Activation of ion transport systems during cell volume regulation.
This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na+-H+ and Cl(-)-HCO3- exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K+ and Cl-conductances, a K-Cl cotransport system, or parallel K+-H+ and Cl(-)-HCO3- exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that traverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na+-H+ and Cl(-)-HCO3- exchange systems. Both Na-Cl and Na-K-2Cl cotransport systems have been identified in the medullary Loop of Henle and it is postulated that the Na-K-2Cl cotransport system predominates during RVI and affects transepithelial NaCl transport while the Na-Cl cotransport system may function during RVD in these cells.


Quality assessment of prostate cancer reports to the Danish Cancer Registry.
The Danish Cancer Registry (DCR) is the oldest nationwide population-based cancer registry in the Nordic countries. At the time of the study the DCR recorded date of diagnosis, tumor stage and initial treatment. The validity of the clinical information reported to the DCR has never been analyzed. Patients diagnosed with prostate cancer from 1 May to 31 December 1997 and living in eight Danish counties were identified through the DCR. Clinical data was retrieved from hospital records where date of diagnosis, stage at diagnosis and treatment received were registered. The mean age at diagnosis was 74.6 years (s.d. 8.6 years). Diagnosis was verified histologically for 87% of cases. Overall 95% of the patients had a difference less than three months between the reported date of diagnosis and the date found in hospital records. Correction of dates of diagnosis had no impact on survival. Hospital records identified 86 patients with T1-2 disease without distant metastases (M0), but only 56 of these patients (65%) were reported to the DCR as having localized disease. According to hospital records a total of 242 patients were confirmed having distant metastases (M1) at diagnosis but only 139 of these cases (57%) were reported to the DCR as such. Considerable "over reporting" of curative treatment was observed. The DCR has been shown to be reliable in terms of new cases being reported. For the majority of cases there were insignificant differences concerning the date of diagnosis. However, the DCR information on stage and treatment was found to be inaccurate. Since 2004 the DCR registration process, including staging according to the TNM classification, has been carried out electronically from several registers. Future comparison between cohorts of different time intervals or international comparison should be interpreted with caution when clinical information is included.


A naturally derived small molecule disrupts ligand-dependent and ligand-independent androgen receptor signaling in human prostate cancer cells.
Continued reliance on androgen receptor (AR) signaling is a hallmark of prostate cancer, including the development of castration-resistant prostate cancer (CRPC), making it an attractive therapeutic target for prostate cancer treatment. Mahanine is a novel carbazole alkaloid derived from the leaves of Murraya koenigii, commonly known as the curry leaf plant, which grows widely across East-Asia. We show here that mahanine possesses the ability to inhibit ligand-dependent and -independent AR transactivation, leading to a prominent decline in AR target gene expression. Mahanine treatment causes a time- and dose-dependent decline in AR protein levels, including truncated AR splice variants, in a panel of androgen-responsive and -independent prostate cancer cells. The decrease in AR levels induced by mahanine occurs posttranslationally by proteasomal degradation, without any change in the AR gene expression. Mahanine treatment induces an outward movement of the AR from the nucleus to the cytoplasm, leading to an initial increase in cytoplasmic AR levels, followed by a gradual decline in the AR levels in both cellular compartments. Ligand-induced AR phosphorylation at Ser-81, a phospho-site associated with prostate cancer cell growth and AR transactivity, is greatly diminished in the presence of mahanine. The decline in AR phosphorylation at Ser-81 by mahanine occurs via the inactivation of mitotic kinase CDK1. Collectively, our data demonstrate that mahanine strongly disrupts AR signaling and inhibits the growth of androgen-dependent and -independent prostate cancer cells, thereby implicating a therapeutic role of mahanine in prostate cancer treatment.


High-resolution 2D 1H-15N NMR characterization of persistent structural alterations of proteins induced by interactions with silica nanoparticles.
The binding of protein to solid surfaces often induces changes in the structure, and to investigate these matters we have selected two different protein-nanoparticle systems. The first system concerns the enzyme human carbonic anhydrase II which binds essentially irreversibly to the nanoparticles, and the second system concerns human carbonic anhydrase I which alternate between the adsorbed and free state upon interaction with nanoparticles. Application of the TROSY pulse sequence has allowed high-resolution NMR analysis for both of the protein-nanoparticle systems. For HCAII it was possible to observe spectra of protein when bound to the nanoparticles. The results indicated that HCAII undergoes large rearrangements, forming an ensemble of molten globule-like structures on the surface. The spectra from the HCAI-nanoparticle system are dominated by HCAI molecules in solution. A comparative analysis of variations in intensity from 97 amide resonances in a 1H-15N TROSY spectrum revealed the effects from interaction with nanoparticle on the protein structure at amino acid resolution.


Psychosocial adjustment in young adulthood of women who experienced an eating disorder during adolescence.
To examine the impact of an adolescent eating disorder on psychosocial adjustment in young adulthood. A randomly selected sample of high school girls was assessed on a wide array of psychosocial and diagnostic variables twice during adolescence (n = 891, n = 810), and a stratified subset (n = 539) was assessed during their 24th year. Based on their history of psychopathology before age 19, participants were categorized into (1) partial- or full-syndrome eating disorder (ED; n = 36); (2) non-comorbid major depressive disorder (MDD; n = 95); (3) non-mood disorder without ED or MDD (NMD; n = 64); and (4) no disorder (ND; n = 138). Discriminant function analysis identified a single significant function (variance = 57%) in which the ED group was significantly elevated (mean = 0.87, SD = 1.20) compared with the other three groups; the MDD (mean = 0.14, SD = 1.00) and NMD (mean = 0.17, SD = 0.99) group means were intermediary and differed from the ND group (mean = -0.40, SD = 0.95). Despite apparent recovery of ED symptoms among most ED cases, women with a history of adolescent ED evidenced significant impairments in health, self-image, and important areas of social functioning. These findings underscore the clinical significance of adolescent ED.


Etiology and epidemiology of viral pneumonia among hospitalized children in rural Mozambique: a malaria endemic area with high prevalence of human immunodeficiency virus.
The role of viruses in pediatric pneumonia remains poorly studied in sub-Saharan Africa, where pneumonia-associated mortality is high. During a 1-year hospital-based surveillance, a nasopharyngeal aspirate (NPA) was collected from children aged <5 years admitted to hospital in rural Mozambique with clinically severe pneumonia. Identification of 12 respiratory viruses was performed by polymerase chain reactions (PCR). Study children were also tested for invasive bacterial infection (IBI), Plasmodium falciparum parasitemia, and HIV. Almost half (394/807) of the children hospitalized with clinically severe pneumonia had at least one respiratory virus detected. A total of 475 viruses were detected among these 394 children, the most prevalent ones were rhinovirus (41%), adenovirus (21%), and respiratory syncytial virus (11%). Eleven percent of viral infected children had concomitant IBI, 15% had malaria parasites, and 25% had HIV coinfection. Viral infection was 5.5 to 16 times more prevalent among HIV-infected children and incidence rate ratios varied according to virus. Inhospital mortality of viral cases was 9%, being highest among cases with IBI coinfection (odds ratio = 7) or HIV infection (odds ratio = 7). Study results highlight the high prevalence of respiratory viruses among hospitalized pneumonia cases in Mozambique. HIV infection is an important contributor to the high burden of disease and associated mortality of viral pneumonia. IBI also contributes to a worse prognosis of viral cases. Strategies to prevent mother-to-child transmission of HIV as well as introduction of Hib and pneumococcal vaccines could have a substantial impact on reduction of viral pneumonia and associated mortality among children in rural Africa.


Shock wave lithotripsy does not impair renal function in a Swine model of metabolic syndrome.
To determine whether shock wave lithotripsy (SWL) may be a risk factor for renal functional impairment in a swine model of metabolic syndrome (MetS). Nine-month-old female Ossabaw pigs were fed an excess calorie atherogenic diet to induce MetS. At 15 months of age, the MetS pigs were treated with 2000 SWs or an overtreatment dose of 4000 SWs targeted at the upper pole calyx of the left kidney (24 kV at 120 SWs/min using the unmodified Dornier HM3 lithotripter; n=5-6 per treatment group). Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured in conscious pigs before and ∼60 days after SWL to provide a qualitative assessment of how well both kidneys were filtering (glomerular filtration rate [GFR]). Bilateral renal function was assessed at ∼65 days post-SWL in anesthetized pigs with GFR and effective renal plasma flow (ERPF) quantified by the renal clearance of inulin and para-amino hippurate, respectively. Cr and BUN values were within normal limits before SWL and remained unchanged after lithotripsy in both the 2000 SW- and 4000 SW-treated pigs. GFR and ERPF of kidneys treated with SWL at either SW dose were similar to the contralateral nontreated kidney. Chronic histological changes in the SW-treated pole of the kidney included interstitial fibrosis, sclerotic glomeruli, and dilated and atrophic tubules. Our results are consistent with the view that a single SWL session does not result in renal impairment, even in the presence of MetS.


Cloning and sequencing of PYBP, a pyrimidine-rich specific single strand DNA-binding protein.
In the human transferrin gene promoter, PRI and DRI are positive cis-acting elements interacting respectively with two families of proteins, Tf-LF1 and Tf-LF2. In this paper, we report the purification from rat liver nuclei, of one of these factors, PYBP, as well as the cloning and the sequencing of its cDNA. PYBP is a DNA-binding protein, purified as a 58 kDa doublet which binds only to single strand pyrimidine-rich DNA present for example in PRI and DRI. The protein binds also to a similar polypyrimidine tract present in one of the two strands of a DNA regulatory element of the rat tyrosine aminotransferase gene enhancer. PYBP gene is transcribed ubiquitously as a roughly 2.8 kb RNA which is likely to be subject to an alternative splicing. PYBP is highly homologous to a mouse nuclear protein, as well as to PTB, its human version, which interacts specifically with the pyrimidine tracts of introns. Primary structure information and predicted secondary structure elements of the protein indicate that PYBP contains four sequence repeats. Each of these repeats appears to exhibit the typical RNA recognition motif found in several proteins interacting with RNA or single strand DNA. Finally several hypotheses concerning the biological function of PYBP are presented.


