Microsporum gypseum Infection Among Two Related Families With a Zoonotic Aspect: A Prospective Case Series.

Background and purpose The Microsporum gypseum complex is a globally distributed group of geophilic dermatophytes that primarily affect animals but can also rarely cause dermatomycoses in humans. With some regional and occupational variations, tinea corporis is the most prevalent presentation of the infection. The aim of this study was to report on the diagnosis and treatment of dermatophytosis cases among related families, and their pets, from southern Saudi Arabia. Up-to-date information on dermatophytes and dermatophytosis is needed. Methods This is a prospective case series undertaken at the Dermatology Outpatient Clinic of King Khalid University, Saudi Arabia. Six patients with suspected dermatophytosis were received at our hospital in 2022 and have been followed for recovery with or without scars. Characteristics of fungal pathogens were examined phenotypically on the basis of microscopic and growth characteristics, and laboratory data were used to initiate treatment with oral fluconazole, topical terbinafine cream, or oral itraconazole. Results Clinical features and culture results confirmed tinea capitis and tinea corporis caused by M. gypseum, which was also present in a pet cat. Tinea capitis cases (n = 4) did not respond to fluconazole and terbinafine treatment, but treatment with itraconazole resulted in a full recovery. Tinea corporis cases (n = 2) were treated with terbinafine, which resulted in a full recovery within four weeks, with no signs of scarring. Conclusions M. gypseum presents with serious persistent lesions and is extremely contagious. Treatment is durable but challenging, and breaking the transmission chain is more difficult.

Haematological Traits in Symptomatic and Asymptomatic COVID-19 Positive Patients for Predicting Severity and Hospitalization.

Objective: The present investigation aims on the clinical attributes and haematological parameters between symptomatic (COVID-19 ICU) and asymptomatic (COVID-19 homes isolation) patients as predisposing sign for COVID-19 related mortality. Materials and Methods: A retrospective cohort research was conducted of admitted patients to ICU, who were suffering from severe COVID-19 in Aseer Central Hospital, Abha, Kingdom of Saudi Arabia (KSA) from July 2020 until September 2020. The study included individuals with COVID -19 and ICU admission as symptomatic group and others who are COVID-19 positives with quarantine as asymptomatic group. Epidemiological, clinical and haematological laboratory data were retrospectively collected, analysed with control subjects. Results: Of the 38 ICU patients studied, the most common symptoms were fever and respiratory distress (100%), cough (86.8%). Majority were of Saudi origin (78.9%). Eighteen (47.4%) COVID-19 ICU patients showed leukocytosis, 6 (15.8%) had severe thrombocytopenia (with most having thrombocytopenia), 18 (47.4%) were anaemic. A significant correlation was observed between the WBC, RBC, Hb, platelets, neutrophil and lymphocyte count between ICU inmates compared with quarantine (p < 0.001) and RBC, Hb, neutrophil and lymphocyte count with control groups (p < 0.001). Conclusion: From the observations it is evident that, the blood tests have potential clinical value in predicting COVID-19 progression. Further, patient characteristics including age, leukocyte count, RBC, platelets and differential leukocyte counts may be significant predictors for monitoring the progression of the critical illness observed in SARS-COV-2 patients. Also, treatment procedures can be re-defined further to reduce COVID-19 mortalities in more critically ill COVID-19 individuals.

Chronic metabolic and induced stress impacts mesenchymal stromal cell differentiation and modulation of dental origin in-vitro.

The impact of induced (smoking) and metabolic stress (diabetes) on dental stem cells with respect to pre-impact consideration on differentiation and bone formation were investigated. The progenitor stem cells isolated from dental pulp, follicle and gingival tissues were phenotyped and subjected to nicotine and high glucose stress mimicking the smoking and diabetic condition in-vitro. The results showed that the cellular viability post treatment with 100 µM nicotine and 10uM glucose was about 86% to 89% respectively in all the three cell types while about 73% in combined nicotine and glucose treatment. No variation in the expression of pro-inflammatory TNF-α, IL-1ß and IL-12 in all the three cell types were noticed. The observed viability in nicotine treated cells were due to elevated IL-6, IL-10 while in glucose was due to brain derived neurotropic factor (BDNF). Higher expression of IL-4, IL-6, IL-10, TGF-ß and heme oxygenase -1 (HO-1) were found high in both stressors treated cells. Differentiation and mineralization markers Alkaline phosphatase (ALP), Collagenase I (COL1), Osteocalcin, Runt related transcription factor 2 (RUNX2), Osteopontin and Bone sialoprotein were expressed in the dental pulp stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) at varying levels post nicotine or glucose treatment while not significantly observed in dental follicular stem cells (DFSCs). Therefore, it is evident that the stem cells of varied dental origin responded to the stress are more or less uniform with physiological delay in differentiation into osteoblast. It is evident from the study that, the metabolic or induced stress subverts the process of regenerative healing by mesenchymal stromal cells with their anatomical niche.

