Electron impact ionization of water-doped superfluid helium nanodroplets: observation of He(H(2)O)(n)(+) clusters.
Electron impact mass spectra have been recorded for helium nanodroplets containing water clusters. In addition to identification of both H(+)(H(2)O)(n) and (H(2)O)(n)(+) ions in the gas phase, additional peaks are observed which are assigned to He(H(2)O)(n)(+) clusters for up to n=27. No clusters are detected with more than one helium atom attached. The interpretation of these findings is that quenching of (H(2)O)(n)(+) by the surrounding helium can cool the cluster to the point where not only is fragmentation to H(+)(H(2)O)(m) (where m < or = n-1) avoided, but also, in some cases, a helium atom can remain attached to the cluster ion as it escapes into the gas phase. Ab initio calculations suggest that the first step after ionization is the rapid formation of distinct H(3)O(+) and OH units within the (H(2)O)(n)(+) cluster. To explain the formation and survival of He(H(2)O)(n)(+) clusters through to detection, the H(3)O(+) is assumed to be located at the surface of the cluster with a dangling O-H bond to which a single helium atom can attach via a charge-induced dipole interaction. This study suggests that, like H(+)(H(2)O)(n) ions, the preferential location for the positive charge in large (H(2)O)(n)(+) clusters is on the surface rather than as a solvated ion in the interior of the cluster.


[Antibiotic therapy of infected cerebrospinal fluid in hydrocephalus treated by a shunt].
Nine hydrocephalic shunted children with infected cerebrospinal fluid (CSF) were treated. Ages ranged from 0 to 10 years. Diagnosis was made through clinical symptoms, CSF examination, echographic and computed tomography (CT). The microorganism which was seen more frequently, was S. epidermidis. This germ was more often found in young children. Treatment of these patients consisted of a systematic change of the shunt which was externally diverted, implantation of a CSF Ommaya reservoir in the lateral ventricle, and intraventricular and systemic administration of antibiotic, were made. Using this protocol CSF sterilization was obtained in all cases, after 5 to 12 days of treatment. CSF shunt infected with S. epidermidis can be effectively cleaned with daily intra-shunt vancomycin, and shunt infected with gram-negative are also cleaned with daily intra-shunt gentamycin.


Salivary cortisol and cardiovascular activity during stress in oppositional-defiant disorder boys and normal controls.
Arousal-regulating mechanisms are important in explaining individual differences in antisocial behavior. Alterations in salivary cortisol concentration and cardiovascular activity were studied in 21 boys with oppositional defiant disorder (ODD) and 31 normal controls (NC) during a 2-hour stressful procedure involving frustration and provocation. Baseline levels of heart rate (HR) were significantly lower in the ODD group, but their HR levels were higher during provocation and frustration. Cortisol levels in the ODD group were overall lower than those of the NC group, and the effect of stress seemed to be minimal and similar for both groups; however, individual differences were large. Since anxiety plays an important mediating role in cortisol response, subjects were divided into one of four groups based on the intensity of their externalizing behavior and anxiousness. Cortisol increase due to stress exposure was strongest in highly externalizing and highly anxious subjects; cortisol decrease was strongest in those subjects who were high in externalizing behavior and low in anxiousness. The results of the study support an important role for hypothalamic-pituitary-adrenal axis sympathetic autonomic functioning in persistent antisocial behavior in young boys.


Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease.
Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn's disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.


MiroRNA-31-3p Promotes the Invasion and Metastasis of Non-Small-Cell Lung Cancer Cells by Targeting Forkhead Box 1 (FOXO1).
To explore the possibility of microRNA miR-31-3p as a biomarker for bone metastasis of non-small-cell lung cancer (NSCLC) and its molecular mechanism to the invasion and metastasis of NSCLC cells. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of miR-31-3p and forkhead box 1 (FOXO1) in NSCLC tissues, serum, and cells to analyze the correlation between the expression levels of miR-31-3p and the clinicopathology of NSCLC. After interference with or overexpressing miR-31-3p, NSCLC cell proliferation, apoptosis, invasion ability, and migration ability were detected by MTT, flow cytometry, Transwell, and scratch experiment, respectively. The interaction between miR-31-3p and FOXO1 was further verified by the dual-luciferase reporter experiment. Western blot was performed to detect the protein expression of FOXO1 in tissues and FOXO1, RhoA, p-RhoA, ROCK-2, and p-ROCK-2 in cells. In tissues, serum, and NSCLC cell line A549 of the NSCLC patients, the expression of FOXO1 was notably lower, and the miR-31-3p expression was significantly higher. Overexpression of miR-31-3p could distinctly improve the proliferation, invasion, and migration of A549 cells, meanwhile inhibit cell apoptosis, and activate the RhoA/ROCK-2 signaling pathway, while interfering with the expression of miR-31-3p has the opposite function. Besides, bioinformatics analysis and luciferase reporter assay confirmed that FOXO1 was a target gene of miR-31-3p. Overexpressing FOXO1 could inhibit the proliferation and metastasis of A549 cells, but overexpressing miR-31-3p reverses the results. This study confirmed that miR-31-3p promotes the proliferation, invasion, and migration of NSCLC cells and inhibits apoptosis through targeted regulating FOXO1 and be a potential therapeutic targets for the treatment of NSCLC.


Functional adrenocortical adenoma in a case with B cell chronic lymphoproliferative disorder.
We describe a B cell chronic lymphocytic leukemia/lymphoma (B-CLL) patient with an adrenocortical adenoma. He was treated initially with oral cyclophosphamide and prednisolone for 2 months, followed by low-dose prednisolone for an additional 2 years, which resulted in the prompt disappearance of CLL cells. After a period of 2 years without therapy, a functional adrenocortical adenoma was found. After adrenalectomy, the CLL cells rapidly increased. Progression of the disease and clinical-hematological relapse was well controlled by low doses of steroids alone, and the patient's condition stabilized. Considering the recent data that corticosteroids can induce apoptosis of CLL cells, the above clinical course suggests that augmented glucocorticoid production from the tumor may have suppressed disease progression.


Right hemisphere dominance for language in a woman with schizophrenia and a porencephalic cyst of the left hemisphere.
A large left hemisphere porencephalic cyst was incidentally found in a 48-year-old woman (MS) with a Diagnostic and Statistical Manual (DSM)-5 diagnosis of schizophrenia. The encephaloclastic characteristics of the cyst indicated that it was acquired between the 22nd and 24th gestational weeks, after the major waves of neuronal migration had tapered off. The cyst destroyed the left temporal and occipital lobes, and the inferior parietal lobule. Surprisingly, MS had no evidence of aphasia, alexia, agraphia, or ideational apraxia; in contrast, cognitive functions dependent on the integrity of the right hemisphere were severely impaired. To test the hypothesis that the development of language in MS took place at the expense of functions that are normally carried out by the right hemisphere, we investigated MS's correlates of oral comprehension with fMRI as a proxy for auditory comprehension and other cognitive functions strongly lateralized to the posterior left hemisphere, such as ideational praxis and reading. Comprehension of spoken language engaged the homologous of Wernicke's area in the right planum temporale. Porencephaly may represent a natural model of neuroplasticity supervening at predictable epochs of prenatal development.


Effect of Sugar versus Mixed Breakfast on Metabolic and Neurofunctional Responses in Healthy Individuals.
We investigated the effects of glucose and diverse breakfasts on glucose increment and ghrelin suppression and cognitive processing of sensory information assessed by frontal P300 evoked potentials. In a randomized crossover design, 12 healthy individuals (6M/6F; BMI 22.2 ± 0.4 kg/m2; 27 ± 1.3 years, mean ± SEM) underwent 50 g OGTT (A) and 3 breakfasts (B1: milk and cereals; B2: milk, apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and hazelnut chocolate cream) to assess plasma glucose-, insulin-, and ghrelin excursions. An electroencephalography was performed before and 100 min after consumption of each load to measure the latency of frontal P300 evoked potentials as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited significantly lower glycemic, but not insulinemic response, as compared to A. Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in all breakfasts with respect to A. P300 latency tended to decrease following each of the three breakfasts, but B3 was the only breakfast capable to elicit a statistically significant reduction in P300 latency with respect to A (p < 0.01), suggesting ameliorated cognitive performance. Such amelioration was correlated with the 2-hour final inhibition of plasma ghrelin concentration (r = 0.61, p = 0.01).


Comparative toxicity of three differently shaped carbon nanomaterials on Daphnia magna: does a shape effect exist?
The acute toxicity of three differently shaped carbon nanomaterials (CNMs) was studied on Daphnia magna, comparing the induced effects and looking for the toxic mechanisms. We used carbon nano-powder (CNP), with almost spherical primary particle morphology, multi-walled carbon nanotubes (CNTs), tubes of multi-graphitic sheets, and cubic-shaped carbon nanoparticles (CNCs), for which no ecotoxicological data are available so far. Daphnids were exposed to six suspensions (1, 2, 5, 10, 20 and 50 mg L-1) of each CNM, and then microscopically analyzed. Ultrastructural analyses evidenced cellular uptake of nanoparticle in CNP and CNT exposed groups, but not in samples exposed to CNCs. Despite this difference, very similar effects were observed in tissues exposed to the three used CNMs: empty spaces between cells, cell detachment from the basal lamina, many lamellar bodies and autophagy vacuoles. These pathological figures were qualitatively similar among the three groups, but they differed in frequency and severity. CNCs caused the most severe effects, such as partial or complete dissolution of the brush border and thinning of the digestive epithelium. Being the cubic shape not allowed to be internalized into cells, but more effective than others in determining physical damages, we can conclude that shape is an important factor for driving nanoparticle uptake by cells and for determining the acute toxicological endpoints. Shape also plays a key role in determining the kind and the severity of pathologies, which are linked to the physical interactions of CNMs with the exposed tissues.


