A retroperitoneal bronchogenic cyst clinically mimicking an adrenal mass: three case reports and a literature review.
Bronchogenic cysts are a congenital primitive foregut-derived developmental malformation, generally occurring in the posterior mediastinum. Their development in the retroperitoneum is extremely rare. Imaging techniques, such as multidetector computed tomography (MDCT), are typically effective in the detection of these lesions. Here, we describe three cases of a retroperitoneal cyst presenting as a para-adrenal mass. Only one boy presented with abdominal pain, and the other two showed no clinical symptoms. Endocrinological evaluation of all three cases was performed, and no adrenal hormone secretion was detected. All three cases were misdiagnosed preoperatively. Each patient underwent surgery, and one symptomatic patient became asymptomatic after surgery. Pathologic examination confirmed all three masses as bronchogenic cysts. The three cases showed some similar MDCT imaging features, including a complete adrenal structure, a cystic or solid mass in the adrenal region, and no obvious enhancement. Therefore, bronchogenic cysts should be considered in the differential diagnosis of retroperitoneal masses, even though accurate preoperative diagnosis remains difficult. A contrast-enhanced MDCT scan may be useful for differentiating hyper-attenuated cysts from other soft tissue masses.


Pathogenesis of poliovirus infection in PVRTg mice: poliovirus replicates in peritoneal macrophages.
The pathogenesis of poliovirus infection, responsible for the induction of a poliovirus-specific mucosal immune response following intraperitoneal (i.p.) inoculation of virus in mice transgenic for the poliovirus receptor (PVRTg mice), was studied. Following inoculation of poliovirus, replication was determined by increase in virus titre (TCID(50)) and by PCR of poliovirus-specific negative-strand RNA in peritoneal macrophages, mesenteric lymph nodes, Peyer's patches, duodenum, brain, kidney and liver. The presence of poliovirus antigens in several cell types was detected by immunolabelling. It was demonstrated that poliovirus replicated in the peritoneal macrophages of PVRTg mice, since the virus titre in peritoneal cells was increased compared to the titre in the inoculum. Negative-strand RNA was detected in these cells and most of the poliovirus-immunostained cells had the morphology of macrophages and expressed the macrophage-specific markers CD86 and M1/70 on their surface. Furthermore, in peritoneal lavage, poliovirus was also present in CD19(+) B cells, but not in dendritic or T cells. Moreover, poliovirus was detected in macrophage-like cells in the lamina propria of the intestine, but not in epithelial cells. Replication of poliovirus in mesenteric lymph nodes, Peyer's patches and brain was followed by excretion of virus in the faeces. This suggests that the virus is transported due to migration of macrophages from the peritoneal cavity to mesenteric lymph nodes and the lamina propria of Peyer's patches. It is likely that this route is responsible for the induction of virus-specific IgA in the gut.


Canadian consensus: a new systemic treatment algorithm for advanced EGFR-mutated non-small-cell lung cancer.
Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised:■ What is the optimal first-line treatment for patients with EGFR-mutated nsclc?■ What is preferred first-line treatment for patients with brain metastasis?■ What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)?■ What is the preferred treatment after osimertinib?■ What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.


ALA-PDT shortens the course of antibiotic therapy for skin infection caused by Mycobacterium marinum.
Recently, the number of cases of Mycobacterium marinum infection has increased. Due to the nonspecific clinical manifestations and lack of standardized treatment guidelines, these infections are often misdiagnosed and are challenging to treat. In this study, four patients had M. marinum skin infections accompanied by a high-risk exposure history and were diagnosed by bacterial culture and gene chip. Two patients were treated with antibiotic therapy alone, and the other two patients were treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics. All four patients enrolled in the study were cured with 100 % efficacy. Two patients were cured after receiving two active antibiotics for 4 months. The other two patients, having considered the drug resistance and intolerance described above, were cured after receiving two active antibiotics for 1-1.5 months along with combination therapy with ALA-PDT. Combination therapy with ALA-PDT and antibiotics was chosen to shorten the duration of antibiotic treatment and reduce the occurrence of adverse reactions.


Male stimuli are necessary for female sexual behavior and uterine growth in prairie voles (Microtus ochrogaster).
In reproductively naive female prairie voles (Microtus ochrogaster) direct contact with male urine or housing in a male-soiled cage, in the absence of physical contact, resulted in increased uterine weights, but did not reliably elicit behavioral estrus (defined by lordosis). Physical contact with an unfamiliar male, for 1 hr or more, followed by 30 or 48 hr of continuous access to a male-soiled cage, induced lordosis in approximately two-thirds of the females tested. When females were physically exposed to a male for 18 hr and tested 6 hr later, 70% showed lordosis. However, when females receiving either 1 or 18 hr of male contact were removed from the presence of the male and placed in a clean cage for 24 hr, only 29-37% of the females subsequently showed lordosis. These results suggest that direct physical contact with the male or chemical stimuli from the male may be necessary to induce and maintain behavioral estrus in female prairie voles.


Patients' experiences and expectations of chiropractic care: a national cross-sectional survey.
Not enough is understood about patients' views of chiropractic care. The aims of this research were to explore patients' experiences and expectations, their perceptions of benefits and risks, and the implications for chiropractors' continuing fitness to practise. Survey questions were formulated from existing literature, published guidance on good practice from the General Chiropractic Council, and from 28 telephone interviews and a small focus group with chiropractic patients using a semi-structured topic guide. In its final form, the survey elicited patients' ratings on expectations regarding 33 aspects of care. In a national cross-sectional survey, a number of sampling methods were required as a consequence of the low practitioner response rate. In total, 544 completed questionnaires were received from chiropractic patients, a lower response rate than expected (8%). The two main benefits that patients reported regarding their chiropractic care were reduced pain (92%) and increased mobility (80%). Of respondents, 20% reported unexpected or unpleasant reactions to their treatment, most commonly tiredness or fatigue (32%), and extra pain (36%). In most cases they expressed low levels of concern about these reactions. Patients' expectations were met for most aspects of care. The four aspects of practice where expectations were least well met comprised: having more information on the cost of the treatment plan at the first consultation (80%); the chiropractor contacting the patient's general practitioner if necessary (62%); having a discussion about a referral to another healthcare practitioner (62%); and providing a method for confidential feedback (66%). Overall, patients reported a high level of satisfaction with the benefits of their chiropractic care, although there is a likelihood of bias towards patients with a positive experience of chiropractic. There were no serious adverse reactions; however, patients reported concern about pain, tingling and numbness in the limbs after chiropractic. In general, patients' expectations were being well met.


Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.
Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 × 10⁻¹⁵). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 × 10⁻¹⁴). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.


Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation.
A highly conserved threonine near the C terminus of gp120 of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) was investigated for its contributions to envelope protein function and virion infectivity. When this highly conserved Thr residue was substituted with anything other than serine (the other amino acid that can accept O-glycosylation), the resulting virus was noninfectious. We found that this Thr was critical for the association of gp120 with the virion and that amino acid substitution increased the amount of dissociated gp120 in the cell culture supernatant. When HIV virions were generated in cells overexpressing polypeptide N-acetylgalactosaminyltransferase 1 (GalNAcT1), viral infectivity was increased 2.5-fold compared to that of virus produced in wild-type HEK293T cells; infectivity was increased 8-fold when the Thr499Ser mutant was used. These infectivity enhancements were not observed when GalNAcT3 was used. Using HEK293T knockout cell lines totally devoid of the ability to perform O-linked glycosylation, we demonstrated production of normal levels of virions and normal levels of infectivity in the complete absence of O-linked carbohydrate. Our data indicate that O-glycosylation is not necessary for the natural replication cycle of HIV and SIV. Nonetheless, it remains theoretically possible that the repertoire of GalNAc transferase isoforms in natural target cells for HIV and SIV in vivo could result in O-glycosylation of the threonine residue in question and that this could boost the infectivity of virions beyond the levels seen in the absence of such O-glycosylation.IMPORTANCE Approximately 50% of the mass of the gp120 envelope glycoprotein of both HIV and SIV is N-linked carbohydrate. One of the contributions of this N-linked carbohydrate is to shield conserved peptide sequences from recognition by humoral immunity. This N-linked glycosylation is one of the reasons that primary isolates of HIV and SIV are so heavily resistant to antibody-mediated neutralization. Much less studied is any potential contribution from O-linked glycosylation. The literature on this topic to date is somewhat confusing and ambiguous. Our studies described in this report demonstrate unambiguously that O-linked glycosylation is not necessary for the natural replication cycle of HIV and SIV. However, the door is not totally closed because of the diversity of numerous GalNAc transferase enzymes that initiate O-linked carbohydrate attachment and the theoretical possibility that natural target cells for HIV and SIV in vivo could potentially complete such O-linked carbohydrate attachment to further increase infectivity.


