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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Study aimed to determine effectiveness of educational program on children with growth hormone deficiency knowledge at and determine relationship between knowledge and their general information.

Dielectrophoresis (DEP) is a non-invasive cell analysis method that uses differences in electrical properties between particles and surrounding medium to determine a unique set of cellular properties that can be used as a basis for cell separation. Cell-based therapies using skeletal stem cells are currently one of the most promising areas for treating a variety of skeletal and muscular disorders. However, identifying and sorting these cells remains a challenge in the absence of unique skeletal stem cell markers. DEP provides an ideal method for identifying subsets of cells without the need for markers by using their dielectric properties. This study used a 3D dielectrophoretic well chip device to determine the dielectric characteristics of two osteosarcoma cell lines (MG-63 and SAOS-2) and an immunoselected enriched skeletal stem cell fraction (STRO-1 positive cell) of human bone marrow. Skeletal cells were exposed to a series of different frequencies to induce dielectrophoretic cell movement, and a model was developed to generate the membrane and cytoplasmic properties of the cell populations. Differences were observed in the dielectric properties of MG-63, SAOS-2 and STRO-1 enriched skeletal populations, which could potentially be used to sort cells in mixed populations. This study provide evidence of the ability to characterize different human skeletal stem and mature cell populations, and acts as a proof-of-concept that dielectrophoresis can be exploited to detect, isolate and separate skeletal cell populations from heterogeneous bone marrow cell populations.

A loss of ability of cells to undergo apoptosis (programmed cell death, whereby the cell ceases to function and destroys itself) is commonly associated with cancer, and many anti-cancer interventions aim to restart the process. Consequently, the accurate quantification of apoptosis is essential in understanding the function and performance of new anti-cancer drugs. Dielectrophoresis has previously been demonstrated to detect apoptosis more rapidly than other methods, and is low-cost, label-free and rapid, but has previously been unable to accurately quantify cells through the apoptotic process because cells in late apoptosis disintegrate, making cell tracking impossible. In this paper we use a novel method based on light absorbance and multi-population tracking to quantify the progress of apoptosis, benchmarking against conventional assays including MTT, trypan blue and Annexin-V. Analyses are performed on suspension and adherent cells, and using two apoptosis-inducing agents. IC50 measurements compared favourably to MTT and were superior to trypan blue, whilst also detecting apoptotic progression faster than Annexin-V.

Background Obstructive sleep apnea ( OSA ) is an important risk factor for the development of cardiovascular diseases including myocardial infarction ( MI ). The aim of this study was to investigate the effects of OSA on prognosis after MI , and to determine which specific measures of OSA severity best predicted outcomes. Methods and Results We performed a prospective study, in which 112 patients without a prior diagnosis of sleep apnea underwent comprehensive polysomnography within a median of 7 days after MI . Patients were followed up at 6‐monthly intervals (±2 weeks) for a total of 48 months. Patients classified with central apnea (n=6) or those using continuous positive airway pressure (n=8) after polysomnography were excluded from analyses. The primary end point was major adverse cardiac events, including death from any cause, recurrent MI , unstable angina, heart failure, stroke, and significant arrhythmic events. Forty of 98 patients (41%) had OSA (apnea‐hypopnea index ≥15 events/h). OSA patients had higher major adverse cardiac event rates when compared to those without OSA (47.5% versus 24.1%; χ 2 =5.41, P =0.020). In a multivariate model that adjusted for clinically relevant variables including age, left ventricular ejection fraction, diabetes mellitus, oxygen desaturation index, and arousal index, significant hypoxemia, as defined by nocturnal nadir oxygen saturation ≤85%, was an independent risk factor for major adverse cardiac events (hazard ratio=6.05, P =0.004) in follow‐up 15 months after baseline. Conclusions Nocturnal hypoxemia in OSA is an important predictor of poor prognosis for patients after MI . These findings suggest that routine use of low‐cost nocturnal oximetry may be an economical and practical approach to stratify risk in post‐ MI patients.

