mdx muscle pathology is independent of nNOS perturbation

In skeletal muscle, neuronal nitric oxide synthase (nNOS) is anchored to the sarcolemma via the dystrophin-glycoprotein complex. When dystrophin is absent, as in Duchenne muscular dystrophy patients and in mdx mice, nNOS is mislocalized to the interior of the muscle fiber where it continues to produce nitric oxide. This has led to the hypothesis that free radical toxicity from mislocalized nNOS may contribute to mdx muscle pathology. To test this hypothesis directly, we generated mice devoid of both nNOS and dystrophin. Overall, the nNOS- dystrophin null mice maintained the dystrophic characteristics of mdx mice. We evaluated the mice for several features of the dystrophic phenotype, including membrane damage and muscle morphology. Removal of nNOS did not alter the extent of sarcolemma damage, which is a hallmark of the dystrophic phenotype. Furthermore, muscle from nNOS-dystrophin null mice maintain the histological features of mdx pathology. Our results demonstrate that relocalization of nNOS to the cytosol does not contribute significantly to mdx pathogenesis.      

Treatment-independent pregnancy rate in patients with severe reproductive disorders

A long waiting list for in-vitro fertilization (IVF) offers the possibility to study treatment-independent pregnancy rates in patients with severe reproductive disorders. We performed a retrospective cohort study with a nested case-control design in which the cases achieved a spontaneous pregnancy while on the waiting list for IVF, or for IVF with intracytoplasmic sperm injection (ICSI), and the controls did not become pregnant while on the waiting list. Spontaneous pregnancies occurred in 76 of 1391 patients on the waiting list. Significant differences between pregnant and non-pregnant patients were found for duration of subfertility (couples on the IVF waiting list), and for progressive sperm motility and basal 17beta-oestradiol (couples on the ICSI waiting list). The 12 months cumulative pregnancy rate for patients on the waiting list was 2.4% (95% CI 1.2-3.9%) for tubal subfertility patients, 5.9 % (3.7-8.7%) for longstanding unexplained subfertility patients, and 6.6% (4.5-9.3%) for male subfertility patients. Of the 76 control patients, 21% of tubal subfertility patients, 18% of unexplained subfertility patients, and 17% of male subfertility patients achieved a pregnancy in their first IVF or ICSI treatment cycle. We confirm that the treatment-independent pregnancy rate in patients with severe reproductive disorders is low. More than 75% of the spontaneous pregnancies in the tubal subfertility and unexplained subfertility couples occurred during their first three months on the waiting list, whereas spontaneous pregnancy rate in male subfertility couples showed a more gradual but persisting increase. We conclude that one cycle of IVF or ICSI is superior to 12 months of expectant management in patients with severely impaired fertility due to tubal, unexplained or male factors.      

Review shows that using surfactant a number of times or as a vehicle for budesonide may reduce the risk of bronchopulmonary dysplasia

Aim

Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD.

Method

We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017.

Results

Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long‐term morbidity and the increased use of healthcare resources. These issues have encouraged researchers to explore potential new treatments that limit the incidence of BPD. Repeated surfactant instillation and the use of surfactant as a vehicle for budesonide are promising strategies for alleviating the burden of chronic lung disease. Ongoing research on surfactant or stem cell therapy may further improve the respiratory prognosis for prematurely born children.

Conclusion

Considerable research has been carried out into the increase in BPD, which has resulted from improvements in neonatal survival. Key areas of research include repeated surfactant administration, using surfactant as a vehicle for budesonide and stem cell therapy.     

