Latent tuberculosis diagnostics: current scenario and review.

This review presents a comprehensive examination of the contemporary landscape pertaining to latent tuberculosis infection (LTBI) diagnostics, with a particular emphasis on the global ramifications and the intricacies surrounding LTBI diagnosis and treatment. It accentuates the imperative of bolstering diagnostic, preventive, and treatment modalities for tuberculosis (TB) to fulfill the ambitious targets set forth by the World Health Organization aimed at reducing TB-related mortalities and the incidence of new TB cases. The document underscores the significance of addressing LTBI as a means of averting the progression to active TB, particularly in regions burdened with high TB prevalence, such as India. An in-depth analysis of the spectrum delineating latent and active TB disease is provided, elucidating the risk factors predisposing individuals with LTBI to progress towards active TB, including compromised immune functionality, concurrent HIV infection, and other immunosuppressive states. Furthermore, the challenges associated with LTBI diagnosis are elucidated, encompassing the absence of a definitive diagnostic assay, and the merits and demerits of tuberculin skin testing (TST) and interferon-γ release assays (IGRAs) are expounded upon. The document underscores the necessity of confronting these challenges and furnishes a meticulous examination of the advantages and limitations of TST and IGRAs, along with the intricacies involved in interpreting their outcomes across diverse demographics and settings. Additionally, attention is drawn towards the heritability of the interferon-γ response to mycobacterial antigens and the potential utility of antibodies in LTBI diagnosis.

A critical assessment on scalable technologies using high solids loadings in lignocellulose biorefinery: challenges and solutions.

The pretreatment and the enzymatic saccharification are the key steps in the extraction of fermentable sugars for further valorization of lignocellulosic biomass (LCB) to biofuels and value-added products via biochemical and/or chemical conversion routes. Due to low density and high-water absorption capacity of LCB, the large volume of water is required for its processing. Integration of pretreatment, saccharification, and co-fermentation has succeeded and well-reported in the literature. However, there are only few reports on extraction of fermentable sugars from LCB with high biomass loading (>10% Total solids-TS) feasible to industrial reality. Furthermore, the development of enzymatic cocktails can overcome technology hurdles with high biomass loading. Hence, a better understanding of constraints involved in the development of technology with high biomass loading can result in an economical and efficient yield of fermentable sugars for the production of biofuels and bio-chemicals with viable titer, rate, and yield (TRY) at industrial scale. The present review aims to provide a critical assessment on the production of fermentable sugars from lignocelluloses with high solid biomass loading. The impact of inhibitors produced during both pretreatment and saccharification has been elucidated. Moreover, the limitations imposed by high solid loading on efficient mass transfer during saccharification process have been elaborated.

Recent advances in the antioxidant activity of metal-curcumin complexes: a combined computational and experimental review.

Curcumin, an extensively studied phytochemical compound, has gained attention for its potential therapeutic applications across a spectrum of diseases. Its notable attributes include its relatively high tolerability within the human body and its perceived absence of adverse side effects. This review article presents a comprehensive overview of the antioxidant effects exhibited by complexes formed by curcumin and curcumin derived ligands with metals like Mn, Cu, Fe, Zn, Ga and In, which leads to toxic effects beyond a certain limit, based on both experimental and theoretical findings. Additionally, the discussion delves into metal-curcumin complexes characterized by stoichiometries of 1:1 and 1:2, exploring their geometric arrangements and corresponding antioxidant activity, as highlighted in recent studies. These complexes hold the promise of improving curcumin's solubility, stability, and bioavailability, potentially augmenting its overall therapeutic potential and expanding its scope for medical applications.

Unlocking the potential of low FODMAPs sourdough technology for management of irritable bowel syndrome.

Consumption of high FODMAP (Fermentable Oligo-, Di-, and Monosaccharides and Polyols) diet is the leading cause of alteration in the human gut microbiome, thereby, causing irritable bowel syndrome (IBS). Therefore, sourdough technology can be exploited for reduction of FODMAPs in various foods to alleviate the symptoms of IBS. Several microorganisms viz. Pichia fermentans, Lactobacillus fetmentum, Saccharomyces cerevisiae, Torulaspora delbrueckii, Kluyveromyces marxianus etc. have been identified for the production of low FODMAP type II sourdough fermented products. However, more research on regulation of end-product and volatilome profile is required for maximal exploitation of FODMAP-reducing microorganisms. Therefore, the present review is focused on utilisation of lactic acid bacteria and yeasts, alone and in synergy, for the production of low FODMAP sourdough foods. Moreover, the microbial bioprocessing of cereal and non-cereal based low FODMAP fermented sourdough products along with their nutritional and therapeutic benefits have been elaborated. The challenges and future prospects for the production of sourdough fermented low FODMAP foods, thereby, bringing out positive alterations in gut microbiome, have also been discussed.

