Adaptation of the gut pathobiont Enterococcus faecalis to deoxycholate and taurocholate bile acids.

Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. This bacterial species is subdominant in a healthy physiological state of the gut microbiota (eubiosis) in adults, but can become dominant and cause infections when the intestinal homeostasis is disrupted (dysbiosis). The relatively high concentrations of bile acids deoxycholate (DCA) and taurocholate (TCA) hallmark eubiosis and dysbiosis, respectively. This study aimed to better understand how E. faecalis adapts to DCA and TCA. We showed that DCA impairs E. faecalis growth and possibly imposes a continuous adjustment in the expression of many essential genes, including a majority of ribosomal proteins. This may account for slow growth and low levels of E. faecalis in the gut. In contrast, TCA had no detectable growth effect. The evolving transcriptome upon TCA adaptation showed the early activation of an oligopeptide permease system (opp2) followed by the adjustment of amino acid and nucleotide metabolisms. We provide evidence that TCA favors the exploitation of oligopeptide resources to fuel amino acid needs in limiting oligopeptide conditions. Altogether, our data suggest that the combined effects of decreased DCA and increased TCA concentrations can contribute to the rise of E. faecalis population during dysbiosis.

Anomalous pressure dependence of the electronic transport and anisotropy in SrIrO3 films.

Iridate oxides display exotic physical properties that arise from the interplay between a large spin-orbit coupling and electron correlations. Here, we present a comprehensive study of the effects of hydrostatic pressure on the electronic transport properties of SrIrO3 (SIO), a system that has recently attracted a lot of attention as potential correlated Dirac semimetal. Our investigations on untwinned thin films of SIO reveal that the electrical resistivity of this material is intrinsically anisotropic and controlled by the orthorhombic distortion of the perovskite unit cell. These effects provide another evidence for the strong coupling between the electronic and lattice degrees of freedom in this class of compounds. Upon increasing pressure, a systematic increase of the transport anisotropies is observed. The anomalous pressure-induced changes of the resistivity cannot be accounted for by the pressure dependence of the density of the electron charge carriers, as inferred from Hall effect measurements. Moreover, pressure-induced rotations of the IrO6 octahedra likely occur within the distorted perovskite unit cell and affect electron mobility of this system.

Public health crisis of road traffic accidents in India: Risk factor assessment and recommendations on prevention on the behalf of the Academy of Family Physicians of India.

Roads are considered a sign of development bringing colossal benefits to community as socioeconomic and logistic facilitator. Yet, growth of road network has brought road crashes leading to civic pain from premature deaths of productive age group. In 2017, 16 citizens were killed and 53 injured every hour on Indian roads as per officially reported data, while a fair number go unreported. This is unacceptably high when compared with international standards. Risk correlates of road traffic injuries (RTIs) need to be redefined so as to form a continuum with other confounding factors that impact to take lives on road. Risk factors impacting RTIs vary from human components to the roles and responsibilities of healthcare stakeholders. We should have made roads safer for all citizens because a large percentage of population - children, pedestrians, cyclists, motorcyclists, and the elderly - are most vulnerable. A taskforce was set up by the Academy of Family Physicians of India to scientifically analyze the literature available to assess risks and put forward appropriate recommendations.

Disruption of NAD(P)H:quinone oxidoreductase 1 gene in mice leads to 20S proteasomal degradation of p63 resulting in thinning of epithelium and chemical-induced skin cancer.

This corrects the article DOI: 10.1038/onc.2010.491.

Stress-induced NQO1 controls stability of C/EBPα against 20S proteasomal degradation to regulate p63 expression with implications in protection against chemical-induced skin cancer.

This corrects the article DOI: 10.1038/onc.2011.600.

Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis.

It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-ß. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL.

Single staged complete length excision of the holocord ependymoma: Team work.

The authors present a case of a 15-year-old male patient who presented with gradually progressive quadriparesis for 3 years. Magnetic resonance imaging of the spine was suggestive of heterogeneously enhancing mass lesion extending from cervicomedullary junction to conus. This holocord spinal tumor was excised in a single stage with standard microsurgical technique. In immediate postoperative period, the patient had deterioration in power in both lower limbs which improved in follow-up at 6 months. Histopathology of the tumor was suggestive of ependymoma. Holocord ependymoma is a rare entity; until now, only six cases have been described in the literature. To the author's best knowledge, this is only the second case of holocord ependymoma excised in a single stage.

Remote cerebellar hemorrhage: Report of 2 cases and review of literature.

