Reduced metabolic flexibility is a predictor of weight gain among liver transplant recipients.

Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (ß-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (ß-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (ß-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.

Patient- and provider-level factors that underlie alcohol use disorder treatment offer and acceptance in veterans with cirrhosis.

BACKGROUND: Untreated alcohol use disorder (AUD) is associated with poor cirrhosis outcomes. We evaluated factors associated with AUD treatment discussions and initiation in the Veterans Health Administration. METHODS: Chart reviews were conducted for veterans with International Classification of Diseases codes for both cirrhosis and AUD who were receiving care at one of three large medical centers in 2020. Factors associated with a 1-year offer of AUD treatment and its acceptance were assessed using regression models, which included as covariates demographic characteristics, comorbidities, and depression, as measured by the patient health questionnaire (PHQ-2) from the electronic health record. RESULTS: The cohort included 654 veterans, 68 of whom were engaged in AUD treatment at baseline and 174 who were documented as being in AUD remission. Treatment was offered to 264 (64%) of the 412 veterans with opportunities to initiate it. AUD treatment discussions were most often documented by practitioners in primary care (n = 162), hepatology (n = 45), or both (n = 41). Multivariable logistic regression modeling revealed that treatment was significantly more likely to be offered to patients with co-occurring bipolar disorder (OR 2.94, p = 0.03) or depression (1.50, p = 0.05) or who were younger (0.97, p = 0.01). Of the 264 patients offered AUD treatment, 107 (40%) agreed to initiate it. Acceptance of an offer of treatment was significantly associated with hospitalization in the prior year (OR 1.74, p = 0.05), prior AUD treatment (9.92, p < 0.0001), and a higher PHQ-2 depression score (2.85, p = 0.004). CONCLUSIONS: We identified factors associated with an offer of AUD treatment and its initiation among veterans with cirrhosis. Application of these findings could increase the likelihood that veterans with alcoholic cirrhosis initiate AUD treatment.

Glutathione and thioredoxin systems of the malaria parasite Plasmodium falciparum: Partners in crime?

In P. falciparum, antioxidant proteins of the glutathione and thioredoxin systems are compartmentalized. Some subcellular compartments have only a partial complement of these proteins. This lack of key anti-oxidant proteins in certain sub-cellular compartments might be compensated by functional complementation between these systems. By assessing the cross-talk between these systems, we show for the first time, that the glutathione system can reduce thioredoxins that are poor substrates for thioredoxin reductase (Thioredoxin-like protein 1 and Thioredoxin 2) and thioredoxins that lack access to thioredoxin reductase (Thioredoxin 2). Our data suggests that crosstalk between the glutathione and thioredoxin systems does exist; this could compensate for the absence of certain antioxidant proteins from key subcellular compartments.

Spontaneous Hepatic Hemorrhage Causing Acute Liver Failure Requiring Liver Transplant.

Spontaneous hepatic hemorrhage (SHH) is a very rare but life-threatening entity that results from a breach in the hepatic parenchyma without any external cause, the most common being hepatocellular carcinoma and hepatic adenoma. We present a case of SHH without any underlying tumor or injury. The cause in our patient remained unclear, but we hypothesize that the patient's SHH was most likely coagulopathy-related.

Biochemical and molecular mechanisms of antibiotic resistance in Salmonella spp.

Salmonella is a diverse Gram-negative bacterium that represents the major disease burden worldwide. According to WHO, Salmonella is one of the fourth global causes of diarrhoeal disease. Antibiotic resistance is a worldwide health concern, and Salmonella spp. is one of the microorganisms that can evade the toxicity of antimicrobials via antibiotic resistance. This review aims to deliver in-depth knowledge of the molecular mechanisms and the underlying biochemical alterations perceived in antibiotic resistance in Salmonella. This information will help understand and mitigate the impact of antibiotic-resistant bacteria on humans and contribute to the state-of-the-art research developing newer and more potent antibiotics.

Clinical implications of COVID-19 in patients with metabolic-associated fatty liver disease.

People across the world are affected by the "coronavirus disease 2019 (COVID-19)", brought on by the "SARS-CoV type-2 coronavirus". Due to its high incidence in individuals with diabetes, metabolic syndrome, and metabolic-associated fatty liver disease (MAFLD), COVID-19 has gained much attention. The metabolic syndrome's hepatic manifestation, MAFLD, carries a significant risk of type-2-diabetes. The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic. Independent of the metabolic syndrome, MAFLD may impact the severity of the viral infections, including COVID-19 or may even be a risk factor. An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics. Many liver markers are seen elevated in COVID-19. MAFLD patients with associated comorbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension, and old age are prone to develop severe disease. There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19. The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19. This review investigates the implications of COVID-19 on liver injury and disease severity and vice-versa. We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.

