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Summary: Background: The standard malaria rapid diagnostic test (RDT) and newer ultra-sensitive RDT (uRDT) target Plasmodium falciparum histidine rich protein-2 (HRP2), which persists post-treatment. The duration of test positivity has not previously been studied in a low transmission setting. Methods: We conducted a longitudinal cohort study in a low transmission setting in Namibia. RDT-positive individuals identified through passive and active case detection were treated and followed weekly for testing by RDT and uRDT, HRP2 quantification, quantitative PCR (qPCR) of parasitemia, and quantitative reverse transcriptase PCR (RT-PCR) of gametocytemia, until RDT and uRDT were negative for two consecutive weeks. Determinants of persistent positivity were identified using Cox proportional hazards models. Findings: Among 137 participants with complete follow-up and no evidence of resurgence during follow-up, median duration of positivity was 42 days (range: 3−98 range) for RDT, compared to 67 days (range 12–105) for uRDT. In a sub-analysis of those with laboratory data before treatment (n = 60), drug resistance did not explain persistent positivity. Younger age (

Segmentation of retinal blood vessels from fundus images is vital to assist ophthalmologists in diagnosing different eye diseases like Arteriosclerosis, Glaucoma, Diabetic Retinopathy, Hypertension, and Choroidal Neovascularization. Accurate detection and timely treatment of these eye diseases can prevent irreversible impairment of vision. In computer-aided automatic diagnosis, Preprocessing of fundus images is necessary to reduce the uneven retinal image illumination, as well as the undesirable effect arising from the contrast differences between the retinal blood vessels and the background. In this study, the Hessian-based Frangi vesselness filter is proposed to enhance vasculature in fundus images. This approach seeks to extract thin vessels to diminish the intensity disparity between thick and thin vessels. Its accuracy has never, however, been thoroughly evaluated. To verify the effectiveness of the suggested filter for boosting vessel-like structures in the fundus images, an experimental approach is presented in this paper. The ability of the filter to improve vessel-like structures in fundus images is validated, and an experimental technique for evaluating filter performance using the U-Net model is described. Five quantitative performances, namely Accuracy, Recall, Specificity, Precision, and F1 Score measures on the DRIVE, HRF, DIARETDB1, DIARETDB0, CHASEDB1, ORIGA, DRISHTI GS, DRIONS DB, FIRE, and FIOT datasets, were evaluated and quantified in these experiments to validate the efficacy of the proposed filter. The results demonstrated a noteworthy improvement by achieving an Accuracy of 99.79 %, 99.84 %, 99.64 %, 99.72 %, 99.57 %, 99.48 %, 99.77 %, 99.05 %, 99.93 %, and 99.40 % respectively. Empirical evidence supports the advantages of this approach.

Simulation can be an excellent teaching and learning method if the scenarios are created appropriately. It starts with assessing the learner's needs and is followed by laying down objectives embracing the SMART principles. While creating a scenario, it is essential to consider the different aspects of realism, such as physical, contextual and psychological aspects. Using moulages and props helps in creating physical realism. The simulation expert should also be aware of the learner's experience and decide the SimZones for their learners based on their level of clinical expertise. The scenario progression needs to be laid down in stages. The role of the embedded participant needs to be decided a priori, and the embedded participant should be well-versed in their role. Pilot testing is a crucial step in simulation development as it keeps the simulation expert aware of the loopholes in the simulation scenario before running.