Controlled synthesis of thorium and uranium oxide nanocrystals.
Very little is known about the size and shape effects on the properties of actinide compounds. As a consequence, the controlled synthesis of well-defined actinide-based nanocrystals constitutes a fundamental step before studying their corresponding properties. In this paper, we report on the non-aqueous surfactant-assisted synthesis of thorium and uranium oxide nanocrystals. The final characteristics of thorium and uranium oxide nanocrystals can be easily tuned by controlling a few experimental parameters such as the nature of the actinide precursor and the composition of the organic system (e.g., the chemical nature of the surfactants and their relative concentrations). Additionally, the influence of these parameters on the outcome of the synthesis is highly dependent on the nature of the actinide element (thorium versus uranium). By using optimised experimental conditions, monodisperse isotropic uranium oxide nanocrystals with different sizes (4.5 and 10.7 nm) as well as branched nanocrystals (overall size ca. 5 nm), nanodots (ca. 4 nm) and nanorods (with ultra-small diameters of 1 nm) of thorium oxide were synthesised.


Extravascular background subtraction using deconvolution analysis of the renogram.
The effect of the intravascular background in the renogram on the calculated renal retention function is known and can be removed. However, the effect of the extravascular background (EVB) has not been thoroughly investigated using patient data. By varying the size of the region of interest containing a single kidney and by deconvolving the 131I-hippuran and 99Tcm-DTPA renograms so generated, the following has been found: (a) the effect of EVB on the mean transit time (MTT) is negligible and EVB subtraction is not necessary, (b) the EVB overestimates the lower relative kidney function (RKF) and underestimates the higher RKF, so that EVB subtraction should be performed if the RKFs are asymmetric. A new method is described in which the correction for EVB is performed following deconvolution. If the RKFs are greater than about 30%, the correction can be performed using a regression equation between the RKFs corrected for EVB and those that are not corrected. When the RKFs are asymmetric to a greater extent, the correction should be performed for each study separately. The proposed method includes a small systematic error due to the inherent limitations of nuclear medicine equipment.


No. 225-Management Guidelines for Obstetric Patients and Neonates Born to Mothers With Suspected or Probable Severe Acute Respiratory Syndrome (SARS).
This document summarizes the limited experience of SARS in pregnancy and suggests guidelines for management. Cases reported from Asia suggest that maternal and fetal outcomes are worsened by SARS during pregnancy. Medline was searched for relevant articles published in English from 2000 to 2007. Case reports were reviewed and expert opinion sought. Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. The Society of Obstetricians and Gynaecologists of Canada.


Bronchial adenoma causing unilateral absence of pulmonary perfusion.
This case of bronchial adenoma is used as a clinical model demonstrating absence of pulmonary perfusion by 131I-MAA scanning secondary to bronchial obstruction. Radiographic and radionuclide studies are correlated and other causes of pulmonary hypoperfusion discussed. The literature and related cases are reviewed.


FINE STRUCTURAL CHANGES IN THE FLAGELLUM OF THE SPERMATID IN EXPERIMENTAL CRYPTORCHIDISM OF THE RAT.
Rat testes were confined to the abdominal cavity by operation. After 1 to 26 days they were excised, fixed with osmium tetroxide, sectioned, and examined with the electron microscope. Changes in the axial filament complex of the spermatid flagellum appeared 2 days after operation, and the arrangement of filaments in the middle- and main pieces of some spermatid tails was disordered as compared to the 9 + 2 filament arrangement in the tails of the control spermatids and in other flagella and cilia. In cross-sections, the filaments in the experimental material were nine or less in number, and each of them was single and dense. Occasionally some were double, and in those instances one filament was dense and the other was light and tubular. The central filaments were obscure. In longitudinal sections,the filaments were not parallel to the main axis of the flagella or to each other. It was assumed that the central filaments were more sensitive to the experimental conditions than the peripheral pairs of filaments. Furthermore, the light filaments of the peripheral pairs were more sensitive than the dense filaments. Besides the axial filament complex, the fibrous sheath which surrounds it in the main piece was also changed. The plasma membrane of the changed flagella disappeared or became fragmented.


Lysophosphatidic acid reduces the organ injury caused by endotoxemia-a role for G-protein-coupled receptors and peroxisome proliferator-activated receptor-gamma.
Exogenous lysophosphatidic acid (LPA) has been shown to beneficial in renal ischemia/reperfusion injury, wound healing and colitis. LPA acts via specific G-protein-coupled receptors and also peroxisome proliferator-activated receptor-gamma (PPAR-gamma). However, activation of PPAR-gamma is dependent on the presence of an unsaturated acyl chain. Here we investigate the effects of saturated LPA (18:0) and unsaturated LPA (18:1) on the organ injury associated with endotoxemia and the receptors mediating LPA activity. Male Wistar rats received either lipopolysaccharide (LPS, 6 mg/kg i.v.) or vehicle. The PPAR-gamma antagonist GW9662 (1 mg/kg i.v.), the LPA receptor antagonist Ki16425 (0.5 mg/kg i.v.) or vehicle was administered 30 min after LPS. LPA 18:0 or LPA 18:1 (1 mg/kg i.v.) or vehicle was administered 1 h after injection of LPS. Endotoxemia for 6 h resulted in an increase in serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase. Therapeutic administration of LPA 18:0 or 18:1 reduced the organ injury caused by LPS. LPA 18:0 also attenuated the increase in plasma IL-1beta caused by LPS. Ki16425, but not GW9662, attenuated the beneficial effects of LPA 18:0, however, Ki16425 and GW9662 attenuated the beneficial effects of 18:1. In conclusion, LPA reduces the organ injury caused by endotoxemia in the rat. Thus, LPA may be useful in the treatment of shock of various aetiologies. The mechanism of action is related to acyl chain saturation, with LPA 18:0 acting via G-protein-coupled receptors and LPA 18:1 acting via G-protein-coupled receptors and PPAR-gamma.


Catalytic Hydroconversion of 5-HMF to Value-Added Chemicals: Insights into the Role of Catalyst Properties and Feedstock Purity.
5-hydroxymethylfurfural (HMF) is an important bio-derived platform molecule that is generally obtained from hexoses via acid-catalyzed dehydration. It can be effectively transformed into a variety of value-added derivatives, thus being an ideal candidate for fossil replacement. Both HMF oxidation and hydrogenation processes enable the synthesis of numerous chemicals, monomers for polymerization, and biofuel precursors. This Review summarizes the most recent advances in heterogeneous catalytic hydroconversion of HMF into valuable chemicals with strong focus on 2,5-bishydroxymethyl furan (BHMF), 2,5-bishydroxymethyltetrahydrofuran (BHMTHF), and 2,5-dimethyltetrahydrofuran (DMTHF). In addition, multifunctional catalytic systems that enable a tunable production of various HMF derived intermediates are discussed. Within this chemistry, the surprising impact of HMF purity on the catalytic performance, such as selectivity and activity, during its upgrading is highlighted. Lastly, the remaining challenges in the field of HMF hydroconversion to the mentioned chemicals are summarized and discussed, taking into account the knowledge gain of catalyst properties and feedstock purity.


Markovnikov versus anti-Markovnikov Hydrophosphination: Divergent Reactivity Using an Iron(II) β-Diketiminate Pre-Catalyst.
The ability to tune between different regioselectivities using a common pre-catalyst is an unusual yet highly desirable process. Here, we report the use of an iron(II) pre-catalyst that can be used to synthesize vinyl phosphines in a Markovnikov-selective manner in benzene, whereas a simple change to dichloromethane as the reaction solvent leads to the Z-selective anti-Markovnikov product. Preliminary mechanistic studies are reported that suggest Markovnikov selectivity is a radical-mediated process, whereas the anti-Markovnikov selectivity is not radical in nature but is due to a change in oxidation state.


Genetic characterization of near full length SIVdrl genomes from four captive drills (Mandrillus leucophaeus).
We sequenced near full length SIVdrl genomes from four captive drills (Mandrillus leucophaeus). All four animals were born in captivity in German zoos. Although serologically SIV negative before acquisition in zoo A in 2008 and 2009, during a routine analysis all four animals were determined to be SIV antibody positive in 2011. Comparisons of the four new SIVdrl sequences showed high identity among each other (90.7-97.7% in env) and to the only published full length sequence SIVdrl FAO (90.5-92.8% in env), which is also derived from a captive drill. SIVdrl infections seem to be highly prevalent in captive drills, probably resulting from frequent animal transfers between the zoos in an effort to maintain this highly endangered species and its genetic diversity. This should be kept in mind as SIVdrl may be transmitted to uninfected animals in open groups and potentially also to animal keepers having contact with these nonhuman primates.


Data resource profile: the Korea National Hospital Discharge In-depth Injury Survey.
The Korea National Hospital Discharge In-depth Injury Survey (KNHDIS), which was started in 2005, is a national probability survey of general hospitals in Korea with 100 or more beds conducted by the Korea Disease Control and Prevention Agency (KDCA). The KNHDIS captures approximately 9% of discharged cases from sampled hospitals using a 2-stage stratified cluster sampling scheme, among which 13% are injury related cases, defined as S00-T98 (injury, poisoning, and certain other consequences of external causes) using International Classification of Diseases, 10th revision codes. The KNHDIS collects information on characteristics of injury-related discharges in order to understand the scale of injuries, identify risk factors, and provide data supporting prevention policies and intervention strategies. The types of data captured include the hospitals' information, detailed clinical information, and injury-related codes such as the mechanism, activities undertaken when injured (sports, leisure activities, work, treatment, and education), external causes of the injury, and location of the occurrence of the injury based on the International Classification of External Causes of Injuries. Furthermore, the means of transportation, risk factors for suicide, and toxic substances are recoreded. Annual reports of the KNHDIS are publicly accessible to browse via the KDCA website (http://www.kdca.go.kr) and microdata are available free of charge upon request via email (firstname.lastname@example.com).


