Role of three-dimensional printing and laser scanning in aesthetic restoration of Parry Romberg's disease using de-epithelialized anterolateral thigh flap: a case report.

Parry Romberg syndrome also known as progressive hemifacial atrophy is an uncommon degenerative condition, characterized by unilateral, slow, and progressive atrophy of face. Patient presents with loss of facial symmetry and neurological manifestations. After the degenerative process settles, reconstructive surgeries are performed to address facial asymmetry. For accurate assessment of volume deficit, laser scanning and three- dimensional printing can be used which offers the advantage of precise surgical planning and good aesthetic outcome. We present a case of soft tissue reconstruction in Parry Romberg syndrome with anterolateral thigh flap with use of three- dimensional laser scanning.

Automatic Identification of Hate Speech - A Case-Study of alt-Right YouTube Videos.

Background: Identifying hate speech (HS) is a central concern within online contexts. Current methods are insufficient for efficient preemptive HS identification. In this study, we present the results of an analysis of automatic HS identification applied to popular alt-right YouTube videos. Methods: This essay describes methodological challenges of automatic HS detection. The case study concerns data on a formative segment of contemporary radical right discourse. Our purpose is twofold. (1) To outline an interdisciplinary mixed-methods approach for using automated identification of HS. This bridges the gap between technical research on the one hand (such as machine learning, deep learning, and natural language processing, NLP) and traditional empirical research on the other. Regarding alt-right discourse and HS, we ask: (2) What are the challenges in identifying HS in popular alt-right YouTube videos? Results: The results indicate that effective and consistent identification of HS communication necessitates qualitative interventions to avoid arbitrary or misleading applications. Binary approaches of hate/non-hate speech tend to force the rationale for designating content as HS. A context-sensitive qualitative approach can remedy this by bringing into focus the indirect character of these communications. The results should interest researchers within social sciences and the humanities adopting automatic sentiment analysis and for those analysing HS and radical right discourse. Conclusions: Automatic identification or moderation of HS cannot account for an evolving context of indirect signification. This study exemplifies a process whereby automatic hate speech identification could be utilised effectively. Several methodological steps are needed for a useful outcome, with both technical quantitative processing and qualitative analysis being vital to achieve meaningful results. With regard to the alt-right YouTube material, the main challenge is indirect framing. Identification demands orientation in the broader discursive context and the adaptation towards indirect expressions renders moderation and suppression ethically and legally precarious.

Reconstructive management of a patient with Tessier number 10 cleft.

Tessier number 10 cleft is one of the rarest facial clefts. Surgical treatment of this type of cleft is challenging due to the complexity of periorbital and temporal soft tissue deformities. A 23-year-old male patient presented with typical facial deformities of Tessier number 10 cleft. The surgical procedure involved using a free anterolateral thigh flap to reconstruct the eye socket, while the superficial temporal artery pedicle scalp flap was used to reconstruct the eyebrow deformity. The patient had no complications and 16 months after surgery, the patient had good aesthetic results. A hair-bearing scalp flap with a pedicle of the frontal branch of the superficial temporal artery combined with an anterolateral thigh-free flap can effectively resolve most soft tissue deformities of Tessier number 10 cleft and reconstruct the orbital socket in a single surgery. At the same time, it augments the soft tissue of the frontotemporal area and provides good aesthetic results.

The Past, Present, and Future of Perforator Flaps in Head and Neck Surgery.

A perforator is a vessel that travels through muscle and perfuses the skin. Perforator flaps require intramuscular dissection and can be used as pedicled or free flap. With improved understanding of microvasculature, they can be tailored to have multiple skin paddles, multiple components, or shaped to conform to any defect. Reliable perforator flap-based reconstruction is a meticulous microvascular technique, ultimately allowing the surgeon to harvest any flap in a freestyle fashion and transplant to any recipient vessel. New technologies improve the safety and reproducibility of this type of reconstruction.

The different associations of serum gamma-glutamyl transferase and alanine aminotransferase with insulin secretion, ß-cell function, and insulin resistance in non-obese Japanese.

