses. Shoot RGR of plants from both treatments and root RGR of control plants showed rapid declines and subsequent recoveries in response to decreasing nitrate availability. Root RGR of SO2-treated plants declined rapidly in response to decreased nitrate availability, but did not recover as quickly or completely as root RGR of control plants. Analysis of specific leaf weights and tissue nitrogen concentrations showed that control plants had significantly higher amounts of nitrogen in tissues after nitrate availability was lowered, and had higher rates of nitrate uptake in comparison to SO2-treated plants; especially when nitrate availability was highest. Furthermore, control plants had temporarily higher rates of root respiration in comparison to SO2-treated plants, suggesting that control plants temporarily allocated more resources to physiological processes occurring in roots, such as nutrient uptake. Although SO2-induced changes in growth and resource allocation of plants were relatively small, it was probable that SO2 treatment of radish plants affected plant nitrogen balance, and subsequently affected the ability of plants to respond to decreased nitrate availibility, by affecting resource partitioning to nitrate uptake and root growth.


Moss-associated methylobacteria as phytosymbionts: an experimental study.
Methylotrophic bacteria inhabit the surface of plant organs, but the interaction between these microbes and their host cells is largely unknown. Protonemata (gametophytes) of the moss Funaria hygrometrica were cultivated in vitro under axenic conditions and the growth of the protonemal filaments recorded. In the presence of methylobacteria (different strains of Methylobacterium), average cell length and the number of cells per filament were both enhanced. We tested the hypothesis that auxin (indole-3-acetic acid, IAA), secreted by the epiphytic bacteria and taken up by the plant cells, may in part be responsible for this promotion of protonema development. The antiauxin parachlorophenoxyisobutyric acid (PCIB) was used as a tool to analyze the role of IAA and methylobacteria in the regulation of cell growth. In the presence of PCIB, cell elongation and protonema differentiation were both inhibited. This effect was compensated for by the addition of different Methylobacterium strains to the culture medium. Biosynthesis and secretion of IAA by methylobacteria maintained in liquid culture was documented via a colorimetric assay and thin layer chromatography. Our results support the hypothesis that the development of Funaria protonemata is promoted by beneficial phytohormone-producing methylobacteria, which can be classified as phytosymbionts.


Rounding with scribes: employing scribes in a pediatric inpatient setting.
Using scribes to document patient encounters for physicians offers both benefits and challenges. A pediatric hospital recounts its experience adding scribes to its inpatient rounding teams.


Diagnosis and Management of Cognitive and Behavioral Changes in Dementia With Lewy Bodies.
Proper diagnosis of dementia with Lewy bodies (DLB) in clinical practice remains suboptimal as many cases are misdiagnosed, usually as Alzheimer disease (AD) or Parkinson's disease (PD) and, in rare cases, psychosis. Therefore, it is important for patients with dementia to be thoroughly evaluated by a specialist who is familiar with current diagnostic tests and treatment options. New diagnostic criteria from the Dementia with Lewy Bodies Consortium have been developed to increase diagnostic sensitivity for DLB (Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium; McKeith et al.; Neurology, 89(1): 88-100). REM sleep behavior disorder (RBD) has been studied more thoroughly in correlation with DLB and is now considered a core feature. D2 receptor blocking antipsychotics, which can cause severe antipsychotic sensitivity, are now rarely prescribed for treatment. Therefore, severe antipsychotic sensitivity, which was a suggestive criterion for DLB diagnosis, is now listed as a supportive feature. Reduced DAT uptake in basal ganglia demonstrated by SPECT or PET imaging has high specificity (90%) for distinguishing DLB from AD. Reduced uptake on metaiodobenzylguanidine myocardial scintigraphy correlates with reduced postganglionic sympathetic cardiac innervation in Lewy body diseases, which can increase specificity for discriminating probable DLB from probable AD in milder cases of dementia. However, the latter is more commonly used in Japan and is not used in the USA. The evidence supporting the benefit of other therapeutic modalities is limited in DLB due to lack of extensive studies. There are no FDA-approved medications for the treatment of DLB, although some effective drugs have been used off label to treat various symptoms.


Acute Coronary Syndrome in Women.
Acute coronary syndrome is pathologically distinct in women and requires an appreciation of the specific risk factors, presenting symptoms, laboratory findings, and imaging results to treat correctly. Persistent disparities in mortality between men and women may be the result of failure to recognize and intervene, especially in the case of women aged less than 55 years. Protocols which establish criteria for activating the cardiac catheterization laboratory and which empower emergency department physicians to do so without delay show signs of eliminating disparities, as does guideline-directed therapy at the time of discharge from the hospital.


Upregulation of hsa_circ_0004812 promotes COVID-19 cytokine storm via hsa-miR-1287-5p/IL6R, RIG-I axis.
SARS-CoV-2 is one of the most contagious viruses in the Coronaviridae (CoV) family, which has become a pandemic. The aim of this study is to understand more about the role of hsa_circ_0004812 in the SARS-CoV-2 related cytokine storm and its associated molecular mechanisms. cDNA synthesis was performed after total RNA was extracted from the peripheral blood mononuclear cells (PBMC) of 46 patients with symptomatic COVID-19, 46 patients with asymptomatic COVID-19, and 46 healthy controls. The expression levels of hsa_circ_0004812, hsa-miR-1287-5p, IL6R, and RIG-I were determined using qRT-PCR, and the potential interaction between these molecules was confirmed by bioinformatics tools and correlation analysis. hsa_circ_0004812, IL6R, and RIG-I are expressed higher in the severe symptom group compared with the negative control group. Also, the relative expression of these genes in the asymptomatic group is lower than in the severe symptom group. The expression level of hsa-miR-1287-5p was positively correlated with symptoms in patients. The results of the bioinformatics analysis predicted the sponging effect of hsa_circ_0004812 as a competing endogenous RNA on hsa-miR-1287-5p. Moreover, there was a significant positive correlation between hsa_circ_0004812, RIG-I, and IL-6R expressions, and also a negative expression correlation between hsa_circ_0004812 and hsa-miR-1287-5p and between hsa-miR-1287-5p, RIG-I, and IL-6R. The results of this in-vitro and in silico study show that hsa_circ_0004812/hsa-miR-1287-5p/IL6R, RIG-I can play an important role in the outcome of COVID-19.


Erythrocyte Sedimentation Rate in Patients with Renal Insufficiency and Renal Replacement Therapy.
Determination of the erythrocyte sedimentation rate (ESR) is a simple diagnostic tool for estimating systemic inflammation. It remains unclear whether ESR is influenced by renal disease or renal replacement therapy (RRT). To report the incidence and extent of ESR elevations in patients with chronic kidney disease (CKD) and the possible impact of RRT. We performed a single-center, retrospective study in inpatients with or without renal disease and in those with RRT, comparing ESR levels and other laboratory and clinical information. A total of 203 patients were included. On average, ESR was elevated (mean [SD], 51.7 [34.6] mm/h), with no statistically significant difference between the patient groups. Only those receiving PD showed significantly higher ESR (78.3 [33.1] mm/h; P < .001). ESR testing can be used without restriction in patients with CKD and in patients undergoing hemodialysis and who have received kidney transplantation; however, this measurement should be monitored carefully in patients with PD.


Early postpartum rooming-in and maternal attachment behaviors in a group of medically indigent primiparas.
Introduction of rooming-in at the study site provided an opportunity to examine the impact of rooming-in on maternal attachment behaviors. Maternal attachment scores for 80 mothers who received rooming-in were compared to 72 mothers who delivered before rooming-in and 35 mothers who requested but did not receive rooming-in. All subjects were medically indigent primiparas with no intrapartum or postpartum complications and term healthy infants. The groups were not significantly different in maternal age, race, or ethnicity. Maternal attachment behaviors were recorded during an infant feeding. Rooming-in mothers had significantly higher maternal attachment scores than both control groups. Rooming-in had an independent effect on maternal attachment after the effects of maternal age, episiotomy or lacerations, epidural anesthesia, infant contact at delivery, and time of feeding observation had been accounted for. Of these prior factors, only maternal age had a significant impact on rooming-in. These results suggest that rooming-in helps primiparas to form early attachments to their babies, and that the impact of rooming-in cannot be explained by the mother's motivation for rooming-in. It is important to provide close contact with the infant during the early postpartum, especially for adolescents who may be at higher than average risk of mothering inadequacies.