Fibroblast-epithelial cell interactions drive epithelial-mesenchymal transition differently in cells from normal and COPD patients.
Epithelial-to-mesenchymal transition (EMT), which involves changes in cellular morphology of highly polarized epithelial cells and the gain of mesenchymal cell phenotype with migratory and invasive capacities, is implicated in smoking-related chronic obstructive pulmonary disease (COPD). However, the interactions of fibroblasts and epithelial cells and the participation of fibroblasts in the EMT processes in COPD are poorly understood. Here, we investigated the hypothesis that EMT is active in human bronchial epithelial (HBE) cells of COPD patients, and that mediators secreted by lung fibroblasts from COPD patients induce EMT. Primary HBE cells from normal subjects and COPD patients were purchased from LONZA. HLFs were derived from resected lung obtained from normal (N) and COPD (D) subjects and their conditioned medium (CM) was collected after 2-day culture in serum-free medium. The expression of epithelial and mesenchymal markers as well as EMT-related transcription factors in lung biopsies, and in HBE cells following stimulation with CM from both normal human lung fibroblasts (NHLF) and COPD human lung fibroblasts (DHLF) was evaluated by immunohistochemistry, qRT-PCR and western blot. Basal mRNA expression of mesenchymal markers and EMT-related transcription factors were increased in DHBE cells compared to normal human bronchial epithelial cells (NHBE) cells as well as in COPD lungs. CM from NHLF significantly induced vimentin expression in both NHBE and COPD human bronchial epithelial cells (DHBE) cells, but only increased N-cadherin expression in DHBE cells. CM from NHLF significantly induced Twist1 and Twist2 expression in NHBE cells and increased Snai2 (Slug) expression in DHBE cells. While CM from NHLF had no effect on such EMT markers, CM from DHLF significantly increased the protein expression of E-cadherin and vimentin in NHBE cells compared to control. N-cadherin expression was upregulated to a greater degree in NHBE cells than DHBE cells. Only CM from DHLF significantly increased E-/N-cadherin ratio in DHBE cells. Our results suggest that DHBE cells have partially undergone EMT under baseline conditions. DHLF-CM promoted EMT in NHBE, suggesting that interactions between fibroblast and epithelial cells may play an important role in the EMT process in COPD.


Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System.
Over the last decade knowledge of the role of astrocytes in central nervous system (CNS) neuroinflammatory diseases has changed dramatically. Rather than playing a merely passive role in response to damage it is clear that astrocytes actively maintain CNS homeostasis by influencing pH, ion and water balance, the plasticity of neurotransmitters and synapses, cerebral blood flow, and are important immune cells. During disease astrocytes become reactive and hypertrophic, a response that was long considered to be pathogenic. However, recent studies reveal that astrocytes also have a strong tissue regenerative role. Whilst most astrocyte research focuses on modulating neuronal function and synaptic transmission little is known about the cross-talk between astrocytes and oligodendrocytes, the myelinating cells of the CNS. This communication occurs via direct cell-cell contact as well as via secreted cytokines, chemokines, exosomes, and signalling molecules. Additionally, this cross-talk is important for glial development, triggering disease onset and progression, as well as stimulating regeneration and repair. Its critical role in homeostasis is most evident when this communication fails. Here, we review emerging evidence of astrocyte-oligodendrocyte communication in health and disease. Understanding the pathways involved in this cross-talk will reveal important insights into the pathogenesis and treatment of CNS diseases.


Ischemic stroke injury is mediated by aberrant Cdk5.
Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke.


Transmission failure in sympathetic nerves produced by hemicholinium.
It has been shown by others that hemicholinium (alpha,alpha'-dimethylethanolamino-4,4'-biacetophenone) inhibits the synthesis of acetylcholine, an effect which is reversed by choline. Hemicholinium produces a failure of response to nerve stimulation in the following sympathetically innervated preparations: guinea-pig isolated vas deferens, rabbit isolated uterus, rabbit isolated colon, perfused rabbit ear, cat isolated atria and the piloerector muscles in the cat's tail. The blocking action of hemicholinium on the responses to postganglionic sympathetic stimulation resembles its blocking action against cholinergic nerve stimulation observed on rabbit isolated atria with vagus nerves, rabbit isolated vagina with pelvic nerves, and guinea-pig isolated diaphragm with phrenic nerve. The failure of transmission produced by hemicholinium in sympathetic nerves and in cholinergic nerves can be reversed by choline. It is suggested that if there were a cholinergic junction at sympathetic nerve endings the mechanism of the blocking action of hemicholinium at these endings could be explained by inhibition of acetylcholine synthesis.


COVID-19 Research: Lessons from Non-Human Primate Models.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates.


Individual, community and societal correlates of insecticide treated net use among pregnant women in sub-Saharan Africa: a multi-level analysis.
Malaria in pregnancy is a crucial public health concern due to the enormous risk it poses to maternal and newborn health. The World Health Organisation therefore recommends insecticide-treated net (ITN) for pregnant women. The world over, sub-Saharan Africa bears the highest prevalence of malaria and its associated complications. This study investigated the individual, community and society level factors associated with ITN use among pregnant women in sub-Saharan Africa. The study was conducted with Demographic and Health Survey data of 21 sub-Saharan African countries. A total of 17,731 pregnant women who possessed ITN participated in the study. Descriptive computation of ITN use by survey country and socio-demographic characteristics was conducted. Further, five multi-level binary logistic regression models were fitted with MLwiN 3.05 package in STATA. The Markov Chain Monte Carlo (MCMC) estimation procedure was used in estimating the parameters whilst the Bayesian Deviance Information Criterion was used for the model fitness test. On average, 74.2% pregnant women in SSA used ITN. The highest prevalence of ITN use occurred in Mali (83.7%) whilst the least usage occurred in Namibia (7%). Women aged 30-34 were more likely to use ITN compared with those aged 45-49 [aOR = 1.14; Crl = 1.07-1.50]. Poorest women were less probable to use ITN relative to richest women [aOR = 0.79; Crl = 0.70-0.89]. Compared to women who did not want their pregnancies at all, women who wanted their pregnancies [aOR = 1.06; Crl = 1.04-1.19] were more probable to use ITN. Women in male-headed households had higher likelihood of ITN use compared to those from female-headed households [aOR = 1.28; Crl = 1.19-1.39]. On the whole, 38.1% variation in ITN use was attributable to societal level factors whilst 20.9% variation was attributable to community level factors. The study has revealed that in addition to individual level factors, community and society level factors affect ITN use in SSA. In as much as the study points towards the need to incorporate community and societal variations in ITN interventions, active involvement of men can yield better outcome for ITN utilisation interventions in SSA.


Phenotypical variation within 22 families with Pompe disease.
Pompe disease has a broad clinical spectrum, in which the phenotype is partially explained by the genotype. The aim of this study was to describe phenotypical variation among siblings with non-classic Pompe disease. We hypothesized that siblings and families with the same genotype share more similar phenotypes than the total population of non-classic Pompe patients, and that this might reveal genotype-phenotype correlations. We identified all Dutch families in which two or three siblings were diagnosed with Pompe disease and described genotype, acid α-glucosidase activity, age at symptom onset, presenting symptoms, specific clinical features, mobility and ventilator dependency. We identified 22 families comprising two or three siblings. All carried the most common mutation c.-32-13 T > G in combination with another pathogenic mutation. The median age at symptom onset was 33 years (range 1-62 years). Within sibships symptom onset was either in childhood or in adulthood. The median variation in symptom onset between siblings was nine years (range 0-31 years). Presenting symptoms were similar across siblings in 14 out of 22 families. Limb girdle weakness was most frequently reported. In some families ptosis or bulbar weakness were present in all siblings. A large variation in disease severity (based on wheelchair/ventilator dependency) was observed in 11 families. This variation did not always result from a difference in duration of the disease since a third of the less affected siblings had a longer course of the disease. Enzyme activity could not explain this variation either. In most families male patients were more severely affected. Finally, symptom onset varied substantially in twelve families despite the same GAA genotype. In most families with non-classic Pompe disease siblings share a similar phenotype regarding symptom onset, presenting symptoms and specific clinical features. However, in some families the course and severity of disease varied substantially. This phenotypical variation was also observed in families with identical GAA genotypes. The commonalities and differences indicate that besides genotype, other factors such as epigenetic and environmental effects influence the clinical presentation and disease course.


Chronic physical conditions and risk for perinatal mental illness: A population-based retrospective cohort study.
One in 5 women experience mental illness in pregnancy or post partum. Universal preventive interventions have not lowered the incidence of perinatal mental illness, perhaps because those at highest risk were not targeted. Outside of pregnancy, chronic physical conditions are known to confer increased risk for mental illness. Our objective was to examine the association between chronic physical conditions and risk of perinatal mental illness. We conducted a population-based retrospective cohort study using linked health administrative data sets in Ontario, Canada, in 2005 to 2015. We compared 77,385 women with chronic physical conditions to 780,619 women without such conditions, all of whom had a singleton live birth. Excluded were women with a mental illness diagnosis within 2 years before pregnancy. Chronic physical conditions were captured using the Agency for Healthcare Research and Quality Chronic Condition Indicator, applied to acute healthcare encounters in the 2 years before pregnancy. The outcome was perinatal mental illness, defined by a mental illness or addiction diagnosis arising between conception and 365 days post partum. The outcome was further defined by timing (prenatal or post partum) and specific diagnosis (psychotic disorder, mood or anxiety disorder, substance use disorder, self-harm, or other). Modified Poisson regression generated relative risks and 95% confidence intervals (CIs), adjusted for age, parity, rural residence, income quintile, and remote history of mental health care. Women in the cohort had an average age of 29.6 years (standard deviation 5.4), 44.2% were primiparous, 11.0% lived in a rural area, 40.1% were in the lowest 2 income quintiles, and 47.9% had a remote history of mental health care. More women with (20.4%) than without (15.6%) a chronic physical condition experienced perinatal mental illness-an adjusted relative risk (aRR) of 1.20 (95% CI 1.18-1.22, p < 0.0001). The aRRs were statistically significant for mental illness in pregnancy (1.12, 95% CI 1.10-1.15, p < 0.0001) and post partum (1.25, 95% CI 1.23-1.28, p < 0.0001). Psychotic disorders (aRR 1.50, 95% CI 1.36-1.65, p < 0.0001), mood or anxiety disorders (aRR 1.19, 95% CI 1.17-1.21, p < 0.0001), substance use disorders (aRR 1.47, 95% CI 1.34-1.62, p < 0.0001), and other mental illness (aRR 1.68, 95% CI 1.50-1.87, p < 0.0001) were more likely in women with than without chronic physical conditions, but not self-harm (aRR 1.14, 95% CI 0.87-1.48, p = 0.34). The study was limited by reliance on acute health care encounters to measure chronic physical conditions and the inability to capture undiagnosed mental health problems. Findings from this study suggest that women with a chronic physical condition predating pregnancy may be at heightened risk of developing mental illness in the perinatal period. These women may require targeted efforts to lower the severity of their condition and improve their coping strategies and supports in pregnancy and thereafter.


