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Natural products have become a promising therapy for many pathogenic infectious conditions. In the present study, leaves of P. cablin were extracted using Hexane and ethyl acetate. Leaf Ethyl acetate extract showed significantly better antimicrobial activity against both Staphylococcus aureus 6538 (Gram-positive) (SA) and Klebsiella pneumonia ATCC 27,736 (Gram-negative) bacteria compared to the Hexane extract and was subjected to phytochemical analysis and chromatographic seperation. Phytochemical analysis of P. cablin leaf EtOAc extract showed the presence of Tannins, Flavanoids and Terpenoids. Subjecting the EtOAc leaf extract to column chromatographic separation resulted in the isolation of a trimethoxy flavone, pachypodol.

OBJECTIVES Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. METHODS Children aged 2 to 15 years and adults (defined as ≥15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. RESULTS Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. CONCLUSION Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.

Background Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden. Methods Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting. Results In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8–152.4) in tier 2 and US$405.7 (95% CI, 366.9–444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure. Conclusions The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed.

Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water–ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol–water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1–4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

Lectins are a cluster of proteins which are capable of recognizing and binding to glycoconjugates and are extensively found in plants, animals, fungi and bacteria. Plant-derived lectins have been gaining importance over the years due to their innumerable biological activities and also have the added possibility of being compatible to the human system while simultaneously exhibiting properties like antimicrobial and antitumor activities. Abelmoschus esculentus (AE) commonly known as okra is a vegetable with medicinal properties. AE extracts are used to treat disorders such as constipation, microbial infection, urine retention, hypoglycemia and inflammation in humans. Previous studies showed that lectin isolated from AE exhibited anti inflammatory, anti nociceptive, anticancer, antioxidant and hemagglutinating activities. However, the antitumor effect of the lectin derived from this plant against neural cancer cells still remains unexplored. Glioblastoma is a malignant tumor of the nervous system. Treatment options for patients afflicted by glioblastoma is limited to surgical resection, preceded by radiation therapy and followed by chemotherapy. Hence it would be of interest to identify novel bio molecules with ability to selectively target glioblastoma with minimum side effects. In this aspect, lectins from vegetables that are commonly used as food products could offer a promising lead as anticancer molecules. The present study proves the anti-proliferative effect of lectin isolated from AE on human U87 glioma cells. MTT assay showed significant concentration dependent cytotoxic activity and the IC50 value was calculated as 21 μg/ml. Further, annexin V/FITC staining by FACS, the expression of caspase 3 and 7 and the circadian genes clock and Bmal1 using RT-PCR and the generation of intracellular ROS, cell cycle analysis by FACS revealed the ability of AEL to induce effective apoptosis.

Background. Despite favorable outcomes of laparoscopic surgery in high-income countries, its implementation in low- and middle-income countries (LMICs) is challenging given a shortage of consumable supplies, high cost, and risk of power outages. To overcome these barriers, we designed a mechanical retractor that provides vertical tension on the anterior abdominal wall. Methods. The retractor design is anatomically and mathematically optimized to provide exposure similar to traditional gas-based insufflation methods. Anatomical data from computed tomography scans were used to define retractor size. The retractor is constructed of biocompatible stainless steel rods and paired with a table-mounted lifting system to provide 5 degrees of freedom. Structural integrity was assessed through finite element analysis (FEA) and load testing. Functional testing was performed in a laparotomy model. Results. A user guide based on patient height and weight was created to customize retractor size, and 4 retractor sizes were constructed. FEA data using a 13.6 kg mass (15 mm Hg pneumoperitoneum) show a maximum of 30 mm displacement with no permanent deformation. Physical load testing with applied weight from 0 to 13.6 kg shows a maximum of 60 mm displacement, again without permanent deformation. Retraction achieved a 57% larger field of view compared to an unretracted state in a laparotomy model. Conclusions. The KeyLoop retractor maintains structural integrity, is easily sterilized, and can be readily manufactured, making it a viable alternative to traditional insufflation methods. For surgeons and patients in LMICs, the KeyLoop provides a means to increase access to laparoscopic surgery.

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has evolved considerably with the introduction of newer agents, such as poly-ADP ribose polymerase (PARP) inhibitors targeting DNA damage repair mutations. Combining and sequencing novel and existing therapies appropriately is necessary for optimizing the management of mCRPC and ensuring better treatment outcomes. The purpose of this review is to provide evidence-based answers to key clinical questions on treatment selection, treatment sequencing patterns, and factors influencing treatment decisions in the management of mCRPC in the era of PARP inhibitors. This article can also serve as a comprehensive guide to clinicians for optimizing genetic testing and counseling and management of patients with mCRPC. Although the PROfound study has validated the concept of PARP sensitivity across multiple genes associated with homologous recombination repair (HRR) in mCRPC and highlighted the importance of genomic testing in this at-risk patient population, it still remains unclear how patients with rarer HRR mutations will respond to PARP inhibitors. Therefore, real-world data obtained through registry-based randomized controlled trials in the future may help produce robust scientific evidence for supporting optimal clinician decision-making in the management of mCRPC.

