Epsilon subunit of T-complex protein-1 from Leishmania donovani: A tetrameric chaperonin.

The cytosolic T-complex protein-1 ring complex (TRiC), also referred as chaperonin containing TCP-1(CCT), comprising eight different subunits stacked in double toroidal rings, binds to around 10 % of newly synthesized polypeptides and facilitates their folding in ATP dependent manner. In Leishmania, among five subunits of TCP1 complex, identified either by transcriptome or by proteome analysis, only LdTCP1γ has been well characterized. It forms biologically active homo-oligomeric complex and plays role in protein folding and parasite survival. Lack of information regarding rest of the TCP1 subunits and its structural configuration laid down the necessity to study individual subunits and their role in parasite pathogenicity. The present study involves the cloning, expression and biochemical characterization of TCP1ε subunit (LdTCP1ε) of Leishmania donovani, the causative agent of visceral leishmaniasis. LdTCP1ε exhibited significant difference in primary structure as compared to LdTCP1γ and was evolutionary close to LdTCP1 zeta subunit. Recombinant protein (rLdTCP1ε) exhibited two major bands of 132 kDa and 240 kDa on native-PAGE that corresponds to the dimeric and tetrameric assembly of the epsilon subunit, which showed the chaperonin activity (ATPase and luciferase refolding activity). LdTCP1ε also displayed an increased expression upto 2.7- and 1.8-fold in the late log phase and stationary phase promastigotes and exhibited majorly vesicular localization. The study, thus for the first time, provides an insight for the presence of highly diverge but functionally active dimeric/tetrameric TCP1 epsilon subunit in Leishmania parasite.

Innovative Technique of Chest Wall Reconstruction After Extensive Tumour Ablation Surgery.

Chest wall reconstruction is among one of the most challenging surgeries because the defect comprises multiple components and each needs to be reconstructed separately with like tissues. Chest wall reconstruction ranges from simple skin cover to complex bony and or mediastinal/precordial reconstruction. Various methods of reconstruction include autologous as well alloplastic techniques. Autologous techniques include regional or distant flaps with or without bone. Whereas alloplastic techniques include the placement of a variety of implant materials like titanium plate/mesh, stainless steel mesh, medpore and biocompatible 3D-printed models. we present this article where extensive resection was performed, aiming to complete removal of recurrent chest wall chondrosarcoma and defect included all components of chest wall including precordial lining. The reconstruction was performed by using combined autologous as well as alloplastic techniques using acrylic implant.

CoII-catalysed synthesis of N-(4-meth-oxy-phen-yl)-5-(pyridin-4-yl)-1,3,4-oxa-diazol-2-amine hemi-hydro-chloride monohydrate.

The title compound, C14H12N4O2·0.5HCl·H2O or H(C14H12N4O2)2 +·Cl-·2H2O, arose from the unexpected cyclization of isonicotinoyl-N-phenyl hydrazine carbo-thio-amide catalysed by cobalt(II) acetate. The organic mol-ecule is almost planar and a symmetric N⋯H+⋯N hydrogen bond links two of them together, with the H atom lying on a crystallographic twofold axis. The extended structure features N-H⋯O and O-H⋯Cl hydrogen bonds, which generate [001] chains. Weak C-H⋯Cl inter-actions cross-link the chains. The chloride ion has site symmetry 2. The major contributions to the Hirshfeld surface are from H⋯H (47.1%), Cl⋯H/H⋯Cl (total 10.8%), O⋯H/H⋯O (7.4%) and N⋯H/H⋯N (6.7%) inter-actions.

Treatment Options for Municipal Solid Waste by Composting and Its Challenges.

Recovery and recycling of municipal solid waste biodegradable fraction (50-55%) are essential for attaining sustainability and a circular economy. Among organic waste treatment methods, composting is used to recycle organic fractions of waste. However, only 10-12% of municipal solid waste is utilized for composting treatment due to a lack of segregation practices and process challenges, including long process periods, odorous and greenhouse gas emissions, nitrogen loss, and low compost quality, which hinders large-scale practice. The current review paper discusses the challenges of composting treatment and its possible solutions. Various strategies were explored to address these challenges, such as utilizing microbial inoculum, additives, and optimization of physicochemical parameters. It also emphasizes the application of metagenomics for exploring key species. The knowledge about the microbial community and biochemical pathways (genome mining) can be exploited for the improvement of treatment efficiency. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01087-4.

