Assessing collagen fibrils molecular damage after a single stretch-release cycle.

Mechanical testing of connective tissues such as tendons and ligaments can lead to collagen denaturation even in the absence of macroscale damage. The following tensile loading protocols, ramp loading to failure, overloading and release, cyclic overloading and cyclic fatigue loading, all yield molecular damage in rat or bovine tendons. Single collagen fibrils extracted from the positional common digital extensor tendon of the forelimb also show molecular damage after tensile loading to failure. Using fibrils from the same source we assess changes to the molecular and supramolecular structure after tensile stress relaxation at strains between 4 and 22% followed by release. We observe no broken fibril and no significant change in D-band spacing. However, we observe significant binding of a fluorescent collagen hybridizing peptide to the fibrils indicating that collagen denaturation occurs in a strain dependent way for relaxation times between 1 s and 1500 s. We also show that peptide binding is associated with a decrease of the cross-sectional area of the fibrils providing an estimate of the dry volume loss due to molecular denaturation as well as an estimate of the mechanical energy density required, 25-110 MJ m-3. In summary we show that collagen molecular damage can occur in the absence of fibril failure and without visible changes to the supramolecular structure.

Lung function impairment in women exposed to biomass fuels during cooking compared to cleaner fuels in Uttar Pradesh, India.

A national survey has shown that approximately 75-80% use of fire wood and chips, 10% of dung cake rural women in Uttar Pradesh, India. Considering the respiratory health risk of biomass fuel exposure to women, a cross sectional study was conducted to elucidate the relationship between cooking smoke and lung function impairments. The present study showed significant decline in air flow limitation based on reduced PEFR (3.69 | sec(-1)) and FEV1 (1.34 | sec(-1)) in women cooking with biomass fuels compared to PEFR (4.26 | sec(-1)) and FEV1 (1.73 | sec(-1)) in women cooking with cleaner fuels. The noxious gases and particles generated from biomass fuels during cooking reported in earlier studies may be the reason for the slight decline in airway status PEFR (3.69 | sec(-1)) and lung volumes FEV1 (1.34 | sec(-1)). The higher mean bio-fuels exposure index (52.5 hr-yrs) can attribute to reduced lung function in rural women.

Transfer learning with fine-tuned deep CNN ResNet50 model for classifying COVID-19 from chest X-ray images.

COVID-19 cases are putting pressure on healthcare systems all around the world. Due to the lack of available testing kits, it is impractical for screening every patient with a respiratory ailment using traditional methods (RT-PCR). In addition, the tests have a high turn-around time and low sensitivity. Detecting suspected COVID-19 infections from the chest X-ray might help isolate high-risk people before the RT-PCR test. Most healthcare systems already have X-ray equipment, and because most current X-ray systems have already been computerized, there is no need to transfer the samples. The use of a chest X-ray to prioritize the selection of patients for subsequent RT-PCR testing is the motivation of this work. Transfer learning (TL) with fine-tuning on deep convolutional neural network-based ResNet50 model has been proposed in this work to classify COVID-19 patients from the COVID-19 Radiography Database. Ten distinct pre-trained weights, trained on varieties of large-scale datasets using various approaches such as supervised learning, self-supervised learning, and others, have been utilized in this work. Our proposed i N a t 2021 _ M i n i _ S w A V _ 1 k model, pre-trained on the iNat2021 Mini dataset using the SwAV algorithm, outperforms the other ResNet50 TL models. For COVID instances in the two-class (Covid and Normal) classification, our work achieved 99.17% validation accuracy, 99.95% train accuracy, 99.31% precision, 99.03% sensitivity, and 99.17% F1-score. Some domain-adapted ( I m a g e N e t _ C h e s t X - r a y 14 ) and in-domain (ChexPert, ChestX-ray14) models looked promising in medical image classification by scoring significantly higher than other models.

3D Echocardiography Is More Efficient In Detail Assessment of Calcification in Chronic Rheumatic Mitral Stenosis.