Combined carotid endarterectomy and cardiac surgery for concomitant carotid and cardiac disease.
Carotid artery disease is one of the important factors of neurological complications after cardiac surgery. In this study we present our surgical experience and discuss its implication for patients with carotid and cardiac disease. Five patients underwent combined carotid endarterectomy (CEA)/cardiac surgery including thoracic aortic repair. There were three male and two female patients, with a mean age of 67+/-10 years (range, 54-75 years). All patients had an 80% or greater stenosis in the unilateral internal carotid artery. Three patients had coronary artery disease and underwent combined CEA/off-pump coronary artery bypass grafting (OPCAB). One patient had an aortic valve stenosis (AS) with repeated syncope and chest pain, and underwent combined CEA/aortic valve replacement. The remaining patient had an extremely large aortic arch aneurysm (90 mm) and underwent combined CEA/total arch replacement. There were no surgical or hospital deaths. No perioperative complications including myocardial infarction and stroke occurred. During the follow-up period, lasting from 2 months to 27 months (mean, 13 months), there were no late deaths, neurological complications nor cardiac events. Combined CEA/cardiac surgery offered an acceptable morbidity in these complex patients. Due to the preliminary nature of our study, further follow-up and experience with our management strategy are necessary.


The effectiveness of screening and treating Helicobacter pylori in the management of dyspepsia.
(1) To investigate the effects of a Helicobacter pylori screening and treatment strategy on open access endoscopy referral rates in dyspeptic patients aged < 40 years. (2) To determine the effectiveness of an H. pylori screening and treatment strategy, compared with endoscopy, in reducing dyspeptic symptoms, and in the utilization of dyspepsia related health care in general practice. Subjects were dyspeptic patients aged < 40 years, who were not taking NSAIDs and were without sinister symptoms. Patients were referred by their general practitioners. The proportion of endoscopies carried out in patients aged < 40 years during the 5 years before the introduction of a screening and treatment strategy was compared with the proportion 2 years afterwards, as determined in a retrospective audit. Dyspepsia scores were obtained from unselected endoscopy patients and those who received a 13C-urea breath test (13C-UBT) at their initial visit and 6 months later. The number of visits made by patients with dyspepsia to their GPs, as well as the number of prescriptions given for antisecretory drugs, during the 6 months before attending for investigation were compared, in the same patient groups, with the same variables during the 6 months after the investigation. There was a 37% reduction in open access endoscopies performed in patients aged < 40 years (95% CI, 34-40%) following the introduction of the 13C-UBT service. Six months after attending the 13C-UBT service there was a significant fall in dyspepsia score (15.5 +/- 7.4 to 7.2 +/- 7.0, P < 0.0001), general practice dyspepsia consultations (2.0 +/- 1.3 to 1.0 +/- 1.7, P < 0.0001), H2 receptor antagonist prescription (14.2 +/- 32.6 tablets to 6.7 +/- 25.6 tablets, P = 0.006) but not proton pump inhibitor prescription (6.9 +/- 21.9 tablets to 7.2 +/- 27.6 tablets, P = 0.90). These changes were not significantly different from those found in the open access endoscopy control patients. An H. pylori screening and treatment strategy reduces the endoscopy workload in young dyspeptic patients. This strategy appears to be as effective as endoscopy in reducing dyspepsia symptoms, dyspepsia consultation rates and the prescribing of anti-secretory drugs.


Disability in adults with hip and knee arthroplasty: a French national community based survey.
To compare levels of disability of people with and without hip and knee arthroplasty in a random national sample. In 1999 a screening questionnaire to classify people into groups of increasing probabilities of disability was sent to 417 500 people; response rate 86%. The study population was obtained by a stratified randomisation, with a high sampling rate for the most severely disabled group and a minimum sampling rate for people without daily living restrictions. A computer assisted interview to assess levels of disability, dependence, and handicap was given to 21 760 people; response rate 78%. A weighting factor was applied to obtain estimates representative of the French population. The presence of chronic conditions, impairments, and disability was ascertained from the subjects' reports. The hip and knee arthroplasty group comprised 815 subjects in the sample, indicating an estimated 691 000 subjects (95% confidence interval (CI) 597 000 to 785 000) in the French non-institutionalised population. The prevalence of arthroplasty is estimated at 1.2%. After adjustments for confounding factors, activity limitations were greater among subjects with arthroplasty for the following activities: climbing stairs (odds ratio (OR)=4.0, 95% CI 2.8 to 5.8); walking distance (OR=3.4, 95% CI 2.5 to 4.6 for a walking distance less than 500 m); bending forward (OR=3.2, 95% CI 2.2 to 4.7); cutting toenails (OR=2.8, 95% CI 1.9 to 3.9); carrying (OR=2.6, 95% CI= 1.8 to 3.8); shopping (OR=2.1, 95% CI 1.5 to 2.9). This study would be useful to policy-makers considering population strategies for managing disabling arthritis.


Integrin-linked kinase regulates senescence in an Rb-dependent manner in cancer cell lines.
Anti-integrin-linked kinase (ILK) therapies result in aberrant mitosis including altered mitotic spindle organization, centrosome declustering and mitotic arrest. In contrast to cells that expressed the retinoblastoma tumor suppressor protein Rb, we have shown that in retinoblastoma cell lines that do not express Rb, anti-ILK therapies induced aberrant mitosis that led to the accumulation of temporarily viable multinucleated cells. The present work was undertaken to: 1) determine the ultimate fate of cells that had survived anti-ILK therapies and 2) determine whether or not Rb expression altered the outcome of these cells. Our data indicate that ILK, a chemotherapy drug target is expressed in both well-differentiated, Rb-negative and relatively undifferentiated, Rb-positive retinoblastoma tissue. We show that small molecule targeting of ILK in Rb-positive and Rb-deficient cancer cells results in increased centrosomal declustering, aberrant mitotic spindle formation and multinucleation. However, anti-ILK therapies in vitro have different outcomes in retinoblastoma and glioblastoma cell lines that depend on Rb expression. TUNEL labeling and propidium iodide FACS analysis indicate that Rb-positive cells exposed to anti-ILK therapies are more susceptible to apoptosis and senescence than their Rb-deficient counterparts wherein aberrant mitosis induced by anti-ILK therapies exhibit mitotic arrest instead. These studies are the first to show a role for ILK in chemotherapy-induced senescence in Rb-positive cancer lines. Taken together these results indicate that the oncosuppressive outcomes for anti-ILK therapies in vitro, depend on the expression of the tumor suppressor Rb, a known G1 checkpoint and senescence regulator.


The effect of motherhood and work on women's time pressure: A cohort analysis using the Australian Longitudinal Study on Women's Health.
The aim of this study was to analyze the prevalence and determinants of time pressure among younger Australian women born between 1973 and 1978 over a 17-year period. Using six surveys (N=14 247 at baseline in 1996) from the Australian Longitudinal Study on Women`s Health (ALSWH), we estimated fixed-effects ordered logistic regression models. More than two thirds of women felt rushed, pressured, too busy every day or a few times a week, and time pressure substantially increased over the observed 17-year period. Baseline estimates show that time pressure is significantly (P<0.001) associated with being employed and being a mother with coefficients ranging from 0.255 [95% confidence interval (95% CI) 0.188-0.322] for being employed to 0.273 (95% CI 0.168-0.377) for having children. The multivariate analysis further indicates that time pressure is significantly related to a number of personal, family, and work characteristics such as number and age of children, economic insecurity such as having financial difficulties, concern about employment stability, or the length of the working week. Understanding the sources of time pressure and identification of certain groups which are particularly vulnerable to it is important if policy-makers aim to design and successfully implement health policies, and family-friendly parental leave and child-care policies.


Comparison of Aspergillus niger phytase and Trichoderma reesei phytase and acid phosphatase on phytate phosphorus availability in pigs fed on maize-soybean meal or barley-soybean meal diets.
The efficacy of Aspergillus niger (APhy) phytase, Trichoderma reesei (TPhy) phytase and acid phosphatase (TAcPh) preparations in improving the utilization of phytin-phosphorus in the maize-soybean meal (SBM) or barley-SBM (800:200 g kg-1) diets was studied in two separate digestibility and balance trials with ten growing pigs using 5 x 5 Latin square designs. The positive control diet contained a total phosphorus (P) of 6.5 g kg-1, while the negative control as well as the APhy, TPhy and TAcPh supplemented diets which did not contain additional inorganic-P, had a total P of 4.1 g kg-1. The APhy and TPhy supplements provided phytase activity of 1000 PU g-1 together with AcPh of 8000 HFU g-1. TAcPh at a level of 8000 HFU g-1 was the only addition to one diet. The intrinsic phytase activity of barley was 355 PU g-1 while maize and soybean meal showed no phytase activity. Phytase supplements of the APhy and TPhy sources increased ash digestibility in both diets but had only a minor effect on nitrogen utilization. The addition of phytase improved absorption of P by 21%-units in barley-SBM diet and 29%-units in maize-SBM diet, without any difference between the two phytase sources. The retained P in diets with phytase was higher than in diets without phytase, 4.4 (APhy), 4.5 (TPhy) vs. 2.9 g d-1 in barley-SBM-diets and 3.7 (APhy), 4.0 (TPhy) vs. 1.8 g d-1 in maize-SBM-diets. No difference was found between the two sources of phytase. TAcPh without additional phytase did not show any effect on P absorption or retention. Ca absorption and retention were improved due to the phytase treatments. Supplementing pig diets with either APhy or TPhy sources seems to be equally effective in enhancing the availability of phytate-P. Consequently, these supplements can reduce the P-excretion of pigs by 32-40% as compared with the diet supplemented with inorganic-P.


