Needle-free injection system delivery of ZyCoV-D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS-CoV-2.

The apprehension of needles related to injection site pain, risk of transmitting bloodborne pathogens, and effective mass immunization have led to the development of a needle-free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCoV-D in rhesus macaques against SARS-CoV-2 infection. Briefly, 20 rhesus macaques were divided into 5 groups (4 animals each), that is, I (1 mg dose by NIS), II (2 mg dose by NIS), III (1 mg dose by NFIS), IV (2 mg dose by NFIS) and V (phosphate-buffer saline [PBS]). The macaques were immunized with the vaccine candidates/PBS intradermally on Days 0, 28, and 56. Subsequently, the animals were challenged with live SARS-CoV-2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5, and 7 days post infection from each animal to determine immune response and viral clearance. Among all the five groups, 2 mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers postvirus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post-SARS-CoV-2 challenge and significant immune response in the immunized animals demonstrated the efficiency of NFIS in delivering 2 mg ZyCoV-D vaccine candidate.

Tobacco and alcohol use among adolescents in Northern India.

Background: Alcohol and cigarette usage are major public health issues that particularly affect young people worldwide. Because most users begin using these drugs well before the age of 18, there are significant psychosocial and health consequences. This study seeks to identify the incidence of underage drinking and smoking in northern India and the multiple risk factors associated with this exposure. Materials and Methods: A cross-sectional study was conducted on adolescents (13-18 years) from Northern India, to assess their knowledge, attitude, and practice of usage of alcohol and tobacco. The study was conducted using a semi-structured questionnaire for interview purposes and analyzed via Epi Info version 7. Results: The mean age of the participants was 16.15 (1.34) years, of which 65.74% are males and 34.26% are females. 18.25% of students stay in a hostel. Of 108 participants, about 24.07% of students have tried their first cigarette before 18 years of age. 28.70% of students have people in their homes, and 41.67% have friends who use tobacco. Among the 108 respondents, 26.85% of students have tried or used alcohol before 18 years of age. Conclusion: It is crucial to create preventive techniques to lessen tobacco use in light of the significant negative health effects that come along with tobacco addiction. Spreading awareness among at-risk children and adolescents by limiting advertising and promotional efforts, early user detection and treatment are all examples of preventive techniques.

Constraining neutron-star matter with microscopic and macroscopic collisions.

Interpreting high-energy, astrophysical phenomena, such as supernova explosions or neutron-star collisions, requires a robust understanding of matter at supranuclear densities. However, our knowledge about dense matter explored in the cores of neutron stars remains limited. Fortunately, dense matter is not probed only in astrophysical observations, but also in terrestrial heavy-ion collision experiments. Here we use Bayesian inference to combine data from astrophysical multi-messenger observations of neutron stars1-9 and from heavy-ion collisions of gold nuclei at relativistic energies10,11 with microscopic nuclear theory calculations12-17 to improve our understanding of dense matter. We find that the inclusion of heavy-ion collision data indicates an increase in the pressure in dense matter relative to previous analyses, shifting neutron-star radii towards larger values, consistent with recent observations by the Neutron Star Interior Composition Explorer mission5-8,18. Our findings show that constraints from heavy-ion collision experiments show a remarkable consistency with multi-messenger observations and provide complementary information on nuclear matter at intermediate densities. This work combines nuclear theory, nuclear experiment and astrophysical observations, and shows how joint analyses can shed light on the properties of neutron-rich supranuclear matter over the density range probed in neutron stars.

Predicted Threshold for Seated Stability: Estimation of Margin of Stability Using Wearable Inertial Sensors.

