LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer.

Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncanonical glutamine pathway that is reliant on the mitochondrial and cytosolic transaminases glutamate pyruvate transaminase 2 (GPT2) and glutamate oxaloacetate transaminase 1 (GOT1), which fuel anabolic metabolism. In particular, we show that gain and loss of function of hepatic LRH-1 modulate the expression and activity of mitochondrial glutaminase 2 (GLS2), the first and rate-limiting step of this pathway. Acute and chronic deletion of hepatic LRH-1 blunts the deamination of glutamine and reduces glutamine-dependent anaplerosis. The robust reduction in glutaminolysis and the limiting availability of α-ketoglutarate in turn inhibit mTORC1 signaling to eventually block cell growth and proliferation. Collectively, these studies highlight the importance of LRH-1 in coordinating glutamine-induced metabolism and signaling to promote hepatocellular carcinogenesis.

Prognostic Value of Diaphragm Diameter, Muscle Volume, and Bone Mineral Density in Critically Ill COVID-19 Patients.

Objective: We aimed to analyze the prognostic value of muscle volume (MV), bone mineral density (BMD), and diaphragm diameter (DD) in COVID-19. Method: The study included 498 patients admitted to the intensive care unit (ICU) with a positive polymerase chain reaction test for COVID-19 from March 11, 2020, through August 31, 2022. The patients' laboratory and demographic data of the patients at the time of ICU admission were recorded. MV, DD, and BMD measurements were performed using computed tomography examinations. Muscle index (MI) was calculated as MV/height2. Quartiles were determined for all 4 measurements. Patients in the lowest quartile were recorded as having low MV, MI, DD, and BMD values. The parameters were evaluated for the whole group and compared according to gender and mortality. The multiple regression analysis was performed for the prediction of mortality. Results: In the mortality group, the male and female patients had significantly statistically lower values in MV (P < .001 and P = .002, respectively), MI (P < .001 and P = .005, respectively), DD (P < .001 and P < .001, respectively), and BMD (P = .002 and P < .001, respectively). In the multiple regression analysis, low MI (OR: 2.03, 95% CI: 1.14-3.61, P = .016) and DD (OR: 10.47, 95% CI: 5.59-19.59, P < .001) values remained significant for the prediction of mortality. Conclusion: BMD is a risk factor for mortality in patients with severe COVID-19, but cannot be used as an independent predictor. However, MI and DD can be used as independent predictors of mortality even in severe cases.

The potential of Raman and FT-IR spectroscopic methods for the detection of chlorine in human nail samples.

Although chlorine (Cl2) has been used as a chemical warfare agent since World War I there is no known specific and reliable biomarker to indicate the presence of chlorine. We distinguished chlorinated human nails from unchlorinated ones using Raman spectroscopy and Fourier Transform Infrared (FT-IR) Spectroscopy. This research was carried out between October 2018 and July 2019 on two nail samples taken from 55 male and 104 female volunteers. One sample from each participant was chlorinated, while the second sample was used as a control. Spectral data were collected from chlorinated and unchlorinated (control) human nails using Raman and FT-IR spectroscopy. Raman measurements were made between 100 and 3200 cm-1, while FT-IR measurements were recorded over the range of 650 to 4000 cm-1. Partial least squares regression-discriminant analysis (PLS-DA) was used to develop classification models for each spectral instrument. Results showed that the control and chlorinated nail samples were successfully discriminated with similar results achieved with both instruments. Minor differences were observed in the performance of classification models. The FT-IR spectroscopy model (sensitivity = 95%, specificity = 99%, accuracy = 97%) was found to be more successful with a smaller margin of error (sensitivity = 95%, specificity = 99%, accuracy = 96%) compared to the Raman spectroscopy model. This method can be used successfully for both ante-mortem and post-mortem diagnosis of chlorine exposure.

High-field dissolution dynamic nuclear polarization of [1-(13)C]pyruvic acid.

