Why Be Temperate: Lessons from Bacteriophage λ.
Many pathogens have evolved the ability to induce latent infections of their hosts. The bacteriophage λ is a classical model for exploring the regulation and the evolution of latency. Here, I review recent experimental studies on phage λ that identify specific conditions promoting the evolution of lysogenic life cycles. In addition, I present specific adaptations of phage λ that allow this virus to react plastically to variations in the environment and to reactivate its lytic life cycle. All of these different examples are discussed in the light of evolutionary epidemiology theory to disentangle the different evolutionary forces acting on temperate phages. Understanding phage λ adaptations yield important insights into the evolution of latency in other microbes, including several life-threatening human pathogens.


Relationship between Epstein-Barr virus genome number, amount of nuclear antigen, and early antigen inducibility in diploid and tetraploid lymphoma cells of related origin.
In a collection of near-diploid and near-tetraploid Raji sublines and somatic Raji/Raji hybrids a linear relationship was found between the number of Epstein-Barr virus (EBV) genome copies and the relative amount of EBV-determined nuclear antigen per cell. Inducibility of the viral cycle by iododeoxyuridine and by P3HR-1 virus superinfection coulb be related to the number of resident EBV genome copies per haploid target cell. The implications of these findings are discussed.


The effect of electrical stimulation, fasting and anesthesia on the carnitine(s) and acyl-carnitines of rat white and red skeletal muscle fibres.
Time courses for the effect of electrical stimulation, fasting and sampling mode (anesthesia vs decapitation) on the quantitative distribution of carnitine and its esters in fast white and fast red skeletal muscle fibres of rats were determined. Both fibre types responded similarly to electrical stimulation with respect to changes in acetyl- and propionylcarnitine, but the time course was very different. The proportion of esterified carnitine decreased with fasting and anesthesia in both fibres compared to the fed decapitated group. This shift in the acylation state of carnitine was mainly due to the decrease of acetylcarnitine levels. The data show that the use of anesthetics may induce significant quantitative changes in specific acylcarnitine levels, presumably reflecting changes in specific acylcoenzyme A levels.


Usefulness of mean corpuscular volume as a surrogate marker for monitoring thiopurine treatment in inflammatory bowel disease.
Thiopurines are commonly used drugs in inflammatory bowel disease. Intracellular levels of thiopurine metabolites [i.e. 6-thioguaninenucleotides (6-TGN)] are associated with efficacy and toxicity. Because 6-TGN measurement is not globally available, the mean corpuscular volume (MCV) has been proposed as a surrogate marker for monitoring thiopurine therapy. To analyze the relationship between MCV and efficacy of thiopurines, defined as either response to therapy or 6-TGN levels. A systematic search on PubMed was performed. Fifteen studies were included. In six studies, a positive association was found between ΔMCV and 6-TGN. In four studies, it was suggested that ΔMCV can be used to predict clinical remission. In five articles, no association was found. In the majority of articles, it was reported that ΔMCV is useful in guiding intracellular metabolite levels. However, there is insufficient evidence showing that ΔMCV can predict clinical remission.


Age-specific differences in the winter foraging strategies of rooks Corvus frugilegus.
Foraging efficiency and intraspecific competition were compared between wild adult and immature rooks Corvus frugilegus with respect to flock size. Behavioural time budgets, and observations of prey selection and prey energetic values revealed that adult rooks in large flocks (> 50 individuals) consumed smaller, less profitable prey, but allocated more time to feeding and fed at a faster rate and with greater success than adults in small flocks. By contrast, immature rooks in flocks of more than 30 individuals allocated proportionally less time to feeding, fed at a lower rate and fed with no increase in success rate than when foraging in smaller flocks. Agonistic encounters and the avoidance of adults by immature rooks appeared responsible for such inefficient foraging. Hence immature rooks showed a preference for smaller flocks (< 50 individuals) with low adult: immature ratios while adults preferred larger flocks (> 50 individuals). We discuss the possible influence of competitive disadvantages on immature rook distribution, flock composition and post-natal dispersal.


Prevalence and risk factors of depression in patients with drug-resistant tuberculosis in Nepal: A cross-sectional study.
Patients with drug-resistant tuberculosis (DR TB) have a protracted course of illness and the available treatment has a low success rate. These factors combined with the associated stigma and financial implications put the patients with DR TB at an increased risk of depression. The psychiatric side effects of anti-tuberculosis drugs further aggravate the problem. This study aimed to estimate the prevalence of depression among patients with DR TB in Nepal and identify risk factors. We conducted this cross-sectional study in April 2018 at all the functioning 11 programmatic DR TB treatment centers across Nepal. We selected 129 patients aged ≥ 16 years receiving treatment for DR TB by non-probability quota sampling. Six trained data collectors conducted face-to-face interviews and administered the Nepali language version of Patient Health Questionnaire 9 (PHQ-9) to screen for depression. We summarized sociodemographic and treatment characteristics with median (Interquartile Range [IQR]) and proportions as appropriate. We performed univariate analysis for the variables hypothesized as risk factors for depression. We fitted a multivariable binary logistic regression model with depression as the outcome variable and the variables with a significance level of < 0.25 as explanatory variables. We regarded a p-value of < 0.05 as significant for individual variables in the logistic regression model. Of the 129 patients studied, 92 (71.3%) were male and the median age was 36 years (IQR 25-48). The majority (109, 84.4%) had multi-drug resistant tuberculosis (MDR TB). We identified 81 patients (62.7%, 95% Confidence Interval [CI] 53.7-71) with the PHQ-9 score of 10 or more signifying probable depressive disorder. In univariate analyses, age, treatment center location, DR TB treatment duration, and duration of current illness had a p-value lower than the pre-specified cut-off of 0.25. In the multivariable logistic regression model, we found a statistically significant association of depression with the duration of illness (adjusted Odds Ratio 1.15, 95% CI 1.07-1.26, p < 0.001). This study has found that a large proportion of the patients with DR TB screened have depression suggesting the need for screening and management of comorbid depression within the National TB Control Program.


Endovascular management of exsanguinating vertebral artery transection.
Vertebral artery (VA) transection is a rarely described entity that may present dramatically with a life-threatening external hemorrhage. A 25-year-old man that was victim of a terrorist attack presented a gunshot wound to the mouth with massive bleeding. The bullet perforated the oropharynx and injured the right VA. Combined antegrade and retrograde endovascular embolization by means of detachable coils allowed rapid control of the bleeding. Bleeding related to VA transection can be managed safely by means of endovascular combined approaches.


Effects of acupuncture on cardiovascular risks in patients with hypertension: a Korean cohort study.
The aim of this study was to investigate the effects of acupuncture on major adverse cardiovascular events (MACE), myocardial infarction, stroke and death in hypertensive patients taking anti-hypertensives. Using the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database, this study identified 59,370 patients taking anti-hypertensives who had been diagnosed with hypertension between 2003 and 2006. They were divided into acupuncture and non-acupuncture groups. The follow-up period ended with the diagnosis of myocardial infarction, stroke or death. After propensity score matching (PSM), there were 18,011 patients each in the non-acupuncture and acupuncture groups. We calculated the incidence rate, hazard ratio (HR) and 95% confidence interval (CI) for MACE, myocardial infarction, stroke and death in patients with hypertension using a stratified Cox proportional hazard model. In addition, secondary outcome analyses for stroke and cardiovascular mortality were performed. After PSM, the HRs for MACE (0.83, 95% CI 0.80-0.86), all-cause mortality (0.73, 95% CI 0.70-0.76) and myocardial infarction (0.85, 95% CI 0.79-0.92) were significantly lower in the acupuncture group than in the non-acupuncture group. Moreover, the HRs for stroke-related mortality, hemorrhage stroke-related mortality, ischemic stroke-related mortality, ischemic heart disease-related mortality and circulatory system disease-related mortality were significantly lower in the acupuncture group than in the non-acupuncture group. This observational study with long-term follow-up extends the evidence base in support of the effectiveness of acupuncture for the management of hypertension and potentially reduce the burden of cardiovascular disease.


Successful fertilization of Varicorhinus macrolepis eggs with sperm subjected to two freeze-thaw cycles.
Although sperm from several fish species have been successfully cryopreserved, few studies have been done in small and/or endangered species. The aim of the present work was to develop a method of freezing and refreezing Varicorhinus macrolepis semen in 1.8 mL cryovials. The effect of extenders and cryoprotectants on the motility of post-thaw sperm was examined. The motility of frozen-thawed sperm in extender D-15 was higher than that in MPRS and fish Ringer solution (P<0.05). Dimethyl sulfoxide (DMSO) and glycerol provided greater protection to sperm than methanol during freezing and thawing; the most effective concentration of DMSO and glycerol was 10%. The fertilization rate of frozen-thawed sperm was not significantly different from that of fresh sperm. Furthermore, mean (+/-S.D.) hatching rate did not differ significantly between frozen-thawed (82.7+/-12.4%) and fresh sperm (90.7+/-4.5%). Although frozen-thawed sperm that was immediately refrozen had 0% post-thaw motility, frozen semen that was refrozen after dilution with D-15 (containing DMSO at a ratio of 1:2) had post-thaw motility of 38.3+/-2.9%. Motility was lower for refrozen than for frozen sperm (P<0.05). Furthermore, fertilization and hatching rates of refrozen sperm were 42.9+/-6.7 and 34.1+/-10.5%, respectively, which were lower than that of fresh sperm (P<0.05).


