Conventional and Alternative Mesenchymal Stem Cell Therapies for the Treatment of Diabetes.

Diabetes is a public health problem affecting millions of people around the world. Despite the availability of many antidiabetic medications, the adequate level of control of the disease and management of diabetic patients remain a huge challenge. Because of the limitations of current therapies and the tremendous potential of non-conventional treatments such as stem cell therapy, herein, we review the applications of mesenchymal stem cells (MSCs) in treating diabetes. Owing to their unique regenerative and immunomodulatory properties, MSCs have been widely utilized in numerous applications both in animal models and human clinical trials for the treatment of diabetes. This review will summarize the latest experimental and clinical studies that have provided evidence of the beneficial role of MSCs in diabetes treatment.

Liver transplantation for alcoholic hepatitis: update.

PURPOSE OF REVIEW: Alcoholic liver disease continues to be a major public health concern in the United States and around the world. Alcoholic liver disease remains the third most common indication for liver transplantation in the United States. Mortality has been reported in up to 30-50% of patients with severe alcoholic hepatitis. Liver transplantation can be lifesaving for patients with alcoholic hepatitis. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence. The majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. The purpose of this review is to provide an update from the most recent peer reviewed articles regarding early liver transplantation of alcoholic hepatitis. RECENT FINDINGS: This review shows that liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria is a key component for a successful transplant. No change in 1-year graft survival between patients who have 6 months sobriety vs. those transplanted prior to 6 months abstinence. Liver transplantation is limited by very narrow selection criteria and limited long-term data. SUMMARY: Liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria of patients has evolved and have become more permissive and the period of sobriety has become less important in the evaluation of process. However, long-term outcomes continue to lack in the literature. On the basis of previous studies, patients with longer pretransplant abstinence, disease process insight, older age at the time of transplant, the presence of social support that lives with the patient in the same dwelling place were noted to have lower rates of return to alcohol use after liver transplantation.

A Review on Acrylamide in Food: Occurrence, Toxicity, and Mitigation Strategies.

Acrylamide (AA) is a food contaminant present in a wide range of frequently consumed foods, which makes human exposure to this toxicant unfortunately unavoidable. However, efforts to reduce the formation of AA in food have resulted in some success. This review aims to summarize the occurrence of AA and the potential mitigation strategies of its formation in foods. Formation of AA in foods is mainly linked to Maillard reaction, which is the first feasible route that can be manipulated to reduce AA formation. Furthermore, manipulating processing conditions such as time and temperature of the heating process, and including certain preheating treatments such as soaking and blanching, can further reduce AA formation. Due to the high exposure to AA, recognition of its toxic effect is necessary, especially in developing countries where awareness about AA health risks is still very low. Therefore, this review also focuses on the different toxic effects of AA exposure, including neurotoxicity, genotoxicity, carcinogenicity, reproductive toxicity, hepatotoxicity, and immunotoxicity.

Knowledge and Attitude Among Lebanese Pregnant Women Toward Cord Blood Stem Cell Storage and Donation.

Background: Umbilical cord blood (UCB) used to be considered waste material and was discarded at birth. However, cord blood is now considered a rich source of adult stem cells that can be used to treat many conditions and diseases. This study was performed to determine pregnant women's knowledge and attitudes toward cord blood stem cell banking and donation in Lebanon. Methods: A descriptive study was conducted in antenatal clinics in Beirut and data were collected using a questionnaire distributed to pregnant women after provision of informed consent. A total of 244 women responded. Results: Less than half of the women (46%) reported knowledge about cord blood banking. However, participants with university and secondary education had significantly higher odds of considering UCB storage compared to those with primary education (odds ratio (OR) 8.62, 95% confidence interval (CI) 2.74-27.15 and OR 21.23,95% CI 6.55-68.86, respectively). Older pregnant women were less likely to think about UCB stem cells storage (OR 0.92, 95% CI 0.85-0.98). Conclusion: Respondents who had an existing knowledge about UCB stem cells banking in general were more likely to consider storing UCB in blood banks if affordable (45.9%). Therefore, it is necessary to inform pregnant women about stem cell banking so that they can make the appropriate decisions for themselves.

