COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Anxiety symptoms in regular school students in Mumbai City, India.

Aim: Anxiety disorders usually remain undiagnosed in school students owing to the internalized nature of their symptoms. The present study was conducted with the primary objective of evaluating the prevalence of anxiety symptoms in school students in Mumbai. A secondary objective was to assess the impact of variables (age, gender, presence of sibling, and type of school curriculum or school) on anxiety symptoms. Materials and Methods: Study cases (8-15 year olds) were recruited by nonprobability sampling from four English-medium schools. Anxiety was measured using Spence Children's Anxiety Scale (SCAS)-child self-report questionnaire. T-scores (total and subscales) were calculated and cut-off scores of> 60 were considered as significant. Results: Symptoms of overall anxiety were present in 10.8% (53/493) of the students. Older students (12-15 year olds) had greater odds of having overall anxiety symptoms (crude OR = 4.36, 95% CI 2.27 to 8.39, P < 0.0001). Symptoms of all anxiety disorders were present in the 493 participants, with obsessions/compulsions and fears of physical injury being the most common (in 29.6% and 27.2%, respectively). Older students and boys had greater odds of having obsessions/compulsions (crude OR = 2.32, 95% CI 1.56 to 3.44, P < 0.0001; and crude OR = 1.54, 95% CI 1.04 to 2.27, P= 0.035, respectively]. Students with sibling (s) had greater odds of having fears of physical injury (crude OR = 0.48, 95% CI 0.30 to 0.78, P= 0.003). Conclusions: There is an urgent need to screen school students in our city for anxiety disorders.

A Case of MDMA-Associated Cerebral and Pulmonary Edema Requiring ECMO.

A 20-year-old female presented with confusion, generalized tonic-clonic seizures, and severe hyponatremia after ingesting 3,4-methylenedioxymethamphetamine (MDMA). Brain computed tomography (CT) demonstrated cerebral edema. Her hospital course was rapidly complicated by respiratory failure and shock requiring intubation and vasopressors. Refractory acute respiratory distress syndrome (ARDS) was diagnosed which was unresponsive to conventional and salvage therapies, requiring initiation of extracorporeal membrane oxygenation (ECMO), leading to normalization of oxygenation parameters. Hyponatremia was corrected and the encephalopathy resolved. The patient was decannulated and extubated after three days. MDMA-induced hyponatremia is hypothesized to result from enhanced serotonergic activity and arginine vasopressin (AVP) release in the brain leading to hyperthermia-induced polydipsia and syndrome of inappropriate antidiuretic hormone (SIADH) secretion. A common but often unrecognized complication of severe hyponatremia is the Ayus-Arieff syndrome where cerebral edema causes neurogenic pulmonary edema via centrally mediated increases in catecholamine release and capillary injury. For our patient, ECMO was required for three days while the hyponatremia was corrected which led to rapid clearing of the cerebral edema and neurogenic pulmonary edema. This case illustrates that, in selecting patients with refractory ARDS from MDMA-associated cerebral and pulmonary edema, ECMO may be a temporizing and life-saving modality of treatment.

Demonstrating an In Situ Topological Band Transition in Cylindrical Granular Chains.

We numerically investigate and experimentally demonstrate an in situ topological band transition in a highly tunable mechanical system made of cylindrical granular particles. This system allows us to tune its interparticle stiffness in a controllable way, simply by changing the contact angles between the cylinders. The spatial variation of particles' stiffness results in an in situ transition of the system's topology. This manifests as the emergence of a boundary mode in the finite system, which we observe experimentally via laser Doppler vibrometry. When two topologically different systems are placed adjacently, we analytically predict and computationally and experimentally demonstrate the existence of a finite-frequency topologically protected mode at their interface.

Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer.

Anti-estrogen and anti-HER2 treatments have been among the first and most successful examples of targeted therapy for breast cancer (BC). However, the treatment of triple-negative BC (TNBC) that lack estrogen receptor expression or HER2 amplification remains a major challenge. We previously discovered that approximately two-thirds of TNBCs express vitamin D receptor (VDR) and/or androgen receptor (AR) and hypothesized that TNBCs co-expressing AR and VDR (HR2-av TNBC) could be treated by targeting both of these hormone receptors. To evaluate the feasibility of VDR/AR-targeted therapy in TNBC, we characterized 15 different BC lines and identified 2 HR2-av TNBC lines and examined the changes in their phenotype, viability, and proliferation after VDR and AR-targeted treatment. Treatment of BC cell lines with VDR or AR agonists inhibited cell viability in a receptor-dependent manner, and their combination appeared to inhibit cell viability additively. Moreover, cell viability was further decreased when AR/VDR agonist hormones were combined with chemotherapeutic drugs. The mechanisms of inhibition by AR/VDR agonist hormones included cell cycle arrest and apoptosis in TNBC cell lines. In addition, AR/VDR agonist hormones induced differentiation and inhibited cancer stem cells (CSCs) measured by reduction in tumorsphere formation efficiency, high aldehyde dehydrogenase activity, and CSC markers. Surprisingly, we found that AR antagonists inhibited proliferation of most BC cell lines in an AR-independent manner, raising questions regarding their mechanism of action. In summary, AR/VDR-targeted agonist hormone therapy can inhibit HR2-av TNBC through multiple mechanisms in a receptor-dependent manner and can be combined with chemotherapy.