Synthetic transit peptides inhibit import and processing of mitochondrial precursor proteins.
We have demonstrated that a synthetic peptide corresponding to the rat mitochondrial malate dehydrogenase (mMDH) transit peptide (TP-28) inhibits the binding of pre-mMDH to isolated mitochondria. Synthetic peptides derived from chloroplast transit peptide sequences, which have a similar net charge, did not inhibit import. In addition, this peptide (TP-28) inhibits import of ornithine transcarbamylase, another mitochondrial matrix protein, thus suggesting that common import pathways exist for both mMDH and ornithine transcarbamylase. A smaller synthetic peptide corresponding to residues 1-20 of the mMDH transit peptide (TP-20) also inhibits binding. However, several substitutions for leucine-13 in the smaller peptide relieve import inhibition, thus providing evidence that this neutral residue plays a crucial role in transit peptide binding to the mitochondrial surface. Proteolytic processing of pre-mMDH by a mitochondrial matrix fraction to both the mature and intermediate forms of mMDH was also inhibited by TP-28. The ability of synthetic peptides to inhibit distinct steps in the import of mitochondrial precursor proteins corresponds precisely to their ability to interact with the same components used by transit peptides on intact precursors. Furthermore, inhibition at multiple points along the import pathway reflects the functions of several independent structures contained within transit peptides.


Validation of the Onco-MPI in predicting short-term mortality in older Indian patients with cancer.
The number of older patients with cancer is increasing exponentially worldwide, and a similar trend has also been noted in India. The Multidimensional Prognostic Index (MPI) strongly correlates the presence of individual comorbidities with mortality, and the Onco-MPI prognosticates patients accurately for overall mortality. However, limited studies have evaluated this index in patient populations beyond Italy. We evaluated the performance of the Onco-MPI index in predicting mortality in older Indian patients with cancer. This observational study was conducted between October 2019 and November 2021 in the Geriatric Oncology Clinic at Tata Memorial Hospital in Mumbai, India. The data of patients aged ≥60 years with solid tumors who underwent a comprehensive geriatric assessment was analysed. The study's primary aim was to calculate the Onco-MPI for patients in the study and correlate it with one-year mortality. A total of 576 patients aged ≥60 years were included in the study. The median age (range) of the population was 68 (60-90) years, and 429 (74.5%) were male. After a median follow-up of 19.2 months, 366 (63.7%) patients had died. The proportion of patients classified as low risk (0-0.46), moderate risk (0.47-0.63) and high risk (0.64-1.0) were 38% (219 patients), 37% (211 patients) and 25% (145 patients), respectively. There was a significant difference in one-year mortality rates between the low-risk patients compared to medium and high-risk patients (40.6% vs 53.1% vs 71.7%; p < 0.001). The current study validates the Onco-MPI as a predictive tool for estimating short-term mortality in older Indian patients with cancer. Further prospective studies need to build on this index to obtain a score with greater discrimination in the Indian population.


Clinical and Serological Biomarkers of Treatment's Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade.
We evaluated the peripheral immune panel of Multiple Sclerosis (MS) patients treated for more than 10 years with interferon-beta1b (IFNβ-1b) and aimed to identify possible biomarkers of treatment response. Serum samples from 70 MS patients treated with IFNβ-1b more than a decade were analysed for 15 cytokines, that were correlated with the disability score, annual relapse ratio (ARR): the total number of relapses-ARR_0, relapse on treatment-ARR_1 and demographic data. Two groups were defined based on the levels of disability, calculated using the Expanded Disability Status Scale (EDSS): G1 - recurrent-remissive and G2 - secondary-progressive. Furthermore, we split the patients based on gender (G1_f, G1_m, G2_f, G2_m). The ARR was reduced after treatment was instituted. We found positive correlations between IL_25 and EDSS in G1_f and G2_f, tumor necrosis factor α (TNFα) and ARR_1 and ARR_0 in G1, and IL_17F with ARR_1. Negative correlations were for IL_25 and ARR_0 and ARR_1. SCD40L intensely positively correlated with IL_31 in G1 and G2. After more than a decade of treatment, IFNβ-1b offers good results by reducing relapses and slowing disability progression. Several biomarkers can be used to assess the patient's response. High levels of IL_17 and TNFα will indicate a more active form of the disease. IL-25 may exert a positive influence in male MS patients and should be considered for future studies, together with the co-modulation between sCD40L and IL_31. Our method allowed us to screen the peripheral immune panel and can be used for assessing the peripheral levels of the above-mentioned cytokines.


Mandated societal lockdown and road traffic accidents.
The effect of mandated societal lockdown to reduce the transmission of coronavirus disease 2019 (COVID-19) on road traffic accidents is not known. For this reason, we performed an in-depth analysis using data from Statewide Traffic Accident Records System. We reviewed data on total 2292 road traffic accident records in Missouri from January 1, 2020 through May 15, 2020. We treated March 23 as the first day of mandated societal lockdown and May 3 as the first day of re-opening. We have found that there was a significant reduction in road traffic accidents resulting in minor or no injuries (mean 14.5 versus 10.8, p < 0.0001) but not in accidents resulting in serious or fatal injuries (mean 3.4 versus 3.7, p = 0.42) after mandated societal lockdown. Furthermore, there was a significant reduction in road traffic accidents resulting in minor or no injuries after the mandated social lockdown (parameter estimate -5.9, p = 0.0028) in the time series analysis. There was an increase in road traffic accidents resulting in minor or no injuries after expiration of mandatory societal lockdown (mean 10.8 versus 13.7, p = 0.04). The mandated societal lockdown policies led to reduction in road traffic accidents resulting in non-serious or no injuries but not those resulting in serious or fatal injuries.


Factors predictive of positive response to steroid therapy in simple bone cysts: an old trick that still works.
The aim of the study was to identify clinical, demographic and radiological factors predicting a positive response to steroid treatment in simple bone cysts (SBCs). A retrospective study was conducted on 62 patients. The mean follow-up period was 9.2 years after the final steroid injection. Recurrences were defined according to Neer's scale as modified by Chang et al.. To identify predictive factors, the group of patients who positively responded to treatment (Neer stages I and II, n = 39, 62.9 %, group 1) were compared with the group in which recurrences occurred (Nerr stages III and IV, n = 23, 37.1 %, group 2). Recurrences were experienced by 37.1 % of the patients (n = 23). Cyst location, numbers of cavities (uni- or multilocular), the area of the cyst and its Enneking stage differed significantly between the groups (p < 0.05). Steroid therapy may be of benefit in patients with unilocular, small-sized, humeral cysts, classified as Enneking stage IA.


Basis operator network: A neural network-based model for learning nonlinear operators via neural basis.
It is widely acknowledged that neural networks can approximate any continuous (even measurable) functions between finite-dimensional Euclidean spaces to arbitrary accuracy. Recently, the use of neural networks has started emerging in infinite-dimensional settings. Universal approximation theorems of operators guarantee that neural networks can learn mappings between infinite-dimensional spaces. In this paper, we propose a neural network-based method (BasisONet) capable of approximating mappings between function spaces. To reduce the dimension of an infinite-dimensional space, we propose a novel function autoencoder that can compress the function data. Our model can predict the output function at any resolution using the corresponding input data at any resolution once trained. Numerical experiments demonstrate that the performance of our model is competitive with existing methods on the benchmarks, and our model can address the data on a complex geometry with high precision. We further analyze some notable characteristics of our model based on the numerical results.


Circ_0000370 Plays an Oncogenic Role in Colorectal Cancer by Regulating the miR-502-5p/SIRT1 Axis.
The importance of circular RNA has been reported in cancer development. However, the role and mechanism of circ_0000370 in CRC progression are still unclear. Quantitative real-time PCR and Western blot assay were performed to measure RNA and protein expression. Cell proliferation was assessed by cell colony formation assay and 5-Ethynyl-2'-deoxyuridine assay. Flow cytometry was used to measure cell apoptosis. Cell migration and invasion were detected by transwell assay. The intermolecular target relations between miR-502-5p and circ_0000370 or SIRT1 were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. A xenograft tumor model was established to examine the role of circ_0000370 in tumor growth in vivo. As compared with controls, the expression of circ_0000370 was upregulated in CRC tissues and cells. Circ_0000370 depletion inhibited CRC cell proliferation, migration and invasion but induced cell apoptosis. Meanwhile, circ_0000370 depletion restrained tumor growth in vivo. In addition, miR-502-5p inhibitor partly reverted the impacts of circ_0000370 knockdown on CRC cells. Moreover, miR-502-5p mimic-caused effects on cell phenotypes were attenuated by SIRT1 overexpression. Circ_0000370 induced the proliferation and metastasis of CRC cells by sponging miR-502-5p and enhancing SIRT1 expression, which provided a possible target for CRC treatment.


Mcl-1 is vital for neutrophil survival.
Upon entry to the systemic circulation, neutrophils exhibit a short mean time to cell death. The viability of most cell types in a steady state is preserved by the interplay of the Bcl-2 family of proteins, wherein the anti-apoptotic members inhibit the action of their pro-apoptotic counterparts. Neutrophils, however, display absent or severely reduced expression of several anti-apoptotic Bcl-2 family proteins. Hence, they rely on the expression of Mcl-1, an anti-apoptotic member of the Bcl-2 family, for survival. This protein is uniquely short-lived relative to related proteins and its loss likely precipitates the induction of apoptosis in neutrophils. This review describes the role of Mcl-1 in the neutrophil in the context of apoptosis and highlights the proteins' importance to the cell. We also address neutrophil apoptosis in the broader context of the cells' response to pathogens, focussing particularly on the strategies used by pathogens to manipulate the apoptotic pathway to their own ends.


Sneddon-Wilkinson disease resistant to dapsone and colchicine successfully controlled with PUVA.
A 28-year-old man with a 6-year history of subcorneal pustular dermatosis (SPD) is presented. This case reviews the clinical features, differential diagnosis, etiology, and treatment options of SPD. In particular, this case emphasizes the absence of response to dapsone and colchicine and control with PUVA therapy.