Glucose and oleic acid mediate cellular alterations in GLP-1-induced insulin-positive differentiating UCBMSCs.

Coordinated effects of glucose and oleic acid on glucagon-like peptide-1 (GLP-1) mediated differentiation of insulin-positive differentiating umbilical cord mesenchymal stromal cells (dUCBMSCs) was studied using a co-culture of NCI-H716 (GLP-1+) and UCBMSCs (insulin+). The addition of 2.5 mM glucose increased the proliferation of NCI-H716 cells by 30% and induced transformation of UCBMSCs into insulin-secreting cells in 18 days as compared to 22 days in control cells. Oleic acid (25 µM) showed decrease in cell proliferation, autophagy, and apoptosis in NCI-H716 cells while no effect was observed in dUCBMSCs. Prolonged glucose and oleic acid resulted in apoptosis and cell cycle changes in dUCBMSCs after day 18 while higher concentrations resulted in cell death. Additionally, the expression of FAS and ACC mRNA was observed in NCI-H716 and dUCBMSCs post 24-hr addition of glucose and/or oleic acid. Absorption of oleic acid was high in NCI-H716 compared to dUCBMSCs. Taken together, optimal concentrations of glucose and oleic acid could be a key factor in stimulating intrinsic GLP-1, which in turn stimulates differentiating MSCs in a glucose-dependent manner. PRACTICAL APPLICATIONS: The aim of this article was to study whether differentiating or differentiated MSCs after mobilization or post-transplant would require optimal glucose and oleic acid to naturally stimulate intrinsic GLP-1, or otherwise, the high or long-term overload of glucose or oleic acid could result in inhibition of differentiated cells resulting in failure of insulin secretion.

Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.

Salient Conclusive Remarks on Epidemiology and Clinical Manifestations of Pediatric COVID-19: Narrative Review.

The ongoing pandemic of COVID-19, which is caused by the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), constituted significant public health concerns and impacted the human populations with massive economic and social burdens worldwide. The disease is known to infect people of all ages, including children, adults, and the elderly. Although several reports about pediatric COVID-19 were seen in the literature, we believe that the epidemiology and pathology of the infection described in these reports are not conclusive. Therefore, in this scientific communication, a narrative review study was performed to shed some light on the characteristic epidemiological features and clinical phenotypes of pediatric COVID-19. In this report, we had compiled and presented the different epidemiological features of the disease related to the age of infection, virus acquisition, explanations of the low infectivity rates, and consequences of infections. The discriminatory clinical manifestations of the disease in children were also addressed and discussed in this review. The search included the data published from the date of the start of the pandemic in December 2019 up to October 2020. Our literature search revealed that children of all ages, including neonates, had been infected by the virus. Despite the fact that pediatric COVID-19 is less common to occur, as compared to the disease in adults, the infected children usually manifest the disease symptomatology in benign form. Asymptomatic and symptomatic adult patients are the primary source of the virus to the children. Intrauterine transmission of the virus and breastfeeding infections to the neonates were hypothesized in some studies but ruled out since they were not confirmed. Intensive review and discussion warranting the low infection rates and benign conditions of COVID-19 in children were also made in this study. As documented in many studies, the infectivity, morbidity, and mortality rates of the disease among the children populations are much lower than those in adults. They also seem to be lower than those observed during SARS-CoV and MERS-CoV epidemics. The described clinical phenotypes of COVID-19 in children do not differ much from those of adults, and complications of the disease seem to be associated with comorbidities.

Serum sCTLA-4 level is not associated with type 1 diabetes or the coexistence of autoantibodies in children and adolescent patients from the southern region of Saudi Arabia.