Was the Maternal Health Cash Transfer Programme in Nigeria Sustainable and Cost-Effective?
Background: The Subsidy Reinvestment and Empowerment Programme (SURE-P), Maternal and Child Health (MCH) was introduced by the Nigerian government to increase the use of skilled maternal health services and reduce maternal mortality. The programme, funded out of a reduction in the fuel subsidy, was implemented between October 2012 and April 2015 and incorporated a conditional cash transfer to women to encourage use of facility based maternal services. We seek to assess the incremental cost effectiveness and long term impact of the conditional cash transfer element of the programme. Methods: An impact analysis and incremental cost-effectiveness analysis of conditional cash transfers (CCTs) is undertaken taking a health service perspective toward costs of the intervention. The study was undertaken in Anambra state, comparing areas that received only the investment in health services with areas that implemented the conditional cash transfer programme. An interrupted time series analysis of the programme outputs was undertaken. These were combined with a programme costing to determine the incremental cost per output. Findings: Maternal services provided to patients in conditional cash transfer areas accelerated rapidly from the middle of 2014 until after the programme in late 2015. The costs of providing services in each Primary Health Center facility was US $52,128 in the areas that only invested in health services compared to US $90,702 in facilities that also provided cash transfers. Much of the additional cost was in managing cash transfers. The incremental cost in the cash transfer areas was $572 for delivery care and $11 for antenatal care. If the programme was to be integrated as a regular service in the public health system, the cost of a delivery is estimated to fall to $389 and to $188 if 2015 levels of activity are assumed. Conclusion: Although the cost of CCTs as originally constituted as a vertical programme are relatively high compared to other similar programmes, these would fall substantially if integrated into the main health system. There is also evidence of sustained impact beyond the end of the funding suggesting that short term programmes can lead to a long-term change in patterns of health seeking behavior.


Red Bone Marrow and Male Breast Doses for a Cohort of Atomic Veterans.
Both red bone marrow and male breast doses with associated uncertainty have been reconstructed for a 1,982-person subset of a cohort of 114, 270 military personnel (referred to as "atomic veterans") who participated in U.S. atmospheric nuclear weapons testing from 1945 to 1962. The methods used to calculate these doses and corresponding uncertainty have been reported in detail by Till et al. in an earlier publication. In this current article we report the final results of those calculations. These doses are being used in a case-cohort design epidemiological investigation of leukemia and male breast cancer. This cohort of atomic veterans is one component in a broader-scope study of approximately one million U.S. persons designed to investigate risk from chronic low-dose radiation exposure. Doses to the atomic veterans in this sub-cohort were relatively low, with approximately two-thirds receiving red bone marrow doses <5 mGy and only four individuals receiving a red bone marrow dose >50 mGy. The average red bone marrow dose for members of the sub-cohort was 5.9 mGy. Doses to male breast were approximately 20% higher than red bone marrow doses. The uncertainty in the estimated doses was relatively low, considering relevant personnel dosimetry was available for only about 25% of the subjects, and most of the doses were reconstructed from film badges worn by co-workers or from the individual's military record and military unit activities. The average coefficient of variation for the individual dose estimates was approximately 0.5, comparable to the uncertainty in doses estimated for the Japanese A-bomb survivors. Although the reconstructed red bone marrow doses were about 36% lower on average than the conservative doses previously estimated by the military for compensation, the overall correlation was quite good, suggesting that the estimates of doses from external exposure by the military for all ∼115,000 cohort members could be adjusted appropriately and used in further epidemiological analyses.


In vitro binding study of adaptor protein complex (AP-1) to lysosomal targeting motif (LI-motif).
Lysosomal membrane glycoproteins carry targeting information in cytoplasmic regions. Two distinct targeting motifs in these regions, GY (glycine-tyrosine) and LI (leucine-isoleucine), have been identified and characterized. Accumulating evidence suggests that the adaptor complexes (AP-1, AP-2, and AP-3) recognize this information in cytoplasmic tails of transmembrane proteins. Here we report two different in vitro analyses (affinity beads and surface plasmon resonance) which revealed specific interaction between the cytoplasmic tail of LGP85 and AP-1 but not so with AP-2. We also noted requirement of the LI motif of the LGP85 tail in binding to the AP-1 complex. Our data and others which indicated the binding of AP-3 to the LIMP II (synonym of LGP85) tail suggest that the cytoplasmic tail of LGP85 interacts with AP-1 at the trans-Golgi network (TGN) and AP-3 at late endosomes, respectively. We propose that this sequential interaction between the lysosomal targeting signal and distinct APs along its transport pathway is responsible for the critical sorting of lysosomal membrane proteins and/or the potential proofreading system of mistargeted molecules.


Rickettsia conorii Israeli tick typhus strain isolated from Rhipicephalus sanguineus ticks in Portugal.
This report describes the first establishment of five isolates of R. conorii Israeli tick typhus (ITT) strain from Rhipicephalus sanguineus ticks in different regions of Portugal. Ticks were collected on two separate expeditions that took place in Bragança, Montesinho Natural Park, and Portalegre City.


Spectroscopic ellipsometry modelling of Cr+ implanted copper oxide thin films.
In this paper, we present modelling of spectroscopic ellipsometry data. The measured samples are thin films of copper oxides modified with the ion implantation method. The samples were prepared using reactive magnetron sputtering. Thin films of CuO and Cu4O3 were deposited and subjected to Cr ion implantation with an energy of 15 keV and a dose of 5 × 1016 ions/cm2. The decrease in crystallinity of the thin film as a result of the implantation was inspected with X-ray diffraction measurements. The implantation of Cr+ ions was simulated using the Stopping and Range of Ions in Matter software by Ziegler and Biersack. Ion beam energy of 15 keV was simulated to estimate the distribution of Cr ions in the copper oxides thin films. Optical parameters, such as refractive index, extinction coefficient, and absorption coefficient of the thin films, were investigated with spectroscopic ellipsometry. Multilayered models based on Tauc-Lorentz oscillators were developed for both oxides. Analysis of the optical properties showed that the ion implantation with Cr decreased the absorption of copper oxides thin films and the modelling proved that the material properties of top layers changed the most.


Integrated analysis of multiple microarray datasets identifies a reproducible survival predictor in ovarian cancer.
Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival. Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation ("batch-effect"). Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high- and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2(nd) validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p < 0.01), 1(st) validation set (median OS 32 months versus not-yet-reached, p = 0.026) and 2(nd) validation set (median OS 43 versus 61 months, p = 0.013) maintaining independent prognostic power in multivariate analysis. There was strong molecular correspondence of the respective high- and low-risk tumors between training and 1(st) validation set. Low and high-risk tumors were enriched for favorable and unfavorable molecular subtypes and pathways, previously defined in the public 2(nd) validation set. Integration of previously generated cancer microarray datasets may lead to robust and widely applicable survival predictors. These predictors are not simply a compilation of prognostic genes but appear to track true molecular phenotypes of good- and poor-outcome.


Methodological and physiological test-retest reliability of (13) C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls.
Glycogen is a major substrate in energy metabolism and particularly important to prevent hypoglycemia in pathologies of glucose homeostasis such as type 1 diabetes mellitus (T1DM). (13) C-MRS is increasingly used to determine glycogen in skeletal muscle and liver non-invasively; however, the low signal-to-noise ratio leads to long acquisition times, particularly when glycogen levels are determined before and after interventions. In order to ease the requirements for the subjects and to avoid systematic effects of the lengthy examination, we evaluated if a standardized preparation period would allow us to shift the baseline (pre-intervention) experiments to a preceding day. Based on natural abundance (13) C-MRS on a clinical 3 T MR system the present study investigated the test-retest reliability of glycogen measurements in patients with T1DM and matched controls (n = 10 each group) in quadriceps muscle and liver. Prior to the MR examination, participants followed a standardized diet and avoided strenuous exercise for two days. The average coefficient of variation (CV) of myocellular glycogen levels was 9.7% in patients with T1DM compared with 6.6% in controls after a 2 week period, while hepatic glycogen variability was 13.3% in patients with T1DM and 14.6% in controls. For comparison, a single-session test-retest variability in four healthy volunteers resulted in 9.5% for skeletal muscle and 14.3% for liver. Glycogen levels in muscle and liver were not statistically different between test and retest, except for hepatic glycogen, which decreased in T1DM patients in the retest examination, but without an increase of the group distribution. Since the CVs of glycogen levels determined in a "single session" versus "within weeks" are comparable, we conclude that the major source of uncertainty is the methodological error and that physiological variations can be minimized by a pre-study standardization. For hepatic glycogen examinations, familiarization sessions (MR and potentially strenuous interventions) are recommended. Copyright © 2016 John Wiley & Sons, Ltd.