Investigation of cerebral autoregulation in the newborn piglet during anaesthesia and surgery.
The relationship between cerebral autoregulation (CA) and the neurotoxic effects of anaesthesia with and without surgery is investigated. Newborn piglets were randomly assigned to receive either 6 h of anaesthesia (isoflurane) or the same with an additional hour of minor surgery. The effect of the spontaneous changes in mean arterial blood pressure (MABP) on the cerebral haemodynamics (oxy- and deoxy-haemoglobin, HbO2 and Hb) was measured using transverse broadband near-infrared spectroscopy (NIRS). A marker for impaired CA, concordance between MABP and intravascular oxygenation (HbD = HbO2 - Hb) in the ultra-low frequency domain (0.0018-0.0083 Hz), was assessed using coherence analysis. Presence of CA impairment was not significant but found to increase with surgical exacerbation. The impairment did not correlate with histological outcome (presence of cell death, apoptosis and microglial activation in the brain).


Alcohol concentration and carbonation of drinks: the effect on blood alcohol levels.
Alcohol absorption and elimination vary considerably amongst individuals, and are subject to influences from a variety of factors. The effects of alcohol concentration and beverage mixer type on the rate of alcohol absorption, in a controlled environment was studied. 21 subjects (12 male, 9 female) consumed a solution containing alcohol, on three separate occasions. The three solutions were, A: Neat vodka (37.5 vol%), B: Vodka mixed with still water (18.75 vol%), C: Vodka mixed with carbonated water (18.75 vol%). The volume of alcohol each subject consumed was determined by Widmark's equation. The alcohol was drunk in a 5 min period following an overnight fast and breath alcohol concentrations were measured over a 4h period using a breathalyser. 20/21 subjects absorbed the dilute alcohol at a faster rate than the concentrated alcohol. The difference between the absorption rates was found to be significant (p<0.001). The use of a carbonated mixer had varying effects on the alcohol absorption rate. 14/21 subjects absorbed the alcohol with the carbonated mixer at a faster rate, with 7 subjects showing either no change or a decrease in rate. The mean absorption rate for solution C was 4.39+/-0.45 (mg/100ml/min), and the difference between this absorption rate and that with the still mixer (1.08+0.36) was significant (p=0.006).


Esophagobronchial fistula complicated by esophageal achalasia treated by per-oral endoscopic myotomy.
A 48-year-old man who underwent balloon dilation for esophageal achalasia more than 20 years prior developed severe dysphagia and cough during mealtimes. Endoscopic findings showed a markedly dilated esophagus with residue, narrowing of the esophagogastric junction (EGJ), and a fistula in the middle thoracic esophagus. Esophagography showed narrowing of the EGJ and outflow of contrast from the esophagus to the bronchus. In addition, computed tomography showed marked esophageal dilatation and diffuse granular shading in both lungs. Based on these imaging findings, the patient was diagnosed with deterioration of esophageal achalasia and an esophagobronchial fistula (EBF) secondary to achalasia. The increased intra-esophageal pressure caused by the achalasia was suspected to have inhibited the closure of the EBF. Therefore, we believed that per-oral endoscopic myotomy (POEM) would help treat the achalasia and simultaneously contribute to closing of the EBF. Immediately after POEM, the dysphagia and cough improved. Furthermore, the EBF was closed. 14 months after POEM, the patient did not exhibit deterioration of esophageal achalasia and EBF. To the best of our knowledge, there have been no reports of POEM implemented in cases of esophageal achalasia complicated by EBF. Therefore, this case is worth reporting.


[Current indications and operative strategy for renal hyperparathyroidism].
Renal hyperparathyroidism results from pathophysiologic changes induced and maintained by terminal renal failure. Surgical treatment is possible using various resection strategies. The aim of this work is to illustrate the indications, techniques and resection strategies for surgical treatment of renal hyperparathyroidism. National and international guidelines regarding the surgical treatment of renal hyperparathyroidism were analyzed. Furthermore, our own practical experience was integrated into the article. While the indications for surgery according to the Surgical Working Group Endocrinology (CAEK) guidelines are given in cases of clinical impairment and renal hyperparathyroidism that cannot be controlled by medication, international guidelines additionally refer to the absolute parathyroid hormone level for deciding for surgery. Individual patient consultation is necessary in the case of renal hyperparathyroidism in order to determine the right time for surgical treatment as well as the most suitable surgical technique, taking into account the individual risk profile and other therapeutic perspectives, including renal transplantation.


Microscopic Versus Endoscopic Myringoplasty: A comparative study.
To compare the results of myringoplasty by using operating microscope (postaural) with that of myringoplasty by using endoscope (permeatal). Our study was conducted in Department of ENT of in Chirayu Medical College and Hospital. Total 60 patients of age group 18-60 were taken for study having chronic otitis media or trauma with central perforation. Patients were randomly selected microscopic or endoscopic myringoplasty. 30 patients for Microscopic Myringoplasty and 30 patients for endoscopic Myringoplasty were selected. Out of total 60 patients 35 were females and the 25 were males, 27 were in the age group 15-30 and 23 were in age group 31-45 and only 10 in the age group of 46-60. 18-30 age group cohort was predominant. The average time taken for endoscopic myringoplasty was 65.5 ± 3.45 min and for microscopic myringoplasty 85.7 ± 3.42 min. 26 were having Large central perforation (LCP), of which 13 underwent microscopic and 13 underwent endoscopic myringoplasty. The graft was taken up in situ in 22 patients while 4 patients had small residual central perforation. Out of these four residual perforations 3 were done by endoscopy and 1 by microscopy. 19 (of 60) were having Medium size central perforation (MCP), 10 were operated with endoscope and 9 with microscope. 15 (60) were having Small central perforation (SCP), 7 done with endoscope and 8 with microscope. In all patient graft take up was well. Large central perforation present in maximum patient and had least graft uptake as compared to MCP and SCP. Out of the 30 these endoscopic myringoplasty 27 patients had good graft uptake and 3 had small central residual perforation after 3 months. Out of the 30 microscopic myringoplasty 29 patients had good graft uptake and 1 patient had small central residual perforation after 3 months. In our study pre operative and post operative Air Bone Gaps (ABGs) were 22.05 ± 2.04 and 9.05 ± 1.36 db respectively in endoscopic myringoplasty and 21.81 ± 1.85 and 8.55 ± 1.44 db respectively in microscopic myringoplasty. Microscopic myringoplasty has greater success rate in larger perforations that is LCP and MCP and equal result in SCP. Advantage of microscope is depth perception and both hands are free for procedure which is limitation of endoscopic myringoplasty (need to use endoscope holder). Advantage of endoscopic permeatal myringoplasty is superior visualization, least tissue trauma and better cosmetic outcome, almost equal graft uptake and hearing outcome with less operative time. Endoscope system is portable, so convenient for surgeon where microscope is not available. Also endoscope is a less costly armamentarium. Our study shows better result in myringoplasty can be achieved if both methods of surgery are used in combination.


Deficiency of periostin impairs liver regeneration in mice after partial hepatectomy.
Periostin (Postn) is a crucial extracellular remodeling factor that has been implicated in the pathogenesis of hepatic inflammation, fibrosis, non-alcoholic fatty liver disease and liver cancer. However, the role of Postn in liver regeneration remains unclear. Here, we demonstrate that Postn mRNA and protein levels are significantly upregulated in the mice after 2/3 partial hepatectomy (PHx). Compared with wild-type mice, Postn-deficient mice exhibit lower liver/body weight ratio and less Ki67-positive cells at days 2, 8 and 14 after PHx. Macrophage infiltration and the levels of TNF-α, IL-6 and HGF in the livers of Postn-deficient mice are significantly decreased compared with wild-type mice one day after PHx. In addition, overexpression of Postn leads to higher liver/body weight ratio and more Ki67-positive cells in the livers of mice and promotes hepatocyte proliferation in vitro. Moreover, liver sinusoidal endothelial cells, biliary epithelial cells and hepatocytes can express Postn after PHx, and Postn deficiency impairs angiogenesis during liver regeneration. Our findings indicate that Postn deficiency impairs liver regeneration in mice after PHx and Postn might be a novel promoter for liver regeneration.


Pacemaker-related myocardial perfusion defects worsen during higher pacing rate and coronary flow augmentation.
Asynchronous activation resulting from right ventricular apical (RVA) pacing can adversely affect left ventricular function and myocardial perfusion despite normal coronary arteries. This situation makes detection of coronary heart disease in paced patients difficult. The purpose of this study was to assess the distribution, extent, and severity of myocardial perfusion defects with RVA pacing at low and high rates and increased coronary blood flow with adenosine. Fourteen patients with permanent RVA pacing and angiographically normal coronary arteries underwent myocardial perfusion single-photon emission computed tomography at rest at low and high pacing rates and with pacing at low rates with adenosine. Data were analyzed semi-quantitatively using a 20-segment scoring model and coded using a four-point scoring system. At rest, 23 (55%) of 42 coronary flow territories showed abnormal perfusion and 52 (19%) of 280 corresponding segments demonstrated abnormal perfusion; mean perfusion score was 0.22. After high-rate pacing, perfusion was abnormal in 31 (74%) of 42 flow territories and 122 (44%) of 280 segments; mean perfusion score was 0.67. Adenosine infusion resulted in 28 (67%) of 42 abnormal flow territories and 90 (32%) of 280 abnormal segments; mean perfusion score was 0.44. Perfusion defects were observed most often in close proximity to the origin of the pacing site. RVA pacing results in myocardial perfusion defects. The false-positive findings are present at rest and more obvious with high-rate pacing than during adenosine infusion. Detection of coronary artery disease should be performed with caution in RVA paced patients because of the high number of perfusion defects observed in the absence of coronary artery disease.


