Ultrastructural findings in progressive macular hypomelanosis indicate decreased melanin production

Background The pathogenesis of progressive macular hypomelanosis (PMH) is unknown. Recently, Westerhof et al. (Arch Dermatol 2004; 140: 210–214) hypothesized that Propionibacterium acnes produces a depigmenting factor that interferes with melanogenesis in the skin, resulting in hypopigmented spots. The purpose of the study is to gain an insight into the pathogenesis of PMH. Materials and methods We took a biopsy of 2‐mm diameter from normal and lesional skin in eight PMH patients. Using electron microscopy, we compared melanization of melanosomes, melanosome transfer and amount of epidermal melanin in normal and lesional skin. Result Compared to non‐lesional skin, we observed a decrease of epidermal melanin and less melanized melanosomes in lesional skin of all patients. When comparing normal and lesional skin of patients with skin type V and VI, we observed a difference in melanosome size and maturation and a switch of transferred melanosomes from single stage IV transferred melanosomes to aggregated stage I, II and III transferred melanosomes, as seen in healthy skin of skin type I to IV. Conclusion Hypopigmentation in PMH seems to be the result of an altered melanogenesis based on a decrease in melanin formation and a change in the distribution of melanosomes. In lesional skin of PMH patients with skin type V and VI less melanized, aggregated melanosomes in stead of single, mature melanosomes are transferred from melanocytes to keratinocytes. This results in a decrease of epidermal melanin. Further investigations are needed to determine the precise role of Propionibacterium acnes in this alteration of melanogenesis.     

Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures

Background

Neural circuits can spontaneously generate complex spatiotemporal firing patterns during development. This spontaneous activity is thought to help guide development of the nervous system. In this study, we had two aims. First, to characterise the changes in spontaneous activity in cultures of developing networks of either hippocampal or cortical neurons dissociated from mouse. Second, to assess whether there are any functional differences in the patterns of activity in hippocampal and cortical networks.

Results

We used multielectrode arrays to record the development of spontaneous activity in cultured networks of either hippocampal or cortical neurons every 2 or 3 days for the first month after plating. Within a few days of culturing, networks exhibited spontaneous activity. This activity strengthened and then stabilised typically around 21 days in vitro. We quantified the activity patterns in hippocampal and cortical networks using 11 features. Three out of 11 features showed striking differences in activity between hippocampal and cortical networks: (1) interburst intervals are less variable in spike trains from hippocampal cultures; (2) hippocampal networks have higher correlations and (3) hippocampal networks generate more robust theta-bursting patterns. Machine-learning techniques confirmed that these differences in patterning are sufficient to classify recordings reliably at any given age as either hippocampal or cortical networks.

Conclusions

Although cultured networks of hippocampal and cortical networks both generate spontaneous activity that changes over time, at any given time we can reliably detect differences in the activity patterns. We anticipate that this quantitative framework could have applications in many areas, including neurotoxicity testing and for characterising the phenotype of different mutant mice. All code and data relating to this report are freely available for others to use.     

Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression

Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL- 6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline- treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.     

Unplanned readmissions after primary total knee arthroplasty in Korean patients: Rate,causes, and risk factors

Background

Unplanned hospital readmissions are indicators of the quality and performance of a health care system, but data on early readmission after primary total knee arthroplasty (TKA) in the Asian population are limited. The purpose of this study was to determine the causes, risk factors, and rate of unplanned readmission after primary TKA at a single institution in Korea.

The effects of dietary hempseed on cardiac ischemia/reperfusion injury in hypercholesterolemic rabbits

