Changing Epidemiology: A New Focus of Kala-azar at High-Altitude Garhwal Region of North India.

Adult cases of visceral leishmaniasis (VL), predominantly males, have been reported in the past decade from natives of high altitude areas of North Indian state of Uttarakhand. We report 14 pediatric cases of VL, who were diagnosed and treated successfully over the past 7 years. All these children were born and brought up in this area and had never visited any of the endemic areas. High prevalence of pallor, splenohepatomegaly, thrombocytopenia and poor association with HIV are cardinal features of VL in this region. Although newer drugs have become available, the protozoan continues to be sensitive to sodium stibogluconate. We conclude that the transmission cycle of VL has been established in this region and VL should be considered in the differential diagnosis of any child presenting with fever and hepatosplenomegaly. However, molecular and epidemiological studies are needed to identify the ancestry, vector and animal reservoir if any in this region.

An electrochemical sensor for nitrobenzene using π-conjugated polymer-embedded nanosilver.

A novel electrochemical sensing platform for nitrobenzene has been developed using silver nanoparticles (AgNPs) embedded in the poly(amic) acid (PAA) polymer matrix (PAA-AgNPs). PAA was synthesized via the polycondensation reaction of para-phenylenediamine and benzene-1,2,4,5-tetracarboxylic dianhydride. PAA-AgNP nanocomposites were synthesized by the in situ reduction of a silver precursor by the polymer at room temperature in a one-step approach without using an extraneous reducing or capping agent. The composite was subsequently characterized in solution and as a thin film. The X-ray diffraction technique revealed the crystalline nature of the PAA films with the embedded AgNPs. Unlike conventional polymers, the synthesized PAA membrane exhibits significant UV/Vis spectroscopic response. The sequestered nanoparticles also show the characteristic surface plasmon resonance (SPR) peaks confirming the presence of AgNPs. Integrated charge areas were 4.826 mC and 2.176 C for PAA/GC and PAA-AgNPs/GC respectively. The charge at the PAA-AgNP/GC electrode is 451 times greater than that at the PAA/GC electrode suggesting that the AgNP composite exhibits higher electroactivity. When tested as a sensor for nitrobenzene, the PAA-AgNP modified GC electrode showed promising potential as an electrochemical sensor. The electrochemical sensors exhibit a wide linear dynamic range (10-600 µM) with a correlation coefficient of 0.9735, a detection limit of 1.68 µM and a sensitivity of 7.88 µA µM(-1). The sensor also exhibited minimal interference effects on structurally-similar nitroaromatic compounds and metal species such as 4-nitroaniline (4-NA), 2-nitrophenol (2-NP), dinitrobenzene (DNB), Pb(2+) and Cd(2+).

Scrub typhus in Uttarakhand & adjoining Uttar Pradesh: Seasonality, clinical presentations & predictors of mortality.

BACKGROUND & OBJECTIVES: Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India. METHODS: Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA. RESULTS: A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death. INTERPRETATION & CONCLUSIONS: The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

Osteolytic lesions of hand and feet: a seven-year experience from a tertiary referral centre of North India.

There are 106 bones in hands and feet but their lesions are not commonly reported. This was a retrospective study of all osteolytic lesions involving bones of the hands or feet presenting to the only tertiary referral centre of the north Indian state of Uttarakhand during the 7-year period from January 2006 to December 2012. A compilation of the various demographic, clinical, radiological and histopathological findings was made. Of the 52 lesions encountered in the 7-year record, 75% were asymptomatic. 20 (38.4%) were benign tumours, 20 (38.4%) tumour-like lesions, 9 (17.3%) inflammatory and post traumatic lesions and only 3 (5.7%) were malignant lesions. Giant cell tumour was the most common benign tumour, aneurysmal bone cyst the most common tumour-like lesion and non-specific osteomyelitis was the most common inflammatory and post-traumatic pathology. All phalangeal lesions were non-malignant and 62% were either giant cell tumours or giant cell reactions. Giant cell reaction was confined to upper limb bones; metatarsals were afflicted exclusively with giant cell tumours (n=3) while malignant lesions affected the metacarpals in two and carpal bones in one instance. Aneurysmal bone cysts were seen exclusively in the tarsal (n=4) and carpal bones (n=2), a very rare finding. More cases need to be studied to define patterns of lesions of hands and feet. The definitive diagnosis is essential as many patients with osteolytic lesions may not require surgical intervention.

Hepatopathy in Scrub Typhus: Clinical Presentation, Association With Morbidity and Impact on Outcome.