The present study investigated the associations of serum gamma-glutamyl transferase (GGT), a marker of fatty liver and oxidative stress, and ALT/AST, a marker of fatty liver, with percentage trunk fat and postload glucose, insulin resistance, and ß-cell function in middle-aged Japanese individuals, whose BMI averaged < 23.0 kg/m2. Pancreatic ß-cell function was assessed using the disposition index calculated by a product of the insulinogenic index (IGI) and Matsuda insulin sensitivity index, a biomarker of early-phase glucose-stimulated insulin secretion and whole-body insulin sensitivity, respectively. Multivariate linear regression analyses revealed that the disposition index was associated inversely with GGT independently of percentage trunk fat, homeostasis model assessment insulin resistance (HOMA-IR), a marker of insulin resistance, and Matsuda index. When IGI was included instead of the disposition index, IGI (inversely) and HOMA-IR were associated with GGT independently of percentage trunk fat and Matsuda index. When the area under the glucose concentration curve (AUCg) during an oral glucose tolerance test was included instead of the disposition index, AUCg and HOMA-IR emerged as independent determinants of GGT. ALT/AST was associated with HOMA-IR alone. Results suggest a different pathophysiologic basis between GGT and ALT/AST in predicting diabetic risk in non-obese Japanese.

Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India.

Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% females and 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereas in the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01). Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However, compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higher bilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift toward prevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHC who are obese and have low platelet counts with higher liver enzymes.

Tailoring of ALT Flap for Optimizing Donor Site Morbidity.

Wide and irregular-shaped defects at the lower trunk region are not uncommon following wide local excision of tumors. Pedicled anterolateral thigh (ALT) perforator flap has been the workhorse for these types of defects. But, in most of the cases flap donor sites cannot be closed primarily due to wide and irregular-shaped flap requirement. We propose a method of harvesting ALT flap in elliptical shape, dividing it into two or more geometrically predesigned islands based on perforators and rearranging them to fit into the defect, and thus achieving primary closure of the flap donor site.

Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.

Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

TFL Perforator Flap Complementing and Completing the ALT-AMT Flap Axis.

Background Anterolateral thigh (ALT) flap is the most common soft tissue flap used for microvascular reconstruction of head and neck. Its harvest is associated with some unpredictability due to variability in perforator characteristics, injury or unfavorable configuration for complex defects. Anteromedial thigh (AMT) flap is an option, but the low incidence and thickness restrict its utility. Tensor fascia lata (TFL) perforator (TFLP) flap is an excellent option to complement ALT. Its perforator is consistent, robust, in vicinity, and lends itself with the ALT perforator. Methods This study was an analysis of 29 cases with a free flap for head neck reconstruction with an element of TFLP flap from July 2017 to May 2021. Results All cases were primarily planned for an ALT reconstruction. There was absence of the ALT perforator in 16 cases but a sizable TFL perforator was available. In 13 cases, the complex defect warranted use of both ALT plus TFL in a conjoint (5), chimeric (5), and multiple (3) free flaps manner. Most common perforator location was septocutaneous between the TFL and gluteus medius. There was complete flap loss in two cases and partial necrosis in two. No adjuvant therapy was delayed. Conclusion TFLP can reliably complement the ALT/AMT axis. Chimeric ALT-TFL can be harvested for large, complex, multicomponent, and multidimensional defects.

5-aza-2'-deoxycytidine induces telomere dysfunction in breast cancer cells.