The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion.
Selectins and fibrin(ogen) play key roles in the hematogenous dissemination of tumor cells, and especially of colon carcinomas. However, the fibrin(ogen) receptor(s) on colon carcinoma cells has yet to be defined along with its relative capacity to bind fibrinogen versus fibrin under flow. Moreover, the functional P-selectin ligand has yet to be validated using intact platelets rather than purified selectin substrates. Using human CD44-knockdown and control LS174T cells, we demonstrate the pivotal involvement of CD44 in the P-selectin-mediated binding to platelets in shear flow. Quantitative comparisons of the binding kinetics of LS174T versus P-selectin glycoprotein ligand-1 (PSGL-1)-expressing THP-1 cells to activated platelets reveal that the relative avidity of P-selectin-CD44 binding is more than sevenfold lower than that of P-selectin-PSGL-1 interaction. Using CD44-knockdown LS174T cells and microspheres coated with CD44 immunoprecipitated from control LS174T cells, and purified fibrin(ogen) as substrate, we provide the first direct evidence that CD44 also acts as the major fibrin, but not fibrinogen, receptor on LS174T colon carcinoma cells. Interestingly, binding of plasma fibrin to CD44 on the colon carcinoma cell surface interferes with the P-selectin-CD44 molecular interaction and diminishes platelet-LS174T heteroaggregation in the high shear regime. Cumulatively, our data offer a novel perspective on the apparent metastatic potential associated with CD44 overexpression on colon carcinoma cells and the critical roles of P-selectin and fibrin(ogen) in metastatic spread and provide a rational basis for the design of new therapeutic strategies to impede metastasis.


Association of Sarcopenia and Body Composition With Short-term Outcomes After Liver Resection for Malignant Tumors.
Previous retrospective studies have shown that sarcopenia substantially alters the postoperative and oncological outcomes after liver resection for malignant tumors. However, the evidence is limited to small retrospective studies with heterogeneous results and the lack of standardized measurements of sarcopenia. To investigate the role of sarcopenia as a risk factor associated with 90-day morbidity after liver resection for malignant tumors. This cohort study included 234 consecutive patients undergoing liver resection for malignant tumors at San Camillo Forlanini Hospital, Rome, Italy, between June 1, 2018, and December 15, 2019. Muscle mass and strength were assessed using the skeletal muscle index (SMI) on preoperative computed tomographic scans and the handgrip strength test, respectively. Patients were then divided into the following 4 groups: group A (normal muscle mass and strength), group B (reduced muscle strength), group C (reduced muscle mass), and group D (reduced muscle mass and strength). The primary outcome of the study was 90-day morbidity. The following secondary outcomes were investigated: 90-day mortality, hospital stay, and readmission rate. Sixty-four major and 170 minor hepatectomies were performed in 234 patients (median age, 66.50 [interquartile range, 58.00-74.25] years; 158 men [67.5%]). The median SMI of the entire population was 46.22 (interquartile range, 38.60-58.20) cm/m2. The median handgrip strength was 30.80 (interquartile range, 22.30-36.90) kg. Patients in group D had a statistically significantly higher rate of 90-day morbidity than patients in the other groups (51.5% [35 of 68] vs 38.7% [29 of 75] in group C, 23.1% [3 of 13] in group B, and 6.4% [5 of 78] in group A; P < .001). Compared with patients in the other groups, those in group D had a longer hospital stay (10 days vs 8 days in group C, 9 days in group B, and 6 days in group A; P < .001), and more patients in this group were readmitted to the hospital (8.8% [6 of 68] vs 5.3% [4 of 75] in group C, 7.7% [1 of 13] in group B, and 0% [0 of 78] in group A; P = .02). Sarcopenia, portal hypertension, liver cirrhosis, and biliary reconstruction were independent risk factors associated with 90-day morbidity. Sarcopenia appears to be associated with adverse outcomes after liver resection for malignant tumors. Both muscle mass measurements on computed tomographic scans and muscle strength assessments with the handgrip strength test should be performed at the first clinical encounter to better classify patients and to minimize the risk of morbidity.


H1 and H2 blockade: a prophylactic principle in anesthesia and surgery against histamine-release responses of any degree of severity: Part 1.
In the perioperative period, histamine release was shown in numerous situations and pathological states. They include diseases or complications of diseases, preparation and premedication of patients, induction of anaesthesia, maintenance of anaesthesia and surgery, and administration of drugs and treatment in the immediate postoperative period. A premedication with histamine H1 and H2 receptor antagonists was developed which in five controlled clinical trials blocked histamine-release responses of all grades of severity. These included single spots of erythema or a wheal up to life-threatening reactions or even death of the patient or laboratory animal. The necessity for a new premedication was investigated by methods of medical decision-making considering the incidence of the reactions, classification of severity, efficiency of prophylaxis and treatment of anaphylactoid reactions, and side-effects. As a result, the premedication with dimethpyrindene (Forhistal, Fenistil) plus cimetidine (Tagamet) was recommended in a series of patients at risk: those with a history of hypersensitivity reactions to intravenous agents or atopy, patients with a second I.V. drug exposure within a few days, those undergoing surgery with a high risk of histamine release, patients of greater than 70 years age, and poor-risk patients with preoperative cardiac, respiratory or liver insufficiency and shock.


Perceptions of health professionals on pain in extremely low gestational age infants.
Extremely low gestational age infants (<28 weeks at birth) experience significant pain from repeated therapeutic procedures while hospitalized in the neonatal intensive care unit. As part of a program of research examining pain in preterm infants, we conducted a qualitatively driven mixed-methods design, supplemented with a qualitative and quantitative component, to understand how health care professionals (HCPs) assess and manage procedural pain for tiny and underdeveloped preterm infants. Fifty-nine HCPs from different disciplines across four tertiary-level neonatal units in Canada participated in individual or focus group interviews and completed a brief questionnaire. Four themes from the content analysis were (a) subtlety and unpredictability of pain indicators, (b) infant and caregiver attributes and contextual factors that influence pain response and practices, (c) the complex nature of pain assessment, and (d) uncertainty in the management of pain. The information gleaned from this study can assist in identifying gaps in knowledge and informing unit-based and organizational knowledge translation strategies for this vulnerable population.


Codevelopment of COVID-19 infection prevention and control guidelines in lower-middle-income countries: the 'SPRINT' principles.
The COVID-19 pandemic has required the rapid development of comprehensive guidelines to direct health service organisation and delivery. However, most guidelines are based on resources found in high-income settings, with fewer examples that can be implemented in resource-constrained settings. This study describes the process of adapting and developing role-specific guidelines for comprehensive COVID-19 infection prevention and control in low-income and middle-income countries (LMICs). We used a collaborative autoethnographic approach to explore the process of developing COVID-19 guidelines. In this approach, multiple researchers contributed their reflections, conducted joint analysis through dialogue, reflection and with consideration of experiential knowledge and multidisciplinary perspectives to identify and synthesise enablers, challenges and key lessons learnt. We describe the guideline development process in the Philippines and the adaptation process in Sri Lanka. We offer key enablers identified through this work, including flexible leadership that aimed to empower the team to bring their expertise to the process; shared responsibility through equitable ownership; an interdisciplinary team; and collaboration with local experts. We then elaborate on challenges including interpreting other guidelines to the country context; tensions between the ideal compared with the feasible and user-friendly; adapting and updating with evolving information; and coping with pandemic-related challenges. Based on key lessons learnt, we synthesise a novel set of principles for developing guidelines during a public health emergency. The SPRINT principles are grounded in situational awareness, prioritisation and balance, which are responsive to change, created by an interdisciplinary team navigating shared responsibility and transparency. Guideline development during a pandemic requires a robust and time sensitive paradigm. We summarise the learning in the 'SPRINT principles' for adapting guidelines in an epidemic context in LMICs. We emphasise that these principles must be grounded in a collaborative or codesign process and add value to existing national responses.


Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis.
To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.


Investigation of the contribution of total creatine to the CEST Z-spectrum of brain using a knockout mouse model.
The current study aims to assign and estimate the total creatine (tCr) signal contribution to the Z-spectrum in mouse brain at 11.7 T. Creatine (Cr), phosphocreatine (PCr) and protein phantoms were used to confirm the presence of a guanidinium resonance at this field strength. Wild-type (WT) and knockout mice with guanidinoacetate N-methyltransferase deficiency (GAMT-/-), which have low Cr and PCr concentrations in the brain, were used to assign the tCr contribution to the Z-spectrum. To estimate the total guanidinium concentrations, two pools for the Z-spectrum around 2 ppm were assumed: (i) a Lorentzian function representing the guanidinium chemical exchange saturation transfer (CEST) at 1.95 ppm in the 11.7-T Z-spectrum; and (ii) a background signal that can be fitted by a polynomial function. Comparison between the WT and GAMT-/- mice provided strong evidence for three types of contribution to the peak in the Z-spectrum at 1.95 ppm, namely proteins, Cr and PCr, the latter fitted as tCr. A ratio of 20 ± 7% (protein) and 80 ± 7% tCr was found in brain at 2 μT and 2 s saturation. Based on phantom experiments, the tCr peak was estimated to consist of about 83 ± 5% Cr and 17 ± 5% PCr. Maps for tCr of mouse brain were generated based on the peak at 1.95 ppm after concentration calibration with in vivo magnetic resonance spectroscopy.


Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats.
Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl "high," alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 μg/kg/infusion) or withdrawal to our knowledge. We established a rat model of xylazine/fentanyl co-SA and withdrawal and evaluated outcomes as a function of biological sex. When administered alone, chronic xylazine (2.5 mg/kg, intraperitoneal) induced unique sex-specific withdrawal symptomatology, whereby females showed delayed onset of signs and a possible enhancement of sensitivity to the motor-suppressing effects of xylazine. Xylazine reduced fentanyl consumption in both male and female rats regardless of whether it was experimenter-administered or added to the intravenous fentanyl product (0.05, 0.10, and 0.5 mg/kg/infusion) when compared to fentanyl SA alone. Interestingly, this effect was dose-dependent when self-administered intravenously. Naloxone (0.1 mg/kg, subcutaneous injection) did not increase somatic signs of fentanyl withdrawal, regardless of the inclusion of xylazine in the fentanyl infusion in either sex; however, somatic signs of withdrawal were higher across time points in females after xylazine/fentanyl co-SA regardless of naloxone exposure as compared to females following fentanyl SA alone. Together, these results indicate that xylazine/fentanyl co-SA dose-dependently suppressed fentanyl intake in both sexes and induced a unique withdrawal syndrome in females that was not altered by acute naloxone treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Trafficking of M(2) muscarinic acetylcholine receptors.
Internalization is an important mechanism regulating the agonist-dependent responses of G-protein-coupled receptors. The internalization of the M(2) muscarinic cholinergic receptors (mAChR) in HEK293 cells has been demonstrated to occur by an unknown mechanism that is independent of arrestins and dynamin. In this study we examined various aspects of the trafficking of the M(2) mAChR in HEK293 cells to characterize this unknown pathway of internalization. Internalization of the M(2) mAChR was rapid and extensive, but prolonged incubation with agonist did not lead to appreciable down-regulation (a decrease in total receptor number) of the receptors. Recovery of M(2) mAChRs to the cell surface following agonist-mediated internalization was a very slow process that contained protein synthesis-dependent and -independent components. The protein synthesis-dependent component of the recovery of receptors to the cell surface did not appear to reflect a requirement for synthesis of new receptors, as no changes in total receptor number were observed either in the presence or absence of cycloheximide. Phosphorylation of the M(2) mAChR did not appear to influence the rate or extent of the recovery of receptors to the cell surface, as the recovery of a phosphorylation-deficient mutant M(2) mAChR, the N,C(Ala-8) mutant, was similar to the recovery of the wild type M(2) mAChR. Finally, the constitutive, nonagonist-dependent internalization and recycling of the M(2) mAChR was very slow and also contained protein synthesis-dependent and -independent components, suggesting that a similar pathway controls the recovery from agonist-dependent and -independent internalization. Overall, these data demonstrated a variety of previously unappreciated facets involved in the regulation of M(2) mAChRs.


Learning from the Pandemic to Improve Care for Vulnerable Communities: The Perspectives and Recommendations from the Rare Disease Community.
The COVID-19 pandemic has brought about health and social care disruptions for millions of people with complex health needs and disabilities, who are amongst the most vulnerable populations. More than ever before, the need for integrated care is pressing, as fragmented health and care systems struggle to face the pandemic and vulnerable individuals are exposed to aggravated health, social and economic hurdles. The implementation of effective integrated care pathways is long due and must build upon the key guidelines being published by experts worldwide. Furthermore, the pandemic is opening the doors for more remote healthcare and care coordination, with both services and care receivers being increasingly more receptive to virtual and digital solutions, so long as they are fit for purpose and do improve care. In this article we will go over the impact that the pandemic has had so far for the community of people living with a rare disease, and how it has aggravated their already vulnerable condition. We will also recall crucial recommendations to achieve integrated care for those with complex needs and will bring to light the most recent perspectives of the rare disease community in regards to remote care. While we are still facing the COVID-19 crisis, we do hope that by 2030 we will look back at this pandemic as the ultimate propeller which led millions of people with vulnerable conditions to finally be supported by effective integrated and holistic care pathways.


Learning-induced modulations of the stimulus-preceding negativity.
The neural basis of feedback expectation, which is crucial in learning theory, has only been minimally studied. Stimulus-preceding negativity (SPN), an ERP component that appears prior to the presentation of feedback, has been proposed as being related to feedback expectation. The present study showed, for the first time, amplitude modulations of the SPN component during learning acquisition in a trial-by-trial associative learning task. The results indicate that SPN could be a plausible electrophysiological index of the cognitive processes engaged while expecting the appearance of relevant feedback during reinforcement learning.


Phospholipase C-gamma 1 is translocated to the membrane of rat basophilic leukemia cells in response to aggregation of IgE receptors.
Aggregation of the high affinity receptor for IgE (Fc epsilon RI) on the surface of mast cells results in the rapid hydrolysis of membrane inositol phospholipids by phospholipase C (PLC). Although at least seven isoenzymes of PLC have been characterized in different mammalian cells, the isoenzyme involved in Fc epsilon RI-mediated signal transduction and the mechanism of its activation have not been demonstrated. We now report that PLC-gamma 1 is translocated to the membrane of mast cells after aggregation of Fc epsilon RI. Activation of rat basophilic leukemia cells, a rat mast cell line, with oligomeric IgE resulted in an increase in PLC activity in washed membrane preparations in a cell free assay containing exogenous [3H]phosphatidylinositol (PI). The increase in PLC activity has the same dose-response to oligomeric IgE as receptor mediated hydrolysis of inositol lipids (PI hydrolysis) in intact cells. Analysis by Western blot probed with anti-PLC-gamma 1 antibody revealed that there is a three- to fourfold increase in PLC-gamma 1 in membranes from activated cells. The increase in PLC activity is augmented a further 20% by the addition of orthovanadate to the incubation medium suggesting that a tyrosine phosphatase is involved in the down-regulation of this phenomenon. These findings demonstrate translocation of PLC-gamma 1 to the membrane following activation of a receptor which does not contain intrinsic tyrosine kinase activity. Activation of PLC-gamma 1 by this pathway may account for Fc epsilon RI-mediated PI hydrolysis.


Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats.
Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses ("cue reactivity") that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2C receptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is approved by the United States Food and Drug Administration (FDA) for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats. We found that lorcaserin inhibited oxycodone intake, an effect blocked by the selective 5-HT2CR antagonist SB242084. Lorcaserin also decreased responding for the discrete cue complex ("cue reactivity") previously associated with delivery of oxycodone (i.e., stimulus lights, infusion pump sounds) in both abstinence and extinction-reinstatement models. The selected dose range of lorcaserin (0.25-1 mg/kg) does not overtly alter spontaneous behaviors nor operant responding on inactive levers in the present study. Taken together, the ability of lorcaserin to reduce the oxycodone self-administration and decrease cue reactivity associated with relapse highlights the therapeutic potential for lorcaserin in the treatment of OUD.


A Non-Isothermal Pore Network Model of Primary Freeze Drying.
In this work, a non-isothermal pore network (PN) model with quasi-steady vapor transport and transient heat transfer is presented for the first time for the application of primary freeze drying. The pore-scale resolved model is physically based and allows for the investigation of correlations between spatially distributed structure and transport conditions. The studied examples were regular PN lattices with a significantly different structure, namely a spatially homogeneous PN, also denoted as monomodal PN, and a PN with significant structure variation, referred to as bimodal PN because of its bimodal pore size distribution. The material properties selected for the solid skeleton in this study are equivalent to those of maltodextrin. The temperature ranges applied here were -28 °C to -18 °C in the PN and -42 °C in the surrounding environment. The environmental vapor pressure was 10 Pa. The PNs were dried with constant temperature boundary conditions, and heat was transferred at the top side by the vapor leaving the PN. It is shown how the structural peculiarities affect the local heat and mass transfer conditions and result in a significant widening of the sublimation front in the case of the bimodal PN. The possibility of spatially and temporally resolved front structures is a unique feature of the PN model and allows the study of situations that are not yet described by classical continuum approaches, namely heterogeneous frozen porous materials. As demonstrated by the thin layers studied here, the pore-scale simulations are of particular interest for such situations, such as in lyomicroscopes or collagen scaffolds, where a length-scale separation between dry and ice-saturated regions is not possible.


Implementation of Point-of-Care Molecular Diagnostics for Mycoplasma pneumoniae Ensures the Correct Antimicrobial Prescription for Pediatric Pneumonia Patients.
Mycoplasma pneumoniae is a leading causative pathogen of pneumonia among pediatric patients, and its accurate diagnosis may aid in the selection of appropriate antimicrobial agents. We established a rapid reporting system of a polymerase chain reaction (PCR) examination for M. pneumoniae that enables physicians to obtain test results approximately 90 minutes after ordering the test. In this study, we evaluated the impact of this system on antimicrobial prescriptions for pediatric pneumonia patients after its implementation from May 2016 to April 2017. In total, we identified 375 pediatric pneumonia patients, and the results of the rapid PCR examinations for Mycoplasma pneumoniae were reported immediately in 90.7% of patients (340/375), with physicians able to use these results to decide on patients' management before the prescription of antimicrobial agents. Of the 375 pediatric pneumoniae patients, M. pneumoniae was detected in 223 (59.5%). Among the 223 M. pneumoniae-positive pneumonia cases, antimicrobial agents for atypical pathogens (macrolides, tetracyclines or quinolones) were prescribed in 97.3% (217/223) at the initial evaluation, and their prescription rates increased to 99.1% (221/223) during management. In contrast, antimicrobial agents for atypical pathogens were prescribed only in 10.5% of 152 M. pneumoniae-negative pneumonia cases at the initial evaluations, and only 1 additional case was prescribed clarithromycin for persistent symptoms during management. In conclusion, we show that molecular technology could be applicable in the field of point-of-care testing in infectious disease, and its implementation will ensure the correct antimicrobial prescription for pediatric pneumonia patients.


