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Mariangela Rondanelli,1,2 Milena Anna Faliva,3 Gabriella Peroni,3 Vittoria Infantino,2 Clara Gasparri,3 Giancarlo Iannello,4 Simone Perna,5 Tariq AbdulKarim Alalwan,5 Salwa Al-Thawadi,5 Angelo Guido Corsico6,7 1IRCCS Mondino Foundation, Pavia 27100, Italy; 2Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia 27100, Italy; 3Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia 27100, Italy; 4General Management, Azienda di Servizi alla Persona “Istituto Santa Margherita”, Pavia 27100, Italy; 5Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; 6Center for Diagnosis of Inherited Alpha 1-Antitrypsin Deficiency, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia 27100, Italy; 7Division of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation, Pavia 27100, ItalyCorrespondence: Gabriella PeroniEndocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia 27100, Italy, Tel +39 0382381739Fax +39 0382381218Email gabriella.peroni01@universitadipavia.itAbstract: Nutritional problems are an important part of rehabilitation for chronic obstructive pulmonary disease (COPD) patients. COPD patients often present with malnutrition, sarcopenia, and osteoporosis with possible onset of cachexia, with an inadequate dietary intake and a poor quality of life. Moreover, diet plays a pivotal role in patients with COPD through three mechanisms: regulation of carbon dioxide produced/oxygen consumed, inflammation, and oxidative stress. A narrative review based on 99 eligible studies was performed to evaluate current evidence regarding optimum diet therapy for the management of COPD, and then a food pyramid was built accordingly. The food pyramid proposal will serve to guide energy and dietary intake in order to prevent and treat nutritionally related COPD complications and to manage progression and COPD-related symptoms. The nutrition pyramid described in our narrative review is hypothetical, even in light of several limitations of the present review; the main limitation is the fact that to date there are no randomized controlled trials in the literature clearly showing that improved nutrition, via the regulation of carbon dioxide produced/oxygen consumed, inflammation and oxidative stress, improves symptoms and/or progression of COPD. Even if this nutritional pyramid is hypothetical, we hope that it can serve the valuable purpose of helping researchers focus on the often-ignored possible connections between body composition, nutrition, and COPD.Keywords: COPD, nutrients, inflammation, fat free mass, antioxidants, gas exchanges

This study investigates the potential of flavonoid compounds from Sandoricum koetjape leaf extracts as tyrosinase inhibitors, using in vitro and in silico methodologies. Tyrosinase is crucial for melanin synthesis, and its excessive activity leads to hyperpigmentation disorders. The extracts underwent maceration, partitioning, and concentration, followed by tyrosinase inhibition assays and LC-MS/MS analysis. The ethyl acetate fraction showed the highest inhibitory activity, revealing key flavonoids like Kaempferol-3-O-β-Dglucopyranoside and Quercimeritrin. Molecular docking and dynamic simulations provided insights into their binding mechanisms. Kaempferol-3-Oβ-D-glucopyranoside exhibited a binding affinity of -8.4 kcal/mol, while Quercimeritrin had -7.7 kcal/mol. PreADME profiles indicated Quercimeritrin’s higher solubility, better skin permeability, and lower environmental toxicity. This comprehensive evaluation underscores the viability of S. koetjape as a natural source for tyrosinase inhibitors, highlighting the need for further optimization and in vivo studies to confirm efficacy and safety for dermatological applications.

Background: One of the common findings in systemic sclerosis (SSc) patients has been long-term exposure to environmental toxins such as pesticides. However, the data available shows an equivocal association between pesticide exposure and autoimmunity in SSc., Methods: We investigated the levels of organochlorine pesticides (OCPs) in blood of 20 SSc patients and 17 healthy controls, and also studied their effect in-vitro on T lymphocytes and their functional responses., Results: We found higher levels of hexachlorocyclohexane (HCH- α-, β-, and γ) and o,p'-dichlorodiphenyltrichloroethane (DDT) metabolite (p,p΄-DDE) in blood of SSc patients. In vitro treatment of SSc patient PBMCs with either of HCH (100 mM) or DDT (50 µM) caused a significant increase merely in CD8 + memory (CD8 + CD45RO + ) T lymphocytes. We also observed reduced FoxP3 expression in CD4 + CD25 + (regulatory T cells) of SSc patients. Neither HCH nor DDT exposure of SSc PBMCs altered significantly the secretion of IL-2, IL-10, or IFN-γ, but both of these pesticides elevated their IL-4 (a pro-fibrotic cytokine) secretion., Conclusion: Taken together, our findings indicate that persistent exposure to these OCPs results in decreased lymphoproliferative activity which promotes disease activity by producing pro-fibrotic cytokine(s). Thus, SSc patients are less able to initiate or augment an immune response to foreign antigens, when there is substantial suppression of lymphocyte function, which increases their susceptibility to infection. Strategies to prevent and control pesticide exposure may play an important role in reducing the morbidity and mortality associated with this disease.