The development of whole-body inhalational chambers for acute toxicity risk assessment of aerosols in rodents is of key importance in clinical and occupational hazard evaluations. The key aim of study is the design, development, optimization, and validation of an inhalational chamber using water aerosol, vehicle, and Aroclor 1232. The second goal has been to apply this chamber in the risk assessment of Aroclor 1232. Broncho-alveolar Lavage fluid cytology and chromatography, and lung histopathology were used to supplement the validation process. PCB concentrations were uniformly distributed across different places inside the chamber and a MMAD generation of 4.3 µm ± 1.7 µm GSD was suggestive of lower airway atomization of PCB particles. The chamber environmental parameters were within acceptable limits for rodents during the experimental procedures. Mouse behavioral alterations were minimal during water aerosolization. Acute exposure to Aroclor 1232 showed reproducibility of behavioral scores. Benchmark dose for further studies using Aroclor 1232 was derived at 4 mg/cu.m. Its toxicities could be verified by correlating the behavioral scores, neurobehavioral functions with concentrations in plasma and BAL fluid samples from Swiss albino mice. The rodent chamber can be utilized for risk assessment of occupational hazards such as complex pollutant mixtures and particulate matter aerosols. The inhalational chamber possesses the versatility to enable assessment of toxicological mixtures across sub-acute toxicity timelines.

Multiple cranial nerve palsies have many possible causes, including infective, inflammatory, neoplastic and infiltrative diseases of the meninges or skull base. We present the clinicopathological conference of a 27-year-old man with a smouldering course of sequential cranial nerve palsies. His imaging showed dural thickening and osteosclerosis of the skull base with otomastoiditis. Cerebrospinal fluid showed lymphocytic pleocytosis with reduced glucose and normal protein concentrations. There was a possible response to corticosteroids and anti-tubercular treatment. Initial biopsy from the thickened and enhancing dura was unremarkable. His condition deteriorated after the steroids were tapered; MR imaging showed progression of lesions and positron emission tomography showed intense hypermetabolism. Subsequently, a diagnostic test revealed the final diagnosis. This case was presented at the All India Institute of Medical Sciences’ monthly clinicopathological conference series in February 2021.

Angiomyolipoma (AML) is a rare benign mesenchymal neoplasm composed of variable admixture of blood vessels, smooth muscle, and adipose tissue; most commonly located in kidney, and is usually associated with tuberous sclerosis. Extrarenal AML has been reported in various sites, although infrequently in female genital tract (FGT). AML in cervix is extremely rare and only six cases have been reported so far. A 46-year-old postmenopausal female presented with lower abdominal pain, bleeding for 4 days and a polypoidal mass protruding through the cervical os. Endometrial curettings were suggestive of endometrial adenocarcinoma—endometrioid type (World Health Organization [WHO]). The subsequent hysterectomy specimen confirmed the diagnosis and the histologic grade was International Federation of Obstetrics and Gynecology (FIGO) grade I and stage was pT1aN0 (American Joint Committee on Cancer [AJCC], 8th edition). Cervical polyp showed AML. CD34 and smooth muscle actin (SMA) showed diffuse positivity in blood vessels and smooth muscle cells, respectively. HMB-45 was negative. This is the first ever reported case of AML coexisting with endometrial carcinoma in the absence of tuberous sclerosis. CD34 is a good marker for delineating the blood vessels and SMA for both the smooth muscle and vascular components. S100 is generally not needed to prove the adipose tissue component. HMB-45 is not consistently expressed in AML of female genital tract.

Pulsed electric field therapy is a novel non-invasive approach for cancer therapy. It serves as a cell permeability enhancing agent for cancer treatment. Nanosecond, high-electrical field pulse power technology is used for delivering variable, controllable, intracellular electrical perturbations in several biological systems. Here, we investigated the effect of nanosecond (ns) electric pulse (nsEP) as a therapeutic tool for cancer. In in-vitro study, the breast cancer cells (MCF-7) were exposed with electric field of ~18kV/cm intensity, ~25ns duration, at 1.5Hz in a 2mm electroporation cuvette. Post exposure, observation shows a significant reduction in cell viability. It was evident that after treatment the viability of MCF-7 cancer cells at 630 pulses are remains ~38% only. The optical microscopic analysis of MCF-7 cells shows cell morphology changes after electrical pulse exposure. Moreover, we have also investigated a comparative study of the effect nano-second electrical pulses on MCF-7 cells and Chinese Hamster Ovary (CHO) cell line. The comparative study, demonstrated that the effect of nsEPF on MCF-7 is more destructive than on CHO cell line. The obtained results support that the pulse electrical field of nanosecond (ns) duration therapy would be a potential solution for cancer treatment. Keywords: Nanosecond Pulse Electric Field; Full Width at Half Maxima; Pulse Forming Line; Pulse Exposure; Viability

Laparoscopic surgery is the standard of care in high-income countries for many procedures in the chest and abdomen. It avoids large incisions by using a tiny camera and fine instruments manipulated through keyhole incisions, but it is generally unavailable in low- and middle-income countries (LMICs) due to the high cost of installment, lack of qualified maintenance personnel, unreliable electricity, and shortage of consumable items. Patients in LMICs would benefit from laparoscopic surgery, as advantages include decreased pain, improved recovery time, fewer wound infections, and shorter hospital stays. To address this need, we developed an accessible laparoscopic system, called the ReadyView laparoscope for use in LMICs. The device includes an integrated camera and LED light source that can be displayed on any monitor. The ReadyView laparoscope was evaluated with standard optical imaging targets to determine its performance against a state-of-the-art commercial laparoscope. The ReadyView laparoscope has a comparable resolving power, lens distortion, field of view, depth of field, and color reproduction accuracy to a commercially available endoscope, particularly at shorter, commonly-used working distances (3-5 cm). Additionally, the ReadyView has a cooler temperature profile, decreasing the risk for tissue injury and operating room fires. The ReadyView features a waterproof design, enabling sterilization by submersion, as commonly performed in LMICs. A custom desktop software was developed to view the video on a laptop computer with a frame rate greater than 30 frames per second and to white balance the image, which is critical for clinical use. The ReadyView laparoscope is capable of providing the image quality and overall performance needed for laparoscopic surgery. This portable low-cost system is well suited to increase access to laparoscopic surgery in LMICs.