Abstract Objectives To describe multiligament stifle injury in dogs and report complications and long‐term outcomes. Methods Medical records of dogs surgically treated for multiligament stifle injury were reviewed from six veterinary hospitals. Long‐term follow‐up was collected from referring veterinarians. Results Twenty‐six client‐owned dogs and 26 stifles were included. Road traffic accidents and limb entrapment were the most common causes of injury. Cranial cruciate and lateral collateral ligament rupture was the most common combination of injury (10 cases). The caudal cruciate ligament was damaged in 12/23 cases but was surgically addressed in only 2 cases. Cranial cruciate ligament rupture was present in all cases and was managed using TPLO (6 cases), extracapsular suture (15 cases) and TTA (2 cases). Postoperative immobilisation with a transarticular external skeletal fixator was used in 4/26 cases. Intraoperative complications were reported in 2/23 cases, short‐term complications in 17/25 cases, of which eight were major, and long‐term complications in 7/18, of which two were major. Patella luxation was seen in one case and is a previously unreported complication. The overall outcome was excellent in 9/24 cases, good in 5/24 cases, fair in 7/24 cases and poor in 3/24 cases. Follow‐up time ranged from 1.5 months to 9 years with the median (IQR) of 9.5 (4.0 to 28.5) months. Conclusions Multiligament stifle injury in dogs is associated with a high rate of major complications. The overall outcome was good to excellent in just over half of the dogs.

Abstract Background Insecticide resistance in malaria vectors can be spatially highly heterogeneous, yet population structure analyses frequently find relatively high levels of gene flow among mosquito populations. Few studies have contemporaneously assessed phenotypic, genotypic and population structure analysis on mosquito populations and none at fine geographical scales. In this study, genetic diversity, population structure, and insecticide resistance profiles of Anopheles funestus and Anopheles arabiensis were examined across mosquito populations from and within neighbouring villages. Methods Mosquitoes were collected from 11 towns in southern Mozambique, as well as from different neighbourhoods within the town of Palmeira, during the peak malaria transmission season in 2016. CDC bottle bioassay and PCR assays were performed with Anopheles mosquitoes at each site to determine phenotypic and molecular insecticide resistance profiles, respectively. Microsatellite analysis was conducted on a subsample of mosquitoes to estimate genetic diversity and population structure. Results Phenotypic insecticide resistance to deltamethrin was observed in An. funestus sensu stricto (s.s.) throughout the area, though a high level of mortality variation was seen. However, 98% of An. funestus s.s. were CYP6P9a homozygous resistant. An. arabiensis was phenotypically susceptible to deltamethrin and 99% were kdr homozygous susceptible. Both Anopheles species exhibited high allelic richness and heterozygosity. Significant deviations from Hardy–Weinberg equilibrium were observed, and high linkage disequilibrium was seen for An. funestus s.s., supporting population subdivision. However, the FST values were low for both anophelines (− 0.00457 to 0.04213), Nm values were high (9.4–71.8 migrants per generation), AMOVA results showed almost 100% genetic variation among and within individuals, and Structure analysis showed no clustering of An. funestus s.s. and An. arabiensis populations. These results suggest high gene flow among mosquito populations. Conclusion Despite a relatively high level of phenotypic variation in the An. funestus population, molecular analysis shows the population is admixed. These data indicate that CYP6P9a resistance markers do not capture all phenotypic variation in the area, but also that resistance genes of high impact are likely to easily spread in the area. Conversely, other strategies, such as transgenic mosquito release programmes will likely not face challenges in this locality.

Introduction: A lesser studied aspect of Parkinson's disease (PD) is its associated peripheral sensory-motor neuropathy. Peripheral neuropathy is an intriguing aspect of PD, a problem not given sufficient attention and which if tackled properly could make a difference to the multifaceted sufferings of the PD patient. Studies regarding the prevalence of peripheral neuropathy and its risk factors in patients with PD are scarce from the Indian subcontinent. Methods: This prospective observational study was conducted in a tertiary care teaching hospital in South India. Patients diagnosed with idiopathic Parkinson's disease (IPD) were screened and enrolled. All the patients underwent detailed evaluation of symptoms, signs, and electrophysiology (Nerve conduction study, Sympathetic skin response), stimulated skin wrinkling with Eutectic Mixture of Local Anesthetics. Patients found to have large/small fiber neuropathy underwent additional tests to exclude other causes of neuropathy. Results: A total of 154 patients with IPD were enrolled in the study (mean age: 61.96 ± 9.15 years, mean duration of disease was 4.08 ± 3.16 years). The mean Hoehn and Yahr (H and Y) score was 2.3 ± 0.825 and the mean Unified Parkinsons Disease Rating Scale (UPDRS)-3 score in the ON state was 23.07 ± 11.14. The mean cumulative levodopa dose was 482.68 ± 651.76 (median: 292; range: 4728.57) grams. Peripheral neuropathy was found in 49 patients (31.8%), large fiber in 28 (18.2%) and small fiber in 47 (30.5%); an overlap of large and small fiber neuropathy was seen in 26 patients (16.9%). Around 34% of patients had serum homocysteine levels >20 mg/dl. In univariate analysis, duration of disease, levodopa cumulative dose, serum homocysteine level, H and Y score, UPDRS-3 ON score, Toronto Clinical Neuropathy Score (P < 0.001 for all), age at presentation, and rigidity predominant presentation (P = 0.02 for both) were associated with large fiber neuropathy. All of these variables were also associated with the presence of small fiber neuropathy (P = 0.004 for age at presentation and P < 0.001 for rest), except the type of PD presentation. However, in multivariate logistic regression analysis, only duration of disease, levodopa cumulative dose, and H and Y score were associated with the presence of large and small fiber neuropathy. Conclusions: In our cohort, majority of the patients were in early-stage PD and around one-fifth and one-third of patients suffer from large and small fiber polyneuropathy, respectively. Large and small fiber neuropathy in PD is mainly associated with duration of disease, levodopa cumulative dose, and H and Y score.