BACKGROUND: The soluble form of CTLA-4 (sCTLA-4) is associated with several autoimmune diseases. The aim of the study is to measure the serum sCTLA-4 levels in type I diabetic (T1DM) patients and to assess the presence of autoantibodies for a possible association. METHODS: One hundred forty-two T1DM patients were enrolled in the study. Fifty of them were serologically positive for co-existing autoantibodies. One hundred and five subjects were enrolled in the study, as non-diabetic controls (1-17 years of age; median age-10 years). The serum samples of all the subjects were analyzed with ELISA to detect the concentration of sCTLA-4 and anti-GAD/IA2 IgG. Standard statistical analysis was conducted as required. RESULTS: Ninety-four (66%) subjects of T1DM patients and five (4.7%) subjects of the non-diabetic group had antibodies positive for anti-GAD/IA2. Serum sCTLA-4 was low in most of the subjects of both the diabetic and control groups (p = 0.18). In the control group, nine individuals (8.6%) were positive for sCTLA-4. Similarly, only seven patients (4.9%) in the T1DM group had high levels of sCTLA-4, of which two were found to be double positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies. In addition, among the T1DM patients, no significant relationships were observed between sCTLA-4 levels and age of onset (p = 0.43), disease duration (p = 0.09), or glycemic control (p = 0.32). CONCLUSION: Despite the previous findings of high sCTLA-4 levels in autoimmune diseases, serum levels of sCTLA-4 are not significantly different between T1DM patients and non-diabetic adolescents. Furthermore, we did not observe any association with autoantibody presence, glycemic control, or disease duration.

Proteomic profiling of various human dental stem cells - a systematic review.

BACKGROUND: The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities. Additional complexity in differentiation and maturation is observed in stem/progenitor cells. The role of functional proteins at the cellular level has long been attributed to anatomical niches, and stem cells do not deflect from this attribution. Human dental stem cells (hDSCs), on the whole, are a combination of mesenchymal and epithelial coordinates observed throughout craniofacial bones to pulp. AIM: To specify the proteomic profile and compare each type of hDSC with other mesenchymal stem cells (MSCs) of various niches. Furthermore, we analyzed the characteristics of the microenvironment and preconditioning changes associated with the proteomic profile of hDSCs and their influence on committed lineage differentiation. METHODS: Literature searches were performed in PubMed, EMBASE, Scopus, and Web of Science databases, from January 1990 to December 2018. An extra inquiry of the grey literature was completed on Google Scholar, ProQuest, and OpenGrey. Relevant MeSH terms (PubMed) and keywords related to dental stem cells were used independently and in combination. RESULTS: The initial search resulted in 134 articles. Of the 134 full-texts assessed, 96 articles were excluded and 38 articles that met the eligibility criteria were reviewed. The overall assessment of hDSCs and other MSCs suggests that differences in the proteomic profile can be due to stem cellular complexity acquired from varied tissue sources during embryonic development. However, our comparison of the proteomic profile suffered inconsistencies due to the heterogeneity of various hDSCs. We believe that the existence of a heterogeneous population of stem cells at a given niche determines the modalities of regeneration or tissue repair. Added prominences to the differences present between various hDSCs have been reasoned out. CONCLUSION: Systematic review on proteomic studies of various hDSCs are promising as an eye-opener for revisiting the proteomic profile and in-depth analysis to elucidate more refined mechanisms of hDSC functionalities.

Rising Klebsiella pneumoniae Infections and Its Expanding Drug Resistance in the Intensive Care Unit of a Tertiary Healthcare Hospital, Saudi Arabia.