It is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose-ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single-arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti-inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/- 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species.

Background: Teleneurology consultations can be highly advantageous since neurological diseases and disabilities often limit patient's access to health care, particularly in a setting where they nee...

Biofluorescence has been detected in several nocturnal-crepuscular organisms from invertebrates to birds and mammals. Biofluorescence in mammals has been detected across the phylogeny, including the monotreme duck-billed platypus (Ornithorhyncus anatinus), marsupial opossums (Didelphidae), and New World placental flying squirrels (Gluacomys spp.). Here, we document vivid biofluorescence of springhare (Pedetidae) in both museum specimens and captive individuals—the first documented biofluorescence of an Old World placental mammal. We explore the variation in biofluorescence across our sample and characterize its physical and chemical properties. The striking visual patterning and intensity of color shift was unique relative to biofluorescence found in other mammals. We establish that biofluorescence in springhare likely originates within the cuticle of the hair fiber and emanates, at least partially, from several fluorescent porphyrins and potentially one unassigned molecule absent from our standard porphyrin mixture. This discovery further supports the hypothesis that biofluorescence may be ecologically important for nocturnal-crepuscular mammals and suggests that it may be more broadly distributed throughout Mammalia than previously thought.

Stable maintenance and partitioning of the 'Fertility' plasmid or the F plasmid in its host Escherichia coli require the function of a ParA superfamily of proteins known as SopA. The mechanism by which SopA mediates plasmid segregation is well studied. SopA is a nucleoid-binding protein and binds DNA in an ATP-dependent but sequence non-specific manner. ATP hydrolysis stimulated by the binding of the SopBC complex mediates the release of SopA from the nucleoid. Cycles of ATP-binding and hydrolysis generate an ATPase gradient that moves the plasmid through a chemophoresis force. Nucleoid binding of SopA thus assumes a central role in its plasmid-partitioning function. However, earlier work also suggests that the F plasmid can be partitioned into anucleate cells, thus implicating nucleoid independent partitioning. Interestingly, SopA is also reported to be associated with the inner membrane of the bacteria. Here, we report the identification of a possible membrane-targeting sequence, a predicted amphipathic helix, at the C-terminus of SopA. Molecular dynamics simulations indicate that the predicted amphipathic helical motif of SopA has weak affinity for membranes. Moreover, we experimentally show that SopA can associate with bacterial membranes, is detectable in the membrane fractions of bacterial lysates, and is sensitive to the membrane potential. Further, unlike the wild-type SopA, a deletion of the C-terminal 29 amino acids results in the loss of F plasmids from bacterial cells.

Introduction Severe open injuries of limbs, especially of the femur and tibia when associated with vascular injuries, present major challenges in management. The decision to amputate or salvage can often be a difficult one even for experienced surgeons. Mangled lower extremity results due to high-energy trauma, especially due to motor vehicle accidents, and is defined as injury to three of the four systems in the extremity that is soft tissues, bone, vascular, and nerve. Open fractures are classified by Gustilo and Anderson's classification in which type 3B is an injury where soft-tissue loss and primary closure of the wound are not possible and type 3C is any open fracture with vascular compromise. Case report We report a series of six ipsilateral fractures of the femur and the tibia treated at the Department of Orthopaedics, Sri Ramachandra Medical College and Hospital, Chennai, Tamil Nadu, over a 3-year period (2014-2017). The mean age of our patients was 30 years old, and there were five men and one woman. The right side lower limb was frequently involved (five cases), and the main etiology was road traffic accidents (six cases). Articular involvement was found in six cases. Skin wounds were noticed in all cases (type III C of the Gustilo classification). Urgent wound care, fluid replacement, and antibiotic therapy were undertaken for open fractures. According to modified Fraser classification, all six cases was classified under type II-C. Mangled extremity severity score for five cases was 7 and for one case it was 8. Ganga Hospital Open Injury Severity Score was also used which was found to be in borderline range of 16 score for three cases, 15 score for two cases, and 14 score for one case. All six cases were managed with serial wound debridement + Ilizarov fixator + soft-tissue repair with involvement of orthopedic, vascular, and plastic surgery team. Limb salvage was done for all six cases after considering all the factors. Postoperatively, rehabilitative care and physiotherapy in the form of non-weight-bearing mobilization with walker support was given to all patients. The patients were followed up for the period of 2 years and doing symptomatically better. Based on current literature guidelines and evidence-based medicine, management for borderline cases is proposed to aid clinical decision-making in these situations. Conclusion With great effort and good team work (like vascular and orthopedic surgeons), badly comminuted compound injuries (Type III C injury) can be managed well with Ilizarov fixation. Even though the decision of amputation versus salvage was based on more scientific/scoring system, patient's option should be taken, especially in borderline cases considering the present medicolegal scenario.

