Blocking the Increase of Intracellular Deuterium Concentration Prevents the Expression of Cancer-Related Genes, Tumor Development, and Tumor Recurrence in Cancer Patients.

The possible role of the naturally occurring deuterium in the regulation of cell division was first described in the 1990s. To investigate the mechanism of influence of deuterium (D) on cell growth, expression of 236 cancer-related and 536 kinase genes were tested in deuterium-depleted (40 and 80 ppm) and deuterium-enriched (300 ppm) media compared to natural D level (150 ppm). Among genes with expression changes exceeding 30% and copy numbers over 30 (124 and 135 genes, respectively) 97.3% of them was upregulated at 300 ppm D-concentration. In mice exposed to chemical carcinogen, one-year survival data showed that deuterium-depleted water (DDW) with 30 ppm D as drinking water prevented tumor development. One quarter of the treated male mice survived 344 days, the females 334 days, while one quarter of the control mice survived only 188 and 156 days, respectively. In our human retrospective study 204 previously treated cancer patients with disease in remission, who consumed DDW, were followed. Cumulative follow-up time was 1024 years, and average follow-up time per patient, 5 years (median: 3.6 years). One hundred and fifty-six patients out of 204 (77.9%) did not relapse during their 803 years cumulative follow-up time. Median survival time (MST) was not calculable due to the extremely low death rate (11 cancer-related deaths, 5.4% of the study population). Importantly, 8 out of 11 deaths occurred several years after stopping DDW consumption, confirming that regular consumption of DDW can prevent recurrence of cancer. These findings point to the likely mechanism in which consumption of DDW keeps D-concentration below natural levels, preventing the D/H ratio from increasing to the threshold required for cell division. This in turn can serve as a key to reduce the relapse rate of cancer patients and/or to reduce cancer incidence in healthy populations.

Maternal overnutrition elevates offspring's blood pressure-A systematic review and meta-analysis.

BACKGROUND: Maternal overnutrition during pregnancy predisposes the offspring to cardiometabolic diseases. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the association between maternal overnutrition and offspring's blood pressure (BP) and the effect of offspring's obesity on this association. DATA SOURCES: PubMed, EMBASE, Clinicaltrials.gov, CENTRAL. STUDY SELECTION AND DATA EXTRACTION: Human studies published in English before October 2021 were identified that presented quantitative estimates of association between maternal overnutrition just before or during pregnancy and the offspring's BP. SYNTHESIS: Random-effect model with the DerSimonian and Laird weighting method was used to analyse regression coefficients or mean differences. RESULTS: After selection, 17 observational studies (140,517 mother-offspring pairs) were included. Prepregnancy body mass index (ppBMI) showed positive correlation with BP in offspring (regression coefficient for systolic: 0.38 mmHg per kg/m2 , 95% confidence interval (CI) 0.17, 0.58; diastolic: 0.10 mmHg per kg/m2 , 95% CI 0.05, 0.14). These indicate 1.9 mmHg increase in systolic and 0.5 mmHg increase in diastolic BP of offspring with every 5 kg/m2 gain in maternal ppBMI. Results on coefficients adjusted for offspring's BMI also showed association (systolic: 0.08 mmHg per kg/m2 , 95% CI 0.04, 0.11; diastolic: 0.03 mmHg per kg/m2 , 95% CI 0.01, 0.04). Independent from ppBMI, gestational weight gain (GWG) showed positive correlation with systolic BP (systolic BP: 0.05 mmHg per kg, 95% CI 0.01, 0.09), but not after adjustment for offspring's BMI. Mean systolic BP was higher in children of mothers with excessive GWG than in those of mothers with optimal GWG (difference: 0.65 mmHg, 95% CI 0.25, 1.05). CONCLUSIONS: Independent from offspring's BMI, higher prepregnancy BMI may increase the risk for hypertension in offspring. The positive association between GWG and offspring's systolic BP is indirect via offspring's obesity. Reduction in maternal obesity and treatment of obesity in children of obese mothers are needed to prevent hypertension.

The Scent of Antifungal Propolis.

