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ObjectiveMucormycosis is a rapidly progressive and fulminant fungal infection mainly affecting the nose and paranasal sinuses and often requiring aggressive surgical debridement, which commonly includes inferior maxillectomy. Conventional inferior maxillectomy involves removal of the bony hard palate and its mucoperiosteum. This can lead to formation of an oroantral fistula and thereby increase the morbidity in these patients leading to prolonged rehabilitation. Subperiosteal inferior maxillectomy involves sparing of the uninvolved mucoperiosteum of the hard palate. This flap is used for closure of the oroantral fistula, which preserves the functional capabilities of the patient, such as speech, mastication and deglutination.MethodThis case series describes the experience of using the technique of mucosa-preserving subperiosteal inferior maxillectomy in five patients with mucormycosis.ResultsWith the technique used in this study, complete oronasal separation was achieved in all six patients. The overall surgery time was also decreased when compared with free tissue transfer. Patients also did not have to bear the weight of prosthesis.ConclusionMucoperiosteal palatal flap-preserving subperiosteal inferior maxillectomy is an excellent approach for all patients with mucormycosis and healthy palatal mucosa.

Summary Background Zoonotic tuberculosis is defined as human infection with Mycobacterium bovis. Although globally, India has the largest number of human tuberculosis cases and the largest cattle population, in which bovine tuberculosis is endemic, the burden of zoonotic tuberculosis is unknown. The aim of this study was to obtain estimates of the human prevalence of animal-associated members of the Mycobacterium tuberculosis complex (MTBC) at a large referral hospital in India. Methods We did a molecular epidemiological surveillance study of 940 positive mycobacteria growth indicator tube (MGIT) cultures, collected from patients visiting the outpatient department at Christian Medical College (Vellore, India) with suspected tuberculosis between Oct 1, 2018, and March 31, 2019. A PCR-based approach was applied to subspeciate cultures. Isolates identified as MTBC other than M tuberculosis or as inconclusive on PCR were subject to whole-genome sequencing (WGS), and phylogenetically compared with publicly available MTBC sequences from south Asia. Sequences from WGS were deposited in the National Center for Biotechnology Information Sequence Read Archive, accession number SRP226525 (BioProject database number PRJNA575883). Findings The 940 MGIT cultures were from 548 pulmonary and 392 extrapulmonary samples. A conclusive identification was obtained for all 940 isolates; wild-type M bovis was not identified. The isolates consisted of M tuberculosis (913 [97·1%] isolates), Mycobacterium orygis (seven [0·7%]), M bovis BCG (five [0·5%]), and non-tuberculous mycobacteria (15 [1·6%]). Subspecies were assigned for 25 isolates by WGS, which were analysed against 715 MTBC sequences from south Asia. Among the 715 genomes, no M bovis was identified. Four isolates of cattle origin were dispersed among human sequences within M tuberculosis lineage 1, and the seven M orygis isolates from human MGIT cultures were dispersed among sequences from cattle. Interpretation M bovis prevalence in humans is an inadequate proxy of zoonotic tuberculosis. The recovery of M orygis from humans highlights the need to use a broadened definition, including MTBC subspecies such as M orygis, to investigate zoonotic tuberculosis. The identification of M tuberculosis in cattle also reinforces the need for One Health investigations in countries with endemic bovine tuberculosis. Funding Bill & Melinda Gates Foundation, Canadian Institutes for Health Research.

Newcastle disease virus (NDV) causes Newcastle disease (ND) in poultry. The ND is a highly contagious disease, which is endemic in several countries despite regular vaccination with live or killed vaccines. Studies on NDV in India are mostly targeted toward its detection and characterization from disease outbreaks. A surveillance study was undertaken to determine NDV prevalence throughout the state of Haryana from March 2018 to March 2020 using a stratified sampling scheme. The state was divided into three different zones and a total of 4,001 choanal swab samples were collected from backyard poultry, commercial broilers, and layers. These samples were tested for the M gene of NDV using real-time RT-PCR. Of the 4,001 samples tested, 392 were positive (9.8% apparent prevalence; 95% CI: 8.9–10.8%) for the M gene. Of these 392 M gene positive samples, 35 (8.9%; 95% CI: 6.4–12.3%) were found to be positive based on F gene real-time RT-PCR. Circulation of NDV in commercial and backyard poultry highlights the importance of surveillance studies even in apparently healthy flocks. The information generated in this study should contribute to better understanding of NDV epidemiology in India and may help formulate appropriate disease control strategies for commercial and backyard birds.

