Search

Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90.Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p = 0.01; 53.84% versus 25%, p = 0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p = 0.11) patients, while ascites resolved in 100% versus 40% survivors (p = 0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p = 0.77; p = 0.70). Median IL1beta decreased by 21.39% (IQR - 73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR - 0.88 to 128.11) (p = 0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality.FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.NCT03827772 available from http://clinicaltrials.gov/ct2/show/NCT03827772 CTRI Reference number: CTRI/2019/02/017538 dated 7 February 2019.

Large quantities of rejects from coal processing plants are currently disposed of as waste piles or in ponds and rivers, resulting in environmental concerns including pollution of rivers and ground and surface water contamination. This work investigates for the first time, a two-stage microbial process for converting coal processing wastes to methane, involving (1) fungal solubilisation of coal rejects and (2) microbial methanation of the solubilised products. Phanerochaete chrysosporium, Trichoderma viride and Neurospora discreta were screened for their ability to solubilise coal rejects. N. discreta was found to be the most suitable candidate based on the extent of bio-solubilisation, laccase activity, and reversed-phase high performance liquid chromatography (RP-HPLC) analysis. Bio-methanation of fungal-solubilised coal rejects was carried out in mesophilic anaerobic reactors with no additional carbon source, using inoculum from an anaerobic food digester. Coal rejects solubilised by N. discreta produced 3 to 6-fold higher methane compared to rejects solubilised by the other two fungi. No methane was produced from untreated coal rejects, demonstrating the importance of the fungal solubilisation stage. A total of 4.1 mmol methane was generated per gram of carbon in 15 days from N. discreta-solubilised coal rejects. This process offers a timely, environment-friendly, and sustainable solution for treatment of coal rejects and the generation of value-added products such as methane and volatile fatty acids.

Parathyroid lesions are identified by subjective enhancement and washout patterns on computed tomography (CT). We have previously proposed "percentage arterial enhancement" (PAE) as an objective index and now aim to validate its performance prospectively.Dual-phase CT was performed in 40 consecutive primary hyperparathyroidism patients. PAE was calculated as [{arterial phase Hounsfield unit (HU)-unenhanced phase HU}/unenhanced phase HU] × 100. PAE 128.9% was considered parathyroid.PAE had 94.2% sensitivity, 100% positive predictive value (PPV) in lateralization, and sensitivity and PPV of 93.9% in quadrant localization of single-gland disease. PAE failed to identify two lesions: an intrathyroidal parathyroid carcinoma in the background of multinodular goiter and another lower enhancing cystic parathyroid adenoma. PAE had 60% sensitivity, and 100% PPV to identify multigland disease. The mean effective dose was 2.74 mSV.PAE is a specific CT index for parathyroid lesions with less radiation exposure. Areas of caution include intrathyroidal and cystic lesions.

Fungi are heterotrophic organisms possessing cryptic lifestyles and have an individual hierarchy in the evolution of microorganisms on earth. Out of which, Keratinophilic fungi are allied molds that produce keratinase enzymes and diminish the keratin matters in or on the soil. Fifty soil samples were collected from various sites of Jaipur district, India to analyze incidence of keratinophilic fungi. Out of 162 isolates, a total of 24 keratinophilic fungal species of 13 genera were recovered, including Trichophyton sp. (17.90%), Aspergillus sp. (17.90%), Chrysosporium sp. (14.81%). Selective keratinophilic fungi were also discussed about phylogenetic studies. In multiple sequence alignment of sequences, species were reported to have closest relationships between teleomorphic and anamorphic form of keratinophilic fungi which exhibited a reason for phase changes between geophilic and dermatophytic fungi by accident or opportunistic where they may cause infections in both humans and animals on the opportunity. In the anti-fungal activity, Eucalyptus globulus (Inhibition Zone: 23.5 mm; Activity Index: 0.82) and Ocimum tenuiflorum (Inhibition Zone: 20.75 mm; Activity Index: 1.46) were inscribed to dispense a greater potential of antifungal activity against all selected keratinophilic fungi.