Protocol for Treatment of Oral Verrucous Carcinoma - A Systematic Review and Meta-Analysis.

Background: The objective of this study is to provide a structured protocol for the treatment of verrucous carcinoma (VC) based on size, bone invasion, recurrence and whether neck dissection is necessary or not. In addition, the study evaluates the probability of a wrong histopathological diagnosis. Data Sources: A search was conducted in the Cochrane Library, PubMed and Google from January 1962 to October 2022 by using MeSH terms and keywords. Studies reporting treatment modalities for VC and different histopathological diagnoses after excision of the lesion were selected except case reports and review articles. Study Eligibility Criteria: Thirteen articles were selected. Six hundred and thirty cases of VC were treated by surgery, surgery + neck dissection, radiotherapy, chemotherapy and combination therapy. Statistical analysis revealed surgical treatment as a preferred option. Despite being enlarged, the lymph node was negative for metastasis. So, in OVC cases neck dissection adds only unnecessary morbidity to patients. Participants and Interventions: Radiotherapy or chemotherapy can be used to downstage the disease. 23.3% of cases reported wrong histopathology diagnosis. Study Appraisal and Synthesis Methods: Patients treated for squamous cell carcinoma (SCC) will only experience unnecessary morbidity unless the correct diagnosis is made between VC and hybrid VC. Irrespective of size VC does not metastasise until there are no foci of SCC. Conclusions: Surgical excision of T1- and T2-sized lesions can be performed under local anaesthetic as a biopsy procedure. T3 or T4 lesion can be resected with a safe margin. If it comes as hybrid VC or VC with close margin (0.5 cm, <0.5 cm), neck dissection and further margin should be excised as a second procedure respectively.

Revisiting extracranial cysticercosis: A rare case series of mycoparasitism affecting the cervicofacial region from an endemic zone.

A systemic parasitic infestation caused by the larval stages of the pork tapeworm, Taenia solium is known as Cysticercosis. While encysted form of the larval stage is attributed to rare variant of Cysticercosis of soft tissues. Muscle infestation by this parasite can lead to vague clinical presentation. We are presenting a series of 4 rare cases of extracranial, cervicofacial cysticercosis their clinical attributes and imaging characteristics leading to diagnosis of cysticercosis and approach to successful outcome with pharmacotherapy alone that spared the need of surgical management.

Omicron BA.2 lineage predominance in severe acute respiratory syndrome coronavirus 2 positive cases during the third wave in North India.

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India. Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7. Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men. Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.

Leishmania donovani Dipeptidylcarboxypeptidase Inhibitor as a Potential Oral Treatment for Visceral Leishmaniasis.

Chemotherapy is the key intervention to control visceral leishmaniasis (VL), a neglected tropical disease. Current regimens include not only a few drugs but also present several drawbacks, including moderate to severe toxicity, cost, long-term administration, patient compliance, and growing drug resistance. Thus, the need for better treatment options against VL is a priority. In an endeavor to find an orally active and affordable antileishmanial agent, we evaluated the therapeutic potential of compounds belonging to the (2Z,2'Z)-3,3'-(ethane-1,2-diylbis(azanediyl))bis(1-(4-halophenyl)-6-hydroxyhex-2-en-1-ones) series, identified as inhibitor(s) of Leishmania donovani dipeptidylcarboxypeptidase, a novel drug target. Among them, compound 3c exhibited best in vivo antileishmanial efficacy via both intraperitoneal and oral routes. Therefore, the present study led to the identification of compound 3c as the lead candidate for treating VL.

Downregulation of gamma subunit of TCP1 chaperonin of Leishmania donovani modulates extracellular vesicles-mediated macrophage microbicidal function.