Rheumatic heart disease is in the declining phase, with the increase of urbanization and increment of availability of healthcare facility. However still it causes a substantial number of morbidity and mortality in South Asia. The prevalence of Rheumatic Fever and Rheumatic heart disease in Bangladesh is still high, 0.6 and 0.3 per thousand populations respectively. In the rheumatic process mitral is the frequently involved valve, mostly in the form of mitral stenosis. Choice of a treatment modality and its success largely depend on the accurate assessment of severity of disease especially the extent and distribution of calcification. Echocardiography has a key role in the determination of the severity of mitral stenosis as well as assessment of details calcification. Conventionally 2 dimensional and Doppler echocardiography is used. Now a days, 3D echocardiography offers better cardiac imaging for detail evaluation. The heart being a complex structure, the 3D evaluation would certainly offer better imaging for the accurate assessment of the mitral stenosis, especially details of presence & distribution calcification. This cross-sectional observational study was done from May 2012 to October 2012 in University Cardiac Centre, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Data were collected with informed written consent, from 50 subjects who underwent transthoracic 2D and 3D Echocardiography for the assessment of rheumatic mitral valve with special emphasis on accurate assessment of severity, extent and distribution of calcification. Precise measurement of MV area is essential in the assessment of severity, which is found comparable by both 2DE (0.98±0.24cm²) and 3DE (0.92±0.23cm²). But in identifying calcification and accurate assessment of severity, more importantly commissural involvement is better detected by 3DE (p=0.002). This has extreme importance in therapeutic decision making in the treatment of chronic rheumatic MS. So, to formulate an efficient management plan, three-dimensional echocardiography has promising prospects in detecting severity & extent of rheumatic calcification.

Transcatheter Closure of Post Infarction Subacute Ventricular Septal Defect: A Case Report.

Ventricular septal rupture (VSR) is an uncommon but lethal complication of acute myocardial infarction (MI). Although early surgical closure is the treatment of choice, hospital mortality after emergency surgery remains high. Transcatheter closure of post myocardial infarction ventricular septal defect (PIVSD) has emerged as a potential treatment option in selected cases. Herein, we report a case present in AFC Health FORTIS Heart Institute, Khulna, Bangladesh on 10 February 2017 of sub acute post-MI VSR that was successfully closed using an Amplatzerseptal occlude (ASD) device. The patient had undergone primary percutaneous coronary intervention (PCI) 15 days earlier in the setting of acute MI.

Vasodilating, spasmolytic, inotropic and chronotropic activities of curcuminoids from Curcuma longa in isolated organ preparations of guinea pigs.

Turmeric is a yellowish orange spice, widely used in Asian cuisine and obtained from the rhizome of Curcuma longa. It is a mixture of three curcuminoids namely, curcumin, demethoxycurcumin and bisdemethoxycurcumin. Turmeric has been used as a medicinal substance since ancient times for respiratory and gastrointestinal problems. The aim of the present study was to investigate which curcuminoid contributes to the observed pharmacological activities, all three curcuminoids, the major curcumin metabolite tetrahydrocurcumin, and the non-enzymatic curcumin hydrolysis products ferulic acid, feruloyl methane and vanillin were analyzed for spasmolytic, inotropic and chronotropic activity. Furthermore, their uptake in respective tissue samples was also investigated and correlated with activity. Spasmolytic activity was determined in guinea pig ileum, aorta and pulmonary artery. Inotropic and chronotropic activity was determined on guinea pig papillary muscles and right atrium respectively, while tissue uptake was quantified by using high-performance liquid chromatography (HPLC). All the curcuminoids exhibited significant spasmolytic activity with highest EC50 values for bisdemethoxycurcumin (5.8 ± 0.6 µM) followed by curcumin (12.9 ± 0.7 µM), demethoxycurcumin (16.8 ± 3 µM) and tetrahydrocurcumin (22.9 ± 1.5 µM). While only demethoxycurcumin was able to significantly relax the pulmonary artery with EC50 value of 15.78 ± 0.85 µM. All three curcuminoids showed mild negative chronotropic effects in the isolated right atrium; tetrahydrocurcumin demonstrated no activity. Curcumin and bisdemethoxycurcumin also showed mild positive inotropic effect whereas demethoxycurcumin and tetrahydrocurcumin exhibited weak negative inotropic one. Interestingly, ferulic acid, feruloyl methane and vanillin demonstrated no pharmacologicical activity at all in the various isolated organs. All three curcuminoids and tetrahydrocurcumin showed high uptake into the various tissues where concentrations correlated with pharmacological activity. The results indicate pronounced differences in the in vitro pharmacological activities of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin which have to be considered in humans after per-oral intake of turmeric powder.