Remote cerebellar hemorrhage (RCH) is an extremely rare and potentially devastating complication of supratentorial and spinal surgeries. While there are numerous postulates explaining the patho-physiology behind this phenomenon, including the most popular CSF over drainage theory, the exact cause for the same is still largely unknown. In this report, we present 2 cases of remote cerebellar hemorrhage encountered following 2 different surgical procedures. One patient had preceding pterional craniotomy for ruptured anterior communicating artery aneurysm while the other one developed RCH after placement of EVD. Both of them had history of poorly controlled hypertension, contrary to most reports where hypertension has not been found to be commonly associated with it. Moreover, while most cases have been reported to occur following supratentorial craniotomies and spinal surgeries, one of our patients developed the same after placement of the EVD, which, to the best of our knowledge, has not been reported earlier.

Enhanced mechanical strength and biocompatibility of electrospun polycaprolactone-gelatin scaffold with surface deposited nano-hydroxyapatite.

In this study for the first time, we compared physico-chemical and biological properties of polycaprolactone-gelatin-hydroxyapatite scaffolds of two types: one in which the nano-hydroxyapatite (n-HA) was deposited on the surface of electrospun polycaprolactone-gelatin (PCG) fibers via alternate soaking process (PCG-HAAS) and other in which hydroxyapatite (HA) powders were blended in electrospinning solution of PCG (PCG-HAB). The microstructure of fibers was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) which showed n-HA particles on the surface of the PCG-HAAS scaffold and embedded HA particles in the interior of the PCG-HAB fibers. PCG-HAAS fibers exhibited the better Young's moduli and tensile strength as compared to PCG-HAB fibers. Biological properties such as cell proliferation, cell attachment and alkaline phosphatase activity (ALP) were determined by growing human osteosarcoma cells (MG-63) over the scaffolds. Cell proliferation and confocal results clearly indicated that the presence of hydroxyapatite on the surface of the PCG-HAAS scaffold promoted better cellular adhesion and proliferation as compared to PCG-HAB scaffold. ALP activity was also observed better in alternate soaked PCG scaffold as compared to PCG-HAB scaffold. Mechanical strength and biological properties clearly demonstrate that surface deposited HA scaffold prepared by alternate soaking method may find application in bone tissue engineering.

Stress-induced NQO1 controls stability of C/EBPα against 20S proteasomal degradation to regulate p63 expression with implications in protection against chemical-induced skin cancer.

Previously, we have shown a role of cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1) in the stabilization of p63 against 20S proteasomal degradation resulting in thinning of the epithelium and chemical-induced skin cancer (Oncogene (2011) 30, 1098-1107). Current studies have demonstrated that NQO1 control of CCAAT-enhancer binding protein (C/EBPα) against 20S proteasomal degradation also contributes to the upregulation of p63 expression and protection. Western and immunohistochemistry analysis revealed that disruption of the NQO1 gene in mice and mouse keratinocytes led to degradation of C/EBPα and loss of p63 gene expression. p63 promoter mutagenesis, transfection and chromatin immunoprecipitation assays identified a C/EBPα-binding site between nucleotide position -185 and -174 that bound to C/EBPα and upregulated p63 gene expression. Co-immunoprecipitation and immunoblot analysis demonstrated that 20S proteasomes directly interacted and degraded C/EBPα. NQO1 direct interaction with C/EBPα led to stabilization of C/EBPα against 20S proteasomal degradation. NQO1 protection of C/EBPα required binding of NADH with NQO1. Exposure of skin and keratinocytes to the chemical stress agent benzo(a)pyrene led to induction of NQO1 and stabilization of C/EBPα protein, resulting in an increase in p63 RNA and protein in wild-type but not in NQO1-/- mice. Collectively, the current data combined with previous data suggest that stress induction of NQO1 through both stabilization of C/EBPα and increase in p63 and direct stabilization of p63 controls keratinocyte differentiation, leading to protection against chemical-induced skin carcinogenesis. The studies are significant as 2-4% human individuals are homozygous and 23% are heterozygous for the NQO1P187S mutation and might be susceptible to stress-induced skin diseases.

Analysis of finit in urine sample using thin layer chromatography.

Finit is a common insecticide generally used to control a variety of insects in homes. Routinely it is analysed by Gas Liquid Chromatography (GLC) and High Performance Liquid Chromatography (HPLC). An attempt has been made to develop a new method for analysis of finit in urine samples using Thin Layer Chromatography (TLC) technique which is inexpensive, accurate and non-destructive. Finit was extracted from urine using solvent extraction methods and then identified on the TLC plates. For detection on developed plates, palladium chloride, silver nitrate, iodine vapour and bromophenol blue were used which successfully increased the sensitivity without dispensing with the simplicity of the method. The method developed is simple, inexpensive, accurate and non-destructive that allows for sensitive and reproducible analysis of finit.

