COVID-19 and environmental -weather markers: Unfolding baseline levels and veracity of linkages in tropical India.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe due to its contagion nature. We hereby report the baseline permanent levels of two most toxic air pollutants in top ranked mega cities of India. This could be made possible for the first time due to the unprecedented COVID-19 lockdown emission scenario. The study also unfolds the association of COVID-19 with different environmental and weather markers. Although there are numerous confounding factors for the pandemic, we find a strong association of COVID-19 mortality with baseline PM2.5 levels (80% correlation) to which the population is chronically exposed and may be considered as one of the critical factors. The COVID-19 morbidity is found to be moderately anti-correlated with maximum temperature during the pandemic period (-56%). Findings although preliminary but provide a first line of information for epidemiologists and may be useful for the development of effective health risk management policies.

Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab.

BACKGROUND: There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE: To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. METHODS: Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. RESULTS: Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. CONCLUSION: During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.

Accurate Quantum Monte Carlo Forces for Machine-Learned Force Fields: Ethanol as a Benchmark.

Quantum Monte Carlo (QMC) is a powerful method to calculate accurate energies and forces for molecular systems. In this work, we demonstrate how we can obtain accurate QMC forces for the fluxional ethanol molecule at room temperature by using either multideterminant Jastrow-Slater wave functions in variational Monte Carlo or just a single determinant in diffusion Monte Carlo. The excellent performance of our protocols is assessed against high-level coupled cluster calculations on a diverse set of representative configurations of the system. Finally, we train machine-learning force fields on the QMC forces and compare them to models trained on coupled cluster reference data, showing that a force field based on the diffusion Monte Carlo forces with a single determinant can faithfully reproduce coupled cluster power spectra in molecular dynamics simulations.

Process-based diagnostics of extreme pollution trail using numerical modelling during fatal second COVID-19 wave in the Indian capital.

The world's worst outbreak, the second COVID-19 wave, not only unleashed unprecedented devastation of human life, but also made an impact of lockdown in the Indian capital, New Delhi, in particulate matter (PM: PM2.5 and PM10) virtually ineffective during April to May 2021. The air quality remained not only unabated but also was marred by some unusual extreme pollution events. SAFAR-framework model simulations with different sensitivity experiments were conducted using the newly developed lockdown emission inventory to understand various processes responsible for these anomalies in PM. Model results well captured the magnitude and variations of the observed PM before and after the lockdown but significantly underestimated their levels in the initial period of lockdown followed by the first high pollution event when the mortality counts were at their peak (∼400 deaths/day). It is believed that an unaccounted emission source was playing a leading role after balancing off the impact of curtailed lockdown emissions. The model suggests that the unprecedented surge in PM10 (690 µg/m3) on May 23, 2021, though Delhi was still under lockdown, was associated with large-scale dust transport originating from the north west part of India combined with the thunderstorm. The rainfall and local dust lifting played decisive roles in other unusual events. Obtained results and the proposed interpretation are likely to enhance our understanding and envisaged to help policymakers to frame suitable strategies in such kinds of emergencies in the future.

Growth of textured nanocrystalline cobalt ferrite thin films by pulsed laser deposition.

Cobalt ferrite thin films have been deposited on fused quartz substrates by pulsed laser deposition at various substrate temperatures, T(s) (25 degrees C, 300 degrees C, 550 degrees C and 750 degrees C). Single phase, nanocrystalline, spinel cobalt ferrite formation is confirmed by X-ray diffraction (XRD) for T(s) > or = 300 degrees C. Conventional XRD studies reveal strong (111) texturing in the as deposited films with T(s) > or = 550 degrees C. Bulk texture measurements using X-ray orientation distribution function confirmed (111) preferred orientation in the films with T(s) > or = 550 degrees C. Grain size (13-16 nm for T(s) > or = 300 degrees C) estimation using grazing incidence X-ray line broadening analysis shows insignificant grain growth with increasing T(s), which is in good agreement with grain size data obtained from transmission electron microscopy.

Pre- and posttreatment MR imaging findings in lead encephalopathy.

A 41-year-old man suspected of having lead poisoning was evaluated with MR imaging before and after British antilewisite therapy. The MR imaging findings showed bilateral symmetric involvement of the occipital lobe, affecting predominantly the gray-white matter junction and the subcortical white matter. A right cerebellar lesion was noted, with focal hyperintensities involving the gray-white matter. Similar lesions were seen in the temporal, parietal, and frontal regions. These lesions resolved after chelation therapy.

Onychoprotothecosis: An uncommon presentation of protothecosis.