Low vigorous physical activity is associated with increased adrenocortical reactivity to psychosocial stress in students with high stress perceptions.
The pathways by which physical activity impacts on participants' health are still not fully understood. The purpose of the present study was to go beyond existing research by combining methods from survey-based and experimental stress research, and by examining whether the potential of vigorous physical activity (VPA) to attenuate physiological and psychological stress responses is moderated by participants' subjective stress perception. The sample consisted of 42 undergraduate students (M=21.2±2.2 years, 52% women). Participants self-reported their stress and wore an accelerometer device for seven consecutive days. To examine differences in the adrenocortical, autonomic and psychological stress reactivity, salivary free cortisol, heart rate, state anxiety, mood and calmness were assessed prior to, during and after the Trier Social Stress Test (TSST). The cut-offs of the American College of Sports Medicine (ACSM) were used to distinguish between students below/above current VPA recommendations. High levels of perceived stress combined with VPA levels below the ACSM's standards (<3×20min/week) were associated with an increased salivary cortisol response to the TSST (p<.05). No significant group differences existed for heart rate. However, students with high stress/low VPA experienced less favourable affect throughout the entire testing session (p<.05). Our study suggests that VPA has a high stress-protective potential among undergraduate students with high stress levels. Our findings highlight that promoting VPA in young adults seems to be a promising strategy to increase physiological and psychological stress resilience.


Response to comment on "Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2".
Further analysis of SARS-CoV-2 genome sequencing data identifies several highly recurrent genetic variants with low allele frequencies, which, if filtered out, provide estimates consistent with tighter transmission bottlenecks.


Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes.
The mechanisms generating precise connections between specific thalamic nuclei and cortical areas remain poorly understood. Using axon tracing analysis of ephrin/Eph mutant mice, we provide in vivo evidence that Eph receptors in the thalamus and ephrins in the cortex control intra-areal topographic mapping of thalamocortical (TC) axons. In addition, we show that the same ephrin/Eph genes unexpectedly control the inter-areal specificity of TC projections through the early topographic sorting of TC axons in an intermediate target, the ventral telencephalon. Our results constitute the first identification of guidance cues involved in inter-areal specificity of TC projections and demonstrate that the same set of mapping labels is used differentially for the generation of topographic specificity of TC projections between and within individual cortical areas.


Hyper-phosphorylation of alpha-enolase in hypertrophied left ventricle of spontaneously hypertensive rat.
Cardiac hypertrophy is one of the main target organ damages of essential hypertension and predicts a poor prognosis of the disease. The molecules involved in this event, especially their posttranslational modifications, remain largely unknown to date. With a combination of phosphoprotein column enrichment and two-dimensional gel electrophoresis separation, here we compared the profiling of enriched phosphoproteins from the left ventricle (LV) of spontaneously hypertensive rats (SHR) to that of age-matched Wistar Kyoto rats. As a result, 19 differential proteins were found in the hypertrophied LV of SHR. Among them, we focused on a glycolysis enzyme alpha-enolase, of which the hyper-phosphorylation was shown in the hypertrophied LV but not in non-hypertrophied atrium and right ventricle of SHR. Furthermore, the alpha-enolase hyper-phosphorylation was accompanied by decreased enzymatic activity. The further investigation based on these results would provide new clues to understand the pathological process of cardiac hypertrophy in SHR.


Involvement of Mitophagy in Aluminum Oxide Nanoparticle-Induced Impairment of Learning and Memory in Mice.
Aluminum oxide nanoparticles (nano-aluminum) have been known to be widespread in the environment for decades. Exposure to nano-aluminum may impair learning and memory, but the potential mechanism has not yet been elucidated. In neurons, efficient clearance of damaged mitochondria through mitophagy plays an important role in mitochondrial energy supply, neuronal survival, and health. However, abnormal mitophagy induces accumulation of damaged mitochondria, which induces cellular dysfunction, contributing to the impairment of learning and memory. It is currently unclear whether nano-aluminum interferes with the function of nerve cells through mitophagy, leading to learning and memory disorders. Institute of Cancer Research (ICR) female mice were randomly divided into four groups, and treated with normal saline (control) and 50 nm nano-aluminum at concentrations of 25, 50, and 75 mg/kg for 30 days. Our results showed that exposure to nano-aluminum impaired the spatial learning and memory of mice. Superoxide dismutase levels decreased, whereas the levels of malondialdehyde increased. Moreover, there were significant pathological changes in the ultra-structure and function of mitochondria. Finally, expression of autophagy-related proteins LC3-II and Beclin-1 was upregulated and p62 expression decreased, but the expression of apoptotic and necrosis-related proteins had no significant difference among groups. Our results suggest that learning and memory impairment induced by nano-aluminum could be related to mitophagy.


Endoscopic challenges and applications in tuberculous meningitis.
Endoscopy for hydrocephalus caused by infectious diseases presents clear challenges to the surgeon. Hydrocephalus caused by tuberculous meningitis is a good model to explore many of the issues that should be considered in the management of these patients. Tuberculous hydrocephalus may be communicating or noncommunicating management options include medical treatment (for communicating hydrocephalus), ventriculoperitoneal shunting, and endoscopic third ventriculostomy. No guidelines exist currently, and therefore management protocols are specific to each center. Because brain ischemia attributable to vasculitis is common in these patients, optimal treatment of intracranial pressure (ICP) is even more important than usual, and this has implications for the management decisions. Effective treatment of these patients should lead to normalization of ICP and resolution of the hydrocephalus, rather than merely avoiding extreme elevations of ICP. However, this also must be weighed against the surgical and long-term complications associated with the procedures used. There are specific endoscopic challenges that occur as the result of abnormal anatomy and the fact that hydrocephalus presents during the acute phase of the disease, rather than being postinfectious. In this article we examine the arguments for various therapeutic approaches and discuss the gathering experience in the literature about endoscopy in tuberculous meningitis in the context of overall management options.


Characterization of T antigens in polyoma-infected and transformed cells.
Polyoma-infected 3T6 cells contain a number of proteins precipitable by serum from rats carrying polyoma-induced tumors. The virus codes for three species having apparent molecular weights of 90,000, 60,000 and 22,000 daltons, as determined by polyacrylamide gel electrophoresis (90K, 60K and 22k). The 90K and 22K species produced by a large plaque and a small plaque wild-type polyoma have similar mobilities, but the 60K species produced by the large plaque wild-type. In cells infected by each of seven polyoma tsA mutants, the 90K species is unstable at the nonpermissive temperature, while the 60K and 22K species are stable. In cells infected by a mutant carrying a deletion between roughly 98 and 3 map units in the early region of the viral genome, the 22K species is present, but the 90K and 60K species are absent. Tryptic peptide analysis of the isolated 90K, 60K and 22K species shows that the three species have common N terminal regions. The 60K and 22K species contain amino acid sequences not found in the 90K species , and the 60K species has several unique, methionine-containing peptides not found in either the 22K or 90K species. Two polyoma-transformed BHK cell lines do not have detectable amounts of the 90K protein.


Improved estimation of rural residential coal emissions considering coal-stove combinations and combustion modes.
Rural residential coal combustion (RRCC) has detrimental effects on air quality, climate, and human health. There are large uncertainties regarding emissions from RRCC owing to the lack of consideration of several key factors (e.g. combination modes of coal and stoves, combustion modes, and high temporal resolution). In this study, we provided a new estimation framework for RRCC emissions through a case study in the Beijing-Tianjin-Hebei (BTH) region, China. The emission estimations were improved according to four aspects, namely (1) coal-specific and stove-specific coal consumption was calculated based on face-to-face field interviews of 6700 valid volunteers/households covering 288 villages in 50 counties; (2) the influences of combustion modes (flaming and smoldering modes) on emissions were considered; (3) emissions of different fuel-stove combinations were estimated based on coal, stove, and combustion mode-specific RRCC consumption and localised emission factors; and (4) a method for emission estimation with high temporal resolution (1 h) was developed. The results indicated that RRCC emitted 413.6 kt SO2, 55.7 kt NOx, 5717.3 kt CO, 149.4 kt VOCs, 167.1 kt PM2.5, 18.2 kt EC, 32.5 kt OC, and 8.2 kt NH3 in 2016. The combination of bituminous coal and an advanced coal stove was the most significant contributor (20.7-71.8%) to various pollutant emissions. Coal combusted under the flaming mode contributed to most (81.9%) of the total coal consumption, and thus emitted the majority (50.8-99.8%) of pollutants, except for VOCs. Meanwhile, that under the smoldering mode only accounted for 18.1% of the total consumption, but contributed 49.2% and 74.7% of the CO and VOCs emissions, respectively. Two clear emission peaks occurred at approximately 7:00-9:00 and 18:00-20:00. The detailed coal consumption and emissions with high temporal and spatial resolution can provide sound data for further research on rural environmental issues and scientific support to pollution control strategies.