Mortality in Patients with Proximal Femoral Fracture During the COVID-19 Pandemic: A U.K. Hospital's Experience.
Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, with a case mortality ratio of approximately 6.4% at the time of writing (May 2020). Mortality increases in elderly patients with comorbidities. Patients with hip fracture have an average age of 80 years, with an estimated 2.8 comorbidities per patient. Evidence is lacking regarding the mortality rate of patients with hip fracture admitted during the COVID-19 pandemic. Our aim was to investigate the mortality rate among patients with a proximal femoral fracture who were admitted to our hospital during the COVID-19 pandemic. We conducted a retrospective review of all patients with a proximal femoral fracture admitted to Southend University Hospital in the U.K. from March to April 2020 (during the COVID-19 pandemic). Data collected included demographics (patient age, body mass index, sex), comorbidities, and blood test values along with COVID-19 diagnosis (based on positive microbiological sample and clinical and radiographic findings) and operative characteristics (time to operation, length of stay, American Society of Anesthesiologists [ASA] classification, Nottingham Hip Fracture Score). The primary outcome was the 30-day mortality rate for patients with a hip fracture who were COVID-19 positive or negative. Kaplan-Meier survival analysis was conducted along with Mann-Whitney U tests and Fisher exact tests. Forty-one patients were included in the study, of whom 37 had an available SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) swab test result. The overall 30-day mortality was 22%. Eleven patients tested positive for COVID-19. There was a significant difference in the mortality rate between those who tested positive and those who tested negative (54.5% versus 7.69%, respectively; Fisher exact test, p = 0.004) and between the operative patients who tested positive and the operative patients who tested negative (37.5% versus 4.34%, respectively; Fisher exact test, p = 0.043). Patients with a proximal femoral fracture may be at higher risk for mortality during the COVID-19 pandemic. We noted that patients with a proximal femoral fracture who tested positive for COVID-19 had a higher 30-day mortality rate compared with those who tested negative. Additional research is required to ascertain the benefits of a reduction in time to operation. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Economic and environmental efficiency of UK and Ireland water companies: Influence of exogenous factors and rurality.
For water companies, benchmarking their performance relative to other companies can be an effective way to identify the scope for efficiency gains to be made through infrastructure investment and operational improvements. However, a key limitation to benchmarking is the confounding effect of exogenous factors, which may not be factored in to benchmarking methodologies. The purpose of this study was to provide an unbiased comparison of efficiency across a sample of water and sewage companies, accounting for important exogenous factors. Bias-corrected economic and environmental efficiency estimates with explanatory factors were evaluated for a sample of 13 water and sewage companies in the UK and Ireland, using a double-bootstrap data envelopment analysis (DEA) approach. Bias correction for economic and environmental efficiency changed the rankings of nine and eight companies, respectively. On average, companies could reduce economic inputs by 19% and carbon outputs by 16% if they performed at the efficiency frontier. Variables explaining efficiency were: source of water, leakage rate, per capita consumption and population density. Population density showed statistical significance with both economic (p-value 0.002) and environmental (p-value 0.001) efficiency. Consequently, a rurality factor was defined for each company's operational area, which was then regressed against normalised water company performance data. More rural water companies spend more per property (R2 of 0.633), in part reflecting a larger number of smaller sewage treatment works serving rural populations (R2 of 0.823). These findings provide new insight into methods for benchmarking, and factors affecting, water company efficiency, pertinent for both regulators and water companies.


A Randomized Controlled Trial on the Usefulness of Mobile Text Phone Messages to Improve the Quality of Care of HIV and AIDS Patients in Cameroon.
HIV and AIDS are major public health problems in the world and Africa. In Cameroon, the HIV prevalence is 5.1%. Cellphones have been found to be useful in the provision of modern health care services using short message services (SMS). This study assessed the effectiveness of SMS in improving the adherence of people living with HIV and AIDS to their treatment and care in Cameroon. This intervention study used a randomized controlled trial design. Ninety participants seeking treatment at the Nkwen Baptist Health Center were recruited between August and September 2011 using a purposive sampling method. They were randomly allocated into the intervention and control groups, each containing 45 participants. In the intervention group, each participant received four SMSs per week at equal intervals for four weeks. The patients were investigated for adherence to ARVs by evaluating the number of times treatment and medication refill appointments were missed. Data were collected using an interviewer-administered questionnaire before and after intervention and analysed on STATA. The baseline survey indicated that there were 55(61.1%) females and 35(38.9%) males aged 23 - 62 years; the mean age was 38.77 ± 1.08. Most participants were teachers [12 (13.3%)], farmers [11 (12.2%)], and businessmen [24 (26.7%)]. Adherence to ARVs was 64.4% in the intervention group and 44.2% in the control group (p = 0.05). 2(4.4%) patients in the control group failed to respect their drug refill appointments while all the 45(100%) participants in the intervention group respected their drug refill appointments. 54.17% of married people and 42.9% of the participants with primary and secondary levels of education missed their treatment. Key reasons for missing treatment were late home coming (54%), forgetfulness (22.5%), and travelling out of station without medication (17.5%). Other factors responsible for non-adherence included involvement in outdoor business (60.87%), ARV stock out (37.8%), and not belonging to a support group (10.23%). Twenty eight (62.22%) subjects in the intervention group were able to take their treatment regularly and on time. SMS improved adherence to ARVs. Key constraints which affect adhere to ARV medication can be addressed using SMS.


Genome-Wide Identification, Evolution, and Expression Analysis of RING Finger Gene Family in Solanum lycopersicum.
RING domain proteins generally have E3 ubiquitin ligase activity and are involved in degrading their substrate proteins. The roles of these proteins in growth, development, and responses to different abiotic stresses have been described well in various plant species, but little is available on tomatoes. Here, we identified 474 RING domains in 469 potential proteins encoded in the tomato genome. These RING genes were found to be located in 12 chromosomes and could be divided into 51 and 11 groups according to the conserved motifs outside the RING domain and phylogenetic analysis, respectively. Segmental duplication could be the major driver in the expansion of the tomato RING gene family. Further comparative syntenic analysis suggested that there have been functional divergences of RING genes during plant evolution and most of the RING genes in various species are under negative selection. Expression profiles derived from a transcriptomic analysis showed that most tomato RING genes exhibited tissue-specific expression patterning. Further RT-qPCR validation showed that almost all genes were upregulated by salt treatment, which was consistent with the microarray results. This study provides the first comprehensive understanding of the RING gene family in the tomato genome. Our results pave the way for further investigation of the classification, evolution, and potential functions of the RING domain genes in tomato.


How to best smash a snail: the effect of tooth shape on crushing load.
Organisms that are durophagous, hard prey consumers, have a diversity of tooth forms. To determine why we see this variation, we tested whether some tooth forms break shells better than others. We measured the force needed with three series of aluminium tooth models, which varied in concavity and the morphology of a stress concentrating cusp, to break a shell. We created functionally identical copies of two intertidal snail shells: the thicker shelled Nucella ostrina and the more ornamented Nucella lamellosa using a three-dimensional printer. In this way, we reduced variation in material properties between test shells, allowing us to test only the interaction of the experimental teeth with the two shell morphologies. We found that for all tooth shapes, thicker shells are harder to break than the thinner shells and that increased ornamentation has no discernible effect. Our results show that for both shell morphologies, domed and flat teeth break shells better than cupped teeth, and teeth with tall or skinny cusps break shells best. While our results indicate that there is an ideal tooth form for shell breaking, we do not see this shape in nature. This suggests a probable trade-off between tooth function and the structural integrity of the tooth.


Effects of temporal integration on the shape of visual backward masking functions.
Many studies of cognition and perception use a visual mask to explore the dynamics of information processing of a target. Especially important in these applications is the time between the target and mask stimuli. A plot of some measure of target visibility against stimulus onset asynchrony is called a masking function, which can sometimes be monotonic increasing but other times is U-shaped. Theories of backward masking have long hypothesized that temporal integration of the target and mask influences properties of masking but have not connected the influence of integration with the shape of the masking function. With two experiments that vary the spatial properties of the target and mask, the authors provide evidence that temporal integration of the stimuli plays a critical role in determining the shape of the masking function. The resulting data both challenge current theories of backward masking and indicate what changes to the theories are needed to account for the new data. The authors further discuss the implication of the findings for uses of backward masking to explore other aspects of cognition.


Septic endarteritis of the femoral artery following angioplasty.
A case of septic endarteritis that occurred in the femoral artery following percutaneous transluminal coronary angioplasty (PTCA) is reported, and nine previously reported cases of this complication are reviewed. In each case Staphylococcus aureus was identified as the pathogen. For all cases in which a complete clinical description was available, endarteritis occurred following repeated PTCA or repuncture PTCA (i.e., a second catheterization at the original site of insertion for diagnostic purposes). The characteristic manifestations of endarteritis in this setting included bacteremia (all 10 cases), the formation of a pseudoaneurysm (six), distal emboli (five), and regional septic arthritis or osteomyelitis (five of six cases that included the information needed to determine the presence of these conditions). In each case, treatment included 4-6 weeks of iv antibiotics and surgery, most frequently resection of the pseudoaneurysm and vascular bypass. We recommend surveillance for the signs of endarteritis, especially after repeated catheterization, and use of the contralateral site when repeated catheterization is indicated. When the ipsilateral site is used, the administration of prophylactic antibiotics should be considered.