In silico studies of the interaction of the minor groove binder Hoechst 33258 with B-DNA.

Interaction of the minor groove binder, Hoechst 33258, with the Dickerson-Drew DNA dodecamer sequence has been investigated using docking, MM/QM, MM/GBSA and molecular dynamics computations to study the modes of binding and the interactions responsible for the binding. Besides the original Hoechst 33258 ligand (HT), a total of 12 ionization and stereochemical states for the ligand are obtained at the physiological pH and have been docked into B-DNA. These states have one or the other or both benzimidazole rings in protonated states, apart from the piperazine nitrogen, which has a quaternary nitrogen in all the states. Most of these states are found to exhibit good docking scores and free energy of binding with B-DNA. The best docked state has been taken further for molecular dynamics simulations and compared with the original HT. This state is protonated at both benzimidazole rings besides the piperazine ring and hence has very highly negative coulombic interaction energy. In both cases, there are strong coulombic interactions, but these are offset by the almost equally unfavorable solvation energies. Thus, the nonpolar forces, particularly van der Waals contacts, dominate the interaction, and the polar interactions highlight subtle changes in the binding energies, leading to more highly protonated states having more negative binding energies.Communicated by Ramaswamy H. Sarma.

Canine Parvovirus and Its Non-Structural Gene 1 as Oncolytic Agents: Mechanism of Action and Induction of Anti-Tumor Immune Response.

The exploration into the strategies for the prevention and treatment of cancer is far from complete. Apart from humans, cancer has gained considerable importance in animals because of increased awareness towards animal health and welfare. Current cancer treatment regimens are less specific towards tumor cells and end up harming normal healthy cells. Thus, a highly specific therapeutic strategy with minimal side effects is the need of the hour. Oncolytic viral gene therapy is one such specific approach to target cancer cells without affecting the normal cells of the body. Canine parvovirus (CPV) is an oncolytic virus that specifically targets and kills cancer cells by causing DNA damage, caspase activation, and mitochondrial damage. Non-structural gene 1 (NS1) of CPV, involved in viral DNA replication is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis. In this review, we discuss the oncolytic properties of Canine Parvovirus (CPV or CPV2), the structure of the NS1 protein, the mechanism of oncolytic action as well as role in inducing an antitumor immune response in different tumor models.

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems.

Cancer remains one of the leading causes of death worldwide in humans and animals. Conventional treatment regimens often fail to produce the desired outcome due to disturbances in cell physiology that arise during the process of transformation. Additionally, development of treatment regimens with no or minimum side-effects is one of the thrust areas of modern cancer research. Oncolytic viral gene therapy employs certain viral genes which on ectopic expression find and selectively destroy malignant cells, thereby achieving tumor cell death without harming the normal cells in the neighborhood. Apoptin, encoded by Chicken Infectious Anemia Virus' VP3 gene, is a proline-rich protein capable of inducing apoptosis in cancer cells in a selective manner. In normal cells, the filamentous Apoptin becomes aggregated toward the cell margins, but is eventually degraded by proteasomes without harming the cells. In malignant cells, after activation by phosphorylation by a cancer cell-specific kinase whose identity is disputed, Apoptin accumulates in the nucleus, undergoes aggregation to form multimers, and prevents the dividing cancer cells from repairing their DNA lesions, thereby forcing them to undergo apoptosis. In this review, we discuss the present knowledge about the structure of Apoptin protein, elaborate on its mechanism of action, and summarize various strategies that have been used to deliver it as an anticancer drug in various cancer models.

Justification of whole-body CT in polytrauma patients, can clinical examination help selecting patients?