INTRODUCTION: Acute liver injury accompanies tropical fevers like scrub typhus. This study was undertaken to evaluate liver injury in scrub typhus and its association with the disease severity. METHODS: This was a single-centre prospective, observational study on in-patients of scrub typhus from north India. All patients were categorized on basis of elevation of transaminases as having normal or abnormal liver function. Those with hepatopathy were sub-categorized as having mild, moderate, severe or very severe liver injury. RESULTS: Liver dysfunction was present in 76/109 of the patients and was significantly associated with eschar, clinically discernible hepatomegaly and splenomegaly. Shock, renal and respiratory insufficiency, need for intensive care and oxygen supplementation were also significantly associated with hepatopathy. Duration of hospitalization and mortality were comparable in patients with/without liver injury; however delayed defervescence (6.2+3.8 vs. 4.5+2.5 days; p=0.025) was observed with hepatopathy. Icterus (p=0.001), hepatomegaly (p=0.015), thrombocytopenia (p<0.001) and raised erythrocyte sedimentation rate (ESR) (p=0.003) were significantly observed with increasing grade of liver injury.  Conclusion: Liver dysfunction and its increased severity in scrub typhus did not translate into increased morbidity and/or poor outcomes.

Enhanced exponential ratio-cum-ratio estimator in ranked set sampling using transformed auxiliary information.

Estimation of population mean is a determined subject issue in sampling surveys and many efforts have been paid by various researchers to enhance the precision of the estimates by utilizing the correlated auxiliary information. In connection with this, we suggest an improved exponential ratio-cum-ratio estimator using transformed auxiliary variables under ranked set sampling scheme. Theoretical comparison between estimators is made in terms of mean square errors (MSEs), percentage relative efficiencies (PREs), and percentage relative root mean squared error (PRRMSE). The numerical expression for the bias and MSE of the suggested estimator is derived up to first order of approximation. Based on the results of actual data sets and a simulation study, it is found that the suggested estimator perform well as compared to its existing counterparts.

Improved modified estimator for estimation of median using auxiliary information under simple random sampling.

This article aims to suggest an improved estimator for estimation of population median using auxiliary information under simple random sampling. The expression for the bias and mean square error are obtained up to first order approximation. We determine the MLE of the optimal values of the describing scalars. The proficiency of the suggested estimator is evaluated in comparison to the preliminary estimators using the MSE threshold. The suggested estimators are compared numerically to the ones that are currently studied in this study. The performance and novelty of the estimators was evaluated using real data sets and a simulation study. To check the efficiency of estimators empirical and theoretical study has been studied. Based on numerical result it is to be noted that our suggested estimator is more efficient as compared to existing estimators which is considered in this article in terms of least MSE and greater PRE.

An improved class of estimators for estimation of population distribution functions under stratified random sampling.

The main objective of the current study is to suggest an enhanced family of log ratio-exponential type estimators for population distribution function (DF) using auxiliary information under stratified random sampling. Putting different choices in our suggested generalized class of estimators, we found some Specific estimators. The bias and MSE expressions of the estimators have been approximated up to the first order. By using the actual and simulated data sets, we measured the performance of estimators. Based on the results, the suggested estimators for DF show better performance as compared to the preliminary estimators considered here. The suggested estimators have a advanced efficiency than the other estimators examined with the estimators F‾ˆlogPR(st)2, and F‾ˆlogPR(st)4 for both the actual and simulated data sets. The magnitude of the improvement in efficiency is noteworthy, indicating the superiority of the proposed estimators in terms of MSE.

Improved estimation of population distribution function using twofold auxiliary information under simple random sampling.

In this article, our main aim is to suggest enhanced families of estimators for estimating the population distribution function (DF) using twofold auxiliary evidence within the framework of simple random sampling. Numerical analysis is performed on four different actual data sets. The precision of the estimators is further investigated exhausting a simulation study. As equated with existing estimators, the suggested families of estimators have minimum mean square error (MSE) and higher percentage relative efficiency (PRE). The succeeding recommended family of estimators outperforms the first family of estimators across all data sets. These are positive indicators of its performance. The theoretical result shows that the recommended family of estimators performs better than the existing estimators. The extent of improvement in efficiency is noteworthy, indicating the superiority of the suggested estimators in terms of minimum MSE.

Periocular granulomatous inflammatory lesions mimicking conjunctival melanoma recurrence in the setting of systemic nivolumab treatment.