Nosocomial infections caused by Klebsiella pneumoniae and other Gram-negative organisms have emerged as a significant health problem especially in intensive care units (ICU). This study aims to examine K. pneumoniae infections in the ICU of Aseer Central Hospital and to determine their antimicrobial susceptibility and their relationship to patients' clinical outcomes. This is a retrospective observational study done in a tertiary care center in the Aseer region in Saudi Arabia. The study spanned from January 2018 to December 2019. Demographic, microbiologic, and patient outcomes were collected from 276 patients with various infections. Identification of isolates and in vitro susceptibility to 32 antimicrobial agents were done by the Vitek 2 automated system (bioMérieux, Marcy-l'Étoile, France). Prevalence of K. pneumoniae bacteria, their susceptibility to antimicrobials, and effect on clinical outcome were studied. Two hundred seventy-six K. pneumoniae were recovered from ICU patients with various infections. K. pneumoniae isolates (n=276) were collected mainly from the respiratory tract (61%) and K. pneumoniae represented 39% of the major causal agents of ICU infections, followed by Acinetobacter spp. (30%), Pseudomonas aeruginosa (10.0%), Escherichia coli (7%), and others (14%). The mortality among the 276 ICU patients was 33.3%; K. pneumoniae was connected to 42% of the cases and 67% of the total deaths were between 50 and 90 years of age. K. pneumoniae demonstrated high sensitivity and hence can be recommended for in vivo treatment for tigecycline (81%), cefazolin (77.2%), colistin (64.9%), and to a lesser extent norfloxacin (60%) and imipenem (55.5%). High resistance was detected for ampicillin (100%), extended-spectrum ß-lactamases-sulbactam (ESBL-SCM) (100%), piperacillin (100%), and ceftazidime (92.5%). Resistance to carbapenems was elevated in ertapenem (65.2%) and meropenem (61.7%). The increase of K. pneumoniae represents a threat to ICU patients, although K. pneumoniae infections were results rather than the causes, as it was connected to almost half of the ICU mortalities. Tigecycline alone or in combination with colistin on high-dose regimens could be a more effective therapy for treating carbapenem-resistant K. pneumoniae infections.

Healthcare workers' perspectives on healthcare-associated infections and infection control practices: a video-reflexive ethnography study in the Asir region of Saudi Arabia.

BACKGROUND: Healthcare-associated infections (HAIs) are a global public health problem. For the fulfillment of Saudi Arabia's Vision 2030, the promotion of preventive care medicine through HAI management is a crucial issue. This study explores the perspectives of Saudi tertiary healthcare workers (HCWs) on HAIs and infection control measures. METHODS: Quantitative data were assessed to determine HCWs' knowledge of HAI and their attitudes towards and practice of infection control measures. Semi-structured interviews were used to collect qualitative data from 40 doctors and nurses. The interviews were audio-recorded and transcribed verbatim. Further, routine sterile procedures in the wards and intensive care units were video recorded, and the footage was discussed by the infection control team and the personnel involved in the videos. This discussion was videographed and transcribed. Both interview data and reflective discussion of the video were analysed using thematic analysis. The quantitative data were analysed using the Kruskal-Wallis test and logistic regression analysis. RESULTS: Kruskal-Wallis test revealed no difference in mean knowledge, attitude, or practice scores between nurses/ doctors or the genders. There was a significant difference in knowledge score and practice scores between the Intensive care unit & the Paediatric ward /infection control department with the maximum scores in knowledge and practice among participants from the intensive care unit. Logistic regression analysis for dependent variables (knowledge and attitude) and independent variables like age, gender, designation, and departments was not significant. The qualitative data yielded four themes: knowledge of HAI and infection control, infection control measures in practice, a shortfall in infection control measures and HAI, and required implementation. Video-reflexive ethnography (VRE) revealed lapses in handwashing practice and proper usage of personal protective equipment (PPE), especially surgical masks. CONCLUSION: Early introduction of training programmes in medical and nursing schools and video demonstrations of appropriate infection control practices during sterile procedures would be highly beneficial to HCWs. A possible reason for the outbreak of Middle East Respiratory Syndrome coronavirus in this part of Saudi Arabia could be a lapse in PPE usage. Intensive training programs for all the HCWs, strict vigilant protocols, and a willingness to change behaviour and practice, will significantly benefit the spread of outbreaks.

Prevalence of toxoplasmosis, rubella, cytomegalovirus, and herpes (TORCH) infections among women attending the antenatal care clinic, maternity hospital in Abha, Southwestern Saudi Arabia.