The mode of delivery in diabetic patients is debatable. This study was designed to assess the pattern of delivery of macrosomic babies with a high prevalence of diabetes mellitus in Bahrain.This retrospective analysis was conducted on mothers who delivered babies weighing ≥4.0 Kgs from 2001 to 2011 at Bahrain Defence Force Hospital. Data regarding patients' age, weight, mode of delivery, diabetic status, gestational age and parity were recorded. The main outcome was the effect of diabetes mellitus on the decision to allow vaginal delivery for macrocosmic babies. Other outcomes were failed trial of labour, parity, maternal age and foetal weight on the trial of labour and neonatal morbidity associated with vaginal births.The incidence of macrosomic babies was 2.2% of total births. Pre-existing diabetes mellitus was 3.9% of the study cohort. The rate of elective Caesarean section increased from 12.5% in non-diabetic mothers to 50% in patients with pre-existing diabetes. In cases of allowing a trial of labour, approximately 70% of patients with pre-existing diabetes had successful vaginal delivery. Patients with a previous delivery were less likely to undergo emergency procedures, but had the same probability for elective Caesarean compared with primigravida. Patient's age and foetal weight had no influence on successful trial of vaginal birth.There was a trend to offer more elective Caesarean sections in patients with macrosomic babies in the presence of pre-existing diabetes. The majority of patients who were offered a trial of labour achieved vaginal delivery with minimal morbidity.إن أسلوب توليد الحوامل من مرضى السكري مختلَف عليه. صُممت هذه الدراسة بغرض تقييم الأنماط المختلفة لتوليد الأطفال كبار الحجوم بسبب ارتفاع معدل انتشار داء السكري في البحرين.تم إجراء هذا التحليل الاستعادي على الأمهات اللواتي أنجبن أطفالا ذوي أوزان٤.٠ كغم من عام ٢٠٠١م إلى عام ٢٠١١م في مستشفى قوة دفاع البحرين. تم تسجيل البيانات المتعلقة بعمر ووزن وأسلوب التوليد والإصابة بداء السكري من عدمه ومدة الحمل وعدد الولادات السابقة. كان المستخرج الرئيس؛ تأثير داء السكري على قرار السماح بالولادة المهبلية للأطفال كبار الحجوم. وشملت المستخرجات الأخرى عدم نجاح محاولة التوليد الطبيعي، وعدد الولادات السابقة، وأثر عمر الأم، ووزن الجنين على قرار محاولة التوليد الطبيعي، ومضاعفات حديثي الولادة المرتبطة بالولادات المهبلية.نسبة المواليد كبار الحجوم في فترة الدراسة كانت ٢.٢٪ من بين المواليد. لوحظت الإصابة المسبقة بداء السكري في ٣.٩٪ من الخاضعات للدراسة. اختلفت نسبة إجراء عمليات قيصرية مجدولة من ١٢.٥٪ في الأمهات اللواتي لا يعانين من داء السكري إلى ٥٠٪ في اللواتي يعانين منه. أما بالنسبة لإعطاء فرصة ولادة طبيعية٬ فقد أتم حوالي ٧٠٪ من المرضى اللواتي يعانين من داء السكري ولادة طبيعية ناجحة. كان احتمال الحاجة إلى إجراء اضطراري أقل في اللواتي سبق لهن الولادة مقارنة باللواتي لم يسبق لهن الولادة٬ إلا أن احتمال القيصرية المجدولة كان متساو بينهما. لم يكن لعمر المريضة ولا لوزن الجنين أي أثر على نجاح محاولة الولادة المهبلية.كان المعتاد في السابق الإكثار من عرض العملية القيصرية المجدولة على الحوامل ذوات الأجنة كبار الحجم في حال كن يعانين من داء السكري. غالبية المرضى الخاضعات لمحاولة الولادة الطبيعية أتممن ذلك بالقليل من المضاعفات.