Heterogeneity in retinal disease and the computational model of the human-rod response.
Abnormal rod-receptor activity can be quantitatively assessed in humans by fitting a computational model of the rod's response to the leading edge of the a wave of the electroretinogram. One purpose of the present study was to compare two procedures for fitting the model to the electroretinogram. A computationally simpler method gives comparable results to the more labor-intensive method used previously. This finding holds for both normal observers and patients with retinodegenerative disease that affects the receptors unevenly. A second purpose of the present study was to consider the effects of a heterogeneous disease process on the parameters of the model. a waves from a heterogeneous retina are computer simulated and are fitted with the receptor model. This analysis suggests that the model will overestimate the change in the healthiest rods and will underestimate the percentage of the rods that are significantly affected.


Health related quality of life in patients treated with radical cystectomy and urinary diversion for urothelial carcinoma of the bladder: development and validation of a new disease specific questionnaire.
The impact of treatment on the health related quality of life (HRQOL) of patients is being recognized with increasing importance, particularly in those with urological malignancies. However, a validated disease and treatment specific instrument to assess HRQOL following radical cystectomy (RC) and urinary diversion (UD) is currently lacking. We report the results of a new questionnaire designed specifically to measure HRQOL in these patients. A 45-item questionnaire consisting of the Functional Assessment of Cancer Therapy (FACT)-General and 17 additional items designed to measure disease and treatment specific health outcomes were combined to form the Vanderbilt Cystectomy Index (FACT-VCI). FACT-VCI and the generic RAND 36-Item Health Survey (SF-36) were administered to 50 patients from our institution RC data base who were more than 1 year from the time of surgery. Each patient was asked to complete the survey at 1 and 4 weeks. The results of the SF-36 and FACT-VCI were correlated along with the first and second administration of the FACT-VCI. Overall FACT-VCI was found to have adequate internal consistency (Cronbach's alpha >0.70). Furthermore, intraclass correlation for the first and second administration of the VCI was 0.79. In addition, there was good correlation between the validated SF-36 and FACT-VCI (r = 0.81). The result was initial validation of a questionnaire for the assessment of HRQOL in patients following RC and UD. Instruments designed to measure accurately HRQOL following RC and UD are in early development. We have now constructed and validated a disease and treatment specific questionnaire that can objectively assess HRQOL following RC and UD. A prospective longitudinal study of FACT-VCI is currently ongoing.


Hepatitis B antigens in serum and liver of chimpanzees acutely infected with hepatitis B virus.
We report the temporal patterns of various immunohistological and serological parameters of acute self-limited hepatitis B virus infection of two chimpanzees, and we provide evidence that the synthesis of hepatitis B core antigen precedes that of hepatitis B surface antigen. Our data suggest that existence of a biphasic hepatitis B virus infection involving a hematogenous reinfection of the liver and indicate that recruitment of liver cells to produce hepatitis B virus may occur in a pattern consistent with a replicative cycle of about 8 days.


The Incidence of Cholelithiasis After Bariatric Surgery in Saudi Arabia and Its Associated Risk Factors.
Saudi Arabia has one of the highest obesity rates (35.4%) in the world, and bariatric surgery (BS) has emerged as the most effective treatment for obesity and its comorbidities. Despite its effectiveness, it is a known risk factor for cholelithiasis. The aim of this study is to identify the incidence and risk factors that contribute to the development of symptomatic cholelithiasis after different types of bariatric surgery in Saudi Arabia. This is a cross-sectional study conducted among the Saudi adult population. The sample size was 706 participants who underwent bariatric surgery from all over Saudi Arabia. Data collection was done through a validated online self-reported survey. Out of 706 participants who fulfilled the inclusion criteria, it was found that the incidence of gallstones (GS) after bariatric surgery was 18.8%. The most incidence was during the first year of surgery, where the number of individuals reached 80.4%. The majority were in females (22.9%) and those who underwent Roux-en-Y gastric bypass (RYGB) surgery (51.2%). Patients who had a body mass index (BMI) of >25 kg/m² significantly had a higher incidence of gallstones (23.1%) compared to those who had a lesser BMI (15.8%). As the analysis showed, the medication used to prevent the occurrence of gallstones can be considered one of the protective factors, where 85.4% of individuals who used these medications did not develop cholelithiasis. The incidence of gallstones after bariatric surgery was high, particularly within the first year of surgery. The increase in postoperative gallstone formation is correlated with hyperlipidemia and Roux-en-Y gastric bypass as basic predictive factors. On the contrary, the medication used to prevent the occurrence of gallstones is considered a protective factor.


Role of carbon nanotracers in lymph node dissection of advanced gastric cancer and the selection of preoperative labeling time.
The incidence of gastric cancer is high. The number of dissected lymph nodes was an independent factor affecting prognosis. Although preoperative labeling is helpful in lymph nodes resection, there are no guidelines for when to perform preoperative labeling. To investigate the role of nanocarbon in lymph node dissection during gastrectomy, and to discuss the relationship between the timing of preoperative injection of carbon nanoparticles and the extent of lymph node dissection. A prospective analysis was performed on the clinical data of 307 patients with advanced gastric cancer who underwent laparoscopic surgery in the General Surgery Department of Weifang People's Hospital between June 2018 and February 2021. The patients were randomly divided into experimental group and control group based on whether they received preoperative nanocarbon injection or not. The experimental group was divided into different groups according to the preoperative labeling time. The number of dissected lymph nodes and the number of lymph nodes with black staining were compared in each group after surgery, and the role of nanocarbon in the number of dissected lymph nodes, pathological staging, and the relationship with prognosis were discussed. The average number of dissected lymph nodes in the experimental group was higher than that in the control group. In the experimental group, the number of lymph node dissections and number of black-staining lymph nodes in the nanocarbon-labeling group at 2 d and 1 d before surgery were higher than in the labeling group on the day before surgery (P < 0.05). Preoperative nanocarbon labeling can safely and effectively guide lymph node dissection. To improve the detection rate of lymph nodes is conducive to subsequent comprehensive anti-tumor therapy.


Alloimmune Neutropenia in a Neonate: Case Report and Review of Literature.
Neonatal alloimmune neutropenia, variably referred to in the literature as NAIN, FNAIN or NIN, is a disorder of neutrophil destruction in newborns similar to better-known conditions such as hemolytic disease of the newborn and neonatal alloimmune thrombocytopenia (FNAIT). Infants affected by this self-limiting condition can present asymptomatically or have a wide range of symptoms, from skin manifestations and mucositis to severe infections such as sepsis and pneumonia. In our case, we report an otherwise asymptomatic term infant born with severe neutropenia to a mother affected by COVID-19 in the 3rd trimester. However, it is unclear if COVID-19 contributed to our patients' neutropenia. Diagnostic testing eventually revealed the presence of anti-neutrophil antibodies, confirming the diagnosis of alloimmune neutropenia. The infant was conservatively managed with early discharge prior to resolution of neutropenia and close post-discharge follow up.


Singapore Neonatal Resuscitation Guidelines 2016.
We present the revised Neonatal Resuscitation Guidelines for Singapore. The 2015 International Liaison Committee on Resuscitation Neonatal Task Force's consensus on science and treatment recommendations (2015), and guidelines from the American Heart Association and European Resuscitation Council were debated and discussed. The final recommendations of the National Resuscitation Council, Singapore, were derived after the task force had carefully reviewed the current available evidence in the literature and addressed their relevance to local clinical practice.


Primary endometrioid adenocarcinoma with coexisting endometrial tuberculosis. A case report.
The most important cause of postmenopausal bleeding is endometrial cancer, whereas genital tuberculosis is uncommon in this age group. The association of these two disorders is extremely rare. Endometrial curettings performed on a 63-year-old woman with a bloody vaginal discharge and thickened endometrium disclosed complex atypical hyperplasia and granulomatous inflammation with caseation necrosis. The uterus contained a well-differentiated endometrial adenocarcinoma with squamous differentiation invading about one-half the myometrial thickness and granulomatous inflammation with caseation necrosis. The lymph nodes were free of disease. Although the coexistence of endometrial cancer and tuberculosis is extremely rare, it may occur in patients who live in the regions with a high prevalence of tuberculosis.


Digital Therapeutics: An Integral Component of Digital Innovation in Drug Development.
Digital therapeutics represent a new treatment modality in which digital systems such as smartphone apps are used as regulatory-approved, prescribed therapeutic interventions to treat medical conditions. In this article we provide a critical overview of the rationale for investing in such novel modalities, including the unmet medical needs addressed by digital therapeutics and the potential for reducing current costs of medical care. We also discuss emerging pathways to regulatory approval and how innovative business models are enabling further growth in the development of digital therapeutics. We conclude by providing some recent examples of digital therapeutics that have gained regulatory approval and highlight opportunities for the near future.


Nitric oxide blunts myogenic autoregulation in rat renal but not skeletal muscle circulation via tubuloglomerular feedback.
This rat renal blood flow (RBF) study quantified the impact of nitric oxide synthase (NOS) inhibition on the myogenic response and the balance of autoregulatory mechanisms in the time domain following a 20 mmHg-step increase or decrease in renal arterial pressure (RAP). When RAP was increased, the myogenic component of renal vascular resistance (RVR) rapidly rose within the initial 7-10 s, exhibiting an approximately 5 s time constant and providing approximately 36% of perfect autoregulation. A secondary rise between 10 and 40 s brought RVR to 95% total autoregulatory efficiency, reflecting tubuloglomerular feedback (TGF) and possibly one or two additional mechanisms. The kinetics were similar after the RAP decrease. Inhibition of NOS (by l-NAME) increased RAP, enhanced the strength (79% autoregulation) and doubled the speed of the myogenic response, and promoted the emergence of RVR oscillations ( approximately 0.2 Hz); the strength (52%) was lower at control RAP. An equi-pressor dose of angiotensin II had no effect on myogenic or total autoregulation. Inhibition of TGF (by furosemide) abolished the l-NAME effect on the myogenic response. RVR responses during furosemide treatment, assuming complete inhibition of TGF, suggest a third mechanism that contributes 10-20% and is independent of TGF, slower than the myogenic response, and abolished by NOS inhibition. The hindlimb circulation displayed a solitary myogenic response similar to the kidney (35% autoregulation) that was not enhanced by l-NAME. We conclude that NO normally restrains the strength and speed of the myogenic response in RBF but not hindlimb autoregulation, an action dependent on TGF, thereby allowing more and slow RAP fluctuations to reach glomerular capillaries.