Propolis contains many effective antifungal compounds that have not yet been identified and evaluated. In addition, distinguishing samples of propolis with high antifungal activity from less active ones would be beneficial for effective therapy. Propolis samples were collected from four different geographical regions in Hungary and used to prepare ethanol extracts for analysis. First, an antifungal susceptibility test was performed on Candida albicans. Then, gas chromatography-mass spectrometry (GC-MS) and an opto-electronic nose were applied for the classification of propolis samples. In three propolis samples, the IC50 was measured between 72 and 134 µg/mL, but it was not calculable in the fourth sample. GC-MS analysis of the four propolis samples identified several compounds belonging to the various chemical classes. In the antifungal samples, the relative concentration of 11,14-eicosadienoic acid was the highest. Based on the opto-electronic electronic nose measurements, 98.4% of the original grouped antifungal/non-antifungal cases were classified correctly. We identified several molecules from propolis with potential antifungal properties. In addition, this is the first report to demonstrate the usefulness of a portable opto-electronic nose to identify propolis samples with high antifungal activity. These results may contribute to the rapid and efficient selection of new fungicide-candidate molecules and effective propolis samples for treatment.

Endoscopic and surgical drainage for pancreatic fluid collections are better than percutaneous drainage: Meta-analysis.

BACKGROUND: Pancreatic pseudocyst (PP) and walled-off necrosis can be managed endoscopically, percutaneously or surgically, but with diverse efficacy. AIMS & METHODS: A comprehensive literature search was carried out from inception to December 2018, to identify articles which compared at least two of the three kinds of treatment modalities, regarding the mortality, clinical success, recurrence, complications, cost and length of hospitalisation (LOH). RESULTS: The outcomes of endoscopic (ED) and percutaneous drainage (PD) were comparable in six articles. The clinical success of endoscopic intervention was better considering any types of fluid collections (OR = 3.36; 95% confidence interval (CI) 1.48, 7.63; p = 0.004). ED was preferable regarding recurrence of PP (OR = 0.23; 95% CI 0.08, 0.66; p = 0.006). Fifteen articles compared surgical intervention with ED. Significant difference was found in postoperative LOH (WMD (days) = -4.61; 95%CI -7.89, -1.33; p = 0.006) and total LOH (WMD (days) = -3.67; 95%CI -5.00, -2.34; p < 0.001) which favored endoscopy, but ED had lower rate of clinical success (OR = 0.54; 95% CI 0.35, 0.85; p = 0.007) and higher rate of recurrence (OR = 1.80; 95% CI 1.16, 2.79; p = 0.009) in the treatment of PP. Eleven studies compared surgical and percutaneous intervention. PD resulted in higher rate of recurrence (OR = 4.91; 95% CI 1.82, 13.22; p = 0.002) and lower rate of clinical success (OR = 0.13; 95% CI 0.07, 0.22, p < 0.001). CONCLUSION: Both endoscopy and surgery are preferable over percutaneous intervention, furthermore endoscopic treatment is associated with shorter hospitalisation than surgery.

The quadrivalent HPV vaccine is protective against genital warts: a meta-analysis.

BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine has been assumed to give protection against genital warts (GW) as well as cervical cancer. Our main question was whether HPV vaccine has any effects on the prevention of GW reported in randomised controlled clinical trials (RCTs) and time-trend analyses. METHODS: This meta-analysis was performed according to the PRISMA guidelines using the PICO format. We searched in three electronic databases (PubMed, Embase, Cochrane Trials), and assessed heterogeneity using the Q-test and I-squared statistics, meta-regression was also performed. Odds ratios (OR) and their confidence intervals (CI) were calculated. The sensitivity was tested by leave-one-out method. We evaluated the presence of publication bias using the funnel plot graph and the Copas selection model. The strength of evidence was assessed using the GRADE approach. RESULTS: Eight RCTs (per-protocol populations) and eight time-trend ecological studies were included in this meta-analysis. A significant reduction (pooled OR = 0.03, 95% CI: 0.01-0.09; I-squared = 53.6%) of GW in young women was recorded in RCTs, and in time-trend analyses both in young women (pooled OR = 0.36, CI 95% = 0.26-0.51; I-squared = 98.2%), and in young men (pooled OR = 0.69, 95% CI = 0.61-0.78; I-squared = 92.7%). In subgroup analysis, a significant reduction of the number of GW events was observed especially in women under 21 years (pooled OR = 0.33, 95% CI = 0.17-0.63). Leave-one-out analysis showed that similar results could be obtained after excluding one study, meta-regression did not show significant difference. CONCLUSIONS: Prophylactic, quadrivalent HPV vaccination can prevent GW in healthy women and men, therefore, it should be included in routine immunization programme.

Effects of medicinal waters on the UV-sensitivity of human keratinocytes - a comparative pilot study.

Balneotherapy has been used to treat several diseases including locomotor, neurological and dermatological conditions. The basis of the "organic hypothesis" of medical balneology is that medicinal waters, especially thermal spa and hot spring waters, contain a high variability of organic components with possible biological effects, including UV photo-protection. The recent study aims to clarify this effect in a human keratinocyte cell line model. Results confirm that organic-rich extract of selected medicinal waters might protect skin-derived cells from DNA damage. These results give a clinical relevance to medicinal waters or pharmaceutical products prepared from them in preventing the adverse effects of solar or artificial UV radiation on the human skin.

Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data.

BACKGROUND: Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. METHODS: To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann-Whitney post hoc (MWph) tests were used. RESULTS: Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. CONCLUSIONS: A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas.

Novel dicistrovirus from bat guano.

A novel dicistrovirus (strain NB-1/2011/HUN, KJ802403) genome was detected from guano collected from an insectivorous bat (species Pipistrellus pipistrellus) in Hungary, using viral metagenomics. The complete genome of NB-1 is 9136 nt in length, excluding the poly(A) tail. NB-1 has a genome organization typical of a dicistrovirus with multiple 3B(VPg) and a cripavirus-like intergenic region (IGR)-IRES. NB-1 shares only 41 % average amino acid sequence identity with capsid proteins of Himetobi P virus, indicating a potential novel species in the genus Cripavirus, family Dicistroviridae.

Association Between AIRE Polymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study.

BACKGROUND/AIM: Autoimmune regulator (AIRE) is a transcription factor that plays pivotal role in controlling autoimmunity. In the thymus, it supports the presentation of peripheral tissue antigens to developing T cells, where recognition of these self-antigens negatively selects the autoimmune naïve T-cells by central tolerance. Studies demonstrated that single-nucleotide polymorphisms (SNPs) in AIRE alter transcription and propagate clonal survival of autoimmune T cells, therefore increase susceptibility to autoimmune diseases. This study intended to identify SNPs in exon and intron sequences that determine AIRE transcription, where their genotypes are associated with rheumatoid arthritis (RA) risk and clinical parameters. PATIENTS AND METHODS: After a thorough in silico research, we enrolled 100 patients with RA and 100 healthy controls to analyze the association of SNP rs870881(C>T) and rs1003854(T>C) in AIRE coding sequence with RA risk by using five different genetic models and selected clinical parameters. Multiplex quantitative polymerase chain reaction was used to determine allelic discrimination of SNPs. RA risk was assessed by odds ratios (ORs) and confidence intervals (CIs). RESULTS: In a recessive model of rs878081, minor allele TT homozygotes were associated with RA (p=0.032, OR=5.44, 95%CI=1.16-25.52); in a recessive model of rs1003854, minor allele CC homozygotes were associated with RA (p=0.047, OR=4.84, 95%CI=1.02-23.02). Higher C-reactive protein (CRP) levels in patients with RA were significantly associated with minor allele homozygotes in recessive and codominant genetic models (p=0.029 and p=0.043, respectively) of rs1003854. CONCLUSION: Genotypes for minor alleles of rs878081 and rs1003854 might be involved in RA pathogenesis and risk prediction.

Genetic Polymorphisms in Exon 5 and Intron 5 and 7 of AIRE Are Associated with Rheumatoid Arthritis Risk in a Hungarian Population.

BACKGROUND: Rheumatoid arthritis (RA) is chronically persistent synovitis and systemic inflammation. Although multiple contributors are detected, only one is pivotal in the neonatal period: the negative selection of autoimmune naïve T-cells by the autoimmune regulator (AIRE) transcriptional factor. METHODS: Single-nucleotide polymorphisms (SNPs) in the DNA-binding site of AIRE may determine its function and expression. We intended to analyse site-specific allelic polymorphisms in two exon (rs878081 and rs1055311) and three intron (rs1003853, rs2075876, and rs1003854) loci with an RA risk. Our analytical case-control study analysed 270 RA patients and 322 control subjects in five different genetic models using quantitative real-time PCR (qPCR) with TaqMan® assays. RESULTS: Statistically significant differences were found between the odds of allelic polymorphisms in the loci of rs878081, rs1003854, and rs1003853 among the controls and RA patients, and the disease activity seemed to be significantly associated with the genotypic subgroups of rs878081 and rs1055311. Our in silico analysis supported this, suggesting that allele-specific alterations in the binding affinity of transcriptional factor families might determine RA activity. CONCLUSION: Our findings highlight the involvement of neonatal self-tolerance in RA pathogenesis, providing novel insights into disease development and paving the way for an analysis of further site-specific genetic polymorphisms in AIRE to expand the intervention time for RA.

Betanin Attenuates Epigenetic Mechanisms and UV-Induced DNA Fragmentation in HaCaT Cells: Implications for Skin Cancer Chemoprevention.

