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BACKGROUND: Hearing loss is an underestimated comorbid condition in type 2 diabetes. OBJECTIVES: Investigate hearing loss as a comorbidity associated with type 2 diabetes mellitus and evaluate the factors associated with hearing loss. DESIGN: Cross-sectional. SETTING: Tertiary care center, diabetes clinic. PATIENTS AND METHODS: Patients with type 2 diabetes, aged 30 to 60 years, were randomly selected to participate. All patients underwent clinical ear examinations and were referred for full audiological evaluation. Otoacoustic emission was used to assess inner function, tympanometry to assess middle-ear function, and pure tone air/bone audiometry to assess hearing sensitivity. Risk factors for hearing loss were assessed by multivariate logistic regression. MAIN OUTCOME MEASURE: Frequency, severity and risk factors for hearing loss. SAMPLE SIZE: 157 RESULTS: Of the 157 patients, 77 had hearing loss in both ears (49.0%), 13 in the right ear only (8.3%), 14 in the left ear only (8.9%), and 53 (33.8%) had normal hearing. In the 181 ears with sensorineural hearing loss, 90 had mild loss (49.7%), 69 moderate loss (38.2%), 16 severe loss (8.8%) and 6 had profound loss (3.3%). Disabling hearing loss was observed in 46 (29%) patients. A higher frequency of hearing loss was present in patients with glycated hemoglobin levels ≥8%. In the multivariate logistic regression analysis, the most important factors associated with hearing loss were longer diabetes duration, poor glycemic control and the presence of hypertension. CONCLUSIONS: Hearing loss is an underestimated comorbid condition in type 2 diabetes that warrants frequent hearing assessments and management. Strict glycemic and hypertension control is essential for the minimization of the effects of diabetes on hearing sensitivity. LIMITATIONS: Small sample size, limited age window (30-60 years), which was chosen to eliminate the natural aging effect on hearing. Cross-sectional nature was not ideal for the assessment of causality. CONFLICT OF INTEREST: None.

Background and Purpose: Chronic Myeloid Leukemia (CML) is a common hematological malignancy. The characteristic molecular abnormality is the presence of Philadelphia chromosome or BCR-ABL fusion gene which is the result of 9:22 translocation. Tyrosine kinase inhibitors (TKIs) form the main stay of treatment in CML with excellent responses. The purpose of this study was to determine the impact of additional chromosomal abnormalities on outcomes in CML.Methods: This is a retrospective chart review of all patients who were diagnosed with CML in chronic phase (CP) with additional chromosomal abnormalities (ACAs) over a period of 5 years from 2010 to 2015 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Results: A total of 283 patients were diagnosed with CML from January 2010 to January 2015. 31 patients out of these were found to have additional chromosomal abnormalities at the time of diagnosis in addition to BCR-ABL fusion gene or Philadelphia chromosome detection. Out of these 31 patients, 23 (74.2%) were males whereas 8 (25.8%) were females. 13 (41.9%) were in the age group of 31 to 50 years whereas the other two groups that is 18 to 30 years and 51 to 70 years had 9 patients each. After approval from the government which usually takes a standard 2-3 weeks’ time, these patients were started on tyrosine kinase inhibitors which was Imatinib in 30 (96.8%) and Nilotinib in 1 (3.2%) patient. Conventional cytogenetic analysis performed for each patient at the time of diagnosis revealed that 11 (35.5%) of patients had variant Philadelphia chromosome followed by 7 patients (22.6%) with trisomy 8. 5 patients (16.1%) had multiple chromosomal abnormalities including trisomy 8, deletion 1 and isochrome 17q. 2 patents each had isochrome 17q, inversion 3 and deletion 9 abnormalities. 1 patient had deletion 7 whereas 1 had variant Philadelphia chromosome with other chromosomal abnormalities. Conclusion: It was evident that frequently occurring ACAs In our CML population were Variant Philadelphia chromosome and trisomy 8.

Homozygous variants of the thrombospondin type-1 domain-containing 1 (THSD1) gene have recently been associated with nonimmune hydrops fetalis (NIHF; OMIM 236750) in infants, as well as with congenital heart disease, hemangiomas, prematurity, and embryonic lethality. Here, we report the first case of a biallelic variant of THSD1 in an extremely premature infant (25 weeks) who suffered from NIHF (eventually resolved) and other manifestations of the THSD1 variant, such as congenital heart disease and hemangiomas. Her prematurity was complicated by pulmonary hypertension and chronic lung disease. This case indicates that biallelic homozygous variants of THSD1 are among the likely causes of NIHF. Information from this case report will aid in determining the prognosis of NIHF caused by such variants in premature infants.

Objective: This study aimed to evaluate whether dietary habits can affect the dysmenorrhea and irregular menstruation. Design: A cross sectional study. Setting: A total of 655 female students from Imam Abdulrahman Bin Faisal University (IAU). A non-quantitative food frequency questionnaire was used to assess their food habits. Participants: Female students in health track in IAU with no health problem, pregnant or even lactating and age from 17 – 26 years were included. Results: The severity of dysmenorrhea was significantly associated with the less intake of seafood (P= 0.007) and low consumption of nuts (P= 0.02). High sweet consumption contributed with pain increased significantly during the menstrual days (P= 0.002), as well as elevates the severity of dysmenorrhea (P= 0.04). Drinking less coffee contributes significantly to the undesired effect of dysmenorrhea (P= 0.04). While there were no significant association between dairy products intake and vegetables consumption with the severity of dysmenorrhea as well as irregular menstruation. Conclusion: Regular consumption of seafood and nuts can alleviate the severity of dysmenorrhea. Eating too many sweets increased the severity of dysmenorrhea among 17 to 26 year old female.