Methionine biosynthetic pathway, essential for the growth of Mycobacterium tuberculosis (Mtb) in the host, represents an attractive target for the development of novel anti-tuberculars. Here, we have biochemically characterized homoserine acetyl transferase (HSAT viz. MetA) of Mtb, which catalyses the first committed step of methionine and S-adenosylmethionine (SAM) biosynthesis. High-throughput screening of a 2300 compound library resulted in identification of thiram, an anti-fungal organosulfur compound, as the most potent MetA inhibitor. Further analysis of thiram analogs led to the identification of orally bioavailable disulfiram (DIS, an anti-alcoholism FDA approved drug) as a novel inhibitor of MetA. Both thiram and DIS restricted the growth of drug-sensitive and drug-resistant Mtb strains in a bactericidal manner. ThermoFlour assay demonstrated direct binding of DIS with MetA. Metabolomic and transcriptomic studies showed DIS mediated perturbation of methionine and redox homeostasis, respectively, in Mtb. In concordance, the effect of DIS on Mtb growth was partially rescued by supplementation with either L-methionine as well as N-acetyl cysteine, suggesting a multi-target killing mechanism. In Mtb-infected mice, DIS administration restricted bacterial growth, increased efficacy of isoniazid, ameliorated lung pathology, modulated lung immune cell landscape and protective immune response. Taken together, our results demonstrate that DIS can be repurposed for designing an effective anti-tubercular therapy.

Methionine biosynthetic pathway, essential for the growth of Mycobacterium tuberculosis (Mtb) in the host, represents an attractive target for the development of novel anti-tuberculars. Here, we have biochemically characterized homoserine acetyl transferase (HSAT viz. MetA) of Mtb, which catalyses the first committed step of methionine and S-adenosylmethionine (SAM) biosynthesis. High-throughput screening of a 2300 compound library resulted in identification of thiram, an anti-fungal organosulfur compound, as the most potent MetA inhibitor. Further analysis of thiram analogs led to the identification of orally bioavailable disulfiram (DIS, an anti-alcoholism FDA approved drug) as a novel inhibitor of MetA. Both thiram and DIS restricted the growth of drug-sensitive and drug-resistant Mtb strains in a bactericidal manner. ThermoFlour assay demonstrated direct binding of DIS with MetA. Metabolomic and transcriptomic studies showed DIS mediated perturbation of methionine and redox homeostasis, respectively, in Mtb. In concordance, the effect of DIS on Mtb growth was partially rescued by supplementation with either L-methionine as well as N-acetyl cysteine, suggesting a multi-target killing mechanism. In Mtb-infected mice, DIS administration restricted bacterial growth, increased efficacy of isoniazid, ameliorated lung pathology, modulated lung immune cell landscape and protective immune response. Taken together, our results demonstrate that DIS can be repurposed for designing an effective anti-tubercular therapy. Funding Statement: The research fellowship to D.C. and T.P.G. from Department of Biotechnology, Govt. of India is acknowledged. Ava.S. fellowship was supported by the University of Grants commission. R.B. acknowledges Department of Science and Technology India and FICCI for providing C.V. Raman International fellowship. R.S. acknowledge THSTI, and Department of Biotechnology, Govt. of India (BT/PR29075/BRB/10/1699/2018) for funding. This research was supported by SIgN A*STAR, A*STAR JCO-CDA grant (#1518251030), and Singapore-India Joint grant (#1518224018) to A.S. Declaration of Interests: None. Ethics Approval Statement: The proposed animal experiments were approved by the institutional animal ethics committee of Defence Science Organization (DSO), Singapore.

Parapharyngeal space is an infrequent site for foreign bodies to lodge. Presence of neurovascular structures in this space mandates immediate and meticulous removal of the foreign body to prevent any complications. In this case report, we present a rare case of metallic foreign body (sewing needle) in the parapharyngeal space that was removed using external approach without any complications after appropriate imaging (contrast-enhanced computed tomography). Only one case has been reported so far in the literature and ours is the second one.