Infrared-Assisted Extraction and HPLC-Analysis of Prunus armeniaca L. Pomace and Detoxified-Kernel and their Antidiabetic Effects.

INTRODUCTION: Prunus armeniaca L. (P. armeniaca) is one of the medicinal plants with a high safety-profile. OBJECTIVES: The aim of this work was to make an infrared-assisted extraction (IR-AE) of P. armeniaca fruit (pomace) and kernel, and analyse them using reverse phase high-performance liquid chromatography (RP-HPLC) aided method. METHODS: IR-AE is a novel-technique aimed at increasing the extraction-efficiency. The antidiabetic-potentials of the P. armeniaca pomace (AP) and the detoxified P. armeniaca kernel extract (DKAP) were monitored exploring their possible hypoglycemic-mechanisms. Acute (6 h), subchronic (8 days) and long-term (8 weeks) assessment of Diabetes mellitus (DM) using glucometers and glycated hemoglobin (HbA1c) methods were applied. RESULTS: Serum-insulin levels, the inhibitory effects on alpha-glucosidase, serum-catalase (CAT) and lipid peroxidation (LPO) levels were also monitored. AP was shown to be rich in polyphenolics like trans-lutein (14.1%), trans-zeaxanthin (10.5%), trans-ß-cryptoxanthin (11.6%), 13, cis-ß-carotene (6.5%), trans 9, cis-ß-carotene (18.4%), and ß-carotene (21.5%). Prunus armeniaca kernel extract before detoxification (KAP) was found to be rich in amygdaline (16.1%), which caused a high mortality rate (50.1%), while after detoxification (amygdaline, 1.4%) a lower mortality rate (9.1%) was found. AP showed significant (p ≤ 0.05, n = 7/group) antidiabetic-activity more prominent than DKAP acutely, subchronically and on longer-terms. IR-AEs displayed more efficient acute and subchronic blood glucose level (BGL) reduction than a conventional extraction method, which might be attributed to IR-AE superiority in extraction of active ingredients. AP showed more-significant and dose-dependent increase in serum-insulin, CAT-levels and body-weights more prominent than those of DKAP. Alpha-glucosidase and LPO levels were inhibited with AP-groups more-significantly. CONCLUSION: In comparison to conventional-methods, IR-AE appeared to be an efficient and time-conserving novel extraction method. The antidiabetic-potentials of pomace and detoxified-kernels of P. armeniaca were probably mediated via the attenuation of glucose-provoked oxidative-stress, the inhibition of alpha-glucosidase and the marked insulin-secretagogue effect. Copyright © 2017 John Wiley & Sons, Ltd.

An exploratory study to assess the knowledge, attitudes and practices of Lebanese residents towards acrylamide.

INTRODUCTION: For years, heat treatment has been an essential method for ensuring mature food that meet the desired quality and safety characteristics. However, this process could lead to the formation of harmful compounds such as acrylamide. In this study we aimed to investigate the knowledge, attitudes and practices (KAPs) of the Lebanese population toward the potential risk associated with acrylamide. MATERIALS & METHODS: An online survey (n = 598) was conducted among residents in Lebanon aged 18 years and above. The survey was divided into five sections including participants' sociodemographic characteristics, knowledge, attitude and practice sections, and some questions related to consumer's preferences. RESULTS & DISCUSSION: The results showed that the majority of the participants had low food safety knowledge regarding acrylamide. Specifically, 82.9% of the consumers had no idea about the chemical, its formation, the foods with a high risk of acrylamide formation and the health risks associated with its exposure. Despite lack of knowledge, good domestic food practices (storage, pre-treatment) were noticed among participants. Moreover, the majority of consumers (> 80%) showed positive attitude towards proper acrylamide labeling. Participants with a bachelor's degree appeared to have a more positive attitude toward food safety compared to those with no qualifications (p<0.001). CONCLUSION: Despite the high consumption of acrylamide by the consumers in Lebanon through fried potatoes, bread, and coffee, the majority have no idea about acrylamide's presence in food, its sources and its adverse health effects. Raising awareness among the public, involving policy makers in addressing the issue of clear labeling and encouraging the adoption of alternative practices to reduce acrylamide are all crucial to protect consumers' health in Lebanon and promote healthier food consumption habits.