Nitric oxide enhancement and blood pressure decrease in patients with metabolic syndrome using soy protein or fish oil.
To verify the effects of fish oil and soy on nitric oxide (NO) and blood pressure in patients with metabolic syndrome (MS). Sixty women with MS were investigated in a parallel randomized design study. The first group maintained their usual diet; the second group received 25 g/day of soy; the third group received 3 g/day of n-3 fatty acids, and the fourth group the same amount previously cited of n-3 fatty acids and soy. Serum nitric oxide metabolites showed significant increase after 90 days in the fish oil and soy groups. Systolic pressure reduced after 45 days of treatment with fish oil, whereas diastolic pressure decreased significantly throughout the study in the soy group. NO increase and blood pressure reduction with fish oil or soy protein reinforce the importance of the influence of NO on blood pressure in patients with MS.


Synergy between artificial intelligence and precision medicine for computer-assisted oral and maxillofacial surgical planning.
The aim of this review was to investigate the application of artificial intelligence (AI) in maxillofacial computer-assisted surgical planning (CASP) workflows with the discussion of limitations and possible future directions. An in-depth search of the literature was undertaken to review articles concerned with the application of AI for segmentation, multimodal image registration, virtual surgical planning (VSP), and three-dimensional (3D) printing steps of the maxillofacial CASP workflows. The existing AI models were trained to address individual steps of CASP, and no single intelligent workflow was found encompassing all steps of the planning process. Segmentation of dentomaxillofacial tissue from computed tomography (CT)/cone-beam CT imaging was the most commonly explored area which could be applicable in a clinical setting. Nevertheless, a lack of generalizability was the main issue, as the majority of models were trained with the data derived from a single device and imaging protocol which might not offer similar performance when considering other devices. In relation to registration, VSP and 3D printing, the presence of inadequate heterogeneous data limits the automatization of these tasks. The synergy between AI and CASP workflows has the potential to improve the planning precision and efficacy. However, there is a need for future studies with big data before the emergent technology finds application in a real clinical setting. The implementation of AI models in maxillofacial CASP workflows could minimize a surgeon's workload and increase efficiency and consistency of the planning process, meanwhile enhancing the patient-specific predictability.


Comparative study of topical regimen for adenoviral kearoconjunctivitis by 0.1% fluorometholone with and without polyvinyl alcohol iodine.
The aim of this study was to compare the efficacy of the topical regimens of iodine/steroids vs. antibiotics/steroids in acute to subacute adenoviral keratoconjunctivitis. A prospective open-label study. Nineteen patients diagnosed with unilateral or bilateral adenoviral conjunctivitis at less than 1 week from onset were enrolled in this study. Patients were divided randomly into two groups; group 1 was treated with 1.5% levofloxacin with 0.1% fluorometholone administered four times a day and group 2 was treated with a sixfold dilution of polyvinyl alcohol iodine (PAI) solution with 0.1% fluorometholone four times a day. Conjunctival samples from all affected eyes were obtained for real-time PCR. The total scores of acute signs (i.e., eyelid edema, conjunctival injecton, conjunctival discharge, follicules, pseudomembranes, subconjunctival hemorrhage) and symptoms, HAdV DNA copy number, and the presence of multiple subepithelial corneal infiltrates (MSI) were evaluated every 5 visits up to Day 30 after diagnosis. Comparing the total scores of acute signs and symptoms and viral load, we observed no significant differences between the two groups. At day 15 after diagnosis the proportion of patients with MSI in group 2 (35.7%) was significantly lower than in group 1 (0%). The impact of topical iodine/steroid therapy on acute signs and symptoms associated with adenoviral conjunctivitis is limited and not substantially different in the responses to antibiotics/steroids. However, this regimen results in a significant decrease in the incidence of MSI during the subacute phase of infection.


Parechovirus A Pathogenesis and the Enigma of Genotype A-3.
ParechovirusA is a species in the Parechovirus genus within the Picornaviridae family that can cause severe disease in children. Relatively little is known on ParechovirusA epidemiology and pathogenesis. This review aims to explore the ParechovirusA literature and highlight the differences between ParechovirusA genotypes from a pathogenesis standpoint. In particular, the curious case of Parechovirus-A3 and the genotype-specific disease association will be discussed. Finally, a brief outlook on ParechovirusA research is provided.


Plant physiology: ARSK1, a regulator of TOR1 and mediator of P-adaptive root growth.
Root growth inhibition under phosphorous deficiency was long hypothesized to be the result of toxic iron levels in root tips. However, a new study reveals ARSK1 and TOR1 regulate root growth within hours of phosphorous starvation prior to changes in iron accumulation.


Effects of telencephalic ablation on habituation of arousal responses, within and between daily training sessions in goldfish.
Goldfish Carassius auratus were presented with a moving shadow stimulus at 2-min intervals and their cardiac and ventilatory responses were monitored. Normal fish, fish with their telencephalon ablated, and those with sham operations were compared for responsiveness and habituation to repeatedly presented stimuli over the 3-day test period. While all groups showed increased habituation on successive days testing, fish with their telencephalon ablated showed significantly slower response habituation within the daily test sessions when compared with the control groups. Subjects with their telencephalon ablated also showed a tendency for increased responsiveness on initial stimulus presentation and poorer retention between days of information relating to the eliciting test stimulus.


The construction and validation of a frailty risk prediction model for older adults with lung cancer: A cross-sectional study.
We aimed to construct and internally validate a frailty risk prediction model in older adults with lung cancer. In total, 538 patients were recruited in a grade A tertiary cancer hospital in Tianjin, and patients were randomly divided into the training group (n = 377) and the testing group (n = 166) at a ratio of 7:3. The Frailty Phenotype scale was used to identify frailty and logistic regression analysis was used to identify the risk factors and establish a frailty risk prediction model. In the training group, logistic regression showed that age, fatigue-related symptom cluster, depression, nutritional status, D-dimer level, albumin level, presence of comorbidities, and disease course were independent risk factors for frailty. The areas under the curve (AUCs) of the training and testing groups were 0.921 and 0.872, respectively. A calibration curve of P = 0.447 validated model calibration. The decision curve analysis demonstrated greater clinical benefit when the threshold probability was >20%. The prediction model had a favorable prediction power for determining the risk of frailty, contributing to the prevention and screening of frailty. Patients with a frailty risk score of more than 0.374 should be regularly monitored for frailty and receive personalized preventive interventions.


Pressurized N2 directly fed to the RuAu/CeO1.76 catalyst porous electrode in a proton exchange membrane electrolyzer favoring electrochemical NH3 production.
The limited N2 solubility in the present aqueous electrolyte critically restricts the selectivity and activity of environment-friendly electrochemical NH3 production at high current density. Here we developed a high-performance electrolyzer for the electrochemical N2 reduction reaction (eNRR) using amorphous RuAu clusters anchored on CeO1.88 nanorods with rich oxygen vacancies (OVs) as the catalyst and a proton exchange membrane (PEM) as the solid-state electrolyte, in which N2 is directly delivered to the electrode across a gas diffusion layer. The PEM electrolyzer achieved a remarkable NH3 yield rate of 185.53 μg mg-1 h-1 at -0.3 V vs. RHE under an applied N2 pressure of 4 bar, which is 5 times higher than that in aqueous electrolyte.


Argon plasma coagulation for treatment of watermelon stomach.
Watermelon stomach or gastric antral vascular ectasia (GAVE) is a rare but well-recognized cause of gastrointestinal blood loss, which typically affects elderly women. Historically patients were treated with antrectomy but this has been largely replaced by endoscopic therapy such as Nd:YAG laser. Argon plasma coagulation (APC) is a new noncontact electocoagulation technique which has several theoretical advantages over laser. The objective of this study was to assess the efficacy of APC in treating GAVE. We retrospectively reviewed the case-records of five patients (four women, one man) with iron deficiency anaemia or gastrointestinal blood loss due to GAVE who were treated with APC and for whom a follow-up of more than 12 months was available. Four patients were transfusion-dependent. Their mean age was 71 years (range 58 - 83). The mode of presentation, number of treatment sessions, response to therapy and recurrence (if any) were recorded. A mean of 2.6 treatment sessions per patient were required. All patients had an endoscopically observed response to therapy and all patients had a sustained rise in hemoglobin level after treatment. Transfusion dependence ceased in all patients. After a mean follow-up of 20 months GAVE recurred in two patients (40 %). Both patients responded to further APC treatment. No major complications were recorded. APC is a safe and effective short-term treatment for GAVE. The natural history of the condition is uncertain, and at medium-term follow-up GAVE is found to recur in a substantial number of patients treated with APC. Re-treatment with APC is an option in these patients.