Keratinophilic fungi are morphologically and physiologically allied molds that produce the keratinase enzyme which degrades the keratin materials in or on the soil. Fifty soil samples were collected from various habitats of Rajasthan namely Jaipur, Ajmer, Alwar and Sikar in India. Out of 154 isolates, a total of 31 keratinophilic fungal species of 16 genera was recovered, including Chrysosporium tropicum (11.04%), Chrysosporium indicum (9.09%), Trichophyton mentagrophytes (8.44%), Fusarium solani (7.79%), Trichophyton rubrum (7.14%), Microsporum canis (5.84%), and Aspergillus terreus (4.19%). The frequency of these keratinophilic fungi is also discussed in relation to soil pH. The most of the fungi (47.40%) were isolated from the soil samples with pH 7.00 to 7.99. Chrysosporium indicum (5.84%) reported since 8.00–8.99 pH, while Fusarium solani (5.19%), Microsporum canis (4.55%) and Trichophyton mentagrophytes (4.55%) between 7.00 and 7.99 pH. This study stipulates that the soils of Rajasthan may be major reservoirs of certain keratinophilic fungi. Keywords: Keratinophilic fungi, Keratinase, Keratin, Chrysosporium, Trichophyton, Fungal biota

Childhood and adolescent primary hyperparathyroidism (PHPT) is a very rare disease. Data on its molecular genetics are scarce. We performed a retrospective analysis (January 2000-January 2021) to determine the deleterious germline variants and genotype-phenotype correlations in children and adolescents 20 years diagnosed with PHPT from a single referral center. Clinical features, biochemistry, imaging, management, and genetics (clinical exome analyzed for 11 PHPT and 7 pancreatitis-associated genes, MLPA for CDC73) were recorded. Thirty-six patients (20 males; median age 17 years) were classified into those with familial and/or syndromic (F/S) or apparently sporadic (AS) presentation. Sixteen (44.4%) harbored pathogenic/likely pathogenic germline variants in PHPT-associated genes. The genetic yield in F/S group was 90% (MEN1:8/10; CDC73:1/10), and AS group was 26.9% (CDC73:4/26; CASR:3/26). F/S group had frequent asymptomatic presentation (60% vs none; P 0.001), lower serum PTH (237.5 vs 1369.1 pg/mL; P = 0.001), and maximum parathyroid dimension (0.9 vs 2.2 cm; P = 0.01) than AS group. Among the AS group, renal involvement was higher in those with molecular diagnoses (71.4% vs 10.5%; P = 0.01). All those with novel CASR variants (including one homozygous) had hypercalciuria and histology-proven parathyroid adenoma/carcinoma. A missense CTRC VUS occurred in one patient with chronic pancreatitis. In summary, Asian Indian children and adolescents with PHPT have high genetic yield, even with apparently sporadic presentation. The phenotypic spectrum of CASR variants is expanded to include childhood/adolescent PHPT with hypercalciuria and single gland neoplasia. The proposed roles for renal involvement to predict molecular diagnosis among those with apparently sporadic presentation require further elucidation.

Background: Modulation of gut dysbiosis with Fecal Microbiota Transplantation (FMT) is a novel modality and has shown promising results in decompensated cirrhosis (DC). We explored the impact of FMT on prognostic scores, complications, ammonia levels, inflammatory markers [(Interleukin -1 (IL-1) and 6 (IL-6)], and 180-day mortality in DC.Methods: Consecutive patients with DC (MELD12-21) were assigned to either FMT (FMT group) delivered as 30gm freshly prepared stool (from a related stool donor) homogenized in 100 ml of normal saline through a nasojejunal tube or standard of care therapy (SOC group). Outcomes were assessed on days 7, 28, 90, and 180.Results: Eighteen patients each with comparable baseline characteristics (88.8% males; mean age, 46.12±6.23 vs. 47.0±4.54; mean CTP, 9.5±0.71 vs. 9.6±0.80; mean MELD, 16.1±1.71 vs. 1.62±1.81) were allocated to FMT or SOC. Although significant differences were noted in the CTP score on day 7 (P=0.02) and day 90 (P=0.01), MELD and MELD-Na scores were similar at all time points. A non-significant reduction in ammonia levels was seen on day 7 and day 28 (P=0.21 and P=0.17; respectively). IL-1 (P=0.01) and IL 6 (P=0.005) levels reduced significantly on day 28. New-onset variceal bleed (P=0.70), breakthrough hepatic encephalopathy events (P=0.61) and 180-day survival (HR, 2.02; 95% CI, 0.37-11.05; P=0.41). were similar. Although transient gastrointestinal side-effects were common (56.2%), no serious adverse events were noted.Conclusion: Single session FMT in DC is safe and leads to selective improvement of CTP scores and systemic inflammatory markers but offers no survival benefit. (ClinicalTrials.gov number, NCT04842539)

Background: Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.Methods: Thirty-three patients [13 in the FMT arm;20 in the standard of care arm (SOC] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days seven, twenty-eight, and ninety. Results: Survival at twenty-eight and ninety days was significantly better in the FMT arm (100% versus 60%, P=0.01; 53.84% versus 25%, P=0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, P=0.11) patients, while ascites resolved in 100% versus 40% survivors (P=0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (P=0.77; P=0.70). Median IL1beta decreased by21.39% (IQR -73.67-7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR -0.88-128.11) (P=0.01). Percentage changes in bilirubin and ALT between baseline and day seven emerged as predictors of ninety-day mortality.Conclusion: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.