Background Early childhood home environment is intricately linked to child development and later cognitive and academic skills. There is limited literature evaluating home environmental trends and predictors in the low- and middle-income country settings. Aims Determine the trends of early childhood home environment changes between 6 and 36 months of age, and the factors associated with these changes. Study design Longitudinal community-based birth cohort follow-up study in a semi-urban slum in Vellore, South India. Subjects Consecutive sampling of a birth cohort between March 2010 and February 2012. Outcome measures Home environment was objectively assessed using the 'Home Observation for the Measurement of the Environment' (HOME) scale. Predictors of change in the home environment over time also were analyzed. Multivariable linear regression models and linear mixed effect models were used to identify the factors associated with HOME score at individual time points and over-a-time period, respectively. Results The birth cohort enrolled 251 children with a follow-up of 235, 228 and 218 children at 6, 24 and 36 months, respectively. The socio-economic status (SES) was the single biggest predictor for the HOME score at each time point, with increasing strength over time. Maternal education predicted home environment at 24 months, while maternal depression was negatively associated at 6 and 24 months of age. SES and maternal factors contributed to the overall change in the HOME score. Maternal factors predicted relational home environmental change over time. Conclusion SES and maternal factors consistently predicted early childhood home environment at 6, 24 and 36 months of age and its change over time. It is important to support maternal education and wellbeing along with socio-economic measures to optimize early childhood environment.

Background: Existing severity measurements in multiple sclerosis (MS) are often cross-sectional, making longitudinal comparisons of disease course between individuals difficult. Objective: The objective of this study is to create a severity metric that can reliably summarize a patient’s disease course. Methods: We developed the nARMSS – normalized ARMSS (age-related MS severity score) over follow-up, using the deviation of individual ARMSS scores from the expected value and integrated over the corresponding time period. The nARMSS scales from −5 to +5; a positive value indicates a more severe disease course for a patient when compared to other patients with similar disease timings. Results: Using Swedish MS registry data, the nARMSS was tested using data at 2 and 4 years of follow-up to predict the most severe quartile during the subsequent period up to 10 years total follow-up. The metric used was area under the curve of the receiver operating characteristic (AUC-ROC). This resulted in measurements of 0.929 and 0.941. In an external Canadian validation cohort, the equivalent AUC-ROCs were 0.901 and 0.908. Conclusion: The nARMSS provides a reliable, generalizable and easily measurable metric which makes longitudinal comparison of disease course between individuals feasible.

Background and objectives Epidural Volume Extension (EVE) involves instillation of normal saline into the epidural space soon after an intrathecal injection, with the aim to augment the sensory block height. Its clinical relevance lies in the possibility of using reduced intrathecal dose and yet achieving the desired sensory block level. Intrathecal dose is a known determinant of the level of sensory block. Whether EVE is dependent on intrathecal dose is not known. Methods We conducted a randomized, controlled, double-blind study to compare the maximum sensory level (Smax) achieved with or without application of EVE to two different reduced intrathecal doses. Eighty four adult male patients of ASA status I or II with body weight between 50–70 kg and height in the range of 150–180 cm, scheduled for orthopedic lower limb surgery using combined spinal epidural anesthesia were randomized to receive, either intrathecal dose (5 or 8 mg) with or without EVE, in accordance to group allocation. Results Smax was lowered by application of EVE to 5 mg intrathecal bupivacaine (T8.9 ± 4.3 vs. T6.4 ± 1.9 with and without EVE respectively; p = 0.030). Smax was similar when EVE was applied to 8 mg intrathecal bupivacaine than without it (T5.8 ± 1.8 vs. T6.4 ± 2.2 respectively; p = 0.324). Conclusion EVE should not be applied to 5 mg plain bupivacaine during a combined spinal epidural block in patients undergoing lower limb orthopedic surgery as it may result in a decrease in the maximum sensory level.

The proposed study compares the electrical, thermal and mechanical performances of thermally aged cellulose pressboard material impregnated in mineral oil, synthetic ester fluid and mixed oil. The electrical insulation characteristics of oil-impregnated pressboard (OIP) are studied by means of surface discharge inception voltage (SDIV) using an ultra-high frequency technique and surface potential measurement analysis. It indicates that OIP aged in mineral oil has higher surface potential due to higher charge trap density compared to that of the mixed oil and synthetic ester fluid. Mechanical and thermal characteristics of the aged OIP are studied by means of tensile strength measurement and thermo-gravimetric analysis, respectively. The change in the chemical composition of OIP is studied by means of laser-induced breakdown spectroscopy, which indicates lower plasma temperature with mineral oil-based OIP indicating higher degradation state. To further understand the microscopic structure of the thermally aged OIP in different oils, scanning electron microscopy and X-ray diffraction studies have been performed. The pressboard thermally aged in synthetic ester fluid and the mixed oil has better electrical, thermal and mechanical properties as compared with the pressboard aged in mineral oil.

Background and Objectives: Medical illnesses seen in persons with psychiatric disorders are important but often ignored causes of increased morbidity and mortality. Hence, a community level intervention program addressing the issue is proposed. Materials and Methods: Patients with severe mental illnesses will be identified by a door-to-door survey and assessed for comorbid physical illnesses like anemia, hypertension, diabetes, and so on. They will then be randomized into two groups. The treatment as usual (TAU) group will not receive intervention from the trained community level workers, while the Intervention group will receive it. Results: The two groups will be compared for the prevalence and severity of comorbid physical illnesses. The expected outcome is compared to the TAU group, the intervention group will have a greater reduction in the morbidity due to physical illnesses and improved mental health. Conclusion: If successful, the module can be incorporated into the community level mental health delivery system of the District Mental Health Program (DMHP).

