Chronic sleep loss disrupts blood–testis and blood–epididymis barriers,and reduces male fertility

Sleep loss increases blood–brain barrier permeability. As the blood–brain barrier and the blood–tissue barriers in the reproductive tract (blood–testis and blood–epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood–testis and blood–epididymis barrier. Therefore, we quantified changes in blood–testis and blood–epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple‐platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home‐cage. At the 10th day, barrier permeability assays were performed with Na‐fluorescein, 10 kDa Cascade blue‐dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1–7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low‐ and high‐molecular‐weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2–3 days progressively re‐established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood–tissue barriers at the reproductive tract, the mechanism involves androgen signalling.     

Evaluación de la función de la mano en las enfermedades reumáticas. Validación y utilidad de los cuestionarios AUSCAN,m-SACRAH,DASH y Cochin en Español

IntroductionQuestionnaires to evaluate hand function are variable in the number of items, domains and diseases in which they had been previously used.Objectivesa) To translate to Spanish and validate the m-SACRAH and AUSCAN questionnaires; b) to do a transcultural adaptation of DASHe, previously validated in Spain), and c) to compare them and the Cochin questionnaire (previously validated in México), in rheumatic patients with variable impairment of hand function.Material and methodsm-SACRAH, AUSCAN and DASH were translated/retro-translated and adapted. The final version was revised to determine content validity and them, plus Cochin were applied to 10 healthy subjects (pilot study) with a variable educational level and in 16 rheumatic patients with variable diagnoses and degrees of hand function impairment; all patients answered 4 questionnaires and were evaluated clinically by blinded investigators.ResultsSeventy six percent were women, mean age 45.7 ± 11.4 years. Cronbach?s alpha > 0.90; time to answer went from 2.3 ± 0.087 (AUSCAN) to 3.5 ± 0.36 minutes (DASH). There was good correlation among them (r = 0.0683 AUSCAN-m-SACRAH to r = 0.889 AUSCAN-DASH) and good capability for discrimination between patients with mild VS moderate to severe impairment was also demonstrated; patients with mild impairment needed less time to answer them and there were no significant differences among questionnaire scores. Patients prefered AUSCAN (10/16), Cochin (4/16) and m-SACRAH (2/16).ConclusionThe 4 questionnaires are useful to evaluate hand function in rheumatic patients and have good discrimination capability. More patients preferred AUSCAN.     

Epigenética y cáncer colorrectal

The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease.     

Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation

Dense deposit disease (DDD) is a severe renal disease characterized by accumulation of electron-dense material in the mesangium and glomerular basement membrane. Previously, DDD has been associated with deficiency of factor H (fH), a plasma regulator of the alternative pathway (AP) of complement activation, and studies in animal models have linked pathogenesis to the massive complement factor 3 (C3) activation caused by this deficiency. Here, we identified a unique DDD pedigree that associates disease with a mutation in the C3 gene. Mutant C3_923ΔDG, which lacks 2 amino acids, could not be cleaved to C3b by the AP C3-convertase and was therefore the predominant circulating C3 protein in the patients. However, upon activation to C3b by proteases, or to C3(H₂O) by spontaneous thioester hydrolysis, C3_923ΔDG generated an active AP C3-convertase that was regulated normally by decay accelerating factor (DAF) but was resistant to decay by fH. Moreover, activated C3b_923ΔDG and C3(H₂O)_923ΔDG were resistant to proteolysis by factor I (fI) in the presence of fH, but were efficiently inactivated in the presence of membrane cofactor protein (MCP). These characteristics cause a fluid phase–restricted AP dysregulation in the patients that continuously activated and consumed C3 produced by the normal C3 allele. These findings expose structural requirements in C3 that are critical for recognition of the substrate C3 by the AP C3-convertase and for the regulatory activities of fH, DAF, and MCP, all of which have implications for therapeutic developments.     

Histological Studies of the Effects of Oral Administration of Aspilia Africana (Asteraceae) Leaf Extract on the Ovaries of Female Wistar Rats

Histological studies of the effects of oral administration of extract of Aspilia africana, used in ethno medical practice in Africa for the management of various ailments, on the ovarian tissues of matured female Wistar rats were studied. The rats (n=24), average weight 182g were randomly assigned into two treatment (n=16) and a control (n=8) group. The rats in the treatment groups received 0.5g/kg and 1g/kg of aqueous extract of Aspilia africana orally through orogastric tube for fourteen days, while the control rats received equal volume of distilled water without the extract of Aspilia added. The rats were fed with growers'' mash and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The ovary was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method. The histological findings indicated that the treated sections of the ovary showed cellular hypertrophy of the theca folliculi, distortion of the basement membrane, degenerative and atrophic changes in the oocyte and zona granulosa. There were marked vacuolations appearing in the stroma cells. These findings indicate that Aspilia africana consumption may probably have adverse effects on the ovaries by its deleterious effects on the oocytes and stroma cells of ovary of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be conducted.     

U.S. medical resident familiarity with national tuberculosis guidelines

Background  

The ability of medical residents training at U.S. urban medical centers to diagnose and manage tuberculosis cases has important public health implications. We assessed medical resident knowledge about tuberculosis diagnosis and early management based on American Thoracic Society guidelines.     

The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patients

The VKORC1 c.-1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4.19 (1.59-11.04)]; amiodarone use [adjusted OR (95% CI) = 9.97 (1.75-56.89)]; or aspirin use [adjusted OR (95% CI) = 8.97 (1.66-48.34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0.50 (0.26-0.99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin.     

六君子汤对终末期肾病合并营养不良患者的补充治疗作用

目的:探讨六君子汤对终末期肾病(ESRD)合并营养不良患者的补充作用。方法:对ESRD合并营养不良48例患者给予六君子汤治疗,每日1剂,分2次服,每次100 ml。30 d为1个疗程,连续观察2个疗程。监测治疗前后白蛋白、前白蛋白、转铁蛋白水平;进行营养评估(SGA);观察患者厌食、乏力及皮肤瘙痒等临床症状的缓解情况。结果:治疗后患者的白蛋白、前白蛋白和转铁蛋白水平有明显提高(P<0.01);治疗前AC、TSF、AMC值均为最小,随着治疗的进展,患者的各项指标均有提高;SGA评分营养不良总发生率降低;患者厌食、乏力症状有改善。结论:在充分透析的同时六君子汤对ESRD合并营养不良患者有较好疗效,可作为补充治疗。