Changes in microbial community structure during the biooxidation of iron and inorganic/organic sulfur provide prediction of acid mine drainage from coal spoil.
To thoroughly investigate the formation mechanism of acid mine drainage (AMD) from coal mine spoil, this study conducted microbial shake flask experiments on gangue possessing inorganic and organic sulfur to predict the future generation of AMD. The results revealed that microbial-mediated sulfur oxidation effectively lowered the pH of leachate and increased metal ion and sulfate concentrations. The oxidation of pyrite sulfur and thiophene sulfur contributed to 70 % and 30 % of the total acid production, respectively, highlighting the importance of both processes in coal mine acidification. The abundance and diversity of the microbial community increased, with "new" iron and sulfur oxidizing bacterial species during acidification, with "new" iron and sulfur oxidizing bacterial species, such as Sulfobacillus sp. and Acidibacillus sp., emerging and constituting approximately one-third of the bacterial population. These bacteria survived desiccation and proliferated faster than A. ferrooxidans YQ-N3 when conditions favored growth.


High plasma concentrations of human urotensin II do not alter local or systemic hemodynamics in man.
Human urotensin II (hUII) is an endocrine hormone that acts as a potent arterial vasoconstrictor in both in vitro and in vivo studies in animals. We examined, for the first time, the local and systemic hemodynamic response to hUII in man in vivo. Four healthy male volunteers took part in pilot studies and 11 in definitive studies. Forearm blood flow (FBF) was measured in response to intra-arterial infusion of authentic, biologically active hUII (incremental rates of 0.001-300 pmol min(-1)) and saline placebo using venous occlusion plethysmography. Blood pressure, heart rate, cardiac output and hUII plasma concentrations were also measured. Forearm studies were repeated in five subjects with inhibition of endothelial mediators using aspirin and a "nitric oxide clamp". Dorsal hand vein diameter was determined by a standard displacement technique in response to local administration of hUII (3-300 pmol min(-1)) with and without nitric oxide synthase inhibition. There was no significant change in FBF during brachial infusion of saline or hUII (dose range, 0.001 to 300 pmol min(-1)). A nitric oxide clamp did not unmask vasoactive effects of hUII. Human UII infusions (100 and 300 pmol min(-1)) significantly increased plasma hUII concentrations from baseline (12 +/- 3 pmol l(-1)) to 106 +/- 15 and 307 +/- 98 pmol l(-1), respectively. Despite high circulating hUII concentrations, no change was seen in systemic hemodynamics and ECGs were unchanged. Human UII had no effect on hand vein diameter (n=6). In contrast to our hypothesised role of hUII, we found no vasoactive responses to hUII in vivo, consistent with recent in vitro studies in human blood vessels, but in contrast to non-human primate studies in vivo. Our data do not support a key role for hUII in the regulation of vascular tone and resting blood pressure in man. However, studies with hUII receptor antagonists are also needed before firm conclusions can be drawn.


GNL3 and PA2G4 as Prognostic Biomarkers in Prostate Cancer.
Prostate cancer is a multifocal and heterogeneous disease common in males and remains the fifth leading cause of cancer-related deaths worldwide. The prognosis of prostate cancer is variable and based on the degree of cancer and its stage at the time of diagnosis. Existing biomarkers for the prognosis of prostate cancer are unreliable and lacks specificity and sensitivity in guiding clinical decision. There is need to search for novel biomarkers having prognostic and predictive capabilities in guiding clinical outcomes. Using a bioinformatics approach, we predicted GNL3 and PA2G4 as biomarkers of prognostic significance in prostate cancer. A progressive increase in the expression of GNL3 and PA2G4 was observed during cancer progression having significant association with poor survival in prostate cancer patients. The Receiver Operating Characteristics of both genes showed improved area under the curve against sensitivity versus specificity in the pooled samples from three different GSE datasets. Overall, our analysis predicted GNL3 and PA2G4 as prognostic biomarkers of clinical significance in prostate cancer.


Steroids in sepsis: another swing of the pendulum in our clinical trials.
Many studies have been conducted to try and find interventions to treat patients with severe sepsis, but with little success. In several cases, initial apparent beneficial effects have not been confirmed in later trials. The story of steroids in sepsis is one example of this pendulum effect, with initial success in the study by Annane et al. tempered by the more recent negative results of the Corticus study. The reasons for this pendulum effect are likely related, at least in part, to issues of clinical trial design and the way in which clinical trials in intensive care unit patients are developed, conducted and assessed needs to be critically reassessed.


Subdural hemorrhagic injury after open heart surgery.
We report two cases of acute subdural hematoma after cardiac surgery using cardiopulmonary bypass. In both patients, emergency removal and drainage of a subdural hematoma was performed by neurosurgeons, and complete recovery followed. Subdural hemorrhagic brain injury after cardiac surgery is rare and devastating; however, we consider early diagnosis and proper treatment to be effective because organic brain damage did not occur.


Schooling in western culture promotes context-free processing.
Culture has been shown to influence the way people apprehend their physical environment. Cognitive orientation is more holistic in East Asian cultures, which emphasize relationships and connectedness among objects in the field, than in Western cultures, which are more prone to focus exclusively on the object and its attributes. We investigated whether, beyond, or in conjunction with culture, literacy and/or schooling may also have an influence on this cognitive orientation. Using the Framed-Line Test both in Portugal and in Thailand, we compared literate schooled adults with two groups of unschooled adults: one of illiterates and one of ex-illiterates. As in former studies on Western people, Portuguese-schooled literates were more accurate in the absolute task than in the relative task. In contrast, Portuguese illiterates and ex-illiterates were more accurate in the relative task than in the absolute task. Such an effect of schooling was not observed in the Thai groups, all of whom performed better on the relative task. Thus, the capacity to abstract from contextual information does not stem only from passive exposure to the culture or the physical environment of Western countries. Western schooling, as part of or in addition to culture, is a crucial factor.


Rapid postmortem changes in the cellular localisation of amino acid transmitters in the retina as assessed by immunocytochemistry.
We have assessed by means of immunocytochemistry, the cellular distributions of the amino acid transmitters GABA, glycine and glutamate, and the free-radical scavenger taurine, in the retinae of adult rabbits at various times after death. Within 10 min of death, horizontal cells began to display immunoreactivity for GABA, whilst displaced amacrine cells began to display immunoreactivity for glycine. By 40 min postmortem, GABA was present in glial cells. Glutamate, which is not normally detectable in retinal glia, was detected in such glia by 20 min postmortem. By contrast immunocytochemically detectable glycine did not accumulate in glia. There was a gradual diminution of immunoreactivity for taurine in glial cells and photoreceptors. By 2 h postmortem, most immunoreactivity had disappeared from the retina. We conclude that amino acid transmitters show rapid changes in their distributions immediately after death, which may be related to changes in the patterns of transmitter release and uptake, and changes in degradation mechanisms. The rapid changes in cellular localisation of amino acid immunoreactivity illustrated in this study, indicate that the fixation of nervous tissues must be performed rapidly. Moreover, the massive loss of immunoreactivity by 2 h postmortem suggests that any assays for content of these transmitters at this, and subsequent time-points, will bear little resemblance to the values obtained at the time of death.


Identifying driving hydrogeomorphic factors of coastal wetland downgrading using random forest classification models.
Coastal wetlands provide critical ecosystem services but are experiencing disruptions caused by inundation and saltwater intrusion under intensified climate change, sea-level rise, and anthropogenic activities. Recent studies have shown that these disturbances downgraded coastal wetlands mainly through affecting their hydrological processes. However, research on what is the most critical driver for wetland downgrading and how it affects coastal wetlands is still in its infancy. This study examined drivers of three types of wetland downgrading, including woody wetland loss, emergent herbaceous wetland loss, and woody wetlands converting to emergent herbaceous wetlands. By using random forest classification models for the wetland ecosystems in the Alligator River National Wildlife Refuge, North Carolina, USA, during 1995-2019, we determined the relative importance of different hydrogeomorphic processes and the dominant variables in driving the wetland downgrading. Results showed that random forest classification models were accurate (> 97 % overall accuracy) in classifying wetland downgrading. Multiple hydrogeomorphic variables collectively contributed to the coastal wetland downgrading. However, the dominant control factors varied across different types of wetland downgrading. Woody wetlands were most susceptible to saltwater intrusion and were likely to downgrade if the saltwater table was shallower than 0.2 m below the land surface. In contrast, emergent herbaceous wetlands were most vulnerable to inundation and drought. The favorable groundwater table for emergent herbaceous wetlands was between 0.34 m above the land surface and 0.32 m below the land surface, beyond which the emergent herbaceous wetland tended to disappear. For downgraded woody wetlands, their distance to canals/ditches played a crucial role in determining their fates after downgrading. The machine learning approach employed in this study provided critical knowledge about the thresholds of hydrogeomorphic variables for the downgrading of different types of coastal wetlands. Such information can help guide effective and targeted coastal wetland conservation, management, and restoration measures.


Theory of gas exchange in the avian parabronchus.
To understand the distribution of oxygen and carbon dioxide in the avian lung, a theoretical treatment of gas exchange in the parabronchus of the avian lung is described. The model is modified after Zeuthen (1942). In addition to bulk flow through the parabronchial lumen, diffusion through the air spaces of both the parabronchial lumen and air capillaries is treated. The relationship of PO2 and PCO2 within the blood capillaries, air capillaries, and parabronchial lumen to parabronchial blood flow and ventilation is graphically shown. The results indicate that the variations of PO2 and PCO2 along an air capillary are less than one torr under resting conditions. Removal of diffusion resistance within the air space of the air capillaries increases calculated parabronchial gas exchange by less than 0.1% at rest. At high or resting ventilation rates the partial pressure profile along the parabronchial lumen calculated considering bulk flow only agrees well with the profile calculated considering bulk flow and axial diffusion, but as the ventilation rate decreases there is increasingly large disagreement. Forward diffusion of O2 toward the parabronchus reduces pre-parabronchial PO2 and backward diffusion of CO2 from the parabronchus increases PCO2. Neglecting diffusion within the air spaces of both the lumen and the air capillaries increases calculated parabronchial gas exchange by less than 2% (CO2) or 6% (O2) at rest.


Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors.
Fifty-nine Type 1 (insulin-dependent) diabetic patients with (group I) and 59 patients without nephropathy (group II) pair-matched according to sex (30 males and 29 females), age (33 years, range 15-48) and diabetes duration (19 years, range 6-42) were followed for a period of 10 years from about 5 years before to 5 years after onset of proteinuria. The cumulative incidence of coronary heart disease was estimated, and blood pressure and serum cholesterol were followed. Within six years after onset of proteinuria the cumulative incidence of coronary heart disease was increased eight-fold in group I (40%) compared with group II (5%), (p less than 0.001). Blood pressure was higher in group I compared with group II from before onset of proteinuria (135/86 +/- 17/9 mmHg vs 129/80 +/- 15/8 mmHg, p less than 0.001), and serum cholesterol elevated from onset of proteinuria in group I (6.3 +/- 1.2 mmol/l) vs. group II (5.5 +/- 1.0 mmol/l), (p less than 0.005). Patients in group I who developed coronary heart disease had similar age (36 years, range 21-51, vs 38 years, range 21-53), sex (50% males vs. 52% males), smoking frequency (50% vs 49%), diabetes duration (22 years, range 9-39, vs 24 years, range 10-42) and serum creatinine (110 mumol/l, range 69-284, vs 108 mumol, range 72-1024) compared with patients not developing coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)


A prognostic view on the application of individualized genomics in Parkinson's disease.
Parkinson's disease is a common age-related progressive neurodegenerative disorder. Over the last 15 years advances have been made in our understanding of the etiology of the disease, with the greatest insights perhaps coming from genetic studies. The identification of a number of genes that harbor pathogenic mutations causing Parkinson's disease have on the whole driven the development of disease model systems and nominated a number of therapeutic targets. As we move towards an era of personalized medicine, genetic determinants will become even more crucial for accurate diagnosis, and assessing prognosis and outcomes. The individual genomic profile and risk assessments will in the long-term determine clinical trial participation, treatment plans and therapeutic dosing. Herein we discuss the status of genetics in Parkinson's disease and how these factors may affect the patient care in the future.


Soluble IL7Rα potentiates IL-7 bioactivity and promotes autoimmunity.
Human soluble interleukin-7 receptor (sIL7R)α circulates in high molar excess compared with IL-7, but its biology remains unclear. We demonstrate that sIL7Rα has moderate affinity for IL-7 but does not bind thymic stromal lymphopoietin. Functionally, sIL7Rα competes with cell-associated IL-7 receptor to diminish excessive IL-7 consumption and, thus, enhances the bioactivity of IL-7 when the cytokine is limited, as it is presumed to be in vivo. IL-7 signaling in the presence of sIL7Rα also diminishes expression of CD95 and suppressor of cytokine signaling 1, both regulatory molecules. Murine models confirm diminished consumption of IL-7 in the presence of sIL7Rα and also demonstrate a potentiating effect of sIL7Rα on IL-7-mediated homeostatic expansion and experimental autoimmune encephalomyelitis exacerbation. In multiple sclerosis and several other autoimmune diseases, IL7R genotype influences susceptibility. We measured increased sIL7Rα levels, as well as increased IL-7 levels, in multiple sclerosis patients with the predisposing IL7R genotype, consistent with diminished IL-7 consumption in vivo. This work demonstrates that sIL7Rα potentiates IL-7 bioactivity and provides a basis to explain the increased risk of autoimmunity observed in individuals with genotype-induced elevations of sIL7Rα.


Minimally invasive repair for pectus excavatum -- aesthetic and/or functional?
Pectus excavatum is the most frequent anterior thoracic wall congenital malformation. This malformation is increasing its effects with the aging process and has its peak during teenage, when the clinical symptoms become more acute and psychological effects are really important. Across the course of time many treatment techniques have been proposed, among which conservative or surgical correction techniques. The minimally invasive repair of pectus excavatum, "Nuss technique", developed after 1987, is the most frequently performed technique world wide. This article analyzes 52 patients, admitted to the University Emergency Military Hospital "Carol Davila" - Thoracic Surgery Department, diagnosed, investigated and surgically treated according to Nuss procedure. Therapeutic and diagnostic protocols will be presented and analyzed: clinical and paraclinical evaluation, indications and contraindications of Nuss procedure, as well as possible intraoperative and postoperative complications. Nuss procedure's benefits will be presented, as well as improvements of functional and aesthetic parameters. Nuss procedure has a series of advantages: minimally invasive surgical procedure reduced operative time, minimal blood loss and fast socio-professional reinstatement.


Lactate infusions in major depression without panic attacks.
Sodium lactate infusion provokes panic attacks in panic disorder patients but not in normal controls. We have previously shown that patients who develop panic disorder during a major depressive episode are similar to panic disorder patients in their rate of panic attacks with lactate. In the present pilot study, nine patients with major depression without panic attacks underwent lactate infusions. These patients differed significantly from panic disorder patients but not from controls in their response to lactate. This argues for the specificity of lactate sensitivity for the phenomenon of panic attacks and gives further evidence for biological differences between panic and depression.


Estimating the number of regular and dependent methamphetamine users in Australia, 2002-2014.
To estimate the number of regular and dependent methamphetamine users in Australia. Indirect prevalence estimates were made for each year from 2002-03 to 2013-14. We applied multiplier methods to data on treatment episodes for amphetamines (eg, counselling, rehabilitation, detoxification) and amphetamine-related hospitalisations to estimate the numbers of regular (at least monthly) and dependent methamphetamine users for each year. Dependent users comprised a subgroup of those who used the drug regularly, so that estimates of the sizes of these two populations were not additive. We estimated that during 2013-14 there were 268 000 regular methamphetamine users (95% CI, 187 000-385 000) and 160 000 dependent users (95% CI, 110 000-232 000) aged 15-54 years in Australia. This equated to population rates of 2.09% (95% CI, 1.45-3.00%) for regular and 1.24% (95% CI, 0.85-1.81%) for dependent use. The rate of dependent use had increased since 2009-10 (when the rate was estimated to be 0.74%), and was higher than the previous peak (1.22% in 2006-07). The highest rates were consistently among those aged 25-34 years, in whom the rate of dependent use during 2012-2013 was estimated to be 1.50% (95% CI, 1.05-2.22%). There had also been an increase in the rate of dependent use among those aged 15-24 years (in 2012-13 reaching 1.14%; 95% CI, 0.80-1.69%). There have been increases over the past 12 years in the numbers of regular and dependent methamphetamine users in Australia. Our estimates suggest that the most recent numbers are the highest for this period, and that the increase has been most marked among young adults (those aged 15-34 years). There is an increasing need for health services to engage with people who have developed problems related to their methamphetamine use.


Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA.
Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.


The "double-edged" role of progesterone in periodontitis among perimenopausal women undergoing or not undergoing scaling and root planing.
Progesterone (PG) is an important sex steroid hormone commonly administered to protect the endometrium in perimenopausal women. The present study aimed to explore differential responses of periodontitis to PG in perimenopausal women who did or did not undergo scaling and root planing (SRP). A total of 129 perimenopausal women with mild-to-moderate periodontitis were enrolled and underwent treatment as follows: SRP (n = 35); SRP + PG (n = 34); PG (n = 31); and no treatment (s) (n = 29). Pocket probing depth (PPD), clinical attachment level (CAL), sulcus bleeding index (SBI), and bleeding on probing (BOP) were measured using periodontal probes. Three inflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) were measured using ELISA techniques. PPD, CAL, SBI, BOP, and levels of inflammatory factors in GCF were all significantly decreased in perimenopausal women with periodontitis after SRP. In patients who did not undergo SRP, 6 months of PG treatment significantly elevated PPD, SBI, BOP, and GCF levels of CRP, IL-6, and TNF-α. In contrast, PG exhibited inhibitory effects on periodontal inflammation in patients who underwent SRP, evidenced by significantly decreased BOP and IL-6, and slightly decreased SBI, CRP, and TNF-α. PG-induced changes dissipated 6 months after withdrawal of PG (at 12 months). Among perimenopausal women with periodontitis, PG enhanced periodontal inflammation in the absence of SRP but inhibited periodontal inflammation in those who underwent SRP.


Metastasis to the lingual lymph node in carcinoma of the tongue.
Lingual lymph nodes are occasionally found along the course of some lymph-vessels of the tongue. However, their existence has received little attention and metastasis of carcinoma of the tongue to them has not previously been reported. Three cases of carcinoma of the tongue with metastasis to the lingual lymph node are described and a discussion of the importance of such metastasis in the treatment of carcinoma of the tongue is presented.


Impact of fertility on the longevity of older rural Chinese women: an analysis of a longitudinal survey.
This study evaluates the impact of fertility during the childbearing period on the longevity of older rural Chinese women and verifies whether any trade-off exists between women's longevity and their number of children to provide empirical evidence for improving health intervention policies and formulating active fertility policies in low-fertility countries. Based on the data of the deaths of 1623 older adults aged 65 and above during 2014-2018 in the Chinese Longitudinal Healthy Longevity Survey, this study explores the relationship between the number of children born and older rural women's longevity using the ordinary least squares method. Furthermore, the impact of fertility on the longevity of men and women in rural and urban areas, along with other reproductive behaviours on older rural women's longevity, were analysed. There was a significant negative correlation between the number of children born and women's longevity (β = - 0.555, p < 0.05). Additionally, their longevity exhibited a decreasing trend with having birthed more sons and an increasing trend with more daughters. Age at first and last births had a significant positive relationship with rural women's longevity; however, the effect of fertility on the longevity of older rural and urban men and older urban women was not significant. It is confirmed that there is a trade-off between fertility and longevity for rural women in China. Future research should focus on compensating for the decline in female longevity caused by the number of children born and promote the concept of a healthy pregnancy, scientific nurture, and gender equality in fertility.