Phenotypic and molecular characterization of ESBL producing Escherichia coli and Klebsiella pneumoniae among Lebanese patients.

Introduction: Antimicrobial resistance is a major public health issue worldwide and became one of the principal international healthcare crises of the 21st century. The production of ESBLs is one of the resistance mechanisms in Enterobacteriaceae, and they are increasingly detected in Escherichia coli and Klebsiella pneumoniae globally. Therefore, the aim of this study was to determine the phenotypic and molecular characteristics of ESBL-producing E. coli and K. pneumoniae among Lebanese patients. Methods: A total of 152 ESBL-producing E. coli and K. pneumoniae were obtained from Geitaoui Hospital in Beirut between September 2019 and October 2020 from various clinical samples. The phenotype of ESBL producers was confirmed by a double-disc synergy test and antibiotic susceptibility was determined using the disc diffusion method. Genotypically, multiplex PCR was used to detect the ESBL genes (blaTEM, blaCTX-M and blaSHV). Results: All strains were confirmed to be ESBL producers (121 isolates were E. coli and 31 isolates were K. pneumoniae). All isolates showed resistance to cefotaxime, cefuroxime, ampicillin and piperacillin. On the other hand, they showed a low susceptibility rate to trimethoprim/sulfamethoxazole and ciprofloxacin. Almost all the isolates were susceptible to ertapenem, imipenem and amikacin. In our study, ESBL genes were detected among 48 (39.67%) E. coli isolates and 8 (58.06%) K. pneumoniae isolates, and the most prevalent gene was blaTEM (25%), followed by blaCTX-M (19.08%) and blaSHV (16.45%). Conclusion: Imipenem and ertapenem are the most effective drugs to treat ESBL producers. However, antibiotic stewardship programs must be implemented immediately to combat antibiotic resistance.

Extended spectrum beta-lactamase carriage among elderly residents of a long-term care facility in Beirut.

BACKGROUND: Antimicrobial resistance is an emerging problem worldwide, endangering antimicrobials efficacy and resulting in high rates of morbidity and mortality. It is one of the major concerns that health care facilities are facing nowadays. Mainly, extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales play a role in hydrolyzing ß-lactams, specifically the third-generation cephalosporins. This study aimed to investigate the prevalence of fecal carriage and molecular characterization of ESBL-producing Enterobacterales among Lebanese elderly residents in a long-term care facility (Dar Al-Ajaza Al Islamia Hospital). METHODS: Rectal culture swab specimens were collected from 132 patients at Dar Al Ajaza Al Islamia hospital between January 2019 till June 2020. The phenotype of ESBL producers was confirmed by a modified double disc synergy test and antibiotic susceptibility was determined using the Kirby-Bauer disk diffusion method. Genotypically, multiplex polymerase chain reaction was used to detect the ESBL genes. RESULTS: The main Enterobacterales strain observed was E coli (90.15%) followed by Klebsiella pneumoniae (4.54%) and Klebsiella oxytoca (3.80%). It has been found that the ESBL percentage rate has decreased when compared to a study conducted previously at the same hospital. Moreover, the predominant ESBL gene was CTX-M (cefotaximase). CONCLUSIONS: This study is the first to demonstrate the improved current status of ESBL in one long-term care facility. In addition, the CTX-M is still the major type in ESBL-producing organisms.