Objective: The aim of this study was to investigate the growth patterns of Bahraini female and male infants/young children aged 0-24 months in the Kingdom of Bahrain., Methods: A cross-sectional approach was employed to track the growth parameters among healthy Bahraini female and male infants/children aged 0-24 months. A multistage probability sampling criteria was used to collect information from official records. Anthropometric measurements (weight and length) and demographic characteristics on feeding practices were gathered. Generalized Additive Models for Location Scale and Shape (GAMLSS)/Lambda-Mu-Sigma methodology was implemented to select distribution type, optimize smoothing parameters, perform regression of growth models, and construct percentiles and Z-score charts and tables for weight for age, length for age, length for weight, and body mass index (BMI) for age., Results: Findings were compared with WHO Multicentre Growth Reference Study (MGRS) data. A total of 403 healthy infants/children (210 males and 193 females) were recruited. At birth, the mean weight, length, and BMI were 3.2±0.4 kg, 3.1±0.4 kg, 49.7±2.3 cm, 48.8±2.1 cm, 13.2±1.6 kg/m2, and 12.8±1.5 kg/m2 for males and females, respectively. Anthropometrics of males were all statistically significantly higher than those of females at all age levels. The length and weight of the Bahraini infants/children were slightly higher than those of the WHO-MGRS., Conclusion: The outcomes of this study, presented as charts and tables, showed significant differences in comparison with the WHO-MGRS reference charts. Specifically, Bahraini children aged between 0 and 24 months of both sexes were taller and heavier than their cohorts in the MGRS reference charts. Further longitudinal studies are needed for monitoring the growth pattern of children using body composition methods, adiposity markers, and determinant factors of growth to investigate this deviation from the WHO-MGRS.

Background: This study aimed to analyse the impact of des-acyl and acyl ghrelin (AG) on a wide range of muscular and metabolic markers and in order to discover the possible relationships and interactions of des-acylated ghrelin (DAG) on eating disorders. Materials & Methods: A total of 88 subjects (64 women and 24 men, with a mean age of 43 years and a mean body mass index (BMI) of 30.20 ± 3.27 kg/m 2 ) were enrolled in the cross-sectional study. Results: The findings showed that for each unit of increase of free fat mass index (FFMI), levels of DAG decreased by -41.11 pg/mL ( p < 0.05). Moreover, similar associations with DAG were found for insulin ( β = -30.67; p < 0.001), leptin ( β = -0.64; p < 0.05), body weight ( β = -14.36; p < 0.001), and free fat mass (FFM) ( β = -30.67; p < 0.001). In addition, associations were found between DAG and resting energy expenditure (REE) ( β = -0.84; p = 0.05) and the binge eating scale (BES) in which a unit increase of the BES score Q3 (depression) correlated with a decrease of DAG levels ( β = -9.98; p = 0.08). Further, a unit increase of AG/DAG ratio correspond with an increase in body weight ( β = 12.20; p < 0.05), BMI ( β = 4.70; p < 0.05) and fat mass ( β = 7.30; p < 0.05). However, the AG/DAG ratio was not associated with FFMI ( β = 2.61; p = 0.165) and FFML/BMI ( β = -0,064; p = 0.625). Conclusion: This study suggests that higher levels of DAG at fasting are indices of poor muscle mass, insulin resistance and depression.