Determination of Wolbachia diversity in butterflies from Western Ghats, India, by a multigene approach.

Members of the genus Wolbachia are intracellular bacteria that are widespread in arthropods and establish diverse symbiotic associations with their hosts, ranging from mutualism to parasitism. Here we present the first detailed analyses of Wolbachia in butterflies from India with screening of 56 species. Twenty-nine species (52%) representing five families were positive for Wolbachia. This is the first report of Wolbachia infection in 27 of the 29 species; the other two were reported previously. This study also provides the first evidence of infection in the family Papilionidae. A striking diversity was observed among Wolbachia strains in butterfly hosts based on five multilocus sequence typing (MLST) genes, with 15 different sequence types (STs). Thirteen STs are new to the MLST database, whereas ST41 and ST125 were reported earlier. Some of the same host species from this study carried distinctly different Wolbachia strains, whereas the same or different butterfly hosts also harbored closely related Wolbachia strains. Butterfly-associated STs in the Indian sample originated by recombination and point mutation, further supporting the role of both processes in generating Wolbachia diversity. Recombination was detected only among the STs in this study and not in those from the MLST database. Most of the strains were remarkably similar in their wsp genotype, despite divergence in MLST. Only two wsp alleles were found among 25 individuals with complete hypervariable region (HVR) peptide profiles. Although both wsp and MLST show variability, MLST gives better separation between the strains. Completely different STs were characterized for the individuals sharing the same wsp alleles.

Using biomarkers to quantify problematic alcohol use.

Direct biomarkers detect alcohol even in small amounts shortly after ingestion. But which one is nearly 100% specific for alcohol use?

Metabolic complications of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.

Effect of Saliva Contamination on Shear Bond Strength of Self-etch Adhesive System to Dentin: An In Vitro Study.

AIM AND OBJECTIVE: This study aimed to evaluate the outcome of saliva contamination on shear bond strength (SBS) of a self-etch adhesive system to dentin. MATERIALS AND METHODS: A total of 60 premolars were selected. Occlusal surfaces of the teeth were severed off. Three groups of 20 teeth in each were formed after the samples were randomly divided. Group I: Not subjected to any contamination (control group). Group II: Contamination with saliva occurred before coating the teeth with a self-etch adhesive system. Group III: Contamination with saliva occurred after coating the teeth with a self-etch adhesive system. After the contamination, the composite was placed with the help of a Teflon tube. Under the universal testing machine, the SBS of these samples was then tested. RESULTS: The data obtained after testing were analyzed using SPSS software. Statistical difference was seen between all the three groups. Group II projected the least SBS. CONCLUSION: Contamination with saliva has a deleterious effect on the SBS. Contamination that occurs before the application of adhesive systems has shown considerably reduced SBS. CLINICAL SIGNIFICANCE: This study successfully established that saliva contamination acts as a major factor in reducing the SBS of the bonding agent. Hence, in clinical situations, it is necessary to ensure sufficient steps are taken to eliminate or reduce the chances of contamination with saliva to aid in the success of the restoration. HOW TO CITE THIS ARTICLE: Chaudhari RR, Srivastava HR, Raisingani D, et al. Effect of Saliva Contamination on Shear Bond Strength of Self-etch Adhesive System to Dentin: An In Vitro Study. Int J Clin Pediatr Dent 2021;14(4):443-446.

A Comparative Evaluation of the Effectiveness of Added Auxiliary Features, Occlusal Surface Modifications, and Reduction of Total Occlusal Convergence on the Resistance of Full Veneer Metal Crowns on a Molar Tooth with Inadequate Resistance Form: An in vitro Study.

INTRODUCTION: Single crowns or fixed partial dentures retainers usually get dislodged due to inadequate resistance form. Hence, it is prudent to evaluate features of a tooth preparation, which can prevent these failures. AIM: To evaluate the effect of auxiliary features, occlusal surface modifications, and total occlusal convergence (TOC) on the resistance of a full veneer crown. MATERIALS AND METHODS: An ivorine mandibular molar tooth was prepared with features of inadequate resistance form, i.e., 2.5 mm axial wall height and TOC of 20°. Seven auxiliary preparation features were subsequently added one by one to it. They were mesiodistal grooves, buccolingual and mesiodistal grooves, buccolingual grooves, mesiodistal boxes, occlusal inclined planes, 8° reduced TOC in the cervical aspect, and mesiodistal grooves added to 8° reduced TOC in the cervical aspect. Ten dies with their respective crowns were prepared for each group. Resistance testing of all the samples was performed on the INSTRON testing machine. RESULTS: Modification of the overtapered die preparation by reducing the TOC to 8° in the cervical 1.5 mm of the axial wall and then subsequently adding mesiodistal grooves to the reduced TOC cervically offered the greatest resistance to dislodgment statistically. CONCLUSION: For an overtapered preparation, reducing the TOC to 8° in the cervical aspect and subsequently adding proximal grooves can provide maximum resistance form.