Onychomycosis is a fairly common condition seen in a dermatology clinic. Dermatophytes Trichophyton and Epidermophyton are the known filamentous fungi implicated. The yeast-like fungi such as Candida less commonly cause Onychomycosis. The genus Prototheca may on preliminary observation resemble yeast-like fungi but a detailed microscopy will reveal the absence of budding and presence of endospores. Onychoprotothecosis is an uncommon presentation of human protothecosis. Of the two Prototheca species (Prototheca zopfii and Prototheca wickerhamii) known to cause the disease, P. wickerhamii has been reported more commonly. We report a culture proven case of this condition caused by P. zopfii. The patient, a 55-year-old housewife presented with discolouration and breaking off of the right thumb and forefinger nails since a period of six months. Samples of nail scrapping sent to the Microbiology Laboratory were culture-positive for Prototheca. Speciation by the automated Vitek-2 system (bioMerieux) identified the isolate as P. zopfii, which was further confirmed at PGI, Chandigarh.

Platelet Na,K-adenosine triphosphatase as a tissue marker of hyperthyroidism.

Platelet Na(+),K(+)-adenosine triphosphatase (ATPase) activity was measured in 34 (15 males, 19 females) healthy subjects, 89 (35 males, 54 females) hyperthyroid patients, and 34 (7 males, 27 females) treated hyperthyroid patients to assess the potential of this measurement as a tissue marker and diagnostic test for hyperthyroidism. Platelet Na(+),K(+)-ATPase activity was measured in platelet lysates by the rate of release of phosphate from adenosine triphosphate (ATP) in the presence and absence of ouabain. Platelet Na(+),K(+)-ATPase activity (median and range) in the hyperthyroid group (271, 169 to 821 pmol/h/g protein) was significantly higher compared with the healthy group (125, 74 to 185 micromol/h/g protein, P <.001 by Mann-Whitney U test). The treated hyperthyroid group had slightly, but significantly higher, free triiodothyronine (FT3) and free thyroxine (FT4), as well as platelet Na(+),K(+)-ATPase activity (147, 98 to 246 micromol/h/g protein, P <.05). If a platelet Na(+),K(+)-ATPase activity of 190 micromol/h/g protein was used as a cut off value, the specificity and sensitivity were 90% and 93%, respectively. We conclude that platelet Na(+),K(+)-ATPase may be a useful tissue marker of hyperthyroidism.

Frequency-domain photon migration measurements for quantitative assessment of powder absorbance: A novel sensor of blend homogeneity.

The measurement and analysis of frequency-domain photon migration (FDPM) measurements of powder absorbance in pharmaceutical powders is described in the context of other optical techniques. FDPM consists of launching intensity-modulated light into a powder and detecting the phase delay and amplitude modulation of the re-emitted light as a function of the modulation frequency. From analysis of the data using the diffusion approximation to the radiative transport equation, the absorption coefficient can be obtained. Absorption coefficient measurements of riboflavin in lactose mixtures are presented at concentrations of 0.1 to 1% (w/w) at near-infrared wavelengths where solution absorption cross sections are difficult to accurately measure using traditional transmission measurements in nonscattering solutions. FDPM measurements in powders enabled determinations of absorption coefficients that increase linearly with concentration (w/w) according to Beer-Lambert relationship. The extension of FDPM for monitoring absorbance of low-dose and ultralow-dose powder blending operations is presented.

In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis.

OBJECTIVE: To examine whether sodium pump activity plays a part in the pathogenesis of thyrotoxic periodic paralysis. DESIGN: Measurement of platelet sodium-potassium ATPase and in vivo sodium pump activities in healthy subjects and thyrotoxic subjects with and without paralysis. SETTING: University hospital in Hong Kong. SUBJECTS: 21 healthy subjects, 23 untreated thyrotoxic subjects, 13 untreated men with periodic paralysis, seven treated thyrotoxic subjects, and six treated men with periodic paralysis. MAIN OUTCOME MEASURES: Platelet Na+, K(+)-ATPase activity and plasma rubidium concentration after oral loading. RESULTS: Median (range) platelet Na+, K(+)-ATPase activity in thyrotoxic subjects was 253 (169-821) mumol inorganic phosphate/h/g protein--significantly higher than that in healthy subjects (134 (81-180) mumol/h/g protein; p less than 0.001). Na+, K(+)-ATPase activity in those with periodic paralysis was 374 (195-1196) mumol/h/g protein, again significantly higher than that in healthy subjects (p less than 0.001) and that in other thyrotoxic subjects (p less than 0.01) despite similar degrees of hyperthyroidism. Activities in treated thyrotoxic subjects with and without periodic paralysis were 148 (110-234) and 131 (86-173) mumol/h/g protein respectively. Mean (95% confidence interval) plasma rubidium concentration five hours after oral administration in thyrotoxic subjects (7.0 (6.6 to 7.5) mumol/l) was significantly lower than in healthy subjects (10.2 (9.5 to 10.9) mumol/l; p less than 0.001) and higher than in those with periodic paralysis (6.0 (5.7 to 6.3) mumol/l; p less than 0.01). CONCLUSIONS: Sodium pump activity in untreated subjects with periodic paralysis is higher than in other thyrotoxic subjects, and this may be responsible for the hypokalaemia.