Background: Being happy in life is very essential to be healthy, which is important for nursing students to grow and adapt well in their professional life. Aim: The aim of this study is to assess the level of happiness and identify the determinants of happiness among nursing students. Materials and Methods: Three hundred and forty-two undergraduate nursing students College of Nursing, All India Institutes of Medicals Sciences, New Delhi, India, enrolled in the study by convenience sampling. Data were collected through demographic information sheets and oxford happiness questionnaires. Frequencies, percentages, mean, standard deviation, Chi-square test, and multiple linear regression were used to analyze the data. Results: The mean happiness score of nursing students was 3.96 ± 0.59 on a scale of 6. The percentage distribution showed that 43.2% of the students responded “not particularly happy,” and 42.1% were “rather happy.” The current year of study, the number of close friends, stress experienced in the past 6 months, and engagement in physical activities contributed 53% of the variance in the happiness score of nursing students (P < 0.001). Further, monthly family income (P = 0.018) and choice of course (P = 0.003) had a significant association with their happiness score. Conclusion: Nursing students had a moderate level of happiness. The study suggests that there is a need to develop strategies to enhance happiness among nursing students in alignment with the identified factors. Educators need to develop a holistic curriculum giving equal importance to academic competencies and personal flourishment.

Purpose: The purpose of this study is aimed to assess the impact of simulation in addition to conventional training on knowledge and self-efficacy of the nursing students in handling common pediatric conditions covered under integrated management of neonatal and childhood illnesses. Methods: In a pretest–posttest control group design, 61 nursing students were randomly assigned to an experimental and control groups. The intervention for the control group consisted of 30 h conventional teaching on the management of common pediatric conditions, while the experimental group received additional simulation training of 5 h duration along with conventional teaching. Results: Both experimental (n = 30) and control groups (n = 30) were similar in demographic characteristics and baseline academic qualifications. There was a significant increase in knowledge and self-efficacy scores in both the groups (P < 0.001) with postintervention scores being significantly higher for knowledge (17.8 [2.1] vs. 15.5 [1.9], P < 0.001) and self-efficacy (34.4 [2.5] vs. 32.3 [2.9], P = 0.004) in the experimental group. Conclusion: An add-on simulation-based training to conventional teaching led to better knowledge and self-efficacy level in handling common pediatric conditions.

