Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2.

Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after birth with neuronal layering abnormalities in the cerebral cortex, a consequence of defective neuronal migration. The similarities in amino acid sequences, expression patterns, and knockout phenotypes raise the question of whether the two proteins have redundant functions. To investigate this topic, we generated "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)). Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they died soon after birth with neuronal layering abnormalities in the cerebral cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially ameliorate the abnormalities associated with lamin B1 deficiency. Similarly, increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that lamins B1 and B2 have unique roles in the developing brain and that increased production of one B-type lamin does not fully complement loss of the other

Representation to the accident and emergency department within 1-year of a fractured neck of femur

Background: The fractured neck of femur (NOF) is a leading cause of morbidity and mortality. The mortality attendant upon such fractures is 10% at 1 month and 30% at one year with a cost to the NHS of £1.4 billion annually. This retrospective study sought to examine rates and prevailing trends in representation to A&E in the year following a NOF fracture in an attempt to identify the leading causes behind the morbidity and mortality associated with this fracture. Methods: 1108 patients who suffered a fractured NOF between 1 January 2002 and 31 December 2007 were identified from a University Hospital A&E database. This database was then used to identify those patients who represented within 1-year following the initial fracture. The presenting complaint, provisional diagnosis and the outcome of this presentation were identified at this time. Results: 234 patients (21%) returned to A&E on 368 occasions in the year following a hip fracture. 77% (284/368) of these presentations necessitated admission. Falls, infection and fracture were the leading causes of representation. Falls accounted for 20% (57/284) of admissions; 20.7% of patients were admitted because of a fracture, while 56.6% of admissions were for medical ailments of which infection was the chief precipitant (28% (45/161)). Discussion: The causes for representation are varied and multifactorial. The results of this study suggest that some of those events or ailments necessitating readmission may be obviated and potentially reduced by interventions that can be instituted during the primary admission and continued following discharge

Comparing neural correlates of conditioned inhibition between children with and without anxiety disorders - A preliminary study

Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improve CBT response. During conditioned inhibition, threat and safety cues appear together, forming a safety compound. Here, we test whether this safety compound elicits a reduced fear response compared to pairing the threat cue with a novel cue (novel compound). The current pilot study compares behavioral, physiological, and neural correlates of conditioned inhibition between children with (n=17, Mage=13.09, SD=3.05) and without (n=18, Mage=14.49, SD=2.38) anxiety disorders. Behavioral and physiological measures did not differ between children with and without anxiety disorders during fear acquisition. During testing, children with anxiety disorders showed overall higher skin conductance response and expected to hear the aversive sound following the novel compound more often than children without anxiety disorders. Children with anxiety disorders showed more activity in the right ventromedial prefrontal cortex (vmPFC) to the safety versus novel compound. Children without anxiety disorders showed the opposite pattern - more right vmPFC activity to the novel versus safety compound (F(1,31)=5.40, p=0.03). No group differences manifested within the amygdala, dorsal anterior cingulate cortex, or hippocampus. These pilot findings suggest a feasible approach for examining conditioned inhibition in pediatric anxiety disorders. If replicated in larger samples, findings may implicate perturbed conditioned inhibition in pediatric anxiety disorders and provide targets for CBT

Vacuum polarization in two-dimensional static spacetimes and dimensional reduction

We obtain an analytic approximation for the effective action of a quantum scalar field in a general static two-dimensional spacetime. We apply this to the dilaton gravity model resulting from the spherical reduction of a massive, non-minimally coupled scalar field in the four-dimensional Schwarzschild geometry. Careful analysis near the event horizon shows the resulting two-dimensional system to be regular in the Hartle-Hawking state for general values of the field mass, coupling, and angular momentum, while at spatial infinity it reduces to a thermal gas at the black-hole temperature.Comment: REVTeX 4, 23 pages. Accepted by PRD. Minor modifications from original versio

Determinants of maternal healthcare services utilization in selected communities in Edo Central Senatorial District Nigeria