Disseminated superficial and warty type of porokeratosis: a rare coexistence.

A 60-year-old male presented with hyperpigmented annular plaques with raised keratotic wall and central groove along with warty plaque involving the trunk and the extremities, respectively. A provisional diagnosis of porokeratosis was made which was confirmed histopathologically. Herein, we report a case of rare coexistence of disseminated superficial and warty porokeratosis.

A case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome.

Involvement of cranial nerves is not uncommon in leprosy with trigeminal and facial nerves being commonly affected. Other cranial nerves can also be involved especially in longstanding cases of leprosy towards the lepromatous pole. Herein, we report a case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome.

Application of Baranyi function to model the antibacterial properties of solvent extract from Irish York cabbage against food spoilage and pathogenic bacteria.

Cabbage is a rich source of a number of bioactive compounds such as flavonoids, glucosinolates and their breakdown products which may have antibacterial, antioxidant and anticancer properties. Outer green leaves of York cabbage were extracted with 60% methanol, ethanol or acetone. Antibacterial activities of vacuum dried crude extracts were estimated against a number of Gram-positive and Gram-negative food spoilage and food pathogenic bacteria. The crude extracts showed a broad spectrum of antibacterial activities but 60% methanol extract exhibited the highest antibacterial effect. Complete growth inhibition for Listeria monocytogenes was achieved with an extract concentration of 1.4%, whereas a two-fold concentration was required to achieve a reduction of 75% and 64% for Salmonella abony and Pseudomonas aeruginosa, respectively. For Enterococcus faecalis methanolic extract showed a weak inhibition only (31%). The lower concentrations of methanolic extract from York cabbage prolonged the lag phase and reduced both the exponential growth rate and final population densities of the culture. Survival of the micro-organisms in presence of methanolic extract was mathematically modeled using Baranyi model equations.

INrf2 (Keap1) targets Bcl-2 degradation and controls cellular apoptosis.

Cytosolic inhibitor of Nrf2 (INrf2) is an adaptor protein that mediates ubiquitination/degradation of NF-E2-related factor 2 (Nrf2), a master regulator of cytoprotective gene expression. In this paper, we demonstrate that INrf2 degrades endogenous antiapoptotic B-cell CLL/lymphoma 2 (Bcl-2) protein and controls cellular apoptosis. The DGR domain of INrf2 interacts with the BH2 domain of Bcl-2 and facilitates INrf2:Cul3-Rbx1-mediated ubiquitination of Bcl-2 by the conjugation of ubiquitin molecules to lysine17 of Bcl-2. Further studies showed that INrf2 enhanced etoposide-mediated accumulation of Bax, increased release of cytochrome c from mitochondria, activated caspase-3/7, and enhanced DNA fragmentation and apoptosis. Antioxidants antagonized Bcl-2:INrf2 interaction, led to the release and stabilization of Bcl-2, increased Bcl-2:Bax heterodimers and reduced apoptosis. Moreover, dysfunctional/mutant INrf2 in human lung cancer cells failed to degrade Bcl-2, resulting in decreased etoposide and UV/γ radiation-mediated DNA fragmentation. These data provide the first evidence of INrf2 control of Bcl-2 and apoptotic cell death, with implications in antioxidant protection, survival of cancer cells containing dysfunctional INrf2, and drug resistance.

Pattern of poisoning cases in a hospital in a Terai district of central Nepal.

Poisoning is a major global health problem and is one of the major causes of hospitalization through emergency. The objective of this study is to evaluate the characteristics of poisoning cases admitted to emergency department over a one year period. A hospital based study was carried out in the emergency department, Mahendra Adarsha Chikitsalaya, Chitwan analyzing the data of the poisoning cases attended for one year duration by searching all the medical records. A total of 921 poisoning cases presented to emergency department in the year 2007. The female to male ratio was 1.17:1. Most of poisoning occurred in the age group 15-24 years. Snake bite was the commonest form of poisoning amongst all cases. By occupation, 46.0% cases were in farmers. Accidental poisoning prevailed over intentional poisoning. Seasonal trend revealed maximum cases being in summer (42.4%). Poisoning shows seasonal trend and hence proper intervention is required in community level.