Molecular mechanism of HIV-1 Tat interacting with human dopamine transporter.
Nearly 70% of HIV-1-infected individuals suffer from HIV-associated neurocognitive disorders (HAND). HIV-1 transactivator of transcription (Tat) protein is known to synergize with abused drugs and exacerbate the progression of central nervous system (CNS) pathology. Cumulative evidence suggest that the HIV-1 Tat protein exerts the neurotoxicity through interaction with human dopamine transporter (hDAT) in the CNS. Through computational modeling and molecular dynamics (MD) simulations, we develop a three-dimensional (3D) structural model for HIV-1 Tat binding with hDAT. The model provides novel mechanistic insights concerning how HIV-1 Tat interacts with hDAT and inhibits dopamine uptake by hDAT. In particular, according to the computational modeling, Tat binds most favorably with the outward-open state of hDAT. Residues Y88, K92, and Y470 of hDAT are predicted to be key residues involved in the interaction between hDAT and Tat. The roles of these hDAT residues in the interaction with Tat are validated by experimental tests through site-directed mutagensis and dopamine uptake assays. The agreement between the computational and experimental data suggests that the computationally predicted hDAT-Tat binding mode and mechanistic insights are reasonable and provide a new starting point to design further pharmacological studies on the molecular mechanism of HIV-1-associated neurocognitive disorders.


Acute lymphoblastic leukemia in elderly patients the Philadelphia chromosome may not be a significant adverse prognostic factor.
Acute lymphoblastic leukemia (ALL) in elderly patients (59 years or older) carries a poor prognosis, and this finding may be attributed to the relatively high frequency of the Philadelphia chromosome (Ph). To test this hypothesis, we reviewed the clinicopathologic features of 23 consecutive, newly diagnosed elderly patients with ALL (14 men, 9 women, aged 59-92 years) uniformly treated at our institution and compared the Ph+ and Ph- groups. Conventional cytogenetic data were available for 21 of 23 cases; 7 (33%) were Ph+. All Ph+ cases were of precursor B-cell type. The remaining 16 tumors were of precursor B-cell (10), mature B-cell (2), precursor T-cell (3), and mixed precursor T-cell/B-cell (1) type. Ph+ and Ph- groups did not differ significantly in median survival (13.4 months vs 19.0 months) or other variables studied. The Ph may not be a significant adverse prognostic factor in ALL in elderly patients.


A method for intervertebral space distraction before stabilization combined with complete ventral slot for treatment of disc-associated wobbler syndrome in dogs.
To evaluate the use of a modified K-wire spacer for maintaining intervertebral distraction after ventral decompression and during stabilization as a treatment for disc-associated wobbler syndrome in large breed dogs. A retrospective study. Dogs (n=7) with disc-associated wobbler syndrome. Medical records (2003-2006) of dogs treated by a modified surgical method were evaluated. Data retrieved were signalment, onset and duration of clinical signs, neurologic abnormalities, diagnostic methods, surgical procedure, immediate, and long-term (>or=1 year) postoperative clinical and radiographic outcome. Mean duration of clinical signs was 4.8 months. Neurologic signs included ataxia (2), ambulatory tetraparesis (2), and non-ambulatory tetraparesis (3). Three dogs had disc protrusion in 2 sites, 2 dogs had the procedure in 1 location and stabilization of both affected sites. All dogs improved dramatically and remained for 1-3 years. One dog had recurrence of cervical discomfort 13 months later. Despite the limited number of dogs, overall initial successful outcome with only 1 dog having mild recurrence 13 months later supports further use and evaluation of this technique. Distraction using a K-wire spacer after ventral decompression followed by stabilization should be considered in dogs with disc-associated wobbler syndrome to prevent collapse of the intervertebral space.


Clinical impact of mineralocorticoid receptor antagonists treatment after acute coronary syndrome in the real world: A propensity score matching analysis.
Recent studies suggest that the benefit of mineralocorticoid receptor antagonists in the acute coronary syndrome setting is controversial. The aim of this study was to examine the current long-term prognostic benefit of mineralocorticoid receptor antagonists in patients with acute coronary syndrome. We conducted a retrospective cohort study of 8318 consecutive acute coronary syndrome patients. Baseline patient characteristics were examined and a follow-up period was established for registry of death, major cardiovascular adverse events and heart failure re-hospitalization. We performed a propensity-matching analysis to draw up two groups of patients paired according to whether or not they had been treated with mineralocorticoid receptor antagonists. The prognostic value of mineralocorticoid receptor antagonists to predict events during follow-up was analysed using Cox regression. Among the study participants, only 524 patients (6.3%) were discharged on mineralocorticoid receptor antagonists. Patients on mineralocorticoid receptor antagonists had a different clinical and pharmacological profile. These differences disappeared after the propensity score analysis. The median follow-up was 40.7 months. After the propensity score analysis, the cardiovascular mortality and heart failure readmission rates were similar between patients who were discharged on mineralocorticoid receptor antagonists and those whose not. The use of mineralocorticoid receptor antagonists was only associated with a reduction in major cardiovascular adverse events (hazard ratio=0.83, 95% confidence interval 0.69-0.97, p=0.001). Our results do not corroborate the long-term benefit of mineralocorticoid receptor antagonists to improve survival after acute coronary syndrome in a large cohort of patients with heart failure or reduced left ventricular ejection fraction and diabetes. Their prescription was associated with a significantly lower incidence of major cardiovascular adverse events during the long-term follow-up without effect on heart failure development.


Haemagglutination-inhibiting activity to type a influenza viruses in the sera of wild birds from the far east of the USSR.
The discovery in migrating birds of influenzaviruses and the demonstration of relationships between strains found in man and in birds show the importance of these investigations for influenzavirus ecology. Investigation of birds in the far-east regions of the USSR is particularly important as many of them migrate to South-East Asia and China, the regions from which human influenza pandemics seem to originate. A total of 262 bird sera from these regions were titrated by the HI method with 20 different influenzavirus antigens (5 human, 2 equine, 1 swine, and 12 avian influenzaviruses). Haemagglutination-inhibiting activity was found in 16.8% of the tested sera, most frequently in sera of Anas formosa, Gallinago gallinago, Anas falcata, and Larus crassirostris. HI activity to A/turkey/Wisconsin/66 (Hav6N2) was found in 7.3% of the sera.


Relation between dietary pattern analysis (principal component analysis) and body mass index: a 5-year follow-up study in a Belgian military population.
Increasing body mass index (BMI) has been related to many chronic diseases. Knowledge of nutritional determinants of BMI increase may be important to detect persons at risk. A longitudinal prospective study design was used in 805 Belgian soldiers. Daily nutrition was recorded with a validated food-frequency questionnaire. Weight and height were recorded from medical military data and principal component analysis was used to detect dietary patterns. During the 5 years follow-up, mean BMI increased from 25.8 (±3.3) kg/m(2) to 27.1 (±3.6) kg/m(2) (p<0.05). Consequently, the prevalence of being overweight and obesity increased from 46.2% and 9.6% to 51.6% and 19.9% (p<0.05), respectively. Mean (SD) weight gain differed between the BMI categories at baseline with a respective weight gain of 3.8 (±3.1) kg for normal weight at baseline, 4.2 (±3.2) kg for overweight and 5.1 (±3.4) kg for obesity (p for trend <0.05). Three dietary patterns were detected by principal component analysis: Meat, Sweet and Healthy dietary pattern. In energy-unadjusted and adjusted linear regressions, no dietary pattern was associated with BMI increase. No specific dietary pattern was related to BMI increase. Prevention of obesity should focus on total energy intake at all BMI categories.


Furosemide ethanol-free oral solutions for paediatric use: formulation, HPLC method and stability study.
Oral liquid solutions of the diuretic active ingredient furosemide (FUR) marketed across Europe do not comply with recent requirements for paediatric preparation owing to their ethanol content and, moreover, in some countries only tablet or injection dosage forms of furosemide are available. To formulate extemporaneous paediatric ethanol-free solutions of FUR (2 mg/mL) with suitable solubility in the aqueous vehicle and an acceptable taste and to evaluate their stability under two different storage conditions during a 9-month study period. Our work presents two developed formulations of FUR ethanol-free paediatric oral solutions 2 mg/mL for easy extemporaneous compounding in a pharmacy. FUR solubility avoiding the use of ethanol was achieved using sodium hydroxide (formulation F1) or disodium hydrogen phosphate dodecahydrate (formulation F2). The preparations were stored at 25°C±3°C or at 40°C±0.5°C and protected from light. For FUR and preservative, methylparaben (MP), a stability assay was conducted by a high-performance liquid chromatography validated method and determination of pH stability. The remaining FUR concentration was >90% of the initial concentration after 270 days in both formulations at both storage conditions, 25°C and 40°C. The concentration of MP decreased significantly in the formulation F2 stored at 40°C. Both formulations were stable when stored at room temperature for up to 9 months; formulation F1 was stable even at 40°C. MP used as an antimicrobial agent fully satisfied the recommended criteria for preservative efficacy in oral preparations according to the European Pharmacopoeia 9.0 (5.1.3).


Morphometric development of the tongue in fetal cadavers.
The tongue is a specific organ for the sense of taste. It consists of the striated muscle and mucous membrane. Furthermore, it helps the functions of speech, chewing, and swallowing. In this study, we aimed to reveal some morphometric properties of the tongue in fetal cadavers. The study was conducted on a total of 45 fetal tongues (25 male tongues, 20 female tongues) aged between 17 and 40 weeks. The fetuses were divided into three groups as trimester II, trimester III, and full term. For each tongue, the length, width, area, free tongue length, and the terminal sulcus angle were measured using Image J program. The free tongue length/tongue length ratio was examined. The obtained data were compared according to the trimester groups and genders. It was determined that the tongue length, width, area, and free tongue length increased during the trimesters and that there was no significant difference in the terminal sulcus angle and the free tongue length/tongue length ratio between the trimesters. No significant difference was found in all parameters between the genders. This study presented significant data on morphometric development of the tongue. These data are thought to be useful for determining the anomaly and variations of the tongue.