Individuals with spinal cord injury suffer from seated instability due to impaired trunk neuromuscular function. Monitoring seated stability toward the development of closed-loop controlled neuroprosthetic technologies could be beneficial for restoring trunk stability during sitting in affected individuals. However, there is a lack of (1) a biomechanical characterization to quantify the relationship between the trunk kinematics and sitting balance; and (2) a validated wearable biomedical device for assessing dynamic sitting posture and fall-risk in real-time. This study aims to: (a) determine the limit of dynamic seated stability as a function of the trunk center of mass (COM) position and velocity relative to the base of support; (b) experimentally validate the predicted limit of stability using traditional motion capture; (c) compare the predicted limit of stability with that predicted in the literature for standing and walking; and (d) validate a wearable device for assessing dynamic seated stability and risk of loss of balance. First, we used a six-segment model of the seated human body for simulation. To obtain the limit of stability, we applied forward dynamics and optimization to obtain the maximum feasible initial velocities of the trunk COM that would bring the trunk COM position to the front-end of the base-of-support for a set of initial COM positions. Second, experimental data were obtained from fifteen able-bodied individuals who maintained sitting balance while base-of-support perturbations were applied with three different amplitudes. A motion capture system and four inertial measurement units (IMUs) were used to estimate the trunk COM motion states (i.e., trunk COM position and velocity). The margin of stability was calculated as the shortest distance of the instantaneous COM motion states to those obtained as the limit of stability in the state-space plane. All experimentally obtained trunk COM motion states fell within the limit of stability. A high correlation and small root-mean-square difference were observed between the estimated trunk COM states obtained by the motion capture system and IMUs. IMU-based wearable technology, along with the predicted limit of dynamic seated stability, can estimate the margin of stability during perturbed sitting. Therefore, it has the potential to monitor the seated stability of wheelchair users affected by trunk instability.

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques.

The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

High-Density Polyethylene Material versus Autogenous Grafts in Craniofacial Augmentation Procedures.

AIM: The objective was to do a comparative study and to evaluate the outcome in overall acceptance for correction of residual facial deformity with autogenous graft versus porous polyethylene implants. MATERIALS AND METHODS: A total of 16 patients in the age group of ≥15 years irrespective of sex, caste, religion, and socioeconomic status presenting with signs and symptoms of residual facial deformities and who were declared fit for surgery were included in the study. The study patients were further divided into two groups, of eight each. Deformity correction using autogenous grafts was performed in Group A and using high-density polyethylene (HDPE) alloplastic implants was performed in Group B. During the follow-up period, patients' and doctor rating of overall acceptance between autogenous and alloplastic (HDPE) bone grafts was recorded on 100-mm visual analog scale (VAS) on the 2nd day and 7th day and at 3, 6, and 12 weeks. RESULTS: The unpaired t-test is used for evaluation. VAS score at all the follow-up periods above stated was significantly higher in alloplastic group than in the autogenous group for both in patients and doctor evaluation. CONCLUSION: From the present study, it can be concluded that porous HDPE implants are an effective alternative to autogenous grafts in accordance of overall acceptance for correction of residual facial deformity when proper case selection, exclusion of negative prognostic factors, and meticulous surgical procedure are followed.

Design and Evaluation of an Instrumented Wobble Board for Assessing and Training Dynamic Seated Balance.

Methods that effectively assess and train dynamic seated balance are critical for enhancing functional independence and reducing risk of secondary health complications in the elderly and individuals with neuromuscular impairments. The objective of this research was to devise and validate a portable tool for assessing and training dynamic seated balance. An instrumented wobble board was designed and constructed that (1) elicits multidirectional perturbations in seated individuals, (2) quantifies seated balance proficiency, and (3) provides real-time, kinematics-based vibrotactile feedback. After performing a technical validation study to compare kinematic wobble board measurements against a gold-standard motion capture system, 15 nondisabled participants performed a dynamic sitting task using the wobble board. Our results demonstrate that the tilt angle measurements were highly accurate throughout the range of wobble board dynamics. Furthermore, the posturographic analyses for the dynamic sitting task revealed that the wobble board can effectively discriminate between the different conditions of perturbed balance, demonstrating its potential to serve as a clinical tool for the assessment and training of seated balance. Vibrotactile feedback decreased the variance of wobble board tilt, demonstrating its potential for use as a balance training tool. Unlike similar instrumented tools, the wobble board is portable, requires no laboratory equipment, and can be adjusted to meet the user's balance abilities. While future work is warranted, obtained findings will aid in effective translation of assessment and training techniques to a clinical setting, which has the potential to enhance the diagnosis and prognosis for individuals with seated balance impairments.

Health Issues among Radiologists: Toll they Pay to their Profession.

In modern era, with tremendous competition, long working hours and more demanding workstyle, nearly every profession is associated with some or the other health hazards. These may develop and progress rapidly or in a gradual way but ultimately add up unwanted morbidities and in long run affects the production and work output. Unfortunately, doctors and other health professionals who look after the health of society, are not the exceptions to this rule and depending upon their specialty, they have to face some or the other health issues. This article highlights some important though underestimated health issues among radiologists and some remedies. It aims to sensitize radiologists about such health issues so that they can take timely remedial measures before it is really late.