Background: Throughout history, society has always employed several means to promote maternal healthcare services to save pregnant women and their unborn babies from expected or unexpected dangers during pregnancy, birth and after birth. This study investigated the determinants of maternal health care services utilization in selected communities. Methods: A descriptive cross-sectional survey design was adopted for this study using a questionnaire as a quantitative tool. The population of the study comprised women of reproductive age group (15-49) Edo Central Senatorial District, Edo State Nigeria. A multi-stage sampling technique was used to select 561 study participants from the target population. A total of 561 copies of the questionnaire were administered but 490 of them were retrieved and found to meet criteria for analysis. Data was analyzed using SPSS version 25 and computed for descriptive statistics- frequency with percentage counts, mean and standard deviations. Additionally, inferential statistics chi-square used to test the stated hypotheses. Results: The finding showed that the women’s mean age of 28±5.37. Residential location of the participants did not significantly influence their utilization of maternal healthcare services. Educational qualifications, were found to influence the utilization of maternal healthcare services than those of lower educational levels (p<0.05). In addition, 364 (74.2%) respondents agree that free or low cost of maternal health services would prompt and promote regular visits to clinic. Conclusions: It is recommended that the government should provide freer or low-cost

Evaluation of the Nutritional Composition of Myrothamnus Flabellifolius (Welw.) Herbal Tea and its Protective Effect Against Oxidative Hepatic Cell Injury

Published ArticleThe nutrient composition of Myrothamnus flabellifolius leaf tea extract (MLTE) and its protective effect against oxidative hepatic cell injury were evaluated. Gallic acid, caffeic acid, ferulic acid, methyl gallate, and epicatechin were identified in MLTE by high‐performance liquid chromatography (HPLC). The tea extract showed an appreciable nutritional content of proximate, sugar, vitamin E, monounsaturated fatty acids, omega 6 and 9 unsaturated fatty acids, as well as considerable amounts of various mineral elements. Nineteen amino acids were found. Moreover, MLTE exhibited potent in vitro antioxidant activities, presumably because of its richness in polyphenols (gallic acid and ferulic acid) and vitamin E. In Chang liver cells, pretreatment with MLTE suppressed oxidative lipid peroxidation (IC50 = 113.11 μg/ml) and GSH depletion (IC50 = 70.49 μg/ml) without causing cytotoxicity. These data support the local consumption of M. flabellifolius herbal tea, which may be used against oxidative stress‐induced diseases while providing the body with necessary nutrients. Practical application Herbal teas are one of the most consumed beverages in the world today, due to their refreshing taste and additional health benefits. Myrothamnus flabellifolius herbal tea is a widely used traditional herbal tea in Southern Africa with potentials for commercialization due to its pleasant flavor. This study, for the first time, reported the nutritional composition of the leaf decoction of M. flabellifolius and its protective effect on hepatic oxidative insults. These results can inform the dietary and nutritional use of the tea for optimum benefits, as well as provide preliminary scientific validation of the use of the herbal tea as an antioxidant beverage with good nutritional value

A comparative analysis of national HIV policies in six African countries with generalized epidemics.

OBJECTIVE: To compare national human immunodeficiency virus (HIV) policies influencing access to HIV testing and treatment services in six sub-Saharan African countries. METHODS: We reviewed HIV policies as part of a multi-country study on adult mortality in sub-Saharan Africa. A policy extraction tool was developed and used to review national HIV policy documents and guidelines published in Kenya, Malawi, South Africa, Uganda, the United Republic of Tanzania and Zimbabwe between 2003 and 2013. Key informant interviews helped to fill gaps in findings. National policies were categorized according to whether they explicitly or implicitly adhered to 54 policy indicators, identified through literature and expert reviews. We also compared the national policies with World Health Organization (WHO) guidance. FINDINGS: There was wide variation in policies between countries; each country was progressive in some areas and not in others. Malawi was particularly advanced in promoting rapid initiation of antiretroviral therapy. However, no country had a consistently enabling policy context expected to increase access to care and prevent attrition. Countries went beyond WHO guidance in certain areas and key informants reported that practice often surpassed policy. CONCLUSION: Evaluating the impact of policy differences on access to care and health outcomes among people living with HIV is challenging. Certain policies will exert more influence than others and official policies are not always implemented. Future research should assess the extent of policy implementation and link these findings with HIV outcomes