[Contamination of bee products and risk for human health: situation in France].
To meet the needs of a colony, bees collect honey, honey-dew, pollen and water from an environment exposed to various bacterial and chemical contaminants, which might be incorporated in products for human consumption. In addition to this environmental pollution, contamination of bee products may also occur during packing. In France, tests for various pollutants are performed more or less systematically, at the request of the Ministry of Agriculture, merchants or producers. Honey and royal jelly contain very little bacterial or chemical contamination, due to both the ability of colonies to eliminate pathogenic and non-pathogenic micro-organisms present in their environment, and to the physico-chemical properties of these products, as well as the role of bees in filtering chemical pollutants. To create the framework for European legislation on the testing of products, bacterial and chemical standards should be created and should be based on standardised techniques. The testing of imported bee products requires greater attention.


Voice outcomes after endoscopic treatment of laryngotracheal stenosis.
This study aimed to assess vocal disability in patients with laryngotracheal stenosis who are managed with endoscopic surgery, comparing patients with posterior glottic stenosis (PGS) to those with subglottic or tracheal stenosis (SGS/TS). Patients who underwent endoscopic treatment for laryngotracheal stenosis with voice outcomes data from 2005 to 2013 were studied. The mean Voice Handicap Index-10 (VHI-10) was compared over the study period. Of those with SGS/TS, the distance from the vocal folds to the proximal portion of the stenosis was obtained and compared to VHI-10. Forty-four patients met inclusion criteria. The mean VHI-10 for all patients was 14.6. Fifty percent were dysphonic (VHI-10>11). The mean VHI-10 for PGS patients was 22.4, and for SGS/TS patients, 10.9 (P=.004). Of those with PGS, 78.6% were dysphonic compared to only 36.7% of those with SGS/TS. Voice Handicap Index-10 improved from 14.1 for those with proximal stenosis to 4 for those with stenosis more than 2 cm distal to the vocal folds. Following endoscopic management of stenosis, those with PGS have poorer voice outcomes compared to those with SGS/TS. The majority of those with SGS/TS are not dysphonic. Vocal outcomes are greatest for those with stenosis beginning at least 2 cm distal to the vocal folds.


Myeloid ZFP36L1 does not regulate inflammation or host defense in mouse models of acute bacterial infection.
Zinc finger protein 36, C3H type-like 1 (ZFP36L1) is one of several Zinc Finger Protein 36 (Zfp36) family members, which bind AU rich elements within 3' untranslated regions (UTRs) to negatively regulate the post-transcriptional expression of targeted mRNAs. The prototypical member of the family, Tristetraprolin (TTP or ZFP36), has been well-studied in the context of inflammation and plays an important role in repressing pro-inflammatory transcripts such as TNF-α. Much less is known about the other family members, and none have been studied in the context of infection. Using macrophage cell lines and primary alveolar macrophages we demonstrated that, like ZFP36, ZFP36L1 is prominently induced by infection. To test our hypothesis that macrophage production of ZFP36L1 is necessary for regulation of the inflammatory response of the lung during pneumonia, we generated mice with a myeloid-specific deficiency of ZFP36L1. Surprisingly, we found that myeloid deficiency of ZFP36L1 did not result in alteration of lung cytokine production after infection, altered clearance of bacteria, or increased inflammatory lung injury. Although alveolar macrophages are critical components of the innate defense against respiratory pathogens, we concluded that myeloid ZFP36L1 is not essential for appropriate responses to bacteria in the lungs. Based on studies conducted with myeloid-deficient ZFP36 mice, our data indicate that, of the Zfp36 family, ZFP36 is the predominant negative regulator of cytokine expression in macrophages. In conclusion, these results imply that myeloid ZFP36 may fully compensate for loss of ZFP36L1 or that Zfp36l1-dependent mRNA expression does not play an integral role in the host defense against bacterial pneumonia.


An increased estimate of the merger rate of double neutron stars from observations of a highly relativistic system.
The merger of close binary systems containing two neutron stars should produce a burst of gravitational waves, as predicted by the theory of general relativity. A reliable estimate of the double-neutron-star merger rate in the Galaxy is crucial in order to predict whether current gravity wave detectors will be successful in detecting such bursts. Present estimates of this rate are rather low, because we know of only a few double-neutron-star binaries with merger times less than the age of the Universe. Here we report the discovery of a 22-ms pulsar, PSR J0737-3039, which is a member of a highly relativistic double-neutron-star binary with an orbital period of 2.4 hours. This system will merge in about 85 Myr, a time much shorter than for any other known neutron-star binary. Together with the relatively low radio luminosity of PSR J0737-3039, this timescale implies an order-of-magnitude increase in the predicted merger rate for double-neutron-star systems in our Galaxy (and in the rest of the Universe).


Diesel exhaust particles cause increased levels of DNA deletions after transplacental exposure in mice.
Diesel exhaust particles (DEP) are a major source of air-borne pollution and are linked to increased risk of disease including lung cancer. Here we investigated effects of exposure to DEP on the frequency of DNA deletions, levels of oxidative DNA damage and DNA adduct formation during embryonic development in mice. Pregnant dams were orally exposed to various doses of DEP (500, 250, 125, 62.5, 31.25 mg/kg/day) at embryonic days 10.5-15.5. We determined the frequency of 70 kb DNA deletions spanning exons 6-18 at the p(un) allele that results in black-pigmented spots in the unpigmented retinal pigment epithelium in the eyes of p(un)/p(un) offspring mice. DEP caused a significant increase in the frequency of DNA deletions. Levels of 8-OH deoxyguanosine indicating oxidative DNA damage were within the limits of the unexposed mouse embryos. 33P post-labeling analysis revealed very low levels of DNA adducts in the embryo tissue. Thus, transplacental exposure to DEP resulted in a significant increase in the frequency of DNA deletions in the mouse fetus and such genetic alterations in the offspring may have pathological consequences later in life.


The pooling of logitudinal studies of aging.
This report describes the pooling of 5 longitudinal studies conducted during the last 20 years in West Germany. The pooling provides the following improvements: By increasing the number of participants the reliability and precision of the results are improved. The sample becomes representative of the whole area of the FRG. Both cohort and age comparisons are improved by extending their ranges. The time-of-testing range is increased from 5 to 17 years. Since the significance of this factor has been recognized often but since few empirical explorations have been made in the past, the extension of the time-of-testing range represents the most important contribution of the present work. The pooling of different studies is possible only if they share a common set of methods. This requirement is met under the present conditions. Moreover, each study adds unique methods to the pool, thus, supplementing the common explorations in a constructive manner.


The role of self-efficacy and self-care agency as mediating factors in the link between health literacy and health-promoting lifestyle among older adults post covid 19 era: A multiple mediator model.
Health-promoting lifestyle is poor in older adults during COVID-19 pandemic. Elucidate the underlying mechanisms between health literacy and health-promoting lifestyle is important. Therefore, we investigated the mediating effect of self-efficacy and self-care agency in relation between health literacy and health-promoting lifestyle among older adults post covid 19 era. A cross-sectional descriptive survey on 200 older adults with the mean age of 68.3 were recruited from Lecai urban community in China, through convenience sampling. Information was assessed using Health literacy Assessment Scale for Infectious Diseases of Chinese Residents, the General Self Efficacy Scale, Chinese version of the Elderly Self-care Ability Scale, and the Health-Promoting Lifestyle Profile-Chinese Elderly. A serial multiple mediation modeling was tested using the PROCESS macro for SPSS to validate the pathways. Results indicated that positive correlations were found between health literacy, self-efficacy, self-care agency and health-promoting lifestyle in older adults. Meanwhile, health literacy was linked to enhanced health-promoting lifestyle through two pathways: (1) self-efficacy; (2) chain combination of self-efficacy and self-care agency. Self-efficacy and self-care agency mediated the relationship between health literacy and health-promoting lifestyle in older adults. Therefore, attention to improving self-efficacy, self-care agency and health literacy should be considered crucial for improving health-promoting lifestyle.


Characterization of a probiotic starter culture with anti-Candida activity for Chinese pickle fermentation.
Probiotic starters for Chinese pickle fermentation were screened from three anti-Candida lactic acid bacteria (LAB). Similar to commercial starters, the candidates Lactobacillus plantarum AT4 and L. plantarum AT28 could acidize the pickle within 10 days. The isolates AT4 and AT28 maintained 6.0-7.0 log cfu ml-1 in the pickle products and their inhibition rates against Candida increased to 83.7% and 92.9% after fermentation, respectively. Only L. plantarum AT4 satisfied the essential probiotic requirements such as tolerance to the gastrointestinal environment (pH 2.0, 0.5% bile salts and 0.5% phenol) and adhesion to Caco-2 cells. The pickle product fermented with L. plantarum AT4 presented comparable levels of lactic and acetic acids, volatile profile and sensory value to the commercial one. The results suggested that L. plantarum AT4 can be used as a probiotic starter for industrial fermentation of Chinese pickle, and the pickled product may be utilized as a promising anti-Candida probiotic.


[Meningococcal meningitis in the adult complicated by cutaneous necrosis: description of a clinical case].
Meningitis and meningococcal sepsis are emergency conditions associated with high mortality. The outcome is worsened by the onset of disseminated intravascular coagulation. This may present, particularly in children, with the clinical picture of purpura fulminans, characterized by extensive necrotic-hemorrhagic skin lesions, ischemia of the extremities and multiorgan failure. It has been observed that depletion of coagulation inhibitors, particularly protein C, plays a key role in the development of this severe complication. We describe the case of a woman who presented in the Emergency Room with signs of meningitis, drowsiness, hypotension and petechie. Bacterioscopic examination of the cerebrospinal fluid evidenced characteristic gram-negative diplococci. Laboratory data disclosed initial disseminated intravascular coagulation with low levels of proteins C and S. Following intravenous infusion of antibiotics, fluids and fresh frozen plasma, the patient's condition rapidly improved. However, multiple skin lesions appeared on her fingers, toes and heels. It is likely that the infusion of coagulation inhibitors contained in fresh frozen plasma, prevented evolution to full-blown purpura fulminans. The first choice treatment for purpura fulminans in meningococcal sepsis is infusion of protein C concentrate, which is not, however, currently available on the market.