Earth has innate background for fungi that cover individual kingdom since evolution. The keratinophilic fungi are allied moulds that produce the keratinase enzyme to degrade the keratinous materials in or on the soil. Keratinous materials are insoluble and resistant to degradation by common proteinase enzymes. It is important to study the microorganism producers of such enzymes for use in the biotechnology industry. In order to present study, two isolates of fungi were evaluated to determine if they had the ability to degrade keratin as nutrient substrate. They were grown in an inundated culture medium containing poultry feathers. Among species, best keratin substrate degradation activity as well as keratinase enzyme activity was recorded in Arthoderma multifidium (KU578107) followed by Chrysosporium tropicum (KU578108) gradually leading manner day by days.

The enzymatic ability of fungi to decompose keratin has long been interpreted as a key innovation in the evolution of animal dermatology. Dermatophytes are keratinophilic fungi which were originally saprophytic, but have adapted themselves to animal and human parasitism during the course of evolution. Dermatophytes are pathogens, which cause superficial mycosis. The dermatophytes have the capacity to invade keratinized tissue (skin, hair and nails) of humans and other animals to produce an infection. The mycoses caused by fungal infections of the skin and nails is widespread and common amongst all type of mycoses. During last decades, mycotic infections raised to more than 20-25% of the world’s population. The review article contains the input of knowledge of various dermatophytes and the diseases caused by them, their identification at the molecular level and treatment strategies. Key words: Dermatology, dermatophytes, mycoses, keratin.

Earth has been documented as a natural territory for fungi which cover individual kingdom with evolution. In subsequently vertebrates developed keratin which was a part of life as a structural aspect. Few moulds have skilled to digest keratin and crop up from soil and wastewater habitats. They take part as a keratinolytic agent in the purification of α-keratins with an incidence of disulphide and hydrogen bonds which are improperly biodegradable. The best moulds genera to decay of keratin are Microsporum, Trichophyton and Epidermophyton. The presences of these genera are open health issues in developing countries where they cause the mortal mycotic contagion. The reason behind this is perceived to be the poor hygienic environment and socioeconomic behaviour among people. The present review is a compilation of updated information concerning the nature of these keratinolytic moulds and abundances of most contributed developing countries including India.

Dermatophytes as the name suggest are the fungus that feed on skin. The chief source of their growth is keratin which is widely available in skin, nails and hairs and causes disease in animals and humans due to their ability to obtain nutrients from keratinized material. The organisms colonize the keratin tissues and inflammation is caused by host response to metabolic byproducts. They are usually restricted to the nonliving cornified layer of the epidermis because of their inability to penetrate viable tissue of an immunocompetent host.

An A-scan ultrasound gives us one dimensional information about the area of interest in the body being examined. Paranasal sinuses are empty air-filled cavities whose functions are to support the weight of the skull, introduce resonance to voice and condition the respired air. They are located in the nasal cavity -maxillary sinuses, above the eyes-frontal sinuses, between the eyes -ethmoidal sinuses and behind the ethmoids- sphenoidal sinuses. The objective of our project is to design an A-mode ultrasound system for the detection of paranasal sinusitis, primarily maxillary sinus. The existent conventionally used methods for detection of paranasal sinuses are the X-ray and CT methods. This amounts to large radiation dose every time the patient undergoes an examination and is more expensive. The reasons behind choosing to use the ultrasound method are that it is relatively inexpensive and can be made portable. It is safe as no ionizing radiation is used. Since the ultrasound technique has limited bone penetration which restricts its use to maxillary sinuses alone.

During the past few decades, increasing use of chemical fertilizers has caused many negative effects in agriculture: development of infectious agent resistance, adverse impact on nontarget species, and reduction in crop yield resulting from the harmful effects of chemical fertilizers on soil quality parameters. Thus, the search for an eco-friendly approach has been emphasized during the past several years. Plant growth-promoting rhizobacteria (PGPR) perform varied functions as (1) biofertilizers, (2) phytostimulators, (3) rhizoremediators, and (4) biopesticides. Plants do not seem to be axenic in natural conditions, and typically are influenced directly by completely different microorganisms such as rhizobacteria, of which several have the ability to provide phytohormones. This chapter sums up data relating to the synthesis, metabolism, regulation, physiological role, and agronomic impact of plant products made by plant growth-promoting rhizobacteria. We have included information regarding the auxins, cytokinins, gibberellins, and ethylene.