Background: The absence of reliable imaging or biological markers of phenotype transition in multiple sclerosis (MS) makes assignment of current phenotype status difficult. Objective: The authors sought to determine whether clinical information can be used to accurately assign current disease phenotypes. Methods: Data from the clinical visits of 14,387 MS patients in Sweden were collected. Classifying algorithms based on several demographic and clinical factors were examined. Results obtained from the best classifier when predicting neurologist recorded disease classification were replicated in an independent cohort from British Columbia and were compared to a previously published algorithm and clinical judgment of three neurologists. Results: A decision tree (the classifier) containing only most recently available expanded disability scale status score and age obtained 89.3% (95% confidence intervals (CIs): 88.8–89.8) classification accuracy, defined as concordance with the latest reported status. Validation in the independent cohort resulted in 82.0% (95% CI: 81.0–83.1) accuracy. A previously published classification algorithm with slight modifications achieved 77.8% (95% CI: 77.1–78.4) accuracy. With complete patient history of 100 patients, three neurologists obtained 84.3% accuracy compared with 85% for the classifier using the same data. Conclusion: The classifier can be used to standardize definitions of disease phenotype across different cohorts. Clinically, this model could assist neurologists by providing additional information.

Recovery of the upper extremity (UE) and hand function is considered the highest priority for people with tetraplegia, because these functions closely integrate with their activities of daily living. Spinal cord transcutaneous stimulation (scTS) has great potential to facilitate functional restoration of paralyzed limbs by neuro-modulating the excitability of the spinal network. Recently, this approach has been demonstrated effective in improving UE function in people with motor complete and incomplete cervical SCI. However, the research thus far is limited by the lack of a comprehensive assessment of functional improvement and neurological recovery throughout the intervention. The goal of this study was to investigate whether scTS can also facilitate UE functional restoration in an individual with motor and sensory complete tetraplegia. A 38-year-old male with a C5 level, ASIA Impairment Scale-A SCI (15 years post-injury, left hand dominant pre- and post-injury), received 18 sessions (60 minutes/session) of scTS combined with task-specific hand training over the course of 8 weeks. The total score of the Graded Redefined Assessment of Strength, Sensibility, and Prehension significantly improved from 72/232 to 96/232 at post-intervention, and maintained ranging from 82/232 to 86/232 during the three months follow-up without any further treatment. The bilateral handgrip force improved by 283.4% (left) and 30.7% (right), respectively at post-intervention. These strength gains were sustained at 233.5% -250% (left) and 11.5%-73.1% (right) during the follow-up evaluation visits. Neuromuscular Recovery Scale demonstrated dramatic and long-lasting improvements following the completion of the intervention. Changes of spinal motor evoked potentials from pre- to post-intervention indicated an increased level of spinal network excitability. The present data offer preliminary evidence that the novel scTS intervention combined with hand training can enhance UE functional use in people with motor and sensory complete SCI.

Background 5-Aminolevulinic acid dehydratase (ALAD) porphyria (ADP) is an ultrarare autosomal recessive disease, with only eight documented cases, all of whom were males. Although classified as an acute hepatic porphyria (AHP), induction of the rate limiting hepatic enzyme 5-aminolevulinic acid synthase-1 (ALAS1) has not been demonstrated, and the marrow may also contribute excess 5-aminolevulinic acid (ALA). Two patients have died and reported follow up for the others is limited, so the natural history of this disease is poorly understood and treatment experience limited. Methods We report new molecular findings and update the clinical course and treatment of the sixth reported ADP patient, now 31 years old and the only known case in the Americas, and review published data regarding genotype-phenotype correlation and treatment. Results Circulating hepatic 5-aminolevulinic acid synthase-1 (ALAS1) mRNA was elevated in this case, as in other AHPs. Gain of function mutation of erythroid specific ALAS2 – an X-linked modifying gene in some other porphyrias – was not found. Seven reported ADP cases had compound heterozygous ALAD mutations resulting in very low residual ALAD activity and symptoms early in life or adolescence. One adult with a germline ALAD mutant allele developed ADP in association with a clonal myeloproliferative disorder, polycythemia vera. Conclusions Elevation in circulating hepatic ALAS1 and response to treatment with hemin indicate that the liver is an important source of excess ALA in ADP, although the marrow may also contribute. Intravenous hemin was effective in most reported cases for treatment and prevention of acute attacks of neurological symptoms.

Background Typhoid fever remains a major public health problem in India. Recently, the Surveillance for Enteric Fever in India program completed a multisite surveillance study. However, data on subnational variation in typhoid fever are needed to guide the introduction of the new typhoid conjugate vaccine in India. Methods We applied a geospatial statistical model to estimate typhoid fever incidence across India, using data from 4 cohort studies and 6 hybrid surveillance sites from October 2017 to March 2020. We collected geocoded data from the Demographic and Health Survey in India as predictors of typhoid fever incidence. We used a log linear regression model to predict a primary outcome of typhoid incidence. Results We estimated a national incidence of typhoid fever in India of 360 cases (95% confidence interval [CI], 297–494) per 100 000 person-years, with an annual estimate of 4.5 million cases (95% CI, 3.7–6.1 million) and 8930 deaths (95% CI, 7360–12 260), assuming a 0.2% case-fatality rate. We found substantial geographic variation of typhoid incidence across the country, with higher incidence in southwestern states and urban centers in the north. Conclusions There is a large burden of typhoid fever in India with substantial heterogeneity across the country, with higher burden in urban centers.