OBJECTIVES: To investigate the presence of toxoplasmosis, rubella, cytomegalovirus, and herpes (TORCH) infections in women attending at the antenatal care clinic in Abha, Kingdom of Saudi Arabia (KSA). Methods: A total of 190 blood samples were collected from Abha maternity hospital in Aseer region, KSA, from February 2018 to May 2019 and screened with the TORCH panel (toxoplasmagondii [IgG/IgM], cytomegalovirus [CMV] [IgG/IgM], rubella [IgG/IgM], and herpes simplex type 1 and 2 [IgG/IgM]). RESULTS: The mean age was 31.42±6.514 years and gestational age was 32.48±6.168 weeks. Serum IgG was positive for Toxoplasma gondii (T. gondii) (27.4%), herpes simplex type 1 (HSV-1) (94.7%), herpes simplex type 2 (HSV-2) (0.5%), CMV (100%), and rubella (88.9%). Serum IgM was positive only for CMV (9.5%). Though, there was an association between abortions from previous pregnancies (26.5%), intrauterine death (5.8%), premature labor (3.2%), microcephaly (1.6%), other congenital diseases (1.6%) and low birth weight (0.5%) with current IgG positivity for TORCH infections, the results were not statistically significant. CONCLUSION: Seropositivity for IgG antibodies correlate with TORCH-associated pregnancy complications in Abha, KSA; however, IgM positive CMV pregnant cases warrant further systematic investigation to understand the implications of CMV on outcomes during pregnancy.

Cytokine physiognomies of MSCs from varied sources confirm the regenerative commitment post-coculture with activated neutrophils.

The interaction of mesenchymal stromal cells (MSCs) with paracrine signals and immunological cells, and their responses and regenerative commitment thereafter, is understudied. In the current investigation, we compared MSCs from the umbilical cord blood (UCB), dental pulp (DP), and liposuction material (LS) on their ability to respond to activated neutrophils. Cytokine profiling (interleukin-1α [IL-1α], IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], transforming growth factor-ß [TGF-ß]), cellular proliferation and osteogenic differentiation patterns were assessed. The results showed largely comparable cytokine profiles with higher TNF-α and IFN-γ levels in LSMSCs owing to their mature cellular phenotype. The viability and proliferation between LS/DP/UCB MSCs were comparable in the coculture group, while direct activation of MSCs with lipopolysaccharide (LPS) showed comparable proliferation with significant cell death in UCB MSCs and slightly higher cell death in the other two types of MSC. Furthermore, when MSCs post-neutrophil exposure were induced for osteogenic differentiation, though all the MSCs devoid of the sources differentiated, we observed rapid and significant turnover of DPMSCs positive of osteogenic markers rather than LS and UCB MSCs. We further observed a significant turnover of IL-1α and TGF-ß at mRNA and cytokine levels, indicating the commitment of MSCs to differentiate through interacting with immunological cells or bacterial products like neutrophils or LPS, respectively. Taken together, these results suggest that MSCs have more or less similar cytokine responses devoid of their anatomical niche. They readily switch over from the cytokine responsive cell phenotype at the immunological microenvironment to differentiate and regenerate tissue in response to cellular signals.

Sero-prevalence and risk factors of brucellosis among suspected febrile patients attending a referral hospital in southern Saudi Arabia (2014-2018).

BACKGROUND: Human brucellosis is an infectious zoonotic disease caused by Brucella spp. It is one of the most public health problems that remains largely neglected in developing counties, including Saudi Arabia. Brucellosis is particularly prevalent among rural people who have constant contact with livestock. METHODS: A cross-sectional sero-epidemiological study conducted in Aseer Central Hospital, South Saudi Arabia, between 2014 and 2018 among 7567 patients. Serum samples were analyzed for Brucella antibodies using slide agglutination test. Serology results and patient's demographic data were analyzed by GraphPad Prism. Results were presented as mean ± SEM and differences between two groups were assessed by t-test and p < 0.05 was considered significant. RESULTS: The prevalence of brucellosis among the admitted suspected 7567 cases was 12.8% (10.4-15.7%; CI 95%). The highest prevalence rate was detected during 2015, the rate decreased to the lowest level during the last three years (p < 0.05). Higher rate of brucellosis was observed among males than females (p < 0.05) and most cases were reported during summer season (p < 0.05). The highest prevalence rate was observed in age group 21-40 year old (40.5%) followed by 41-60 years (27.7%). The lowest prevalence rate was noticed in old and young children (15 and 3%, respectively). Cross-transmission of brucellosis was seen within family (1%) and high titers (> 1280) was noticed in 22% of the hospitalized patients. The major symptoms were fatigue, hyperhidrosis, fever and joint pain. CONCLUSION: Our findings showed a high prevalence of human brucellosis among suspected patients in Aseer region. This indicates that clinical suspicion is a valid criterion and the endemic nature of the disease. The disease status requires early laboratory detection and confirmation to start prompt treatment to decrease patients suffering.