In vitro release of 5-[3H]hydroxytryptamine from rat spinal trigeminal nucleus.
A potassium-evoked release of 5-[3H]hydroxytryptamine (5-HT), newly synthesized from [3H]tryptophan, was obtained from slices of the subnucleus caudalis of rat spinal trigeminal nucleus by means of an in vitro perfusion system. This release was dose-dependent and calcium-sensitive and quantitatively comparable to the 5-HT release in substantia nigra. The putative transmitter of the primary sensory afferents, substance P, stimulates the spontaneous 5-HT release, whereas another peptide, neurotensin, has no effect.


Is there a relation between number of adjustments and results after gastric banding?
Laparoscopic adjustable gastric banding (LAGB) is a standard restrictive bariatric procedure. Previous studies have shown that patients lost to follow-up do worse than patients who remain in follow-up. However, it is unknown if this is purely because of a lack of band adjustments. The aim of this study was to study the relation between number of adjustments and results. Patients who underwent primary LAGB from October 2006 until March 2009 were included. The following parameters were collected: demographic characteristics, preoperative and postoperative weight, preoperative and postoperative status of co-morbidities, type of band, short- and long-term complications, reoperations, date, number and volume of adjustments, total amount of inserted volume, and last measured volume. One hundred seventy-four patients underwent primary LAGB. Twelve patients did not attend follow-up visits after 24 months (8.1%). Mean follow-up was 46 months, and excess weight loss, 47%. Eleven patients (8.1%) developed long-term complications, and 12 patients (8.8%) underwent revisional surgery. Patients underwent a mean number of 5 adjustments with a range of 0 to 18. The mean volume of totally inserted milliliters was 8 mL, with a range of 0 to 14 mL. There was a strong positive relation between number of adjustments and weight loss as well as reduction in obesity-related co-morbidities (r = .22; P<.01). There was no significant relation between number of adjustments and complications or revisional surgery. There is a strong relation between the number of band adjustments and weight loss, whereas complications and reoperations seem to be independent of the number of adjustments. A continual and lifelong follow-up of LAGB patients, including regular band volume adjustments, is necessary.


Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma.
The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC. Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC (n = 40), LC with HCC (n = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression. Hsa-miR-21-5p correlated with intermediate monocytes (r = 0.30, p = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes (r = - 0.316, p = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders. Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved.


Centre-of-mass and minimal speed limits of the great hammerhead.
The great hammerhead is denser than water, and hence relies on hydrodynamic lift to compensate for its lack of buoyancy, and on hydrodynamic moment to compensate for a possible misalignment between centres of mass and buoyancy. Because hydrodynamic forces scale with the swimming speed squared, whereas buoyancy and gravity are independent of it, there is a critical speed below which the shark cannot generate enough lift to counteract gravity, and there are anterior and posterior centre-of-mass limits beyond which the shark cannot generate enough pitching moment to counteract the buoyancy-gravity couple. The speed and centre-of-mass limits were found from numerous wind-tunnel experiments on a scaled model of the shark. In particular, it was shown that the margin between the anterior and posterior centre-of-mass limits is a few tenths of the product between the length of the shark and the ratio between its weight in and out of water; a diminutive 1% body length. The paper presents the wind-tunnel experiments, and discusses the roles that the cephalofoil and the pectoral and caudal fins play in longitudinal balance of a shark.


Original and liposome-modified indocyanine green-assisted fluorescence study with animal models.
Medical diagnosis heavily relies on the use of bio-imaging techniques. One such technique is the use of ICG-based biological sensors for fluorescence imaging. In this study, we aimed to improve the fluorescence signals of ICG-based biological sensors by incorporating liposome-modified ICG. The results from dynamic light scattering and transmission electron microscopy showed that MLM-ICG was successfully fabricated with a liposome diameter of 100-300 nm. Fluorescence spectroscopy showed that MLM-ICG had the best properties among the three samples (Blank ICG, LM-ICG, and MLM-ICG), as samples immersed in MLM-ICG solution achieved the highest fluorescence intensity. The NIR camera imaging also showed a similar result. For the rat model, the best period for fluorescence tests was between 10 min and 4 h, where most organs reached their maximum fluorescence intensity except for the liver, which continued to rise. After 24 h, ICG was excreted from the rat's body. The study also analyzed the spectra properties of different rat organs, including peak intensity, peak wavelength, and FWHM. In conclusion, the use of liposome-modified ICG provides a safe and optimized optical agent, which is more stable and efficient than non-modified ICG. Incorporating liposome-modified ICG in fluorescence spectroscopy could be an effective way to develop novel biosensors for disease diagnosis.


Metabolic stability of 3-epi-1α,25-dihydroxyvitamin D3 over 1 α 25-dihydroxyvitamin D3: metabolism and molecular docking studies using rat CYP24A1.
3-epi-1α,25-dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3), a natural metabolite of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), exhibits potent vitamin D receptor (VDR)-mediated actions such as inhibition of keratinocyte growth or suppression of parathyroid hormone secretion. These VDR-mediated actions of 3-epi-1α,25(OH)2D3 needed an explanation as 3-epi-1α,25(OH)2D3, unlike 1α,25(OH)2D3, exhibits low affinity towards VDR. Metabolic stability of 3-epi-1α,25(OH)2D3 over 1α,25(OH)2D3 has been hypothesized as a possible explanation. To provide further support for this hypothesis, we now performed comparative metabolism studies between 3-epi-1α,25(OH)2D3 and 1α,25(OH)2D3 using both the technique of isolated rat kidney perfusion and purified rat CYP24A1 in a cell-free reconstituted system. For the first time, these studies resulted in the isolation and identification of 3-epi-calcitroic acid as the final inactive metabolite of 3-epi-1α,25(OH)2D3 produced by rat CYP24A1. Furthermore, under identical experimental conditions, it was noted that the amount of 3-epi-calcitroic acid produced from 3-epi-1α,25(OH)2D3 is threefold less than that of calcitroic acid, the analogous final inactive metabolite produced from 1α,25(OH)2D3 . This key observation finally led us to conclude that the rate of overall side-chain oxidation of 3-epi-1α,25(OH)2D3 by rat CYP24A1 leading to its final inactivation is slower than that of 1α,25(OH)2D3. To elucidate the mechanism responsible for this important finding, we performed a molecular docking analysis using the crystal structure of rat CYP24A1. Docking results suggest that 3-epi-1α,25(OH)2D3, unlike 1α,25(OH)2D3, binds to CYP24A1 in an alternate configuration that destabilizes the formation of the enzyme-substrate complex sufficiently to slow the rate at which 3-epi-1α,25(OH)2D3 is inactivated by CYP24A1 through its metabolism into 3-epi-calcitroic acid.


Species correlation in long-term carcinogenicity studies.
Species correlation in neoplastic response was examined for 266 long-term toxicology and carcinogenicity studies. The overall concordance between rats and mice exposed to the same chemical was 74% (198/266). Within a species, the results for males and females were also highly correlated (87% concordance for rats and 89% for mice). Had only male rats and female mice been utilized in these experiments, the same conclusions regarding carcinogenicity would have been reached in 96% of the studies (255/266). The high interspecies correlation shown in these studies supports the view that extrapolation of carcinogenicity outcomes to other species, including humans, is appropriate.


Jump exercise during hindlimb unloading protect against the deterioration of trabecular bone microarchitecture in growing young rats.
Three-dimensional femoral trabecular architecture was investigated in tail-suspended young growing rats and the effects of jump exercise during the period of tail-suspension were also examined. Eight-week-old male Wistar rats (n = 24) were randomly assigned to three body weight-matched groups: a tail suspended group (SUS, n = 8); a sedentary control group (CON, n = 8) and rats primed with jump exercise during the period of tail suspension (JUM, n = 8). The jump exercise protocol consisted of 30 jumps/day, five days/week with a 40 cm jump height. After 3 weeks of jump exercise, bone mineral density (BMD) of the entire right femur was measured using dual energy X-ray absorptiometry. Three-dimensional trabecular bone architecture at the distal femoral metaphysis was evaluated using microcomputed tomography (micro-CT). Tail suspension caused a decrease in femoral BMD (-5%, p < 0.001) and trabecular bone architectural deterioration. Deterioration in the trabecular network during hindlimb unloading was mostly attributed to the reduction of trabecular number (-32%, p < 0.001) in the distal femoral metaphysis. Jump exercise during the tail suspension period increased trabecular thickness (14%, p < 0.001) and the reduction of trabecular number was suppressed. The present data indicate that jump exercise applied during hindlimb unloading could be able to inhibit bone loss and trabecular bone architectural deterioration caused by tail suspension.


Operational DGT threshold values for metals in seawater from protected coastal areas in Sardinia (Western Mediterranean).
Diffusive gradients in thin films (DGTs) were used for monitoring metal (Cd, Cu, Ni, and Pb) concentrations in protected and non-protected coastal areas in Sardinia (Western Mediterranean). The deployment of DGTs in relatively undisturbed areas enabled calculation of operational DGT threshold values, which can be used for assessments of the environmental quality of coastal areas. The DGT thresholds were defined as the median metal concentrations that were found in protected areas, which ensured consideration of the natural variability of the different study sites. The calculated DGT thresholds were 11.6 ng L-1 for Pb, 5.1 ng L-1 for Cd, 63 ng L-1 for Cu and 152 ng L-1 for Ni. A comparison of the calculated DGT thresholds with previous DGT studies in the area demonstrated their suitability for identifying sites of environmental concern in the Western Mediterranean.