Correlation between human ether-a-go-go-related gene channel inhibition and action potential prolongation.

BACKGROUND AND PURPOSE: Human ether-a-go-go-related gene (hERG; Kv 11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro-arrhythmic drug effects. This study used a library of dofetilide derivatives to investigate the relationship between standard measures of hERG current block in an expression system and changes in action potential duration (APD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The interference from accompanying block of Cav 1.2 and Nav 1.5 channels was investigated along with an in silico AP model. EXPERIMENTAL APPROACH: Drug-induced changes in APD were assessed in hiPSC-CMs using voltage-sensitive dyes. The IC50 values for dofetilide and 13 derivatives on hERG current were estimated in an HEK293 expression system. The relative potency of each drug on APD was estimated by calculating the dose (D150 ) required to prolong the APD at 90% (APD90 ) repolarization by 50%. KEY RESULTS: The D150 in hiPSC-CMs was linearly correlated with IC50 of hERG current. In silico simulations supported this finding. Three derivatives inhibited hERG without prolonging APD, and these compounds also inhibited Cav 1.2 and/or Nav 1.5 in a channel state-dependent manner. Adding Cav 1.2 and Nav 1.2 block to the in silico model recapitulated the direction but not the extent of the APD change. CONCLUSIONS AND IMPLICATIONS: Potency of hERG current inhibition correlates linearly with an index of APD in hiPSC-CMs. The compounds that do not correlate have additional effects including concomitant block of Cav 1.2 and/or Nav 1.5 channels. In silico simulations of hiPSC-CMs APs confirm the principle of the multiple ion channel effects.

Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro.

Proteoglycan 4 (PRG4/lubricin) is secreted by cells that reside in articular cartilage and line the synovial joint. Lubricin may play a role in modulating inflammatory responses through interaction with CD44. This led us to examine if lubricin could be playing a larger role in the modulation of inflammation/immunity through interaction with Toll-like receptors (TLRs). Human Embryonic Kidney (HEK) cells overexpressing TLRs 2, 4 or 5 and surface plasmon resonance were employed to determine if full length recombinant human lubricin was able to bind to and activate TLRs. Primary human synovial fibroblasts were also examined using flow cytometry and Luminex multiplex ELISA. A rat destabilization model of osteoarthritis (OA) was used to determine if lubricin injections were able to regulate pain and/or inflammation in vivo. Lubricin can bind to and regulate the activity of TLRs, leading to downstream changes in inflammatory signalling independent of HA. We confirmed these findings in vivo through intra-articular injections of lubricin in a rat OA model where the inhibition of systemic inflammatory signaling and reduction in pain were observed. Lubricin plays an important role in regulating the inflammatory environment under both homeostatic and tissue injury states.

Bypass graft for coronary arterial stenosis following radiation therapy.

A 48-year-old man developed symptoms of progressive angina pectoris leading to myocardial infarction 12 years after two large doses of radiation for treatment of superior vena caval syndrome. Angiographic studies showed an isolated critical stenosis in the left anterior descending coronary artery, for which a successful surgical procedure for saphenous vein bypass graft was was performed. Coronary arterial stenosis following radiation therapy has been reported rarely, but this case supports the thesis that such lesion can be treated surgically.