Background: Thirst is reported as a troublesome symptom in patients with heart failure (HF), and very few studies have been done to assess thirst in these patients. Therefore, this study aims to assess thirst intensity, thirst distress, and practices of HF patients to manage thirst. Methods: A descriptive, cross-sectional study was conducted on 75 HF patients admitted to the cardiology department. Purposive sampling technique was used for collecting data from July 2019 to November 2019. Visual analog scale (0–100 mm) was used to assess thirst intensity, and 8-item thirst distress scale was used to assess thirst distress. The practices of the participants were assessed using a self-developed questionnaire. Results: The mean age of the participants was 44.83 ± 15.51 years and the majority (72%) was male. The majority of the participants (82.7%) had fluid restriction, and almost 97.3% of all of the participants were receiving diuretics. The median (interquartile range) thirst intensity was 33 (16–50) mm. About 66.7% of the participants had moderate-to-severe thirst distress. Both thirst intensity and thirst distress were associated with fluid restriction, New York Heart Association functional class, and serum urea level. The participants reported that they drink a small amount of water frequently, gargle with water, eat cucumber, drink buttermilk, lemon juice, and coconut water. Very few participants had made changes in their food habits and lifestyle. Conclusion: Two-thirds of the participants had moderate-to-severe thirst distress. Fluid restriction was associated with both thirst intensity and thirst distress. Thus, nurses are responsible to assess thirst among HF patients and help them to manage their thirst effectively.

The role of subpatent infections for malaria transmission and elimination is unclear. Here, Slater et al. analyse several malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections.

Case summary A 15-year-old neutered male domestic shorthair cat presented with a 4-week history of dysphonia and reluctance to chew hard food. Oral examination revealed a mass lesion on the caudal soft palate. Biopsy was performed and histopathology with immunohistochemistry was most consistent with histiocytic sarcoma. CT of the head identified a discrete, left-sided, soft tissue mass lesion cranial to the tonsil with bilaterally symmetrical regional lymph nodes. CT of the thorax was unremarkable. Surgical removal achieved cytoreduction but not complete removal. Adjuvant chemotherapy with lomustine 10 mg (30 mg/m 2 ) was initiated. The patient developed suspected pancreatitis 2–3 weeks postoperatively, so further chemotherapy treatment was discontinued, but supportive treatment with pain relief and appetite stimulants was provided. Three months postoperatively, the patient developed recurrent dysphonia, and oral examination revealed a suspicion of local recurrence. Confirmation of diagnosis (cytopathology or histopathology) was not obtained. Supportive treatment to maintain a good quality of life was continued and the patient was euthanased 6 months after diagnosis owing to progressive disease. Relevance and novel information Only a few reports have been published describing histiocytic diseases of cats. To our knowledge, this is the first report of a feline histiocytic sarcoma of the oral cavity. Therefore, histiocytic sarcoma should be considered as a differential diagnosis in feline patients with an oral mass, especially if histopathology suggests a pleomorphic and poorly differentiated sarcoma. Immunohistochemistry for the confirmation of cell line origin would be strongly recommended.

The current management of COVID-19 is mostly limited to general supportive care and symptomatic treatment. Ivermectin is a broad-spectrum anti-parasitic drug used widely for the treatment of onchocerciasis and lymphatic filariasis. Apart from its anti-parasitic effect it also exhibits antiviral activity against a number of viruses both in vitro and in vivo. Hence, we conducted this systematic review and meta-analysis to assess the currently available data on the therapeutic potential of ivermectin for the treatment of COVID‐19 as add on therapy. A total of 629 patients were included in the 4 studies and all were COVID-19 RT-PCR positive. Among them, 397 patients received ivermectin along with usual therapy. The random effect model showed the overall pooled OR to be 0.53 (95%CI: 0.29 to0.96) for the primary outcome (all-cause mortality) which was statistically significant (P=0.04). Similarly, the random effect model revealed that adding ivermectin led to significant clinical improvement compared to usual therapy (OR=1.98, 95% CI: 1.11 to 3.53, P=0.02). However, this should be inferred cautiously as the quality of evidence is very low. Currently, many clinical trials are on-going, and definitive evidence for repurposing this drug for COVID-19 patients will emerge only in the future.

Many key biologics are scheduled to lose their patent by the year 2020, which will provide the opportunity to other biopharmaceutical companies to develop the similar biologics. Biosimilar or similar biologic used has increased in the recent year following the approval of the first biosimilar in early 2000. India is one of the leading manufacturers of similar biologics. India has developed a new guideline in 2012 for the pre- and post-marketing approval of similar biologics.