Background Lack of reliable data in India drove the “Surveillance of Enteric Fever in India” (SEFI) concept. Hybrid surveillance, combining facility-based surveillance for the crude incidence, and a community-based healthcare utilization survey (HCUS) to calculate the factor needed to arrive at the adjusted incidence, was used in 6 sites. The HCUS aimed to determine the percentage of utilization of study facilities by the catchment population for hospitalizations due to febrile illness. Methods Population proportional to size sampling and systematic random sampling, in 2 stages, were used to survey 5000 households per site. Healthcare utilization was assessed. Results Febrile illness accounted for 20% of admissions among 137 990 individuals from 30 308 households. Only 9.6%–38.3% of those admitted with febrile illness sought care in the study hospitals. The rate of rural utilization of the private sector for hospitalization was 67.6%. The rate of hospitalization for febrile illness, per 1000 population, ranged from 2.6 in Manali to 9.6 in Anantapur; for 25.8% of the deaths associated with febrile illness, no facility was used before death. Conclusions One in 5 hospitalizations were associated with fever. Rural utilization of the private sector for hospitalization due to febrile illness was more than that of the public sector. Healthcare utilization patterns for hospital admissions due to febrile illness varied across sites. A meticulously performed HCUS is pivotal for accurate incidence estimation in a hybrid surveillance. Clinical Trials Registration ISRCTN72938224.

Background Blood culture, despite low sensitivity, is the gold standard for enteric fever diagnosis. Understanding predictors of blood culture positivity may help design strategies to optimize enteric fever diagnosis. Methods A cohort of 6760 children aged 0.5–15 years was followed for 3 years for enteric fever with blood cultures in an automated system, for fevers >3 days. Factors affecting test positivity in fevers and participant-level predictors for culture refusals were analyzed using regression models. Results Overall, 6097 suspected typhoid/paratyphoid fever (STF) episodes were reported, of which 5703 (93.5%) STFs had sampling for blood cultures, with 394 (6.5%) refusals. Salmonella enterica serovar Typhi/Paratyphi positivity was culture-confirmed in 3.8% (218/5703) of STF episodes. Older children (odds ratio [OR], 1.96 [95% CI, 1.39–2.77]), larger blood volume inoculated (OR, 2.82 [95% CI, 1.71–4.66]), higher temperatures during fever (OR, 3.77 [95% CI, 2.89–4.91]), and fevers diagnosed as suspected typhoid or acute undifferentiated fever (OR, 6.06 [95% CI, 3.11–11.78]) had a higher probability of culture positivity. Antibiotics before culture did not decrease culture positivity. Blood culture refusals were higher for children from wealthier households or with milder illness. Conclusions Performing blood cultures in older children with fever, especially those fevers with toxic presentation and increasing blood volume for inoculation are strategies to improve enteric fever detection in surveillance settings.

The optimal timing of debridement of open fractures has been a debatable topic for many years. The purpose of the present study was to evaluate the relationship between the timing of initial debridement and the development of subsequent infection in open long bone fractures of lower limb presenting to our institution. We did a retrospective cohort study in 89 cases of open long bone fractures of lower limb who had underwent wound debridement and fracture fixation. Patients were grouped as Group A (44 patients) in which debridement of open fractures were done within 12 hours of injury and Group B (45 patients) wherein debridement was carried out after 12 hours of injury. Out of 44 patients in group A, 21 patients had infection and 23 had no signs of infection at the end of 1 year. In group B, out of 45 patients, 19 were infected and 26 had no signs of infection at 1year follow-up. Statistical analysis showed that there was no significant relationship between the timing of debridement and infection rate (p value – 0.6). Hence open fractures can safely be debrided even after 12 hours of injury without increasing the chances of infection provided the antibiotics are started on time and the surgery is carried out by adequately rested and trained surgical team.

The present study aims to implement family-centered care (FCC) in neonatal intensive care unit (NICU). FCC facilitates mother-infant bonding with benefits for both families and health system. The authors used quality-improvement (QI) methods to implement FCC in level-2 NICU from an existing baseline of 30% to 80% over a period of 6 mo. Using the Institute of Healthcare model for improvement, the authors implemented strategies for family participation in caregiving activities, oral feeding and kangaroo care for neonates admitted in level-2 NICU. Eligibility criteria included the availability of at least one family member, preferably the mother for at least 6 h/d and a stable neonate based on physiological criteria irrespective of gestational age. The key interventions were: (1) adoption of a unit protocol for FCC with expanded visitation hours; (2) parental education through audio-visual aids, and (3) capacity building through training and peer support. Between August 2019 and January 2020, 1587 neonates were admitted to the NICU and 505 admitted in level-2 were enrolled. The proportion of eligible mother-infant dyads participating in FCC increased from a baseline of 32% to 44% during intervention and to 66% in the postintervention phase. The number of days per month FCC was tracked increased from 67% in the baseline to 82% in postintervention phase. There was no increase in the incidence of sepsis after implementation of FCC. Orientation of parents to FCC using audio-visual aids, provision of hands-on training and peer-support facilitated them to become active participants in their neonates’ care.