The question whether food choice and eating behavior influence the mood or are influenced by the mood has been inquisitive to scientists and researchers. The purpose of this review is to support or refuse the argument that mood is affected by food or vice versa. The association between food and mood has been comprehensively elucidated in this review based on several studies that include participants from different ages, cultural backgrounds, and health status. The correlation among food, mood, and diseases such as diabetes mellitus, obesity, and depression was thoroughly investigated. The effect of different foods and nutrients on the mood was further explained. It is concluded that the mood significantly affects food intake and food choices. On the other hand, food also influences the mood, which affects the diseases either positively or negatively. Appropriate food choices play a significant role in mood enhancement. Advertisement is another crucial factor that negatively affects food choices and mood and contributes to many diseases. Understanding the interaction between food and mood can help to prevent or alleviate undesired health issues.

Osseous metaplasia of the breast is considered to be one of the rare breast conditions. It is characterized by the presence of normal bone tissue within the breast. We report a case of benign osseous metaplasia in a 58-year-old woman presenting with mastalgia and mass in the right breast. A lumpectomy was performed. On the pathological examination, the mass was composed completely of benign bone trabeculae with no epithelial component which was confirmed by negativity of immunohistochemistry.

Even in nonexcitable cells, the membrane potential Vm is fundamental to cell function, with roles from ion channel regulation, development, to cancer metastasis. Vm arises from transmembrane ion concentration gradients; standard models assume homogeneous extracellular and intracellular ion concentrations, and that Vm only exists across the cell membrane and has no significance beyond it. Using red blood cells, we show that this is incorrect, or at least incomplete; Vm is detectable beyond the cell surface, and modulating Vm produces quantifiable and consistent changes in extracellular potential. Evidence strongly suggests this is due to capacitive coupling between Vm and the electrical double layer, rather than molecular transporters. We show that modulating Vm changes the extracellular ion composition, mimicking the behaviour if voltage-gated ion channels in non-excitable channels. We also observed Vm-synchronised circadian rhythms in extracellular potential, with significant implications for cell–cell interactions and cardiovascular disease.

Forensic mortuaries have always presented a potential threat to workers who come into contact with dead bodies. This research aims to identify hazards faced by forensic mortuary personnel, including forensic pathologists and technicians working in forensic mortuaries in forensic medicine centres throughout Saudi Arabia, to recognise the prevalence of exposure to workplace hazards and to discover the degree of awareness and use of safety practices. A descriptive, cross-sectional study was conducted in a total of 20 forensic medicine centres, using an online questionnaire distributed among forensic mortuary personnel. A total of 113 participants responded to the questionnaire. Just over half (53%) of workplaces always provided personal protective equipment, and 75% of participants always used them. The most common hazards were needle-prick wounds and accidental slips or falls. Almost two thirds (64%) of participants witnessed or experienced a work-related accident in the forensic mortuary. The lack of previous studies concerning hazard exposure among forensic mortuary personnel in Saudi Arabia means that this study provides foundational evidence for future research concerning forensic autopsy-related work accidents in Saudi Arabia.

Drawing stimulus from interpersonal acceptance-rejection theory, this multicultural study examined relations between men's versus women's remembrances of maternal and paternal acceptance-rejection in childhood and their current level of loneliness, as mediated by adults' self-reported psychological maladjustment. Adults (N =899) from five nations (Iraq, Italy, the Netherlands, Pakistan, and the United States) responded to the Adult version of the Parental Acceptance-Rejection Questionnaire-short form for mothers and fathers, the Adult version of the Personality Assessment Questionnaire-short form, and the Interpersonal Acceptance-Rejection Loneliness Scale. Adults' remembrances of maternal and paternal rejection in childhood significantly and independently predicted feelings of loneliness but remembered paternal rejection was more strongly related to these feelings than were remembrances of maternal rejection. Psychological maladjustment fully mediated the effect of remembered maternal rejection but only partially mediated the effect of remembered paternal rejection on loneliness. There were no significant differences in these results across the five countries or genders. Overall, the results suggest that adults' remembrances of parental rejection in childhood—along with the theoretically expected development of psychological maladjustment—are likely to be associated panculturally with the experience of loneliness in adulthood.