Epidemiology and psychosocial assessment of COVID-19 among workers of the Nigeria Centre for Disease Control infected with COVID-19.

Background: COVID-19 is a global health crisis. By 2021, Nigeria had 230,000 cases. As the national public health institute, NCDC leads the COVID-19 response. Due to constant contact with infected patients, agency employees are a t high-risk. Here, we describe the transmission and psychosocial effects of COVID- 19 among infected NCDC workers as a learning curve for minimizing occupational transmission among frontline public health workers in future outbreaks. Methods: We approved and enrolled all NCDC COVID-19- infected personnel from November to December 2020. We collected data using SurveyMonkey. STATA 14 analyzed the data. Results: 172 of 300 afflicted NCDC staff participated in this study. One-third were between 30 and 39; most were male (104, 60.5%). Most participants worked in the lab (30%) or surveillance (24%). Only 19% (33/172) of participants confirmed pandemic deployment. Most reported interaction with a confirmed case (112/65.1%). Most people (78, 45.3%) felt unhappy when diagnosed. Anger, worry, and low motivation also ranked high (19). The majority reported adequate financial, moral, or psychosocial assistance (26, 70.6%). Conclusions: NCDC staff had a high SARS-CoV-2 infection rate and emotional damage. We urge stricter infection control methods when sending staff for outbreaks response to prevent additional transmission, as well as ongoing psychosocial and economic assistance for afflicted workers.

Adapting public health response through lessons learnt: Nigeria's experience from Lassa fever and COVID-19.

Response to public health emergencies requires continued adaptation and innovation. The Nigeria Centre for Disease Control (NCDC) is the country's public health institute with the mandate to protect the health of Nigerians. Achieving such mandate in resource-limited settings with divergent demographic characteristics of the citizens, necessitates the readiness to learn from experience and to develop policies and activities in line with lessons learnt and best practices. This practice paper describes the initiatives of the NCDC towards adapting its public health response activities by establishing learning systems across its structure. The paper informs on some of the steps taken by the Centre regarding learning from the Lassa fever outbreak and the COVID-19 pandemic in Nigeria. It concludes that commitment and investments are key requirements for learning and adapting public health responses to achieve success with combating infectious diseases.

In Vivo Effects of Conditioned Medium from Human Uterine Cervical Stem Cells in an Ovarian Cancer Xenograft Mouse Model.

BACKGROUND/AIM: Ovarian cancer is the most lethal of all gynecological cancers, despite advances in surgical techniques and medical treatments. During the last years, therapies based on mesenchymal stem cells and particularly their secretome (conditioned medium, CM) have emerged as promising treatments for various types of tumors. MATERIALS AND METHODS: In the present study, we evaluated the in vivo antitumor effect of human uterine cervical stem cell conditioned medium (hUCESC-CM) after intraperitoneal administration in an ovarian cancer mouse model. RESULTS: We found that intraperitoneal injection of hUCESC-CM in immunodeficient mice, injected fifty days previously with the human ovarian adenocarcinoma SKOV-3 cell line, significantly reduced abdominal tumor growth, and significantly increased overall survival, compared to control mice. CONCLUSION: hUCESC-CM could be an alternative approach to intraperitoneal treatment of ovarian cancer, either administered alone and/or with conventional chemotherapy.

Epidemiology, diagnostics and factors associated with mortality during a cholera epidemic in Nigeria, October 2020-October 2021: a retrospective analysis of national surveillance data.