Successful laparoscopic fundoplication in children with ventriculoperitoneal shunts.
We reported successful laparoscopic fundoplication in 2 pediatric cases with VPS and discuss the safety and feasibility of the procedure. Case 1: A 13-year-old girl with VPS underwent laparoscopic fundoplication. Case 2: a 9-year-old boy with VPS underwent laparoscopic fundoplication. In both cases, laparoscopic Nissen fundoplication was performed with a standard five-port technique with a low pressure of a pneumoperitoneum. The VPS system had no effect on port layout and intraabdominal manipulation and no adverse complications were observed in either case. The effect of a pneumoperitoneum in the VPS system remains controversial, however, the author emphasized that advanced laparoscopic surgery can be performed safely with creating a low pressure of a pneumoperitoneum.


Patient-reported outcomes and pharmacist actions in patients with multiple sclerosis managed by health-system specialty pharmacies.
This study evaluated patient-reported outcomes (PROs) and pharmacist actions for patients on disease-modifying therapies (DMTs) for multiple sclerosis (MS) through health-system specialty pharmacies (HSSPs). A multisite, prospective cohort study of patients utilizing an HSSP for DMT fulfillment was performed. Primary outcomes were affirmative answers to PRO questions regarding impacted productivity, hospitalization, and relapse and pharmacist actions. Rates of pharmacist actions were reported as the number of person-years of treatment per action. Univariate and multivariate logistic regression were used to evaluate the association between each PRO and covariates, including the number of pharmacist actions performed, age, sex, insurance, site, and route of administration. The 968 patients included had 10,562 fills and 6,946 PRO assessments. The most common affirmative PRO was impacted productivity (14.6%). Pharmacists performed 3,683 actions, most commonly general medication education (42.6%) and safety (33.3%). Rates of general medication education and nonfinancial coordination of care actions were similar across medication classes; other pharmacist actions varied by medication class. Insurance type was significantly associated with reporting impacted productivity; patients with Medicare and Medicaid were 2.2 and 3.1 times more likely to have reported impacted productivity, respectively (P < 0.001) than commercially insured patients. Patients who reported impacted productivity had more pharmacist actions (P < 0.001). Patients on DMTs through an HSSP reported low rates of impacted productivity, relapse, and hospitalization due to MS, although patients with noncommercial insurance were more likely to have impacted productivity. Patients reporting impacted productivity and those taking certain DMTs may require more frequent pharmacist actions.


Extracts from Radix Astragali and Radix Rehmanniae promote keratinocyte proliferation by regulating expression of growth factor receptors.
Chinese herbal medicine has long been used as a treatment for wounds. However, the underlying cellular and molecular mechanisms remain largely unknown. In this study it was shown that the proliferation of keratinocytes, which is known to play an important role in wound healing as the major cell type in the epidermis, was promoted by three herbal extracts/natural compounds: NF3 (an extract from the mixture of Radix Astragali (RA) and Radix Rehmanniae (RR) in the ratio of 2:1), stachyose (an isolated compound from Radix Rehmanniae) and extract P2-2 (a sub-fraction from the extract of Radix Astragali). The effect of the herbal extracts/natural compounds on the growth of keratinocytes was not influenced by a high glucose level, a condition similar to diabetic patients who usually suffer from diabetic foot ulcers. Real time RT-PCR results showed that the expression of epidermal growth factor (EGF) receptor, but not transforming growth factor-β (TGF-β) receptor, was up-regulated by NF3. Moreover, treatments with the EGF receptor kinase inhibitor AG1478 and the MEK inhibitor U0126 resulted in the diminishment of the effect of the three herbal extracts/natural compounds on keratinocyte proliferation, indicating that EGF receptor might have a significant role in this action. This study has further elucidated the molecular mechanism under which herbal extracts/natural compounds exert their effects on the wound healing process.


Nerve conduction studies of the lateral femoral cutaneous nerve. Implications in the diagnosis of meralgia paresthetica.
The diagnosis of meralgia paresthetica, while based on clinical suspicion, can be confirmed via electrophysiological testing. Previous testing of the sensory conduction of the lateral femoral cutaneous nerve placed the stimulating electrode one centimeter medial to the anterior superior iliac spine (ASIS). This position is both uncomfortable for the patient and difficult for the operator to perform. The following article suggests an alternate position for the stimulating electrode, four centimeters distal to the ASIS. Twenty subjects served as their own controls and both the old technique and the new technique were performed. Using the old technique, the response rate was 35% (7 out of 20 subjects). Using the new technique, the response rate was 90% (18 out of 20 subjects). These results indicate a significantly higher response rate when the only variable altered is the electrode placement. This simple change in technique requires no more effort, cost, or training on the part of the operator yet produces a much higher percentage of responses.


The prevalence of rheumatoid arthritis in middle-aged and elderly people living in Naqu City, Tibet, Autonomous Region of China.
To estimate the prevalence of rheumatoid arthritis (RA) in the Tibet Autonomous Region (China). A population-based cross-sectional survey was conducted on 1458 residents of Luoma Town, Tibet Autonomous Region, who were aged ≥ 40 years old. We interviewed participants using questionnaires, and rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and C-reactive protein (CRP) were determined. The identification of RA in this study was on the basis of criteria issued by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guideline. Herein, 782 participants completed all items of RA. The overall prevalence of RA was 4.86%, and the prevalence was higher in women than that in men (7.14% vs. 2.56%, p = 0.005). The age-standardized prevalence of RA was 6.30% (95% confidence interval (CI) 4.20-8.64%), which was 2.46% (95% CI 1.04%, 4.10%) and 9.59% (95% CI 5.93%, 13.77%) in men and women, respectively. The prevalence of RA is relatively higher in the Tibet than that in other areas of China.


Vasoactive intestinal peptide: autocrine growth factor in neuroblastoma.
Neuroblastoma is the most common solid tumor of children less than 5 years of age; yet the biology of this tumor is poorly understood. Neuroblastoma tumors are derived from neural crest precursors; they synthesize both adrenergic and peptidergic neurotransmitters. This study determined VIP receptor expression in primary neuroblastoma tumors prior to chemotherapy. The VIP receptor was expressed in 12 of 15 neuroblastoma tumors as determined by direct binding studies (KD = 1.3-12.4 nM) and VIP-mediated stimulation of adenylate cyclase. The VIP stimulation index for adenylate cyclase in the primary tumor was inversely correlated with the VIP content of the tumor, suggesting that VIP regulates its own receptor expression. Similar observations were made in vitro by comparison of two human neuroblastoma cell lines, IMR32 and SKNSH. Both cell lines were demonstrated to express specific, high affinity VIP receptors (KD = 4 nM and 2.5 nM for IMR32 and SKNSH, respectively). IMR32 cells contained very low levels of VIP (0.6 pg VIP/10(6) cells). Exogenous VIP stimulated adenylate cyclase 22-fold over basal activity and VIP inhibited proliferation of IMR32 cells by 49% in 6-day cultures. On the other hand, SKNSH cells synthesized high levels of VIP (6.3 pg/10(6) cells), metabolized VIP rapidly and demonstrated a low level of VIP-mediated stimulation of adenylate cyclase; their proliferation rate was minimally inhibited by exogenous VIP. These observations help validate the hypothesis that VIP serves as an autocrine growth factor in neuroblastoma.


Optimization of biobleaching of paper pulp in an expanded bed bioreactor with immobilized alkali stable xylanase by using response surface methodology.
Purified alkali stable xylanase from Aspergillus fischeri was immobilized on polystyrene beads using diazotization method. An expanded bed bioreactor was developed with these immobilized beads to biobleach the paper pulp in continuous mode. Response surface methodology was applied to optimize the biobleaching conditions. Temperature (degrees C), flow rate of pulp (ml/min) and concentration of the pulp (%) were selected as variables in this study. Optimal conditions for biobleaching process were reaction temperature 60 degrees C, flow rate of 2 ml/min and 5% (w/v) of pulp. The kappa number reduced from 66 in the unbleached pulp to 20 (reduction of 87%). This system proves to be a better option for the conventional chlorine based pulp bleaching.