Background: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, resulting in the degradation of the myelin sheath. Diet especially fish oils and omega-3 has been found to play an important role in MS. This work aimed to review the literature systematically for evidence on the effect of omega-3 fatty acids (EPA, DPA and DHA) on MS progression in adults.Methods: The literature search was conducted in PubMed, Oxford, Cochrane, Embase, International pharmaceutical abstract, PsychINFO, and clinical trials government. The inclusions were studies performed on humans both male and female, aged 18 years at minimum, diagnosed with MS according to McDonald 2010 criteria. Otherwise, all studies were excluded.Results: A total of 5554 studies were screened and seven were thoroughly focused on as they typically met the inclusion criteria. These studies showed the beneficial roles of fish oil supplementation and omega-3 fatty acids in improving the quality of life of MS patients. These roles were attributed to their beneficial effects on inflammatory markers, glutathione reductase, reducing the relapsing rate, and achieving balanced omega-6 to omega-3 ratios.Conclusion: Omega-3 and fish oils supplementations have beneficial effects on reducing the relapsing rate, inflammatory markers, and improving the quality of life for MS patients.

The scientific-practical conference Dietoogy In Practice Of Endocrinologist was held during the VIII Russian diabetology congress with international participation Diabetes Mellitus XXIth Century Pandemia. It was chaired by Academician of RAS M.V. Shestakova (Moscow), Professors L.A. Ruyatkina (Novosibirsk ) and L.A. Suplotova (Tyumen). The expediency of this event was dictated by the necessity to create a unified national regulated guidelines for the diet therapy of obesity and associated diseases for the medical community and patients. The program of the meeting included a discussion about the formation of a healthy diet and its effect on the body, starting from the pregnant women, fetal development, the breastfeeding period, in the period of perimenopause and postmenopause, in the presence of concomitant pathology of heart and kidneys.

Pathologic evaluation is crucial to the study of medical devices and integral to the Food and Drug Administration and other regulatory entities’ assessment of device safety and efficacy. While pathologic analysis is tailored to the type of device, it generally involves at a minimum gross and microscopic evaluation of the medical device and associated tissues. Due to the complex nature of some implanted devices and specific questions posed by sponsors, pathologic evaluation inherently presents many challenges in accurately assessing medical device safety and efficacy. This laboratory’s experience in numerous collaborative projects involving veterinary pathologists, biomedical engineers, physicians, and other scientists has led to a set of interrelated assessments to determine pathologic end points as a means to address these challenges and achieve study outcomes. Thorough device evaluation is often accomplished by utilizing traditional paraffin histology, plastic embedding and microground sections, and advanced imaging modalities. Combining these advanced techniques provides an integrative, comprehensive approach to medical device pathology and enhances medical device safety and efficacy assessment.

Calciphylaxis is a rare but highly fatal vascular calcification disorder with a predilection for patients with end stage renal disease (ESRD). The pathogenesis of calciphylaxis is unknown, however, several risk factors have been identified such as hypercalcemia, hyperphosphatemia, hyperparathyroidism, low serum albumin, and history of warfarin therapy. This article presents a case of calciphylaxis induced by warfarin in a COVID-19 patient.

It is known that cells grown in 3D are more tolerant to drug treatment than those grown in dispersion, but the mechanism for this is still not clear; cells grown in 3D have opportunities to develop inter-cell communication, but are also closely packed which may impede diffusion. In this study we examine methods for dielectrophoresis-based cell aggregation of both suspension and adherent cell lines, and compare the effect of various drugs on cells grown in 3D and 2D. Comparing viability of pharmacological interventions on 3D cell clusters against both suspension cells and adherent cells grown in monolayer, as well as against a unicellular organism with no propensity for intracellular communication, we suggest that 3D aggregates of adherent cells, compared to suspension cells, show a substantially different drug response to cells grown in monolayer, which increases as the IC50 is approached. Further, a mathematical model of the system for each agent demonstrates that changes to drug response are due to inherent changes in the system of adherent cells from the 2D to 3D state. Finally, differences in the electrophysiological membrane properties of the adherent cell type suggest this parameter plays an important role in the differences found in the 3D drug response.

Reports on pediatric multisystem inflammatory syndrome (PMIS) temporally related to coronavirus disease 2019 (COVID-19) are increasing. African and Afro-Caribbean children constituted about 37% of the cases in these reports. Although glucose-6-phosphatase dehydrogenase (G6PD) deficiency is common among this population, the G6PD status of these cases has not been reported. We report the first case of PMIS related to COVID-19 from Saudi Arabia. This case was a Saudi G6PD deficient girl who died with PMIS related to COVID-19. G6PD deficiency induces redox imbalance and exaggerates the inflammatory response; thus, it might contribute to the development or the grave outcome of our case. We urgently need to assess the association between G6PD deficiency and COVID-19 in a large study as the G6PD deficiency may be a useful predictor for the progression of the COVID-19.

Fluorescent spot test for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed in 5 boys and 14 girls who had confirmed COVID-19. Out of those, 4 (80%) boys and 5 (36%) girls were found to be G6PD deficient.