[1-(13)C]pyruvate is the most widely used hyperpolarized metabolic magnetic resonance imaging agent. Using a custom-built 7.0 T polarizer operating at 1.0 K and trityl radical-doped [1-(13)C]pyruvic acid, unextrapolated solution-state (13)C polarization greater than 60% was measured after dissolution and rapid transfer to a spectrometer magnet, demonstrating the signal enhancement attainable using optimized hardware. Slower rates of polarization under these conditions can be largely overcome with higher radical concentrations.

Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe.

The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of γ-Glu-[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the chemical shift between γ-Glu-[1-(13) C]Gly and its metabolic product, [1-(13) C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that γ-Glu-[1-(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.

The effects of topical aloe vera on an experimentally designed penile fracture model in rats.

BACKGROUND: This study assessed the histopathological and oxidative effects of topical Aloe Vera (AV) on penile fractures (PF) formed experimentally in a rat model. METHODS: Forty Wistar albino rats (220-250 g) were used. The PF model was created experimentally with a number 15 lancet. Then, the rats were randomly and equally divided into five groups. In the first group (C), no incision was formed. In the second group (P), an incision was formed. In the third group (PR), the incision line was closed primarily. In the fourth group (PA), AV was locally applied onto the incision without suturing for three days. In the last group (PRA), AV was applied to the primary repair region for three days. All groups were compared to each other according to histopathological and biochemical data. RESULTS: Hyperemia-bleeding was observed to be suppressed in the PRA group compared to the other groups (p<0.001). Inflammation was observed only in Groups PR and PRA (p<0.001). Significant fibrosis was observed in the PA and PRA groups compared to the other groups (p<0.001). Superoxide Dismutase (SOD) and Glutathione (GSH) values increased in favor of Group PRA (p=0.009 and p=0.035, respectively). Total Oxidative Status (TOS) and Malondialdehyde (MDA) values decreased in favor of Group PA (p=0.036 and p=0.026, respectively). Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1 beta (IL-1ß) levels decreased mostly in the PRA group, but these changes did not reach statistical significance (p>0.05). CONCLUSION: Topical AV application reduces tissue inflammation and oxidative stress but appears to increase the development of fibrosis after PF.

Social media video analysis methodology for sarin exposure.

As social media becomes increasingly ubiquitous, many events are recorded and released on social media platforms, including chemical weapon attacks. We develop an objective tool in order to evaluate brief and unstructured social media videos for analysing sarin exposure from a civilian medical pathology perspective. We developed and validated this new questionnaire using a standardized procedure that includes content domain specification, item pool generation, content validity evaluation, a pilot study, and assessment of reliability and validity. In total, 51 sarin attacks and 48 matched videos were analysed. Cronbach's α for all 20 items was 0.75, which indicates adequate internal reliability. The test-retest reliability was 0.96, which indicates good internal reliability. The inter-observer intraclass correlation coefficient was 0.97. After verifying sampling adequacy with the Kaiser-Meyer-Olkin measure and the factorability of the items with Barlett's test of sphericity, a factor analysis was performed. According to the principal axis factoring, a six-factor solution explained 51.86% of the total variance. The receiver-operating characteristic curve analysis showed that the Video Score Questionnaire has a sensitivity of 0.817, a specificity of 0.478, and an efficiency of 65.3. Therefore, the Video Score Questionnaire is reliable and valid for evaluating sarin attacks from brief and unstructured social media videos.Key pointsChemical weapons are still used as a method of warfare.Social media videos are an important source of information.We developed a validated scale which can analyse sarin exposure in short and unstructured videos.

Naked mole-rats maintain cardiac function and body composition well into their fourth decade of life.

The prevalence of cardiovascular disease increases exponentially with age, highlighting the contribution of aging mechanisms to cardiac diseases. Although model organisms which share human disease pathologies can elucidate mechanisms driving disease, they do not provide us with innate examples how cardiac aging might be slowed or attenuated. The identification of animal models that preserve cardiac function throughout most of life offers an alternative approach to study mechanisms which might slow cardiac aging. One such species may be the naked mole-rat (NMR), a mouse-sized (40 g) rodent with extraordinary longevity (> 37 years), and constant mortality hazard over its four decades of life. We used a cross-sectional study design to measure a range of physiological parameters in NMRs between 2 and 34 years of age and compared these findings with those of mice aged between 3 months and 2.5 years. We observed a rapid decline in body fat content and bone mineral density in old mice, but no changes in NMRs. Similarly, rhythm disorders (premature atrial and ventricular complexes) occurred in aged mice but not in NMRs. Magnetic resonance and ultrasound imaging showed age-dependent increases in cardiac hypertrophy and diastolic dysfunction in mice which were absent in NMRs. Finally, cardiac stress tests showed an age-dependent decline in normalized cardiac output in mice, which was absent in NMRs. Unlike mice, that manifest several aspects of human cardiac aging, NMRs maintain cardiac function and reserve capacity throughout their long lives and may offer insights on how to delay or prevent cardiac aging.