Malignant melanoma associated with human immunodeficiency virus infection in three homosexual men.
This report concerns three patients with human immunodeficiency virus (HIV) infection in whom malignant melanoma developed. One patient had metastatic malignant melanoma, one had iris melanoma, and one had a single skin melanoma. All three had lower absolute numbers of CD4+ cells than a control group, and the severity of their disease was inversely proportional to the absolute number of CD4+ cells. This report suggests an association between the immunodeficiency resulting from HIV infection and the development of malignant melanoma.


Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance.
Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggests that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.


Light-induced synthesis of silver nanoprisms as a surface-enhanced Raman scattering substrate for N-acetyl procainamide drug quantification.
Triangle-shaped silver nanoprisms (AgNPMs) were prepared by a photo-induced method through a seed-mediated growth process and were successfully employed as an ultra-sensitive surface-enhanced Raman scattering (SERS) substrate for the detection of the chemotherapeutic N-acetyl procainamide (NAPA) compound. The transformation of the morphology of the nanoprisms substrate could be noted with a remarkable change in color, possessing an average size of 95 nm. The shape-modified AgNPMs exhibited interesting optical characteristics owing to the truncated dual edges, which led to a pronounced longitudinal localized surface plasmonic resonance (LLSPR) behavior. The nanoprisms-based SERS substrate demonstrated an outstanding sensitivity for NAPA in aqueous solutions with the lowest ever reported detection limit of 0.5 × 10-13 M corresponding to excellent recovery and stability. A steady linear response with a broad dynamic range (10-4-10-12 M) and an R2 of 0.945 was also achieved. The results proved that the NPMs demonstrated excellent efficiency, reproducibility (97%), and stability (30 days) with a superior Raman signal enhancement reaching an ultralow detection limit of 0.5 × 10-13 M compared to the nanosphere particles which could show an LOD of 0.5 × 10-9 M.


The role of lymphadenectomy in the management of renal cell carcinoma.
The role of lymphadenectomy in the management of renal cell carcinoma has been established in staging but is less well defined as a therapeutic maneuver. Level one evidence suggests no survival benefit or increased complication rate with lymphadenectomy when performed concurrently with radical nephrectomy. However, several retrospective studies have identified a survival benefit when patients with increased risk of micrometastatic lymph node disease undergo lymphadenectomy. We perform a selective review of the literature and present the historical basis, risk assessment, use and development of nodal templates, and therapeutic benefits associated with the use of lymphadenectomy in the management of renal cell carcinoma.


Specificity of molecular changes in neurons involved in memory storage.
Evidence implicating molecular steps in memory storage is discussed, particularly with reference to molecular specificity and uniqueness and the possible relevance of these steps to other types of long-lasting transformations such as those of development, regeneration, and tumorigenesis. The role of protein kinase C-mediated phosphorylation of identified protein subtrates, such as a 20,000-dalton GTP-binding protein, is described for associative memory of the snail Hermissenda, associative conditioning of the rabbit, and long-term potentiation. Cyclic AMP-mediated phosphorylation during sensitization of the snail Aplysia is also examined.


High prevalence of parkinsonism in patients with MCI or mild Alzheimer's disease.
The objective of this study was to examine the prevalence of the coexistence of parkinsonism in patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD). Outpatients were evaluated with Mini-Mental State Examination, Clinical Dementia Rating Scale, NIA-AA criteria, MRI, and 123I-IMP SPECT (3D-SSP). Parkinsonism in patients diagnosed with MCI (Mini-Mental State Examination ≥24, n = 63) or mild AD (Mini-Mental State Examination 20-23, n = 43) was examined using the Unified Parkinson's Disease Rating Scale-III and 123I-FP-CIT dopamine transporter SPECT. One hundred six patients (60-97 years) were enrolled. Fifty-six patients (52.8%) were diagnosed as having concomitant parkinsonism with rigidity and resting tremor and dopamine transporter reduction in the basal ganglia. The mean (SD) age (n = 56) was 80.6 (6.1) years, significantly older than patients without parkinsonism [77.6 (7.0) years, n = 50] (P < .05). The mean (SD) UPDRS-III score was 5.8 (2.4). The prevalence rate of the coexistence of mild parkinsonism in MCI or mild AD may be higher than previously recognized.


Expression of epidermal growth factor, transforming growth factor-alpha and their receptor genes in human gastric carcinomas; implication for autocrine growth.
The expressions of mRNA for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and EGF receptor (EGFR) genes were examined in 7 human gastric carcinoma cell lines and 15 gastric carcinoma tissues and the corresponding normal mucosas. All of the gastric carcinoma cell lines expressed mRNA for EGFR and TGF-alpha genes. TMK-1 and MKN-28 cells also expressed EGF mRNA. Production of EGF, TGF-alpha and EGFR protein by gastric carcinoma cell lines was also confirmed by EGF and TGF-alpha specific monoclonal antibody binding. As for surgical specimens, EGFR and TGF-alpha mRNA were detected at high levels in all the tumor tissues. Interestingly, EGF mRNA was detected in 5 (33.3%) of the 15 gastric carcinomas but it was not detected in normal tissues. Moreover, anti-EGF and anti-TGF-alpha monoclonal antibodies inhibited the spontaneous 3H-TdR uptake by gastric carcinoma cells. These results suggest that EGF and/or TGF-alpha produced by tumor cells act as autocrine growth factors for gastric carcinomas.


A study of longitudinal data examining concomitance of pain and cognition in an elderly long-term care population.
To examine if a concomitant relationship exists between cognition and pain in an elderly population residing in long-term care. Prior research has found that cognitive load mediates interpretation of a stimulus. In the presence of decreased cognitive capacity as with dementia, the relationship between cognition and increasing pain is unknown in the elderly. Longitudinal cohort design. Data collected from the Minimum Data Set-Resident Assessment Instrument (MDS-RAI) from the 2001-2003 annual assessments of nursing home residents. A covariance model was used to evaluate the relationship between cognition and pain at three intervals. The sample included 56,494 subjects from nursing homes across the United States, with an average age of 83 ± 8.2 years. Analysis of variance scores (ANOVAs) indicated a significant effect (P < 0.01) for pain and cognition, with protected t test revealing scores decreasing significantly with these two measures. Relative stability was found for pain and cognition over time. Greater stability was found in the cognitive measure than the pain measure. Cross-legged effects observed between cognition and pain measures were inconsistent. A concomitant relationship was not found between cognition and pain. Even though the relationship was significant at the 0.01 level, the correlations were low (r ≤ 0.08), indicating a weak association between cognition and pain. Understanding the concomitance of pain and cognition aids in defining additional frameworks to extend models to include secondary needs, contextual factors, and resident outcomes. Cognitive decline, as with organic brain diseases, is progressive. Pain is a symptom that can be treated and reduced to improve resident quality of life. However, cognition can be used to determine the most appropriate method to assess pain in the elderly, thereby improving accuracy of pain detection in this population.


Matching kinetics of synaptic vesicle recycling and enhanced neurotransmitter influx by Ca2+ in brain plasma membrane vesicles.
Using native plasma membrane vesicle suspensions from the rat cerebral cortex under conditions designed to alter intravesicular [Ca2+], we found that Ca2+ induced 47 +/- 5% more influx of [3H]GABA, [3H]D-aspartate and [3H]glycine at 37 degrees C with half-times 1.7 +/- 0.5, 1.3 +/- 0.4 and 1.3 +/- 0.4 min, respectively. We labelled GABA transporter sites with the uptake inhibitor, [3H]-(R,S)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid and found that Ca2+ induced a partial dissociation of the bound inhibitor from GABA transporter sites with a similar half-time. By means of rapid kinetic techniques applied to native plasma membrane vesicle suspensions, containing synaptic vesicles stained with the amphipathic fluorescent styryl membrane probe N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl]pyrid inium dibromide, we have measured the progress of the release and reuptake of synaptic vesicles in response to Ca2+ and high-[K+] depolarization in the 0.0004-100 s range of time. Synaptic vesicle exocytosis, strongly influenced by external [Ca2+], appeared with the kinetics accelerated by depolarization. These results are consistent with the potential involvement of Ca2+ in taking low-affinity transporters to the plasma membrane surface via exocytosis.