Objective To examine whether experimentally induced weight gain raises ambulatory blood pressure (BP) in healthy subjects and identify any relationship between changes in BP and changes in regional fat distribution. Patients and Methods Twenty-six normal weight subjects were randomized to 8 weeks of weight gain through overfeeding (n=16; age, 30.4±6.6 years) or to weight maintenance (controls; n=10; age, 27.1±7.7 years) between July 2004 and August 2010. Measures of body composition via dual energy X-ray absorptiometry and computed tomography, circulating biomarkers, and 24-hour ambulatory BP were obtained at baseline and after the 8-week experimental phase. Results Overfeeding resulted in 3.7 kg (95% CI, 2.9-4.5) increase in body weight in weight gainers, with increments in total (46.2 cm2; 95% CI, 27.6-64.9), visceral (13.8 cm2; 95% CI, 5.8-21.9), and subcutaneous fat (32.4 cm2; 95% CI, 13.5-51.3). No changes occurred in the maintenance group. Increases in 24-hour systolic BP (4 mm Hg; 95% CI, 1.6-6.3), mean BP (1.7 mm Hg; 95% CI, 0.3-3.3), and pulse pressure (2.8 mm Hg; 95% CI, 1.1-4.4) were evident after weight gain in the experimental group, whereas BP remained unchanged in controls. Changes in mean BP correlated only with changes in visceral fat (ρ=0.45; P=.02), but not with changes in other body composition measures. Conclusion Modest weight gain causes elevation in 24-hour BP in healthy subjects. The association between increased BP and abdominal visceral fat accumulation suggests that visceral deposition of adipose tissue may contribute specifically to the enhanced risk of hypertension associated with weight gain.

Background Large hepatocellular carcinoma (HCC) treatment options have obvious limitations. Our trial comprises ipsilateral hepatic artery ligation and extrahepatic collaterals division (HALED, reinforced by percutaneous tumor injection controlling residual HCC arterial supply. We aimed to evaluate the long term safety and feasibility of the Combined Surgical and Injection of alcohol Treatment (COSIT) as a novel therapy for the large HCC. Material and methods Candidates' clinical data of the of this case series were prospectively and sequentially reported in accordance with stage 2a development IDEAL (Idea, Development, Exploration, Assessment and Long-term monitoring) recommendations. It included adult patients with HCC (diameter >5 cm) subjected to COSIT coming to our center during a five years' trial evaluating the long term outcome measures. Study ID (NCT03138044 ClinicalTrials.gov). Results Patients were 21, their mean age (±standard deviation) was 61·9 (±9·3) years. Eleven (52.4%) patients had tumors diameter >10 cm. 17 (80.9%) patients were advanced BCLC stage. Six modifications were made in this injection phase till it came to a stability. The mean alcohol volume was 72.0 mls. The mean follow-up duration was 16 months. The median overall survival duration was 14 months. The one, three and five years' survival was 71.4%, 23.8% and 4.8%, respectively. Grade 3/4 and 4 Common Toxicity Criteria for Adverse Effects (v4.03) were encountered in 10 (47.6%) and one (4.8%) patients, respectively. Conclusion This preliminary findings of COSIT can be a promising alternative treatment for patients having large HCC. Consequently, a multicenter stage 2b Exploration IDEAL trial is suggested., Highlights • Complexity of large hepatocellular carcinoma dictated combined treatment especially in advanced cases. • Our procedure took the advantage of the invasive surgical and minimally invasive percutaneous approaches. • Our novel combined therapy suggests a good palliative hope for many advanced and terminal cases of HCC. • Our preliminary results of mortality and morbidity are relatively low compared to other treatment options.

Sleep apnea (SA) is associated with intermittent hypoxemia that may lead to ischemic preconditioning in the myocardium. This potential cardioprotective effect of SA may play a role in the development of non-ST-elevation myocardial infarction (NSTEMI) versus ST-elevation myocardial infarction (STEMI) during acute ischemia. However, there is limited evidence about the relative prevalence of NSTEMI versus STEMI in SA patients. We therefore prospectively investigated the prevalence of these two types of MI in patients with SA.We prospectively studied 782 consecutive patients admitted with the diagnosis of acute MI (both NSTEMI and STEMI). All subjects underwent sleep evaluations using a portable diagnostic device after at least 48h post-admission, provided they were in stable condition. Six hundred and seven out of 782 patients had technically adequate sleep studies, and therefore were included in the final analysis.SA was present in 65.7% (n=399) and NSTEMI in 30% (n=182) of patients. Increasing severity of SA was associated with increasing likelihood of NSTEMI, and with decreasing likelihood of STEMI (p0.001). Relative frequency of NSTEMI in the moderate to severe SA group (AHI≥15events/h) was 40.6% versus 29.9% for STEMI (p=0.01).The prevalence of NSTEMI increases with increasing severity of SA. This finding may suggest a cardioprotective role of SA, which may attenuate the development of STEMI, perhaps through ischemic preconditioning.

Tissue engineering of human fetal osteoblast cells was investigated on gelatin-hydroxyapatite (HA), crosslinked, electrospun oriented fiber scaffolds at the different HA concentrations of 0, 10, 20, and 25 wt % in the dry fibers and different fiber diameter, pore size and porosity of scaffolds. Rheological tests and proton nuclear magnetic resonance spectroscopy were conducted for all solutions used for electrospinning. It was found that 25 wt % HA-gelatin scaffolds electrospun at 20 kV led to the greatest cell attachment, cell proliferation and extracellular matrix (ECM) production while fiber orientation improved the mechanical properties, where crosslinked electrospun 25 wt % HA-gelatin fiber scaffolds yielded a Young's modulus in the range of 0.5-0.9 GPa and a tensile strength in the range of 4-10 MPa in the fiber direction for an applied voltage of 20-30 kV, respectively, in the electrospinning of scaffolds. Biological characterization of cell seeded scaffolds yielded the rate of cell growth and ECM (collagen and calcium) production by the cells as a function of time; it included cell seeding efficiency tests, alamar blue cell proliferation assay, alkaline phosphate (ALP) assay, collagen assay, calcium colorimetric assay, fluorescence microscopy for live and dead cells, and scanning electron microscopy for cell culture from 1 to 18 days. After 18 days, cells seeded and grown on the 25 wt % HA-gelatin scaffold, electrospun at 20 kV, reached production of collagen at 370 μg/L and calcium production at 0.8 mM. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1911-1926, 2017.