[13C]bicarbonate labelled from hyperpolarized [1-13C]pyruvate is an in vivo marker of hepatic gluconeogenesis in fasted state.

Hyperpolarized [1-13C]pyruvate enables direct in vivo assessment of real-time liver enzymatic activities by 13C magnetic resonance. However, the technique usually requires the injection of a highly supraphysiological dose of pyruvate. We herein demonstrate that liver metabolism can be measured in vivo with hyperpolarized [1-13C]pyruvate administered at two- to three-fold the basal plasma concentration. The flux through pyruvate dehydrogenase, assessed by 13C-labeling of bicarbonate in the fed condition, was found to be saturated or partially inhibited by supraphysiological doses of hyperpolarized [1-13C]pyruvate. The [13C]bicarbonate signal detected in the liver of fasted rats nearly vanished after treatment with a phosphoenolpyruvate carboxykinase (PEPCK) inhibitor, indicating that the signal originates from the flux through PEPCK. In addition, the normalized [13C]bicarbonate signal in fasted untreated animals is dose independent across a 10-fold range, highlighting that PEPCK and pyruvate carboxylase are not saturated and that hepatic gluconeogenesis can be directly probed in vivo with hyperpolarized [1-13C]pyruvate.

Endovascular closure of an arterivenous graft for dialysis-associated steal syndrome of lower extremity.

Steal syndrome causing limb ischemia is a rare but important complication of arteriovenous fistulas. When surgical or endovascular means to resolve ischemia are inconclusive, closure of the fistula becomes required. Our case presented with lower extremity ischemia resulting from an arteriovenous fistula graft. We present the successful endovascular closure of the lower extremity graft using the Amplatzer Vascular Plug.

A new and simple parameter for diagnosis pulmonary edema: Expiratory air humidity.

PURPOSE: Acute pulmonary edema is characterized by increased levels of fluid in the interstitial and alveolar space of the lung and requires emergency treatment. In acute pulmonary edema, the amount of fluid in the intra-alveolar, interstitial space, and pleural space vary considerably and this fluid will evaporate in different amounts compared to the physiological fluid. The aim of this study was to compare the humidity rates of expiratory air measured before and after pulmonary edema induced by α-naphthylthiourea (ANTU) in rats. METHODS: The study included twenty healthy adult rats divided equally into a healthy control group and a pulmonary edema group. Pulmonary edema was induced by administering ANTU intraperitoneally in the rats in the study group. Humidity, temperature, lung weight, pleural effusion, and histopathological changes in the respiratory system due to pulmonary edema were examined in the ANTU group. Control measurments were taken before administration of ANTU and again 4 h after administration of ANTU when lung damage was considred to be at maximum levels. RESULTS: Mean expiratory air humidity was 71.22±3.59% before ANTU and 56.28±3.94% after administration of ANTU. The mean humidity difference of -14.94±5.96% was considered statistically different (p = 0.01). CONCLUSION: Humidity rate in expiratory air was significantly lower in rats with acute pulmonary edema compared to healthy rats. This result supports the hypothesis that humidity in expiratory air can be considered an important parameter in patients during clinical are follow-up for pulmonary edema.

The preventative effect of of Ro5-4864 (peripheral benzodiazepine receptor agonist) on spinal epidural fibrosis after laminectomy in a rat model.