Adipose tissue in health and disease.
Adipose, or fat, tissue (AT) was once considered an inert tissue that primarily existed to store lipids, and was not historically recognized as an important organ in the regulation and maintenance of health. With the rise of obesity and more rigorous research, AT is now recognized as a highly complex metabolic organ involved in a host of important physiological functions, including glucose homeostasis and a multitude of endocrine capabilities. AT dysfunction has been implicated in several disease states, most notably obesity, metabolic syndrome and type 2 diabetes. The study of AT has provided useful insight in developing strategies to combat these highly prevalent metabolic diseases. This review highlights the major functions of adipose tissue and the consequences that can occur when disruption of these functions leads to systemic metabolic dysfunction.


Effect of Acidic Beverages on Color Stability and Microhardness of Various Esthetic Restorative Materials: A Comparative Study.
The aim of this study was to assess the effect of acidic beverages on color stability and microhardness of various esthetic restorative materials. A total of 60 samples were included in the present study. Group I: Microhybrid composite resin, Group II: Nanoceramic, Group III: ORMOCER (Organically Modified Ceramics). 10 mm internal diameter and 5 mm depth of cylindrical aluminum mold of were utilized to prepare the samples. All the esthetic restorative samples were submerged for 10 min in 25 ml of acidic drink (Coca-Cola) each day up to 15 days. Vickers diamond intender was used to measure the microhardness of each sample. These values were calculated with baseline, 7th, and 15th days for final microhardness values. The mean surface microhardness of 63.20 ± 0.46 was shown by Group III which was slightly more than that in Group II (60.08 ± 0.34) and Group I (58.10 ± 1.76). Analysis of covariance did not show any statistically significant difference between the groups. The samples in Group I showed the highest reduction in surface microhardness value after immersion into acidic drink, followed by Group II and Group III on 7th day and 15th day. A statistically significant difference (P < 0.001) was found on the 7th day. The present study concludes that the Organically Modified Ceramics esthetic restorative material showed the finest behavior after being dipped in the acidic drink followed next by Nanoceramic and Microhybrid composite resin.


Tuneable synthetic reduced graphene oxide scaffolds elicit high levels of three-dimensional glioblastoma interconnectivity in vitro.
Three-dimensional tissue scaffolds have utilised nanomaterials to great effect over the last decade. In particular, scaffold design has evolved to consider mechanical structure, morphology, chemistry, electrical properties, and of course biocompatibility - all vital to the performance of the scaffold and how successful they are in developing cell cultures. We have developed an entirely synthetic and tuneable three-dimensional scaffold of reduced graphene oxide (rGO) that shows good biocompatibility, and favourable mechanical properties as well as reasonable electrical conductivity. Importantly, the synthesis is scaleable and suitable for producing scaffolds of any desired geometry and size, and we observe a high level of biocompatibility and cell proliferation for multiple cell lines. In particular, one of the most devastating forms of malignant brain cancer, glioblastoma (GBM), grows especially well on our rGO scaffold in vitro, and without the addition of response-specific growth factors. We have observed that our scaffold elicits spontaneous formation of a high degree of intercellular connections across the GBM culture. This phenomenon is not well documented in vitro and nothing similar has been observed in synthetic scaffolds without the use of response-specific growth factors - which risk obscuring any potential phenotypic behaviour of the cells. The use of scaffolds like ours, which are not subject to the limitations of existing two-dimensional substrate technologies, provide an excellent system for further investigation into the mechanisms behind the rapid proliferation and success of cancers like GBM. These synthetic scaffolds can advance our understanding of these malignancies in the pursuit of improved theranostics against them.


MUSCLE: a multiple sequence alignment method with reduced time and space complexity.
In a previous paper, we introduced MUSCLE, a new program for creating multiple alignments of protein sequences, giving a brief summary of the algorithm and showing MUSCLE to achieve the highest scores reported to date on four alignment accuracy benchmarks. Here we present a more complete discussion of the algorithm, describing several previously unpublished techniques that improve biological accuracy and / or computational complexity. We introduce a new option, MUSCLE-fast, designed for high-throughput applications. We also describe a new protocol for evaluating objective functions that align two profiles. We compare the speed and accuracy of MUSCLE with CLUSTALW, Progressive POA and the MAFFT script FFTNS1, the fastest previously published program known to the author. Accuracy is measured using four benchmarks: BAliBASE, PREFAB, SABmark and SMART. We test three variants that offer highest accuracy (MUSCLE with default settings), highest speed (MUSCLE-fast), and a carefully chosen compromise between the two (MUSCLE-prog). We find MUSCLE-fast to be the fastest algorithm on all test sets, achieving average alignment accuracy similar to CLUSTALW in times that are typically two to three orders of magnitude less. MUSCLE-fast is able to align 1,000 sequences of average length 282 in 21 seconds on a current desktop computer. MUSCLE offers a range of options that provide improved speed and / or alignment accuracy compared with currently available programs. MUSCLE is freely available at http://www.drive5.com/muscle.


The prevalence of previously undiagnosed leprosy in the general population of northwest bangladesh.
The prevalence of previously undiagnosed leprosy (PPUL) in the general population was determined to estimate the background level of leprosy in the population and to compare this with registered prevalence and the known PPUL in different levels of contacts of leprosy patients. Multistage cluster sampling including 20 clusters of 1,000 persons each in two districts with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the cluster sample was 27 (19 SLPB, 8 PB2-5), giving a PPUL rate of 15.1 per 10,000. PPUL in the general population is six times higher than the registered prevalence, but three times lower than that in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. Full village or neighbourhood surveys may be preferable to contact surveys where leprosy is highly endemic.


A targeted covalent small molecule inhibitor of HIV-1 fusion.
We describe a low molecular weight covalent inhibitor targeting a conserved lysine residue within the hydrophobic pocket of HIV-1 glycoprotein-41. The inhibitor bound selectively to the hydrophobic pocket and exhibited an order of magnitude enhancement of anti-fusion activity against HIV-1 compared to its non-covalent counterpart. The findings represent a significant advance in the quest to obtain non-peptide fusion inhibitors.


Cytotoxicity of Snake Venoms and Cytotoxins From Two Southeast Asian Cobras (Naja sumatrana, Naja kaouthia): Exploration of Anticancer Potential, Selectivity, and Cell Death Mechanism.
Venoms of cobras (Naja spp.) contain high abundances of cytotoxins, which contribute to tissue necrosis in cobra envenomation. The tissue-necrotizing activity of cobra cytotoxins, nevertheless, indicates anticancer potentials. This study set to explore the anticancer properties of the venoms and cytotoxins from Naja sumatrana (equatorial spitting cobra) and Naja kaouthia (monocled cobra), two highly venomous species in Southeast Asia. The cytotoxicity, selectivity, and cell death mechanisms of their venoms and cytotoxins (NS-CTX from N. sumatrana: NS-CTX; N. kaouthia: NK-CTX) were elucidated in human lung (A549), prostate (PC-3), and breast (MCF-7) cancer cell lines. Cytotoxins were purified through a sequential fractionation approach using cation-exchange chromatography, followed by C18 reverse-phase high-performance liquid chromatography (HPLC) to homogeneity validated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and identified by liquid chromatography-tandem mass spectrometry (LCMS/MS). The cobra venoms and their respective cytotoxins exhibited concentration-dependent growth inhibitory effects in all cell lines tested, with the cytotoxins being more potent compared to the corresponding whole venoms. NS-CTX and NK-CTX are, respectively, P-type and S-type isoforms of cytotoxin, based on the amino acid sequences as per LCMS/MS analysis. Both cytotoxins exhibited differential cytotoxic effects in the cell lines tested, with NS-CTX (P-type cytotoxin) being significantly more potent in inhibiting the growth of the cancer cells. Both cytotoxins demonstrated promising selectivity only for the A549 lung cancer cell line (selectivity index = 2.17 and 2.26, respectively) but not in prostate (PC-3) and breast (MCF-7) cancer cell lines (selectivity index < 1). Flow cytometry revealed that the A549 lung cancer cells treated with NS-CTX and NK-CTX underwent necrosis predominantly. Meanwhile, the cytotoxins induced mainly caspase-independent late apoptosis in the prostate (PC-3) and breast (MCF-7) cancer cells lines but lacked selectivity. The findings revealed the limitations and challenges that could be faced during the development of new cancer therapy from cobra cytotoxins, notwithstanding their potent anticancer effects. Further studies should aim to overcome these impediments to unleash the anticancer potentials of the cytotoxins.


Atmospheric Physics and Earth Observations: Observations of Lyman-agr Emissions of Hydrogen and Deuterium.
A spectrophotometer was flown on Spacelab 1 to study various mechanisms of Lyman-alpha emission in the upper atmosphere. The use of absorption cells filled with H(2) and D(2) gases allowed us to discriminate a number of weak Lyman-alpha emissions heretofore masked by the strong H geocoronal emission due to resonance scattering of solar photons. Preliminary results are presented on three topics: the first optical detection of the deuterium Lyman-alpha emission at 110 kilometers, with an intensity of 330 rayleighs indicating an eddy diffusion coefficient of 1.3 x 10(6) square centimeters per second; auroral proton precipitations seen on both the night and the day side; and an emission located above 250 kilometers of altitude, interpreted as the result of charge exchange of magnetospheric protons with geocoronal atoms.