AIMS: Azacitidine, a drug that epigenetically modifies DNA, is widely used to treat haematological malignancies. However, at low doses, it demethylates DNA, and as a result, can alter gene expression. In our previous publication, we showed that low doses of azacitidine induce telomere length elongation in breast cancer cells. In this study, we aim to identify the mechanisms which lead to telomere length increases. METHODS: Breast cancer cell lines representing different molecular sub-types were exposed to 5-aza-2'-deoxycytidine (5-aza) in 2 and 3D cultures, followed by DNA, RNA, and protein extractions. Samples were then analysed for telomere length, DNA damage, telomerase, and ALT activity. RESULTS: We show that treatment of the cell lines with 5-aza for 72 h induced DNA damage at the telomeres and increased ALT activity 3-fold. We also identified a gene, POLD3, which may be involved in the ALT activity seen after treatment. CONCLUSION: Our results indicate that while 5-aza is a useful drug for treating haematological cancers, surviving cancer cells that have been exposed to lower doses of the drug may activate mechanisms such as ALT. This could lead to cancer cell survival and possible resistance to 5-aza clinically.

Seroepidemiology of hepatitis B virus (HBV) and relationship to serum transaminase levels in Indian population.

Background: Hepatitis B virus (HBV) infection is a serious public health issue that must be addressed. Aim: The goal of this study was to investigate the correlation between serological status for hepatitis Be antigen (HBeAg)/anti-HBe, serum transaminase levels, and serum HBV-DNA in patients with chronic HBV infection. Methods: A retrospective observational study with 620 patients with persistent HBV infection (mean age, 36.35 years; 506 men) was conducted. All patients tested positive for hepatitis B surface antigen (HBsAg). Liver profile, HBeAg, and anti-HBe antibody tests were conducted for all patients. Additionally, serum HBV DNA was examined using a DNA assay in these individuals. Results: Of 620 patients, 114 (18.39%) were HBeAg-positive and 506 (81.61%) HBeAg-negative. A detectable level of HBV DNA was found in 89.79% of HBeAg-positive/anti-HBe negative patients compared to HBeAg-negative/anti-HBe positive carriers 33.69% (P value <0.0001). The median viral load was significantly higher in HBeAg-positive cases (4.72 log10 copies/mL) than in HBeAg-negative individuals (4.23 log10 copies/mL; P = 0.997). Additionally, a higher proportion of HBeAg-positive samples (P = 0.0001) had HBV-DNA levels above 10,000 copies/mL.

VRAM Versus ALT Flap Reconstruction for Large Head and Neck Defects: Does Weight Influence Complication Rate?

Background: Obesity remains a high-level risk factor for various cancers. Yet, some research has shown that higher BMIs may improve survival outcomes, particularly for head and neck squamous cell carcinoma (HNSCC). While this is a clear deviation from the norm, it raises the question of what other effects obesity may have on head and neck cancer patients, including surgical outcomes. Choosing the most appropriate flap for patients can be difficult for even experienced surgeons. Head and neck reconstructive surgeries are no exception to this rule and can be especially challenging. To produce the most favorable outcomes, a physician must be able to combine all flap attributes including donor and recipient site location, flap thickness, as well as each patient's individual risk factors such as prior radiation. Purpose: The purpose of this study was to compare the outcomes of vertical rectus femoris myocutaneous (VRAM) and anterolateral thigh (ALT) flaps in overweight and obese individuals with varying head and neck cancers leaving large-sized defects to the outcomes in normal and underweight patients. Methods: A retrospective chart review was conducted of VRAM and ALT flaps performed over a period of 12 months at our university hospital for large head and neck reconstruction. Results: Of the 17 ALT patients, 80% (4/5) of the underweight patients, 57% (4/7) of the normal weight patients, 50% (1/2) of the overweight patients, and 33% (1/3) of the obese patients experienced complications. Of the 15 VRAM patients, 40% (2/5) of the underweight patients, 83% (5/6) of the overweight patients, and 50% (1/2) of the obese patients experienced complications. Conclusions: In our small sample size, a smaller percentage of obese patients with head and neck cancer who underwent flap reconstruction surgery had complications when undergoing ALT flaps than VRAM flaps, which contrasts with the normal and underweight patients, who had less complications with VRAM flaps than ALT flaps.

Protective Effect of Minimally Invasive Approach on Postoperative Peak Transaminase Following Liver Resection: A Single-Center Propensity Score-Based Analysis.

