Food as a Driver of a Cholera Epidemic in Jijiga, Ethiopia-June 2017.

We conducted a case-control study to identify risk and protective factors during a cholera outbreak in Jijiga, Ethiopia, in June 2017. A case-patient was defined as anyone > 5 years old with at least three loose stools in 24 hours who was admitted to a cholera treatment center in Jijiga on or after June 16, 2017. Two controls were matched to each case by type of residency (rural or urban) and age group. We enrolled 55 case-patients and 102 controls from June 16 to June 23, 2017. Identified risk factors for cholera were male sex, eating cold food, and eating food outside the home. Eating hot food was protective, as was reported handwashing after defecation; no other reported water, sanitation, and hygiene factors were associated with cholera risk. Recommendations included continuing messaging about safe food handling practices at home, the dangers of consuming meals prepared away from home, and the importance of hand hygiene practices.

Human amniotic membrane products for patients with diabetic foot ulcers. do they help? a systematic review and meta-analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most serious diabetic complications. DFU is an open wound that usually occurs in the foot sole due to poor blood glucose control, peripheral neuropathy, and poor circulation. The human amniotic allograft membrane is a biological wound dressing derived from the amniotic membrane. It contains amino acids, nutrients, cytokines, and growth factors that make the growth process easier. OBJECTIVE: To compare dehydrated human amnion and chorion allograft (DHACA) plus the standard of wound care (SOC) with the SOC alone. METHODS: We searched for randomized clinical trials (RCTs) on PubMed, Scopus, Cochrane, and Web of Science till April 2021 using relevant keywords. All search results were screened for eligibility. We extracted the data from the included trials and pooled them as mean difference (MD) or risk ratio (RR) with the 95% confidence interval (CI) using Review Manager software (ver. 5.4). RESULTS: The pooled effect estimate from 11 RCTs showed that DHACA was superior to SOC regarding the complete wound healing in both 6th and 12th week (RR = 3.78; 95% CI: [2.51, 5.70]; P < 0.00001) and (RR = 2.00; 95% CI: [1.67, 2.39], P < 0.00001 respectively). Also, the analysis favored the DHACA regarding the mean time to heal in the 12th-week (MD = -12.07, 95%CI: [-19.23, -4.91], P = 0.001). The wound size reduction was better with DHACA (MD = 1.18, 95%CI: [-0,10, 2.26], P = 0.03). CONCLUSION: Using DHACA with SOC is safer and more effective than using SOC alone for DFU patients.

Congenital heart disease in a patient with COVID-19 infection during early pregnancy: a case report.

BACKGROUND: Since the end of 2019, the world has been afflicted by a coronavirus pandemic caused by coronavirus 2 (severe acute respiratory syndrome) (SARS-CoV-2). COVID-19 causes a wide range of signs and symptoms with varying consequences. The impact of the COVID-19 infection on pregnant women and their fetuses is still under investigation. CASE PRESENTATION: A case of a 34-years-old non-vaccinated pregnant woman who had a COVID-19 infection in the first month of her pregnancy and went into premature labor at 34 weeks was reported. Congenital heart disease and hydrops were present in the fetus. The infant girl was cyanotic after delivery, experienced bradycardia, and was in poor overall condition; she was admitted to the NICU and died 5 days later. CONCLUSIONS: Some theories suggest that SARS-CoV-2 may be transmitted vertically from mother to fetus. Congenital abnormalities can be caused by a variety of viruses. Although, congenital heart diseases can occur due to different causes, we suggest that COVID-19 may play a role in the development of congenital heart defects.

Epidemiology of pediatric trauma in the Kingdom of Bahrain: a national pediatric trauma registry pilot study.