Asian Indians have markedly increased mortality due to coronary artery disease (CAD). Impaired endothelial function has been linked to an increased risk of acute cardiovascular events. We tested the hypothesis that endothelial function was attenuated in Asian Indians and Caucasians.We studied 14 Asian Indians [mean age: 30 ± 6 years; mean body mass index (BMI): 25 ± 3 kg/m(2)] and 11 Caucasians (mean age: 30 ± 5 years; mean BMI: 26 ± 2 kg/m(2)). All 25 subjects were healthy men and nonsmokers without any history of CAD or diabetes and were not taking medications. Endothelial function was evaluated by ultrasound measures of flow-mediated dilatation (FMD) and endothelium-independent nonflow mediated vasodilatation (NFMD) of the brachial artery, in the morning immediately after awakening (6 a.m.) in a fasting state.Mean age, BMI, apnea-hypopnea index, heart rate, and blood pressure were similar in both groups (P = 0.05). When correcting for body surface area, brachial artery diameter was not different between the two groups (2.1% ± 0.3% vs. 2.2% ± 0.4%; P = 0.29). FMD and NFMD were similar in Asian Indians and Caucasians (5.9% ± 4.1% vs. 5.7% ± 2.6%, P = 0.70; 16.4% ± 8% vs. 14.8% ± 4.1%, P = 0.58, respectively).Endothelial function in Asian Indian men is not attenuated in comparison to Caucasian men.

Background The Berlin Questionnaire (BQ) has been used to identify patients at high risk for sleep-disordered breathing (SDB) in a variety of populations. However, there are no data regarding the validity of the BQ in detecting the presence of SDB in patients after myocardial infarction (MI). The aim of this study was to determine the performance of the BQ in patients after MI. Methods We conducted a cross-sectional study of 99 patients who had an MI 1 to 3 months previously. The BQ was administered, scored using the published methods, and followed by completed overnight polysomnography as the "gold standard." SDB was defined as an apnea-hypopnea index of ≥ 5 events/h. The sensitivity, specificity, and positive and negative predictive values of the BQ were calculated. Results Of the 99 patients, the BQ identified 64 (65%) as being at high-risk for having SDB. Overnight polysomnography showed that 73 (73%) had SDB. The BQ sensitivity and specificity was 0.68 and 0.34, respectively, with a positive predictive value of 0.68 and a negative predictive value of 0.50. Positive and negative likelihood ratios were 1.27 and 0.68, respectively, and the BQ overall diagnostic accuracy was 63%. Using different apnea-hypopnea index cutoff values did not meaningfully alter these results. Conclusion The BQ performed with modest sensitivity, but the specificity was poor, suggesting that the BQ is not ideal in identifying SDB in patients with a recent MI.

Background Obstructive sleep apnea (OSA) has been recognized as a risk factor for cardiovascular disease and mortality. The aim of this study was to determine the feasibility and efficacy of implementing a screening program for OSA in early outpatient cardiac rehabilitation (CR) and to estimate the risk for OSA in this population. Methods From 535 consecutive patients enrolled in early outpatient CR we screened 383 (72%) patients and classified them as low- vs. high-risk for OSA using the Berlin questionnaire. Those considered at high-risk for OSA were referred for further evaluation. We assessed the yield and feasibility of the screening program, patient compliance with referral, and the percentage of patients diagnosed with OSA after polysomnography. Results Mean age was 63 ± 12 years, 70% were men, 20% had diabetes, 65% had hypertension, and 58% had experienced a recent myocardial infarction. Two hundred and one patients (52%) had a high risk for OSA based on the questionnaire. Of the 169 who completed the CR program, only 111 (78%) were referred for further evaluation ( Fig. 1 ). Of the 74 patients who completed their OSA work-up, 39 were found to have OSA with an apnea–hypopnea index of ⩾5 events/h. Conclusions Implementation of a simple screening program for OSA in early outpatient CR is feasible with minimal incremental resources. A significant percentage of patients at high-risk decline further evaluation, suggesting that their perceived risk for OSA and its consequences may be low.