Acoustic streaming enhances the Multicyclic CO2 capture of natural limestone at Ca-looping conditions.
The Ca-Looping (CaL) process, based on the multicyclic carbonation/calcination of CaO at high temperatures, is a viable technology to achieve high CO2 capture efficiencies in both precombustion and postcombustion applications. In this paper we show an experimental study on the multicyclic CO2 capture of a natural limestone in a fixed bed at CaL conditions as affected by the application of a high-intensity acoustic field. Our results indicate that sound promotes the efficiency of CO2 sorption in the fast carbonation phase by enhancing the gas-solids mass transfer. The fundamentals of the physical mechanism responsible for this effect (acoustic streaming) as well as the technical feasibility of the proposed technique allows envisaging that sonoprocessing will be beneficial to enhance multicyclic CO2 capture in large-scale applications.


Urban and rural factors associated with life satisfaction among older Chinese adults.
This study compared urban and rural factors associated with life satisfaction among older adults in mainland China. Study data were extracted at random from 10% of the Sample Survey on Aged Population in urban/rural China in 2006 for 1980 participants aged 60 and older, including 997 from urban cities and 983 from rural villages. In this study, 54.6% of urban older adults and 44.1% of rural older adults reported satisfaction with their lives. Binary logistic regression analysis showed that financial strain, depressive symptoms, filial piety, and accessibility of health services were significantly associated with life satisfaction for both urban and rural participants, but age and financial exchange with children were only associated with life satisfaction among urban older adults. Findings are consistent with some previous studies that indicated the importance of financial strain, depressive symptoms, filial piety, and accessibility of health services to life satisfaction among the older adults in both urban and rural areas. This study also demonstrated the importance of age and family financial exchange to the life satisfaction of urban older adults.


Vitamin and herbal extracts use in patients diagnosed with dementia: what do health professionals know and think?
Vitamins and herbal extracts are associated with various side effects, potential serious drug interactions and mostly unproven efficacy. Yet, research has shown that nearly half of dementia patients are receiving such medication. Health professionals caring for older people with dementia are central to the safe management of this practice. Therefore, the aim of this study was to assess the views, knowledge and practices of professionals in relation to this issue. Such information is essential to identify potential problems and to inform targeted intervention strategies. Cross-sectional survey carried out across East Sussex in the UK based on a self-administered postal questionnaire. Out of 350 questionnaires sent, 200 responded (57%). Health professionals greatly underestimated the prevalence of over-the-counter medication use (68% believed that less than 10% of patients receive such medication) when compared to published data. A considerable minority (38.7%) reported that vitamins and herbal extracts should be recommended for individuals at risk of developing dementia, despite lack of evidence to support such use. Further, only 24.4% always or often discussed potential side effects/interactions of these supplements with their patients. The views and practices of many health professionals are inconsistent with current best practice. Many professionals do not appear to enquire routinely about non-prescribed medicinal products and adequate advice may not be given to patients/carers. The data highlights a significant issue and calls for urgent action through targeted educational interventions directed not only at dementia patients and their carers, but at health professionals as well.


Trends in Hospital Admission for Diabetic Ketoacidosis in Adults With Type 1 and Type 2 Diabetes in England, 1998-2013: A Retrospective Cohort Study.
This study determined trends in hospital admission for diabetic ketoacidosis (DKA) in adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) from 1998 to 2013 in England. The study population included 23,246 adults with T1DM and 241,441 adults with T2DM from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). All hospital admissions for DKA as the primary diagnosis from 1998 to 2013 were identified. Trends in hospital admission for DKA in incidence, length of hospital stay, 30-day all-cause readmission rate, and 30-day and 1-year all-cause mortality rates were determined using joinpoint regression, negative binomial regression, and logistic regression models. For T1DM, the incidence of hospital admission for DKA increased between 1998 and 2007 and remained static until 2013. The incidence in 2013 was higher than that in 1998 (incidence rate ratio 1.53 [95% CI 1.09-2.16]). For T2DM, the incidence increased 4.24% (2.82-5.69) annually between 1998 and 2013. The length of hospital stay decreased over time for both diabetes types (P ≤ 0.0004). Adults with T1DM were more likely to be discharged within 2 days compared with adults with T2DM (odds ratio [OR] 1.28 [1.07-1.53]). The 30-day readmission rate was higher in T1DM than in T2DM (OR 1.61 [1.04-2.50]) but remained unchanged for both diabetes types over time. Trends in 30-day and 1-year all-cause mortality rates were also stable, with no difference by diabetes type. In the previous two decades in England, hospitalization for DKA increased in adults with T1DM and in those with T2DM, and associated health care performance did not improve except decreased length of hospital stay.


Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington's nucleus CRH neurons.
Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating Barrington's nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. BarrCRH neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRHCre mice show that BarrCRH neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.


Clonning and sequence analysis of the 26 kDa glutathiones-transferase gene of Schistosoma mekongi.
The number of genomic DNA or cDNA sequences of Schistosoma mekongi accessible in Genbank or EMBL is very limited up to now. Recently, two reports have appeared on the molecular phylogeny of Schistosoma species inferred from partial sequence data of rRNA genes; no further sequence data of S. mekongi is available yet. Knowledge of the molecular structure of protein coding genes of S. mekongi will provide a better understanding of gene function in the genus Schistosoma. A cDNA library of S. mekongi adult male was constructed and a cDNA encoding the 26 kDa glutathione S-transferase protein of this species was cloned. Sequence analysis of this cDNA confirmed the close phylogenetic relationship of S. mekongi to S. japonicum.


Hierarchy and Assortativity as New Tools for Binding-Affinity Investigation: The Case of the TBA Aptamer-Ligand Complex.
Aptamers are single stranded DNA, RNA, or peptide sequences having the ability to bind several specific targets (proteins, molecules as well as ions). Therefore, aptamer production and selection for therapeutic and diagnostic applications is very challenging. Usually, they are generated in vitro, although computational approaches have been recently developed for the in silico production. Despite these efforts, the mechanism of aptamer-ligand formation is not completely clear, and producing high-affinity aptamers is still quite difficult. This paper aims to develop a computational model able to describe aptamer-ligand affinity. Topological tools, such as the conventional degree distribution, the rank-degree distribution (hierarchy), and the node assortativity are employed. In doing so, the macromolecules tertiary-structures are mapped into appropriate graphs. These graphs reproduce the main topological features of the macromolecules, by preserving the distances between amino acids (nucleotides). Calculations are applied to the thrombin binding aptamer (TBA), and the TBA-thrombin complex produced in the presence of Na+ or K+. The topological analysis is able to detect several differences between complexes obtained in the presence of the two cations, as expected by previous investigations. These results support graph analysis as a novel computational tool for testing affinity. Otherwise, starting from the graphs, an electrical network can be obtained by using the specific electrical properties of amino acids and nucleobases. Therefore, a further analysis concerns with the electrical response, revealing that the resistance is sensitively affected by the presence of sodium or potassium, thus suggesting resistance as a useful physical parameter for testing binding affinity.


Plankton biodiversity along a gradient of productivity and its mediation by macrophytes.
We studied the effect of aquatic vegetation on the process of species sorting and community assembly of three functional groups of plankton organisms (phytoplankton, seston-feeding zooplankton, and substrate-dwelling zooplankton) along a primary productivity gradient. We performed an outdoor cattle tank experiment (n = 60) making an orthogonal combination of a primary productivity gradient (four nutrient addition levels: 0, 10, 100, and 1000 microg P/L; N/P ratio: 16) with a vegetation gradient (no macrophytes, artificial macrophytes, and real Elodea nuttallii). We used artificial plants to evaluate the mere effects of plant physical structure independently from other plant effects, such as competition for nutrients or allelopathy. The tanks were inoculated with species-rich mixtures of phytoplankton and zooplankton. Both productivity and macrophytes affected community structure and diversity of the three functional groups. Taxon richness declined with increasing plankton productivity in each functional group according to a nested subset pattern. We found no evidence for unimodal diversity-productivity relationships. The proportional abundance of Daphnia and of colonial Scenedesmus increased strongly with productivity. GLM analyses suggest that the decline in richness of seston feeders was due to competitive exclusion by Daphnia at high productivity. The decline in richness of phytoplankton was probably caused by high Daphnia grazing. However, partial analyses indicate that these explanations do not entirely explain the patterns. Possibly, environmental deterioration associated with high productivity (e.g., high pH) was also responsible for the observed richness decline. Macrophytes had positive effects on the taxon richness of all three functional plankton groups and interacted with the initial productivity gradient in determining their communities. Macrophytes affected the composition and diversity of the three functional groups both by their physical structure and through other mechanisms. Part of the macrophyte effect may be indirect via a reduction of phytoplankton production. Our results also indirectly suggest that the often reported unimodal relationship between primary productivity and diversity in nature may be partially mediated by the tendency of submerged macrophytes to be most abundant at intermediate productivity levels.


[The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis].
The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.