Decision‐making around resuscitation of extremely preterm infants in the Philippines: A consensus guideline

While the vast majority of preterm births globally occur in low‐ and middle‐income countries, existing published guidelines relating to the decision‐making and resuscitation of extremely preterm infants (EPIs) largely focus on high‐income countries. In 2018–2019, a working group of the Philippine Society of Newborn Medicine aimed to develop the first national guideline relating to the care of EPIs. The working group reviewed data on the outcomes of EPIs in the Philippines, surveyed paediatricians and neonatologists in the Philippines about current practice and held a consensus workshop. This paper describes the guideline development process and presents a summary of the guidelines. The national guidelines endorse consistency in decision‐making. Health professionals should take into consideration the views and wishes of the infant's parents and the availability of resources to treat the newborn infant. Active management would be appropriate to provide for potentially viable preterm infants at moderate to high risk of poor outcomes, where parents have expressed their wish for this management (and where there are resources available to provide this treatment). For such infants, where parents have expressed their wish to withhold active management, palliative management would also be appropriate to provide. The guideline endorses a grey zone for neonatal resuscitation from approximately 24 to 28 weeks’ gestation in the Philippines, reflecting the context for resuscitation in low‐ and middle‐income countries. Disparities in resource availability are themselves an ethical concern for neonatologists and should be a stimulus for advocacy and improvements in health‐care delivery.     

Antenatal diagnosis of abdominothoracic alimentary tract duplication: a case report

Summary Alimentary tract duplications are rare, linked in their tubular form with a disturbance of organogenesis at the time of the separation of the notochord during the 4th week of gestation. Its division leads to the formation of a supernumerary esophagus, situated in the posterior mediastinum, associated with vertebral malformations and connected at its distal extremity with the alimentary tract. We report a case of esophageal duplication revealed antenatally as an ultrasound image of fluid tonality in the posterior mediastinum, causing a major pleural effusion. The other diagnostic possibilities are discussed in terms of the anatomy, embryogenesis and ultrasonographic appearance of the lesion.

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Duplication digestive abdominothoracique à révélation anténatale A propos d'une observation

Résumé Les duplications digestives sont rares, liées dans leur forme tubulaire à un trouble de l'organogenèse datant de l'isolement de la notochorde lors de la 4e semaine de gestation: sa division aboutit à la formation d'un sophage surnuméraire, se trouvant dans le médiastin postérieur, associé à des malformations vertébrales et relié à son extrémité distale au tractus digestif. Nous rapportons une observation de duplication sophagienne à révélation anténatale, sous la forme d'une image échographique de tonalité liquidienne du médiastin postérieur, à l'origine d'un épanchement pleural important. A la lumière de l'anatomie, de l'embryogenèse, et de l'aspect échographique de la lésion, les autres diagnostics possibles sont discutés.

     

中国卫生地理信息系统基础数据库的构建

目的：构建可用于中国卫生地理信息系统（GIS）应用研究的基础数据库，以合理应用已有的数据资源，并成为一个空间决策系统。方法：采集不同资料来源，经统一标化后构成基本资料源。主要的资料源包括：（1）覆盖中国地区的卫星遥感图片库；（2）GIS数字化地图库；（3）疾病资料库与相关模型库。结果：已获卫星遥感图片库中的植被指数遥感图片、地面温度遥感图片、数字化高程图片、数字化土地利用图片等；GIS数字化地图库中的中国行政区划数字化地图、环境数据矢量地图、人口分布图、气象资料分布图等；疾病资料库与相关模型库中包括了多种疾病的调查报告、疾病防治年报表等资料，以及疾病的传播模型和媒介／中间宿主潜在自然孳生地模型，及恶性肿瘤发病因素相关图。结论：该数据库的构建使不同来源的数据达到统一性，数据库收集的数据量以足能为国内卫生专业人员应用为前提，希望通过更多疾病的应用，使数据库得以完善。     

定义实验室参考值和决定限：人群，区间范围及其解读

简要概述多种分析人类精液检测结果的方法。参考区间（参考值范围）是最常用的解释临床实验结果的工具。参考值范围概念的发展,有赖于20世纪80年代临床化学专家国际联盟对这一概念的详尽阐述。这些指南要求：健康参考人群至少应包括120个健康个体,并对其进行分类,辨别最外延5％的参考值数据来确定双侧或单侧参考区间的界限值。最近,基于流行病学结果分析得出的决定限,也已用来解读分析检测结果。参考群体必须根据检验项目的临床使用要求严格定义：如果参考值范围用于评估男性生育能力,12个月内使配偶成功妊娠的男性应当是最合适的参考人群;如果用于精液检测结果的流行病学评估,随机选择的健康男性应该是最为理想的参考群体。虽然男性个体精液检测结果基于参考值和决定限无疑会在不久的将来成为解释结果的工具,但从长远看,解释精液检查结果的多因素方法或结合女性有关因素的分析,似乎是检测生育能力低下夫妇妊娠可能性的最佳方式。     