BACKGROUND: Whole-body computed tomography (WBCT) is used indiscriminately in trauma cases, just on the suspicion of them being polytrauma cases. A good clinical examination done pre-emptively could prevent the need for this investigation and its undesirous effects. We did this study with an overall aim to assess, if WBCT can be limited to subgroup of trauma patients without compromising clinical safety. METHODS: Retrospective database analysis of 150 cases of polytrauma who underwent WBCT in 2017 was performed. We recorded age, gender, radiation dose and CT findings in all cases and calculated mean age, number of total patients and female patients less than 25 years of age, number of normal WBCT scans, mean radiation dose in the normal and total scans. We also compared pre-test clinical requests with whole-body CT findings, and categorised them in following seven categories: Category 1-Normal Scans; Category 2-Clinically expected Major Injuries; Category 3-Clinically expected Minor Injuries (low risk injuries with no risk of morbidity or mortality if remained undiagnosed), Category 4-Clinically expected CT findings with unexpected Minor (non-serious) injuries; Category 5-Clinically expected CT findings with unexpected Major (serious) injuries, Category 6-Unexpected Minor (non-serious) injuries; Category 7-Unexpected Major (serious) injuries. Categories 2 &3 of clinically expected major and minor injuries included patients with fewer injuries than expected. On the other hand, Category 4 & 5 consist of clinically expected findings with other unexpected injuries, including minor and major injuries respectively. Body injuries were reported in seven areas as per our institutional reporting protocol- Head (including face), Cervical Spine, Thoracolumbar Spine, Chest, Abdomen, Pelvis and Appendicular Skeleton (if asked for). RESULTS: Overall, we found statistically significant correlation between clinical suspicion raised and WBCT findings with good clinical correlation noticed in 106 (70.66%) cases (including 61 cases of clinically suspected major injuries, 15 cases of clinically suspected minor injuries and 25 nearly normal scans with no obvious clinical concern). Isolated unexpected serious injury without any clinical suspicion was seen in only 1 case. Surprisingly, 25 scan requests were made due to high risk mechanism of injury with no obvious clinical concern and were found normal in 20 cases and showed very subtle injuries in 5. Notably, 30 cases of expected major and minor injuries showed highly accurate clinical findings with no injury other than the region of concern and in these cases, limited scan requests would have been sufficient. Mean radiation dose of the entire study group was 22.45 mSv and those to normal patients was 21.19 mSv. CONCLUSIONS: This study re-emphasizes the significance of good clinical examination in the era of evidence based medicine, which would reduce the high number of unnecessary high dose WBCT (25 scans with no positive findings on clinical examination were nearly normal and in 30 cases limited CT would have been sufficient), thereby, decreasing radiation exposure and its potential side effects on polytrauma patients without affecting their survival.

Identification of novel urease inhibitors: pharmacophore modeling, virtual screening and molecular docking studies.

Pharmacophore modeling and atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) have been developed on N-acylglycino- and hippurohydroxamic acid derivatives, which are known potential inhibitors of urease. This is followed by virtual screening and ADMET (absorption, distribution, metabolism, excretion and toxicity) studies on a large library of known drugs in order to get lead molecules as Helicobacter pylori urease inhibitors. A suitable three-featured pharmacophore model comprising one H-bond acceptor and two H-bond donor features (ADD.10) has been found to be the best QSAR model. An external library of compounds (∼3000 molecules), pre-filtered using Lipinski's rule of five, has been further screened using the pharmacophore model ADD.10. By analyzing the fitness of the hits with respect to the pharmacophore model and their binding interaction inside the urease active site, four molecules have been predicted to be extremely good urease inhibitors. Two of these have significant potential and should be taken up for further drug-designing process.

Multiplexed Autoantibody Signature for Serological Detection of Canine Mammary Tumours.