BackgroundZoonotic tuberculosis (zTB) is the transmission ofMycobacterium tuberculosiscomplex (MTBC) subspecies from animals to humans. zTB is generally quantified by determining the proportion of human isolates that areMycobacterium bovis. Although India has the world’s largest number of human TB cases and the largest cattle population, where bovine TB is endemic, the burden of zTB is unknown.MethodsTo obtain estimates of zTB in India, a PCR-based approach was applied to sub-speciate positive MGIT® cultures from 940 patients (548 pulmonary, 392 extrapulmonary disease) at a large referral hospital in India. Twenty-five isolates of interest were subject to whole genome sequencing (WGS) and compared with 715 publicly available MTBC sequences from South Asia.FindingsA conclusive identification was obtained for 939 samples; wildtypeM. boviswas not identified (95% CI: 0 – 0.4%). There were 912M. tuberculosis sensu stricto(97.0%, 95% CI: 95.7 – 98.0), 7M. orygis(95% CI: 0.3 – 1.5%); 5M. bovisBCG, and 15 non-tuberculous mycobacteria. WGS analysis of 715 MTBC sequences again identified noM. bovis(95% CI: 0 – 0.4%). Human and cattle MTBC isolates were interspersed within theM. orgyisandM. tuberculosis sensu strictolineages.InterpretationM. bovisprevalence in humans is an inadequate proxy of zTB in India. The recovery ofM. orygisfrom humans, together with the finding ofM. tuberculosisin cattle, underscores the need for One Health investigations to assess the burden of zTB in countries with endemic bovine TB.FundingBill & Melinda Gates Foundation, Canadian Institutes for Health Research

Bromelain, a cysteine protease exhibits promising potential in amelioration of wide variety of inflammatory disorders. Its denaturation or aggregation in gastric milieu depletes its therapeutic potential along with unpredictable prophylactic hypersensitivity reactions. Hence, efficient carrier system to improve bromelain's stability and avoid related side effects is of utmost importance. Therefore, present investigation was undertaken to prepare bromelain loaded nanostructured lipid carriers (Br-NCs) with high drug loading, stability and efficacy in rheumatoid arthritis management. Br-NCs fabricated via double emulsion solvent evaporation method were characterized for physical properties, morphology and stability. Optimized batch exhibited spherical shape, nanometric size (298.23 nm) and entrapment efficiency ~77% with sustained release behavior and improved gastric stability. Br-NCs exhibited 4.63-folds improvement in shelf-life compared to bromelain at room temperature. The protective potential of orally administered Br-NCs in rheumatoid arthritis was evaluated via assessing arthritis severity in wistar rats along with biochemical, hematological and immunological parameters. Br-NCs remarkably (p 0.05) diminished paw edema, joint stiffness, mechanical allodynia and tissue damage along with alleviation of oxidative stress and immunological markers. Radiological joint alterations were also notably preserved with Br-NCs. Thus, preclinical studies distinctly manifested that Br-NCs formulation opens new avenue for development of novel effective therapeutic modality for rheumatoid arthritis management.

Salinity stress severely affects growth, nodulation and yield of chickpea (Cicer arietinum L.). However, inoculation with Mesorhizobium strains containing 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase improves the plant growth by reducing the level of ethylene induced by salt stress. Fifty (50) Mesorhizobium isolates were obtained from nodules of chickpea plants on yeast extract mannitol agar (YEMA) medium. Mesorhizobium isolates were screened for ACC utilization and growth at different salt concentrations in YEMA medium. Six salt tolerant Mesorhizobium isolates were checked for their role in plant growth promotion under pot house conditions in chillum jar assembly. Mesorhizobium strains having ACC utilization ability caused an increase in the nodule number, nodule weight and shoot dry weight after plant growth for 50 and 80 days, both with and without NaCl. Mesorhizobium isolate MBD26 showed 294 mg/plant shoot dry weight without salt condition after 50 days of plant growth. Mesorhizobium isolate MBD26 increased shoot dry weight by 49.52% (without salt) and 41.53% in the presence of salt (40 mM NaCl) after 80 days of plant growth. It was observed that inoculation with Mesorhizobium isolates containing ACC-deaminase improved nodulation and plant growth of chickpea over ACC deaminase lacking isolates. Thus, inoculation with Mesorhizobium strains possessing ACC utilization ability could be a sustainable approach to improve plant growth under salinity stress. Key words: 1-Aminocyclopropane-1-carboxylic acid (ACC) utilization, salt stress, Mesorhizobium, chickpea, nodulation, plant growth.