Most oral cancers are oral squamous cell carcinomas (OSCC) that arise from the epithelial lining of the oral mucosa. Given that the oral cavity is easily accessible, the disease lends itself to early detection; however, most oral cancers are diagnosed at a late stage, and approximately half of oral cancer sufferers do not survive beyond five years, post-diagnosis. The low survival rate has been attributed to late detection, but there is no accepted, reliable and convenient method for the detection of oral cancer and oral pre-cancer. Dielectrophoresis (DEP) is a label-free technique which can be used to obtain multi-parametric measurements of cell electrical properties. Parameters such as cytoplasmic conductivity and effective membrane capacitance (C(Eff)) can be non-invasively determined by the technique. In this study, a novel lab-on-a-chip device was used to determine the cytoplasmic conductivity and C(Eff) of primary normal oral keratinocytes, and pre-cancerous and cancerous oral keratinocyte cell lines. Our results show that the electrical properties of normal, pre-cancerous and cancerous oral keratinocytes are distinct. Furthermore, increasing C (Eff) and decreasing cytoplasmic conductivity correlate with disease progression which could prove significant for diagnostic and prognostic applications. DEP has the potential to be used as a non-invasive technique to detect oral cancer and oral pre-cancer. Clinical investigation is needed to establish the reliability and temporal relationship of the correlation between oncologic disease progression and the electrical parameters identified in this study. To use this technique as an OSCC detection tool in a clinical setting, further characterisation and refinement is warranted.

Objectives The aim of this study was to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. Background Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. Methods A randomized controlled study was conducted to assess the effects of fat gain on endothelial function. Forty-three normal-weight healthy volunteers were recruited (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n = 35) or to maintain weight (n = 8). Endothelial function (brachial artery flow-mediated dilation [FMD]) was measured at baseline, after fat gain (8 weeks), and after weight loss (16 weeks) for fat gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition was measured by dual-energy X-ray absorptiometry and abdominal computed tomographic scans. Results After an average weight gain of 4.1 kg, fat gainers significantly increased their total, visceral, and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight maintainers. FMD decreased in fat gainers (9.1 ± 3% vs. 7.8 ± 3.2%, p = 0.003) but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho = −0.42, p = 0.004), but not with subcutaneous fat gain (rho = −0.22, p = 0.15). Conclusions In normal-weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. (Fat Gain and Cardiovascular Disease Mechanisms; NCT00589498 )

Objectives This study sought to evaluate the day–night variation of acute myocardial infarction (MI) in patients with obstructive sleep apnea (OSA). Background Obstructive sleep apnea has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night. Methods We prospectively studied 92 patients with MI for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography. Results For patients with and without OSA, we compared the frequency of MI during different intervals of the day based on the onset time of chest pain. The groups had similar prevalence of comorbidities. Myocardial infarction occurred between 12 am and 6 am in 32% of OSA patients and 7% of non-OSA patients (p = 0.01). The odds of having OSA in those patients whose MI occurred between 12 am and 6 am was 6-fold higher than in the remaining 18 h of the day (95% confidence interval: 1.3 to 27.3, p = 0.01). Of all patients having an MI between 12 am and 6 am , 91% had OSA. Conclusions The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI. Patients having nocturnal onset of MI should be evaluated for OSA, and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events.