Spontaneously occurring canine mammary tumours (CMTs) are the most common neoplasms of female unspayed dogs and are of potential importance as models for human breast cancer as well. Mortality rates are thrice higher in dogs as compared to humans with breast cancer, which can partly be attributed to lack of diagnostic techniques for their early detection. Human breast cancer studies reveal role of autoantibodies in early cancer diagnosis and also the usefulness of autoantibody panels in increasing the sensitivity, as well as, specificity of diagnostic assays. Therefore, in this study, we took advantage of high-throughput Luminex technique for developing a multiplex assay to detect autoantibody signatures against 5 canine mammary tumour-associated autoantigens (TAAs). These TAAs were expressed separately as fusion proteins with halo tag at the N-terminus, which allows easy and specific covalent coupling with magnetic microspheres. The multiplex assay, comprising a panel of candidate autoantigens (TPI, PGAM1, MNSOD, CMYC & MUC1) was used for screening circulating autoantibodies in 125 dog sera samples, including 75 mammary tumour sera and 50 healthy dog sera. The area under curve (AUC) of the combined panel of biomarkers is 0.931 (p < 0.0001), which validates the discriminative potential of the panel in differentiating tumour patients from healthy controls. The assay could be conducted in 3hrs using only 1ul of serum sample and could detect clinical cases of canine mammary tumour with sensitivity and specificity of 78.6% and 90%, respectively. In this study, we report for the first time a multiplexed assay for detection of autoantibodies in canine tumours, utilizing luminex technology and halo-tag coupling strategy. Further to the best of our knowledge, autoantibodies to CMYC and MUC1 have been reported for the first time in canines in this study.

In Silico study of the active site of Helicobacter pylori urease and its inhibition by hydroxamic acids.

Hydroxamic acids have emerged as the most promising candidates from among the different classes of inhibitors of urease. In order to understand the mechanism of their action, we have studied in detail using quantum mechanics the active site of Helicobacter pylori urease complexed with acetohydroxamic acid. A diverse library of ligands having the hydroxamate moiety has been prepared and docked into the active site of urease using the QM/MM methodology. It is found that hydroxamic acids with hydrophobic groups attached to them are more potent inhibitors of urease because they can easily penetrate the hydrophobic environment surrounding the active site. The -CONHO- moiety of the hydroxamic acid is also found to be absolutely necessary for chelation and inhibition of urease. In order to determine the roles of residues His 221 and Ala 365, which are not part of the active site, but are nevertheless involved in hydrogen bonding with the ligand, we have performed Molecular Dynamics simulations, both on the wild urease and also on its mutated counterpart, with the two residues substituted, respectively, by alanine and glycine.

Xylose transport in yeast for lignocellulosic ethanol production: Current status.

Lignocellulosic ethanol has been considered as an alternative transportation fuel. Utilization of hemicellulosic fraction in lignocelluloses is crucial in economical production of lignocellulosic ethanol. However, this fraction has not efficiently been utilized by traditional yeast Saccharomyces cerevisiae. Genetically modified S. cerevisiae, which can utilize xylose, has several limitations including low ethanol yield, redox imbalance, and undesired metabolite formation similar to native xylose utilizing yeasts. Besides, xylose uptake is a major issue, where sugar transport system plays an important role. These genetically modified and wild-type yeast strains have further been engineered for improved xylose uptake. Various techniques have been employed to facilitate the xylose transportation in these strains. The present review is focused on the sugar transport machineries, mechanisms of xylose transport, limitations and how to deal with xylose transport for xylose assimilation in yeast cells. The recent advances in different techniques to facilitate the xylose transportation have also been discussed.

Idiopathic heterotopic ossification of bilateral subscapularis tendons: illustration of a rare entity and a concise literature review.

Ossification of the subscapularis tendon is an extremely uncommon, poorly described lesion with little known about its etiopathogenesis and clinical significance. To the best of our knowledge, only three cases of this entity have been reported till now, which were all unilateral. The authors present first case of ossification of bilateral subscapularis tendons in a 57-year-old male and hope that with increase in the number of reported cases, proper guidelines for management of such cases can be formulated.

Intrathoracic gastric perforation secondary to corrosive ingestion: a rare complication.

This case report describes a rare and serious case of acid ingestion in a 50-year-old man who developed necrosis and perforation of gastric fundus and diaphragm with extension of air and fluid collection in the thorax. To the best of our knowledge, this complication has not been described so far in the literature.

Effect of Evolutionary Adaption on Xylosidase Activity in Thermotolerant Yeast Isolates Kluyveromyces marxianus NIRE-K1 and NIRE-K3.