The demand for petroleum and petroleum products is increasing day by day, while oil spills and improper discharge of industrial wastes contributes to the rising contamination of the environment with petroleum hydrocarbon. Petroleum hydrocarbon spills cause various carcinogenic and neurotoxic effects, and thus effective treatment strategies are required. The various physical and chemical methods currently in use are costly and leave toxic residues in the environment. In contrast, bioremediation is a promising technology in the treatment of petroleum hydrocarbon contamination because of its high effectiveness, lower cost and environmental synergy. Here, we review the biodegradation of petroleum hydrocarbon and various factors influencing this process.

Dermatophytes are a group of morphologically and physiologically related moulds, which cause well-defined infection called dermatophytosis. The enzymatic ability of fungi to decompose keratin has long been interpreted as a key innovation in the evolution of animal dermatology. In the present study, keratinase activity profile among Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Microsporum gypseum isolated on keratin substrates such as human hair, human nail and chicken feather at variable environmental conditions of temperature, pH and metal ions was elucidated. All the above-mentioned fungal strains were isolated from soil using To-KA-Va baiting technique and keratinolytic activity was measured spectrophotometrically. In the temperature range of 30-40 °C and slightly alkaline pH (7.0-8.0), Trichophyton produced the highest activity of keratinase. It can be presumed that high enzyme production of Trichophyton species at normal body temperature range and pH could be an attribute for obligate anthropization in some dermatophytes.

The human T-cell lymphotropic virus type-1 (HTLV-1) infects CD4+ T cells and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal (59, 61, 65, 83). HTLV-1-infected leukemic lymphocytes exhibit deregulated cell cycle progression and characteristic multinucleation or polyploidy (evidenced by the appearance of flower-shaped or lobulated nuclei). A conserved sequence, known as pX, located within the 3′ terminus of the HTLV-1 genome, encodes at least five nonstructural regulatory factors, including the viral transactivator Tax and an alternative splice-variant, p30II (or Tax open reading frame II [ORF II], Tof), which was shown to possess a functional transactivation domain (6, 13, 15, 29, 34, 35, 66, 86, 87). The pX sequence is generally retained in the majority of ATLL patient isolates, even those containing partially deleted proviruses (33, 68), indicative of its importance for pathogenesis. The viral Tax protein transcriptionally activates numerous lymphoproliferative pathways (NF-κB, CREB/ATF, and p67SRF) (29, 72, 73, 74, 75, 80, 84, 88) and has been shown to inhibit transcription functions associated with the tumor suppressor p53, which likely contributes to a loss of G1/S-phase checkpoint control in HTLV-1-infected T cells (8, 46, 58). Many of the pleiotropic effects of Tax upon cellular signaling may derive from its aberrant recruitment of the transcriptional coactivators, p300/CREB-binding protein (p300/CBP) and p300/CBP-associated factor (P/CAF) (9, 22, 23, 27, 36, 37, 49, 50, 77, 78). Further, Tax interacts with cell cycle modulators, including D-type cylin-cdk4/6 complexes, retinoblastoma (Rb) protein, and the human mitotic arrest deficiency type 1 (hMAD-1) protein (21, 28, 31, 32, 39, 47, 52, 76). Although HTLV-1 Tax expression markedly promotes G1/S transition (38, 40, 64), Tax has been demonstrated to inhibit Myc-dependent transactivation and prevent Myc-associated anchorage-independent cell growth (67). As ATLL patient-derived lymphocytes and tumors from HTLV-1 pX transgenic mice are known to possess deregulated Myc functions, these findings collectively suggest that other pX-encoded factors may influence Myc to promote cellular transformation by HTLV-1 (20, 43, 63). The Myc transcription factor promotes S-phase cell cycle entry, induces apoptosis or programmed cell death, and causes neoplastic cellular transformation (2, 3, 7, 12, 19, 41, 51). The expression of the Myc protooncogene is deregulated in many solid tumors and hematological malignancies, including ATLL, diffuse large-cell lymphomas, CD30+ anaplastic large-cell lymphomas, and Burkitt's B-cell lymphomas (18, 24, 26, 43, 55, 60). The transforming viruses, HTLV-1 and Epstein Barr virus, deregulate Myc functions associated with development of ATLL and Burkitt's lymphomas, respectively (11, 18, 26, 43, 63, 67). Our preliminary studies indicated that the HTLV-1 accessory protein p30II markedly increases S-phase cell cycle progression and induces significant polyploidy. As relatively little is known with respect to the roles of pX-encoded factors (e.g., p30II, p13II, p12I, and Rexp27) in HTLV-1-associated pathogenesis (6, 29, 34, 35), we sought to characterize the molecular mechanism by which p30II promotes Myc-dependent S-phase progression and multinucleation. While others have proposed that p30II's transcriptional functions are targeted against the viral LTR to repress HTLV-1 gene expression (1, 86, 87), the physiological role of p30II in ATLL-development remains unclear. Using microarray analyses, we now demonstrate that numerous cellular genes are transcriptionally activated by HTLV-1 p30II in a 60-kDa Tat-interacting protein (TIP60)-dependent or TIP60-independent manner. Nicot et al. (48) and Younis et al. (85) have shown that p30II binds and inhibits nuclear export of the doubly spliced Tax/Rex HTLV-1 mRNA, and it is intriguing that p30II might perform diverse functions to regulate viral gene expression and promote altered cellular growth, as has been noted for Tax, which drives LTR transactivation and deregulates host lymphoproliferative-signaling pathways (13, 21, 28, 29, 38, 40, 47, 52, 64, 72-76, 84). Robek et al. (62) have previously demonstrated that p30II is dispensable for immortalization and transformation of human peripheral blood mononuclear cells by an infectious HTLV-1 molecular clone, ACH.p30II, which is defective for p30II production; however, the ACH.p30II mutant exhibited an approximately 20 to 50% reduction in transformation efficiency compared to the wild-type ACH.wt (62), suggesting that p30II is required for the full transforming potential of HTLV-1. Importantly, our findings indicate that HTLV-1 p30II is a novel retroviral modulator of Myc transcriptional and of transforming activities that may significantly contribute to adult T-cell leukemogenesis through stabilization of Myc-TIP60 transcriptional interactions.