Background: Thalassemia is one of the most common genetic blood disorders in Asia. Consanguineous marriages and avoiding pre-marital and antenatal screening are common in Pakistan due to psychosocial, cultural, and religious factors. Few studies have investigated the beliefs regarding thalassemia, especially in a developing country. The aim of this study was to assess the knowledge, beliefs, and practices regarding thalassemia in an urban population. Method: A cross-sectional descriptive study was conducted in the urban areas of Karachi, Pakistan over a period of six months during March 2016 through August 2016. Participants selected by representative sampling were interviewed face-to-face using a pre-designed, pre-tested questionnaire. The questionnaire was divided into four parts. The first part inquired about general demographic variables, while the second part assessed knowledge of the participant regarding thalassemia. The third and fourth parts were concerning the beliefs and practices regarding thalassemia. Data were entered and analyzed using the Statistical Package for Social Sciences (SPSS) Statistics, v. 24.0 (IBM SPSS Statistics, Armonk, NY). Results: Only 53% (n = 720) of the respondents had heard about thalassemia. The mean knowledge score was 5.8. The total possible score ranged between 0 - 12 with the higher scores indicating better knowledge. About three-quarters (70%) of the sample did not know that an individual can be a carrier of thalassemia. Less than half (38%) of the participants viewed premarital screening for thalassemia as necessary, with only 10% agreeing that thalassemia carriers should not marry. There was no pre-marriage counseling done in 98% of the families. Conclusion: Our study highlights the prevalence of numerous myths and a low level of knowledge regarding thalassemia in an urban population of Pakistan.

Background Rapid growth and invasiveness of hepatocellular carcinoma (HCC) largely depends on its vascularity and active angiogenic capacity. That feature was used to control the tumor in the past with some limitations. These deficiencies were addressed in our new procedure by hepatic artery ligation and extrahepatic collaterals division (HALED) of the liver lobe containing large HCC. This study tried to assess the feasibility, safety and the short term effects of HALED. Materials and methods This is a prospective stage 2a development IDEAL (Idea, Development, Exploration, Assessment and Long-term monitoring) case series. It included adult patients with large-sized HCC (diameter > 5 cm) subjected to HALED carried out in our center during five years' trial evaluating one-month postoperative outcomes. Patients will be reported prospectively in a sequential order with explanation of reasons for rejected cases and description of changes to technique or indication as the procedure evolved. This study registry number is NCT03129685 at the ClinicalTrials.gov. Results The first HALED operation was carried out safely on 2013, followed by nineteen patients by 2018. Patients' mean age (±standard deviation) was 62·45 (±9·27), range 38–76 years. Eleven (55%) patients had tumors diameter > 10 cm 13 (65%) patients were advanced BCLC stage. Seven modifications were made on the technique and indications of the procedure towards stability. According to the modified response evaluation criteria in solid tumors, 13 patients (65%) attained complete response. Operative mortality was 5% (one patient) and major morbidity was 10% (two patients). Liver infarction and abscess formation were not noticed in this study. Conclusion Our forerunner study showed that HALED for large HCC is safe and induces tumor necrosis. Further long-term studies are suggested before starting the 2b stage.

Temperature compensation and period determination by casein kinase 1 (CK1) are conserved features of eukaryotic circadian rhythms, whereas the clock gene transcription factors that facilitate daily gene expression rhythms differ between phylogenetic kingdoms. Human red blood cells (RBCs) exhibit temperature-compensated circadian rhythms, which, because RBCs lack nuclei, must occur in the absence of a circadian transcription-translation feedback loop. We tested whether period determination and temperature compensation are dependent on CKs in RBCs. As with nucleated cell types, broad-spectrum kinase inhibition with staurosporine lengthened the period of the RBC clock at 37°C, with more specific inhibition of CK1 and CK2 also eliciting robust changes in circadian period. Strikingly, inhibition of CK1 abolished temperature compensation and increased the Q10 for the period of oscillation in RBCs, similar to observations in nucleated cells. This indicates that CK1 activity is essential for circadian rhythms irrespective of the presence or absence of clock gene expression cycles.