Subaxial cervical pedicle screw insertion with newly defined entry point and trajectory: accuracy evaluation in cadavers.

Successful placement of cervical pedicle screws requires accurate identification of both entry point and trajectory. However, literature has not provided consistent recommendations regarding the direction of pedicle screw insertion and entry point location. The objective of this study was to define a guideline regarding the optimal entry point and trajectory in placing subaxial cervical pedicle screws and to evaluate the screw accuracy in cadaver cervical spines. The guideline for entry point and trajectory for each vertebra was established based on the recently published morphometric data. Six fresh frozen cervical spines (C3-C7) were used. There were two men and four women. After posterior exposure, the entry point was determined and the cortical bone of the entry point was removed using a 2-mm burr. Pilot holes were created with a cervical probe based on the guideline using fluoroscopy. After tapping, 3.5-mm screws with appropriate length were inserted. After screw insertion, every vertebra was dissected and inspected for pedicle breach. The pedicle width, height, pedicle transverse angulation and actual screw insertion angle were measured. A total of 60 pedicle screws were inserted. No statistical difference in pedicle width and height was found between the left and right sides for each level. The overall accuracy of pedicle screws was 83.3%. The remaining 13.3% screws had noncritical breach, and 3.3% had critical breach. The critical breach was not caused by the guideline. There was no statistical difference between the pedicle transverse angulation and the actual screw trajectory created using the guideline. There was statistical difference in pedicle width between the breach and non-breach screws. In conclusion, high success rate of subaxial cervical pedicle screw placement can be achieved using the recently proposed operative guideline and oblique views of fluoroscopy. However, careful preoperative planning and good surgical skills are still required to ensure screw placement accuracy and to reduce the risk of neural and vascular injury.

Hepatoid Adenocarcinoma Presenting as Pancreatitis.

Hepatoid adenocarcinoma (HAC) is an uncommon and aggressive type of adenocarcinoma, typically affecting the middle-aged and elderly. The morphological features of the HAC resemble hepatocellular carcinoma. Presenting symptoms may include upper abdominal pain, hematemesis, back pain, and palpable abdominal mass. HAC has no proven therapy, and the prognosis is extremely poor. Early surgical removal with chemotherapy remains the standard of care. We describe one of the youngest patients in the literature with HAC who presented with acute pancreatitis. The diagnostic workup was confused by diffuse lymphadenopathy and elevated ß-human chorionic gonadotropin making lymphoma and germ cell tumor likely possibilities until immunohistochemistry confirmed the diagnosis.

Hypothalamic-pituitary-adrenal axis suppression - The value of salivary cortisol and cortisone in assessing hypothalamic-pituitary-adrenal recovery.

BACKGROUND: The 0.25 mg short synacthen test is used to assess recovery from hypothalamic-pituitary-adrenal suppression due to chronic glucocorticoid administration. We assessed the potential role of salivary cortisol and cortisone in predicting hypothalamic-pituitary-adrenal function using the short synacthen test as the gold standard test. METHOD: Between 09:00 and 10:30, salivary and blood samples were collected just prior to a short synacthen test to assess hypothalamic-pituitary-adrenal axis recovery in patients previously treated with oral glucocorticoids. The cut-off for a normal short synacthen test was a 30-min cortisol ≥450 nmol/L. RESULTS: Fifty-six short synacthen tests were performed on 47 patients. Of these, 15 were normal. The area under receiver operating characteristic curves for serum cortisol, salivary cortisone and salivary cortisol were 0.772, 0.785 and 0.770, respectively. From the receiver operating characteristic analysis, the cut-offs for baseline serum cortisol (≥365 nmol/L) and salivary cortisone (≥37.2 nmol) predicted hypothalamic-pituitary-adrenal axis recovery with 100% specificity in 26.7% of pass short synacthen tests, whereas salivary cortisol predicted none. Baseline serum cortisol (≤170 nmol/L), salivary cortisone (≤9.42 nmol/L) and salivary cortisol (≤1.92 nmol/L) predicted hypothalamic-pituitary-adrenal suppression with 100% sensitivity in 58.5%, 53.7% and 51.2% of failed short synacthen tests, respectively. Using these cut-offs, baseline serum cortisol, salivary cortisone and salivary cortisol could reduce the need for short synacthen tests by 50%, 46% and 37%, respectively. CONCLUSION: Although marginally inferior to early morning serum cortisol, early morning salivary cortisone may be used as a first-line test for assessing hypothalamic-pituitary-adrenal function. We plan to incorporate salivary cortisone into a home-based patient pathway to identify patients with hypothalamic-pituitary-adrenal recovery, continuing hypothalamic-pituitary-adrenal suppression and those who require a short synacthen test.