A 16 week feeding trial was conducted with 140 White Leghorn layers of 22-23±0.08 weeks of age which were distributed randomly into seven experimental groups, having 4 replicates with 5 birds in each. The laying hens of control group (T1) were fed a basal diet (CP 18.04%), while in treatment groups T2, T3, T4 basal diet was supplemented with probiotic (containing 5×108 cfu/g of Lactobacillus fermentum, 1×109 cfu/g of Bacillus spp., 1×109cfu/g of Saccharomyces cerevisiae) at levels of 0.5g, 1.0 g and 2.0 g /kg feed, respectively, while in T5, T6, and T7 0.5g, 1.0g and 2.0g/kg feed of prebiotic (mannonoligosacchride of Saccharomyces cell wall-47g, formic acid-32g) was supplemented, respectively. The percent hen day egg production and feed efficiency (kg/dozen eggs and kg/kg egg mass) were improved (P less than 0.05) in probiotic and prebiotic incorporated diets. The mRNA expression levels of Toll like receptors (TLRs) TLR2 and TLR4 was increased (P less than 0.05) when graded levels of the probiotic and prebiotic were supplemented, while, TLR7 did not show any significant change. Thus, it can be inferred that the inclusion of the probiotic and prebiotic could enhance the production performance and immune status of birds by augmenting the T cell mediated immune response.

Brucellosis is one of the zoonotic diseases of major concern and can cause huge economic losses to livestock industry. Serological tests and bacterial isolation are considered as the gold standard assay for diagnosis of Brucella spp. but they are time-consuming, hazardous and lack specificity. To control and eradicate a disease, a confirmatory diagnostic method which is sensitive, quick and specific is the foremost requirement. Therefore in this study, we evaluated the performances of two newly designed TaqMan real-time PCR assays targeting the BruAB_0168 gene and BMEII0466 gene for Brucella abortus and Brucella melitensis (respectively). Both the assays were found to be highly specific in differentiation of respective species. Both the assays can detect as low as 0.02 fg of DNA and there was no detectable difference found in sensitivity of these two tests. R2 value and efficiency of these tests ranged from 0.992 - 0.998 and 100- 106%, respectively showing that these assays are highly efficient. Compared to conventional PCR assays these qPCR assays were 100 times higher sensitive. In conclusion, the present study showed that the developed real-time PCR assays are more sensitive, specific, have high reproducibility and repeatability and are faster than serological and conventional PCR methods for differentiation of Brucella abortus and Brucella melitensis.

A rare case of splenic abscess occurring after blunt abdominal trauma in a previously healthy boy is reported. The diagnosis was made by ultrasonography. The patient recovered after splenectomy and drainage of subphrenic and intraperitoneal pus.

Renal vein thrombosis (RVT) may be fatal, particularly when it occurs bilaterally. We report a neonate who recovered from bilateral RVT on supportive management alone. A 2450 g male infant was born at term gestation to a non-diabetic mother. The anmiotic fluid contained particulate mecoilium. The Apgar scores were 1 and 3 at 1 and 5 minutes, respecfivelyl Postnatal course was complicated by shock and meconium aspiration syndrome. At 36 hours of age, he developed gross hematuria and oliguria. Abdominal examination revealed smooth, firm masses in both flanks. Urinanlysis showed gross hematufia, proteinuria (2+) and epithelial casts. Blood urea and serum creafinine were 110 mg/dl,. and 3.8 mg/dl, respectively. Serum electrolytes were normal. Hemoglobin was 16 g/dl; platelets 75,000/cu ram; prothrombin time 24.2 sec (control 13 sec); and partial thromboplastin time 65 sec (control 50 sec). Ultrasonography showed enlargement of both tl,e kidneys, the fight measuring 62 mm and the left 67 nun. The thrombus was not visualized. An intravenous pyetogram done on the 13th day of illness showed nonvisualizafion of both the kidneys with faint opacificafion of the bladder. Doppler study was not performed.