Clinico-epidemiological profile of cutaneous tuberculosis at a tertiary care teaching hospital of South Rajasthan

Background: Cutaneous tuberculosis represents only 1-2% of total tuberculosis cases but due to difficulty in diagnosis even with molecular methods and non-availability of such tests at resource poor set ups, actual burden of cutaneous TB remains under-estimated. The present study was performed to analyse the magnitude and clinico-epidemiological profile of cutaneous tuberculosis at our tertiary level referral centre. Methods: All the clinically suspected cases of cutaneous tuberculosis attending the dermatology and paediatric outpatient department during a period of 30 months (from October 2015 to March 2018) were enrolled in the study. All patients were subjected to routine blood tests, Chest X-ray, sputum for Ziehl-Neelsen staining, HIV-ELISA, Mantoux test and cutaneous punch biopsy of the lesions for further confirmation. Results: During the study period of 30 months, total 30 patients were recruited with male to female ratio of 1.5:1 and mean age of 27 years. Mean disease duration was 13 months with head and neck region (60%) being most commonly affected. Most common clinical type of cutaneous tuberculosis was scrofuloderma (60%), followed by lupus vulgaris (26.7%), tuberculosis verrucosa cutis (10%) and papulonecrotic tuberculid (3.3%). Mantoux test was positive in 56.7% patients. All the patients were put on antitubercular treatment as per guidelines of national tuberculosis control programme. Conclusions: Tuberculosis in developing countries is still an important cause of skin lesions which remains doubtful in most case scenarios even after years of its advent due to difficulty in diagnosis. Clinical diagnosis and therapeutic trials are still helpful in managing most of the cases

Obstructive sleep apnea in middle age male smokers

OBJECTIVE: Obstructive sleep apnea is the most common type of sleep apnea. This was designed to establish the relationship between smoking and obstructive sleep apnea. Methods:This cross-sectional study was conducted at the outpatient department of Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from August 2018 to November 2018 (dates mentioned in methods are different) and comprised of males aged 30-50 years. Participants were divided into two groups of smokers and non-smokers and Berlin questionnaire was used to collect data employing systemic random sampling. SPSS 22 was used for analysis. Results:There were 768 male participants in the study equally split between smokers and non-smokers. Mean age was 39±5.76 years. Percentage of high-risk group among smokers was 36.5% and among non-smokers was 16.7%. Percentage of low risk group among smokers was 63.5% and among non-smokers was 83.3%. The odds ratio of obstructive sleep apnea was 2.87 times more in smokers than non-smokers. Conclusion:Long term smoking had a strong association with obstructive sleep apnea

Clinically proven natural products in aid of treating Parkinson\u27s disease: a comprehensive review

Parkinson\u27s disease (PD) is a neurodegenerative disorder that is caused by degeneration of nerve cells in the part of the brain called the substantia nigra, which controls movement. Although there is some considerable evidence with conventional drugs for PD, treating patients becomes increasingly difficult due to their short- and long-term adverse effects and other restrictions. This dire circumstance emphasizes the need for an innovative, strong alternative treatment for PD. Plants and natural products are considered one of the most important sources of bioactive molecules against a wide range of health disorders. With mechanistic insights, this systematic review explains the efficacy of clinically proven natural products in managing PD. This review is based on comprehensive literature searches from PubMed, Science Direct, Scopus, and Google Scholar databases using the keywords- “plants or natural products in Parkinson\u27s”, “plants or herbs used in Parkinson\u27s treatment”, or keywords that are similar to those. Natural products that have been clinically proven for their anti-Parkinson effect have only been selected for this study, and the products are- Mucuna pruriens, Caffeine, Camellia sinensis or green tea leaves, and a traditional Chinese herbal called Jiawei-Liujunzi Tang. In comparison to currently available medications, we firmly feel that the mentioned clinically proven natural products would be more effective at treating PD while having fewer adverse effects. However, further study is required to confirm their exact mechanism of action

Quality of care in early detection and management of pre-eclampsia/eclampsia in health facilities in Afghanistan