Aims To evaluate the safety, pharmacokinetics and pharmacodynamics of single- and multiple-rising doses (MRDs) of BI 705564 and establish proof of mechanism. Methods BI 705564 was studied in 2 placebo-controlled, Phase I clinical trials testing single-rising doses (1-160 mg) and MRDs (1-80 mg) of BI 705564 over 14 days in healthy male volunteers. Blood samples were analysed for BI 705564 plasma concentration, Bruton's tyrosine kinase (BTK) target occupancy (TO) and CD69 expression in B cells stimulated ex vivo. A substudy was conducted in allergic, otherwise healthy, MRD participants. Safety was assessed in both studies. Results All doses of BI 705564 were well tolerated. Geometric mean BI 705564 plasma terminal half-life ranged from 10.1 to 16.9 hours across tested doses, with no relevant accumulation after multiple dosing. Doses ≥20 mg resulted in ≥85% average TO that was maintained for ≥48 hours after single-dose administration. Functional effects of BTK signalling were demonstrated by dose-dependent inhibition of CD69 expression. In allergic participants, BI 705564 treatment showed a trend in wheal size reduction in a skin prick test and complete inhibition of basophil activation. Mild bleeding-related adverse events were observed with BI 705564; bleeding time increased in 1/12 participants (8.3%) who received placebo vs 26/48 (54.2%) treated with BI 705564. Conclusion BI 705564 showed efficient target engagement through durable TO and inhibition of ex vivo B-cell activation, and proof of mechanism through effects on allergic skin responses. Mild bleeding-related adverse events were probably related to inhibition of platelet aggregation by BTK inhibition.

The dielectric properties of 20% synthetic ester oil mixed with mineral oil were studied for its potential applications as an insulator in transformers. The corona inception voltage of mixed oil under AC and DC voltages was measured by the ultra-high frequency (UHF) technique. A statistical study of the breakdown voltage of mixed oil under AC, DC and standard lightning impulse voltages was carried out to obtain a database which would be useful for designing transformer insulation. Further, the mixture was subjected to continuous breakdown studies under AC voltage with lightning impulse voltages, at regular intervals and characterised through measurement of interfacial tension, flash point, ionic mobility as well as UV–vis spectroscopy and frequency-domain spectroscopy studies to understand the liquid's chemical stability. The results of the study have shown that the mixture was stable even after several breakdowns. The ionic mobility and polarisation current have increased, indicating higher losses in the oil. UHF signal energy analysis and phase-resolved partial discharge analysis have revealed a reduction in discharge activity with mixed oils.

Objective We evaluate the potential utility of F-18 FDG PET in addition to MRI in the diagnostic work-up of patients with autoimmune epilepsy (AE) and propose the inclusion of functional imaging in the antibody prevalence in epilepsy (APE) scoring system. Methods This was a retrospective analysis in 60 patients, diagnosed and treated for AE, of whom 40 were antibody negative (presumed AE) and 20 were antibody positive (definitive AE). All patients had undergone a dedicated brain and whole body FDG-PET in the department of Nuclear Medicine. Results In the antibody negative group, MRI supported a diagnosis of AE in 23 patients. Both MRI and PET were indicative in 12 cases, and standalone PET was positive in 8. While MRI alone was diagnostic in 57% (23/40), the combined yield of both modalities was 77% (31/40). When PET scores were added to assign the APE score in MRI negative cases, average APE score was 5.4. In the antibody positive group, MRI supported the diagnosis of AE in 7 patients. Both MRI and PET were positive in 4 patients and standalone PET was positive in 5 patients. While MRI alone was diagnostic in 35% (7/20), the combined yield of both modalities was 60 % (12/20). When PET scores were added to assign the APE score in MRI negative cases, average APE score was 6.1. Conclusion The inclusion of metabolic information from PET distinctly improved (the sensitivity of) APE scores to predict autoimmune origin even in antibody negative cases. A larger prospective study of similar type could justify adoption of FDG PET into the standard diagnostic procedure.

Objective We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to conduct a systematic review of external validity reporting in integrated primary care (IPC) interventions for mental health concerns. Methods We searched Medline, CINAHL, PsycINFO, the Cochrane Center Register of Controlled Trials, and relevant literature to identify publications from 1998 to 2018 reporting on open, randomized, or quasi-randomized trials of IPC interventions that targeted child (ages 0–18 years) psychological symptoms. For each publication, we extracted the information reported in each RE-AIM domain and calculated the proportion of the total studies reviewed. Results Thirty-nine publications describing 25 studies were included in the review. Publications rarely reported some indicators of external validity, including the representativeness of participants (12%), rate of adoption clinics or providers (16%), cost of implementation (8%), or evidence of maintenance (16%). Few studies reported on key pragmatic factors such as cost or organizational change processes related to implementation and maintenance. Strengths of some studies included comparisons of multiple active treatments, use of tailorable interventions, and implementation in “real world” settings. Conclusions Although IPC interventions appear efficacious under research conditions, there are significant knowledge gaps regarding the degree to which they reach and engage target recipients, what factors impact adoption and implementation of IPC interventions by clinicians, how fidelity can be maintained over time, and cost-effectiveness. Pediatric IPC researchers should embrace dissemination and implementation science methods to balance internal and external validity concerns moving forward.