Multidrug-resistant Vibrio cholerae O1 in Belgaum, south India.

An outbreak of acute diarrhoea occurred in the Belgundi area (population 3896) of Belgaum Taluka (population 815 581) in Karnataka, South India, in June 2010. An estimated 16.22 % of people were affected and 0.16 % deaths were reported. Vibrio cholerae O1 El Tor was isolated from 18 of the 147 stool samples cultured. Seven out of eight drinking water samples collected from different sources were found to be grossly contaminated with faecal coliforms. All isolates were multidrug resistant, with some showing resistance to quinolones, gentamicin and cephalosporins in addition to co-trimoxazole and tetracycline, the drugs that were being used by the state health authorities for empirical treatment. Two serotypes and at least eight genotypes of V. cholerae were observed among the isolates. Cholera was confirmed as one, if not the only, cause of the outbreak, which, to our belief, is the first report of cholera from this region. It might have occurred due to a 'flare up' in the number of endemic strains triggered by shortage of portable water, onset of monsoon rains and breakdown of sanitation systems, rather than being a de novo outbreak arising out of new exogenous infectious sources. A change in the empirical treatment, coupled with chlorination, improvement in sanitation measures and extensive Information Education Communication activities, resulted in decline of the outbreak and prevention of further deaths.

A fatal case of empyema thoracis by Nocardia farcinica in an immunocompromised patient.

Empyema thoracis by Nocardia farcinica infection is uncommon. Here we report a rare and fatal infection in a 27-year-old HIV- seropositive male who presented with cough, expectoration, and breathlessness. Nocardia farcinica was isolated from sputum and pus from the pleural cavity. Confirmation of the isolate and minimum inhibitory concentrations (MIC) for various antibiotics was done at the Aerobic Actinomycetes Reference Laboratory, Centres for Disease Control and Prevention (CDC), Atlanta. Patient was treated with suitable antibiotics and antiretroviral drugs in spite of which he eventually succumbed to the disease.

Meningitis due to Rhodotorula glutinis in an HIV infected patient.

Rhodotorula spp, though considered a common saprophyte, recently has been reported as causative agent of opportunistic mycoses. We present a case of meningitis in an immunocompromised human immunodeficiency virus infected patient who presented with longstanding fever. He was diagnosed as a case of chronic meningitis. Diagnosis was confirmed by cell cytology, India ink preparation, Gram staining and culture of cerebrospinal fluid (CSF) sample. CSF culture grew Rhodotorula glutinis. Therapy with amphotericin B was successful in eliminating the yeast from CSF and the patient was discharged after recovery.

Review of clinical and laboratory features of human brucellosis.

Infection with Brucella spp. continues to pose a human health risk globally despite strides in eradicating the disease from domestic animals. Brucellosis has been an emerging disease since the discovery of Brucella melitensis by Sir David Bruce in 1887. Although many countries have eradicated B. abortus from cattle, in some areas B. melitensis and B. suis have emerged as causes of this infection in cattle, leading to human infections. Currently B. melitensis remains the principal cause of human brucellosis worldwide including India. The recent isolation of distinct strains of Brucella from marine mammals as well as humans is an indicator of an emerging zoonotic disease. Brucellosis in endemic and non-endemic regions remains a diagnostic puzzle due to misleading non-specific manifestations and increasing unusual presentations. Fewer than 10% of human cases of brucellosis may be clinically recognized and treated or reported. Routine serological surveillance is not practiced even in Brucella - endemic countries and we suggest that this should be a part of laboratory testing coupled with a high index of clinical suspicion to improve the level of case detection. The screening of family members of index cases of acute brucellosis in an endemic area should be undertaken to pick up additional unrecognised cases. Rapid and reliable, sensitive and specific, easy to perform and automated detection systems for Brucella spp. are urgently needed to allow early diagnosis and adequate antibiotic therapy in time to decrease morbidity / mortality. The history of travel to endemic countries along with exposure to animals and exotic foods are usually critical to making the clinical diagnosis. Laboratory testing is indispensable for diagnosis. Therefore alertness of clinician and close collaboration with microbiologist are essential even in endemic areas to correctly diagnose and treat this protean human infection. Existing treatment options, largely based on experience gained > 30 years ago, are adequate but not optimal. In our experience, an initial combination therapy with a three drug-regimen followed by a two-drug regimen for at least six weeks and a combination of two drugs with a minimum of six weeks seems warranted to improve outcome in children and adult patients respectively with laboratory monitoring. A safe and effective vaccine in humans is not yet available. Prevention is dependent upon the control of the disease in animal hosts, effective heat treatment of dairy produce and hygienic precautions to prevent occupational exposure. This review compiles the experiences and diagnostic and treatment paradigms currently employed in fighting this disease.