This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences. As a result of this review, we summarized the effects of Berberine in different models and the related mechanism of actions. In preclinical models, Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Moreover, in animal models, Berberine explicates an action on glucose through the inhibition of α-glycosidase at a dose of 200 mh/kg/day. Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day. Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380 mg/kg/day. All the above preclinical data are confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. For all these reasons, this review gives an important good account of the impact of Berberine in obesity treatment and prevention., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Musculoskeletal disorders in aging and pain are closely connected because of multiple mechanisms leading to loss of mobility and autonomy. Pain is predictive of diability and worsening frailty and the strength of this relationship increases with the severity of pain. This study presents a systematic review of randomized controlled trials, cross sectional studies, and observational studies based on treatment of pain in adults with musculoskeletal disorders using nutritional non-pharmacological (nutrients and antioxidants) interventions. The review found the efficiency of the following topics: (a) accession of the patient to a dietary counselling (e.g., daily recommended amount of protein-equivalent to at least of 1 g of protein per kilogram of body weight); (b) intake of glutamic acid-rich such as soy, egg, and cod and tryptophan-rich foods such as milk and peanuts-or taking quick-acting, free-form supplements; (c) supplementation of vitamin D and magnesium, if lacking; (d) weekly consumption of fish or supplements of omega-3 fatty acids; and (e) availability of botanicals, in particular curcumin and gingerol. These non-pharmacological interventions can help the pain therapist to create a personalized medicine (precision medicine), acting with the maximum efficacy and safety, and also reducing the dosage of analgesic drugs needed.

We compare bioimpedance analysis (BIA) with dual-energy X-ray absorptiometry (DXA) in the assessment of free fat mass (FFM), fat mass (FM) and percentage of body fat under different conditions in relation to age categories, hydration parameters, body mass index (BMI) and sarcopenia. A cross-sectional analysis of body composition was estimated by BIA and DXA in 379 hospitalized elderly patients. In addition, estimates of FFM, FM and percentage of body fat were investigated across different conditions. Paired t-tests, Bland-Altman plot and intraclass correlation coefficient analysis were used to compare methods. Data showed an underestimation of means (BIA versus DXA) of FFM (women: 0,97 kg, p<0,01; men: 1,99 kg; p<0,01), and an overestimation of both the FM (women: +1,11 kg; p<0,01; men: +1,67 kg; p<0,01) and percentage of body fat (women: +2,07 %, p<0,01; men: +2,82 %, p<0,01). BIA underestimated FFM and overestimated FM and percentage of body fat in patients from the age group of 75 to 85 years, in patients with a total body water content <60%, in underweight and normal weight patients and in patients with sarcopenia (p<0,01). The intraclass coefficient results were indicative of poor reproducibility between BIA and DXA for FFM (women: +0,197; men: +0,250) and FM (women: +0,141; men +0,144). BIA is a good alternative for estimation of FFM and FM only in overweight or obese patients or in patients with good hydration status. BIA, on the other hand, is not an accurate method for assessing FFM in sarcopenic patients.

Background/aims: The ideal end point of treatment for chronic hepatitis B virus (HBV) infection is sustained off-therapy hepatitis B surface antigen (HBsAg) loss with or even without seroconversion to anti-HBs. We investigated the role of adding PEGylated interferon (PEG IFN) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance., Patients and Methods: In this randomized controlled trial, chronic HBV patients who have been receiving tenofovir for >6 months with HBV viral load <2000 IU/ml were randomized into two groups. One group (add-on therapy) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir. Patients in the other group received only tenofovir 300 mg orally on a daily basis. Patients in both groups were followed up for a total of two years, and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance., Results: Twenty-three patients were allocated to the PEG IFN and tenofovir (add-on therapy) group, and another 25 patients were recruited to the tenofovir monotherapy group. Before randomization, patients had received tenofovir for 1135 mean days (range203 to 1542 days). One patient (4.3%) in add-on therapy lost HBsAg and seroconverted. Within two years, mean HBsAg decreased significantly with add-on therapy (from 4753 IU/ml to 2402; P= 0.03); and it decreased from 5957 IU/ml to 4198; P= 0.09 in tenofovir monotherapy group. More patients in the add-on group developed serious side effects, with treatment discontinuation, and dose reductions (P = 0.3)., Conclusion: PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3% of the patients. Add-on therapy patients had a significant decrease in HBsAg levels in two years; and no significant decrease in HBsAg levels with the tenofovir monotherapy. With no significant HBsAg clearance, the utility of this combination regimen is questionable.