Purpose: Conjunctival melanoma is a rare neoplasm with high rates of recurrence and metastasis. Traditional management includes surgical excision and cryotherapy, followed by adjuvant therapy as needed. Immune checkpoint inhibitors, including nivolumab, are a targeted treatment option with improved survival rates. However, various immune-related adverse effects have been reported with these drugs. While systemic granulomatous inflammation is a documented systemic side effect, it has rarely been reported in the conjunctiva and ocular adnexa. Observation: A patient with a history of recurrent metastatic conjunctival melanoma presented with both a left sub-conjunctival and upper eyelid lesion after the commencement of treatment with nivolumab. The lesions were excised with a clinical suspicion for metastasis and consisted of noncaseating granulomatous inflammation with no evidence of malignancy on histopathologic examination. Infectious and primary autoimmune etiologies were ruled out. Conclusion and importance: This is a biopsy-proven case of periocular immune checkpoint inhibitor-associated granulomatous inflammation.

Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.

Purpose: Lack of valid end points impedes developing therapeutic strategies for early age-related macular degeneration (AMD). Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The relationship between RMDA and the status of outer retinal bands on optical coherence tomography (OCT) have not been well defined. This study aims to characterize these relationships in early and intermediate AMD. Methods: Baseline data from 476 participants was assessed including eyes with early AMD (n = 138), intermediate AMD (n = 101), and normal aging (n = 237). Participants underwent volume OCT imaging of the macula and rod intercept time (RIT) was measured. The ellipsoid zone (EZ) and interdigitation zone (IZ) on all OCT B-scans of the volumes were segmented. The area of detectable EZ and IZ, and mean thickness of IZ within the Early Treatment Diabetic Retinopathy Study (ETDRS) grid were computed and associations with RIT were assessed by Spearman's correlation coefficient and age adjusted. Results: Delayed RMDA (longer RIT) was most strongly associated with less preserved IZ area (r = -0.591; P < 0.001), followed by decreased IZ thickness (r = -0.434; P < 0.001), and EZ area (r = -0.334; P < 0.001). This correlation between RIT and IZ integrity was not apparent when considering normal eyes alone within 1.5 mm of the fovea. Conclusions: RMDA is correlated with the status of outer retinal bands in early and intermediate AMD eyes, particularly, the status of the IZ. This correlation is consistent with a previous analysis of only foveal B-scans and is biologically plausible given that retinoid availability, involving transfer at the interface attributed to the IZ, is rate-limiting for RMDA.

Probing Deposit-Driven Age-Related Macular Degeneration Via Thicknesses of Outer Retinal Bands and Choroid: ALSTAR2 Baseline.

Purpose: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort. Methods: Subjects ≥ 60 years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups. Results: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant. Conclusions: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.

The influence of the 2:1 yogic breathing technique on essential hypertension.

In 2:1 breathing exhalation is twice of inhalation. The study was performed to study the influence of 2:1 yogic breathing technique on patients of essential hypertension. 30 patients of essential hypertension between ages of 20-50 years were selected. After a rest of 15-20 minutes in a comfortable sitting posture their baseline physiological parameters recorded on a digital polygraph were, Electromyogram (EMG), Galvanic skin response (GSR), Finger tip temperature (FTT), Heart rate(HR) and Respiratory rate(RR). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded by automated digital Sphygmomanometer. Then they were guided to do 2:1 breathing maintaining respiratory rate of around 6/min. Subjects were then instructed to do 2:1 breathing twice a day for 5-7 minutes for next 3 months. Subjects reported back weekly for recording of BP. The physiological parameters of the subjects were assessed again by polygraph at the end of three months of practicing 2:1 yogic breathing. The mean fall of SBP over 12 weeks was 12 mm Hg (8%) and DBP was 7 mm Hg (7%). P value < 0.001 in both. After practicing 2:1 breathing for 3 months there was statistically significant reduction of SBP, DBP, HR RR, EMG, GSR and rise in FTT. The study showed that 2:1 breathing technique caused a comprehensive change in body physiology by altering various parameters that are governed by the autonomic nervous system. It is an effective modality for management of essential hypertension.

Haematological factors and anaemia in acute malaria: A prospective hospital-based cross-sectional observational study.