Anticonvulsant activity of the fractionated extract of Crinum jagus bulbs in experimental animals

ObjectiveTo investigate the anticonvulsant activity of the bulbs of Crinum jagus in experimental animals.MethodsThe uprooted bulbs were air dried for a week and ground into creamy-paste. 200g of paste was macerated each in 2 litres of water, ethanol and petroleum ether and filtered after 48 h. The obtained filtrates were each evaporated at the appropriate temperature to solid residue. The residues were further fractionated with successive changes of petroleum ether, ethyl acetate and n-butanol into a pooled filtrate which was further evaporated to dry solid brown-paste. Phytochemistry was carried out based on Treas and Evans method of 1987. The acute toxicity study (LD50) was carried based on Lorke's 1983 method. Convulsion was induced using maximum electric shock (MEST), pentylenetetrazole(PTZ), strychnine and Picrotoxin in the appropriate animal models. Seizures onset time and death time were used as successful induction of convulsion while prolongations of these features were taken as anticonvulsant activity. Results where possible, were statistically analyzed using SPSS-16.0 version.ResultsThe LD₅₀was got at 1118.003mg/kg (IP) in mice using Lorke's 1983 method. Fractionated extract of Crinum jagus exhibited dose dependent antiseizure against MEST induced seizure (P<0.001) and comparable to that of phenytoin, a standard anti generalized tonic-clonic seizure. There were also observable antiseizure activity of the fractionated extracts against PTZ, strychnine and Picrotoxin induced seizure and comparable to their standard corresponding antiseizures.ConclusionsWe conclude that the bulbs of Crinum jagus possess proven broad spectrum antiseizure and perhaps antiepileptogenic activity thus justifies its use in traditional medicine. Clinical trial in man is recommended.     

Paliperidone Prevents Brain Toll-Like Receptor 4 Pathway Activation and Neuroinflammation in Rat Models of Acute and Chronic Restraint Stress

Background:

Alterations in the innate immune/inflammatory system have been proposed to underlie the pathophysiology of psychotic disease, but the mechanisms implicated remain elusive. The main agents of the innate immunity are the family of toll-like receptors (TLRs), which detect circulating pathogen-associated molecular patterns and endogenous damage-associated molecular patterns (DAMPS). Current antipsychotics are able to modulate pro- and anti-inflammatory pathways, but their actions on TLRs remain unexplored.

Methods:

This study was conducted to elucidate the effects of paliperidone (1mg/Kg i.p.) on acute (6 hours) and chronic (6 hours/day during 21 consecutive days) restraint stress–induced TLR-4 pathway activation and neuroinflammation, and the possible mechanism(s) related (bacterial translocation and/or DAMPs activation). The expression of the elements of a TLR-4-dependent proinflammatory pathway was analyzed at the mRNA and protein levels in prefrontal cortex samples.

Results:

Paliperidone pre-treatment prevented TLR-4 activation and neuroinflammation in the prefrontal cortices of stressed rats. Regarding the possible mechanisms implicated, paliperidone regulated stress-induced increased intestinal inflammation and plasma lipopolysaccharide levels. In addition, paliperidone also prevented the activation of the endogenous activators of TLR-4 HSP70 and HGMB-1.

Conclusions:

Our results showed a regulatory role of paliperidone on brain TLR-4, which could explain the therapeutic benefits of its use for the treatment of psychotic diseases beyond its effects on dopamine and serotonin neurotransmission. The study of the mechanisms implicated suggests that gut-increased permeability, inflammation, and bacterial translocation of Gram-negative microflora and HSP70 and HGMB1 expression could be potential adjuvant therapeutic targets for the treatment of psychotic and other stress-related psychiatric pathologies.