Background: Falciparum malaria is one of the causes of morbidity and mortality in third world , the pathogenesis of the infection results from the sequestration of infected hematological change in vital organs. Aim: this study aim to measuring hematological changes and D- dimer among children affected with P falciparum. Methods: The total study group100 children, 60 as case study infected with Plasmodium Falciparum and 40 as control group healthy children. Hematological parameter measuring by hematological analyzer and D dimer measured by fluorescence Immunoassay used I. Chroma instrument. Results: Statistical analysis results of sixty children infected with malaria falciparum participated in the study the mean±SD had a significantly lower Hb (8.14gm/dl ± 2.2) and haematocrit (24.4% ± 6.6) than control children (p

Background: Diabetic foot ulcer (DFU) is considered a major social and economic problem, and it is also known as a leading cause of morbidity and mortality. Patients with DFUs frequently require amputation of the lower limbs, and in more than half of the cases, infection is the predominant factor. The aim of this systemic review is to highlight the risk factors such as age and gender associated with DFU infections, whether the infection is caused by single bacteria or polymicrobial infection and what is the most prevalent bacteria and their susceptibility pattern to currently used antibiotics. Methods: Three databases were searched from December 2020 to February 2021 including PubMed, Hinari, and Google Scholar. A total of 12 articles were included in the current meta-analysis. Results: Higher frequency of DFU in males than in females and maximum number of DFU mostly occur within the age group 40–60 years was reported. Monomicrobial infections in DFU were higher than monomicrobial infection. Escherichia coli, Pseudomonas, and Staphylococcus aureus were the most prominent microorganism. The higher grades of the DFUs were infected with more than one organism. High resistance rates of the isolated bacteria to the most commonly used antibiotics were documented and there were alarming growing resistance rate to Carbapenems which were considered the most effective Antibiotics nowadays. Conclusions: DFU infections are one of the major social and economic problems. There is an urgent need for continuous antibiotic sensitivity testing for the isolated bacteria to choose the appropriate antibiotics during the management and limit the spreading of multidrug-resistant bacteria and reduce the burden of health-care cost.

Objective Sleep disturbance following concussion has been linked to more severe symptoms and longer recovery times. However, it is unclear whether this association may be affected by pre-injury and mood factors. This study examines whether acute symptom severity was associated with poorer sleep quality among recovered vs not-yet-recovered adolescents at 3-months following injury after adjusting for age, sex and anxiety. Method Adolescents aged 12–18 (N = 449) presenting □7 days to ConTex specialty concussion clinics were studied. Of these, 60 reported not being recovered at 3-month follow-up (Mage = 15.23, Nmales = 27, Nfemales = 33). Participants completed the Sport Concussion Assessment Tool-3rd Edition (SCAT-3) Symptom Checklist, Pittsburgh Sleep Quality Index (PSQI), and General Anxiety Disorder-7 (GAD-7). Hierarchical linear regressions assessed if initial symptoms as measured by the SCAT-3 total symptom score, predicted sleep quality at 3-month follow-up, controlling for initial data of age, sex, PSQI, and GAD-7. Results Initial total symptom scores did not predict higher PSQI scores at 3-months for either recovered or non-recovered subjects [F (1, 362, p = .550 and F (1,48), p = .307, respectively]. For recovered subjects, initial sleep ratings (p Conclusions Sleep disturbance was not associated with severity of concussion symptoms when accounting for age, sex, and initial sleep quality. These findings do suggest, however, that females were more likely to report lower sleep quality when experiencing longer recovery.

Introduction: Tobacco smoking is one of the largest and highly preventable public health threats worldwide. In the United Arab Emirates, around 15.7% adult males and 2.4% adult females are current tobacco smokers. Primary healthcare clinics (PHCs) have an important role in battling the smoking epidemic by raising awareness among patients attending them daily. The aim of our study was to assess the knowledge, attitude, and practice regarding smoking among patients attending PHCs. Methods: A cross-sectional descriptive study was conducted on patients attending primary healthcare clinics in Dubai. Data was collected using a pretested self-administered questionnaire developed by the researchers and was adopted from the Global Adult Tobacco Survey. Results: Among a total of 500 patients, around 66.4% were never smokers, 23.6% were current smokers, and 10.0% were ex-smokers. The age of first time smoking among current smokers was the highest between 18 and 19 years, with friends being the source of first attempt of smoking (53.4%). Around 53.4% of the current smokers had poor knowledge, while most of never and ex-smokers had a good knowledge level (47.9%, 70.0%), respectively (P value for both

Background: Abdominal fat elevates while lower-body (LB) fat diminishes cardiovascular risk. However, molecular mechanisms differentiating the two fat depots are not completely understood. MicroRNA (miRNA) are important regulators of gene expression with widespread effects on several proteins. Objective: To explore miRNA differences between the two fat depots using unbiased next-generation sequencing (NGS) approach. Methods: Total RNA isolated from paired subcutaneous (sc) fat tissue obtained from abdomen (ABD) and LB (femoral) region of 12 healthy subjects (7 male; age: 27 ± 5 years; BMI: 23.5 ± 3.2 kg/m 2 ) was used to quantify miRNA expression. Body fat distribution was determined using dual-energy X-ray absorptiometry and abdominal computed tomography scans. RNA was prepped using the NEBNext small RNA library prep kit and sequenced using Illumina HiSeq 2000. Raw sequence data were processed using CAP-miRSeq pipeline. miRNA expression between the two depots was evaluated using EdgeR. Relationship between miRNA and regional fat depots were examined using Spearman’s correlation. Adjusted or unadjusted P value Results: Using NGS, 383 ± 55 known miRNA with ≥5 raw reads were detected in the study samples. Principal component analysis including all miRNAs showed no any clear separation between ABD or LB fat tissue. However, 37 miRNAs were found to have altered expression in the two depots. miR-196a-5p (log2FC=1.138, p Conclusions: Several miRNAs are differentially expressed between ABD and LB fat tissue which may partly contribute to depot specific alterations in adipose tissue function and consequent cardiometabolic risk. Furthermore, the associations between miRNA and regional fat depots suggest a functional role of these miRNA in fat distribution.