Beta-papillomavirus infection and skin cancer.
The development of highly sensitive PCR techniques and multiplex bead-based Luminex platforms has accelerated the search for a specific role of human papilloma viruses in the development of squamous cell carcinoma. Human papillomaviruses are most likely indirectly involved in this process by facilitating UV-related carcinogenesis via preventing UV-induced apoptosis or impairing DNA repair, but other mechanisms are also possible.


Facilitators and Barriers to Interacting With Clinical Decision Support in the ICU: A Mixed-Methods Approach.
Clinical decision support systems (CDSSs) are used in various aspects of healthcare to improve clinical decision-making, including in the ICU. However, there is growing evidence that CDSS are not used to their full potential, often resulting in alert fatigue which has been associated with patient harm. Clinicians in the ICU may be more vulnerable to desensitization of alerts than clinicians in less urgent parts of the hospital. We evaluated facilitators and barriers to appropriate CDSS interaction and provide methods to improve currently available CDSS in the ICU. Sequential explanatory mixed-methods study design, using the BEhavior and Acceptance fRamework. International survey study. Clinicians (pharmacists, physicians) identified via survey, with recent experience with clinical decision support. An initial survey was developed to evaluate clinician perspectives on their interactions with CDSS. A subsequent in-depth interview was developed to further evaluate clinician (pharmacist, physician) beliefs and behaviors about CDSS. These interviews were then qualitatively analyzed to determine themes of facilitators and barriers with CDSS interactions. A total of 48 respondents completed the initial survey (estimated response rate 15.5%). The majority believed that responding to CDSS alerts was part of their job (75%) but felt they experienced alert fatigue (56.5%). In the qualitative analysis, a total of five facilitators (patient safety, ease of response, specificity, prioritization, and feedback) and four barriers (excess quantity, work environment, difficulty in response, and irrelevance) were identified from the in-depth interviews. In this mixed-methods survey, we identified areas that institutions should focus on to improve appropriate clinician interactions with CDSS, specific to the ICU. Tailoring of CDSS to the ICU may lead to improvement in CDSS and subsequent improved patient safety outcomes.


Online listing data and their interaction with market dynamics: evidence from Singapore during COVID-19.
With the emergence of Property Technology, online listing data have drawn increasing interest in the field of real estate-related big data research. Scraped from the online platforms for property search and marketing, these data reflect real-time information on housing supply and potential demand before actual transaction data are released. This paper analyzes the interactions between the keywords of online home listings and actual market dynamics. To do so, we link the listing data from the major online platform in Singapore with the universal transaction data of resale public housing. We consider the COVID-19 outbreak as a natural shock that brought a significant change to work modes and mobility and, in turn, consumer preference changes for home purchases. Using the Difference-in-Difference approach, we first find that housing units with a higher floor level and more rooms have experienced a significant increase in transaction prices while close proximity to public transportation and the central business district (CBD) led to a reduction in the price premium after COVID-19. Our text analysis results, using the natural language processing, suggest that the online listing keywords have consistently captured these trends and provide qualitative insights (e.g. view becoming increasingly popular) that could not be uncovered from the conventional database. Relevant keywords reveal trends earlier than transaction-based data, or at least in a timely manner. We demonstrate that big data analytics could effectively be applied to emerging social science research such as online listing research and provide useful information to forecast future market trends and household demand.


Severe reactional state in lepromatous leprosy simulating Sweet's syndrome.
A male patient with underlying lepromatous leprosy mimicked Sweet's syndrome clinically. He was believed to be in an atypical reactional state recognized as a variant form of erythema nodosum leprosum. In addition to the antileprosy treatment, steroid hormone was required to control the systemic symptoms.


Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events.
Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here we make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Our screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways. The associations are often highly reproducible across cancer types, and while many lncRNAs are co-expressed with their protein-coding hosts or neighbours, some are intergenic and independent. We highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. Our study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers.


Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
To date, PACS1-neurodevelopmental disorder (PACS1-NDD) has been associated with recurrent variation of Arg203 and is considered diagnostic of PACS1-NDD, an autosomal dominant syndromic intellectual disability disorder. Although incompletely defined, the proposed disease mechanism for this variant is altered PACS1 affinity for its client proteins. Given this proposed mechanism, we hypothesized that PACS1 variants that interfere with binding of adaptor proteins might also give rise to syndromic intellectual disability. Herein, we report a proposita and her mother with phenotypic features overlapping PACS1-NDD and a novel PACS1 variant (NM_018026.3:c.[755C > T];[=], p.(Ser252Phe)) that impedes binding of the adaptor protein GGA3 (Golgi-associated, gamma-adaptin ear-containing, ARF-binding protein 3). We hypothesize that attenuating PACS1 binding of GGA3 also gives rise to a disorder with features overlapping those of PACS1-NDD. This observation better delineates the mechanism by which PACS1 variation predisposes to syndromic intellectual disability.


Dieting as a case of behavioural decision making. Does self-control matter?
To be a successful dieter, one has to be able to consistently resist immediate temptations in order to achieve the bigger, but delayed rewards of weight loss, increased attractiveness and better health. These long-term benefits are by no means guaranteed as the delayed rewards are more uncertain than the immediate rewards. Several researchers have suggested that the population of restrained eaters consists of two populations: unsuccessful dieters who score high on restraint and high on disinhibition, and successful dieters who score high on restraint but low on disinhibition. The present study examines to what extent restrained eating in combination with individual differences in self-control (akin to low disinhibition) is related to successful decision making on a task that mimics the uncertainty of dieting (measured with the Iowa Gambling Task). As expected, self-control moderated the association between restraint and decision making: restrained eating was related to worse decision making when self-control was low, but to better decision making when self-control was high. This suggest that those high in restraint and high in self-control may be more successful in their dieting attempts because they are generally better at inhibiting short-term rewards in order to gain better long-term outcomes.


ISMP Adverse Drug Reactions: Adalimumab-Induced Aseptic Meningitis Pill Desiccant -Induced Acute Hypoxic Respiratory Failure Rivastigmine Patch -Induced Angioedema Acute Liver Failure Due to Etodolac Severe Cognitive Impairment Due to High Free Valproic Acid Levels.
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of revention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA) MedWatch program (800-ßDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with ur readers. E-mail email@example.com). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.


Empty threat: Hospitals could see more vacancies as demand for outpatient care grows and financial pressure builds to curb inpatient admissions.
Markets with too many hospital beds could see trouble as providers seek to control spending and avoid expensive hospitalizations. "You'll need a lot fewer hospitals and hospital beds" because providers will do more to keep patients healthy enough not to need them, says Frank Trembulak, of Geisinger Health System.


Complications of tissue plasminogen activator therapy after vitrectomy for diabetes.
Human recombinant tissue plasminogen activator (25 micrograms) was injected into seven eyes of six patients who had developed massive fibrin deposition after vitrectomy surgery for diabetes. Six eyes had developed pupillary membranes and recurrence of tractional retinal detachment from fibrin membranes, and one eye had developed only a pupillary membrane. All pupillary membranes resolved within one hour of administration of tissue plasminogen activator, and five tractional retinal detachments resolved within 24 hours. All eyes developed evidence of intraocular bleeding after tissue plasminogen activator injection. Subsequently, six of seven eyes developed recurrence of fibrin accumulation and tractional retinal detachment.


Unusual small intestinal obstruction in adolescent girls: the abdominal cocoon.
Ten cases of small intestinal obstruction seen over a period of 6 years (1971-6) in young girls within the narrow age range of 13-18 years are described. The patients were all within 2 years of menarche. In all these cases the obstruction was due to a membrane encasing the small intestine in the manner of a cocoon. There was no previous history of abdominal operation, peritonitis or prolonged drug intake. The clinical features, operative findings and management of the cases are presented. Possible causes of the condition are discussed. In view of the similar clinical presentation in all these patients, their conditions can be grouped as a clinical entity--'the abdominal cocoon'.


Further evidence of preserved priming and impaired recall in adults with Asperger's syndrome.
Two experiments compared incidental (implicit) and intentional (explicit) memory performance in adults with Asperger's syndrome and individually matched controls. Experiment 1 involved perceptual tests using word fragment cues, following study tasks in which the participants either generated the words from contextual cues or read the words alone, with no contextual cues. Experiment 2 involved conceptual tests using paired associate cues, following study tasks in which the paired associates were rated either for their relatedness or for their readability. Performance in both the incidental tests was similar for both groups. Performance in both the intentional tests was also similar for both groups, with one exception. The adults with Asperger's syndrome were more likely to falsely recall words that had not actually been studied. These findings further delimit the nature of memory impairments in adults with Asperger's syndrome, which seem restricted to certain aspects of episodic memory that include the tendency to make more intrusion errors in recall.