Is anxiety more common in school students with newly diagnosed specific learning disabilities? A cross-sectional questionnaire-based study in Mumbai, Maharashtra, India.

BACKGROUND AND OBJECTIVES: School students with specific learning disabilities (SpLDs) experience chronic academic underachievement and resultant stress. The present study aimed to determine if school students with newly diagnosed SpLD were more likely to have anxiety than their regular peers. MATERIALS AND METHODS: The study cases (aged 8-15 years) were recruited from our institute's learning disability clinic. The matched controls were recruited from four schools in Mumbai, Maharashtra, India. Anxiety was measured using the Spence Children's Anxiety Scale (SCAS)-child self-report version questionnaire. Median SCAS scores and the proportion of students with an SCAS score in the "clinical anxiety" range were compared between the groups. RESULTS: SCAS scores were significantly higher in 8-11-year-old learning-disabled male and female students (P < 0.0001 for both groups) and 12-15-year-old female students (P = 0.004), as compared with matched controls. A significantly higher number of learning-disabled students were found to have "clinical anxiety" [24.64% vs. 4.35%, crude odds ratio (OR) = 7.19, 95% confidence interval (CI) 2.91-17.78, P = 0.0001], as compared with the controls regardless of gender, age group, presence of comorbid attention-deficit/hyperactivity disorder (ADHD), or associated medical conditions. A significantly higher proportion of 8-11-year-old learning-disabled students, especially males, were found to have "clinical anxiety" as compared with 12-15-year-old learning-disabled students (crude OR = 4.38, 95% CI 1.94-9.92, P = 0.0004). Gender, presence of comorbid ADHD or associated medical conditions, and type of school attended or curriculum did not impact the prevalence of "clinical anxiety" in learning-disabled students. INTERPRETATION AND CONCLUSIONS: Students with newly diagnosed SpLD have greater odds of being "clinically anxious" relative to their regular peers. We recommend screening for anxiety in children with SpLD immediately after diagnosis so that their optimum rehabilitation can be facilitated.

Caregiving, dyadic quality of life and dyadic relationships in lupus.

AIMS: Systemic lupus erythematosus (SLE) mostly affects young women, adversely affecting their quality of life (QOL). Caregivers may experience caregiver burden (CGB), and it may lower the quality of their relationship. Herein we studied caregiving and CGB and their effects on QOL and relationships in SLE. METHODS: We recruited 10 dyads from the Lupus Clinic. Data collected included demographics, CGB (CGB Scale, screen for CGB), QOL (SF-36) and the quality of the dyadic relationship (Dyadic Adjustment Scale (DAS)). We calculated correlation coefficients for associations between (i) CGB and (ii) dyadic QOL or DAS. RESULTS: The mean (± SD) age of SLE patients was 35.2 (± 9) years and of caregivers was 37.3 (± 9.64) years. The mean (± SD, min-max) total CGB score was 9.1 (± 5.8, 0-19). The caregiver's QOL correlated strongly with some of the domains of the patient's QOL. The SLE-related CGB was associated with the caregiver's own QOL and their SLE partner's QOL. The dyadic DAS was linked to the patient's QOL. CONCLUSIONS: Because (i) CGB in SLE is associated with the caregiver's own QOL and with their SLE partner's QOL, and because (ii) the dyadic DAS score is linked primarily to the patient's QOL, then to optimize patient health outcomes and to decrease CGB, focus should be not only on the patient but should include the dyadic unit.Significant findings: To optimize patient outcomes of SLE patients, focus should be on the dyadic unit. CGB in SLE is associated with the caregiver's own QOL and with the SLE partner's QOL, making it crucial to study this relationship in more detail.

Screening patients with tuberculosis for diabetes mellitus in Gujarat, India.