Background Excessive daytime sleepiness ( EDS ), a common symptom among patients with sleep‐disordered breathing, is closely associated with the development of cardiovascular diseases, but its long‐term prognostic value is not completely understood. The aim of this study was to investigate whether EDS would be an independent prognostic factor after myocardial infarction. Methods and Results We prospectively recruited 112 post–myocardial infarction patients. The Epworth Sleepiness Scale was completed before polysomnography, and EDS was defined as a score ≥11. After exclusion of 8 patients who accepted treatment with continuous positive airway pressure, 104 patients were followed up for 48 months. The primary composite end point was major adverse cardiac events. Patients with EDS had higher rates of major adverse cardiac events (48.4% versus 27.4%, χ 2 =5.27, P =0.022) and reinfarction (29.0% versus 5.5%, χ 2 =13.51, P =0.0002) compared with those without EDS . In the Cox proportional hazards model, patients with EDS had 2.15 times (95% confidence interval, 1.08–4.18; P =0.030) higher crude risk of major adverse cardiac events, with prognostic significance persisting after adjusting for age, diabetes mellitus, depression, left ventricular ejection fraction, apnea–hypopnea index, and nocturnal nadir oxygen saturation (hazard ratio: 2.13, 95% confidence interval, 1.04–4.26, P =0.039). Furthermore, among participants with moderate to severe sleep‐disordered breathing, the presence of EDS was associated with higher risk of major adverse cardiac events than those without EDS , after adjusting for age and nadir oxygen saturation (hazard ratio: 3.17, 95% confidence interval, 1.22–7.76, P =0.019). Conclusions EDS may be an independent prognostic factor of adverse outcome in post–myocardial infarction patients with moderate to severe sleep‐disordered breathing. Evaluation of EDS may shed new light on risk stratification and identify treatment responders for this patient population.

Crosslinked, multi-layer electrospun gelatin fiber scaffolds with generally ±45 degree fiber orientation have been used to grow human umbilical vein smooth muscle cells (HUVSMCs) to create a vascular tunica media graft. Scaffolds of different fiber diameter (2-5 μm in wet state), pore size, and porosity (16-21% in wet state) were assessed in terms of cell adherence and viability, cell proliferation, and migration in both in-plane and transverse directions through the scaffold as a function of time under static cell culture conditions. HUVSMC cell viability reached between 80 and 92% for all scaffolds after 9 days in culture. HUVSMCs adhered, elongated, and orientated in the fiber direction, and migrated through a scaffold thickness of 200-235 μm 9 days post-seeding under static conditions. The best scaffold was then used to assess the tissue engineering of HUVSMCs under dynamic conditions for a rotating, cell seeded, tubular scaffold in the bioreactor containing the culture medium. Dynamic conditions almost doubled the rate of cell proliferation through the scaffold, forming full tissue throughout a scaffold of 250-300 μm thickness 6 days post-seeding.

Background/Objective Adiponectin exerts beneficial effects by reducing inflammation, and improving lipid metabolism and insulin-sensitivity. Although adiponectin is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. Methods/Results Forty four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8-weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8 ± 1.2 kg resulted in increased adiponectin (p=0.03) while weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (p=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, while a leptin-antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in adipose tissue from normal-weight participants, but did not do so in adipose tissue from obese participants; and second, that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. Conclusions Modest weight gain in healthy individuals is associated with increases in adiponectin, which correlate positively with changes in leptin. In-vitro, leptin induces adiponectin expression which is attenuated by increased caveolin-1 expression. Additionally, adipose tissue from obese subjects shows increased caveolin-1 expression, and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.

Apoptosis is characterised by many cellular events, but the standard Annexin-V assay identifies two; the transfer of the phospholipid phosphatidylserine (PS) from inner to outer leaflets of the plasma membrane, acting as an "eat me" signal to macrophages, and the permeabilisation of the plasma membrane. In this paper we compare the results from the Annexin-V assay with electrophysiology data obtained in parallel using dielectrophoresis, which highlights two changes in cell electrophysiology; a change in cytoplasmic conductivity which correlates with PS expression, and a membrane conductance spike that correlates with permeabilisation. Combining results from both methods shows a strong inverse relationship between conductivity and PS externalisation. One mechanism which may explain this correlation is related to intracellular Ca(2+), which is known to increase early in apoptosis. PS expression occurs when enzymes called scramblases swap external and internal phospholipids, and which are usually activated by Ca(2+), whilst the change in cytoplasmic conductivity may be due to K(+) efflux from intermediate conductance (IK) ion channels that are also activated by Ca(2+).