Efficient use of xylose along with glucose is necessary for the economic production of lignocellulosic based biofuels. Xylose transporters play an important role in the microorganisms for efficient utilization of xylose. In the present study, a novel method has been developed for a rapid assay of xylose transport activity in the xylose-utilizing isolates and other known yeasts. An assay was conducted to compare the activity of ß-xylosidase using p-nitrophenyl-ß-D-xylopyranoside (pNPX) in the intact, intracellular, and extracellular yeasts cells showing xylose transporter. Saccharomyces cerevisiae (MTCC 170) showed no xylosidase activity, while little growth was observed in the xylose-containing medium. Although other yeasts, i.e., Kluyveromyces marxianus NIRE-K1 (MTCC 5933), K. marxianus NIRE-K3 (MTCC 5934), and Candida tropicalis (MTCC 230), showed xylosidase activity in intact, intracellular, and extracellular culture. The xylosidase activity in intact cell was higher than that of extracellular and intracellular activity in all the yeast cells. The enzyme activity was higher in case of K. marxianus NIRE-K1 and K. marxianus NIRE-K3 rather than the C. tropicalis. Further, better xylosidase activity was observed in adapted K. marxianus cells which were 2.79-28.46 % higher than that of native (non-adapted) strains, which indicates the significant improvement in xylose transportation.

Enhancement in xylose utilization using Kluyveromyces marxianus NIRE-K1 through evolutionary adaptation approach.

The evolutionary adaptation was carried out on the thermotolerant yeast Kluyveromyces marxianus NIRE-K1 at 45 °C up to 60 batches to enhance its xylose utilization capability. The adapted strain showed higher specific growth rate and 3-fold xylose uptake rate and short lag phase as compared to the native strain. During aerobic growth adapted yeast showed 2.81-fold higher xylose utilization than that of native. In anaerobic batch fermentation, adapted yeast utilized about 91% of xylose in 72 h and produced 2.88 and 18.75 g l⁻¹ of ethanol and xylitol, respectively, which were 5.11 and 5.71-fold higher than that of native. Ethanol yield, xylitol yield and specific sugar consumption rate obtained by the adapted cells were found to be 1.57, 1.65 and 4.84-fold higher than that of native yeast, respectively. Aforesaid results suggested that the evolutionary adaptation will be a very effective strategy in the near future for economic lignocellulosic ethanol production.

Sikhs in Minnesota: Dental Care Access, Ethnicity, and Acculturation.

To explore the dental care experiences of one of Minnesota's ethnic communities, the authors conducted pilot study among members of Sikh temple. The Sikhs, a religious group from the Punjab region of India, number roughly 1,500-2,000 individuals in the Twin Cities. Forty-seven adults from the Bloomington, Minnesot temple completed the survey, which was administered during interviews with one of the authors, himself a Sikh. Respondents, who ranged in age from 29 to 92, have been in the United States for an average of 16 years, and had educational backgrounds ranging from undergraduate, Masters, to doctoral degrees. Their self-reported oral health is deemed good. They regularly seek dental care, including preventive services. Their experiences with dental practices have largely been positive, and they have found little discrimination when encountering dental office staff members. Some degree of communication issues was reported by 25% of respondents. Roughly half of the persons surveyed seek care in private practices, but a surprisingly high percentage (13%) visit the University of Minnesota School of Dentistry clinics. Most respondents were comfortable discussing their culture and religion with dental office staff members, and they seemed to hold a positive view of Minnesota's dental profession. Sikh weddings are always full of rituals, traditions, and celebrations. The wedding usually takes place in the morning and is held in front of the Sikh holy book Shri Guru Granth Sahib. A bride may traditionally be dressed in red, as the color red symbolizes love and commitment in Indian culture. The groom wears a colored turban and scarf and carries a kirpan, a ceremonial sword a dagger. The priest leading this ceremony explains the Sikh philosophy of marriage. Family members, relatives, and friends gather to congratulate and bless the new couple, and the whole wedding can last three to four days, made up of a number of rituals.

Incidental finding of elongated ventral duct in a case of pancreatic divisum mimicking double pancreatic ducts on magnetic resonance cholangiopancreaticography-a rare normal variant.

Anatomic variations and developmental anomalies of the pancreas and pancreatic duct are often noticed as an incidental finding on imaging. However, knowledge of these variants may prove to be crucial during surgery as it may prevent unintentional ductal injury. We report a case of pancreatic divisum with codominant ventral duct mimicking double pancreatic ducts along with the elongated uncinate process of pancreas. It was picked incidentally on magnetic resonance cholangiopancreaticography (MRCP) done to rule out cholelithiasis and choledocholithiasis. It is a rare anatomic variant and to the best of our knowledge has not been reported so far.