Anesthetic and Perioperative Management of Nontransplant Surgery in Patients After Liver Transplant.
We aimed to document the anesthetic management and metabolic, hemodynamic, and clinical outcomes of liver-graft recipients who subsequently undergo nontransplant surgical procedures. We retrospectively analyzed the data of 96 liver-graft recipients who underwent 144 nontransplant surgeries between October 1998 and April 2016 at Başkent University Hospital. The median patient age at the time of nontransplant surgery was 32 years, and 35% were female (n = 33). The median time between transplant and nontransplant surgery was 1231 days. The most frequent types of nontransplant surgery were abdominal (22%), orthopedic (16%), and urologic (13%). Seventy patients had an American Society of Anesthesiologists status of 2 (49%); the status was 3 in 71 patients (49%) and 4 in 3 patients (2%). Of the 144 procedures, 23 were emergent (16%) and 48% were abdominal. General anesthesia was used in 69%, regional anesthesia in 19%, and sedoanalgesia in 11%. Twenty-five patients required intraoperative blood-product transfusion (17%). Intraoperative hemodynamic instability developed in 17% of patients, and hypoxemia developed in 2%. Eleven patients remained intubated at the end of surgery (8%). Of the 144 procedures, 19 (13%) required transfer to the intensive care unit, 108 (75%) transferred to the ward, and the remaining 17 (12%) were discharged on the same day. Eight patients developed respiratory failure (6%), 7 had renal dysfunction (5%), 4 had coagulation abnormalities (3%), and 10 had infectious complications (7%) in the early postoperative period. The median hospital stay was 4 days, and 5 patients (4%) developed rejection during hospitalization. Five patients died of respiratory or infectious complications (4%). Most liver-graft recipients who undergo nontransplant surgery are given general anesthesia, transferred to the ward after the procedure, and discharged without major complications. We suggest that orthotopic liver transplant recipients may undergo nontransplant surgery without any postoperative graft dysfunction.


The speed of adaptation is dependent on the load type during target reaching by intact human subjects.
When lifting or moving a novel object, humans are routinely able to quickly characterize the nature of the unknown load and swiftly achieve the desired movement trajectory. It appears that both tactile and proprioceptive feedback systems help humans develop an accurate prediction of load properties and determine how associated limb segments behave during voluntary movements. While various types of limb movement information, such as position, velocity, acceleration, and manipulating forces, can be detected using human tactile and proprioceptive systems, we know little about how the central nervous system decodes these various types of movement data, and in which order or priority they are used when developing predictions of joint motion during novel object manipulation. In this study, we tested whether the ability to predict motion is different between position- (elastic), velocity- (viscous), and acceleration-dependent (inertial) loads imposed using a multiaxial haptic robot. Using this protocol, we can learn if the prediction of the motion model is optimized for one or more of these types of mechanical load. We examined ten neurologically intact subjects. Our key findings indicated that inertial and viscous loads showed the fastest adaptation speed, whereas elastic loads showed the slowest adaptation speed. Different speeds of adaptation were observed across different magnitudes of the load, suggesting that human capabilities for predicting joint motion and manipulating loads may vary systematically with different load types and load magnitudes. Our results imply that human capabilities for load manipulation seems to be most sensitive to and potentially optimized for inertial loads.


[Chimeric drift in blood erythrocyte population in BALB/c----C57BL/10 and BALB----B10.D2 mice].
Genotypic composition of the erythrocyte population of peripheral blood in 16 aggregation chimeras: BALB/c (H-2dd)----C57BL/10(H-2bb) and BALB/c(H-2dd)----B10.D2(H-2dd) was studied during 10 months. The proportion of cells of parental components was defined visually in the coat and by electrophoresis of allozyme variants at the Gpi-1 locus in blood. The similar increase of blood cells percentage was observed in blood of both types of chimeras with age. In chimeras the skin grafts of both parental types survive. Chimeric drift is not caused by H-2 haplotypes differences between cells of two strains or disturbance of immunological tolerance in the chimeric mice. We propose that chimeric drift results from interaction of hemopoietic cells of different strains in early stages of hemopoiesis.


Childhood misery and disease in later life: the effects on mortality in old age of hazards experienced in early life, southern Sweden, 1760-1894.
This paper assesses the importance of early-life conditions relative to the prevailing conditions for mortality by cause of death in later life using historical data for four rural parishes in southern Sweden for which both demographic and economic data are very good. Longitudinal demographic data for individuals are combined with household socio-economic data and community data on food costs and the disease load using a Cox regression framework. We find strong support for the hypothesis that the disease load experienced during the first year of life has a strong impact on mortality in later life, in particular on the outcome of airborne infectious diseases. Hypotheses about the effects of the disease load on mothers during pregnancy and access to nutrition during the first years of life are not supported. Contemporary short-term economic stress on the elderly was generally of limited importance although mortality varied by socio-economic group.


Incidental Detection of Ovarian Thecoma by 99mTc-MDP Whole-Body Bone Scan: Contribution of Hybrid SPECT/CT.
Ovarian thecoma is a benign and rare neoplasm that accounts for 0.5% to 1% of all ovarian tumors. A 55-year-old woman with known breast cancer underwent a metastatic workup before surgery. The Tc-MDP whole-body bone scan revealed intense uptake in the left pelvic region. Hybrid SPECT/CT imaging showed that the elevated Tc-MDP activity was in a tumor with calcification in the left adnexa. Dynamic enhanced MRI revealed marked enhancement of the tumor. Resection of the tumor was subsequently performed, and pathologic analysis confirmed the diagnosis of an ovarian thecoma.


Minimally invasive reversed Z sternotomy for aortic valve replacement.
The minimally invasive reversed Z sternotomy is a surgical approach for aortic valve operations that provides an excellent view of the aortic root and allows access to the right atrium. It confers the advantages of preservation of the sternocostal articulations and both internal thoracic arteries with no need to enter either pleural cavity. It facilitates aortic and atrial cannulation for cardiopulmonary bypass and allows access for a superior pulmonary vein cardiac vent.


Osmotic demyelination syndrome as the initial manifestation of a hyperosmolar hyperglycemic state.
Osmotic demyelination syndrome (ODS) is a life-threatening demyelinating syndrome. The association of ODS with hyperosmolar hyperglycemic state (HHS) has been seldom reported. The aim of this study was to present and discuss previous cases and the pathophysiological mechanisms involved in ODS secondary to HHS. A 47-year-old man arrived to the emergency room due to generalized tonic-clonic seizures and altered mental status. The patient was lethargic and had a Glasgow coma scale of 11/15, muscle strength was 4/5 in both lower extremities, and deep tendon reflexes were diminished. Glucose was 838 mg/dL; serum sodium and venous blood gas analyses were normal. Urinary and plasma ketones were negative. Brain magnetic resonance revealed increased signal intensity on T2-weighted FLAIR images with restricted diffusion on the medulla and central pons. Supportive therapy was started and during the next 3 weeks the patient progressively regained consciousness and muscle strength and was able to feed himself. At 6-month follow-up, the patient was asymptomatic and MRI showed no residual damage. In conclusion, the association of ODS with HHS is extremely rare. The exact mechanism by which HHS produces ODS still needs to be elucidated, but we favor a rapid hypertonic insult as the most plausible mechanism.


Lateralization of short- and long-term visual memories in an insect.
The formation of memories within the vertebrate brain is lateralized between hemispheres across multiple modalities. However, in invertebrates evidence for lateralization is restricted to olfactory memories, primarily from social bees. Here, we use a classical conditioning paradigm with a visual conditioned stimulus to show that visual memories are lateralized in the wood ant, Formica rufa. We show that a brief contact between a sugar reward and either the right or left antenna (reinforcement) is sufficient to produce a lateralized memory, even though the visual cue is visible to both eyes throughout training and testing. Reinforcement given to the right antenna induced short-term memories, whereas reinforcement given to the left antenna induced long-term memories. Thus, short- and long-term visual memories are lateralized in wood ants. This extends the modalities across which memories are lateralized in insects and suggests that such memory lateralization may have evolved multiple times, possibly linked to the evolution of eusociality in the Hymenoptera.


Mechanistic Picture for Chemomechanical Coupling in a Bacterial Proton-Coupled Oligopeptide Transporter from Streptococcus Thermophilus.
Proton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemomechanical couplings involved in substrate/proton transport and protein structural changes is missing. Therefore, we performed microsecond-level molecular dynamics simulations of bacterial POT PepTSt, which shares ∼80% sequence identity with the human POT, PepT1, in the substrate-binding region. Three different conformational states of PepTSt were simulated, including (i) occluded, apo, (ii) inward-facing, apo, and (iii) inward-facingoccluded, Leu-Ala bound. We propose that the interaction of R33 with E299 and E300 acts as a conformational switch (i.e., to trigger the conformational change from an inward- to outward-facing state) in the substrate transport. Additionally, we propose that E299 and E400 disengage from interacting with the substrate either through protonation or through coordination with a cation for the substrate to get transported. This study provides clues to understand the chemomechanical couplings in POTs and paves the way to decipher the molecular-level underpinnings of the structure-function relationship in this important family of transporters.


The costs of long-term catheterization in the community.
The prevalence of long-term catheterization in the adult population is of the order of 0.03-0.07%, rising to 0.5% in those over 75 years and 2% in those over 85 years old. Studies have shown that the prevalence of urinary incontinence increases with age and is higher in females. Little is known about the costs of long-term catheterization, which have consequences for care decisions. A pilot study was conducted to test (a) the applicability in the UK of a methodology developed in the USA for measuring the cost of long-term catheterization in community-based patients, and (b) the feasibility of using it in larger-scale community-based studies. The study made use of the method developed in the USA by Wagner and Hu (1998) to assess the true costs in the population. Patients were selected in order to represent as broad as possible a range of underlying disease processes and social circumstances. Eight patients were selected, drawn from 3 distinct groups of patients. The pilot study demonstrated wide variation in direct costs for 7 patients living in the community over a 3-month period, ranging from pound 118.80 to pound 2585.26. Since staffing is - for the most part - the most significant cost element, this indicates significant variation in levels of need. Resources deployed for one nursing procedure clearly impact on opportunities to undertake other procedures. An understanding of the costs of any procedure is necessary in order to make best use of the limited resources available.


Polymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary Syndrome and associated pregnancy disorders in South Indian Women.
Polycystic Ovary syndrome (PCOS) is the most common endocrine disorder affecting 5 - 10% of all women of reproductive age group. The present research was carried out to study the impact of Plasminogen Activator Inhibitor (PAI-1) 4G/5G polymorphism (rs1799889) in PCOS, and the risk of developing PCOS in South Indian Population. The study was carried out in 60 subjects of South Indian population (30 PCOS and 30 Non PCOS) recruited from ARC Research and Fertility Centre, Chennai, India. Genotype and Allelic frequencies were compared by Fisher exact test, Hardy Weinberg equilibrium. p<0.05 was considered statistically significant. The Genotype frequency difference between PCOS and non-PCOS was observed as statistically non-significant (p=0.4647, OR=1.3077, 95% CI 0.63-2.68). The allelic frequency distribution in Spontaneous Abortion (SAB) cases in total subjects is not found to be statistically significant (p=0. 29), however the PCOS women carrying mutant homozygous and heterozygous genotype are more prone to recurrent pregnancy loss. Out of 17 Implantation failure cases, 23.52% were found to carry mutant homozygous (4G/4G), and 66.66% carried mutant heterozygous (4G/5G), and 5.88% carried wild type homozygous (5G/5G), the allelic difference was highly significant with 4G (62.5%), and 5G (37.5%). P value is highly significant and recorded at p=0.0164. The positive correlation between PAI-1 4G/5G polymorphism and PCOS risk was not observed in this study, however, the correlation between Recurrent Pregnancy Loss (RPL) and Implantation failures were observed in PCOS cases.


[Effect of the cultivation conditions on alkaloid biosynthesis by Penicillium gorlenkoanum].
The effect of a carbohydrate component of the medium, trace elements and aeration on biosynthesis of the alkaloids costaclavine and epicostaclavine was studied with Penicillium gorlenkoanum. Alkaloid biosynthesis was shown to depend on the nature of a carbohydrate component: virtually no alkaloids were accumulated in media with glucose and fructose although these were synthesized at a high rate in a medium with mannitol. The quantity of synthesized alkaloids and the dynamics of the biosynthesis depended on carbohydrate concentration. The growth and alkaloid synthesis were influenced by traces of zinc, iron, copper and manganese. A more intensive aeration stimulated biomass accumulation but suppressed alkaloid biosynthesis.


[Minor antigens - major impact. The role of minor histocompatibility antigens in allogeneic hematopoietic stem cell transplantation].
Allogeneic hematopoietic cell transplantation (HCT) is often the only curative treatment option for patients with malignant and non-malignant hematological diseases. There is striking evidence that immunological Graft-versus-Leukemia (GvL)-reactions efficiently eradicate malignant cells after transplant. After HLA-matched HCT both the beneficial GvL-effect and the detrimental Graft-versus-Host Disease (GvHD) are mediated by donor derived T-cells specific for minor histocompatibility antigens (mHag) that differ between patient and stem cell donor. In addition, tumor-specific antigens can also be targeted and contribute to GvL-reactivity. This review summarizes the state-of-the-art knowledge on mHag and presents the potential therapeutical options on example of the mHag HA-1. HA-1 is currently the best characterized mHag and particularly attractive for immunotherapy due to the restricted expression on hematopoietic cells and on some solid tumors but not on cells involved during GvHD. This would allow amplifying the endogenous GvL-effect and selectively targeting malignant HA-1-positive cells without causing GvHD. HA-1-specific immunotherapy in eligible patient and donor pairs may range from vaccination with the immunogenic HA-1 peptide to the infusion of HA-1-specific cytotoxic T-cells (adoptive immunotherapy).


Comparison of Long-Term Outcomes of Infliximab versus Adalimumab Treatment in Biologic-Naïve Patients with Ulcerative Colitis.
The tumor necrosis factor-α inhibitors infliximab and adalimumab are standard treatments for moderate to severe ulcerative colitis (UC). However, there has been no headto- head comparison of treatment efficacy and outcomes between the two agents. The aim of this study was to compare the efficacy and long-term outcomes of infliximab versus adalimumab treatment in biologic-naïve patients with UC. We retrospectively analyzed the records of 113 biologic-naïve patients with UC who were treated between September 2012 and December 2017 (the infliximab group [n=83] and the adalimumab group [n=30]). We compared remission and response rates between these groups at 8 and 52 weeks. We used Kaplan-Meier curves to compare long-term outcomes, and logistic regression analysis and Cox-proportional hazard regression models to assess factors affecting outcomes. The median follow-up duration was 25.8 months. Baseline clinical characteristics were similar between groups. There were no significant differences between the two groups in the rate of clinical remission or clinical response at 8 or 52 weeks. Multivariate analyses also showed that long-term outcomes were not significantly different (adjusted hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.81 to 2.56; p=0.208). An elevated C-reactive protein level (greater than 5 mg/L) was a significant predictive factor for poor outcomes (adjusted HR, 2.25; 95% CI, 1.37 to 3.70; p=0.001). During the follow-up period, the rates of adverse event were not significantly different between the two groups (p=0.441). In our study, infliximab and adalimumab had similar treatment efficacy and longterm outcomes in biologic-naïve patients with moderate to severe UC.


Contralateral noise effects on otoacoustic emissions and electrophysiologic responses in normal-hearing adults.
Contralateral noise inhibits the amplitudes of cochlear and neural responses. These measures may hold potential diagnostic utility. The medial olivocochlear (MOC) reflex underlies the inhibition of cochlear responses but the extent to which it contributes to inhibition of neural responses remains unclear. Mertes and Leek [J. Acoust. Soc. Am. 140, 2027-2038 (2016)] recently examined contralateral inhibition of cochlear responses [transient-evoked otoacoustic emissions (TEOAEs)] and neural responses [auditory steady-state responses (ASSRs)] in humans and found that the two measures were not correlated, but potential confounds of older age and hearing loss were present. The current study controlled for these confounds by examining a group of young, normal-hearing adults. Additionally, measurements of the auditory brainstem response (ABR) were obtained. Responses were elicited using clicks with and without contralateral broadband noise. Changes in TEOAE and ASSR magnitude as well as ABR wave V latency were examined. Results indicated that contralateral inhibition of ASSRs was significantly larger than that of TEOAEs and that the two measures were uncorrelated. Additionally, there was no significant change in wave V latency. Results suggest that further work is needed to understand the mechanism underlying contralateral inhibition of the ASSR.


Masculinizer gene controls sexual differentiation in Hyphantria cunea.
The Masculinizer gene, Masc, encodes a lepidopteran-specific novel CCCH-type zinc finger protein, which controls sex determination and dosage compensation in Bombyx mori. Considering the potential application of it in pest control, it is necessary to investigate the function of Masc gene in Hyphantria cunea, a globally invasive forest pest. In the present study, we identified and functionally characterized the Masc gene, HcMasc, in H. cunea. Sequence analysis revealed that HcMASC contained the conserved CCCH-type zinc finger domain, nuclear localization signal, and male determining domain, in which the last was confirmed to be required for its masculinization in BmN cell line. However, expression data showed that unlike male-biased expression in B. mori, HcMasc gene expresses in main all developmental stages or tissues in both sexes. Clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated protein 9-based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes. Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H. cunea and provide a foundation for developing better strategies to control this pest.


Subcompartments of the G1 phase of cell cycle detected by flow cytometry.
Cellular DNA and RNA were simultaneously quantitated in individual cells of cycling and quiescent populations by flow cytometry. Based on differences in RNA content, two distinct subcompartments, G1A and G1B, were recognized in the G1 phase of exponentially growing cells. After mitosis, cells reside in the low-RNA, G1A compartment from which they cannot enter the S phase directly. An increase in RNA above a critical level is required for G1 cells to be able to initiate DNA replication; G1 cells with RNA values above this level are classified as G1B. Cell transition from G1A to G1B and from G1B to S was analyzed in a stathmokinetic experiment on L1210 cells with a doubling time of 10 hr. The half-time of cell residence in the indeterminate state of G1 was found to be 1 hr, and the duration of the deterministic portion of G1 phase was 2 hr. The indeterminate state, although not identical with G1A, is most likely located in G1A. Cell quiescence induced by serum deprivation (3T3 cells) or by addition of n-butyrate (L1210) results in cell arrest at a state which, judged by RNA content, is similar to that of G1A of exponentially growing cells. The exit from this state, however, is much slower after stimulation of these blocked cells than the transition of G1A to G1B in cells growing exponentially. Thymidine or hydroxyurea arrest cells in G1B or perhaps at the border between G1B and S. Prolonged incubation of 3T3 cells to confluence results in a marked loss of cellular RNA below the level of the G1A state. This deep quiescent state (G1Q) is distinctly different from the G1A state of cycling cells or cells blocked in G1A by serum deprivation.


Ischemic foot: definition, etiology and angiosome concept.
Ischemic foot is a condition of decreased arterial perfusion. It has several etiologies, atherosclerotic peripheral arterial disease, including that secondary to diabetes mellitus, being the most common. Other potential causes of ischemic foot are acute embolism from cardiac, arterial or paradoxical sources, and thrombosis secondary to arterial blood clots due to procoagulative states (e.g. vasculitis and hematologic disorders), arterial spasms or injury resulting from drug use or from external or iatrogenic trauma. Prompt diagnosis and revascularization of the affected limb play a crucial role in the treatment of ischemic foot. The angiosome principle, defined by Ian Taylor's landmark anatomic study in 1987, divides the body into three-dimensional anatomic units of tissue fed by a source artery (the angiosome). Detailed knowledge of the vascular anatomy of the leg, and in particular of angiosomes in the foot, helps the clinician make better decisions when dealing with ischemic foot. The physician can better estimate the possibility of wound healing, and decide which type of revascularization has the most chance of success, given the existing blood supply. If surgical or endovascular revascularization is successful, the foot should no longer appear ischemic and painful, and the wounds should granulate. Newly granulating wounds should be carefully protected, and meticulous daily local wound care should be performed to promote healing and prevent infection. The quality of subsequent wound care is also a critical component in promoting healing and avoiding further tissue loss.