Recognition of Small Airways Obstruction in Asthma and COPD - The Road Less Travelled.

The small airways, once regarded as the silent zone in the air conducting system of the lungs are now known to be one of the initial sites of involvement in diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD). Identification of the involvement of distal airways in these diseases is often difficult to assess, clinically as well as by conventional pulmonary function tests and therefore, usually remains undiscovered in early stages. Early recognition of their involvement in asthma and COPD and timely management may reduce long term morbidity in these conditions. This article aims to highlight the relatively lesser recognized facts about small airways involvement in asthma and COPD and role of imaging and newer modalities for detection.

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India.

Aspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study analyzed the distribution and in vitro antifungal susceptibility profiles of rare Aspergillus species in clinical samples from patients with suspected aspergillosis in 8 medical centers in India. Further, a matrix-assisted laser desorption ionization-time of flight mass spectrometry in-house database was developed to identify these clinically relevant Aspergillus species. ß-Tubulin and calmodulin gene sequencing identified 45 rare Aspergillus isolates to the species level, except for a solitary isolate. They included 23 less common Aspergillus species belonging to 12 sections, mainly in Circumdati, Nidulantes, Flavi, Terrei, Versicolores, Aspergillus, and Nigri Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified only 8 (38%) of the 23 rare Aspergillus isolates to the species level. Following the creation of an in-house database with the remaining 14 species not available in the Bruker database, the MALDI-TOF MS identification rate increased to 95%. Overall, high MICs of ≥2 µg/ml were noted for amphotericin B in 29% of the rare Aspergillus species, followed by voriconazole in 20% and isavuconazole in 7%, whereas MICs of >0.5 µg/ml for posaconazole were observed in 15% of the isolates. Regarding the clinical diagnoses in 45 patients with positive rare Aspergillus species cultures, 19 (42%) were regarded to represent colonization. In the remaining 26 patients, rare Aspergillus species were the etiologic agent of invasive, chronic, and allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, keratitis, and mycetoma.

Pulmonary Aspergillosis: What CT can Offer Before it is too Late!

Aspergillus is a large genus of saprophytic fungi which are present everywhere in the environment. However, in persons with underlying weakened immune response this innocent bystander can cause fatal illness if timely diagnosis and management is not done. Chest infection is the most common infection caused by Aspergillus in human beings. Radiological investigations particularly Computed Tomography (CT) provides the easiest, rapid and decision making information where tissue diagnosis and culture may be difficult and time-consuming. This article explores the crucial role of CT and offers a bird's eye view of all the radiological patterns encountered in pulmonary aspergillosis viewed in the context of the immune derangement associated with it.

Comparative Evaluation of Several Gene Targets for Designing a Multiplex-PCR for an Early Diagnosis of Extrapulmonary Tuberculosis.

PURPOSE: Diagnosis of extrapulmonary tuberculosis (EPTB) poses serious challenges. A careful selection of appropriate gene targets is essential for designing a multiplex-polymerase chain reaction (M-PCR) assay. MATERIALS AND METHODS: We compared several gene targets of Mycobacterium tuberculosis, including IS6110, devR, and genes encoding MPB-64 (mpb64), 38kDa (pstS1), 65kDa (hsp65), 30kDa (fbpB), ESAT-6 (esat6), and CFP-10 (cfp10) proteins, using PCR assays on 105 EPTB specimens. From these data, we chose the two best gene targets to design an M-PCR. RESULTS: Among all gene targets tested, mpb64 showed the highest sensitivity (84% in confirmed cases and 77.5% in clinically suspected cases), followed by IS6110, hsp65, 38kDa, 30kDa, esat6, cfp10, and devR. We used mpb64+IS6110 for designing an M-PCR assay. Our M-PCR assay demonstrated a high sensitivity of 96% in confirmed EPTB cases and 88.75% in clinically suspected EPTB cases with a high specificity of 100%, taking clinical diagnosis as the gold standard. CONCLUSION: These M-PCR results along with the clinical findings may facilitate an early diagnosis of EPTB patients and clinical management of disease.

The role of fungal sensitisation in clinical presentation in patients with chronic obstructive pulmonary disease.