BACKGROUND: Postoperative serum ALT levels are one of the most frequently used marker to detect liver tissue damage following liver resection. The aim of this study was to evaluate if minimally invasive liver surgery (MILS) may result in less hepatic injury than open hepatectomy by assessing the differences of postoperative ALT levels. METHODS: Patients who underwent MILS between 2009 and 2019 at our unit were included and compared with open liver resections. Median ALT levels was measured on postoperative day (POD) 1, 3 and 5. Postoperative peak transaminase (PPT) of ALT was determined on POD 1. The stabilized inverse probability treatment weighing (SIPTW) process was used to balance the two groups. A multivariable logistic regression analysis was used to analyze factors associated with high PPT. RESULTS: After SIPTW, 292 MILS were compared with 159 open resections. Median ALT levels on POD 1, 3 and 5 were significantly higher in the open group than in the MILS group (301 vs. 187, p = 0.002; 180 vs. 121, p < 0.0001; 104 vs. 60, p < 0.0001; respectively). At the multivariable logistic regression analysis, MILS showed a protective effect for high PPT. CONCLUSIONS: MILS was associated with significantly lower postoperative ALT levels compared with open liver resections. MILS showed a protective effect for high PPT.

Nutraceutical composition (yeast ß-glucan, prebiotics, minerals, and silymarin) predicts improvement of sleep quality and metabolic parameters: A randomized pilot study.

BACKGROUND & AIMS: The search for integrative and natural therapies that favor homeostasis to boost sleep and diet quality took place for young adult populations as a non-pharmacological strategy for long-term good quality of life. Thus, the present pilot study aims to investigate the effects of 90-day consumption of a nutraceutical composition on the neuro-immune-endocrine axis, providing better sleep quality and health improvement. METHODS: For this, from March 2021 to June 2021, twenty-two Brazilian young adult volunteers (women and men) with BMI between 18.5 and 34.9 kg/m2 were divided into three distinct supplementation groups: NSupple; NSupple plus_S, and NSupple plus. Briefly, the supplement compositions included yeast ß-glucan, prebiotics, and minerals in different concentrations associated or not with the herbal medicine silymarin. Neither nutritional nor physical activity interventions were performed during this pilot study period. The anthropometrics measures, questionnaires answer data, and harvest blood for metabolic, inflammatory, and hormonal tests were collected at baseline time (day zero-T0) and day 90 (T90) post-supplementation. RESULTS: Our results highlight that the supplementation reduced body mass index (BMI), Waist-to-height ratio (WHtR), waist circumference, AST/ALT ratio, alkaline phosphatase, and HbA1c. Post-supplementation the IL-6 and IL-10 levels and the sleep, humor, and quality of life scores were suggested to improve. Sleep quality improvement seems to predict the reduction of adiposity-related body measures. CONCLUSION: In sum, the nutraceutical supplementation might be related to anthropometric, metabolic, and endocrine parameters after 90 days reflecting on perception of humor, sleep, and life quality enhancement. However, it is important to recognize the limitation of the data presented considering that this was a pilot study. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04810572 registered on 20th February 2021.

Investigating the structural and functional consequences of germline single nucleotide polymorphisms located in the genes of the alternative lengthening of telomere (ALT) pathway.