Abstract Background The detection of submicroscopic infections in low prevalence settings has become an increasingly important challenge for malaria elimination strategies. The current field rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria are inadequate to detect low-density infections. Therefore, there is a need to develop more sensitive field diagnostic tools. In parallel, a highly sensitive laboratory reference assay will be essential to evaluate new diagnostic tools. Recently, the highly sensitive Alere™ Malaria Ag P.f ELISA (HS ELISA) was developed to detect P. falciparum histidine-rich protein 2 (HRP2) in clinical whole blood specimens. In this study, the analytical and clinical performance of the HS ELISA was determined using recombinant P. falciparum HRP2, P. falciparum native culture parasites, and archived highly pedigreed clinical whole blood specimens from Karen village, Myanmar and Nagongera, Uganda. Results The HS ELISA has an analytical sensitivity of less than 25 pg/mL and shows strong specificity for P. falciparum HRP2 when tested against P. falciparum native culture strains with pfhrp2 and pfhrp3 gene deletions. Additionally, the Z′-factor statistic of 0.862 indicates the HS ELISA as an excellent, reproducible assay, and the coefficients of variation for inter- and intra-plate testing, 11.76% and 2.51%, were acceptable. Against clinical whole blood specimens with concordant microscopic and PCR results, the HS ELISA showed 100% (95% CI 96.4–100) diagnostic sensitivity and 97.9% (95% CI 94.8–99.4) diagnostic specificity. For P. falciparum positive specimens with HRP2 concentrations below 400 pg/mL, the sensitivity and specificity were 100% (95% CI 88.4–100) and 88.9% (95% CI 70.8–97.6), respectively. The overall sensitivity and specificity for all 352 samples were 100% (CI 95% 96–100%) and 97.3% (CI 95% 94–99%). Conclusions The HS ELISA is a robust and reproducible assay. The findings suggest that the HS ELISA may be a useful tool as an affordable reference assay for new ultra-sensitive HRP2-based RDTs.

Abstract Background As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100–200 parasites/µL (p/µL) and 800–1000 pg/mL histidine-rich protein 2 (HRP2), respectively, are unable to detect these infections. A novel ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT) was evaluated in laboratory conditions to define the test’s performance against recombinant HRP2 and native cultured parasites. Results The uRDT detected dilutions of P. falciparum recombinant GST-W2 and FliS-W2, as well as cultured W2 and ITG, diluted in whole blood down to 10–40 pg/mL HRP2, depending on the protein tested. uRDT specificity was 100% against 123 archived frozen whole blood samples. Rapid test cross-reactivity with HRP3 was investigated using pfhrp2 gene deletion strains D10 and Dd2, pfhrp3 gene deletion strain HB3, and controls pfhrp2 and pfhrp3 double deletion strain 3BD5 and pfhrp2 and pfhrp3 competent strain ITG. The commercial Standard Diagnostics, Inc. BIOLINE Malaria Ag P.f RDT (SD-RDT) and uRDT detected pfhrp2 positive strains down to 49 and 3.13 p/µL, respectively. The pfhrp2 deletion strains were detected down to 98 p/µL by both tests. Conclusion The performance of the uRDT was variable depending on the protein, but overall showed a greater than 10-fold improvement over the SD-RDT. The uRDT also exhibited excellent specificity and showed the same cross-reactivity with HRP3 as the SD-RDT. Together, the results support the uRDT as a more sensitive HRP2 test that could be a potentially effective tool in elimination campaigns. Further clinical evaluations for this purpose are merited.

Context: Elder abuse is a serious problem that has adverse consequence on health. Still, research on elder abuse is sparse in India. Aims: This study aimed to find the nature, prevalence, and factors such as depression and physical problems associated with elder abuse in an urban North Indian community. Materials and Methods: A cross-sectional study was conducted with 222 elders with 97 males, aged 60 years or older residing in an urban community of Delhi. Elders were assessed for abuse by modified Vulnerability to Abuse Screening Scale questionnaire, Geriatric Depression Scale, and self-reported questions on health problems. Results: Mean age of the study population was 66.3 ± 4.2 years. The overall prevalence of any type of elder abuse was 24.3%. Psychological abuse was the most common type (22.9%) followed by financial abuse (5.8%), physical abuse (1.4%), and anti-constitutional abuse (nil). Among the abused, nearly 20% experienced more than one type of abuse. Thirty-seven women (30%) and 17 men (18%) reported elder abuse. Low income (