The effect of scleral spur identification methods on structural measurements by anterior segment optical coherence tomography.
To assess methods for and variations in identifying the scleral spur (SS) position in anterior segment optical coherence tomography. In images of 51 eyes (patients) with open and closed anterior chamber angles, we compared the success rate and the variability of 3 approaches for identifying the SS: the ciliary muscle (CM), bump, and Schwalbe line (SL) methods using mixed effects regression models. The effect of incremental variation in SS position on anterior chamber parameters using the Anterior Segment Analysis Program (ASAP) was analyzed in 8 images. Automated ASAP measurements were compared with manual ImageJ measurements in 46 images. The SS could be identified in 98% of images by each observer using the 3 methods in combination. The SL and CM approaches more successfully identified the SS (82% and 81% success, respectively) than the bump method (59%, P<0.001). The intraobserver, interobserver, and intermethod variabilities of the CM and bump methods were superior to those of the SL method. The SS was more likely to be identified in open angle than angle closure eyes (OR=2.26, P=0.03) and brown eyes were less likely than blue eyes (OR=0.36, P=0.04). Movement of SS position resulted in substantial differences in the angle parameters and iris concavity ratio, whereas iris area and volume were less affected. The CM method was the most successful and least variable method of SS marking, which was more difficult in narrow angle and brown eyes. Variability of SS placement had a large effect on angle parameters and iris concavity ratio.


Predicting Problematic Behavior in Autism Spectrum Disorder Using Medical History and Environmental Data.
Autism spectrum disorder (ASD), characterized by social, communication, and behavioral abnormalities, affects 1 in 36 children according to the CDC. Several co-occurring conditions are often associated with ASD, including sleep and immune disorders and gastrointestinal (GI) problems. ASD is also associated with sensory sensitivities. Some individuals with ASD exhibit episodes of challenging behaviors that can endanger themselves or others, including aggression and self-injurious behavior (SIB). In this work, we explored the use of artificial intelligence models to predict behavior episodes based on past data of co-occurring conditions and environmental factors for 80 individuals in a residential setting. We found that our models predict occurrences of behavior and non-behavior with accuracies as high as 90% for some individuals, and that environmental, as well as gastrointestinal, factors are notable predictors across the population examined. While more work is needed to examine the underlying connections between the factors and the behaviors, having reasonably accurate predictions for behaviors has the potential to improve the quality of life of some individuals with ASD.


Learning styles of medical students at Taibah University: Trends and implications.
Understanding the learning styles of medical students can drive the institutions to adapt instructional materials to enhance students' learning of knowledge and skills. This study explored the learning styles of undergraduate medical students, comparing gender variations in terms of their significant preferences. A cross-sectional observational study was performed in 2012-2013, incorporating 1(st)-5(th) year undergraduate medical students of Taibah University. The instrument used was a Learning Style Questionnaire, with four learning styles (activist, reflector, theorist and pragmatist) and 40 items. Of 450 students, 384 responded (response rate; 85%). No single learning style predominated; 96 (25%) reflectors, 78 (20%) theorists, 68 (17%) pragmatists, and 37 (9%) activists. Combined reflector and theorist was the predominant dual learning style in 27 (7%) students. Among genders, theorist style had a significant result (P = 0.071) indicating that theorists varied among genders due to their different opinions. Learning style preferences of theorists and pragmatists also showed a significant result (P = 0.000 each), depicting that both genders had unique preferences. Males had fewer variations of preferences, when compared with females who showed a significant difference of opinions (P < 0.05). The students in the study preferred diverse learning styles, which were unevenly distributed, reflectors being the most common and activists as the least common. The results reflect the need to promote self-directed learning and modifications of instructional strategies, with expectant tilt in the students' learning styles towards activists and pragmatists.


Management of male erectile dysfunction: a review.
Male erectile dysfunction is common although some patients are embarrassed and delay seeking medical advice. Recent improvements in the understanding of the anatomy, physiology and pharmacotherapy of penile erections, and the introduction of intracavernosal pharmacotherapy has resolved most of the controversies regarding the aetiology of erectile dysfunction. Impotence is equally divided into organic and psychogenic causes. Arterial insufficiency, alcoholism, venosinusoidal, neurological and endocrine disorders are known to cause organic erectile dysfunction. Two most popular options in the management of erectile dysfunction are intracavernosal injections with vasoactive drugs like papavarine, phentolamine, and prostaglandin EI with discontinuation rates of 40-50%, and the use of external vacuum devices whose limitations include failure to achieve and maintain full erection. The use of inflatable penile prostheses is successful but limited with periprosthetic infection and cylinder erosion through the skin or urethra. Surgical procedures have included revascularisation of penile vessels without good results. Surgical ligation of penile veins for venosinusoidal incompetence has been successful compared to excision and embolisation which has disappointing results. Currently the role of oral medications in the treatment of erectile dysfunction is limited. However, there are now several new agents including sildenafil, a phosphodiasterase inhibitor, which is undergoing clinical trials that appear to be effective.


Choking on a foreign body: a physiological study of the effectiveness of abdominal thrust manoeuvres to increase thoracic pressure.
The Heimlich manoeuvre is a well-known intervention for the management of choking due to foreign body airway occlusion, but the evidence base for guidance on this topic is limited and guidelines differ. We measured pressures during abdominal thrusts in healthy volunteers. The angle at which thrusts were performed (upthrust vs circumferential) did not affect intrathoracic pressure. Self-administered abdominal thrusts produced similar pressures to those performed by another person. Chair thrusts, where the subject pushed their upper abdomen against a chair back, produced higher pressures than other manoeuvres. Both approaches should be included in basic life support teaching.


A Novel Anomaly-Based Intrusion Detection Model Using PSOGWO-Optimized BP Neural Network and GA-Based Feature Selection.
Intrusion detection systems (IDS) are crucial for network security because they enable detection of and response to malicious traffic. However, as next-generation communications networks become increasingly diversified and interconnected, intrusion detection systems are confronted with dimensionality difficulties. Prior works have shown that high-dimensional datasets that simulate real-world network data increase the complexity and processing time of IDS system training and testing, while irrelevant features waste resources and reduce the detection rate. In this paper, a new intrusion detection model is presented which uses a genetic algorithm (GA) for feature selection and optimization algorithms for gradient descent. First, the GA-based method is used to select a set of highly correlated features from the NSL-KDD dataset that can significantly improve the detection ability of the proposed model. A Back-Propagation Neural Network (BPNN) is then trained using the HPSOGWO method, a hybrid combination of the Particle Swarm Optimization (PSO) and Grey Wolf Optimization (GWO) algorithms. Finally, the hybrid HPSOGWO-BPNN algorithm is used to solve binary and multi-class classification problems on the NSL-KDD dataset. The experimental outcomes demonstrate that the proposed model achieves better performance than other techniques in terms of accuracy, with a lower error rate and better ability to detect different types of attacks.


Oro-facial gangrene (noma/cancrum oris): pathogenetic mechanisms.
Cancrum oris (Noma) is a devastating infectious disease which destroys the soft and hard tissues of the oral and para-oral structures. The dehumanizing oro-facial gangrenous lesion affects predominantly children ages 2 to 16 years, particularly in sub-Saharan Africa, where the estimated frequency in some communities varies from 1 to 7 cases per 1000 population. The risk factors are poverty, malnutrition, poor oral hygiene, residential proximity to livestock in unsanitary environments, and infectious diseases, particularly measles and those due to the herpesviridae. Infections and malnutrition impair the immune system, and this is the common denominator for the occurrence of noma. Acute necrotizing gingivitis (ANG) and oral herpetic ulcers are considered the antecedent lesions, and ongoing studies suggest that the rapid progression of these precursor lesions to noma requires infection by a consortium of micro-organisms, with Fusobacterium necrophorum (Fn) and Prevotella intermedia (Pi) as the suspected key players. Additional to production of a growth-stimulating factor for Pi, Fn displays a classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin, and a hemolysin. Without appropriate treatment, the mortality rate from noma is 70-90%. Survivors suffer the two-fold afflictions of oro-facial mutilation and functional impairment, which require a time-consuming, financially prohibitive surgical reconstruction.


Risk factors and preventive measures of cerebral hyperperfusion syndrome after carotid artery interventional therapy.
This study sought to investigate the risk factors for cerebral hyperperfusion syndrome (CHS) after carotid artery interventional therapy, and to explore potential preventive measures. Three hundred and eighty-two patients treated with carotid artery stenting at the Huanhu Hospital (Tianjin, China) between January 2010 and January 2016 were divided into CHS and non-CHS groups. A retrospective analysis of patient clinical data was made. The CHS group had more patients presenting coronary heart disease, diabetes, progressive neurological disease and transient recurrent cerebral hemorrhage than the non-CHS group. More patients in the CHS group presented stenosis of the internal carotid artery siphon. More CHS group patients showed plaque formation extending >3 cm to the distal end of the internal carotid artery. Finally, more CHS group patients had pressure gradients >60 mmHg (p<0.05). Logistics regression analysis showed that preoperative diabetes mellitus and carotid pressure gradient ≥60 mmHg were independent risk factors for CHS (p<0.05). The ROC curve of carotid pressure gradients ≥60 mmHg were made to predict CHS, with the area under curve being 0.949 (p<0.05). The best cut-off value was 60 mmHg. Therefore, preoperative diabetes and a carotid pressure gradient ≥60 mmHg are risk factors for CHS, and these indicators need to be examined prior to operation.