Plasma profiles of matrix metalloproteinases and tissue inhibitors of the metalloproteinases predict recurrence of atrial fibrillation following cardioversion.
Atrial fibrosis is considered to contribute to atrial fibrillation (AF) recurrence following cardioversion. This study tested the hypothesis that circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can predict AF recurrence postcardioversion. Precardioversion plasma samples (n = 82) were assayed for MMPs (eight types), TIMPs (all four types), N-terminus pro B-type natriuretic peptide, and high-sensitivity C-reactive protein levels. Patients were followed for AF recurrence postcardioversion. Despite 100 % restoration of sinus rhythm, 36 (44 %) reverted to AF within 3 months. Left atrial volume was increased in patients in whom AF recurred. Precardioversion MMP-9 was higher and TIMP-4 lower with AF recurrence. MMP-9, MMP-3, and TIMP-4 independently predicted AF recurrence. In multivariate analysis, combination of MMP-9, MMP-3, and TIMP-4 increased prediction of AF recurrence. Circulating levels of MMPs and TIMPs predict AF recurrence postcardioversion and may be used in a novel biomarker panel to guide AF stratification and therapy.


Primary structure of human alpha 2-macroglobulin. I. Isolation of the 26 CNBr fragments, amino acid sequence of 13 small CNBr fragments, amino acid sequence of methionine-containing peptides, and alignment of all CNBr fragments.
The isolation of the 26 CNBr fragments from the identical Mr = 180,000 subunits of human alpha 2-macroglobulin is described. The fragments have been purified by combinations of gel chromatography, ion-exchange chromatography, high voltage paper electrophoresis, paper chromatography, and high performance liquid chromatography. The complete amino acid sequences of 13 small CNBr fragments have been determined. These fragments include CB1 (residues 1-9), CB3 (residues 79-98), CB4 (residues 99-128), CB9 (residues 442-477), CB10 (residues 478-497), CB13 (residues 644-650), CB14 (residues 651-665), CB15 (residues 666-674), CB16 (residues 675-690), CB19 (residues 937-945), CB20 (residues 946-954), CB24 (residues 1356-1362), and CB25 (residues 1363-1375). The fragments determined account for 200 of the 1451 residues of the subunits of alpha 2-macroglobulin. Most likely, Cys-6 of CB9 is bound to the corresponding residue in CB9 from another subunit, thus forming an interchain disulfide bridge in alpha 2-macroglobulin. Cys-1 of CB15 is bound to Cys-35 of CB12. CB15 contains a pair of Gln residues that can react covalently with amines in a factor XIIIa-catalyzed process (Gln-5 and Gln-6). CB16 contains the primary cleavage sites for proteinases in the bait region of alpha 2-macroglobulin (-Arg7-Val-Gly-Phe-Tyr-Glu-). CB20 contains the residues which in native alpha 2-macroglobulin presumably form an internal reactive beta-cysteinyl-gamma-glutamyl thiol ester (Cys-4 and Glx-7). Partial NH2- and COOH-terminal sequence data are given for the 13 large CNBr fragments. Complete or partial sequence determination of 19 methionine-containing peptides or variants thereof allow the alignment of all the CNBr fragments.


Macrophage activation by lipopolysaccharide, interferon-gamma and interleukin-4: effect of fatty acid metabolism.
The aim of this study was to investigate the effects of interferon-gamma and -beta (IFN-gamma, -beta), interleukin-4 and -10 (IL-4, -10) and Hpopolysaccharide (LPS) on the metabolism and composition of phospholipid fatty acids in macrophages. Murine J774.2 macrophages were incubated with radiolabelled fatty acids and the appropriate stimulus and the incorporation and composition of the phospholipid classes was determined. IFN-gamma and IL-4 specifically stimulated enhanced incorporation of [(14)C]-linoleic acid into the phosphatidytethanolamine fraction. IL-4 (in contrast to IFN-gamma and LPS) reduced incorporation of [(14)C]- arachidonic acid into phosphatidylinositol. Incubation of J774.2 cells with linoleic acid significantly increased TNFalpha and nitric oxide production; arachidonic acid enhanced TNFalpha production but reduced nitric oxide production. It is concluded that IFN-gamma, IL-4 and IL-10 may differentially regulate macrophage activation via effects on the metabolism of polyunsaturated fatty acids.


Artificial RNA aptamer production by the marine bacterium Rhodovulum sulfidophilum: improvement of the aptamer yield using a mutated transcriptional promoter.
Noncoding small RNAs and artificial RNA aptamers are now expected to be potential candidates for RNA therapeutic agents. We previously proposed a unique method for economical production of these RNAs using the marine phototrophic bacterium Rhodovulum sulfidophilum. This bacterium does not produce any ribonucleases but does produce extracellular nucleic acids in the culture medium in nature. Using this bacterium and an engineered plasmid containing the rrn promoter for the RNA expression, we developed a method for production of the streptavidin RNA aptamer in the culture medium. However, the yield of this RNA product in the culture medium by this method was not enough for practical use. In the present paper, we improved the yield of this product by modification of the -35 region of the rrn promoter so as to escape from the Fis protein control and the use of a new vector plasmid. Using this system, the extracellular RNA aptamer of approximately 200 ng and the total RNA aptamer (both extra- and intracellular form) of about 20 μg from 1 L culture were accomplished by constitutive expression of the gene.


The need for quality improvement in sweat testing infants after newborn screening for cystic fibrosis.
The proportion of insufficient sweat tests after positive newborn screening for cystic fibrosis was determined. Infants ≤ 3 months old had a mean (± standard deviation) rate of 7.2% (± 7.6) (range, 0% to 40%). Collection methods did not affect the rates. The high and variable rates indicate a need for quality improvement.


Effect of Family Size and Type on Maternal Rejection of Children With ADHD.
This study examined the impact of family size and type on maternal rejection and its relationship with emotional-behavioral difficulties in children with ADHD compared to those typically developing. The participants were mothers of 7- to 12-year-old children with ADHD (n = 102) and mothers of typically developing children (n = 102) in Kazakhstan. In this cross-sectional study, multiple linear regression analysis was performed to explore the relationship between variables. Family size affected maternal rejection after accounting for children's emotional-behavioral difficulties only in mothers of children with ADHD. The effect of family type on maternal rejection was statistically significant in both groups. Family size exacerbated the relationship between children's emotional-behavioral difficulties and maternal rejection only in children with ADHD. The moderating effect of family type was not found in either group. Our findings suggest that family size and type contribute to maternal rejection of children with ADHD.


An assessment of the levels of phthalate esters and metals in the Muledane open dump, Thohoyandou, Limpopo Province, South Africa.
This work reports the determination of the levels of phthalate esters (dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), diethyl hexyl phthalate (DEHP)) and metals (lead, cadmium, manganese, zinc, iron, calcium) in composite soil samples. The soil samples were collected randomly within the Muledane open dump, Thohoyandou, Limpopo province, South Africa. Control samples were collected about 200 m away from the open dump. The phthalate esters were separated and determined by capillary gas chromatography with a flame ionization detector, whilst the metals were determined by atomic absorption spectrophotometry. Open dump values for the phthalate esters and metals to be generally higher in comparison to control samples for DMP, DEP, DBP and DEHP - the mean values calculated were 0.31 +/- 0.12, 0.21 +/- 0.05, 0.30 +/- 0.07, and 0.03 +/- 0.01 mg/kg, respectively, for the open dump soil samples. Nonetheless, the mean open dump values for lead, cadmium, manganese, zinc, iron and calcium were 0.07 +/- 0.04, 0.003 +/- 0.001, 5.02 +/- 1.92, 0.31 +/- 0.02, 11.62 +/- 9.48 and 0.12 +/- 0.13 mg/kg, respectively. The results were compared statistically. Our results revealed that the discarding of wastes into the open dump is a potential source of soil contamination in the immediate vicinity and beyond, via dispersal. Increased levels of phthalate esters and metals in the soil pose a risk to public health, plants and animals. Sustained monitoring of these contaminants is recommended, in addition to upgrading the facility to a landfill.


Compliance, low literacy, and locus of control.
Compliance remains a critical, complex issue in health care today. As outlined, many interrelated factors affect levels of compliance and noncompliance. Assessing literacy and locus of control may assist the health care professional in identifying persons less likely to comply with medical treatments. Although compliance remains difficult to predict, these components should be considered carefully in patient-professional relationships and patient education.