Dermal photoaging refers to the skin's response to prolonged and excessive ultraviolet (UV) exposure, resulting in inflammation, changes to the tissue, redness, swelling, and discomfort. Betanin is the primary betacyanin in red beetroot (Beta vulgaris) and has excellent antioxidant properties. Yet, the specific molecular mechanisms of betanin in HaCaT cells have not been fully clarified. The objective of this study was to investigate the activity of betanin and the underlying mechanisms in HaCaT cells; furthermore, in this study, we explored the protective effect of various concentrations of betanin against UVB irradiation on HaCaT cells. Additionally, we assessed its influence on the transcription of various epigenetic effectors, including members of the DNA methyltransferase (DNMT) and histone deacetylase (HDAC) families. Our findings demonstrate a notable downregulation of genes in HaCaT cells, exhibiting diverse patterns upon betanin intake. We considered the involvement of DNMT and HDAC genes in distinct stages of carcinogenesis and the limited exploration of the effects of daily exposure dosages. Our results indicate that betanin may protect the skin from damage caused by UV exposure. Further investigation is essential to explore these potential associations.

Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.

Deuterium depleted water effects on survival of lung cancer patients and expression of Kras, Bcl2, and Myc genes in mouse lung.

Although advances in cancer therapies continue to develop, the shortness of the survival of lung cancer patients is still disappointing. Therefore, finding new adjuvant strategies is within the focus of cancer cure. Based on observations that deuterium depletion inhibits the growth of cancer cell lines and suppresses certain proto-oncogenes, we have conducted a clinical study in 129 patients with small cell and nonsmall cell lung cancers who consumed deuterium-depleted drinking water (DDW) as a nontoxic agent in addition to conventional chemotherapy and radiotherapy. Median survival time (MST) was 25.9 mo in males and 74.1 mo in female patients; the difference between genders was statistically significant (p < 0.05). Median survival of subjects with brain metastasis was 27.1 mo. Cumulative 5-yr survival probabilities were 19%, 52%, and 33% in males, females, and all patients with brain metastasis, respectively. Gene expression analysis in mouse lung indicated that DDW attenuates 7,12-dimethylbenz(a)anthracene (DMBA)-induced expression of Bcl2, Kras, and Myc in females. In conclusion, DDW counteracts the DMBA-induced overexpression of Bcl2, Kras and Myc genes in mouse lung, and it may extend survival of lung cancer patients as a nontoxic anticancer dietary supplement, especially for women with tumors overexpressing cancer-related genes, because MST of DDW-consuming group was 2-4 times longer than it is generally observed in lung cancer patients.

Tartrazine Modifies the Activity of DNMT and HDAC Genes-Is This a Link between Cancer and Neurological Disorders?

In recent years, artificial additives, especially synthetic food colorants, were found to demonstrate wider properties compared to their natural equivalents; however, their health impact is still not totally mapped. Our study aimed to determine the long-term (30 and 90 days) exposure effect of one of the commonly used artificial food colorants, tartrazine, on NMRI mice. The applied dose of tartrazine referred to the human equivalent dose for acceptable daily intake (ADI). Further, we evaluated its impact on the transcription of a range of epigenetic effectors, members of the DNA methyltransferase (DNMT) as well as histone deacetylase (HDAC) families. Following the exposure, organ biopsies were collected from the lungs, kidneys, liver, and spleen, and the gene expression levels were determined by real-time quantitative reverse transcription PCR (RT-qPCR). Our results demonstrated significant upregulation of genes in the tested organs in various patterns followed by the intake of tartrazine on ADI. Since DNMT and HDAC genes are involved in different steps of carcinogenesis, have roles in the development of neurological disorders and the effect of dose of everyday exposure is rarely studied, further investigation is warranted to study these possible associations.

Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes.

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2-1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

The effect of fenugreek on the gene expression of arachidonic acid metabolizing enzymes.

The main bioactive compounds of Trigonella foenum graecum L. (fenugreek) seeds are protodioscin, trigoneoside, diosgenin and yamogenin, which have anticarcinogenic potency through inhibition of cell proliferation and inhibition of prostaglandin synthesis. The effect of fenugreek on ALOX and COX genes was examined in AKR/J H-2(k) mice exposed to dimethylbenz[α]anthracene (DMBA), a potent carcinogen. The expression pattern of these genes was determined by detecting the mRNA expression in various tissues (the lungs, liver, spleen and the kidneys) in four groups of mice. Two groups were fed with normal and two of them with fenugreek containing nutriment. Each group divided into DMBA treated and control groups. Mice were autopsied on day 7 after DMBA treatment for mRNA isolation. Fenugreek consumption itself did not change gene expression compared with the control group. DMBA could increase the expression of ALOX12, ALOX15, ALOX5 genes mainly in all organs. Fenugreek consumption was generally protective in each organ in a different manner. DMBA treatment increased COX2 gene expression, but fenugreek was protective in all tissues examined. In COX1 gene, the fenugreek diet could suppress the expression, except for spleen, independently from carcinogen exposure. Therefore by inhibiting the arachidonic acid metabolism fenugreek may prevent tumorigenesis.