OBJECTIVE: To investigate the histopathological effects of a peripheral benzodiazepine receptor agonist (Ro5-4864) on epidural fibrosis (EF) in an experimental study model (post-laminectomy) in rats. METHODS: A total of 32 albino Wistar rats were randomly divided into four equal groups (n = 8). In Group 1, no treatment was applied after laminectomy (control group). In Group 2, hemostasis was achieved after Laminectomy, and the surgical procedure was terminated by placing a 2-mm absorbable gelatin sponge dipped in saline into the epidural space. In Group 3, low-dose (4 mg/kg) Ro5-4864 was administered 30 minutes before the surgery. In Group 4, high-dose (8 mg/kg) Ro5-4864 was administered 30 minutes before the surgery. A histopathological examination was performed to evaluate arachnoidal invasion and EF. RESULTS: Our data revealed the EF was significantly reduced in rats treated with high-dose Ro5-4864 (Group 4) compared to the control and saline-soaked Spongostan groups (p = 0.000 and p = 0.006, respectively). There was no significant difference between the groups treated with high- and low-dose Ro5-4864. Arachnoidal invasion was not seen in any of the rats in the high-dose R05-4864 group. However, the arachnoidal invasion results did not significantly differ between the study groups (p = 0.052 = 0.05). CONCLUSIONS: Our study showed that Ro5-4864 could be effective in reducing EF in rats after.

Noninvasive rapid detection of metabolic adaptation in activated human T lymphocytes by hyperpolarized 13C magnetic resonance.

The metabolic shift induced in human CD4+ T lymphocytes by stimulation is characterized by an upregulation of glycolysis, leading to an augmentation in lactate production. This adaptation has already been highlighted with various techniques and reported in several previous studies. We herein propose a method to rapidly and noninvasively detect the associated increase in flux from pyruvate to lactate catalyzed by lactate dehydrogenase using hyperpolarized 13C magnetic resonance, a technique which can be used for in vivo imaging. It was shown that the conversion of hyperpolarized 13C-pyruvate to 13C-lactate during the one-minute measurement increased by a mean factor of 3.6 in T cells stimulated for 5 days as compared to resting T cells. This method can be extended to other metabolic substrates and is therefore a powerful tool to noninvasively analyze T cell metabolism, possibly in vivo.

Two possible cases of Trichosporon infections in bone-marrow-transplanted children: the first case of T. japonicum isolated from clinical specimens.

Trichosporon spp. are emerging as opportunistic agents that cause systemic diseases in immunocompromised hosts. Trichosporonosis carries a poor prognosis in neutropenic patients. Trichosporon japonicum was isolated from the air and named by Sugita et al. Here we present the first case of T. japonicum isolated from a clinical specimen. Two cases of acute myeloid leukemia who had Trichosporon isolates are discussed because of their rarity and growing importance. T. asahii was isolated from the throat, feces and urine of the first patient. T. japonicum was isolated from the sputum of the second patient. Both cases produced high MICs to itraconazole, and low MICs to fluconazole and voriconazole. In virulance factor investigations there was (++) biofilm formation in T. japonicum but not in T. asahii. Conventional mycological studies were not adequate for the identification of the isolate at the species level. In our second case as in the first one, the isolate was identified as T. asahii with 99.9% accuracy by API 20C AUX. Although two T. asahii isolates from the same patient yielded identical typing profiles by arbitrary primed-PCR, the isolates of the two different patients showed different arbitrary primed-PCR typing profiles. However, the genetic identification of the other patient's strain gave the result of T. japonicum.

Current prevalence of goiter determined by ultrasonography and associated risk factors in a formerly iodine-deficient area of Turkey.