Evaluation of dextran-flufenamic acid ester as a polymeric colon-specific prodrug of flufenamic acid, an anti-inflammatory drug, for chronotherapy.
Dextran-flufenamic acid ester (Dex-FFA) with varied degree of substitution (DS) was prepared by imidazolide method. Dex-FFA was stable in pH 1.2 or pH 6.8 buffer. The depolymerization degree of Dex-FFA by dextranase decreased as DS increased. Dex-FFA with DS of 13 or 20 released FFA up to 70% or 21% of the dose, respectively, on 24 h-incubation with the 10% cecal contents. FFA was liberated up to 29% of the dose on 24 h-incubation of dextranase pre-treated Dex-FFA with the homogenates of the upper intestine, whereas no FFA was detected devoid of dextranse-pretreatment. Upon oral administration of Dex-FFA (DS 13, 20 mg equivalent of FFA/kg) or FFA (10 mg/kg) to rats, t(max) for FFA with Dex-FFA administration delayed approximately 6 h compared with that of free FFA administration, while C(max) for FFA was similar. The plasma level for FFA became greater around 6 h after administration of Dex-FFA than free FFA and it was maintained throughout the period of 24 h-experiment. Dex-FFA markedly attenuated gastric ulcerogenicity of FFA. Taken together, Dex-FFA could be useful as a colon-specific prodrug which possesses anti-inflammatory properties and offers opportunities as a chronotherapeutic approach for the treatment of arthritis.


Interrater Agreement of EEG Interpretation After Pediatric Cardiac Arrest Using Standardized Critical Care EEG Terminology.
We evaluated interrater agreement of EEG interpretation in a cohort of critically ill children resuscitated after cardiac arrest using standardized EEG terminology. Four pediatric electroencephalographers scored 10-minute EEG segments from 72 consecutive children obtained 24 hours after return of circulation using the American Clinical Neurophysiology Society's (ACNS) Standardized Critical Care EEG terminology. The percent of perfect agreement and the kappa coefficient were calculated for each of the standardized EEG variables and a predetermined composite EEG background category. The overall background category (normal, slow-disorganized, discontinuous, or attenuated-featureless) had almost perfect agreement (kappa 0.89).The ACNS Standardized Critical Care EEG variables had agreement that was (1) almost perfect for the seizures variable (kappa 0.93), (2) substantial for the continuity (kappa 0.79), voltage (kappa 0.70), and sleep transient (kappa 0.65) variables, (3) moderate for the rhythmic or periodic patterns (kappa 0.55) and interictal epileptiform discharge (kappa 0.60) variables, and (4) fair for the predominant frequency (kappa 0.23) and symmetry (kappa 0.31) variables. Condensing variable options led to improved agreement for the continuity and voltage variables. These data support the use of the standardized terminology and the composite overall background category as a basis for standardized EEG interpretation for subsequent studies assessing EEG background for neuroprognostication after pediatric cardiac arrest.


Enhancement of photothermal heat generation by metallodielectric nanoplasmonic clusters.
A four-member homogenous quadrumer composed of silver core-shell nanostructures is tailored to enhance photothermal heat generation efficiency in sub-nanosecond time scale. Calculating the plasmonic and photothermal responses of metallic cluster, we show that it is possible to achieve thermal heat flux generation of 64.7 μW.cm-2 and temperature changes in the range of ΔT = 150 K, using Fano resonant effect. Photothermal heat generation efficiency is even further enhanced by adding carbon nanospheres to the offset gap between particles and obtained thermal heat flux generation of 93.3 μW.cm-2 and temperature increase of ΔT = 172 K. It is also shown that placement of dielectric spheres gives rise to arise collective magnetic dark plasmon modes that improves the quality of the observed Fano resonances. The presented data attests the superior performance of the proposed metallodielectric structures to utilize in practical tumor and cancer therapies and drug delivery applications.


Overcoming Barriers and Advancements in Endovascular Robotics: A Review of Systems and Developments.
Endovascular robots have the potential to revolutionize the field of vascular interventions by enhancing procedural efficiency, accuracy, and standardization. They aim to reduce radiation exposure, as well as physical strain on operators and medical staff, while enabling precise navigation of catheters through challenging anatomical structures. However, the widespread adoption of these robots faces barriers, such as real estate constraints, setup time, limited range of compatible tools, and high costs. This paper discusses these barriers and highlights Hansen Medical's Magellan and the Liberty robotic systems as notable examples. New developments will offer cost-effective, intuitive, and disposable approaches to endovascular procedures. Despite challenges, endovascular robots hold promise for improving access to endovascular therapy and transforming patient care in various healthcare settings.


Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial.
Several small studies have indicated that the systemic administration of pentoxifylline may accelerate healing of venous leg ulcers. The goal of this study was to further evaluate these findings in a larger scale placebo controlled trial and to explore the effect of the dose of pentoxifylline on healing. The study used a prospective, randomized, double-blind, parallel group placebo controlled design in a multicenter outpatient setting. Patients with one or more venous ulcer were enrolled, with all patients receiving standardized compression bandaging for treatment for their ulcers. Patients were also randomized to receive either pentoxifylline 400 mg, pentoxifylline 800 mg (two 400 mg tablets), or placebo tablets three times a day for up to 24 weeks. The main outcome measure was time to complete healing of all leg ulcers, using life table analysis. The study was completed as planned in 131 patients. Patients receiving 800 mg three times a day of pentoxifylline healed faster than placebo (p = 0.043, Wilcoxon test). The median time to complete healing was 100, 83, and 71 days for placebo, pentoxifylline 400 mg, and pentoxifylline 800 mg three times a day, respectively. Over half of all patients were ulcer free at week 16 (placebo) and at week 12 in both pentoxifylline groups. Whereas the placebo group had only achieved complete healing in half of the cases by week 16, all of the subjects remaining in the group receiving the high dose of pentoxifylline had healed completely. Treatment with pentoxifylline was well tolerated with similar drop-out rates in all three treatment groups. Complete wound closure occurred at least 4 weeks earlier in the majority of patients treated with pentoxifylline by comparison to placebo. A higher dose of pentoxifylline (800 mg three times a day) was more effective than the lower dose. We conclude that pentoxifylline is effective in accelerating healing of leg ulcers.


Genetic interdependence of Lyn and negative regulators of B cell receptor signaling in autoimmune disease development.
Ab-mediated autoimmune disease is multifaceted and may involve many susceptibility loci. The majority of autoimmune patients are thought to have polymorphisms in a number of genes that interact in different combinations to contribute to disease pathogenesis. Studies in mice and humans have implicated the Lyn protein tyrosine kinase as a regulator of Ab-mediated autoimmune disease. To examine whether haploinsufficiency of Lyn gives rise to cellular and clinical manifestations of autoimmune disease, we evaluated the phenotype of Lyn(+/-) mice. We find that their B cell compartment is significantly perturbed, with reduced numbers of marginal zone and transitional stage 2 B cells, expansion of plasma cells, downregulation of surface IgM, and upregulation of costimulatory molecules. Biochemical studies show that Lyn(+/-) B cells have defects in negative regulation of signaling, whereas Lyn(+/-) mice develop IgG autoantibodies and glomerulonephritis with age. Because Lyn has a pivotal role in the activation of inhibitory phosphatases, we generated mice harboring double heterozygous loss-of-function mutations in Lyn and SHP-1 or Lyn and SHIP-1. Partial inactivation of SHP-1 or SHIP-1 amplifies the consequence of Lyn haploinsufficiency, leading to an accelerated development of autoantibodies and disease. Our data also reveal that the BALB/c background is protective against autoimmune-mediated glomerulonephritis, even in the face of high titer autoantibodies, whereas the C57BL/6 background is susceptible. This study demonstrates that Lyn is a haploinsufficient gene in autoimmune disease and importantly shows that quantitative genetic variation in Lyn-regulated pathways can mirror the complete loss of a single critical inhibitory molecule.


Enzymatic degradation of dimensionally constrained polyhydroxybutyrate films.
The effect of dimensional constraint, imparted by a variation in film thickness, on the enzymatic degradation of polyhydroxybutyrate (PHB) is reported. The characterization of the crystalline structure and the surface topography of solvent-cast PHB thin films revealed strong correlations between film thickness and both crystallinity and crystal anisotropy, with the polymer film becoming more amorphous with decreasing thickness. The enzymatic degradation of the PHB films was characterized using a high precision diffraction metrology, which enabled the visualization of small variations in the degradation behavior. The results show that the degradation rate increases with decreasing thickness due to the corresponding decrease in crystallinity. However, in a nanoscopic ultra-thin PHB specimen, produced by μ-transfer molding, enzymatic degradation was impeded. The enzymatic degradation rate of the PHB films therefore was found to exhibit a discontinuous trend with respect to film thickness: initially increasing as film thickness was reduced, and then decreasing dramatically once the thickness was reduced to tens of nanometers. In this regime, enzymatic degradation was hindered by the absence of crystalline regions in the films. These results show that a nano-dimensional constraint on PHB films can result in specimens with a tunable response to extracellular enzymes.


[Infections during Immunosuppression].
Infections during Immunosuppression Abstract. Immunomodulating and immunosuppressive therapies are being used more and more frequently. Depending on the mechanism of action and the underlying disease, there is an increased risk of infection with these therapies. In everyday clinical practice, the individual risk of infection depends on a large number of patients, and environmental as well as pathogen-specific factors. Elderly and multimorbid patients are at particular risk of infection. Classical bacterial infections with possible atypical manifestation, hepatitis B virus, herpes viruses, mycobacteria and other granulomatous infections are prevalent. Typical clinical signs of infections may be missing and laboratory chemical parameters may fail as diagnostic tools. Systematic screening for latent or chronic infections prior to initiation and close monitoring of patients during immunomodulatory or immunosuppressive therapy are necessary to reduce morbidity and mortality.


