Linkage mapping of a nonspecific form of X-linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X-linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X-linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2-26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081.     

Nociceptin and the ORL-1 ligand [Phe1psi (CH2-NH)Gly2]nociceptin(1-13)NH2 exert anti-opioid effects in the Freund's adjuvant-induced arthritic rat model of chronic pain

1 Stimulation of the opioid receptor-like1 (ORL-1) receptor by nociceptin (NC) produces hyperalgesia and reverses the antinociceptive effects induced by opioids. Most studies concerning the central effects of NC were conducted using acute pain models. The role NC may play in chronic inflammation remains unelucidated. 2 The present study was undertaken to assess the action of NC in the Freund's adjuvant-induced monoarthritic rat model. The effects of drugs known to act as analgesics in this model were evaluated. The effects of NC, NCNH2, and the ORL-1 ligand, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2), were also studied alone or in association with morphine. 3 NC (1 - 30 nmol, i. c.v.) was inactive, whilst NCNH2 (10 nmol, i.c.v.) exerted hyperalgesic effects (-4.5+/-0.9 vs -0.7+/-0.8 s of vehicle-treated animals). [F/G]NC(1-13)NH2 (0.01 - 10 nmol, i.c.v.) induced hyperalgesia in the arthritic paw (-3.3+/-0.6 vs -0.3+/-0.5 s of vehicle-treated animals; 10 nmol). 4 Both NC (0.01 - 10 nmol, i.c.v. ) and [F/G]NC(1-13)NH2 (0.01 - 1 nmol, i.c.v), 30 min after morphine (3 mg kg-1, s.c.) induced an immediate and short-lived reversal of morphine effects (2.6+/-0.3 vs 10.4+/-1.0 and 1.2+/-1.5 vs 9.3+/-1.1 s of morphine alone, respectively), therefore displaying anti-opioid activity. 5 In the Freund's adjuvant-induced rat model of arthritis, both NC and [F/G]NC(1-13)NH2 act as anti-opioid peptides. Furthermore, NCNH2 and [F/G]NC(1-13)NH2 induce hyperalgesia when given alone. Further investigations and the identification of a centrally acting ORL-1 antagonist are necessary to better understand the role of NC in pain mechanisms.     

Three months of COVID‐19: A systematic review and meta‐analysis

The pandemic of 2019 novel coronavirus (SARS‐CoV‐2019), reminiscent of the 2002‐SARS‐CoV outbreak, has completely isolated countries, disrupted health systems and partially paralyzed international trade and travel. In order to be better equipped to anticipate transmission of this virus to new regions, it is imperative to track the progress of the virus over time. This review analyses information on progression of the pandemic in the past 3 months and systematically discusses the characteristics of SARS‐CoV‐2019 virus including its epidemiologic, pathophysiologic, and clinical manifestations. Furthermore, the review also encompasses some recently proposed conceptual models that estimate the spread of this disease based on the basic reproductive number for better prevention and control procedures. Finally, we shed light on how the virus has endangered the global economy, impacting it both from the supply and demand side.     

Poly-Ingredient Formulation Bresol? Ameliorates Experimental Chronic Obstructive Pulmonary Disease (COPD) in Rats

In the present study, the protective effect of Bresol^® – a polyherbal formulation – was evaluated in an experimental model of cigarette smoke (CS)-induced COPD in rats. Ten minutes daily exposure to CS for 7 weeks caused significant elevation of TNF-α (p<0.01) and total protein (p<0.01) in the bronchoalveolar lavage fluid (BALF) of positive untreated control animals, indicating ongoing inflammatory process in the lungs. Further, histopathological findings have confirmed the presence of pathological lesions in the trachea and lungs. Five weeks of post-treatment with Bresol^® (250 and 500 mg/kg, p.o.) showed significant and dose-dependent anti-inflammatory effects against CS-induced lung abnormalities by maintaining the TNF-α and total protein levels within the normal range. Additionally, Bresol^®-treated animals showed normal cyto-architecture of the trachea and lungs. In conclusion, Bresol^® showed dose-dependent protection against CS-induced lung and tracheal injury in rats, which further indicates, Bresol^® is a useful healing agent, may help to decelerate the progression of COPD, and reduce the exacerbations in patients.     

Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial

A hypercoagulable state has, in observational studies, been associated with increased risk of thromboembolic events. The aim of this trial was to study whether dual antiplatelet therapy (DAPT) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions, thromboembolic events, and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery. A total of 1683 patients were screened for eligibility, among which 165 patients were randomized and 133 patients underwent multislice computed tomography scan to evaluate their grafts. Thrombelastography (TEG) and multiplate aggregometry were performed before and after surgery, and again at three months follow up. TEG hypercoagulability was defined as the maximum amplitude above 69 mm. At three months follow up, 17 out of 66 (25.7%) DAPT patients and 15 of 67 (22.4%) aspirin patients had significant graft stenosis or occlusions (p = 0.839). Saphenous vein grafts (SVGs) were stenosed or occluded in 15 (22.7%) patients in the DAPT group and 7 (10.4%) in the aspirin group (p = 0.167). Thromboembolic events and death after the second postoperative day (when clopidogrel was started) were numerically, but not statistically, lower in the DAPT group, 3 (3.8%) vs. 8 (9.9%), p = 0.211. In univariate logistic regression analysis, only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion, OR 1.020 [1.002–1.039], p = 0.033. This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients. Due to the low enrollment and high loss to follow up, our results can only be viewed as hypothesis generating. We found a high rate of graft occlusions in this patient population. Our results were not suggestive of that DAPT improved saphenous vein graft patency. A trend was observed in patients on DAPT toward fewer MI and deaths. Postoperative response to aspirin therapy was found to be associated with early SVG occlusion.     

Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion

Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild-type mice but not Ildr1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation was associated with increased [Ca²⁺]_i, consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.     

Immunological appraisal of wheat varieties in relation to chapatti-making characteristics

The current research work was conducted to characterize wheat proteins through immunochemical techniques and to find out their relationship with wheat quality traits. The results revealed that wheat variety AARI-11 possessed higher protein content (11.96%), wet gluten (31.39%), dry gluten (9.66%), Pelshenke value (190.52 min), and SDS-Sedimentation value (28.27 ml) than other tested varieties. The chapattis prepared from the wheat variety AARI-11 got significantly higher sensory scores owing to its higher protein contents. The wheat variety AARI-11 also exhibited significantly the highest antibody response against all the assessed protein fractions. The results of the present study suggest that anti-glutenin and anti-high molecular weight glutenin subunits (HMW-GS) antibody response was found positively correlated to the quality characteristics of flours and chapattis. The present study suggests that the use of antibodies response against glutenin and HMW-GS offers good tool for predicting quality and suitability of wheat to chapatti-making quality.