BackgroundAfghanistan faces a high burden of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy, including pre-eclampsia and eclampsia (PE/E), are among the most common causes of maternal and neonatal complications. Hypertensive disorders of pregnancy can lead to fatal complications for both the mother and fetus. The 2016 Afghanistan National Maternal and Newborn Health Quality of Care Assessment assessed quality of early detection and management of PE/E in health facilities and skilled birth attendants' (SBAs) perceptions of their working environment.MethodsAll accessible public health facilities with an average of at least five births per day (n=77), a nationally representative sample of public health facilities with less than five births per day (n=149), and 20 purposively selected private health facilities were assessed. Methods included a facility inventory and record review, interviews with SBAs, and direct clinical observation of antenatal care (ANC), intrapartum care and immediate postnatal care (PNC), as well as severe PE/E case management.ResultsMost facilities had supplies and medicines for early detection and management of PE/E.At public health facilities, 357 of 414 (86.2%) clients observed during ANC consultations had their blood pressure checked and 159 (38.4%) were asked if they had experienced symptoms of PE/E. Only 553 of 734 (72.6%) SBAs interviewed were able to correctly identify severe pre-eclampsia described in a case scenario. Of 29 PE/E cases observed, 17 women (59%) received the correct loading dose of magnesium sulfate (MgSO4) and 12 women (41%) received the correct maintenance dose of MgSO4.At private health facilities, 39 of 45 ANC clients had their blood pressure checked and 9 of 45 (20%) were asked about symptoms of PE/E. Fifty-four of 64(84.4%) SBAs in private facilities correctly identified severe pre-eclampsia described in a case scenario.ConclusionNotable gaps in SBAs' knowledge and clinical practices in detection and management of PE/E in various health facilities increase the risk of maternal and perinatal mortality. Continuing education of health care providers and increased investment in focused quality improvement initiatives will be critical to improve the quality of health care services in Afghanistan

Redox Behavior of Anticancer Chalcone on a Glassy Carbon Electrode and Evaluation of its Interaction Parameters with DNA

The interaction of anticancer chalcone [AMC, 1-(4′-aminophenyl)-3-(4-N,N-dimethylphenyl)-2-propen-1-one] with DNA has been explored using electrochemical, spectroscopic and viscometric techniques. A shift in peak potential and decrease in peak current were observed in cyclic voltammetry and hypochromism accompanied with bathochromic shift were noticed in UV-Vis absorption spectroscopy. These findings were taken as evidence for AMC –DNA intercalation. A binding constant (K) with a value of 6.15 × 105 M−1 was obtained from CV data, which was also confirmed by UV-Vis absorption titration. Moreover, the diffusion coefficient of the drug with and without DNA (Db and Du), heterogeneous electron transfer rate constant (ko) and electron affinity (A) were also calculated from electrochemical data

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of β-amyloid plaques associated with Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by β-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of β-amyloid plaques.</p> <p>Rationale</p> <p>We previously reported the inhibition of cholinesterases by 2,3-dihydro-1, 5-benzothiazepines, and considered this class of compounds as promising inhibitors for the cure of Alzheimer's disease. One compound from the same series, when substituted with a hydroxy group at C-3 in ring A and 2-thienyl moiety as ring B, showed greater activity against butyrylcholinesterase than to acetylcholinesterase. To provide insight into the binding mode of this compound (Compound A), molecular docking in combination with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases.</p> <p>Conclusion</p> <p>Molecular docking studies revealed that the potential of Compound A to inhibit cholinesterases was attributable to the cumulative effects of strong hydrogen bonds, cationic-π, π-π interactions and hydrophobic interactions. A comparison of the docking results of Compound A against both cholinesterases showed that amino acid residues in different sub-sites were engaged to stabilize the docked complex. The relatively high affinity of Compound A for butyrylcholinesterase was due to the additional hydrophobic interaction between the 2-thiophene moiety of Compound A and Ile69. The involvement of one catalytic triad residue (His438) of butyrylcholinesterase with the 3'-hydroxy group on ring A increases the selectivity of Compound A. C-C bond rotation around ring A also stabilizes and enhances the interaction of Compound A with butyrylcholinesterase. Furthermore, the classical network of hydrogen bonding interactions as formed by the catalytic triad of butyrylcholinesterase is disturbed by Compound A. This study may open a new avenue for structure-based drug design for Alzheimer's disease by considering the 3D-pharmacophoric features of the complex responsible for discriminating these two closely-related cholinesterases.</p

Bleeding disorders in the tribe: result of consanguineous in breeding

<p>Abstract</p> <p>Objective</p> <p>To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages.</p> <p>Design</p> <p>Cross Sectional Study</p> <p>Introduction</p> <p>Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia.</p> <p>Patients & Methods</p> <p>Our team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested.</p> <p>Results</p> <p>The family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders.</p> <p>Conclusion</p> <p>Consanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community.</p

The Interplay of Design and Materials in Orthopedics: Evaluating the Impact of Notch Geometry on Fatigue Failure of UHMWPE Joint Replacements