SETTING: Anklav Tuberculosis Unit, Anand, Gujarat, India. OBJECTIVE: To determine in a cohort of TB patients 1) the prevalence of diabetes (DM) and impaired fasting glucose (IFG), 2) the time taken for diagnosis, 3) demographic and clinical factors associated with DM and IFG, and 4) the number needed to screen (NNS) for diagnosing new cases of DM and IFG. DESIGN: Descriptive study. TB patients registered between January and September 2012 were asked whether they had a history of DM. Those with unknown DM were tested for random and fasting blood glucose (FBG). FBG of ≥126 mg/dl and 110-125 mg/dl were considered indicative of DM and IFG, respectively. RESULTS: Of 556 TB patients, 553 (99%) were assessed: 36 (6.5%) had diabetes (14 had been previously diagnosed DM and 22 were newly diagnosed), and 39 (7%) had IFG. The median (interquartile range) time to DM diagnosis was 5 (1-17) days. Age ≥35 years was associated with DM. The NNS was 25 and 14 for one new case of DM and IFG, respectively, with a lower NNS in males, those aged ≥35 years, those with smear-positive pulmonary TB, retreatment patients and smokers. CONCLUSION: This pilot project shows that it is feasible and valuable to screen patients with TB for DM in a routine setting, resulting in earlier identification of DM and opportunities for better management of comorbidity.

A novel intravaginal delivery system for itraconazole: in vitro and in vivo evaluation.

The purpose of the present study was to formulate and systematically evaluate in vitro, ex vivo and in vivo performances of itraconazole containing bioadhesive vaginal film. We introduce here a novel intravaginal delivery system for itraconazole based on solid dispersion of itraconazole and hydroxypropyl methylcellulose E15 that improve drug solubility and produce bioadhesive system in presence of other ingredients. Solid dispersions of itraconazole were prepared with hydroxypropyl methylcellulose by a spray drying method and characterized by X-ray diffraction and differential scanning calorimetry. The film was prepared using a solvent evaporation technique. In the in vitro antimicrobial study, it was found that solid dispersion containing formulation improves antimicrobial action of itraconazole. From the ex vivo retention study, it was found that the bioadhesive polymers hold the film upto 7 hours on the vaginal mucosa. In vivo antifungal activity tested against Candida albicans vaginitis in female rats, was found to significantly improve the therapeutic benefit of the drug. At 6 days post-dose, the c.f.u. of Candida albicans was more than 10(3) fold decreased in film treated groups without affecting the morphology of vaginal mucosa. These studies suggested that bioadhesive vaginal film is a novel approach for delivery of itraconazole as topical drug delivery system for treating vaginal candidiasis.

Simultaneous determination of salbutamol sulphate, bromhexine hydrochloride and etofylline in pharmaceutical formulations with the use of four rapid derivative spectrophotometric methods.

Four simple, rapid, accurate, precise, reliable and economical spectrophotometric methods have been proposed for simultaneous determination of salbutamol sulphate (SS), bromhexine hydrochloride (BH) and etofylline (ET) in pure and commercial formulations without any prior separation or purification. They were first derivative zero crossing spectrophotometry (method 1), simultaneous equation method (method 2), derivative ratio spectra zero crossing method (method 3) and double divisor ratio spectra derivative method (method 4). The ranges for SS, BH and ET were found to be 1-35 microg mL(-1), 4-40 microg mL(-1) and 5-80 microg mL(-1). For methods 1 and 2, the values of limit of detection (LOD) were 0.2314 microg mL(-1), 0.4865 microg mL(-1) and 0.2766 microg mL(-1) and the values of limit of quantitation (LOQ) were 0.7712 microg mL(-1), 1.6217 microg mL(-1) and 0.9221 microg mL(-1) for SS, BH and ET, respectively. For method 3, LOD values were 0.3297 microg mL(-1), 0.2784 microg mL(-1) and 0.7906 microg mL(-1) and LOQ values were 0.9325 microg mL(-1), 0.9282 microg mL(-1) and 2.6352 microg mL(-1) for SS, BH and ET, respectively. For method 4, LOD values were 0.3161 microg mL(-1), 0.2495 microg mL(-1) and 0.2064 microg mL(-1) and LOQ values were 0.9869 microg mL(-1), 0.8317 microg mL(-1) and 0.6879 microg mL(-1) for SS, BH and ET. The precision values were less then 2% R.S.D. for all four methods. The common excipients and additives did not interfere in their determinations. The results obtained by the proposed methods have been statistically compared by means of Student t-test and by the variance ratio F-test.

Magnetic resonance identification of an accessory submandibular duct and gland: an unusual variant.

UNLABELLED: We report a case of an accessory submandibular gland and duct which is extremely rare. MATERIAL AND METHODS: A 20-year-old male presented with complaints of painful swelling in the right submandibular region. As a part of the radiological investigation, a radiograph occlusal view was taken digital sialography, magnetic resonance imaging and magnetic resonance sialography were performed. RESULTS: Digital sialography revealed a small calculus distal to the punctum with diffuse dilatation of the main duct and intraglandular branches, which passed out spontaneously prior to magnetic resonance examination. The presence of an accessory submandibular duct was well delineated on both digital as well as magnetic resonance sialography. CONCLUSIONS: Magnetic resonance sialography is helpful in delineating the anatomy of the submandibular duct non-invasively and without associated radiation exposure. To the best of our knowledge this is the first report of magnetic resonance identifying an accessory submandibular duct and gland.