Disruption of NAD(P)H:quinone oxidoreductase 1 gene in mice leads to 20S proteasomal degradation of p63 resulting in thinning of epithelium and chemical-induced skin cancer.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that protects cells against chemical and radiation-induced oxidative stress and skin cancer. Disruption of NQO1 gene in mice showed thinning of skin epithelium and loss of cytokeratin 14, an early marker of skin differentiation. Immunohistochemistry and western analysis demonstrated downregulation of p63 in NQO1-/- mouse skin, as compared with wild-type (WT) mouse. Further analysis including modulation of NQO1 expression revealed a direct correlation between the levels of NQO1 and p63 in skin-derived keratinocytes and dermal fibroblasts. Modulation of proteasomal activity revealed that p63 is degraded by 20S proteasome and that this degradation is significantly rescued by NQO1. Coimmunoprecipitation studies showed that NQO1 interacts directly with p63 but not 20S to protect against this degradation. In addition, benzo[a]pyrene treatment led to induction of NQO1 and stabilization of p63 in WT but not in NQO1-/- mouse skin and keratinocytes. These data suggest that NQO1 controls stabilization of p63 and progression towards keratinocyte differentiation leading to normal skin development and presumably skin carcinogenesis.

Glioblastoma with melanotic differentiation.

A 54-year-old male presented with the history of headache and vomiting. MRI of the head showed right posterior temporal mass which was surgically excised. Histopathological examination revealed features of glioblastoma with pigmented cells. The pigment was demonstrated to be melanin which was confirmed by special stains and immunohistochemistry. This is the first description of glioblastoma with melanotic differentiation reported in the literature. The relevant literature is briefly reviewed.

Monocular visual loss due to herniation of gyrus rectus: A case report with review of literature.

The authors present an unusual case of a polar mass in the frontal lobe of the brain, causing acute monocular visual loss in a 50-year-old woman with history of breast carcinoma treated with surgery, radiation and chemotherapy. Neuroimaging demonstrated herniation of the gyrus rectus into the suprasellar cistern resulting in compression of the anterior visual pathway.

Prevalence of pharmacotherapy in the department of paediatric dentistry.

BACKGROUND: Pharmacotherapy plays important role in the management of paediatric dental patients in the department of paediatric dentistry. Many children at their early age suffer from different kinds of dental conditions such as acute and chronic irreversible pulpitis, acute and chronic alveolar abscesses, dentoalveolar and vestibular abscesses, etc along with physiological tooth movement that requires professional help for dental treatment. Treatment of such conditions most frequently requires pharmacotherapy as an either adjunct to dental therapeutic procedure or as a monotherapy. OBJECTIVE: To assess the prescribing patterns vis-a-vis generic or trade name, generic class, dosage form, route, frequency, duration, number of drugs per patient, cost and indication of drug therapy, patterns of dental treatment and Frankl's behavioral rating. MATERIALS AND METHODS: Prescriptions of 200 paediatric dental patients undergoing dental treatment in the department of paediatric dentistry were analyzed prospectively for a period of six months in a dental teaching hospital. RESULTS: 133 (56.5%) patients were males and 87 (43.5%) females and age group 6-10 years was the most frequent group (70%, P = 0.0000000) and all the patients received pharmacotherapy. Total numbers of 357 drugs were prescribed. Out of them, 212 (59.4%, P = 0.0000008) were analgesic agents, 133 (37.3%) antimicrobial agents (AMAs) and 12 (3.3%) other drugs. Extended spectrum Penicillins were the most commonly prescribed (90.2%) AMA followed by Metronidazole (9.8%). 247 drugs (69.2%, P = 0.0000000) were prescribed by trade names. 60% (P = 0.0000002) drugs were prescribed in the form of tablet or capsule followed by syrup 37% and administered entirely through oral route. Percentage of patients receiving three drugs, two drugs and one drug was 13.5%, 56.5% (P = 0.0000000) and 30% respectively and one patient received on average 1.78 medicines. 133 patients (56.5%, P = 0.0000000) received both AMA and analgesic agent. Minimum to maximum number of days for pharmacotherapy were 2 to 15 and highest frequency was up to four times a day. Cost of medicines was in the range of 10-150 Nepalese Rupees. Chronic irreversible pulpitis was the commonest diagnosis (28%) and extraction (92.5%) was the commonest dental procedure. Frankl's behaviour rating showed that 78.5% (P = 0.0000000) patients had positive attitude towards the dental procedures. CONCLUSION: Findings of the study suggest that pharmacotherapy is the mainstay in therapy to treat the paediatric dental patients along with dental procedures either to control the dental pain or odontogenic infection. Age group 6-10 years, chronic irreversible pulpitis and dental extraction are the commonest age group, diagnosis and dental procedure respectively in the department of paediatric dentistry. Analgesic (non-steroidal anti-inflammatory drugs- Nimesulide, Ibuprofen and Paracetamol) and Amoxicillin are the most frequently prescribed drugs mostly in the solid dosage forms in trade names via oral route. Duration of pharmacotherapy ranges from 2 to 15 days with highest frequency being up to 4 times a day. Majority of the patients are manageable without any behavioural modification technique- physical or pharmacological.