ALONG WITH THE EPIDEMIC OF obesity, there is a growing awareness of sleep-disordered breathing as a potential and treatable risk factor for cardiovascular disease. The repetitive nocturnal hypoxemia experienced by patients with obstructive sleep apnea (OSA) is associated with activation of a number of neural, humoral, thrombotic, metabolic, and inflammatory disease mechanisms, all of which have also been implicated in the pathophysiology of cardiac and vascular disease. Activation of these mechanisms is often evident even in patients with OSA who are free of overt cardiovascular disease, suggesting that OSA may conceivably contribute to the initiation and progression of cardiovascular disease (FIGURE 1). SleepapneacanbecategorizedasOSA, in which there is preserved and increased respiratory effort despite partial or complete occlusion of the upper airway; or as central sleep apnea (CSA), in which there is absence of both respiratory efforts and airflow. The apneahypopnea index (ie, the number of apneic and hypopneic events per hour) is used as one index of the presence and severity of sleep apnea. For OSA, an apnea-hypopnea index of 5 to 15 indicates mild apnea; of 15 to 30, moderate apnea; and of greater than 30, severe apnea. Approximately 1 in 5 adults has at least mild OSA (apnea-hypopnea index, 5-15), and 1 in 15 adults has at least moderate OSA (apnea-hypopnea index, 15-30). Other measures of the severity of sleep apnea include the severity of oxygen desaturation and the level of daytime sleepiness. Obstructive sleep apnea is commonly associated with obesity and also is often present in patients with

Body mass index (BMI) is the most widely used measure to diagnose obesity. However, the accuracy of BMI in detecting excess body adiposity in the adult general population is largely unknown. A cross-sectional design of 13 601 subjects (age 20–79.9 years; 49% men) from the Third National Health and Nutrition Examination Survey. Bioelectrical impedance analysis was used to estimate body fat percent (BF%). We assessed the diagnostic performance of BMI using the World Health Organization reference standard for obesity of BF%>25% in men and>35% in women. We tested the correlation between BMI and both BF% and lean mass by sex and age groups adjusted for race. BMI-defined obesity (⩾30 kg m−2) was present in 19.1% of men and 24.7% of women, while BF%-defined obesity was present in 43.9% of men and 52.3% of women. A BMI⩾30 had a high specificity (men=95%, 95% confidence interval (CI), 94–96 and women=99%, 95% CI, 98–100), but a poor sensitivity (men=36%, 95% CI, 35–37 and women=49%, 95% CI, 48–50) to detect BF%-defined obesity. The diagnostic performance of BMI diminished as age increased. In men, BMI had a better correlation with lean mass than with BF%, while in women BMI correlated better with BF% than with lean mass. However, in the intermediate range of BMI (25–29.9 kg m−2), BMI failed to discriminate between BF% and lean mass in both sexes. The accuracy of BMI in diagnosing obesity is limited, particularly for individuals in the intermediate BMI ranges, in men and in the elderly. A BMI cutoff of⩾30 kg m−2 has good specificity but misses more than half of people with excess fat. These results may help to explain the unexpected better survival in overweight/mild obese patients.

Leptin, an adipose tissue-derived hormone, has been linked to cardiovascular outcomes; however, data are limited in the United States population, especially women. To assess the association between leptin concentrations and history of myocardial infarction (MI) and stroke independently of traditional cardiovascular risk factors, we analyzed data from 6,239 subjects (mean age 47 years; 3,336 women) with measurements of serum leptin and full assessment of cardiovascular risk factors from the National Health and Nutrition Examination Survey (NHANES) III. Logistic regression was used to estimate the cross-sectional association of leptin concentrations (highest quartile versus lowest quartile) and history of MI, stroke, and the composite end point of MI or stroke (MI/stroke). Gender-specific models of leptin were adjusted for age, race, dyslipidemia, hypertension, diabetes, smoking, and obesity status. There were 212 men with MI/stroke (5.4%), 154 with MI (4.1%), and 82 with stroke (1.7%). There were 135 women with MI/stroke (2.6%), 74 with MI (1.5%), and 78 with stroke (1.4%). In multivariate analysis, high leptin level was significantly and independently associated with MI/stroke in men (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.93) and women (OR 4.26, 95% CI 1.75 to 10.73); with MI in men (OR 3.16, 95% CI 1.40 to 7.37) and women (OR 3.96, 95% CI 1.29 to 12.72), and with stroke in women (OR 3.20, 95% CI 1.04 to 10.54) but not in men (OR 1.37, 95% CI 0.38 to 3.88). In conclusion, in the United States population, increased leptin concentrations are significantly associated with MI/stroke in men and women independently of traditional cardiovascular risk factors and obesity status.