T-complex protein-1 (TCP1) is a group II chaperonin, known to fold various proteins like actin and tubulin. In Leishmania donovani only one subunit that is gamma subunit (LdTCP1γ) has been functionally characterized as a homo-oligomeric complex that exhibits ATP-dependent protein folding. The gene is essential for the survival and infectivity of the parasite. Leishmania parasite releases extracellular vesicles (EVs) containing numerous virulence factors, which play an essential role in parasite pathogenesis and modulate host immune cell signaling. The present study demonstrates that LdTCP1γ is secreted in the EVs and modulates host macrophage functions. EVs isolated from LdTCP1γ single-allele-replacement mutants significantly upregulate the microbicidal function of LPS-induced macrophage as evident by increased levels of proinflammatory cytokines (TNF-α, IL-6), iNOS and NO production. Further, the comparative proteomics of wild-type and single-allele-replacement mutant EVs showed that out of 876 identified proteins, 207 were significantly modulated. Among them, the top 50 modulated and abundantly secreted proteins constitute ∼40% of the total identified protein intensity and include virulence factors such as GP63, peroxiredoxin, enolase, HSP70, elongation factor 2, amastin, eukaryotic translation initiation factor and α-tubulin. The comparative proteomic analysis revealed that the proteome enrichment of the EVs from LdTCP1γ single-allele replacement mutants significantly differs from wild-type EVs, which may be responsible for the altered host microbicidal responses. Thus, our data provide new insight into the role of LdTCP1γ in EVs-mediated host-parasite interactions.

Ultrafine particle number concentration and its size distribution during Diwali festival in megacity Delhi, India: Are 'green crackers' safe?

Since the air pollution and noise generated from fireworks are related to air quality and human health, the regulatory bodies had implemented the eco-friendly "Green Crackers" in megacity Delhi, India, to celebrate Diwali 2019 with the permission of a specific time slot (8:00 p.m. to 10:00 p.m.). The present study was conducted on a residential educational institute campus to evaluate the particle number size distribution (PNSD) of green cracker emissions. During the Diwali event period, the high peak of particle number concentration (PNC) reached 1.7 × 105 # cm-3 with a geometric mean diameter (GMD) of ∼44 nm. The average PNC increment on Diwali day was 138% and 97% compared to pre (October 26, 2019) and post (October 28, 2019) Diwali period, respectively, including 468%, 142%, 65%, 75% on pre-Diwali and 485%, 110%, 32%, 26% on post- Diwali 2019 period in terms of Nucleation mode (10 nm < Dp < 20 nm), Small Aitken mode (20 nm < Dp < 50 nm), Large Aitken mode (50 nm < Dp < 100 nm), and Accumulation mode (100 nm < Dp < 1000 nm), respectively. Unlike traditional firework emissions, green crackers had a high UFP/Ntotal ratio of 0.72, including Nucleation mode-0.35, Aitken mode-0.30, and Accumulation mode 0.35, distinguishing it from other pre-and post-Diwali particle number size distribution-dN/dlogDp curves. These observations indicate that green crackers emit more particles with smaller diameters than traditional crackers. Recommendations for using green crackers for Diwali celebrations may be an option if lower size-diameter particle emission could be controlled by changing the material composition of the green crackers. More research studies need to be conducted to assess atmospheric emissions of green crackers and their health impacts to evaluate whether they are better or worse than traditional crackers.

Progress in Diagnosis and Treatment of Neonatal Sepsis: A Review Article.

Neonatal sepsis is a serious condition in which the pathogens infiltrate the bloodstream, multiply and produce toxins causing deleterious effects to the health of neonates. It is divided into two types on the basis of the time of onset. Early onset sepsis occurs within 72 hours of birth and late onset sepsis begins after 72 hours of delivery. Neonatal sepsis continues to be a common and significant health care burden, especially in very low birth weight infants (with birthweight less than 1500 grams). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remain a challenge. Keywords: cytokines; immunoglobulin; neonatal sepsis; procalcitonin.

Dipeptidylcarboxypeptidase of Leishmania donovani: A potential vaccine molecule against experimental visceral leishmaniasis.

Visceral leishmaniasis is one of the deadliest parasitic diseases in the world. In the absence of an efficient and cost-effective drugs, development of an effective vaccine is the need of the day. In spite of several efforts, a successful vaccine against the disease has been elusive. We have evaluated immunoprophylactic efficacy of recombinant dipeptidycarboxypeptidase (rLdDCP), predominantly expressed in amastigotes, in chronic hamster model. rLdDCP induced in vitro lymphoproliferation and NO production in cured hamsters. Immunization with rLdDCP alone, or with BCG, caused significant reduction in parasite load suggesting strong protective response. The molecule also augmented the CMI response as depicted by an increased lymphocyte proliferation, NO production, DTH responses and increased levels of IgG2 in immunized hamsters. The vaccinated hamsters exhibited a surge in IFN-γ, TNF-α, IL-12 and iNOS levels but down-regulation of IL-10 and IL-4. Thus, the results suggest the potentiality of the rLdDCP as a strong candidate vaccine.