Background: The Alternative Lengthening of Telomeres (ALT) pathway represents a non-canonical mechanism of telomere maintenance that operates independently of the conventional telomerase activity. The three biologically significant proteins, designated as SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1), DAXX (Death domain-associated protein 6) and ATRX (alpha-thalassemia/mental retardation, X-linked) are associated with ALT in certain cancer types. The purpose of this study was to identify the most high-risk nsSNPs (non-synonymous Single Nucleotide Polymorphisms) within these three genes and assess their impacts on the structure and function of the proteins they encode. Methods: The reported genetic polymorphisms of SMARCAL1, DAXX and ATRX genes were retrieved from the Ensembl database. Later, various computational tools like PROVEAN, PolyPhen2, SNPs and GO, SNAP2, Predict-SNP, Panther and PMut were used to predict the most deleterious nsSNPs. MutPred was used to understand the underlying molecular reasons of those nsSNPs being deleterious, followed by prediction of Post Translational Modification Sites (PTMs) using ModPred. I-Mutant and MUpro were used to predict the effect of SNP on energy stability. Later, 3D clustering analysis was done using Mutation 3D server. Moreover, ConSurf was utilized to identify the conservation scores of wild-type amino acids. Additionally, the NCBI conserved domain search tool was employed to pinpoint conserved domains within these three proteins. Project-Hope helped for biophysical validation, followed by prediction of these genes' interaction and function by using GeneMANIA. Result: Analysis on SMARCAL1 protein revealed that among 665 nsSNPs, four were identified as the most deleterious: L578S, T581S, P582A, and P582S. Similarly, within the DAXX protein, among a pool of 480 nsSNPs, P284S, R230C, and R230S were found out to be the most deleterious variants. In case of ATRX protein, V178D, R246C, and V277G, from the total of 1009 nsSNPs, were predicted to be the most deleterious. All these nsSNPs were found to occur at residue positions that are 100 % conserved within protein domains and were predicted to be most damaging from both structural and functional perspectives and highly destabilizing to their corresponding proteins. Conclusion: Computational investigation on the 3 proteins-SMARCAL1, DAXX and ATRX through different bioinformatics analysis tools concludes that the identified high risk nsSNPs of these proteins are pathogenic SNPs. These variants potentially exert functional and structural influences, thus making them valuable candidates for future genetic studies.

Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study.

BACKGROUND & AIMS: This was a randomized, double-blind, placebo-controlled study to assess the effects of pemvidutide, a glucagon-like peptide-1 (GLP-1)/glucagon dual receptor agonist, on liver fat content (LFC) in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Subjects with a BMI ≥28.0 kg/m2 and LFC ≥10% by magnetic resonance imaging-proton density fat fraction were randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks. Participants were stratified according to a diagnosis of type 2 diabetes mellitus (T2DM). The primary efficacy endpoint was relative reduction (%) from baseline in LFC after 12 weeks of treatment. RESULTS: 94 subjects were randomized and dosed. Median baseline BMI and LFC across the study population were 36.2 kg/m2 and 20.6%; 29% of subjects had T2DM. At Week 12, relative reductions in LFC from baseline were (1.2 mg) 46.6% [95% CI -63.7 to -29.6], (1.8 mg) 68.5% [95% CI -84.4 to -52.5], and (2.4 mg) 57.1% [95% CI -76.1 to -38.1] versus 4.4% [95% CI -20.2 to 11.3] in placebo subjects (p <0.001 vs. placebo, all treatment groups), with 94.4% and 72.2% of subjects achieving 30% and 50% reductions in LFC and 55.6% achieving normalization (≤5% LFC) at the 1.8 mg dose. Maximal responses for weight loss (-4.3%; p <0.001), alanine aminotransferase (-13.8 IU/L; p = 0.029), and corrected cT1 (-75.9 ms; p = 0.002) were all observed at the 1.8 mg dose. Pemvidutide was well-tolerated at all doses with no severe or serious adverse events. CONCLUSIONS: In subjects with MASLD, weekly pemvidutide treatment yielded significant reductions in LFC, markers of hepatic inflammation, and body weight compared to placebo. IMPACT AND IMPLICATIONS: MASLD, and MASH, are strongly associated with overweight and obesity and it is believed that the excess liver fat associated with obesity is an important driver of these diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonists elicit weight loss through centrally and peripherally mediated effects on appetite. Unlike GLP-1R agonists, glucagon receptor (GCGR) agonists act directly on the liver to stimulate fatty acid oxidation and inhibit lipogenesis, potentially providing a more potent mechanism for liver fat content (LFC) reduction than weight loss alone. This study demonstrated the ability of once-weekly treatment with pemvidutide, a dual GLP-1R/GCGR agonist, to significantly reduce LFC, hepatic inflammatory activity, and body weight, suggesting that pemvidutide may be an effective treatment for both MASH and obesity. CLINICAL TRIAL NUMBER: NCT05006885.