The early detection of oral squamous cell carcinoma by non-invasive methods has the potential to hasten diagnosis and thus lessen the morbidity associated with tumour therapy. Dielectrophoresis (DEP) can non-invasively determine electrophysiological parameters such as conductivity and permittivity of cellular cytoplasm and membrane. The present study demonstrates that DEP can be utilised to characterise H357 and UP cells and reveals that there are significant differences in these parameters between malignant and more normal epithelial cell lines. The present results suggest that DEP has potential for the early detection of cancerous from non-cancerous cells in a clinical setting.

We thank Dr. Kuwada for the comments related to our study and are pleased to provide specific answers below. Prevalence and Type of Sleep Disordered Breathing in Patients Post Acute Myocardial Infarction: We fully agree that the polygraphy device used in our study does not necessarily allowdifferentiation between obstructive and central sleep disordered breathing (SDB) events. Therefore, we used the overall apnea–hypopnea index, without specific subanalysis for obstructive and central events. Indeed, we specifically note the inability to discriminate between obstructive and central events as a significant limitation of our study.

While sleep apnea (SA) might be a modifiable cardiovascular risk factor, recent data suggest that SA is severely underdiagnosed in patients after acute myocardial infarction (MI). There is limited evidence about day-night variation of onset of MI on dependence of having SA. We therefore investigated the prevalence of SA and examined the day-night variation of onset of MI in acute MI patients.We prospectively studied 782 consecutive patients admitted to the hospital with the diagnosis of acute MI. All subjects underwent sleep evaluations using a portable device after at least 48 h post-admission. Using the apnea-hypopnea index (AHI), groups were defined as patients without SA (5 events/h), mild SA (5-15 events/h), moderate SA (15-30 events/h), and severe SA (≥ 30 events/h).Almost all patients (98%) underwent urgent coronary angiography and 91% of patients underwent primary PCI. Using a threshold of AHI ≥ 5 events/h, SA was present in 65.7% of patients after acute MI. Mild SA was present in 32.6%, moderate in 20.4% and severe in 12.7%. The day-night variation in the onset of MI in all groups of SA patients was similar to that observed in non-SA patients. From 6 AM to 12 PM, the frequency of MI was higher in both SA and non-SA patients, as compared to the interval from 12 AM to 6 AM (all p0.05).There is a high prevalence of SA in patients presenting with acute MI. Peak time of MI onset in SA patients was between 6 AM and noon, similar to that in the general population. Whether diagnosis and treatment of SA after MI will significantly improve outcomes in these patients remains to be determined.

The scope of this work was to synthesize a novel bifunctionalized vanadyl(VO)(2+)/vitamin B 6 complex. The diabetic therapeutic efficacy of the new complex was investigated in alloxan-induced diabetic mice. The results suggested that vanadyl(VO)(2+)/vit B6 complex has an anti-diabetic potency, improved the lipid profile and liver and kidney functions. The new complex possesses an antioxidant activity. The current results support the therapeutic potentiality of vanadyl(VO)(2+)/vitamin B 6 complex for the management of diabetes.

Rationale: The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1–dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known. Objective: To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans. Methods and Results: We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P =0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis. Conclusions: In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

Background An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF. Methods We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB. Results Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m 2 , and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low ( R 2 = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively. Conclusions Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.