Seroprevalence of Toxoplasma gondii in the Iranian pregnant women: A systematic review and meta-analysis.
Toxoplasmosis is a common and serious parasitic disease with high prevalence and global distribution in human and other warm-blooded vertebrates. Though the infection of Toxoplasma gondii is usually asymptomatic in healthy people, it can lead to severe pathological effects to the fetus of infected women and immunocompromised patients. So pinpointing the risk factors and control procedures are of important works among these populations. In order to reach this goal, we conducted a systematic review and meta-analysis to identify the seroprevalence rate of T. gondii infection among Iranian pregnant women population to achieve a comprehensive explanation of the disease condition in Iran for future use. English electronic databases (PubMed, Science Direct, Scopus, Ovid and Cochrane) and Persian language databases (Scientific Information Database, Iran Medex, Magiran and Iran Doc) were searched. Furthermore, the proceedings of Iranian parasitology congresses were explored manually. Our review resulted in a total of 50 publications meeting the inclusion criteria during Jan 1990-June 2015. Totally, 20221 women had been tested during this period of which 7724 women had seropositivity for IgG. According to results of heterogeneity test, either Der Simonian and Laird's random-effects method or Mantel-Haenszel's fixed-effects method were used to pool the estimations. Weighted overall prevalence of toxoplasmosis in pregnant women were obtained using random-effects model, which was estimated 41% (95% CI=36-45%). Also IgG and IgM antibodies was obtained 38% (95% CI=34-42%) and 4% (95% CI=3-5%), respectively. The highest and the lowest seroprevalence of toxoplasmosis in five geographical zones of Iran were observed in South 53% (95% CI=30-77%) and East 33% (95% CI=23-42%), respectively. In order to detect publication bias, Egger's regression test was done which revealed that publication bias might not have a significant influence on overall prevalence estimate (P=0.89). Multivariate analysis showed that there's a statistically significant correlation between toxoplasmosis and two risk factors including "place of residence" (P=0.005) and "contact with cat" (P=0.002). There was no significant difference between toxoplasmosis and the other surveyed risk factors. It is highly recommended to further study for the aim of better disease management and developing more efficient diagnostic tests.


Morphological and immunohistochemical analysis of proteins CASPASE 3 and XIAP in rats subjected to cerebral ischemia and chronic alcoholism.
To evaluate histopathological and ultrastructural changes and expression of proteins related to apoptosis CASPASE 3 and XIAP after experimental induction of temporary focal cerebral ischemia (90 minutes) due to obstruction of the middle cerebral artery in alcoholism model. Forty adult Wistar rats were used, subdivided into 5 experimental groups: control group (C); Sham group (S); Ischemic group (I); Alcoholic group (A); and Ischemic and Alcoholized group (I+A): animals submitted to the same treatment of group A and after four weeks were submitted to focal cerebral ischemia during 90 minutes, followed by reperfusion of 48 hours. Were processed for histopathological analysis and immunohistochemistry (for the protein expression of CASPASE -3 and XIAP). Greater histopathological changes were observed in the animals of groups I and I+A in the three areas analyzed. The neuronal loss was higher in the medial striatum region of the animals of groups I and I + A. The protein expression of CASPASE -3 was higher than that of XIAP in the groups I and I + A for both proteins. The expression of XIAP was slightly higher where the histopathological changes and expression of CASPASE -3 was less evident.


Use of Matrigel in culture affects cell phenotype and gene expression in the first trimester trophoblast cell line HTR8/SVneo.
There is inconsistent use of Matrigel for experiments with the HTR8/SVneo first trimester trophoblast and other cell lines. We quantified the effects of Matrigel on the expression of genes considered to be markers of extravillous cytotrophoblast (EVT) differentiation and invasive potential. Culture on Matrigel promoted formation of "endothelial-like" tubes and reduced mRNA expression of matrix metalloproteinase 2 (MMP2), cytokeratin 7 (KRT7) and integrin alpha 1 (ITGA1), while increasing VE-cadherin (CDH5) expression consistent with a vascular phenotype. This process may constitute part of the endothelial cell mimicry exhibited by endovascular EVTs invading the maternal spiral arteries. HTR8/SVneo appears to be phenotypically polymorphic and adopt endovascular morphology on Matrigel.


2G waste lignin to fuel and high value-added chemicals: Approaches, challenges and future outlook for sustainable development.
Lignin is produced as a byproduct in cellulosic biorefinery as well in pulp and paper industries and has the potential for the synthesis of a variety of phenolics chemicals, biodegradable polymers, and high value-added chemicals surrogate to conventional petro-based fuels. Therefore, in this critical review, we emphasize the possible scenario for lignin isolation, transformation into value addition chemicals/materials for the economic viability of current biorefineries. Additionally, this review covers the chemical structure of lignocellulosic biomass/lignin, worldwide availability of lignin and describe various thermochemical (homogeneous/heterogeneous base/acid-catalyzed depolymerization, oxidative, hydrogenolysis etc.) and biotechnological developments for the production of bio-based low molecular weight phenolics, i.e. polyhydroxyalkanoates, vanillin, adipic acid, lipids etc. Besides, some functional chemicals applications, lignin-formaldehyde ion exchange resin, electrochemical and production of few targeted chemicals are also elaborated. Finally, we examine the challenges, opportunities and prospects way forward related to lignin valorization.


Influence of surface modification on structure formation and micromechanical properties of spray-dried silica aggregates.
Spray drying processes were utilized for the production of hierarchical materials with defined structures. The structure formation during the spray drying process and the micromechanical properties of the obtained aggregates depend on the particle-particle interactions, the primary particle size and morphology as well as the process parameters of the spray drying process. Hence, the effect of different primary particle systems prepared as stable dispersions with various surface modifications were investigated on the colloidal structure formation and the micromechanical properties of silica particles as model aggregates and compared to theoretical considerations. The obtained results show that the structure formation of aggregates during the spray drying process for stable suspensions is almost independent on the functional groups present at the particle surface. Further, the mechanical properties of these aggregates differ considerably with the content of the bound ligand. This allows the defined adjustment of the aggregate properties, such as the strength and surface properties, as well as the formation of defined hierarchical aggregate structures.


Fluoride bioaccumulation by hydroponic cultures of camellia (Camellia japonica spp.) and sugar cane (Saccharum officinarum spp.).
The ability of hydroponic cultures of camellia and sugar cane adult plants to remove fluoride was investigated. Plants were grown in a 50% Steiner nutrient solution. After an adaptation period to hydroponic conditions, plants were exposed to different fluoride concentrations (0, 2.5, 5 and 10 mg L(-1)). Fluoride concentration in the culture medium and in tissues was measured. In sugar cane, fluoride was mainly located in roots, with 86% of it absorbed and 14% adsorbed. Sugar cane plants removed 1000-1200 mg fluoride kg(-1) dry weight. In camellia plants the highest fluoride concentration was found in leaf. Roots accumulated fluoride mainly through absorption, which was 2-5 times higher than adsorption. At the end of the experiment, fluoride accumulation in camellia plants was 1000-1400 mgk g(-1) dry weight. Estimated concentration factors revealed that fluoride bioaccumulation is 74-221-fold in camellia plants and 100-500-fold in sugar cane plants. Thus, the latter appear as a suitable candidate for removing fluoride from water due to their bioaccumulation capacity and vigorous growth rate; therefore, sugar cane might be used for phytoremediation.


Patient sexual orientation and gender identity disclosure.
In the UK, 2.3% of men and 1.6% of women identify as lesbian, gay or bisexual (LGB). Of the UK population, 1% are estimated to identify as transgender (T). Of the LGB population, 46% do not disclose their sexual orientation to health care professionals (HCPs) and 18% of transgender patients avoid health care altogether. Non-disclosure of sexual orientation and/or gender identity contributes to worse health outcomes for LGBT patients. This study aimed to explore medical students' perceptions of the barriers to health care for LGBT patients and the importance of patient disclosure of sexual orientation or gender identity. Focus groups included medical students across five year-groups from a medical school in the South East of England. Discussions followed a pre-approved topic guide with a primary and co-facilitator present. Focus groups were audio-recorded, transcribed verbatim and the data underwent framework analysis. Forty-five undergraduate medical students participated (40% of whom were non-heterosexual). Most participants believed that the incorrect use of pronouns and discrimination would be a cause for non-disclosure of gender identity and sexual orientation to HCPs. Several participants thought it was more important to know a patient's gender identity than sexual orientation. Many participants felt that collecting sexual orientation information on healthcare registration forms is acceptable. More education regarding LGBT health needs and ways to encourage patient disclosure of sexual orientation or gender identity should be included in the undergraduate medical school curricula to increase the competency of future doctors when interacting with LGBT patients.