Abstract Background Plasmodium gametocytes are sexual stages transmitted to female Anopheles mosquitoes. While Plasmodium parasites can be differentiated microscopically on Giemsa-stained blood smears, molecular methods are increasingly used because of their increased sensitivity. Molecular detection of gametocytes requires methods that discriminate between asexual and sexual stage parasites. Commonly tested gametocyte-specific mRNAs are pfs25 and pfs230 detected by reverse transcription polymerase chain reaction (RT-PCR). However, detection of these unspliced mRNA targets requires preceding DNase treatment of nucleic acids to eliminate co-purified genomic DNA. If gametocyte-specific, spliced mRNAs could be identified, DNase treatment could be eliminated and one-step multiplexed molecular methods utilized. Results Expression data was used to identify highly-expressed mRNAs in mature gametocytes that were also low in antisense RNA expression in non-gametocyte stages. After testing numerous candidate mRNAs, the spliced female Pf3D7_0630000 mRNA was selected as a Plasmodium falciparum gametocyte-specific biomarker compatible with Plasmodium 18S rRNA RT-PCR. This mRNA was only detected in samples containing mature gametocytes and was absent in those containing only asexual stage parasites or uninfected human blood. PF3D7_0630000 RT-PCR detected gametocytes across a wide range of parasite densities in both spiked and clinical samples and agreed with pfs25 RT-PCR, the gold standard for RT-PCR-based gametocyte detection. PF3D7_0630000 multiplexed with Plasmodium 18S rRNA RT-PCR was more sensitive than other spliced mRNA targets for one-step RT-PCR gametocyte detection. Conclusions Because the spliced target does not require DNase treatment, the PF3D7_0630000 assay can be multiplexed with Plasmodium 18S rRNA for direct one-step detection of gametocytes from whole human blood.

Carbon dots (CDs) are optically active carbon-based nanomaterials. These nanomaterials can change their light emission properties in response to various external stimuli such as pH, temperature, pressure, and light. The CD’s remarkable stimuli-responsive smart material properties have recently stimulated massive research interest for their exploitation to develop various sensor platforms. Herein, an effort has been made to review the major advances made on CDs, focusing mainly on its smart material attributes and linked applications. Since the CD’s material properties are largely linked to their synthesis approaches, various synthesis methods, including surface passivation and functionalization of CDs and the mechanisms reported so far in their photophysical properties, are also delineated in this review. Finally, the challenges of using CDs and the scope for their further improvement as an optical signal transducer to expand their application horizon for developing analytical platforms have been discussed.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Diabetes Mellitus (DM) is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. Subcutaneous insulin and Oral Hypoglycaemic Agents (OHA) constitute the main treatment option for DM. Insulin is administered by injection or continuous infusion to control glucose levels mainly in Type I diabetes. Newer routes both oral and non oral, for insulin administration are current direction of insulin research as insulin injection therapy is burdensome and painful for many patients. Inhalational insulin is an attractive alternative for systemic administration of insulin given its accessibility and large alveolar-capillary network of lungs for drug absorption. Afrezza, inhaled insulin has been recently approved by Food and Drug Administration (FDA). It is a new, quicker acting inhalable insulin with a different and safer pharmacokinetic profile in comparison to previously failed inhaled form of insulin.

Following publication of the original article [1], the authors flagged an error concerning a reference to a product in the Methods section.

Stroke in young is now a major health concern in developing countries along with coronary artery disease (CAD), according to various Indian studies, its prevalence is 25-34%. Among the undetermined etiological factors thrombophilic disorders constitute 60% cases of stroke. A 19 year old young male presented with symptoms of left middle cerebral artery (MCA) thrombosis, on evaluation homocysteinemia is noticed. In this case homocysteinemia seems to be the only risk factor responsible for stroke.