Obesity has been associated with increased cardiac sympathetic activation during wakefulness, but the effect on sleep-related sympathetic modulation is not known. The aim of this study was to investigate the effect of fat gain on cardiac autonomic control during wakefulness and sleep in humans. We performed a randomized, controlled study to assess the effects of fat gain on heart rate variability. We recruited 36 healthy volunteers, who were randomized to either a standardized diet to gain ≈4 kg over 8 weeks followed by an 8-week weight loss period (n=20) or to serve as a weight-maintainer control (n=16). An overnight polysomnogram with power spectral analysis of heart rate variability was performed at baseline, after weight gain, and after weight loss to determine the ratio of low-frequency to high-frequency power and to examine the relationship between changes in heart rate variability and changes in insulin, leptin, and adiponectin levels. Mean weight gain was 3.9 kg in the fat gain group versus 0.1 kg in the maintainer group. Low frequency/high frequency increased both during wakefulness and sleep after fat gain and returned to baseline after fat loss in the fat gain group and did not change in the control group. Insulin, leptin, and adiponectin also increased after fat gain and fell after fat loss, but no clear pattern of changes was seen that correlated consistently with changes in heart rate variability. Short-term fat gain in healthy subjects is associated with increased cardiac sympathetic activation during wakefulness and sleep, but the mechanisms remain unclear.

Impaired brachial flow-mediated dilation (FMD) is associated with risk for subsequent cardiovascular events in patients after myocardial infarction (MI). These patients often have obstructive sleep apnea (OSA). We tested the hypothesis that patients with OSA post MI will exhibit more severe impairment in FMD.We studied 64 patients with MI admitted to our hospital. OSA was determined using polysomnography. FMD was measured using high-resolution ultrasonography, with researchers blind to the OSA diagnosis.The mean age was 60 ± 11 years, and the mean BMI was 29 (26, 32 kg/m(2)), 84% of patients were men, 39% had moderate to severe OSA (apnea-hypopnea index [AHI]15), and 31% of the patients had mild OSA (5 ≤ AHI15). FMD was severely impaired in patients with moderate to severe OSA (0.8% ± 0.7%) as compared with patients without OSA (4.7% ± 0.8%, P = .001) and with mild OSA (3.9% ± 0.8%, P = .015). Linear regression showed that FMD was associated with log nocturnal nadir oxygen saturation (minSaO(2)) (β = 31.17, P = .0001), age (β = -0.11, P = .006). MinSaO(2) was an independent predictor of FMD after adjustment for possible confounders (β = 26.15, P = .001).FMD is severely impaired in patients with moderate to severe OSA post MI, which may be partially related to nocturnal hypoxemia. Patients with OSA may, therefore, be at higher risk for subsequent cardiovascular events after an MI. Identifying and treating OSA may have important implications in the long-term prognosis of patients post MI. Further studies are necessary to determine if the presence of OSA would affect the long-term occurrence of cardiovascular events after an MI.