Each year, roughly 750,000 patients in the US receive a total joint replacement (TJR), or a synthetic medical device that serves to replace the natural joint to restore function and relieve pain. TJRs have had a long history of use in the hip, knee and shoulder, yet still retain the same standard design of a hard-on-soft bearing coupling. Today, those bearings are primarily composed of hard cobalt chrome (CoCr) surface articulating against ultrahigh molecular weight polyethylene (UHMWPE), a polymer with notable mechanical toughness and biocompatibility that have driven its 50-plus years of use in vivo. TJRs have seen tremendous success for older patient cohorts for whom these devices were designed. However, increasing demand from younger patients has motivated the need for more durable materials that can sustain higher, more variable loading for a longer time. UHMWPE has become central to this mission, with limitations in its long-term wear resistance, oxidative stability and fracture/fatigue properties coming under the limelight in recent years.Explanted devices that have been retrieved from patients following failure have provided significant insight into the vulnerabilities of different UHMWPE formulations currently in the market, especially with respect to component fracture. Three cases examined in this work describe fracture failures of UHMWPE components seen in the knee, hip and shoulder to demonstrate existing tradeoffs in material sterilization and processing. Irradiation crosslinked blends, initially introduced to the orthopedic market to improve wear resistance, exhibits reduced resistance to both oxidation and fatigue crack propagation. Such tradeoffs are shown to contribute to the failure of two fractured knee tibial inserts, a single fractured hip acetabular cup, and a series of severely fractured glenoid components used in the shoulder. The former two cases exhibit an additional precursor to fracture that has been recognized but largely ignored in the fatigue characterization of crosslinked UHMWPE: the existence of stress concentrations (notches). Incidences of component fracture like the three reviewed in this work have motivated significant study of UHMWPE’s mechanical deformation as a function of microstructural changes. In addition, computational studies have sought to establish how changes in design may reduce local stresses in UHMWPE components to mitigate failure. Material and design influences have thus predominantly been studied in isolation. The latter half of this work demonstrates how previous methodologies using linear elastic fracture mechanics (LEFM) and theoretical approaches to notch fatigue can been merged to elucidate the influence that notch geometry (notch-root radius) has on crack behavior in UHMWPE formulations. A robust computational analysis of existing theories regarding LEFM notch stress intensity and notch plasticity is presented, lending credibility to the use of the Dowling (1979) approach in characterizing the crack driving force in the vicinity of the notch. Standard compact tension (CT) specimens were modified to include one of five notch geometries: a sharp (0.13 mm) radius (control specimen), two crack-like radii (0.75 and 1 mm) and two blunt keyhole-type radii (2 and 3 mm). All radii were chosen to reflect geometries seen in modern TJR features, such as a tibial post in the knee or a liner locking mechanism in a hip. Cracks from 0.1 to 1 mm in length were created at each notch root using a sharp razor blade. Cyclic tensile loading (stress ratio, R = 0.1) was applied to impose an increasing cyclic stress intensity (ΔK), and crack growth was monitored optically. The fatigue crack propagation (FCP) behavior was mapped using the Paris law to compare the relative crack speeds at a given applied ΔK for each notch geometry and material formulation. Crack growth ahead of each notch was found to overlap with sharp crack data, further supporting the use of the Dowling approach in characterizing near-notch crack growth. This overlap in data implied that mechanisms of crack growth near the notch were similar to those further away from the notch (outside the “notch-affected zone”, as calculated for each notch radius using the Dowling approach). The congruency of all notch-emanating crack data also revealed microstructure-driven trends between each material cohort that have been noted in previous sharp crack studies. Highly crosslinked and remelted UHMWPE (RXLPE) was found to display the least resistance to FCP, while highly crosslinked and Vitamin E blended (VXLPE) formulations demonstrated a notable improvement. Virgin UHMWPE consistently demonstrated the best resistance to FCP. The reduction in FCP resistance seen in highly crosslinked materials was associated with reduced local plasticity in amorphous regions that otherwise serves to mitigate crack advance. Above-melt annealing (“remelting”) in RXLPE has been shown to minimize oxidation and subsequent embrittlement in vivo through free radical elimination, but can result in reduced percent crystallinity and lamellae quality that can further diminish FCP resistance. Blending Vitamin E similarly serves to reduce oxidation for VXLPE, but retains the crystalline quality and quantity of virgin UHMWPE. However, blended Vitamin E also diminishes crosslinking efficiency, thereby improving VXLPE’s resistance to FCP relative to RXLPE but with a tradeoff in optimal wear resistance. This study demonstrated that fatigue crack growth in UHMWPE primarily defers to microstructural influences, even when considering varying notch geometries within the vicinity of a crack. This work demonstrates that this methodology of investigating notch effects on crack behavior can be leveraged for polymeric materials, despite its primary origin from crystalline metals. Furthermore, by mimicking previous specimen types, sample dimensions and loading conditions, the methodology used in this work is easily translatable to orthopedic manufactures or research groups seeking to evaluate notch effects in novel UHMWPE formulations. Results shown here reveal that blunter notches do serve to mitigate catastrophic failure by reducing local driving forces (lower ΔK) within a larger notch-affected zone than sharp notches. However, this reduction may not offset the tradeoff in fatigue properties exhibited by highly crosslinked UHMWPE and a focus on optimizing the microstructure of this polymer may be more prudent for increasing its durability in vivo