Antineoplastic Effects of Ankaferd Hemostat.
Up to June 2022, literature searches were performed using the internet search engines Medline, Google Scholar, and Embase: Ankaferd. PRISMA flow diagram described the Ankaferd search. ABS have important effects in several cellular processes, like control of the cell cycle, apoptosis, angiogenesis, signal transduction, inflammation, immunologic, and metabolic mechanisms. The molecular basis of antineoplastic roles of ABS depends on its proteomics, metabolomics, and transcriptomics features. ABS has antineoplastic effects on solid tumors like colon, bladder, breast, and osteosarcoma cancer cells. Also, ABS effects renal tubular apoptosis and has antitumoral roles on malign melanoma cells. ABS inhibits hematological tumors like myeloma and lymphoid cells. ABS induces apoptosis in retinal cells and has inhibitory effects on mesenchymal stem cells. It has an antiproliferative role on gastrointestinal tumors like hepatocellular carcinoma cells. Moreover, ABS has a treatment supportive role in cancer since it can prevent oxidative DNA damage and decrease the intestinal damage in necrotizing enterocolitis. Furthermore, it has chemopreventive and hepatoprotective features and can be used for prophylaxis and treatment of oral mucositis. ABS alters cell metabolism and cell cycle. ABS has antineoplastic role on cancer cells. The expanding context of ABS compromises anti-infective, antineoplastic, and wound healing features. ABS may also be used for the palliative, adjuvant, neoadjuvant, or supportive use by interventional radiology procedures for the treatment of solid tumors. Future controlled studies are necessary to clarify the pleiotropic role of ABS like antineoplastic, antithrombotic, anti-inflammatory, anti-infective, antifungal, and antioxidative effects.


Etretinate therapy reduces polymorphonuclear leukocyte chemotaxis--enhancing properties of psoriatic serum.
Using a Boyden chamber technic, we measured the directed chemotaxis of polymorphonuclear leukocytes obtained from control subjects or psoriasis patients when the leukocytes were placed in sera obtained from control subjects or psoriasis patients. The samples from patients were obtained before therapy and after 2 and 4 weeks of etretinate administration. Compared with control sera, the sera from seven untreated psoriasis patients significantly enhanced the chemotaxis of polymorphonuclear leukocytes from control subjects toward a chemotaxin (p less than 0.05). After 4 weeks of etretinate therapy, the chemotaxis-stimulating ability of the sera from psoriasis patients was no longer significantly greater than that of the control sera. This decline in the chemotaxis-stimulating activity of our patients' sera preceded significant clearing of their psoriasis. The levels of circulating etretinate in the blood of our patients could not account for the reduction. Etretinate therapy had no apparent direct effect on the chemotactic activity of polymorphonuclear leukocytes from the psoriasis patients but may act in part by reducing the inflammatory effects of psoriatic sera.


Interim use of Hyrax Screw Assembly for Single-Step Closure of Small Alveolar Cleft before Anterior Maxillary Distraction Osteogenesis.
Anterior maxillary distraction osteogenesis (AMDO) is often used for the correction of maxillary retrognathia in select cleft lip and palate cases. The restoration of alveolar arch continuity is desirable before the initiation of AMDO in these cleft maxillary deformities; however, AMDO is technically difficult in a patient with coexisting alveolar cleft where there is a discontinuity of the defect that presents a challenge in terms of adequate vector control of the movement of the anterior segment and the potential risk of tipping of teeth, which already have compromised anchorage/bone support on the cleft side. The treatment becomes more challenging when ongoing management is compounded by failed previous alveolar cleft grafting procedures, along with the patient's reluctance to undergo further grafting of alveolar clefts. This technical note demonstrates a novel application of the modification of the Hyrax screw where an initially fully opened Hyrax screw was utilised as an interim assembly for accomplishing the single-step closure of a small alveolar cleft before the commencement of anterior maxillary distraction osteogenesis. This technique may prove to be feasible for patients presenting with alveolar cleft defects of smaller widths of up to 5 mm and relatively well-aligned upper arches.


Antioxidants and breast cancer risk- a population-based case-control study in Canada.
The effect of antioxidants on breast cancer is still controversial. Our objective was to assess the association between antioxidants and breast cancer risk in a large population-based case-control study. The study population included 2,362 cases with pathologically confirmed incident breast cancer (866 premenopausal and 1,496 postmenopausal) and 2,462 controls in Canada. Intakes of antioxidants from diet and from supplementation as well as other potential risk factors for breast cancer were collected by a self-reported questionnaire. Compared with subjects with no supplementation, 10 years or longer supplementation of zinc had multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of 0.46 (0.25-0.85) for premenopausal women, while supplementation of 10 years or longer of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc had multivariable-adjusted ORs (95% CIs) of 0.74 (0.59, 0.92), 0.58 (0.36, 0.95), 0.79 (0.63-0.99), 0.75 (0.58, 0.97), and 0.47 (0.28-0.78), respectively, for postmenopausal women. No significant effect of antioxidants from dietary sources (including beta-carotene, alpha-carotene, lycopene, lutein and zeaxanthin, vitamin C, vitamin E, selenium and zinc) or from supplementation less than 10 years was observed. This study suggests that supplementation of zinc in premenopausal women, and supplementation of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc in postmenopausal women for 10 or more years may protect women from developing breast cancer. However, we were unable to determine the overall effect of total dose or intake from both diet and supplement.


The phenomenology of death, embodiment and organ transplantation.
Organ transplantation is an innovative 21st century medical therapy that offers the potential to enhance and save life. In order to do so it depends on a supply of organs, usually from cadaveric donors who have suffered brain stem death. Regardless of whether and how the deceased recorded their wishes about donation, health professionals will approach the bereaved relatives, before organs are removed. In this article, the results from 19 semi-structured interviews with Scottish donor families will be presented. These accounts will focus exclusively on the families' beliefs about death, the dead body and bonds with the deceased, and whether these affected the donation decision or the organs donated. What the families said about brain stem death (BSD); how and when they understood that death had occurred; and whether the families thought that death caused a 'disembodiment' (that the self was no longer embodied) will be explored. Finally, attention will turn to the bereaved's previous relationship with the embodied person. I conclude that the phenomenology of embodiment, death and organ transplantation offers new answers to the question of 'Who am I'? That is, in order to understand what identity is, one might look for what it is that is lost at death; the body, the self and relationships with others.


Genetic structure, population demography and seasonal occurrence of blacktip shark Carcharhinus limbatus in Bimini, the Bahamas.
A longline survey was conducted from 2004 to 2014 to investigate the demographic population structure and seasonal abundance of the blacktip shark Carcharhinus limbatus in the Bimini Islands, the Bahamas. All individuals sampled (n = 242) were sub-adult or adults [70·1-145·1 cm pre-caudal length (LPC) range] with no neonates or YOY recorded in Bimini. Carcharhinus limbatus abundance peaked in September, coincident with the largest ratio of female to male sharks and a peak in fresh mating wounds on females. Mitochondrial control region (mtCR) DNA sequences were obtained from C. limbatus at Bimini to test whether Bimini C. limbatus are most closely related to geographically proximate populations sampled on the south-eastern coast of the U.S.A., the closest known nursery areas for this species. Nine mtCR haplotypes were observed in 32 individuals sampled at Bimini [haplotype diversity (h) = 0·821, nucleotide diversity (π) = 0·0015]. Four haplotypes observed from Bimini matched those previously found in the northern Yucatan (Mexico)-Belize and two matched a haplotype previously found in the U.S.A. Four haplotypes were novel but were closely related to the northern Yucatan-Belizean haplotypes. Pair-wise ΦST analysis showed that Bimini was significantly differentiated from all of the populations previously sampled (U.S.A. Atlantic, U.S.A. Gulf of Mexico, northern Yucatan, Belize and Brazil). This indicates that C. limbatus sampled from Bimini are unlikely from the described, proximate U.S.A. nurseries.


The Circassians and the Chechens in Jordan: results of a decade of epidemiological and genetic studies.
Circassians and Chechens in Jordan, both with Caucasian ancestry, are genetically isolated due to high rate of endogamous marriages. Recent interest in these populations has led to studies on their genetic similarities, differences, and epidemiological differences in various diseases. Research has explored their predisposition to conditions like diabetes, hypertension, and cancer. Moreover, pharmacogenetic (PGx) studies have also investigated medication response variations within these populations, and forensic studies have further contributed to understanding these populations. In this review article, we first discuss the background of these minority groups. We then show the results of a principle component analysis (PCA) to investigate the genetic relationships between Circassian and Chechen populations living in Jordan. We here present a summary of the findings from the 10 years of research conducted on them. The review article provides a comprehensive summary of research findings that are truly valuable for understanding the unique genetic characteristics, diseases' prevalence, and medication responses among Circassians and Chechens living in Jordan. We believe that gaining deeper comprehension of the root causes of various diseases and developing effective treatment methods that benefit the society as a whole are imperative to engaging a wide range of ethnic groups in genetic research.


The relationship between the uptake of glucose and 3-O-methylglucose and soluble carbohydrate and polysaccharide in the fungus Dendryphiella salina.
When mycelium of Dendryphiella salina, pre-incubated in D-[I-14C]mannitol such that this is the only major labelled soluble carbohydrate present, absorbs glucose or the non-metabolized sugar 3-O-methylglucose, there is a specific stimulation of incorporation of 14C into alkali-insoluble, trichloroacetic-acid-soluble (1 leads to 4)-alpha-glucan, probably glycogen. There is also a net increase in the amount of glucan caused by stimulation of synthesis and inhibition of breakdown. Addition of 3-O-methylglucose results in the loss of mannitol into the medium. This loss and the reduced rate of replenishment from the glucan is important in the osmotic regulation of the hyphae. If osmotic adjustment does not occur, the hyphae do not show the specific incorporation of 14C into the glucan.