This prospective, observational, cross-sectional study was undertaken to estimate the burden of anaemia in malaria and to evaluate the contribution of haematogenic factors and haemolysis in its pathogenesis. Haematogenic factors (vitamin B12, folic acid, lactate dehydrogenase, ferritin, total iron binding capacity, direct Coombs test) were estimated in patients with malaria at the time of admission. They were categorized as anaemics or non-anaemics and their complications and outcomes were recorded. P. vivax (97/112) and P. falciparum (13/112) mono-infections dominated; anaemia was seen in 63.3%. Patients with and without anaemia were comparable in terms of haemolysis and the haematogenic factors evaluated. Bleeding events, acute kidney injury and acute liver injury were comparable; however, the need for mechanical ventilation and transfusion of blood products was significantly higher amongst the anaemics. We concluded that haemolysis and presumably transient bone marrow suppression contribute to anaemia in malaria. Pre-existing nutritional deficiencies do not, however, predispose to severe malaria.

Improved family of estimators for the population mean using supplementary variables under PPS sampling.

In this article, we suggest an enhanced family of estimators for estimation of population mean employing the supplementary variables under probability proportional to size sampling. Up to the first order of approximation, numerical formulations of the bias and mean square error of estimators are obtained. From our suggested improved family of estimators, we give sixteen different members. The recommended family of estimators has specifically been used to derive the characteristics of sixteen estimators based on the known population parameters of the study as well as auxiliary variables. The performances of the suggested estimators have been assessed using three actual data. Furthermore, a simulation investigation is also accompanied to evaluate the effectiveness of estimators. The proposed estimators have a smaller MSE and an advanced PRE when linked to existing estimators, which are based on actual data sets and simulation studies. Theoretically and empirically studies also reveal that the suggested estimators accomplish well than the usual estimators.

A case series of 2,4 diethylamine poisoning - what the future holds for us.

2,4-Diethylamine (2,4-D) is a chlorphenoxy herbicide widely used in north India, marketed as 'Sohna' and 'Zura'. Multi-organ dysfunction and mortality is high in cases of accidental or suicidal ingestion owing to the lack of any antidote. We report a case series of 2,4-D poisoning from a single tertiary centre of north India managed with variable outcomes.

New generalized class of estimators for estimation of finite population mean based on probability proportional to size sampling using two auxiliary variables: A simulation study.

This article aims to suggest a new generalized class of estimators based on probability proportional to size sampling using two auxiliary variables. The numerical expressions for the bias and mean squared error (MSE) are derived up to the first order of approximation. Four actual data sets are used to examine the performances of a new improved generalized class of estimators. From the results of real data sets, it is examined that the suggested estimator gives the minimum MSE and the percentage relative efficiency is higher than all existing estimators, which shows the importance of the new generalized class of estimators. To check the strength and generalizability of our proposed class of estimators, a simulation study is also accompanied. The consequence of the simulation study shows the worth of newly found proposed class estimators. Overall, we get to the conclusion that the proposed estimator outperforms as compared to all other estimators taken into account in this study.

Pure Red Cell Aplasia Encountered in a Tertiary Care Hematology Laboratory: A Series of Nine Distinctive Cases.

Pure red cell aplasia (PRCA) is characterized by severe anemia with reticulocytopenia and bone marrow erythroblastopenia. The early erythroblasts are markedly decreased; however, in rare instances, they may be normal or raised in number. There are varied etiologies, namely congenital or acquired and primary or secondary. The congenital PRCA is known as "Diamond-Blackfan anemia." Thymomas, autoimmune disease, lymphomas, infections, and drugs also may be familiar associates. However, the etiologies of PRCA are numerous, and many diseases/infections can be associated with PRCA. The diagnosis rests on clinical suspicion and appropriate laboratory workup. We evaluated nine cases of red cell aplasia, having severe anemia with reticulocytopenia. Nearly half of the cases showed adequate erythroid (> 5% of the differential count) but with a maturation arrest. The adequacy of the erythroid could confuse the hematologist and may even delay the diagnosis. Hence, it is empirical that PRCA could be considered a differential in every case of severe anemia with reticulocytopenia, even in the presence of adequate erythroid precursors in the bone marrow.

A simulation study: An enhanced generalized class of estimators for estimation of population proportion using twofold auxiliary attribute.

The article introduces a novel class of estimators designed for estimating finite population proportions. These estimators utilize dual auxiliary attributes and are applicable under simple random sampling. The proposed class of estimators includes various members with distinct characteristics. The article provides numerical terminologies for the bias and MSE of the estimators, acquire up to first order of approximation. Four actual data sets are used. Additionally, a simulation study is accompanied to perceive the presentations of estimators. The MSE criterion is used to assess how well the proposed estimator performed as likened to the preliminary estimators. The simulation analysis revealed that, in contrast to other examined estimators, the suggested class of estimators provided better results. The empirical investigation offers evidence to substantiate the findings of the argument. Theoretical research also displays that the suggested class of estimators outperforms its competitors.