Intra-subject variability in lung dose in healthy volunteers using five conventional portable inhalers.

High intra-subject variability in lung dose achieved when using aerosol delivery systems may impact on the efficacy of treatment in clinical practice. While the dose delivered by metered dose inhalers (pMDIs) is highly reproducible when tested in vitro, the variability in dose delivered to the lungs is known to be high. It has been suggested that newer delivery systems such as dry powder inhalers (DPIs) or breath actuated pMDIs significantly reduce the intra-subject variability in lung dose, but this remains untested. The 30-min urinary salbutamol technique was used to assess intra-subject variability in lung dose for five portable inhaler devices. Thirteen healthy adult subjects inhaled salbutamol from five different devices. Each device was used at five separate study days, a total of 25 visits. The devices studied were the Evohaler pMDI, a pMDI with Volumatic (pMDI + HC), the Easibreath, the Accuhaler and the Turbohaler. Subjects inhaled 400 microg of salbutamol and produced a urine sample exactly 30 min later. Quantities of salbutamol contained in the urine were determined using an HPLC technique. The mean coefficient of variation (CV% and range) for lung dose were 31.8% (20.1-87.4) for the pMDI + HC, Easi-breathe 35.9% (10.4-66.2), Accuhaler 40.4% (15.6-75.2), Turbohaler 42.4% (20.7-74.2), and 52.0% (27.1-49.3) for the pMDI alone. There was no significant statistical significant difference between any of the devices. In seven of 13 subjects, the greatest lung dose was achieved with the Volumatic. The observed intra-subject in health volunteers is similar to the reported intra-subject variability of bioavailability for a number of oral medications. Though there was trend towards higher variability when using the pMDI, this was not statistically significant and was largely attributable to one subject in with a poor technique.

Chloramphenicol ototoxicity. A case report.

A case of bilateral profound sensori-neural hearing loss following systemic administration of chloramphenicol is reported because of its rarity. The hearing loss was gradually progressive, involving one ear; and with a repeat course of the drug, the other ear too was involved. An idiosyncratic or allergic response to previous exposure to the drug may be the cause of the toxicity. One should be careful in prescribing the drug repeatedly; when this is done, the patient must be carefully observed for possible toxic effects.

Giant parotid calculus--an unusual presentation.

We describe a case of a giant sialolith of Stensen's duct in a 48-year-old woman. The patient was investigated and treated with a mistaken diagnosis of chronic inflammation until the clue to the diagnosis was provided by plain radiography. This is an unusual presentation of a salivary calculus and to our knowledge such a huge parotid calculus has not been reported so far in the literature.

Sailocele of Stenson's duct (a case report).

A case of dilatation of Stenson's duct is described. This was associated with a non-functioning parotid gland. The dilated part was constantly fed by saliva from the accessory parotid gland (Sailocele). The unusual presentation prompted us to report this case. Dilatation of Stenson's duct should be considered in the differential diagnosis of cystic swellings in the soft tissues of the cheek.

Laryngeal leiomyoma.

A case of leiomyoma arising from the left false cord is reported. In the larynx the lesion is very rare and the literature reports only 14 cases. Among those reported we were unable to find any case reported from India.

Metronidazole ototoxicity--report of two cases.

Two cases of bilateral moderate to severe sensorineural hearing loss due to oral administration of metronidazole are reported. There has been only one case report of deafness following metronidazole therapy in the world literature. The hearing loss recovered gradually in a period of four to six weeks following withdrawal of drug and oral steroid therapy. The possible mechanism of ototoxicity is discussed. Awareness by the treating physician of ototoxicity due to any drug is stressed.

Dumb-bell schwannoma of brachial plexus.

A rare case of extradural dumb-bell schwannoma of brachial plexus, arising from C6 root is reported along with review of literature. The clinical and radiological features useful in diagnosing the lesion are presented. The treatment policy to be adopted and the importance of adequate surgical exposure is discussed.