The human immunodeficiency virus type-1 (HIV-1) infects microglia, macrophages, and astrocytes in the central nervous system (CNS) and may cause severe neurological diseases, such as AIDS-related dementias or progressive encephalopathies, as a result of CNS inflammation and neurotrophin signaling defects associated with expression of viral antigens and HIV-1 replication in the brain. The HIV Tat protein can be endocytosed by surrounding uninfected cells; interacts with transcriptional coactivators/acetyltransferases, p300/CREB-binding protein, and p300/CREB-binding protein-associated factor (PCAF); and induces neuronal apoptosis. Since nerve growth factor (NGF) receptor and brain-derived neurotrophic factor receptor signaling through CREB requires p300 and PCAF histone acetyltransferases, we sought to determine whether HIV-1 Tat coactivator interactions interfere with neurotrophin receptor signaling in neuronal cells. Here, we demonstrate that Tat-coactivator interactions inhibit NGF- and brain-derived neurotrophic factor-responsive CRE trans-activation and neurotrophin protection against apoptosis in PC12 and IMR-32 neuroblastoma cells. Purified recombinant Tat or Tat-derived synthetic peptides, spanning p300- and PCAF-binding sequences, inhibit histone H3/H4 acetylation in vitro. A Tat mutant, TatK28A/K50A, defective for binding p300 and PCAF, neither repressed NGF-responsive CRE transactivation nor inhibited histone acetylation. HIV-1 Tat interacts in PCAF complexes in post-mortem CNS tissues from donor neuro-AIDS patients, as determined by fluorescence resonance energy transfer immunoconfocal microscopy. Importantly, these findings suggest that HIV-1 Tat-coactivator interactions may contribute to neurotrophin signaling impairments and neuronal apoptosis associated with HIV-1 infections of the CNS.

Dermatophytes are a group of morphologically and physiologically related moulds, which cause well-defined infection called dermatophytosis. The enzymatic ability of fungi to decompose keratin has long been interpreted as a key innovation in the evolution of animal dermatology. In the present study, keratinase activity profile among Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Microsporum gypseum isolated on keratin substrates such as human hair, human nail and chicken feather at variable environmental conditions of temperature, pH and metal ions was elucidated. All the above-mentioned fungal strains were isolated from soil using To-KA-Va baiting technique and keratinolytic activity was measured spectrophotometrically. In the temperature range of 30-40 °C and slightly alkaline pH (7.0-8.0), Trichophyton produced the highest activity of keratinase. It can be presumed that high enzyme production of Trichophyton species at normal body temperature range and pH could be an attribute for obligate anthropization in some dermatophytes.