Depredation loss drives human-wildlife conflict perception in the Trans-Himalayas.

Communities in and around protected areas are exposed to a higher level of human-wildlife interactions. The conservation practice with persistently adverse local livelihood outcomes can potentially aggravate such interactions leading to conflict. In our study, we examined how perceptions of HWC have formed in a protected area of the Trans-Himalayas whose conservation program collides with a centuries-long tradition of transhumance pastoralism. To examine determinants of depredation and how conflict perception has developed there, along with the socioeconomic and ecological interactions underlying those trends, we collected data using household surveys, key informant interviews, and focus group discussions. We employed Poisson-logit maximum-likelihood hurdle, binary logit, and multinomial ordered logit regressions in order to explore the determinants of annual livestock depredation, predator attacks on the shed, and household-level perceptions of HWC, respectively. Depredation and encounters with wildlife were the principal causes of perceived HWC, and depredation caused an average household-level loss of US $422.5, up to 23.28% of annual income in some households. Predators' attacks on high-quality sheds were relatively infrequent but more common in areas with perceived habitat degradation. Social customs, pastoral practices, and the present compensation mechanism were identified as being antithetical to conflict reduction and sustainable pastureland management. Further analysis revealed that a diversity of livelihoods, however, lowered conflict perception formation. The identified socio-ecological factors will continue to increase depredation, exacerbate perceived HWC, and degrade pastureland unless local conservation authorities take appropriate remedial measures.

Unraveling of interacting protein network of chaperonin TCP1 gamma subunit of Leishmania donovani.

T-complex polypeptide-1 (TCP1) is a group II chaperonin that folds various cellular proteins. About 10% of cytosolic proteins in yeast have been shown to flux through the TCP1 protein complex indicating that it interacts and folds a plethora of substrate proteins that perform essential functions. In Leishmania donovani, the gamma subunit of TCP1 (LdTCP1γ) has been shown to form a homo-oligomeric complex and exhibited ATP-dependent protein folding activity. LdTCP1γ is essential for the growth and infectivity of the parasite. The interacting partners of L. donovani TCP1γ, involved in many cellular processes, are far from being understood. In this study, we utilized co-immunoprecipitation assay coupled with liquid chromatography-mass spectrometry (LC-MS) to unravel protein-protein interaction (PPI) networks of LdTCP1γ in the L. donovani parasite. Label-free quantification (LFQ) proteomic analysis revealed 719 interacting partners of LdTCP1γ. String analysis showed that LdTCP1γ interacts with all subunits of TCP1 complex as well as other proteins belonging to pathways like metabolic process, ribosome, protein folding, sorting, and degradation. Trypanothione reductase, identified as one of the interacting partners, is refolded by LdTCP1γ. In addition, the differential expression of LdTCP1γ modulates the trypanothione reductase activity in L. donovani parasite. The study provides novel insight into the role of LdTCP1γ that will pave the way to better understand parasite biology by identifying the interacting partners of this chaperonin.

Assessment of the effect of the judicial prohibition on firecracker celebration at the Diwali festival on air quality in Delhi, India.

Diwali (the festival of lights and crackers) is celebrated grandly, resulting in a significant drop in the city's air quality. To study the impact of the judicial prohibition in Delhi to improve air quality, a comprehensive and comparative analysis was conducted over two consecutive years, namely 2015-2016 (when no significant regulations on the sale or usage of firecrackers were imposed) and 2017-2018 (when radically different regulations were implemented). Data on PM10, PM2.5, NOx, and CO were analysed, and their trends and levels with various regulations in place were compared. In 2017, the concentrations of PM10, PM2.5, NOx, and CO were reduced by 50%, 50%, 71%, and 64%, respectively, compared to 2016. However, in 2018, there was an increase of 32% in PM10 and PM2.5 concentrations, as well as a 25% increase in CO concentrations, with the exception of NOx, which decreased to 25% on Diwali day. The data was also examined in conjunction with the entire timeline of the various court rulings and regulations imposed in Delhi. The questionnaire survey study revealed that, despite the legislation in place, ambient air quality continued to deteriorate, necessitating a deeper dive into the policy's structure and implementation to fine-tune its feasibility and applications. Air pollution-related health effects were recognized by 82% of participants. Despite this, only 13% of people were observed without a mask, and only 12% of people were aware of green crackers as of 2018. To combat this deteriorating situation, the national capital must enact radical and well-thought-out legislation and regulations governing firecrackers, as well as raise public awareness amongst its citizens.