BACKGROUND: A pediatric trauma registry for the Kingdom of Bahrain would be a novel public health tool for the Bahraini health system. The aim of this study was to explore the epidemiology of pediatric trauma at the national level by describing the distribution of pediatric injury in the Kingdom, and quantifying the burden of injury shouldered by the study population. METHODS: This multicenter observational cross-sectional study was conducted in Bahrain using data from the Pediatric Trauma Registry (PTR), which was a short-term paper-based prospective trauma registry that collected data over a three-month period in 2018. PTR was based in the pediatric emergency departments (ED) of the three national referral hospitals in the Kingdom. By simultaneously collecting data from all three trauma hospitals in the country, it was assumed that during the data collection period all major pediatric trauma patients in the country would be captured by the study, and that the data collected would provide national estimates of trauma. Inclusion criteria for the study was any individual under the age of 14, that arrived at the ED seeking care for intentional and unintentional injuries. RESULTS: A total of 1328 patients were included in the study. Sixty-nine percent of patients were treated and discharged from the ED, 30.5% were admitted to the hospital, admitted for surgery, or seen by a specialist, and 0.5% were declared deceased. The percentage of patients documented as unrestrained during Motor Vehicle Collisions (MVC) was 92.3%, and amongst those involved in MVC, 12% were ejected from the cabin of the vehicle. CONCLUSIONS: There are significant implications that this study holds for policy implementation and practice surrounding injury prevention in the Kingdom of Bahrain. Low seatbelt utilization and the high proportion of ejection amongst MVC victims warrant immediate public health policy implementation, including enforcement of seat belt laws, strengthening of the traffic court system, and awareness campaigns for MVC prevention. Additionally, pediatric drowning prevention programs centered on constant adult supervision, pool isolation fencing, personal flotation devices, and swimming education should be created to address the mortality attributable to drowning in this study.

Multimodal affect analysis of psychodynamic play therapy.

Objective: We explore state of the art machine learning based tools for automatic facial and linguistic affect analysis to allow easier, faster, and more precise quantification and annotation of children's verbal and non-verbal affective expressions in psychodynamic child psychotherapy. Method: The sample included 53 Turkish children: 41 with internalizing, externalizing and comorbid problems; 12 in the non-clinical range. We collected audio and video recordings of 148 sessions, which were manually transcribed. Independent raters coded children's expressions of pleasure, anger, sadness and anxiety using the Children's Play Therapy Instrument (CPTI). Automatic facial and linguistic affect analysis modalities were adapted, developed, and combined in a system that predicts affect. Statistical regression methods (linear and polynomial regression) and machine learning techniques (deep learning, support vector regression and extreme learning machine) were used for predicting CPTI affect dimensions. Results: Experimental results show significant associations between automated affect predictions and CPTI affect dimensions with small to medium effect sizes. Fusion of facial and linguistic features work best for pleasure predictions; however, for other affect predictions linguistic analyses outperform facial analyses. External validity analyses partially support anger and pleasure predictions. Discussion: The system enables retrieving affective expressions of children, but needs improvement for precision.

Effect of Hydrophilic Polymers on Complexation Efficiency of Cyclodextrins in Enhancing Solubility and Release of Diflunisal.

The effects of three hydrophilic polymers, namely, carboxymethyl cellulose sodium (CMC-Na), polyvinyl alcohol (PVA) and poloxamer-188 (PXM-188) on the solubility and dissolution of diflunisal (DIF) in complexation with ß-cyclodextrin (ßCD) or hydroxypropyl ß-cyclodextrin (HPßCD), were investigated. The kneading method was used at different drug to cyclodextrin weight ratios. Increases in solubility and drug release were observed with the DIF/ßCD and DIF/HPßCD complexes. The addition of hydrophilic polymers at 2.5, 5.0 and 10.0% w/w markedly improved the complexation and solubilizing efficiency of ßCD and HPßCD. Fourier-transform infrared (FTIR) showed that DIF was successfully included into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) confirmed stronger drug amorphization and entrapment in the molecular cage of cyclodextrins. The addition of PVA, CMC-Na or PXM-188 reduced further the intensity of the DIF endothermic peak. Most of the sharp and intense peaks of DIF disappeared with the addition of hydrophilic polymers. In conclusion, PXM-188 at a weight ratio of 10.0% w/w was the best candidate in enhancing the solubility, stability and release of DIF.