Diversification of mandarin citrus by hybrid speciation and apomixis

The origin and dispersal of cultivated and wild mandarin and related citrus are poorly understood. Here, comparative genome analysis of 69 new east Asian genomes and other mainland Asian citrus reveals a previously unrecognized wild sexual species native to the Ryukyu Islands: C. ryukyuensis sp. nov. The taxonomic complexity of east Asian mandarins then collapses to a satisfying simplicity, accounting for tachibana, shiikuwasha, and other traditional Ryukyuan mandarin types as homoploid hybrid species formed by combining C. ryukyuensis with various mainland mandarins. These hybrid species reproduce clonally by apomictic seed, a trait shared with oranges, grapefruits, lemons and many cultivated mandarins. We trace the origin of apomixis alleles in citrus to mangshanyeju wild mandarins, which played a central role in citrus domestication via adaptive wild introgression. Our results provide a coherent biogeographic framework for understanding the diversity and domestication of mandarin-type citrus through speciation, admixture, and rapid diffusion of apomictic reproduction

A Comparative Analysis of National HIV Policies in Six African Countries with Generalized Epidemics

To compare national human immunodeficiency virus (HIV) policies influencing access to HIV testing and treatment services in six sub-Saharan African countries. We reviewed HIV policies as part of a multi-country study on adult mortality in sub-Saharan Africa. A policy extraction tool was developed and used to review national HIV policy documents and guidelines published in Kenya, Malawi, South Africa, Uganda, the United Republic of Tanzania and Zimbabwe between 2003 and 2013. Key informant interviews helped to fill gaps in findings. National policies were categorized according to whether they explicitly or implicitly adhered to 54 policy indicators, identified through literature and expert reviews. We also compared the national policies with World Health Organization (WHO) guidance. There was wide variation in policies between countries; each country was progressive in some areas and not in others. Malawi was particularly advanced in promoting rapid initiation of antiretroviral therapy. However, no country had a consistently enabling policy context expected to increase access to care and prevent attrition. Countries went beyond WHO guidance in certain areas and key informants reported that practice often surpassed policy. Evaluating the impact of policy differences on access to care and health outcomes among people living with HIV is challenging. Certain policies will exert more influence than others and official policies are not always implemented. Future research should assess the extent of policy implementation and link these findings with HIV outcomes

International variation in survival after out-of-hospital cardiac arrest : A validation study of the Utstein template

Introduction: Out-of-hospital cardiac arrest (OHCA) survival varies greatly between communities. The Utstein template was developed and promulgated to improve the comparability of OHCA outcome reports, but it has undergone limited empiric validation. We sought to assess how much of the variation in OHCA survival between emergency medical services (EMS) across the globe is explained by differences in the Utstein factors. We also assessed how accurately the Utstein factors predict OHCA survival. Methods: We performed a retrospective analysis of patient-level prospectively collected data from 12 OHCA registries from 12 countries for the period 1 Jan 2006 through 31 Dec 2011. We used generalized linear mixed models to examine the variation in survival between EMS agencies (n = 232). Results: Twelve registries contributed 86,759 cases. Patient arrest characteristics, EMS treatment and patient outcomes varied across registries. Overall survival to hospital discharge was 10% (range, 6% to 22%). Overall survival with Cerebral Performance Category of 1 or 2 (available for 8/12 registries) was 8%(range, 2% to 20%). The area-under-the-curve for the Utstein model was 0.85 (Wald CI: 0.85-0.85). The Utstein factors explained 51% of the EMS agency variation in OHCA survival. Conclusions: The Utstein factors explained 51%. of the variation in survival to hospital discharge among multiple large geographically separate EMS agencies. This suggests that quality improvement and public health efforts should continue to target modifiable Utstein factors to improve OHCA survival. Further study is required to identify the reasons for the variation that is incompletely understood.Peer reviewe