Serum free thyroxine levels in cats maintained on diets relatively high or low in iodine.
Excessive or deficient intake of iodine may play a role in the development of goitre and hyperthyroidism in cats. Previous investigations have shown that the serum free thyroxine level of cats is affected by brief administration of food high or low in iodine content. We have now measured serum free thyroxine levels in groups of cats fed relatively high or low iodine diets for much longer periods (5 months). In contrast to our earlier findings, the chronic ingestion of relatively high or low iodine diets did not lead to statistically significant differences in serum free thyroxine levels. The results of the present investigations show that the cat is able to maintain normal levels of thyroid hormone despite prolonged high or low iodine diets. It may be that the adaptive mechanisms that are called into play during chronic high or low iodine intake lead to thyroid disease, particularly in certain predisposed individuals.


Emerging foodborne diseases: an evolving public health challenge.
The epidemiology of foodborne disease is changing. New pathogens have emerged, and some have spread worldwide. Many, including Salmonella, Escherichia coli O157:H7, Campylobacter, and Yersinia enterocolitica, have reservoirs in healthy food animals, from which they spread to an increasing variety of foods. These pathogens cause millions of cases of sporadic illness and chronic complications, as well as large and challenging outbreaks over many states and nations. Improved surveillance that combines rapid subtyping methods, cluster identification, and collaborative epidemiologic investigation can identify and halt large, dispersed outbreaks. Outbreak investigations and case-control studies of sporadic cases can identify sources of infection and guide the development of specific prevention strategies. Better understanding of how pathogens persist in animal reservoirs is also critical to successful long-term prevention. In the past, the central challenge of foodborne disease lay in preventing the contamination of human food with sewage or animal manure. In the future, prevention of foodborne disease will increasingly depend on controlling contamination of feed and water consumed by the animals themselves.


Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques.
The loss of CD4(+) T cells and the impairment of CD8(+) T cell function in HIV infection suggest that pharmacological treatment with IL-7 and IL-15, cytokines that increase the homeostatic proliferation of T cells and improve effector function, may be beneficial. However, these cytokines could also have a detrimental effect in HIV-1-infected individuals, because both cytokines increase HIV replication in vitro. We assessed the impact of IL-7 and IL-15 treatment on viral replication and the immunogenicity of live poxvirus vaccines in SIV(mac251)-infected macaques (Macaca mulatta). Neither cytokine augmented the frequency of vaccine-expanded CD4(+) or CD8(+) memory T cells, clonal recruitment to the SIV-specific CD8(+) T cell pool, or CD8(+) T cell function. Vaccination alone transiently decreased the viral set point following antiretroviral therapy suspension. IL-15 induced massive proliferation of CD4(+) effector T cells and abrogated the ability of vaccination to decrease set point viremia. In contrast, IL-7 neither augmented nor decreased the vaccine effect and was associated with a decrease in TGF-beta expression. These results underscore the importance of testing immunomodulatory approaches in vivo to assess potential risks and benefits for HIV-1-infected individuals.


Extragingival Pregnancy Pyogenic Granuloma on the Lip.
Pregnancy pyogenic granuloma is considered a benign common growth that usually develops on the gingiva in the second and third trimester of gestation, in response to local irritation, trauma or hormonal factors. Here, the authors report a case of a primigravida who presented an extragingival pyogenic granuloma with a rapid progression in the post-partum. The occurrence on the lower lip in the first few days after delivery was a relatively rarity in the present case which provoked a meaningful state of anxiety and cancerophobia to the female. Complete excision was curative and brought immediate relief of pain and discomfort. This clinical report highlights the possibility of pyogenic granuloma presenting like a rapid-growing mass on the lip and the importance of clinical differential diagnosis of such presentation in this atypical location.


Heterogenous Intrapulmonary Distribution of Aerosolized Model Compounds in Mice with Bleomycin-Induced Pulmonary Fibrosis.
Background: A distinctive pathological feature of idiopathic pulmonary fibrosis (IPF) is the aberrant accumulation of extracellular matrix components in the alveoli in abnormal remodeling and reconstruction following scarring of the alveolar structure. The current antifibrotic agents used for IPF therapy frequently result in systemic side effects because these agents are distributed, through the blood, to many different tissues after oral administration. In contrast to oral administration, the intrapulmonary administration of aerosolized drugs is believed to be an efficient method for their direct delivery to the focus sites in the lungs. However, how fibrotic lesions alter the distribution of aerosolized drugs following intrapulmonary administration remains largely unknown. In this study, we evaluate the intrapulmonary distribution characteristics of aerosolized model compounds in mice with bleomycin-induced pulmonary fibrosis through imaging the organs and alveoli. Methods: Aerosolized model compounds were administered to mice with bleomycin-induced pulmonary fibrosis using a Liquid MicroSprayer®. The intrapulmonary distribution characteristics of aerosolized model compounds were evaluated through several imaging techniques, including noninvasive lung imaging using X-ray computed tomography, ex vivo imaging using zoom fluorescence microscopy, frozen tissue section observation, and three-dimensional imaging with tissue-clearing treatment using confocal laser microscopy. Results: In fibrotic lungs, the aerosolized model compounds were heterogeneously distributed. In observations of frozen tissue sections, model compounds were observed only in the fibrotic foci near airless spaces called honeycombs. In three-dimensional imaging of cleared tissue from fibrotic lungs, the area of the model compound in the alveolar space was smaller than in healthy lungs. Conclusion: The intrapulmonary deposition of extracellular matrix associated with pulmonary fibrosis limits the intrapulmonary distribution of aerosolized drugs. The development of delivery systems for antifibrotic agents to improve the distribution characteristics in fibrotic foci is necessary for effective IPF therapy.


Theoretical investigation on the photophysical properties of model ruthenium complexes with diazabutadiene ligands [Ru(bpy)(3-x)(dab)(x)](2+) (x = 1-3).
In this study we report a theoretical comparative study of some photophysical properties in the [Ru(bpy)(3-x)(dab)(x)](2+) (x = 0-3) series. Density functional theory calculations, validated by highly correlated ab initio benchmark calculations, were used to investigate the absorption and emission properties of the complexes with x = 1-3. The presence of a 1,4-diaza-1,3-butadiene (dab) ligand dramatically changes these properties because of the strong π-acceptor character of this ligand. As a result, comparing to the reference [Ru(bpy)(3)](2+) complex previously studied, we observed (i) a strong red-shift of the maximum of the absorption band, (ii) a strong decrease of the emission energy of the lowest triplet metal-to-ligand charge transfer state, with all the [Ru(bpy)(3-x)(dab)(x)](2+) (x = 1-3) complexes luminescent in the near-infrared region, while [Ru(bpy)(3)](2+) emits in the visible region, and (iii) the triplet metal-centered states become inaccessible in all the [Ru(bpy)(3-x)(dab)(x)](2+) (x = 1-3) complexes. Consequently, these complexes could be potential candidates for infrared light-emitting diodes and probes.


Factors associated with sow stayability in 6 genotypes.
The purpose of this study was to determine the association of production factors with stayability to parity 4 (STAY4) under controlled experimental conditions. Data were from 2,293 female pigs, sampled from 6 genetic lines that were entered into the National Pork Producers Council Maternal Line National Genetic Evaluation Program. Genetic lines evaluated included Newsham (NH), National Swine Registry (NSR), American Diamond Swine Genetics (ADSG), Danbred (DAN), and 2 Dekalb-Monsanto lines (DK44 and GPK347). Stepwise logistic regression was utilized in the analysis of STAY4. All effects were nested within genetic line. Categorical effects in the model were arrival date to the wean-to-finish unit (entry date) and breed-gestation-farrowing facility (farm). Continuous effects in the model were gilt backfat, LM depth, ADG, age at puberty, age at first farrowing, and traits recorded before the last litter of the sow (prefarrow backfat, number born alive, number weaned, litter weaning weight, lactation feed intake, lactation backfat loss, and lactation length). Factors significant for STAY4 included farm, entry date, age at first farrowing, ADG, gilt backfat, and lactation before removal effects, as well as feed intake, number born alive, and lactation length. Age at first farrowing and lactation feed intake affected all genetic lines. Regression coefficients for STAY4 on age at first farrowing were -0.014, -0.022, -0.017, -0.016, -0.011, and -0.021 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN genetic lines. Regression coefficients for STAY4 on lactation feed intake were 0.043, 0.049, 0.051, 0.061, 0.120, and 0.097 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN females. Age at puberty, age at first farrowing, and lactation feed intake had the greatest effect on STAY4.


Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1.
Micro-RNAs are approximately 21-25-nucleotide-long noncoding RNAs that regulate gene expression primarily at the post-transcriptional level in animals. Here, we report that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down-regulated in human primary lung cancer tissues and cell lines. In situ hybridization demonstrated localization of miR-1 in bronchial epithelial cells. The tumor suppressor C/EBPalpha, frequently suppressed in lung cancer, reactivated miR-1 expression in the lung cancer cells. Repressed miR-1 was also activated in lung cancer cells upon treatment with a histone deacetylase inhibitor. These observations led us to examine the antitumorigenic potential of miR-1 in lung cancer cells. Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as growth, replication potential, motility/migration, clonogenic survival, and tumor formation in nude mice. Exogenous miR-1 significantly reduced expression of oncogenic targets, such as MET, a receptor tyrosine kinase, and Pim-1, a Ser/Thr kinase, frequently up-regulated in lung cancer. Similarly, the levels of two additional targets, FoxP1, a transcription factor with oncogeneic property, and HDAC4 that represses differentiation-promoting genes, were reduced in miR-1-expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth with concomitant elevation of these targets. Further, ectopic miR-1 induced apoptosis in A549 cells in response to the potent anticancer drug doxorubicin. Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1, and depletion of anti-apoptotic Mcl-1 contributed to the sensitivity of miR-1-expressing cells to doxorubicin. Thus, miR-1 has potential therapeutic application against lung cancers.