Rats sniff out pulmonary tuberculosis from sputum: a diagnostic accuracy meta-analysis.

In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and meta-analysis of the data to see if this novel method is comparable to traditional laboratory screening and detection methods like Ziehl-Neelsen stain-based assays (ZN) and bacterial culture. The search and data processing strategy is registered at PROSPERO (CRD42019123629). Medline via PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for the keywords "pouched rat" and "tuberculosis". Data from 53,181 samples obtained from 24,600 patients were extracted from seven studies. Using sample-wise detection, the sensitivity of the studies was 86.7% [95% CI 80.4-91.2%], while the specificity was 88.4% [95% CI 79.7-93.7%]. For patient-wise detection, the sensitivity was 81.3% [95% CI 64.0-91.4%], while the specificity was 73.4% [95% CI 62.8-81.9%]. Good and excellent classification was assessed by hierarchical summary receiver-operating characteristic analysis for patient-wise and sample-wise detections, respectively. Our study is the first systematic review and meta-analysis of the above relatively inexpensive and rapid screening method. The results indicate that African giant pouched rats can discriminate healthy controls from TB individuals by sniffing sputum with even a higher accuracy than a single ZN screening.

γ-Aminobutyric Acid and Derivatives Reduce the Incidence of Acute Pain after Herpes Zoster - A Systematic Review and Meta-analysis.

Herpes zoster (HZ) causes considerable pain and distress, and γ-Aminobutyric acid (GABA) and its derivatives are assumed to control this, but the available data are inconsistent. This meta-analysis and systematic review aimed to assess the effectiveness of GABA derivatives in the prevention of acute herpetic pain. The metaanalysis was conducted following the PRISMA guidelines using PICO format, registered in PROSPERO number CRD42018095758. PubMed, Web of Science, Ovid, Scopus, and EMBASE databases were searched. Records were included if they were randomized controlled trials of patients undergoing HZ infection, investigating the effect of GABA derivatives versus placebo in the treatment of HZ pain. Eligible trials were evaluated for the risk of bias. Then data were extracted and analysed. The number of patients with observed presence of pain after treatment was used to calculate odds ratio in a random effect model with the DerSimonian-Laird estimator. The I2 statistic was analysed for heterogeneity. The potential risk of bias was measured using Egger's regression test. The meta-analysis included three randomized controlled trials with a total of 297 patients. The incidence of acute HZ pain events for GABA group was significantly lower compared to placebo group,18/148 vs 44/149, respectively (OR = 0.36; 95% CI = 0.14 to 0.93; Z = 2.11; P = 0.035), Egger's test yielded P = 0.308. In conclusion, the present meta-analysis demonstrates that GABA derivatives reduce the incidence of acute herpetic pain. However, additional, well-designed randomized clinical trials are needed to determine their dose- and time-dependency regarding this symptom.

LIFEStyle, Prevention and Risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study.

INTRODUCTION: Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. METHODS AND ANALYSIS: LIFESPAN is an observational, multicentre international case-control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. ETHICS AND DISSEMINATION: The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access. TRIAL REGISTRATION NUMBER: ISRCTN25940508; Pre-results.

Systemic antibiotic prophylaxis does not affect infectious complications in pediatric burn injury: A meta-analysis.

In pediatric burns the use of systemic antibiotic prophylaxis is a standard procedure in some burn centers, though its beneficial effect on the infectious complications is debated. The present meta-analysis aimed at determining whether systemic antibiotic prophylaxis prevents infectious complications in pediatric patients with burn injuries. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to August 2019. We included 6 studies, in which event rates of infectious complications were reported in children with burn injuries receiving or not receiving systemic antibiotic prophylaxis. We found that the overall odds ratio (OR) of developing an infection (including local and systemic) was not different between the groups (OR = 1.35; 95% CI, 0.44, 4.18). The chances for systemic infectious complications alone were also not different between antibiotic-treated and non-treated patients (OR = 0.74; 95% CI, 0.38, 1.45). Based on the age, affected total body surface area, and country income level, we did not find any subgroup that benefited from the prophylaxis. Our findings provide quantitative evidence for the inefficacy of systemic antibiotic prophylaxis in preventing infections in pediatric burns. To validate our conclusion, multinational, randomized trials in a diverse population of children with burn injuries are warranted.