OBJECTIVES: Nigeria reported an upsurge in cholera cases in October 2020, which then transitioned into a large, disseminated epidemic for most of 2021. This study aimed to describe the epidemiology, diagnostic performance of rapid diagnostic test (RDT) kits and the factors associated with mortality during the epidemic. DESIGN: A retrospective analysis of national surveillance data. SETTING: 33 of 37 states (including the Federal Capital Territory) in Nigeria. PARTICIPANTS: Persons who met cholera case definition (a person of any age with acute watery diarrhoea, with or without vomiting) between October 2020 and October 2021 within the Nigeria Centre for Disease Control surveillance data. OUTCOME MEASURES: Attack rate (AR; per 100 000 persons), case fatality rate (CFR; %) and accuracy of RDT performance compared with culture using area under the receiver operating characteristic curve (AUROC). Additionally, individual factors associated with cholera deaths and hospitalisation were presented as adjusted OR with 95% CIs. RESULTS: Overall, 93 598 cholera cases and 3298 deaths (CFR: 3.5%) were reported across 33 of 37 states in Nigeria within the study period. The proportions of cholera cases were higher in men aged 5-14 years and women aged 25-44 years. The overall AR was 46.5 per 100 000 persons. The North-West region recorded the highest AR with 102 per 100 000. Older age, male gender, residency in the North-Central region and severe dehydration significantly increased the odds of cholera deaths. The cholera RDT had excellent diagnostic accuracy (AUROC=0.91; 95% CI 0.87 to 0.96). CONCLUSIONS: Cholera remains a serious public health threat in Nigeria with a high mortality rate. Thus, we recommend making RDT kits more widely accessible for improved surveillance and prompt case management across the country.

Turning round: multipotent stromal cells, a three-dimensional revolution?

Mesenchymal stromal cells (MSC) can be isolated from adult tissues and induced to differentiate into skeletal cells, such as osteoblasts, chondrocytes and adipocytes. Consequently, ex vivo MSC are valuable systems for studying the mechanisms that control tissue-context lineage commitment and may offer broad therapeutic applications in the orthopedic theater and beyond. To date, most of these studies have used MSC grown on two-dimensional (2-D) plastic surfaces. The use of three-dimensional (3-D) in vitro growth techniques for MSC may accelerate these areas of research by providing a more representative 'in vivo-like' environment, where cells interact with each other and their cellular products, rather than a plastic surface. We introduce some of the techniques used for 3-D in vitro cultures and how they relate to the MSC field. We will present evidence of how MSC grown as 3-D spheroids not only permits appropriate MSC-like behavior, but appears to promote their stem-cell attributes and therapeutic benefit in applications ranging from regenerative medicine to anti-inflammatory treatments and cancer therapy. 3-D culture techniques also allow de/reconstruction of the specialized in vivo niche of the tissue-resident stem cell where microenvironmental influences can be recognized.

Clinical update on the use of mesenchymal stem cells in COVID-19.

The COVID-19 pandemic has evoked the scientific community to combine all efforts needed to find a cure for the disease. With the limited therapeutic effects of pharmacological therapies, attention has been drawn to alternative ones such as stem-cell based therapy particularly with mesenchymal stem cells (MSCs). Recently, a large number of clinical trials are ongoing to evaluate the safety and efficacy of MSCs in patients with COVID-19; however, only very few data are released. Thereby, we anxiously await the results of FDA-approved trials to provide more definitive data on the use of MSCs in COVID-19 patients, especially the critically ill. Herein, we shed light on the therapeutic agents that have been tested and used for the treatment of COVID-19 and provide an insight into MSC-based approaches for COVID-19 at both preclinical and clinical levels.

Effect of Adipose derived mesenchymal stem cells on multiple Organ Injuries in diet-induced obese mice.