The aim of this study was to determine the prevalence of goiter and related risk factors in an adult population in a formerly iodine-deficient area of Turkey. In this cross-sectional study, we enrolled 2,500 subjects (1,270 women and 1,230 men, aged over 20 years) by multistage sampling. Blood and urine specimens were collected for the assessment of thyroid function. Thyroid ultrasonography (USG) was performed to measure thyroid volume and evaluate nodules. The overall goiter prevalence was 26.5 % (28.4 % in women, 24.5 % in men, P < 0.05). Median thyroid volume was 15.59 mL (13.65 mL in women, 17.96 mL in men, P < 0.0001). Median urinary iodine was 122.79 µg/L. USG revealed thyroid nodules in 35.2 % of the subjects (38.4 % in women, 31.8 % in men, P < 0.005). Age group analysis revealed the lowest rate in the 20-29-year age group (12.5 %), which increased with age, reaching the highest level (38.4 %) in the 70+ years age group. The prevalence of goiter was negatively correlated with education level and positively correlated with body mass index (BMI) and positive family history. According to occupation, goiter prevalence was highest in farmers (35.3 %) and housewives (32.2 %). Despite a normal range of current urinary iodine excretion levels, prevalence of goiter in this adult population in a formerly iodine-deficient province of Turkey remained high, even about 10 years after salt iodine supplementation program introduction. In addition, the goiter prevalence was higher for female gender, advanced age, positive family history of goiter, low education level, and high BMI.

Epilepsy prevalence in the 0-17 age group in trabzon, Turkey.

OBJECTIVE: Epilepsy is a most common serious neurological disorder and is one of the world's most prevalent non-communicable diseases. The aim of this study was to determine the prevalence and risk factors of epilepsy in 0-17 year old children in Trabzon, Turkey. METHODS: A cross-sectional epidemiological investigation was performed in two phases, a screening phase and a confirmation of the diagnosis phase. The gold standard was a clinical investigation and neurological examination. The diagnosis of epilepsy followed clinical guidelines proposed by the International League against Epilepsy (ILAE). The chi-square test was used in analysis of the results and P-value <0.05 was calculated. FINDINGS: The prevalence per 1000 participants of epilepsy was 8.6 (5.9-11.4; (95%)CI). We detected 37 cases (18 males and 19 females) of epilepsy. The male/female ratio was 0.95. This study showed an increased risk for epilepsy with low socioeconomic level, a history of postpartum seizure, meningitis, head trauma, febrile convulsion and family history of epilepsy. More than one seizure type was present in 15 (40.5%) of epileptic children. Generalized tonic-clonic seizures were determined in 24 patients (64.9%) and absence type in 9 (24.3%). It was found that 25.0% of children with epilepsy had never visited the school at the time the study was performed due to the disease and attendant seizures. CONCLUSION: The prevalence of epilepsy in Trabzon is low compared to other parts of Turkey and other developing countries.

Factors contributing to regular smoking in adolescents in Turkey.

PURPOSE: The objectives of this study were to determine the levels of lifetime cigarette use, daily use, and current use among young people (aged 15-19 years) and to examine the risk factors contributing to regular smoking. METHODS: The number of students was determined proportionately to the numbers of students in all the high schools in the province of Trabzon in Turkey. The data were gathered using the questionnaire method. A total of 4666 students participated in the study. The chi-square test and logistic regression analysis were used in data analysis. RESULTS: Of the 4666 students who took part in the study, the level of lifetime cigarette use was 38.2% (n = 1796), that of lifetime daily cigarette use was 10.5% (n = 491), and that of current cigarette use was 9.5% (n = 447). Male students (P < .0005), those whose mothers were smokers (P < .0005), those whose fathers smoked (P = .005), those whose siblings smoked (P<.0005), those whose friends smoked (P < .0005), those whose teachers smoked (P = .001), and low achievers in school (P < .0005) stated that they significantly smoked on a more regular basis. According to the results of the logistic regression analysis, the following risk factors were statistically significant: male students smoked 3.02 times (95% CI 2.20-4.16) more than females, those whose mothers were smokers smoked 1.57 times (95% CI 1.09-2.28) more than those whose mothers were not, those whose friends were smokers smoked 2.42 times (95% CI 1.73-3.39) more than those whose friends were non-smokers, poor achievers in school smoked 2.62 times (95% CI 1.97-3.49) more than high achievers, and those without poor grades smoked 1.75 times more (95% CI 1.23-2.40), the risk rising 1.06 times (95% CI 1.01-1.11) with earlier age at first experimentation. The risk of daily cigarette use was observed to decline by 0.91 times (95% CI 0.84-0.98) with increasing numbers of siblings. CONCLUSION: Effective smoking prevention programs should take into account the dominant influence of peer groups in the onset and continuation of smoking.