The real magnitude of antituberculosis (anti-TB) drug resistance in Saudi Arabia is still unknown because the available data are based on retrospective laboratory studies that were limited to hospitals or cities. A representative national survey was therefore conducted to investigate the levels and patterns of anti-TB drug resistance and explore risk factors. Between August 2009 and July 2010, all culture-positive TB patients diagnosed in any of the tuberculosis reference laboratories of the country were enrolled. Isolates obtained from each patient were tested for susceptibility to first-line anti-TB drugs by the automated Bactec MGIT 960 method. Of the 2,235 patients enrolled, 75 cases (3.4%) were lost due to culture contamination and 256 (11.5%) yielded nontuberculous mycobacteria (NTM). Finally, 1,904 patients (85.2% of those enrolled) had available drug susceptibility testing results. Monoresistance to streptomycin (8.1%; 95% confidence interval [CI], 7.2 to 9.1), isoniazid (5.4%; 95% CI, 4.7 to 6.2), rifampin (1%; 95% CI, 0.7 to 1.3) and ethambutol (0.8%; 95% CI, 0.5 to 1.2) were observed. Multidrug-resistant TB (MDR-TB) was found in 1.8% (95% CI, 1.4 to 2.4) and 15.9% (95% CI, 15.4 to 16.5) of new and previously treated TB cases, respectively. A treatment history of active TB, being foreign-born, having pulmonary TB, and living in the Western part of the country were the strongest independent predictors of MDR-TB. Results from the first representative national anti-TB drug resistance survey in Saudi Arabia suggest that the proportion of MDR-TB is relatively low, though there is a higher primary drug resistance. A strengthened continuous surveillance system to monitor trends over time and second-line anti-TB drug resistance as well as implementation of innovative control measures, particularly among immigrants, is warranted.

Introduction: The role of serum interferon-γ-inducible protein-10 kDa (IP-10) level in the treatment of chronic hepatitis C genotype-4 (HCV-4) and its various subtypes remains unknown. We aimed to study the impact of pretreatment IP-10 levels on the sustained viral response (SVR) in HCV-4 patients (n=64) undergoing peginterferon α-2a/ribavirin therapy., Patients and Methods: Pretreatment IP-10 levels and HCV-4 subtypes (4a=48.4%, 4d=39%, others=12.5%) were measured and correlated with treatment responses. Variables significantly associated with SVR on univariate analysis were included in a multivariate logistic regression model., Results: Patients with SVR had lower pretreatment IP-10 levels (462.4±282.7 vs. 840.1±490.6 pg/ml; P=0.002), but the levels were not significantly different in those with a rapid (P=0.245) or an early viral response (P=0.221). IP-10 levels were similar across all subtypes. The pretreatment level was significantly lower in subtype 4d patients with SVR (465.9±349.1) compared with non-SVR patients (904.9±532.1; P<0.001), but not when compared with genotype 4a patients (564.7±288.9 vs. 658.6±374.9, respectively; P=0.330). IP-10 levels [odds ratio (OR), 0.998; 95% confidence interval (CI): 0.996-0.999; P=0.006], low viremia (OR, 8.852; 95% CI: 1.244-63.03; P=0.029), and early viral response (OR, 4.162; 95% CI: 1.023-16.94; P=0.046) were independent predictors of SVR. Receiver operating characteristic curve analysis identified a threshold IP-10 level of 359 pg/ml (area under receiver operating characteristic curve, 0.737; sensitivity, 81.8%; specificity, 45.2; positive predictive value, 43.9%; negative predictive value, 82.6%) for SVR., Conclusion: Pretreatment serum IP-10 level is a predictor for SVR in HCV-4-infected patients. The baseline IP-10 level is significantly lower in responders among HCV genotype-4d patients as compared with 4a patients.