A New Assessment of Two Transferase-Based Liver Enzymes in Low- and High-Fibrosis Patients Chronically Infected with Hepatitis B Virus: A Meta-Analysis and Pilot Study.

Background: The detection of fibrosis remains a necessity for the evaluation of hepatitis B virus (HBV)-infected patients, but the most accurate technique is invasive. Current studies aim to develop a novel noninvasive biomarker for fibrosis assessment, but no-one has found the ideal candidate. This study is a meta-analysis combined with a pilot study to investigate the connection between two transferase compounds and the levels of fibrosis. Methods: We studied data from PUBMED, Web of Science, and Scopus, retrieving 28,896 articles. Following PRISMA guidelines, we finally analyzed full-text articles written in English. The excluded items were duplicates, non-article entries, and irrelevant papers. We assessed the variations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels between patients with high and low levels of fibrosis. Joanna Briggs Institute tools were used to assess article quality. We used R 4.2.2 for statistics. The pilot study included 14 randomly chosen patients with different fibrosis levels. Results: We found significant differences in ALT and GGT levels between patients with high and low fibrosis. The GGT/ALT ratio correlated with the levels of fibrosis and the fibrosis-4 (FIB-4) score. Conclusions: This meta-analysis assessed ALT and GGT levels in chronic HBV patients with fibrosis. The pilot study identified the first association between fibrosis and the GGT/ALT ratio in a Romanian cohort of chronic patients. This brings new ideas for future research.

Telomere Elongation During Pre-Implantation Embryo Development.

The primary mechanism of telomere elongation in mammals is reverse transcription by telomerase. An alternative (ALT) pathway elongates telomeres by homologous recombination in some cancer cells and during pre-implantation embryo development, when telomere length increases rapidly within a few cell cycles. The maternal and paternal telomeres in the zygote are genetically and epigenetically distinct, with differences in telomere length and in chromatin packaging. We discuss models for how these asymmetries may contribute to telomere regulation during the earliest embryonic cell cycles and suggest directions for future research.

Effectiveness of mobile health intervention for non alcoholic fatty liver disease- A meta analysis of randomized controlled trials.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Lifestyle modification is the mainstay of management, however, most patients find it difficult to significantly modify their lifestyle. Mobile health is an innovative healthcare system that has an established role in treating chronic diseases like asthma, cancer and cardiovascular disease. Hence, we conducted an updated meta analysis to evaluate the efficacy of mobile health intervention (mHI) for NAFLD. METHODS: Literature search of five electronic databases was performed from the inception of the paper till 15th May, 2024. Studies were included if they met the inclusion criteria; Randomized controlled trials evaluating use of mHI along with standard care in comparison to standard care only for patients with NAFLD over 18 years. Primary outcomes of interest included changes in weight, body mass index (BMI), and liver markers from baseline to post intervention. Risk of bias was evaluated using the Cochrane bias assessment tool while the Mantel-Haenszel Random-effects model on Review manager was used to pool outcomes. RESULTS: Outcomes were pooled from 7 RCTs comprising a total of 621 participants. There was a significant decrease in weight (P < 0.0001), aspartate aminotransferase (AST) (P = 0.002) and alkaline aminotransferase (ALT) (P = 0.0009) from baseline to follow-up in the intervention group as compared to the control group. However, the reduction in BMI was found to be non-significant (P = 0.64). CONCLUSION: Our meta analysis reports that mHI plays an important role in significantly reducing weight and liver markers in patients with NAFLD. Considering that the improvement of these factors plays a key role in the management of the disease, mHI could be the key towards paving better outcomes for patients with NAFLD.

Significant liver histological change is common in HBeAg-positive chronic hepatitis B with normal ALT.

BACKGROUND AND AIMS: Numerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true "immune tolerant" patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. METHODS: 179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change. RESULTS: 57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. CONCLUSIONS: HBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.