Biocatalytic decolourisation of molasses by Phanerochaete chrysosporium.

Bioremediation potential of Phanerochaete chrysosporium strains NCIM 1073, NCIM 1106 and NCIM 1197 to decolourise molasses in solid and liquid molasses media was studied. Strains varied in the pattern of molasses decolourisation on solid medium by Giant colony method. Under submerged cultivation conditions, strain NCIM 1073 did not decolourise molasses while, strains NCIM 1106 and NCIM 1197 could decolourise molasses up to 82% and 76%, respectively. Under stationary cultivation conditions, none of the strains could decolourise molasses. This was overcome by increasing the surface area of the culture in flat bottom glass bottles under stationary cultivation conditions. Under submerged cultivation conditions, growth was more or less same in all strains. However, the lignin peroxidase and manganese peroxidase activities were significantly less in the strain NCIM 1073. Under stationary cultivation conditions, none of the strains could produce enzymes lignin peroxidase, manganese peroxidase and laccase. However, all of them could produce lignin peroxidase and manganese peroxidase when cultivated in flat bottom glass bottles under stationary cultivation conditions.

Gross alpha determination in drinking water using a highly specific resin and LSC.

Some results of experiments concerning a new highly specific resin for the extraction of alpha-emitting nuclides from drinking water samples are presented. The product used during these experiments is a new extraction chromatographic resin which consists of a combination of several reagents and extractants supported on inert polymeric substrates, called "Resin" hereafter. It shows strong affinity for Actinides in the tri-, tetra- and hexavalent oxidation state, as well as for radium, even in presence of large amounts of calcium. Gross-alpha activities were determined using alpha-/beta-discrimination liquid scintillation counting (alpha-/beta-LSC) by direct measurement of the dried resin after extraction. Counting conditions were optimised accordingly. A method for the determination of alpha-emitting nuclides in drinking water was developed and tested using intercomparison and spiked drinking water samples.

In vitro and in vivo anti-Candida activity and toxicology of LY121019.

LY121019 (N-p-octyloxybenzoylechinocandin B nucleus) is a semisynthetic antifungal antibiotic that possesses potent anti-Candida activity. The MIC50 and the MIC90 for both LY121019 and amphotericin B were 0.625 and 1.25 micrograms/ml, respectively. Only an 8-fold increase in the MIC against C. albicans occurred during 34-day exposure to subinhibitory concentrations indicating that LY121019 has a low potential for causing resistance development. Scanning electron microscopic studies revealed that LY121019 caused severe damage to the C. albicans cell. The ED50's for LY121019 and amphotericin B administered parenterally to mice were 7.4 and 2.5 mg/kg, respectively. Parenterally administered LY121019 at doses of 6.25 mg/kg significantly reduced the recovery of C. albicans from infected mouse kidneys. Orally administered 50 and 100 mg/kg doses of LY121019 were effective in eliminating C. albicans from the gastrointestinal tract of infected mice. Topical application of 5% LY121019 was as effective as 3% nystatin in the treatment of superficial C. albicans infections. Local administration of LY121019, nystatin, or miconazole was effective against rat vaginal candidiasis. LY121019 was administered intravenously to dogs at doses up to 100 mg/kg/day, 5 days a week for 3 months; all dogs survived. Compound related effects included a histamine-like reaction, increased serum alkaline phosphatase and SGPT, fatty vacuolization of the liver, and some tissue damage at the injection site. The no effect dose in dog was 10 mg/kg. LY121019 had no more than 1/20 the toxicity of amphotericin B in the dog.

A32390A, a new biologically active metabolite. III. In vitro and in vivo antifungal activity.

A32390A, an isonitrile-containing derivative of mannitol, represents a new class of antifungal antibiotics. In vitro antifungal activity of A32390A was found against Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum. In vivo antifungal activity of A32390A was demonstrated in mice infected with C. albicans. Accumulative doses of 37.5 approximately 600 mg/kg, administered subcutaneously over a 24-hour period, showed significant activity without demonstrating toxicity. A32390A was effective, but not as effective as amphotericin B, in reducing the number of Candida cells isolated from the kidney of infected mice. Urinary excretion of A32390A accounted for only 10% of the administered dose. Improved bioavailability of A32390A was accomplished when the antibiotic was combined with polyvinyl pyrrolidone (PVP) in a solid dispersion. Administration of A32390A as a 10% dispersion in PVP resulted in increased urinary excretion of the drug and reduced the amount of drug required for in vivo activity.