Immunological characterization of rLdTCP1γ for its prophylactic potential against visceral leishmaniasis in hamster model.

Visceral leishmaniasis (VL) is a chronic tropical disease responsible for devastating epidemics worldwide. Though current treatment relies on drugs, the emergence of resistance, toxic side-effects, and strenuous administration has led to an ineffective remedy. Hence, vaccination remains an alternative and desirable approach for VL control. Though extensive research on anti-leishmanial vaccine candidates has been carried out in past decades, presence of an effective molecule is still missing. In the present study, we have evaluated the immunogenicity and prophylactic potential of a recombinant T-complex protein-1 gamma subunit of L. donovani (rLdTCP1γ), against VL in hamster model. The antigen exhibited in vitro stimulation of lymphoproliferative and NO response in miltefosine and amphotericin B treated hamsters depicting its immunotherapeutic/immunogenic nature. Immunization with rLdTCP1γ revealed a strong protective response against experimental VL as indicated by reduced parasite load in the spleen of immunized group compared to infected control. The immunized animals gained body weight and exhibited significant reduction in the spleen and liver weight as compared to infected controls on days 60, 90, 120 post-challenge. A substantial augmentation of cell-mediated immune response as depicted by an increased lymphocyte proliferation, nitric oxide production, DTH responses and increased levels of IgG2 was observed in rLdTCP1γ immunized hamsters. The Th1 stimulatory potential, imparted by the antigen, was found to be intensified in the presence of adjuvant Bacillus Calmette-Guérin (BCG). The efficacy was further assisted by an upregulated mRNA transcript of Th1 induced cytokines (IL-12, IFN-γ and TNFα) and downregulation of IL-4 and IL-10. The results are thus suggestive of rLdTCP1γ having the potential of a strong vaccine candidate against VL.

Hypothyroidism Induced Hyponatremia: A Case Report.

Thyroid hormones have various effects on the body which include electrolyte and water hemostasis. It is also involved in renal development and physiology. Hyponatremia is a serious electrolyte imbalance that can be associated with the involvement of different body systems and a wide range of deleterious changes. We report a case of a 62-years-old female with the symptoms of severe hyponatremia like altered mental sensorium with a serum sodium level of 110 meq/l. After ruling out other causes, a final diagnosis of hypothyroidism was made. On treating hypothyroidism the symptoms of hyponatremia were resolved. Therefore, thyroid stimulating hormone determination is mandatory during the evaluation of hyponatremia. And, those patients should be treated with fluid restriction and treatment of hypothyroidism.

Status Dystonicus with Atypical Presentation in Developmentally Delay Child: A Case Report.

Status dystonicus is characterised by involuntary sustained or intermittent muscle contractions of muscles causing repetitive twisting movements, abnormal postures of the body, or both is a rare but life-threatening movement disorder. Early diagnosis and management of status dystonicus prevent serious complications. We report a 2 years old previously developmental delay diagnosed girl who presented with generalised contractions of the whole body. Tightening of limbs is aggravated by touching her backside which is a very unique feature. Dystonia is associated with severe sweating and was confused with a seizure event. The patient was treated with midazolam, clonidine, phenytoin, gabapentin, pyridoxine, baclofen, and trihexyphenidyl. She was admitted to the intensive care unit for monitoring. The patient partially recovered after 10 days of treatment. Keywords: aspiration; children; dystonia; epilepsy; pneumonia.

Case Report: Ovarian fibroma: typical presentation with Meigs's Syndrome.

Meigs's syndrome is characterized by a triad of ovarian fibroma, ascites, and pleural effusion which can be managed surgically. Pleural effusion and ascites are usually transudative. Ovarian fibroma is an uncommon tumor. We herein report a case of Meigs's syndrome in a 61-year-old woman who presented with complaints of abdominal pain for two-three months along with decreased appetite and constipation. On examination, there was decreased air entry in the right side of the chest, generalized abdominal distention, and a firm irregular mass was felt which was mobile and extending from upper border of symphysis pubis to just above the umbilicus on abdominal palpation. Chest X ray showed right sided pleural effusion, ultrasonogram (USG) abdominal and pelvis showed gross ascites, and a very large complex right ovarian cyst was confirmed by computed tomography (CT) scan. She underwent staging laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy and omental resection for biopsy. Biopsy showed right ovarian fibroma.