Sequence analysis of homogeneous peptides of shark immunoglobulin light chains by tandem mass spectrometry: correlation with gene sequence and homologies among variable and constant region peptides of sharks and mammals.
Morphologically, sharks are living fossils that are remarkably similar to their Devonian ancestors of ca. 400 million years ago. If a parallel conservation in biochemical properties characterizes shark evolution, knowledge of the properties of shark immunoglobulins should provide information on the structure of primordial immunoglobulins and their genes. The problem of polyclonality of shark immunoglobulins has precluded detailed analysis of shark immunoglobulin light polypeptide chains. Here, we approach the problem of obtaining direct sequence information on polyclonal light chains of shark immunoglobulins by isolating homogeneous peptides from tryptic digests of shark light chains and sequencing these by tandem mass spectrometry. To confirm the location of the peptides, we isolated a complementary DNA (cDNA) clone from a sandbar shark cDNA library in the expression vector lambda gt11, identifying the clone by its ability to produce a peptide serologically detectable using rabbit antibody to purified shark light chain. The correspondence between peptide sequence and that derived from gene sequence provided direct proof that the gene studied was that of a major expressed serum light chain. Using this combined approach, we isolated homogeneous peptides from both constant and variable regions. The variable region peptides showed homology to corresponding sequences of mammalian V lambda and V kappa sequences. The constant region gene sequence we obtained was homologous to mammalian C lambda sequence. The four constant region tryptic peptides we sequenced corresponded exactly to stretches of the C lambda sequence derived from the DNA sequence. The combined approach described here shows that shark light chains exhibit heterogeneity at both the protein and gene level, but that the constant regions of these chains can be identified as homologs of mammalian lambda chains and that evolutionary conservation has occurred in V region sequences ranging from elasmobranchs to man.


A comprehensive review of vine tea: Origin, research on Materia Medica, phytochemistry and pharmacology.
Vine tea is a popular folk tea that has been consumed in China for more than 1200 years. It is often used in ethnic medicine by ethnic groups in southwest China with at least 35 aliases in 10 provinces. In coastal areas, vine tea is mostly used to treat heatstroke, aphtha, aphonia, toothache, etc. In contrast, in the southwest inland regions, vine tea is mostly used to clear away heat and toxic materials, antiphlogosis and relieving sore-throat, lowering blood pressure and lipid levels, and alleviating fatigue. Three main species have been used as the source of vine tea, Nekemias grossedentata, Nekemias cantonensis and Nekemias megalophylla. Among them, the leaves of Nekemias grossedentata were considered as new food resource in complicance with regulations, according to the Food Safety Standards published by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China. At present, the comprehensively summary of Materia Medica on the history and source of vine tea is currently unavailable. The current article summed up the Materia Medica, species origin and pharmacological effects of all 3 major species used in vine tea to fill the knowledge gaps. We also aim to provide a reference for future research on historical textual, resource development and medicinal utilization of vine tea. Adhering to the literature screening methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this review encompasses 148 scholarly research papers from three database, paper ancient books, local chronicles and folklore through field investigations. We then comprehensively summarized and discussed research progresses in scientific and application studies of vine tea. The historical records indicated that vine tea could have been used as early as Southern and Northern Dynasties (AC 420-589). Nekemias grossedentata, Nekemias cantonensis and Nekemias megalophylla, were used to considered as vine tea in the ethnic medicine. The main phytochemicals found in three plants are flavonoids, polyphenols and terpenoids, among which dihydromyricetin (DHM) is the most important and most studied active substance. The key words "Ampelopsis grossedentata" (Synonym of Nekemias grossedentata) and "dihydromyricetin/DHM" showed the highest frequency over the last 27 year based on the research trend analysis. And the ethnopharmacology studies drawn the main activities of vine tea are antioxidant, antibacterial, hepatoprotective, neuroprotective and anti-atherosclerosis activities. This review systematically summarized and discussed vine tea from the following five aspects, history, genetic relationship, phytochemistry, research trend and ethnopharmacology. Vine tea has a long historical usage in Chinese ethnic medicine. Its outstanding therapeutic efficacies have attracted extensive attention in other places in the world at present. Nekemias cantonensis and Nekemias megalophylla are quite similar to Nekemias grossedentata in terms of many aspects. However, the current research has a narrow focus on mainly Nekemias grossedentata and DHM. We propose that future studies could be carried out to determine the synergistic effect of multi-components and multi-targets of vine tea including all 3 species to provide valuable knowledge.


Efficacy of continuous follow-up for preventing the involuntary readmission of psychiatric patients in Japan: a retrospective cohort study.
Providing aftercare to psychiatric inpatients is important for preventing frequent readmissions; however, the lack of social resources is a problem in Japan. The prefectural Tama-Fuchu Public Health Centre has attempted to establish a new continuous follow-up system for all discharged psychiatric patients in order to reduce the frequency of readmissions. This study aims to evaluate the efficacy of this system. The subjects of the present study were 200 psychiatric inpatients from the Tokyo catchment area. The continuous follow-up system was applied to 130 subjects for one year in addition to conventional standard care (the intervention group). Seventy subjects received conventional care alone (the comparison group). The incident rate ratios (IRR) of total and involuntary readmission to hospital were compared by survival analysis. During the observation period, there were 41 readmissions and 29 involuntary readmissions in 49,731 person-days. The patients subjected to continuous follow-up showed a trend towards a lower overall risk of readmission (IRR = 0.56, 95% CI: 0.29-1.10, p = .057) and a significantly reduced risk of involuntary admission (IRR = 0.48, 95% CI: 0.22-0.96, p = .047). This study provides empirical evidence that providing continuous follow-up examinations as aftercare for discharged psychiatric patients significantly reduces the incidence of involuntary readmission.


Glucose tolerance and pancreatic hormones in thyroidectomized and thyroid hormone-injected cockerels.
The effect of surgical thyroidectomy and of T4/T3 injections on basal and glucose-induced concentrations of plasma insulin and glucagon has been investigated in 20-week-old domestic chickens. Birds injected daily (im) for 2 weeks with T4/T3 (50 micrograms/day) had marginally lower fasting glucose concentrations whereas thyroidectomy had no effect. Glucose tolerance to an intravenous injection of glucose (0.5 g/kg) was impaired in T4/T3 injected animals although the peak hyperglycemia was identical with sham-operated animals. This was associated with significantly reduced basal and glucose-induced insulin concentrations. However, fasting plasma glucagon concentrations were significantly elevated in this group as was the magnitude of the glucose-induced suppression of glucagon release 10 min after injection (48% decline vs 34% in sham-operated animals). Basal concentrations of plasma insulin were markedly elevated in thyroidectomized animals and were associated with only mildly depressed plasma glucagon levels. The absolute concentrations of plasma insulin remained higher in the thyroidectomized birds as compared with those of sham-operated or T4/T3 injected animals after the glucose challenge, although within 30 min after glucose injection they had significantly declined below preinjection levels. This was associated both with significantly reduced plasma glucose concentrations 30 min after injection and the lowest absolute levels of plasma glucagon. The rebound in plasma glucagon in sham-operated animals in response to the rapid decline in glucose concentrations was not as pronounced in either thyroidectomized or T4/T3 injected animals. In conclusion these studies illustrate the secretory dynamics of avian pancreatic endocrine islets in response to both absolute glucose levels and glucose requirements as affected by the thyroid state of the bird.


Failure to generate baseline muscle motor evoked potentials during spine surgery: Risk factors and association with the postoperative outcomes.
To identify factors associated with the failure to generate baseline muscle motor evoked potentials (mMEPs) during spinal surgery, and to determine the association between baseline mMEP generation and postoperative outcomes. A total of 345 patients who underwent spine surgery with intraoperative mMEP monitoring were included, and we retrospectively reviewed their demographic/clinical parameters, and mMEP recording results according to lesion locations. Multivariable logistic regression analysis revealed that preoperative Medical Research Council grade of the weakest muscle <3 was significantly associated with failure of baseline mMEP generation in both cervical and thoracic lesions. In addition, high intramedullary T2 signal intensity on spine MRI for cervical lesions and male sex for thoracic lesions were also significantly associated with baseline mMEP generation failure. Moreover, the failure of baseline mMEP generation was a significantly associated factor for poor functional outcome in patients with thoracic lesions. Sex, radiological abnormality, and preoperative functional status were associated with baseline mMEP generation failure during spine surgery with different patterns according to lesion location. Moreover, baseline mMEP generation failure in thoracic lesion could be associated with risk of postoperative deficits. The risk of baseline mMEP recording failure could be evaluated based on preoperative clinical parameters.


A new method of localize the choroid point of the PICA and the venous copular point on the lateral projection of vertebral angiography.
The location of the choroid arterial point as well as of the copular venous point with reference to a line, dealing with the anatomical structure at the level of the cervicooccipital joint, was found to be a quick and accurate method for the diagnosis of tonsillar herniation. The application of this method has the advantage of giving the location of the choroid arterial point, and a control of the venous time of arteriography by the location of the copular point.


Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration.
A study in genetic epidemiology of disc degeneration, based on lifetime exposure data, findings on magnetic resonance imaging, and genotyping of intragenic markers. To pursue the potential correlation between common allelic variations in the vitamin D receptor locus and degeneration of the intervertebral disc. Familial aggregation has been observed in intervertebral disc degeneration, but the relative significance of the genetic component and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specify a genetic component and increase our understanding of the etiopathogenesis of disc degeneration. From the population-based Finnish Twin cohort, 85 pairs of male monozygotic twins were selected based on exposure to suspected risk factors for disc degeneration. Interview data were gathered on relevant lifetime exposures, and thoracic and lumbar disc degeneration was determined through quantitative and qualitative assessments of signal intensity on magnetic resonance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible associations were examined between disc degeneration measures and two polymorphisms of the coding region of the vitamin D receptor locus. Two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration. Quantitatively assessed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% worse in men with the Taql tt genotype and 4.5% worse in men with the Tt genotype, compared with signal intensity in men with the TT genotype (age adjusted P = 0.003). A similar pattern was found between disc signal intensity and Fokl genotypes; men with the ff and Ff genotypes had mean signal intensities that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively assessed signal intensity, bulging, and disc height were 4.0% and 6.9% worse in men with Ff and ff genotypes, respectively, when compared with those in men with the FF genotype (age-adjusted P = 0.029). Specific vitamin D receptor alleles were associated with intervertebral disc degeneration as measured by T2-weighted signal intensity, demonstrating for the first time, the existence of genetic susceptibility to this progressive, age-related degenerative process.