TO THE EDITOR: Obstructive sleep apnea (OSA) is highly prevalent in the general population and has been associated with arrhythmias, hypertension, stroke, and heart failure (1). Identification of OSA in cardiovascular patients is especially important as untreated OSA may be accompanied by increased cardiovascular events, and this risk may be attenuated by treatment with continuous positive airway pressure (CPAP)(2). We sought to investigate how the rates of recognition and diagnosis of obstructive sleep apnea compare to the actual prevalence of OSA in patients after myocardial infarction (MI). This study comprised two parts: a chart review of consecutive patients presenting with acute MI, and a prospective evaluation of MI patients who were recruited to undergo polysomnography. These studies were approved by the Institutional Review Board. First, we reviewed the medical records of 798 consecutive patients who were hospitalized with a diagnosis of acute MI between January and September 2007. Electronic records, including admission and dismissal notes were searched for diagnosed or suspected sleep disordered breathing, and especially for mention of OSA during the MI hospitalization. In the event of several hospital admissions for the same patient, only the first admission was used in our analysis. We further prospectively studied 74 patients who were hospitalized with acute myocardial infarction between 2004 and 2008, and were recruited to undergo attended overnight polysomnography, which is the gold standard in the diagnosis of OSA (Compumedics Siesta Wireless Sleep Recorder, Oxford Instruments, UK). All polysomnographies were performed within 6 weeks of the MI hospitalization, and scored by standard criteria (1). OSA was defined as present when the apnea hypopnea index (AHI) was >5. The diagnosis of MI was based on standard guidelines, and was made by the attending physicians who were blinded to this study. Patients were approached during their MI hospitalization, and their participation was based on their consent and availability of the study personnel and equipment. There was no systematic selection for specific demographic or patient characteristics. A review of electronic and paper records of these patients was also performed in similar fashion to that of the first part of our study. Between January and September 2007 there were 798 patients admitted to our institution with the diagnosis of acute MI. The mean age of this cohort was 69±14 years, and 512 (64%) were male. Diagnosed and suspected OSA was recorded in 97 (12%) patient records. The prospective cohort of 74 patients had a mean age of 62±13 years, and 46 (78%) were male. On review of their hospital records, 10 (14%) had documentation of diagnosed or suspected OSA. All of these patients underwent overnight polysomnography (PSG). For this group the mean AHI was 17±18 events/hour. OSA was present in 51 (69%), and severe OSA (AHI >15) in 30 (41%) patients. The main finding of this study was the low rate of documented or suspected OSA in patients hospitalized for acute MI, contrasting with the high prevalence of OSA in those in whom we conducted prospective PSG studies. This suggests a lack of awareness and recognition of OSA during treatment of acute MI. A high prevalence of OSA in the unselected general population has been well documented (1). Our results suggest that only 12 percent of patients hospitalized with acute MI had documentation of diagnosed or suspected OSA. When prospectively evaluated by overnight PSG a subgroup of patients had a much higher actual prevalence of OSA (over two thirds had at least mild OSA) but even in these patients with proven sleep apnea the possibility of OSA was documented in only 14 percent of patients. There are several limitations to our study. First, documentation in the medical record does not necessarily reflect the entire scope of medical evaluation; it is possible that in some patients OSA was suspected and they were verbally recommended to have an OSA evaluation which was not documented in the records, or this was left for a follow-up visit. Even so, it would be advantageous to arrange for screening for OSA during the hospitalization, just as we routinely initiate aspirin, beta-blocker, statin, and ACE inhibitor therapy before patient discharge. Cardiovascular disease patients with untreated severe OSA are thought to have worse cardiovascular outcomes (2,3), which may be improved with CPAP. Randomized controlled trials testing this assumption are lacking. Demonstrated beneficial effects of CPAP could lead to significant practice and guidelines changes. An absence of such clinical trials may help explain the relatively low awareness of OSA as an important consideration in the patient with MI.

We investigated breathing patterns and the occurrence of arrhythmias and ST-segment changes during sleep in patients with Brugada syndrome. Patients with Brugada syndrome are more likely to die from ventricular arrhythmias during sleep. ST-segment changes have been correlated with risk of sudden cardiac death. Whether sleep disturbances may contribute to arrhythmogenesis is unknown. Patients with Brugada syndrome underwent overnight polysomnography with simultaneous 12-lead electrocardiographic recording. A control group matched by age, gender, and body mass index (BMI) also underwent polysomnography. Twenty patients were included (50 ± 15 years old, 75% men). Despite their normal BMI (24.7 ± 2.7 kg/m 2 ), 45% had sleep-disordered breathing (SDB), with a mean apnea-hypopnea index of 17.2 ± 14 events/hour. In patients with a high risk of arrhythmias, 5 (63%) had SDB. In the control group, 27% had SDB. Atrial or ventricular arrhythmias were not observed. Spontaneous ST-segment changes occurred in 2 patients over 45 different time points. Most ST-segment changes were observed during rapid eye movement sleep (31%) or within 1 minute of arousals (44%). Regarding respiratory events, 25 (56%) of ST-segment changes were related to occurrence of apnea or hypopnea. In conclusion, patients with Brugada syndrome have a high prevalence of SDB even in the setting of normal BMI. The higher incidence of nocturnal death in patients with Brugada syndrome may be conceivably related to co-morbid SDB. Moreover, autonomic instability encountered in rapid eye movement sleep and arousals could potentiate the risk of arrhythmias.