Comparative transcriptomic analysis of human and Drosophila extracellular vesicles.
Extracellular vesicles (EVs) are membrane-enclosed nanoparticles containing specific repertoires of genetic material. In mammals, EVs can mediate the horizontal transfer of various cargos and signaling molecules, notably miRNA and mRNA species. Whether this form of intercellular communication prevails in other metazoans remains unclear. Here, we report the first parallel comparative morphologic and transcriptomic characterization of EVs from Drosophila and human cellular models. Electronic microscopy revealed that human and Drosophila cells release similar EVs with diameters ranging from 30 to 200 nm, which contain complex populations of transcripts. RNA-seq identified abundant ribosomal RNAs, related pseudogenes and retrotransposons in human and Drosophila EVs. Vault RNAs and Y RNAs abounded in human samples, whereas small nucleolar RNAs involved in pseudouridylation were most prevalent in Drosophila EVs. Numerous mRNAs were identified, largely consisting of exonic sequences displaying full-length read coverage and enriched for translation and electronic transport chain functions. By analogy with human systems, these sizeable similarities suggest that EVs could potentially enable RNA-mediated intercellular communication in Drosophila.


Carvedilol (Kredex) reduces infarct size in a canine model of acute myocardial infarction.
Carvedilol (Kredex) is a multiple action, antihypertensive agent that may also prove to be useful in the treatment of angina and congestive heart failure. Carvedilol combines in one molecule both beta-adrenoceptor blocking and vasodilating activities. Inasmuch as beta-adrenoceptor blocking agents are known to be cardioprotective and thereby reduce infarct size, it is logical to assume that carvedilol, likewise, would possess this desirable activity. Furthermore, the additional vasodilating activity of carvedilol could contribute to further reductions in infarct size by reducing myocardial work (and therefore myocardial oxygen demand) through reductions in both afterload and myocardial wall tension. As such, we have investigated the ability of carvedilol to reduce infarct size in a canine model of acute myocardial infarction. Carvedilol (1 mg/kg i.v.) or its vehicle, dimethylformamide, were administered 15 min before left circumflex coronary artery (LCX) occlusion. Following 1 h of LCX occlusion, dogs were reperfused through a critical stenosis and then allowed to recover for 24 h. Carvedilol-treated animals exhibited a 78% reduction in infarct size compared to vehicle controls, such that the percentage of the left ventricle infarcted was reduced significantly from 16.2 +/- 4.1% in control animals to 3.6 +/- 1.3% in animals treated with carvedilol (p = 0.017, n = 6). Stained tissue sections of the left ventricle were photographed, digitized and color-enhanced using an Image Analysis Computer System, and three-dimensional reconstruction of the left ventricle, including the infarcted areas, was performed.(ABSTRACT TRUNCATED AT 250 WORDS)


Fluorine Compounds of Xenon and Radon.
Xenon and fluorine combine readily. Xenon tetrafluoride is a colorless crystalline material, stable at room remperature. The existence of at least one other fluoride and two oxyfluorides has been demonstrated. The heaviest "inert gas," radon, also reacts with fluorine, yielding a compound less volatile than xenon tetrafluoride.


Three-dimensional nanoscopy of whole cells and tissues with in situ point spread function retrieval.
Single-molecule localization microscopy is a powerful tool for visualizing subcellular structures, interactions and protein functions in biological research. However, inhomogeneous refractive indices inside cells and tissues distort the fluorescent signal emitted from single-molecule probes, which rapidly degrades resolution with increasing depth. We propose a method that enables the construction of an in situ 3D response of single emitters directly from single-molecule blinking datasets, and therefore allows their locations to be pinpointed with precision that achieves the Cramér-Rao lower bound and uncompromised fidelity. We demonstrate this method, named in situ PSF retrieval (INSPR), across a range of cellular and tissue architectures, from mitochondrial networks and nuclear pores in mammalian cells to amyloid-β plaques and dendrites in brain tissues and elastic fibers in developing cartilage of mice. This advancement expands the routine applicability of super-resolution microscopy from selected cellular targets near coverslips to intra- and extracellular targets deep inside tissues.


[Application of Ethyol during chemotherapy in patients with impaired kidney function. Description of three cases].
Nephrotoxicity is observed in 30% of patient's treated with chemotherapy schedules based on cisplatin analogues. Ethyol (amiphostin) was used as a protectant of kidney in 3 paediatric patients with neoplastic disease. Two patients suffered from Wilms tumour. One of them, a 5 month old boy presented with agenesis of the right kidney and stage II tumour in the left kidney. Bilateral Wilms tumour was recognised in a 6 year old girl. In both cases glomerular filtration was diminished. The third patient was a girl aged 5 who had isolated relapse of neuroblastoma in the central nervous system. Primary treatment caused nephrotoxic complications such as Fanconi syndrome and diminished glomerular filtration (66 ml/min). In these 3 cases Ethyol was used every lime before analogues of cisplatin were given. Tolerance and the effect of this protectant were good.


The standpoint of gene therapy programs.
The 10th Annual Meeting of the American Society of Gene Therapy focused on the development of a wide variety of gene delivery systems, clinical trials, preclinical studies, problems related to gene expression, engineering of cell and animal models for the study of various pathological conditions, immunogenicity of adenoviral-derived vectors and use of gene transfer technology for genetic immunization purposes. A major emphasis was placed on the improvement of vector design and safety issues, such as insertional mutagenesis and host immune responses to gene delivery systems.


[Value of polymerase chain reaction (PCR) in diagnosis of tuberculosis and mycobacterium infections caused by ubiquitous mycobacteria].
The rise in both incidence and the number of multi-drug-resistant strains has made tuberculosis an alarming health problem even in some developed countries. Moreover, due to the HIV pandemic an increase in mycobacterial diseases caused by ubiquitous mycobacteria has been observed. The microbiological standard procedures are critical diagnostic tools, and a more rapid detection of mycobacteria by new laboratory techniques would be helpful. We investigated the role of the polymerase chain reaction (PCR) in the detection of M. tuberculosis complex and of ubiquitous mycobacteria. 580 clinical specimens obtained from 525 patients were examined. The majority of sampled material was bronchoalveolar lavage fluid. Based on cultural identification of mycobacteria, the incidence of tuberculosis in our patients was 3.4%. For detection of M. tuberculosis complex the insertion sequence IS 6110 was used. Relative to cultural identification, diagnostic specificity of PCR was 99.5%, and sensitivity was 66.7%, respectively. In 3.0% of the total patient group and in 8.8% of HIV-infected patients an infection by ubiquitous mycobacteria was found. Ubiquitous mycobacteria were detected using the hypervariable region of the 16S-rRNA-gene, and species-identification was done by sequence analysis. For ubiquitous mycobacteria, sensitivity of PCR was 60.0% relative to cultural identification and 62.5% relative to a proven disease. PCR is a useful method in the rapid diagnosis of pulmonary tuberculosis with excellent specificity but lack of sensitivity.


The design, synthesis and activity of pentapeptide pp60c-src inhibitors containing L-phosphotyrosine mimics.
Efficient syntheses of 4-(R,S-hydroxyphosphonomethyl)-L-phenylalanine and 4-carboxy-L-phenylalanine within the context of the pentapeptide Ac-Ile-X-Gly-Glu-Phe-NH2 (wherein X = the unnatural amino acid) illustrate the use of a divergent synthetic strategy from an advanced common peptide intermediate to more readily access peptide-based tyrosine kinase inhibitors. The key intermediate, Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2, was synthesized by a facile palladium-catalyzed carbonylation of Ac-Ile-Phe(4-iodo)-Gly-Glu(O-tBu)-Phe-NH2. Oxidation of Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2 with tetrabutylammonium permanganate or addition of di-t-butylphosphite, both followed by trifluoroacetic acid deprotection, gave the target pentapeptide inhibitors wherein X = 4-carboxy-L-phenylalanine or 4-(R,S-hydroxyphosphonomethyl)-L-phenylalanine, respectively. These two peptides gave somewhat more potent inhibition of the tyrosine kinase pp60c-src than the corresponding pentapeptide wherein X = L-phenylalanine, demonstrating that appended functionalities at the 4-position are accepted and can enhance binding through added interactions within the catalytic region of the active site.


[Care of the aged population].
Topical problems in the care of geriatric patients are presented. Qualified estimations suggest that subjects above 60 years of age represent more than one half of the daily clientele of a district physician. The basic characteristics of elderly people are their fragility, readily attained decompensation and diminished adaptability. Their hospitalization is thus demanding and involves risks. Geriatric patients require comprehensive care. Treatment without removing their social fears and psychic anxiety does not yield adequate effect. Active involvement of relatives into the program of care may prove a beneficial contribution. The main aim is to provide comprehensive health and social care primarily at the patient's home. (Ref. 10.)


Health Care Waste Management Practice in Health Care Institutions of Nepal.
Medical waste is considered as a major public health hazard. In a developing country like Nepal, there is much concern about the management practice of medical waste. This study aimed to assess Health Care Waste Management practice among Health Care Institutions in Nepal. A cross sectional study was carried out between July 2012 to June 2013 in 62 different Health Care Institutions, selected from stratified proportionate random sampling technique from all administrative regions of Nepal. A structured questionnaire and observation checklist were used for data collection. The waste generation rate is found significantly correlated with bed capacity, patient flow rate and annual budget spent in the hospital. It is found significantly higher in Teaching hospital than other Health Care Institutions of Nepal. An average of 3.3 kg/day/patient of medical waste (2.0 kg/day/patient non-hazardous and 1.0 kg/day/patient hazardous waste) was generated during the study period. Further, it was found that most of the Health care wastes were not disinfected before transportation to waste disposal sites. Very limited number of Health Care Institutions had conducted Environmental Assessment. Similarly, some of the Health Care Institutions had not followed Health care waste management guideline 2009 of Nepal Government. We found poor compliance of medical waste management practice as per existing legislation of Government of Nepal. Hence, additional effort is needed for improvement of Health care waste management practice at Health Care Institutions of Nepal.


Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions.
Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors. We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used. As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions. It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury. Cite this article: Bone Joint Res 2015;4:170-175.


The Progetto Nazionale Emorragia Digestiva (PNED) system vs. the Rockall score as mortality predictors in patients with nonvariceal upper gastrointestinal bleeding: A multicenter prospective study.
The predictive scale for mortality risk in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) proposed by Italy's PNED (Progetto Nazionale Emorragia Digestiva) group has not been validated in Latin America since its original publication. To compare the PNED system and the Rockall score as mortality predictors in patients hospitalized for NVUGIB. A multicenter, prospective, cross-sectional, analytic study was conducted that recruited patients diagnosed with nonvariceal upper gastrointestinal bleeding within the time frame of 2011 to 2015. Six Mexican hospital centers participated in the study. The Rockall and PNED system scores were calculated, classifying the patients as having mild, moderate, or severe disease. The association between mortality and risk was determined through the chi-square test and relative risk (RR) calculation. Statistical significance was set at a P<.05. Information on 198 patients was collected. Only 8 patients (4%) died from causes directly associated with bleeding. According to the Rockall score, 46 patients had severe disease (23.2%), 5 of whom died, with a RR of 5.5 (CI 1.35-22.02, P=.006). In relation to the PNED, only 8 patients had severe disease (4%), 5 of whom died, with a RR of 38.7 (CI 11.4-137.3, P=.001). The PNED system was more selective for classifying a case as severe, but it had a greater predictive capacity for mortality, compared with the Rockall score.


Induction of human T cell proliferation by a monoclonal antibody to CD5.
A mouse mAb, TS 43, which recognized the human CD5 molecule, was found to induce the proliferation of human peripheral blood T cells. TS 43 mAb precipitated from 125I-radiolabeled T cells a 67-kDa band, which comigrated with the 67-kDa band precipitated by the anti-CD5 mAb OKT1. Preclearing of cell lysates with OKT1 mAb abolished the capacity of TS 43 mAb to precipitate radiolabeled material from T cell lysates. Furthermore, a mouse T cell hybridoma transfected with human CD5 was stained by TS 43 mAb. T cell proliferation mediated by TS 43 mAb was monocyte dependent, and was accompanied by IL-2R expression and by IL-2 synthesis. T cell activation by TS 43 mAb involved a rise in intracellular calcium level (CA2+)i and was dependent on the expression of the TCR/CD3 complex because no rise in (Ca2+)i was observed in a TCR-beta-deficient Jurkat T cell mutant. This study indicates that CD5 should be added to the list of surface molecules that can signal T cells to proliferate.


Neurological adverse events associated with PD-1/PD-L1 immune checkpoint inhibitors.
Immunotherapy is a promising method for cancer treatment. Among them, immune checkpoint inhibitors targeting PD-1/PD-L1 are increasingly used for certain cancers. However, with the widespread use of such drugs, reports of immune-related adverse events (irAEs) are also increasing. Neurological adverse events (nAEs) are one of the irAEs that affect the peripheral and central nervous systems. They are characterized by low incidence, hard to diagnose, and life-threatening risks, which have a significant impact on the prognosis of patients. Biomarker-based early diagnosis and subsequent treatment strategies are worthy of attention, and comprehensive management of irAEs is important for optimizing patients' quality of life and long-term outcomes. In this review, we summarized the mechanisms, common symptoms, early biomarkers, treatments, and future research directions of nAEs, in order to provide a comprehensive overview of immune checkpoint inhibitor-related nAEs targeting PD-1/PD-L1.


MiR-3571 modulates the proliferation and migration of vascular smooth muscle cells by targeting claudin 1.
Background and aims: The miRNA-based post-transcription modification has been extensively studied in hypertension. It however remains elusive how miRNA expression is regulated in this pathological process. We hypothesize that hydroxymethylation in the promoter regions tightly controls the levels of key miRNAs, which in turn affects the development of hypertension. Methods: The levels of hydroxymethylation in the promoter regions from thoracic aortic tissues were compared between spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs), using hydroxymethylcytosine DNA immunoprecipitation (hMeDIP) sequencing. The altered hydroxymethylation level of miR-3571 was confirmed by glucosylation-coupled hydroxymethylation-sensitive qPCR. We further identified claudin 1(CLDN1) as a key target of miR-3571 via bioinformatic prediction (targetscan) and dual-luciferase activity assays. Finally, we analyzed the contribution of miR-3571/CLDN1 axis in the proliferation and migration of vascular smooth muscle cells (VSMCs). Results: The hydroxymethylation level of miR-3571 promoter region in thoracic aortic tissue from spontaneously hypertensive rats was lower than that from normotensive Wistar-Kyoto rats. Accordingly, the expression of miR-3571 was lower during hypertension, with up-regulated CLDN1 protein levels. More importantly, we found that miR3571 overexpression led to phenotypic changes of VSMCs, and inhibited the proliferation and migration of muscle cells via suppressing CLDN1 as well. Our findings further suggested that CLDN1 up-regulation increase the activity of ERK1/2 in VSMCs. Conclusions: Our study suggested that hydroxymethylation in the promoter regions controlled the level of miR-3571 and revealed the important roles of miR-3571 and CLDN1 in VSMCs during the development of hypertension. In addition, our results also indicated that miR-3571/CLDN1 axis regulated the functions of VSMCs via the ERK1/2 pathway. Taken together, our findings support miR-3571 as a novel biomarker for the diagnosis and prevention of hypertension.


Bioinformatics and Network Pharmacology-Based Approaches to Explore the Potential Mechanism of the Antidepressant Effect of Cyperi Rhizoma through Soothing the Liver.
Major depressive disorder (MDD) has become the second most common disease worldwide, making it a threat to human health. Cyperi Rhizoma (CR) is a traditional herbal medicine with antidepressant properties. Traditional Chinese medicine theory states that CR relieves MDD by dispersing stagnated liver qi to soothe the liver, but the material basis and underlying mechanism have not been elucidated. In this study, we identified the active compounds and potential anti-MDD targets of CR by network pharmacology-based approaches. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we hypothesized that the anti-MDD effect of CR may be mediated by an altered response of the liver to lipopolysaccharide (LPS) and glucose metabolism. Through bioinformatics analysis, comparing normal and MDD liver tissue in rats with spontaneous diabetes, we identified differentially expressed genes (DEGs) and selected PAI-1 (SERPINE1) as a target of CR in combating MDD. Molecular docking and molecular dynamics analysis also verified the binding of the active compound quercetin to PAI-1. It can be concluded that quercetin is the active compound of CR that acts against MDD by targeting PAI-1 to enhance the liver response to LPS and glucose metabolism. This study not only reveals the material basis and underlying mechanism of CR against MDD through soothing the liver but also provides evidence for PAI-1 as a potential target and quercetin as a potential agent for MDD treatment.


Single-cell transcriptomics provide insight into metastasis-related subsets of breast cancer.
Breast cancer metastasis is a complex, multi-step process, with high cellular heterogeneity between primary and metastatic breast cancer, and more complex interactions between metastatic cancer cells and other cells in the tumor microenvironment. High-resolution single-cell transcriptome sequencing technology can visualize the heterogeneity of malignant and non-malignant cells in the tumor microenvironment in real time, especially combined with spatial transcriptome analysis, which can directly compare changes between different stages of metastatic samples. Therefore, this study takes single-cell analysis as the first perspective to deeply explore special or rare cell subpopulations related to breast cancer metastasis, systematically summarizes their functions, molecular features, and corresponding treatment strategies, which will contribute to accurately identify, understand, and target tumor metastasis-related driving events, provide a research basis for the mechanistic study of breast cancer metastasis, and provide new clues for its personalized precision treatment.


Establishing the Essential Role of Household Extenders for Surgeon Wellbeing.
The aim of this study was to investigate the association between a change in household support during the Covid-19 pandemic and surgeon stress. The hours and unpredictability of surgical practice often necessitate the employment of household extenders (eg, child caregivers) to maintain a safe home environment for surgeons and their families. The Covid-19 pandemic destabilized these relationships and provided an opportunity to reflect on the role that household extenders play in a surgical household. A multi-institutional telephone survey of surgeons practicing at five geographically diverse academic institutions was conducted (May 15, 2020-June 5, 2020). Surgeons were classified by change in household extenders (HE) during the pandemic (decrease, increase, no change, or none). The primary outcome was self-reported surgeon stress level. Multivariable linear regression was used to examine the relationship between change in HE and surgeon stress, adjusting for training and relationship status, the presence of pets and children in the household, and study site. The majority (182, 54.3%) of surgeons employed HE before the pandemic; 121 (36.1%) reported a decrease in HE during the pandemic, 9 (2.7%) reported an increase, and 52 (15.5%) reported no change. Stress scores varied significantly by change in HE group ( P = 0.016). After controlling for potential confounders, having an increase in HE was associated with a higher stress score (+1.55 points) than having no decrease in HE (P = 0.033), and having a decrease in HE was associated with a higher stress score (+0.96 points) than having no decrease ( P = 0.004). Household extenders play a vital and complex role in enabling the healthcare workforce to care of the population. Surgeons who experienced a change in household extenders reported the highest stress levels. We suggest that health systems should proactively support surgeons by supporting the household extender workforce.