Exosomes Extraction and Identification.

Exosomes are small endosome-derived lipid nanoparticles (50-120 nm in diameter), actively secreted by exocytosis in most living cells. Recently, there is a growing interest of research focused on studying the exosome functions and to understand ways to use them for therapeutic applications in a wide variety of disorders, such as cancer, cardiovascular, neurodegenerative, and musculoskeletal diseases. Recently, a number of techniques have been developed for the isolation of exosomes such as ultracentrifugation, micro-filtration centrifugation, gradient centrifugation, and size-exclusion chromatography. In this chapter, we reveal the protocol and key insights into the isolation, purification, and characterization of exosomes using ultracentrifugation method.

Application of Metabolomics to Osteoarthritis: from Basic Science to the Clinical Approach.

PURPOSE OF THE REVIEW: Osteoarthritis (OA) is a multifactorial and progressive disease affecting whole synovial joint. The extract pathogenic mechanisms and diagnostic biomarkers of OA remain unclear. In this article, we review the studies related to metabolomics of OA, discuss the biomarkers as a tool for early OA diagnosis. Furthermore, we examine the major studies on the application of metabolomics methodology in the complex context of OA and create a bridge from findings in basic science to their clinical utility. RECENT FINDINGS: Recently, the tissue metabolomics signature permits a view into transitional phases between the healthy and OA joint. Both nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry-based metabolomics approaches have been used to interrogate the metabolic alterations that may indicate the complex progression of OA. Specifically, studies on alterations pertaining to lipids, glucose, and amino acid metabolism have aided in the understanding of the complex pathogenesis of OA. The discovery of identified metabolites could be important for diagnosis and staging of OA, as well as for the assessment of efficacy of new drugs.

Efficacy of microneedling with topical vitamin C in the treatment of melasma.

BACKGROUND: Despite the wide therapeutic options available for the treatment of melasma, including many active topical medications, technologies with lights and peelings, clinical control of this disorder is extremely challenging. OBJECTIVES: To evaluate the effect of microneedling with topical vitamin C in the treatment of melasma. METHODS: Thirty female patients with melasma received six sessions of microneedling with addition of topical vitamin C every two weeks. At each session, photos were taken and Melasma Area and Severity Index (MASI) score was calculated to assess the clinical improvement. RESULTS: Mean age of the eligible patients was 33.2 ± 5.77 years. About 50% of cases were of Fitzpatrick skin type III. All patients showed improvement at the end of the sessions. Mean MASI score in the first session was 8.61 ± 4.45 and there was a gradual decline in its value till it reached a mean of 5.75 ± 4.16 in the last session (P < 0.0001). CONCLUSION: Microneedling with topical vitamin C is an effective and safe treatment option for epidermal melasma especially in Fitzpatrick skin phototypes I-III.

The effect of the type of dietary protein on the development of ovarian cancer.

We evaluated whether different dietary protein qualities (isocaloric diets involving animal (casein) or plant protein (soy protein) could inhibit the ovarian cancer growth in mice and improve their prognosis and whether chemotherapy had different tumor reducing effects on these mice. In the mice of the 20% plant protein group, the ovarian cancer growth at 5 weeks after tumor implantation was clearly reduced in comparison to the mice in the 20% animal protein group (p< 0.001). The serum levels of insulin and IGF-1 levels were both lower in the mice of the 20% plant protein group than in the mice of the 20% animal protein group (p<0.001 and p<0.01, respectively). Immunohistochemistry revealed that the level of eukaryotic initiation factor 4E-binding protein 1 (p-4EBP1) activity-one of the major downstream effectors of the mTOR pathway -of the plant protein group was significantly weaker than that of the animal protein group (p<0.001). The prognosis of the 20% plant protein group was better than that of the 20% animal protein group (log-rank test, p=0.0062). The ovarian cancer growth in the 20% plant protein plus cisplatin treatment group was not significantly reduced in comparison to the 20% animal protein plus cisplatin treatment group. Our findings suggest that a diet high in plant protein reduces the growth of human ovarian cancer cells in mice compared to a diet high in animal protein, -possibly through the lack of activation of the IGF/Akt/mTOR pathway, and leads to a better prognosis with or without cisplatin treatment.

Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle.

Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused by severe injury, congenital defects or tumour ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells. Here we used MYOD1 to establish its capacity to induce skeletal muscle transdifferentiation of human dermal fibroblasts under baseline conditions. We found significant transdifferentiation improvement via transforming growth factor-ß/activin signalling inhibition, canonical WNT signalling activation, receptor tyrosine kinase binding and collagen type I utilization. Mechanistically, manipulation of individual signalling pathways modulated the transdifferentiation process via myoblast proliferation, lowering the transdifferentiation threshold and inducing cell fusion. Overall, we used transdifferentiation to achieve the robust derivation of human skeletal myotubes and have described the signalling pathways and mechanisms regulating this process. Copyright © 2017 John Wiley & Sons, Ltd.

Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N-substituted amino and N-sulfonamide derivatives of pyrimidines.

A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.

Nucleic acid components and their analogs: Design and synthesis of novel cytosine thioglycoside analogs.

The synthesis of a new category of novel cytosine 4-thioglycoside analogs has been first accomplished. The main step of this strategy is the synthesis of sodium pyrimidine-4-thiolate through the condensation of 2-cyano-N-arylacetamides with sodium cyanocarbonimidodithioate, followed by coupling with α-bromo-sugars to afford the corresponding cytosine 4-thioglycoside analogs. The free thioglycosides were also prepared. Subsequent studies on the application of this strategy for the preparation of other potent pyrimidine thioglycosides are reported.

Crystal structure of (E)-2-amino-4-methyl-sulfanyl-6-oxo-1-{[(thiophen-2-yl)-methyl-idene]-amino}-1,6-di-hydro-pyrimidine-5-carbo-nitrile.

The title compound, C11H9N5OS2, a 1-thio-phen-2-yl-methyl-ene-amino-pyrimidine derivative, displays an essentially planar C-NH2 group. The conformation across the N=C bond linking the pyrimidine and thienyl groups is E. The pyrimidine and thienyl ring systems subtend an inter-planar angle of 42.72 (5)°. In the crystal, mol-ecules are linked by N-H⋯Nnitrile and N-H⋯O=C hydrogen bonds, forming chains parallel to the b axis.

Adsorption, kinetic and thermodynamic studies for manganese extraction from aqueous medium using mesoporous silica.

This paper describes studies of functionalized mesoporous silica employed as adsorbent for Mn(II) from aqueous solutions. The surface area of MCM-41 and diethylenetriamine functionalized-MCM-41 used in this study were 760 and 318 m(2) g(-1) (N2 adsorption). A strong dependence on pH in the Mn(II) adsorption capacity and best results were obtained at pH 6.5-7. The adsorption onto the diethylenetriamine functionalized-MCM-41 followed the pseudo-second-order kinetic model and the highest reaction rate 0.324 min(-1) was observed at low initial concentration 10 ppm. The equilibrium data showed excellent correlation with the Langmuir isotherm model and the maximum adsorption capacity of Mn(II) reached 88.9 mg/g for DETA-MCM-41 indicating that the adsorption occurs on a homogeneous surface by monolayer sorption without interaction between the adsorbed ions. These data contribute to the understanding of mechanisms involved in mesoporous silica and provide some practical clues to improve the adsorption efficiency (uptake capacity and kinetics) of Mn(II) ions.

Zein-based oral drug delivery system targeting activated macrophages.