A new insight into the adsorption-dissolution growth mechanism of zinc oxide hollow hexagonal nanotowers.

The formation mechanism of zinc oxide (ZnO) hollow hexagonal nanotowers (h-HNTs) synthesized using a simple hydrothermal method was studied. Crystal growth and dissolution mechanism were correlated to the formation of voids and grain boundaries in the nanotowers and are supported by imaging evidence for the first time. Elevated reaction temperature, various ions present in the reaction medium and these voids are responsible for the adsorption-dissolution process and formation of ZnO h-HNTs.

Membrane and luminal proteins reach the apicoplast by different trafficking pathways in the malaria parasite Plasmodium falciparum.

The secretory pathway in Plasmodium falciparum has evolved to transport proteins to the host cell membrane and to an endosymbiotic organelle, the apicoplast. The latter can occur via the ER or the ER-Golgi route. Here, we study these three routes using proteins Erythrocyte Membrane Protein-1 (PfEMP1), Acyl Carrier Protein (ACP) and glutathione peroxidase-like thioredoxin peroxidase (PfTPxGl) and inhibitors of vesicular transport. As expected, the G protein-dependent vesicular fusion inhibitor AlF4- and microtubule destabilizing drug vinblastine block the trafficking of PfEMP-1, a protein secreted to the host cell membrane. However, while both PfTPxGl and ACP are targeted to the apicoplast, only ACP trafficking remains unaffected by these treatments. This implies that G protein-dependent vesicles do not play a role in classical apicoplast protein targeting. Unlike the soluble protein ACP, we show that PfTPxGl is localized to the outermost membrane of the apicoplast. Thus, the parasite apicoplast acquires proteins via two different pathways: first, the vesicular trafficking pathway appears to handle not only secretory proteins, but an apicoplast membrane protein, PfTPxGl; second, trafficking of apicoplast luminal proteins appear to be independent of G protein-coupled vesicles.

Characterization of anticonvulsant and antiepileptogenic potential of thymol in various experimental models.

The present study was to investigate the anticonvulsant and antiepileptogenic potential of thymol. Anticonvulsant activity of thymol (5-100 mg/kg i.p.) was studied using maximal electroshock, pentylenetetrazole (PTZ), strychnine and 4-aminopyridine (4-AP) models. Thymol at the selected dose was also studied for its effect on locomotion. Antiepileptogenic property of thymol (5-25 mg/kg) was evaluated using PTZ-induced kindling model along with its effect on malondialdehyde and glutathione levels. Thymol (50 and 100 mg/kg, i.p.) showed anticonvulsant activity against maximal electroshock and pentylenetetrazole (66.66 and 83.33 % protection at 50 and 100 mg/kg, respectively) model but not against strychnine and 4-aminopyridine models. Thymol exhibited decreased locomotor activity in dose-dependent manner at the same dose range. Thymol at the dose of (25 mg/kg, i.p.) significantly decreased the seizure score, increased glutathione levels and decreased malondialdehyde levels in pentylenetetrazole-induced kindling model. Thymol exhibited significant anticonvulsant and antiepileptogenic property.

A novel trafficking pathway in Plasmodium falciparum for the organellar localization of glutathione peroxidase-like thioredoxin peroxidase.

Although common in plants, very few proteins are currently known to be localized to both the plastid and the mitochondrion in Plasmodium falciparum. One such protein is P. falciparum glutathione peroxidase-like thioredoxin peroxidase (PfTPx(Gl)) which we show, by immunofluorescence imaging and bioinformatics predictions, is localized to the apicoplast, the mitochondrion and the cytosol. The distribution of PfTPx(Gl) was random in the population, with the protein localizing to any one organelle in some parasites and to both in others. It has been proposed that targeting to each organelle occurs via independent pathways that do not proceed via the Golgi. However, for PfTPx(Gl), both incubation at low temperature (15 °C) and Brefeldin A treatment reversibly blocked targeting to these organelles, suggesting the involvement of a novel trafficking route, most probably via the endoplasmic reticulum and Golgi. This idea is further supported by the lack of cleavage of the putative N-terminal signal sequence of PfTPx(Gl), and this N-terminal extension did not compromise PfTPx(Gl) enzyme activity. In the context of evolution, a common pathway for the dual localization of a single gene product, such as the primitive endoplasmic reticulum-Golgi route, may have been retained as opposed to optimization for individual organellar import pathways.