Background: Obesity is a complex disease involving the accumulation of body fat that can inflict a substantial risk to health due to the potent role it plays in the development of a series of chronic diseases including cardiovascular diseases (CVD), nonalcoholic fatty liver diseases (NAFLD), kidney diseases, diabetes, and some cancers. Despite all efforts made, no therapy has succeeded in reversing the obesity pandemic and its associated diseases. Herein, the aim was to study the effect of adipose-derived mesenchymal stem cells on obesity-induced multi-organ injuries in a diet-induced obese mouse model. Male C57BL/6 mice were fed with regular chow diet or high fat diet (HFD) to induce obesity for 15 weeks after which the mice were administered two doses of adipose-derived mesenchymal stem cells (ASC-treated groups) or media as control (media-treated groups). Animals were sacrificed and adipose, hepatic, renal, and cardiac tissues were obtained for histopathological evaluation. Mice on HFD showed excessive pathological alterations such as epididymal adipose tissue expansion, hepatic fat accumulation, glomerular swelling, and cardiomyocyte hypertrophy. However, treatment with ASCs significantly reversed the significant histopathological abnormalities induced by obesity. In conclusion, this study demonstrated the therapeutic effects of adipose-derived mesenchymal stem cells on obesity-associated complications such as NAFLD, CVD, and kidney disorders in a diet-induced obese animal model, which were partly due to the attenuation of inflammatory cytokines such as TNF-α and IL-6.

Three-Dimensional Cell Culture Models to Study Respiratory Virus Infections Including COVID-19.

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.

The therapeutic effects of adipose-derived mesenchymal stem cells on obesity and its associated diseases in diet-induced obese mice.

Obesity is a global public health concern associated with increased risk of several comorbidities. Due to the limited effectiveness of current therapies, new treatment strategies are needed. Our aim was to examine the effect of adipose-derived mesenchymal stem cells (AD-MSCs) on obesity and its associated diseases in a diet-induced obese (DIO) animal model. C57BL6 mice were fed with either high fat diet (HFD) or CHOW diet for 15 weeks. Obese and lean mice were then subjected to two doses of AD-MSCs intraperitoneally. Mice body weight and composition; food intake; blood glucose levels; glycated hemoglobin (HbA1c), intraperitoneal glucose tolerance test and atherogenic index of plasma (AIP) were measured. Pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were also determined. AD-MSCs treatment reduced blood glucose levels, HbA1c and AIP as well as improved glucose tolerance in DIO mice. In addition, MSCs caused significant attenuation in the levels of inflammatory mediators in HFD-fed mice. Taken together, AD-MSCs were effective in treating obesity-associated diabetes in an animal model as well as protective against cardiovascular diseases as shown by AIP, which might be partly due to the attenuation of inflammatory mediators. Thus, AD-MSCs may offer a promising therapeutic potential in counteracting obesity-related diseases in patients.

Are Lockdown Measures Effective Against COVID-19?

As the Coronavirus Disease 2019 (COVID-19) pandemic progresses, countries around the world are increasingly implementing a range of responses that are intended to help prevent the transmission of this disease. In the absence of a COVID-19 vaccine, we assess the potential role of containment measures to suppress the virus transmission, thereby slowing down the growth rate of cases and rapidly reducing case incidence. The aim of this study is to show that country lockdown has a critical and significant impact on the pandemic. This is explored using real time incidence data in Lebanon. We analyze COVID-19 cases in Lebanon before and after lockdown measures have been implemented. The findings show that the nationwide lockdown was effective in reducing cases and has been successful in, so far, containing the virus. This study could be an evidence-based call to continue with the lockdown measures, based on real time incidence data. Further research is encouraged.

COVID-19: Test, Test and Test.

A new virus was identified in late December 2019 when China reported the first cases of pneumonia in Wuhan, and a global COVID-19 pandemic followed. The world was not late to respond, with a number of sweeping measures ranging from social distancing protocols, stringent hygienic practices, and nation-wide lockdowns, as well as COVID-19 testing campaigns in an attempt to prevent the transmission of the disease and contain the pandemic. Currently, different types of diagnostic testing have been adopted globally, such as nucleic acid detection tests, immunological tests and imaging approaches; however, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) remains the "gold standard" for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pre-analytical factors, such as specimen selection and collection, are crucial for RT-PCR, and any suboptimal collection may contribute to false-negative results. Herein, we address some of the specimen types that have been used in molecular detection methods for COVID-19. However, the pandemic is still evolving, and information might change as more studies are conducted.