Atopic patients with chronic obstructive pulmonary disease (COPD) demonstrate more severe symptoms than their non-atopic counterparts. Also, Aspergillus hypersensitivity is known in COPD. However, allergic sensitisation to non-Aspergillus fungi has never been studied in COPD patients. To evaluate the prevalence of fungal sensitisation and its impact on the clinical presentation and outcome of COPD patients. Sensitisation to 17 fungi was studied in 55 COPD patients through skin prick tests, fungus-specific IgE, precipitating antibodies, total IgE and eosinophil counts. The clinical symptoms of patients were monitored thorough a patient-administered questionnaire. Overall, 5.4% (n = 3) of COPD patients were fungus sensitive. The sensitisation was noted to Alternaria alternata and Schizophyllum commune in two patients each, whereas another was sensitive to A. tamarii, Rhizopus spp. and Aspergillus fumigatus. Eosinophils were higher in fungus-sensitised patients (P = 0.001 vs. 0.003). No differences were noted in the clinical presentation of patients sensitised to fungi compared to those not sensitised to fungi or non-atopic. Although low, fungal sensitisation occurs in COPD but it is not limited to Aspergilli alone. Fungus-sensitised patients exhibit greater eosinophilia, implying more severe inflammation. Thus, such patients should be followed up regularly to recognise clinical worsening or development of ABPM.

Molecular epidemiology and in-vitro antifungal susceptibility of Aspergillus terreus species complex isolates in Delhi, India: evidence of genetic diversity by amplified fragment length polymorphism and microsatellite typing.

Aspergillus terreus is emerging as an etiologic agent of invasive aspergillosis in immunocompromised individuals in several medical centers in the world. Infections due to A. terreus are of concern due to its resistance to amphotericin B, in vivo and in vitro, resulting in poor response to antifungal therapy and high mortality. Herein we examined a large collection of molecularly characterized, geographically diverse A. terreus isolates (n = 140) from clinical and environmental sources in India for the occurrence of cryptic A. terreus species. The population structure of the Indian A. terreus isolates and their association with those outside India was determined using microsatellite based typing (STR) technique and Amplified Fragment Length Polymorphism analysis (AFLP). Additionally, in vitro antifungal susceptibility of A. terreus isolates was determined against 7 antifungals. Sequence analyses of the calmodulin locus identified the recently described cryptic species A. hortai, comprising 1.4% of Aspergillus section Terrei isolates cultured from cases of aspergilloma and probable invasive aspergillosis not reported previously. All the nine markers used for STR typing of A. terreus species complex proved to be highly polymorphic. The presence of high genetic diversity revealing 75 distinct genotypes among 101 Indian A. terreus isolates was similar to the marked heterogeneity noticed in the 47 global A. terreus population exhibiting 38 unique genotypes mainly among isolates from North America and Europe. Also, AFLP analysis showed distinct banding patterns for genotypically diverse A. terreus isolates. Furthermore, no correlation between a particular genotype and amphotericin B susceptibility was observed. Overall, 8% of the A. terreus isolates exhibited low MICs of amphotericin B. All the echinocandins and azoles (voriconazole, posaconazole and isavuconazole) demonstrated high potency against all the isolates. The study emphasizes the need of molecular characterization of A. terreus species complex isolates to better understand the ecology, acquisition and transmission of this species.

Recognizing filamentous basidiomycetes as agents of human disease: A review.

Filamentous basidiomycetes (BM) are common environmental fungi that have recently emerged as important human pathogens, inciting a wide array of clinical manifestations that include allergic and invasive diseases. We reviewed 218 reported global cases of BM fungi. The most common etiologic agent was Schizophyllum commune in 52.3% (114/218) of the cases followed by Hormographiella aspergillata (n = 13; 5.9%), Ceriporia lacerata (n = 11; 5%), and, rarely, Volvariella volvacea, Inonotus tropicalis, Irpex lacteus, Phellinus undulates, Perenniporia species, Bjerkandera adusta, Sporotrichum pruinosum, Phanerochaete steroids, and Cyclomyces tabacinus. These fungi are present in the environment as gilled mushrooms, shelf fungi, and bracket fungi. However, in clinical settings, they usually present as nonsporulating white moulds that are difficult to identify. Moreover, the GenBank database of these fungi is limited. Regarding the country-wise distribution of cases, Japan topped the list with about 43% (n = 94) of globally reported cases, followed by India (57; 26%), the United States (4%), Austria (3.2%), Iran (3.2%), France (2.8%), and the remaining one-third from 16 other countries. The respiratory tract was the most commonly afflicted site (n = 71), with the majority of the cases (42; 59.1%) being allergic in etiology and comprising 34 cases of allergic bronchopulmonary mycosis. Also, B. adusta has been implicated in a recently described clinical entity, that is, fungus associated chronic cough, reported exclusively from Japan. BM fungi-incited diseases are currently underdiagnosed due to lack of awareness and expertise, warranting comprehensive epidemiological and susceptibility studies to determine their prevalence and to predict a more appropriate therapy.