Human metapneumovirus in Pediatric Patients with Acute Respiratory Tract Infections in the Aseer Region of Saudi Arabia.

BACKGROUND: Human metapneumovirus (hMPV) is a Paramyxovirus known to cause acute respiratory tract infections in children and young adults. To date, there is no study from the Aseer region of Saudi Arabia determining the proportion and severity of hMPV infection among pediatric hospitalized patients with respiratory infections. OBJECTIVES: The objective of this study is to determine the presence of hMPV antigens in the nasopharyngeal secretions of pediatric patients hospitalized with respiratory tract infections in the Aseer region of Saudi Arabia. MATERIALS AND METHODS: This prospective, serological hospital-based study included all pediatric patients who were admitted to Aseer Central Hospital, Abha, Saudi Arabia, from July 2016 to November 2017 with upper and/or lower respiratory tract infections. Basic demographics of patients and their clinical data on and after admission were recorded. Direct fluorescent antibody assay was used to detect the presence of hMPV antigens in the obtained nasopharyngeal secretion specimens. RESULTS: During the study, 91 pediatric patients were hospitalized due to upper and/or lower respiratory tract infections, of which 9.9% were positive for hMPV. These patients were aged 9 months to 16 years, were from Abha city or its surrounding localities and were mostly (77.8%) hospitalized during autumn or winter. The most common diagnosis on admission was bronchopneumonia (55.5%) and aspiration pneumonia (22.2%), and some patients also had underlying chronic conditions such as chronic heart disease (22.2%) and bronchial asthma (11.1%). CONCLUSIONS: The results obtained indicated that hMPV is a potential etiologic factor for the commonly occurring acute respiratory infections in hospitalized children from the Aseer region of Saudi Arabia. hMPV infection was also found to be associated with complicated respiratory conditions such as bronchopneumonia, chronic heart disease and bronchial asthma.

Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro.

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-ß, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-κB and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-ß, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-κB and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.

Feasibility of cord blood bank in high altitude Abha: preclinical impacts.

We explored the possibility of the cryo-storage of cord blood hematopoietic stem cells (CBHPSC) with respect to the quantity, quality and biologic efficacy of high altitude (HA) region Abha against sea level (SL) region. The results of the post-processed total nucleated cell count was 8.03 ± 0.31 × 107 and 8.44 ± 0.23 × 107 cells in the HA and SL regions respectively. The mean post processing viability of the nucleated cells was about 87.03 ± 1.39 (HA) and 88.33 ± 1.55% (SL) while post thaw cells were 85.61 ± 1.44 (HA) and 86.58 ± 1.61% (SL) after transient cryo-storage. The proliferation of CBHSCs after thawing were comparable between the HA and SL regions. The results of the colony forming unit (CFU) assays of CFU-E, CFU-GEMM, CFU-GM and BFU-E were comparable between HA and SL in both fresh and post thaw, while a declining trend with viability was significant. The differentiation capability of post thaw samples into adipocytes and osteocytes were comparable between HA and SL regions. Overall from the results, it can be evidenced that HA cord blood collection, processing or storage does not hinder the quality or biological efficacy of the CBHPSC.

MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and scavenging the pro-inflammatory cytokines.

The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro-inflammatory cytokines TNF-α, IL-1ß, IFN-ɤ and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co-culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4, IL-10 and TGF-ß and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca2+ ]i and cROS, the portent behind the NFκB/Caspase-3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p < 0.05) and lowered high amplitude of compound muscle action potentials (CMAPs) (control: 12.36 ± 0.41, DPN: 7.52 ± 0.61 mV, DPN + MSCs: 8.79 ± 0.53 mV, p < 0.05), while slowly restoring the plasma glucose levels. Together, all these results showed that administration of BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine signaling and [Ca2+ ]i homeostasis.