Reactive oxygen species (ROS) play an important role in the pathogenesis of rheumatoid arthritis (RA). ROS such as hydrogen peroxide and superoxide are overproduced by activated macrophages in RA. As scavengers of ROS, enzymatic proteins such as catalase and superoxide dismutase (SOD) have a great therapeutic potential; however, in vivo application is limited especially when they are orally administered. Although, the oral route is the most convenient for drug administration, therapeutic proteins are easily degraded in vivo by the harsh conditions of gastrointestinal (GI) tract. Here, we introduce a novel drug delivery system composed of zein, a plant storage protein derived from maize. We demonstrate that zein nanoparticles can protect therapeutic proteins, catalase and SOD, from the harsh conditions of GI tract. Folate-conjugated catalase or SOD in zein nanoparticles can target the activated macrophages and scavenge the ROS generated by macrophages in vitro. This novel drug delivery system will be applicable to other orally administered treatments based on the protective property in the harsh conditions of GI tract.

The kidney in heart failure: friend or foe?

Heart failure constitutes a significant source of morbidity and mortality in the United States and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This complex interaction is characterized by a pathophysiological disequilibrium between the heart and the kidney, in which cardiac malfunction promotes renal impairment, which in turn feeds back for further deterioration of cardiovascular function. Multiple neurohumoral and hemodynamic mechanisms are involved in this cardiorenal dyshomeostasis, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with cardiorenal dysfunction can be challenging and should be individualized. Emerging therapies must address the impairment of both organs to secure better clinical outcomes. To this end, a multidisciplinary approach is warranted to achieve optimal results.

Origin and development of forensic medicine in the Kingdom of Saudi Arabia.

The medicolegal death investigation system in the Kingdom of Saudi Arabia (KSA) is unique in the world. It is exclusively derived from Islamic judiciary based on Shari'ah law, which is the definitive Islamic law or doctrine. This law is applied on Saudi citizens as well as foreigners. This is different from other Islamic countries, which have a combination of Islamic and other judiciary systems.The forensic medicine centers in KSA are related administratively to the Ministry of Health (MOH) and its subdivisions in the different governorates. They are concerned with forensic medical examination and autopsy, as well as the clinical forensic medical examination of sexual assault cases, and those injured in civil and criminal cases. The assisting laboratories (forensic histopathology, microbiology, serology, forensic chemistry) are working independently under the funding of MOH, whereas the DNA laboratory and other departments of forensic sciences, for example, counterfeiting and forgery unit are related administratively to the Ministry of Interior represented by the Administration of Criminal Evidences. Efforts concerning crime scene investigations are shared with Administration of Criminal Evidences' crime scene investigators.Forensic medicine education in KSA developed in the past few years after the foundation of Saudi specialty certificate in forensic medicine. The certificate is a postgraduation qualification equivalent to a doctorate degree in forensic medicine and requires completion of a 4-year training program in both MOH- and Ministry of Interior-related departments, as well as passing annual evaluation and examination.This review is aimed at providing in the next decade the medicolegal centers with national forensic specialists throughout the kingdom and granting skillful headships for the next generations. Moreover, this review suggests more scientific associations with the academic universities in the various fields of forensic sciences through academic cooperation.

Obesity hypertension: the regulatory role of leptin.

Leptin is a 16-kDa-peptide hormone that is primarily synthesized and secreted by adipose tissue. One of the major actions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake and elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect mechanisms, may play an important role in cardiovascular and renal regulation. While the relevance of endogenous leptin needs further clarification, it appears to function as a pressure and volume-regulating factor under conditions of health. However, in abnormal situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for direct renal, vascular, and cardiac damage.

El síndrome cardiorenal en insuficiencia cardíaca: un paradigma en evolución / The cardiorenal syndrome in heart failure: an envolving paradigm

Background: Heart failure constitutes a significant source of morbidity and mortality in the United States and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This interaction, termed the cardiorenal syndrome, is a complex phenomenon characterized by a pathophysiological disequilibrium between the heart and the kidney, in which malfunction of one organ subsequently promotes the impairment of the other. Multiple neuro-humoral mechanisms are involved in this cardiorenal interaction, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with the cardiorenal syndrome can be challenging and should be individualized. Emerging therapies must address the function of both organs in order to secure better clinical outcomes. To this end, a multidisciplinary approach is recommended to achieve optimal results.