Background and Objectives: In January 2008, the Clinical Laboratory Standard Institute (CLSI) revised the Streptococcus pneumoniae breakpoints for penicillin to define the susceptibility of meningeal and non-meningeal isolates. We studied the impact of these changes. In addition, the pneumococcal resistance rate to other antimicrobial agents was reviewed., Design and Setting: Laboratory data on peumococcal isolates collected retrospectively from hospitalized children in tertiary care hospital in Riyadh, Saudi Arabia from January 2006 to March 2012., Patients and Methods: Only sterile samples were included from cerebrospinal fluids, blood, sterile body fluids and surgical tissue. Other samples such as sputum and non sterile samples were excluded. We included samples from children 14 years old or younger. The minimum inhibitory concentration (MIC) for penicillin, cefuroxime, ceftriaxone and meropenem were determined by using the E-test, while susceptibility to erythromycin, cotrimoxazole and vancomycin were measured using the disc diffusion methods following the guideline of CLSI., Results: Specimens were analyzed in two different periods: from January 2006 to December 2007 and from January 2008 to March 2012. During the two periods there were 208 samples of which 203 were blood samples. Full penicillin resistance was detected in 6.6% in the first period. There was decrease in penicillin nonmeningeal resistance to 1.5% and an increase in resistance in penicillin meningeal 68.2% in the second period (P=.0001). There was an increase in rate of resistance among S pneumoniae isolates over the two periods to parenteral cefuroxime, erythromycin and cotrimoxazole by 34.6%, 35.5% and 51.9%, respectively. Total meropenem resistance found 4.3% and no vancomycin resistance was detected., Conclusions: The current study supports the use of the revised CLSI susceptibility breakpoints that promote using penicillin to treat nonmeningeal pneumococcal disease, and might slow the development of resistance to broader-spectrum antibiotics.

Background/aim: Hepatitis C virus genotypes 4 (HCV-4) is the most prevalent genotype in Saudi Arabia, although it's various subtypes, mode and route of transmission remains unknown. The aim of this study was to analyze (i) the variability of the HCV-4 subtypes, the route and source of HCV transmission and (ii) the influence of HCV-4 subtypes on their therapeutic response., Patients and Methods: Sixty-four HCV-4 patients were analyzed retrospectively for the prevalence of various sub-genotypes and the possible mode of transmission, and it was correlated with their treatment response to pegylated interferon (PEG-IFN) α-2a and ribavirin therapy., Results: Positive history of blood or blood products transfusion was noted in 22 patients (34%), hemodialysis in 10 patients (15.6%), surgery in 7 patients (11%), and unknown etiology in 25 patients (39%). Prevalence of HCV-4 subtypes was 4a = 48.4% (31/64), 4d = 39% (25/64), 4n = 6.25% (4/64), and remaining combined (4m, 4l, 4r, 4o) 6.25% (4/64). No significant correlation between subtypes and the source of transmission was recognized ( P = 0.62). Sustained virological response in all HCV-4 patients was 64% (41/64), while in each subtypes separately it was 4a 77.4% (24/31), 4d 52% (13/25), and combined (4n, 4m, 4l, 4r, 4o) 62.5% (5/8) ( P = 0.046)., Conclusion: No obvious cause for the mode of HCV transmission was noted in majority of the patients. No significant correlation was observed between HCV-4 subtypes and the source of HCV infection. 4a and 4d subtypes were the most common in Saudi Arabia, and patients infected with 4a subtype responded significantly better to combination therapy than to 4d subtype.

Objective: To determine the rate and type of anti-tuberculosis drug resistance at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Design: Review of microbiology and infection control databases for all patients with culture-positive Mycobacterium tuberculosis between June 1981 and May 2003 at the hospital. BACTEC 460TB radiometry then MGIT 960 were used for both mycobacterial detection and antimicrobial susceptibility testing., Results: A total of 764 M. tuberculosis isolates were obtained from 764 patients. Resistance to first-line agents (isoniazid, rifampicin, ethambutol and streptomycin) was noted in 65 (8.5%). Resistance to isoniazid was the highest, noted in 54 (7.1%); resistance to rifampicin, streptomycin and ethambutol was found in respectively 21 (2.7%), 29 (3.8%) and 12 (1.6%) isolates. Polyresistance was noted in eight (1%) isolates and monoresistance in 38 (5%) isolates. Multidrug-resistant M. tuberculosis was found in 19 (2.5%) isolates. There were 54 primary resistant isolates (7.6%), and 11 (22%) with acquired resistance. The median age of patients with resistant isolates was 38 years compared to 48 years for patients with sensitive isolates (P = 0.002)., Conclusion: Resistance to first-line anti-tuberculosis agents and multidrug-resistant M. tuberculosis remain relatively low in Saudi Arabia.