Background/Purpose: Combating Antibiotic resistance has become a great challenge for clinicians due to inappropriate use of antibiotics. Antibiotics once considered being magic bullet is no more having that title. Recommendation in "AMR situation in India by Department of Biotechnology (DBT)" and "Treatment Guidelines for Antimicrobial Use by Indian Council of Medical Research (ICMR) India" emphasized the need for regional surveillance starting from the level of state to an individual hospital has been motivation behind the study. Method: Three hospitals in region of Cuddalore in Tamilnadu (India) have been the source of specimen for isolation of Escherichia coli during the period of January to July 2017. Antibiogram reports were collected during the study period and utilized for the study. Result: Among 124 isolates Urine, High vaginal swab, Pus, Serum, Oral swab and Amniotic fluid occupied 81.45%(n-101), 08.06%(n-10), 5.64%(n-7), 2.41%(n-3), 1.62%(n-2) and 0.81%(n-1) respectively. Antibiogram for the Escherichia coli isolates revealed 90% of resistance to Cefepime, 68% to Ciprofloxacin, 50% to Tetracyclin, 30% to Meropenum etc., Similarly high percentage of sensitiveness was evident in Cefotaxime (95.94%), Imipenum (95.91%), Piperacillin/Tazobactem (86%), Meropenum (70%) etc. Conclusion: On comparison with the 2014 ICMR (Antimicrobial Susceptibility) data percentage of resistance and susceptibility has a drastic change both in resistance and sensitivity. From the study it is clear that the generic recommendations on antibiotic use at national level can't be a desirable solution or recommendations to clinicians. The study signifies the importance of local surveillance and infection control programs. Funding Statement: No funding was obtained for this study. Declaration of Interest: The authors report no conflict of interest. Ethics Approval Statement: The samples were not collected exclusively for this study, and since it is a retrospective study where we have analysed the sensitivity pattern of the isolates in reference to ICMR-Antimicrobial use guidelines. Similarly international guidelines such as Consolidated Standards of Reporting trials (CONSORT) and uniform requirements for manuscripts submitted to biomedical journals(URM) states that ethics approval is required when animal or human are to be used for teaching or new intervention research. Since our study is not coming under prospective randomised trials we have not gone for Ethical clearance.

The local intrinsic abductor digiti minimi muscle flap is ideal for lateral, plantar lateral traumatic or diabetic foot wounds following adequate surgical debridement to eradicate any soft tissue and/or osseous infection. Although the indications and surgical technique have been well-described in the literature, the authors present a unique modification of tunnelling the harvested muscle flap directly from the donor site to the plantar recipient foot wound by maintaining the intact overlying skin island at the surface of the fifth metatarsal base. This modification allows preservation of the patient's skin integrity in this area, thereby minimising potential morbidity at the major pedicle site. After the harvested muscle is tunnelled through the intact skin island, an adjacent local random flap mobilisation, autogenous or allogeneic skin graft can then be used for coverage over the muscle inset if primary wound closure is not feasible. Simultaneous soft tissue or osseous surgical procedures and/or surgical offloading with external fixation at the time of index surgery may be necessary to achieve optimal outcomes. The authors present a modified surgical technique for the abductor digiti minimi muscle flap that can be performed in the surgical reconstruction of a soft tissue wound in patients with diabetic Charcot neuroarthropathy.

Objectives There is an increasing demand for wound healing products of natural origin. Our objective was to develop a spray formulation from Jatropha curcas (J. curcas) L. latex extracts for wound healing applications. Materials and methods J. curcas L. latex was subjected to solvent extraction. The phytochemical structure was elucidated by 1H-NMR and confirmed by liquid chromatography-mass spectrometer spectrometry. A topical spray formulation prepared from J. curcas latex extracts was evaluated in terms of its antimicrobial activity and radical scavenging activity. The toxicity of the formulation on fibroblast cell lines, collagen production, and wound healing activities were tested. Results The 1H-NMR and mass spectrometric analyses revealed the pure compound as curcacycline A. The J. curcas latex extract formulation had radical scavenging and antibacterial activities. Moreover, the formulation was not toxic to the human fibroblast cells and it stimulated collagen production and healed cell injury in 24 h. Conclusion The J. curcas latex extract promoted wound healing after cell injury. Our findings indicate the possibility of utilizing the J. curcas latex extract spray formulation as a potential antibacterial, antioxidant, and wound healing product from nature.

Objective:Early childhood factors can have persisting effects on development and cognition in children. We propose to explore the trends of Fe deficiency and Pb toxicity in early childhood and their association with child development at 2 years of age and cognition at 5 years.Design:Longitudinal birth cohort study.Setting:Urban slum, Vellore, India.Participants:Children enrolled at birth were followed up regularly in the first 2 years with developmental and cognitive assessments at 2 and 5 years of age, respectively.Results:The birth cohort enrolled 251 children with 228 children followed up at 2 years and 212 at 5 years of age. Fe deficiency (ID) was highest at 15 months of age and improved subsequently at 24 months. Blood Pb levels (BLL) remained high at all age groups with an increasing trend with age; 97 % at 36 months having high BLL. Persistent high mean BLL at 15 and 24 months had negative association with both cognition and expressive language raw scores of 24 months, while high mean BLL at 15, 24 and 36 months had no significant association with any of the domains of cognition at 5 years of age. Early childhood cumulative body Fe status at 7, 15 and 24 months did not show any association with child development at 2 years, but was associated with verbal, performance and processing speed components of cognition at 5 years.Conclusions:Optimising body Fe status and limiting Pb exposure in early childhood can augment child development and school entry cognition.