The pivotal role of thrombin in cancer biology and tumorigenesis.
The association of cancer and thrombosis has been known for nearly 150 years. Compared with patients without cancer, those with cancer have an increased risk of thrombosis and recurrent thrombosis. It is now well accepted that patients with idiopathic venous thromboembolism are also at increased risk of later being diagnosed with cancer. This is further confirmation of the intertwined nature of cancer and thrombosis. Although the mechanisms of this association are still under examination, much work has accrued over the past two decades to suggest an influence of thrombin on cancer biology. This review focuses on the important role of thrombin in cancer research; recent in vitro work illustrating the mechanisms by which thrombin may affect cancer angiogenesis, cell invasion, and enhanced tumor metastasis; and on clinical trials investigating the potential role of antithrombotics in cancer incidence and survival.


Red Wine Consumption and Cardiovascular Health.
Wine is a popular alcoholic beverage that has been consumed for hundreds of years. Benefits from moderate alcohol consumption have been widely supported by the scientific literature and, in this line, red wine intake has been related to a lesser risk for coronary heart disease (CHD). Experimental studies and meta-analyses have mainly attributed this outcome to the presence in red wine of a great variety of polyphenolic compounds such as resveratrol, catechin, epicatechin, quercetin, and anthocyanin. Resveratrol is considered the most effective wine compound with respect to the prevention of CHD because of its antioxidant properties. The mechanisms responsible for its putative cardioprotective effects would include changes in lipid profiles, reduction of insulin resistance, and decrease in oxidative stress  of low-density lipoprotein cholesterol (LDL-C). The aim of this review is to summarize the accumulated evidence correlating moderate red wine consumption with prevention of CHD by focusing on the different mechanisms underlying this relationship. Furthermore, the chemistry of wine as well as chemical factors that influence the composition of the bioactive components of red wine are also discussed.


Clinical application of cine-MRI in the visual assessment of mitral regurgitation compared to echocardiography and cardiac catheterization.
Detecting and quantifying the severity of mitral regurgitation is essential for risk stratification and clinical decision-making regarding timing of surgery. Our objective was to assess specific visual parameters by cine-magnetic resonance imaging (MRI) in the determination of the severity of mitral regurgitation and to compare it to previously validated imaging modalities: echocardiography and cardiac ventriculography. The study population consisted of 68 patients who underwent a cardiac MRI followed by an echocardiogram within a median time of 2.0 days and 49 of these patients who had a cardiac catheterization, median time of 2.0 days. The inter-rater agreement statistic (Kappa) was used to evaluate the agreement. There was moderate agreement between cine MRI and Doppler echocardiography in assessing mitral regurgitation severity, with a kappa value of 0.47, confidence interval (CI) 0.29-0.65. There was also fair agreement between cine MRI and cardiac catheterization with a kappa value of 0.36, CI of 0.17-0.55. Cine MRI offers a reasonable alternative to both Doppler echocardiography and, to a lesser extent, cardiac catheterization for visually assessing the severity of mitral regurgitation with specific visual parameters during routine clinical cardiac MRI.


The impact of factors on information sharing: An application of meta-analysis.
Information sharing plays a key role in supply chain performance. According to previous individual studies, technology, trust, commitment, and uncertainty are four potential factors affecting information sharing. However, most studies focus on testing a positive relationship between each factor and information sharing. Therefore, it is necessary to evaluate the effect of each factor on information sharing. To determine the accurate effect of factors on sharing information and propose key factors to support decision-makers in improving their information sharing. Correlation coefficients between factors are collected from 41 individual studies with a total of 8,983 samples on Google Scholar. Using the rank correlation test and Egger's regression test to test publication bias. The meta-analysis method is used to perform analysis models, including fixed-effect, random-effect, and Hunter and Schmidt methods. Commitment plays the most important role in information sharing when compared to technology, trust, and uncertainty. Commitment accounts for 19% in the Hunter and Schmidt method and 22% in both fixed-effect and random-effect models. In addition, the result indicates that there are around 50% of other factors that affect the efficiency of sharing information besides four factors in our studies. Technology, trust, and commitment significantly affect information sharing, of which the impact of commitment on information sharing is strongest and should be a priority in improving the effectiveness of information sharing. Our study contributes two findings to literature in the field of supply chain information sharing: 1) certain confirming the important role of commitment on sharing information, and 2) the necessity of considering other factors besides these four elements.


Increased parenteral nutrition calcium and phosphorus for very-low-birth-weight infants using computer software assisted ordering.
Providing adequate calcium (Ca) and phosphorus (P) in an appropriate ratio to preterm very-low-birth-weight (VLBW: BW < 1500 g) infants receiving parenteral nutrition (PN) is difficult because Ca:P solubility in PN is relatively low. Computer software assisted ordering (CSAO) was developed to integrate PN Ca:P solubility with clinical data to improve parenteral Ca and P administration. Our hypothesis was that CSAO would improve the system of designing PN by increasing the amount of Ca and P ordered without Ca:P precipitation. Control PN orders were designed using proprietary preprinted PN forms which incorporated predefined PN Ca and P concentrations to prevent precipitation, independent of patient Ca or P administration. CSAO assessed total daily fluids and correlated parenteral volume with Ca:P solubility during order entry to recommend daily Ca and P doses. PN orders which provided > or = 80% of total nutrition volume as PN were analyzed. PN was designed with more Ca (60.3 +/- 16.7 mg/k/day, mean +/- 1 SD) and P (32.8 +/- 13.9 mg/k/day) using CSAO compared to control group Ca (50.0 +/- 17.1 mg/k/day) and P (25.1 +/- 9.1 mg/k/day), both Ca and P, p < 0.001, CSAO provided > or = 80% of the minimum recommended daily Ca in 82% of PN orders compared to 51% of the control orders, p < 0.001. No PN mixture demonstrated Ca:P precipitation. The system of designing PN was improved using computer software assisted ordering indicated by increased PN Ca and P content without Ca:P precipitation.


Specification of pen rail spacing and trough heights to prevent escape and enable good access to feed by sheep during sea shipments from New Zealand.
A trial was carried out to determine the optimal height of feeding troughs above floor level and the spacing between pen railings which would enable sheep to access feed troughs but prevent them from getting out of pens during sea voyages. The trial involved a group of 16 large (79 kg) wether sheep and 24 small (30 kg) wether lambs which were held in pens and trained to eat lucerne pellets. Feed troughs similar to those used on ships were constructed 260 mm deep and 220 mm wide. A system of adjustable railings were used to alter the trough height and to determine the optimal spacing to allow the large sheep to get their heads through, but to prevent small sheep from escaping. In order that sheep of various sizes can access feed from the bottom of feed troughs, the height of the top edge of the trough should not exceed 360 mm above floor level for 30 kg sheep or 460 mm for mature sheep. This range is due to differences between the groups in their shoulder height, and variation between individuals within each group. Shoulder heights of the small sheep used in this trial ranged from 505 to 590 mm, and for the 16 mature animals the range was 610-715 mm. It is important that the feed troughs are low enough for all animals to access the feed on offer. Mature sheep were able to pass their heads between rails spaced at 200 mm without difficulty, but some difficulty was experienced when the space was reduced to 180 mm. The maximum rail spacing which prevented the escape of 30 kg lambs could not be determined with certainty because they could pass through a space of only 180 mm when laid on their side, but the smallest space through which they passed voluntarily was 220 mm. Hence the optimal spacing between railings which would allow all sheep good access to feed and would prevent almost all small sheep from escaping is about 190-210 mm.


Local innovations provide managed care for the uninsured.
A number of communities in the United States are adopting a managed care approach to caring for low-income uninsured individuals. This Issue Brief focuses on such programs in five of the 12 communities that the Center for Studying Health System Change (HSC) is tracking intensively. It describes the local market factors that motivated the creation and varying design of these initiatives, all of which seek to increase access to primary and preventive care while managing the use of more costly inpatient and emergency care. The Issue Brief also discusses the long-term viability of these programs as they attempt to simultaneously expand access to services and contain costs for this growing population.


Effects of hydrostatic pressure on permeability of airway epithelium.
The presence of blood proteins and excess liquid in the airway lumen during airway inflammation may be secondary to extravasation and elevation of subepithelial hydrostatic pressure. This study examines how hydrostatic pressures of 5-20 cm H2O affect hydraulic conductivity and macromolecular permeability of primary cultures of bovine tracheal epithelium. Hydraulic conductivity was not altered by transepithelial pressure gradients of up to 20 cm H2O directed from the mucosal to serosal side of the tissue (m-s). By contrast, a 20-cm H2O s-m pressure resulted in a marked increase in hydraulic conductivity with the critical pressure lying between 10 and 20 cm H2O. Electrical conductance (i.e., permeability to ions) was not altered by m-s pressure gradients, or by a 5-cm H2O s-m gradient, but was increased by s-m pressures > or = 10 cm. Fluxes (s-m and m-s) of fluorescein and fluorescent dextrans (70 and 2000 kDa) were not altered by pressures of up to 20 cm H2O m-s. By contrast s-m pressure gradients of 20 cm H2O dramatically increased the s-m fluxes of these probes. The increases in flux were completely reversible. The results indicate that s-m pressure gradients greatly increase the hydraulic conductivity of airway epithelium by creating pores with an effective diameter greater than 54 nm.