Allergic bronchopulmonary mycosis due to fungi other than Aspergillus: a global overview.

Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity-mediated disease of worldwide distribution. We reviewed 143 reported global cases of ABPM due to fungi other than aspergilli. The commonest etiologic agent was Candida albicans, reported in 60% of the cases, followed by Bipolaris species (13%), Schizophyllum commune (11%), Curvularia species (8%), Pseudallescheria boydii species complex (3%) and rarely, Alternaria alternata, Fusarium vasinfectum, Penicillium species, Cladosporium cladosporioides, Stemphylium languinosum, Rhizopus oryzae, C. glabrata, Saccharomyces cerevisiae and Trichosporon beigelii. India accounted for about 47% of the globally reported cases of ABPM, attributed predominantly to C. albicans, followed by Japan (16%) where S. commune predominates, and the remaining one-third from the USA, Australia and Europe. Notably, bronchial asthma was present in only 32% of ABPM cases whereas its association with development of allergic bronchopulmonary aspergillosis (ABPA) is known to be much more frequent. The cases reviewed herein revealed a median IgE value threefold higher than that of ABPA, suggesting that the etiologic agents of ABPM incite a stronger immunological response than that by aspergilli in ABPA. ABPM is currently underdiagnosed, warranting comprehensive basic and clinical studies in order to elucidate its epidemiology and to devise a more effective therapy.

A case of allergic fungal rhinosinusitis due to Ceratocystis adiposa.

Ceratocystis adiposa known as phytopathogen of conifers has not been recognized so far as a human pathogen. Herein, we report for the first time a case of allergic fungal rhinosinusitis due to C. adiposa. The fungus was identified by sequencing internal transcribed spacer of rDNA and D1/D2 of larger subunit region.

First neonatal case of fungaemia due to Pseudozyma aphidis and a global literature review.

The Ustilaginomycetous basidiomycete yeast, Pseudozyma aphidis has recently been implicated in potentially fatal disorders ranging from subcutaneous mycoses to disseminated infections. Till date a solitary case of P. aphidis fungaemia in a paediatric patient has been reported. We present a case of fungaemia due to P. aphidis in a rhesus factor-isoimmunised, low-birth-weight neonate. The isolate was identified by sequencing the D1/D2 domain of the LSU region. Antifungal susceptibility of the isolate revealed susceptibility to amphotericin B, voriconazole, itraconazole, isavuconazole and posaconazole. It had high minimum inhibitory concentrations of fluconazole and was resistant to flucytosine and echinocandins. Consequently, the patient was successfully treated with intravenous amphotericin B. Although the source of infection could not be traced, as the neonate developed fungaemia on the first day of life, it could possibly be from the maternal urogenital tract or intrahospital transmission. A review of previously published cases revealed that risk factors for invasive Pseudozyma spp. infections were similar to those previously reported for non-albicans Candida spp. Pseudozyma species are underreported due to the difficulty of identifying this rare yeast pathogen by commercial identification systems. Considering that Pseudozyma spp. cause invasive fungal infections globally and are resistant to flucytosine, fluconazole and echinocandins, this pathogen assumes a greater clinical significance.

Voriconazole-Resistant Penicillium oxalicum: An Emerging Pathogen in Immunocompromised Hosts.

Penicillium species are rarely reported agents of infections in immunocompromised patients. We report 3 cases of invasive mycosis caused by voriconazole-resistant Penicillium oxalicum in patients with acute myeloid leukemia, diabetes mellitus, and chronic obstructive pulmonary disease, while on voriconazole therapy. Penicillium oxalicum has not been previously recognized as a cause of invasive mycoses.