Seroprevalence of coeliac disease in at-risk subjects at the main tertiary hospital, southwest of Saudi Arabia.

BACKGROUND AND STUDY AIMS: Coeliac disease (CD) is a gluten-induced autoimmune inflammation of small bowel villi, leading to atrophy and malabsorption. The current study aims to assess the prevalence of CD in high-risk subjects in the Aseer region, southwest of Saudi Arabia and to investigate the associated presentations. PATIENTS AND METHODS: This is a retrospective case-finding study of the laboratory records for a 3-year period (2009-2012) at the main tertiary hospital (Aseer Central Hospital). Serum anti-tissue transglutaminase (atTG) and endomysial antibody (EmA) levels were determined along with small intestinal histopathological examination. RESULTS: The proportion of cases that tested positive for at least one coeliac antibody marker was 18.4% (58/315). Forty cases underwent endoscopic examination during the analysis, among which 22 were confirmed to have CD. The individual antibody positivity for atTG and EmA was 17.5% and 15.6%, respectively. The most common clinical condition (47%) associated with these markers was type 1 diabetes mellitus (T1DM). Interestingly, gastrointestinal presentations constituted only 11.5%. CONCLUSIONS: The rate of CD among hospital requests, including non-gastrointestinal symptomatic patients, at the Aseer main tertiary hospital seems to be high. Determining the prevalence of CD and also investigating the high-risk group commonly affected by CD warrant more screening studies.

Pattern of thyroid, celiac, and anti-cyclic citrullinated peptide autoantibodies coexistence with type 1 diabetes mellitus in patients from Southwestern Saudi Arabia.

OBJECTIVES: To investigate the seroprevalence of coexisting autoantibodies among type 1 diabetes mellitus (T1DM) patients, and to look for possible correlations with age at diagnosis, diabetes duration, and glycemic control. METHODS: This is a cross-sectional study conducted at Aseer Central Hospital, Abha, Kingdom of Saudi Arabia from March 2013 to June 2014. A total of 202 T1DM patients were screened for serum anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), anti-tissue transglutaminase (aTTG), anti-endomysial (EMA), and anti-cyclic citrullinated peptide (anti-CCP) antibodies along with glycated hemoglobin, and biometric data. RESULTS: From the 202 T1DM patients (96 males, and 106 females) (mean age: 11.3 years), 33 (16.3%) were positive for thyroid autoantibodies. Specifically, 19 (9.4%) were positive for TG and 25 (12.8%) were positive for TPO, and 11 were double positive. There were 21 (10.4%) patients that showed a double positive for both aTTG-IgA and EMA, and only one case of T1DM was positive for anti-CCP. No significant correlations were noticed between the presence of autoantibodies and the age at diagnosis, diabetes duration, body mass index, and glycemic control. CONCLUSION: The prevalence of thyroid and celiac disease autoantibodies is high among T1DM patients, while anti-CCP remains low and might be weakly associated with T1DM in the southwestern region of Saudi Arabia. No significant correlation between the age at T1DM diagnosis, duration, and glycemic control, and the presence of autoantibodies was found.

Tacrolimus Ointment for Treatment of Vernal Keratoconjunctivitis.

PURPOSE: To evaluate the safety and efficacy of tacrolimus 0.1% ointment for the treatment of refractory vernal keratoconjunctivitis (VKC). MATERIALS AND METHODS: This prospective, nonrandomized case series enrolled 20 patients (40 eyes) with severe VKC, who were treated with tacrolimus 0.1% ointment. The mean age of the patients was 18.25 ± 4.2 years (range, 9-31 years). Each patient completed a follow-up period of at least 24 months. The main outcome measure was the clinical response to treatment. RESULTS: Significant improvements in clinical signs and symptoms were achieved in all patients 6 weeks after starting treatment with topical tacrolimus. Treatment was gradually reduced, with increasing intervals between applications. VKC recurred in all patients who attempted to discontinue treatment. No additional medications were required and no significant changes in visual acuity or refraction were documented. Five patients discontinued treatment due to a severe burning sensation and were excluded from the study. CONCLUSIONS: Tacrolimus, 0.1% ointment, is a safe and effective treatment for VKC refractory to standard treatment and may be used as a substitute for steroid treatments used to controlled disease activity. However, adverse effects could cause poor patient compliance.