Whilst personalized medicine (where interventions are precisely tailored to a patient's genotype and phenotype, as well as the nature and state of the disease) is regarded as an optimal form of treatment, the time and cost associated with it means it remains inaccessible to the greater public. A simpler alternative, stratified medicine, identifies groups of patients who are likely to respond to a given treatment. This allows appropriate treatments to be selected at the start of therapy, avoiding the common "trial and error" approach of replacing a therapy only once it is demonstrated to be ineffective in the patient. For stratification to be effective, tests are required that rapidly predict treatment effectiveness. Most tests use genetic analysis to identify drug targets, but these can be expensive and may not detect changes in the phenotype that affect drug sensitivity. An alternative method is to assess the whole-cell phenotype by evaluating drug response using cells from a biopsy. We assessed dielectrophoresis to assess drug efficacy on short timescales and at low cost. To explore the principle of assessing drug efficacy we examined two cell lines (one expressing EGFR, one not) with the drug Iressa. We then further explored the sensitive cells using combinations of chemotherapeutic and radiotherapeutic therapies. Our results compare with known effects of these cell/treatment combination, and offer the additional benefit over methods such as TUNEL of detecting drug effects such as cell cycle arrest, which do not cause cell death.

Currently, cell separation occurs almost exclusively by density gradient methods and by fluorescence- and magnetic-activated cell sorting (FACS/MACS). These variously suffer from lack of specificity, high cell loss, use of labels, and high capital/operating cost. We present a dielectrophoresis (DEP)-based cell separation method, using 3D electrodes on a low-cost disposable chip; one cell type is allowed to pass through the chip whilst the other is retained and subsequently recovered. The method advances usability and throughput of DEP separation by orders of magnitude in throughput, efficiency, purity, recovery (cells arriving in the correct output fraction), cell losses (those which are unaccounted for at the end of the separation) and cost. The system was evaluated using three example separations; live and dead yeast; human cancer cells/red blood cells; and rodent fibroblasts/red blood cells. A single-pass protocol can enrich cells with cell recovery of up to 91.3% at over 300,000 cells/second with >3% cell loss. A two-pass protocol can process 300,000,000 cells in under 30 minutes, with cell recovery of up to 96.4% and cell losses below 5%, an effective processing rate >160,000 cells/second. A three-step protocol is shown to be effective for removal of 99.1% of RBCs spiked with 1% cancer cells, whilst maintaining a processing rate of ~170,000 cells/second. Furthermore, the self-contained and low-cost nature of the separator device means that it has potential application in low-contamination applications such as cell therapies, where GMP compatibility is of paramount importance. Significance statement. Cell separation is a fundamental process in biomedicine, but is presently complicated, cumbersome and expensive. We present a technique that can sort cells at a rate equivalent to or faster than gold-standard techniques such as FACS and MACs, but can do label-free and with very low cell loss. The system uses dielectrophoresis (DEP) to sort cells electrostatically, using a novel electrode chip that eschews microfabrication in favour of a laminate drilled with 397 electrode-bearing wells. This high level of parallelisation makes the system immune to the bubbles that limit labs-on-chip, whilst also increasing capacity and throughput to unprecedented levels, whilst the chip is cheap enough to be disposable, preventing inter-separation contamination.

The effect of an exercise program on the body composition, muscular strength (MS), biochemical markers, and bone mineral density (BMD) of individuals undergoing gastric bypass is unclear. We assessed lean mass (LM), MS, bone remodeling markers, and BMD before and after supervised weight-bearing and aerobic exercise training in obese patients who underwent Roux-en-Y gastric bypass (RYGB).This study included 37 obese patients (81.1% women, mean age 38.2 years, mean body mass index 42.4 ± 0.5 kg/mAfter 1 year, the TG showed a lower decrease in total BMD and at the lumbar spine and right hip compared with the CG (p 0.001). The TG had lower mass reduction and an increase in upper limb LM compared with the CG (both p 0.05). There was no significant difference between groups in bone markers or calcium metabolism. MS was higher in the TG than the CG (p 0.05).The supervised exercise program attenuated lumbar spine and right hip BMD loss and improved LM in the arms and overall MS but did not affect bone remodeling.

The goal of our study was to develop a simple and practical method for simulating diving in humans using facial cold exposure and apnea stimuli to measure neural and circulatory responses during the stimulated diving reflex. We hypothesized that responses to simultaneous facial cold exposure and apnea (simulated diving) would be synergistic, exceeding the sum of responses to individual stimuli. We studied 56 volunteers (24 female and 32 male), average age of 39 years. All subjects were healthy, free of cardiovascular and other diseases, and on no medications. Although muscle sympathetic nerve activity (MSNA), blood pressure, and vascular resistance increased markedly during both early and late phases of simulated diving, significant reductions in heart rate were observed only during the late phase. Total MSNA during simulated diving was greater than combined MSNA responses to the individual stimuli. We found that simulated diving is a powerful stimulus to sympathetic nerve traffic with significant bradycardia evident in the late phase of diving and eliciting synergistic sympathetic and parasympathetic responses. Our data provide insight into autonomic triggers that could help explain catastrophic cardiovascular events that may occur during asphyxia or swimming, such as in patients with obstructive sleep apnea or congenital long QT syndrome.