Kinetic modeling of microalgal growth and lipid synthesis for biodiesel production.
A mathematical modeling of microalgae biomass is an essential step to optimize the biomass and lipid production rate and to reduce the cost of microalgal biodiesel production system. In the present study, kinetic studies were carried out to describe the growth and neutral lipid production of two marine microalgae Chlorella salina and Nannochloropsis oculata under the nitrogen-repleted and -depleted conditions using logistic and Luedeking-Piret equations. This research paper provides the information on mathematically efficient procedure to predict suitable environment condition for biomass and lipid production. The predicted results were compared with experimental data, which showed that this model closely agreed with simulated results. From this investigation, it was found that nitrogen was an essential nutrient for algal growth, which increased under nitrogen-rich condition, whereas during nitrogen-limited condition some loss in growth was observed but with increased lipid content. Since metabolic changes occurred under nitrogen- depleted state, the protein and carbohydrate pathways were shifted to lipid biosynthesis.


CUI-Net: a correcting uneven illumination net for low-light image enhancement.
Uneven lighting conditions often occur during real-life photography, such as images taken at night that may have both low-light dark areas and high-light overexposed areas. Traditional algorithms for enhancing low-light areas also increase the brightness of overexposed areas, affecting the overall visual effect of the image. Therefore, it is important to achieve differentiated enhancement of low-light and high-light areas. In this paper, we propose a network called correcting uneven illumination network (CUI-Net) with sparse attention transformer and convolutional neural network (CNN) to better extract low-light features by constraining high-light features. Specifically, CUI-Net consists of two main modules: a low-light enhancement module and an auxiliary module. The enhancement module is a hybrid network that combines the advantages of CNN and Transformer network, which can alleviate uneven lighting problems and enhance local details better. The auxiliary module is used to converge the enhancement results of multiple enhancement modules during the training phase, so that only one enhancement module is needed during the testing phase to speed up inference. Furthermore, zero-shot learning is used in this paper to adapt to complex uneven lighting environments without requiring paired or unpaired training data. Finally, to validate the effectiveness of the algorithm, we tested it on multiple datasets of different types, and the algorithm showed stable performance, demonstrating its good robustness. Additionally, by applying this algorithm to practical visual tasks such as object detection, face detection, and semantic segmentation, and comparing it with other state-of-the-art low-light image enhancement algorithms, we have demonstrated its practicality and advantages.


Fronto-striatal dynamic connectivity is linked to dopaminergic motor response in Parkinson's disease.
Differences in dopaminergic motor response in Parkinson's disease (PD) patients can be related to PD subtypes, and previous fMRI studies associated dopaminergic motor response with corticostriatal functional connectivity. While traditional fMRI analyses have assessed the mean connectivity between regions of interest, an important aspect driving dopaminergic response might lie in the temporal dynamics in corticostriatal connections. This study aims to determine if altered resting-state dynamic functional network connectivity (DFC) is associated with dopaminergic motor response. To test this, static and DFC were assessed in 32 PD patients and 18 healthy controls (HC). Patients were grouped as low and high responders using a median split of their dopaminergic motor response. Patients featuring a high dopaminergic motor response were observed to spend more time in a regionally integrated state compared to HC. Furthermore, DFC between the anterior midcingulate cortex/dorsal anterior cingulate cortex (aMCC/dACC) and putamen was lower in low responders during a more segregated state and correlated with dopaminergic motor response. The findings of this study revealed that temporal dynamics of fronto-striatal connectivity are associated with clinically relevant information, which may be considered when assessing functional connectivity between regions involved in motor initiation.


Successful treatment with 5-fluorouracil of conjunctival intraepithelial neoplasia refractive to mitomycin-C.
To describe the histopathological findings and successful treatment with 5-fluorouracil (5-FU) of a conjunctival intraepithelial neoplasia with limbal stem cell deficiency that was refractive to topical mitomycin-C (MMC). Interventional case report. A 64-year-old male patient presented with a diffuse conjunctival intraepithelial neoplasia (CIN) that was excised with concurrent keratoepithelioplasty. Because of a recurrence and the presence of limbal stem cell deficiency, he was placed on topical MMC. Despite two courses of MMC, the tumor size did not decrease, and topical 5-FU was started 1 year after MMC therapy began. Limbal autograft transplantation was performed thereafter. The clinical and histopathologic findings including impression cytology and biomicroscopic observations. After 5-FU treatment, the patient was free of the tumor clinically and cytologically, and the corneal surface had cleared. No recurrence was observed during the 30 months after the 5-FU therapy. Serious complications have not been observed. Topical 5-FU may be a therapeutic option for the treatment of patients with MMC-resistant CINs. The success of 5-FU is believed to be the result of a difference in the mechanism of cytotoxicity of MMC and 5-FU or the additive effects of the two agents.


Analysis of motility and mucociliary function of tracheal epithelial cilia.
The airway epithelium contains numerous multiciliated cells. The apical surface of multiciliated cells is covered with cilia that move at 15-25Hz. Ciliary movement is not a simple reciprocal movement and distinctly has forward and reverse movements called effective and recovery strokes, respectively. These "asymmetric" ciliary strokes push away the mucus covering the mucosa of the airway epithelium. Mucus flow created by ciliary stroke is important for capturing and expelling dust, pollen, PM2.5, pathogens, and other particles that enter the airways from outside the body. This mechanism for protecting the airways produced by ciliary movement is called mucociliary function. Defects in ciliary motility lead to impairment of mucociliary function, resulting in recurrent airway infections such as bronchitis and pneumonia, and consequently, bronchiectasis. While the analysis of ciliary beat frequency is relatively easy, the analyses of the amplitude, velocities of strokes, and the asymmetric level require specific techniques and tips. In this chapter, we present methods for the analysis of ciliary movements of a group of cilia on the luminal surface of the trachea ex vivo and individually isolated and ATP-reactivated cilia in vitro. In addition, a method for the analysis of mucociliary function is also presented.


On the stabilization of animal numbers. Problems of testing : 2. Conforntation with data from the field.
When testing for regulation of population numbers, rather than using Bulmer's second test in cases where population numbers are estimated instead of measured, we prefer to correct Bulmer's first test for estimation error. A correction method is expounded, discussed, and applied to two series of census data: the pine looper of Klomp and the garden chafer of Milne. In neither case the tentative conclusion from using the uncorrected test was changed after correction. Therefore, in practice Bulmer's first test without correction can be used well as a first orientation. Twelve long series (more than 10 years) of census data of both univoltine and semelparous (a necessary condition) insects were tested for significant density dependence in the fluctuations of numbers with the randomization test of Pollard et al. None of the series, all we could find to meet the necessary condition as well as being longer than 10 years, showed significant density dependence at the 0.05 level, though the pine looper of Klomp did so at the 0.1 level. Next, the same series were tested for regulation in the sense of "keeping density within limits" with both the first test of Bulmer and the permutation test of Reddingius and Den Boer. Onky Klomp's pine looper population at "Hoge Veluwe" scored significantly. In a following paper this population will be considered more closely, in order to enable understanding of this test result.


Equilibrium and kinetic selectivity profiling on the human adenosine receptors.
Classical evaluation of target selectivity is usually undertaken by measuring the binding affinity of lead compounds against a number of potential targets under equilibrium conditions, without considering the kinetics of the ligand-receptor interaction. In the present study we propose a combined strategy including both equilibrium- and kinetics-based selectivity profiling. The adenosine receptor (AR) was chosen as a prototypical drug target. Six in-house AR antagonists were evaluated in a radioligand displacement assay for their affinity and in a competition association assay for their binding kinetics on three AR subtypes. One of the compounds with a promising kinetic selectivity profile was also examined in a [(35)S]-GTPγS binding assay for functional activity. We found that XAC and LUF5964 were kinetically more selective for the A1R and A3R, respectively, although they are non-selective in terms of their affinity. In comparison, LUF5967 displayed a strong equilibrium-based selectivity for the A1R over the A2AR, yet its kinetic selectivity thereon was less pronounced. In a GTPγS assay, LUF5964 exhibited insurmountable antagonism on the A3R while having a surmountable effect on the A1R, consistent with its kinetic selectivity profile. This study provides evidence that equilibrium and kinetic selectivity profiling can both be important in the early phases of the drug discovery process. Our proposed combinational strategy could be considered for future medicinal chemistry efforts and aid the design and discovery of different or even better leads for clinical applications.