BACKGROUND: Hempseed is a novel functional food that contains several health-promoting polyunsaturated fatty acids (PUFAs). PUFAs, such as those found in flaxseed and fish, have been shown to protect the heart against arrhythmias following ischemia/reperfusion. OBJECTIVE: TO INVESTIGATE THE POTENTIAL OF DIETARY HEMPSEED AS A CARDIOPROTECTIVE AGENT AGAINST GLOBAL ISCHEMIA AND SUBSEQUENT REPERFUSION BY ASSESSING SEVERAL MEASUREMENTS OF CARDIAC PERFORMANCE: QT interval duration, left ventricular pressure, arrhythmia incidence and arrhythmia duration. METHODS: MALE NEW ZEALAND WHITE RABBITS WERE FED ONE OF SIX DIETS: a control diet; or one supplemented with 10% hempseed, 10% delipidated hempseed, 0.5% cholesterol, 0.5% cholesterol plus 10% hempseed or 5% coconut oil. After eight weeks on their respective diets, the hearts were excised and subjected to 30 min of global ischemia and 45 min of reperfusion. Electrocardiogram traces were recorded throughout the experiment and were subsequently analyzed for QT interval duration, left ventricular pressure, arrhythmia incidence and arrhythmia duration. Plasma and cardiac tissue were analyzed for fatty acid content and composition. RESULTS: Cholesterol-fed animals exhibited significantly higher PUFA levels in their plasma, but this did not directly translate into higher PUFA levels in their cardiac fractions. There were no significant differences among the groups in the incidence or duration of ischemia-derived arrhythmias. During reperfusion, there was a significant decrease in the incidence of fibrillation in the hearts obtained from cholesterol-fed and hempseed- plus cholesterol-fed rabbits compared with the hearts from delipidated hempseed-fed rabbits. CONCLUSIONS: Dietary hempseed induced limited beneficial effects on cardiac function during ischemia/reperfusion challenge. The present study does not support the use of dietary hempseed to protect the heart during ischemic insult in this experimental model.     

Impact of COVID-19 on follow-up and medication adherence in patients with glaucoma in a tertiary eye care centre in south India

Purpose:COVID-19 pandemic has affected the healthcare system worldwide hindering the continuum of treatment of chronic disease patients. The objective of the study is to analyze the barriers encountered by the glaucoma patients for the follow-up visit and medication adherence during the pandemic.Methods:This cross-sectional study included glaucoma patients who did not attend the scheduled appointment from April 1, 2020 to July 31, 2020 in a tertiary eye care center (88.21%). Eligible patients of age >18 years and advised antiglaucoma medication in Madurai Zone were interviewed with validated questionnaire through telephonic call.Results:363 patients answered the questionnaire through telephonic interview. 57.3% of the patients were found to be non-adherent to medication. The main barriers for glaucoma follow-up visit during the pandemic were lockdown restriction, transport problem, and financial difficulties. The top barriers for medication adherence were non availability of medication (54.81%), financial difficulties (30.29%), did not feel much improvement with eye drops (20.19%). On multiple regression analysis, longer distance to hospital, low socioeconomic status, more than one antiglaucoma medication use, lack of awareness of glaucoma, non-complaint before COVID-19 and stress due to the pandemic were found to be significant factors for medication non adherence.Conclusion:COVID-19 pandemic has emphasized the need for reformation in health care system for accessibility of medical care to patients in rural areas. Decentralization of health system to primary care level and utilization of teleophthalmology should be considered by health care planners in future.     

主动脉弓钙化影响因素的调查与分析

目的 探讨生活习惯及生理生化因素对主动脉弓钙化(AAC)的影响.方法 收集"广州生物库队列研究"第一、二期的研究对象20430名,年龄50～85岁的基线资料,体格检查、实验室检查和胸部X线的AAC诊断结果及详细的问卷调查数据;用logistic回归分析某些生活习惯及生理生化因素与AAC患病率之间的关系.结果 (1)2名高级放射诊断医师独立阅片对AAC诊断符合率为85%,Kappa值为0.68(P<0.01),显示AAC诊断是可靠的;(2)除血压外,男女性在某些生理生化特征上有明显差别(P<0.05);(3)年龄、吸烟、LDL-C及高血压是男女性患AAC的危险因素(P<0.01),其OR值(95%CI):年龄男性为1.11(1.10～1.12),女性1.12(1.12～1.13);吸烟男性为1.31(1.17～1.47),女性1.31(1.09～1.57);LDL-C男性为1.16(1.06～1.27),女性为1.38(1.22～1.56);高血压男性为1.33(1.18～1.50),女性为1.27(1.18～1.38);女性患糖尿病增加患AAC的风险(P<0.001),其OR值(95%CI)为1.38(1.22～1.56).结论 年龄、吸烟、高血压、LDL-C是患AAC的危险因素,糖尿病增加女性患AAC的风险.     

Angiotensin-converting-enzyme gene polymorphisms, smoking and chronic obstructive pulmonary disease

While tobacco smoking is the main risk factor for chronic obstructive pulmonary disease (COPD) only a fraction of smokers go on to develop the disease. We investigated the relationship between the insertion (I) – deletion (D) polymorphisms in the Angiotensin converting enzyme (ACE) gene and the risk of developing COPD in smokers by determining the distribution of the ACE genotypes (DD, ID and II) in 151 life-long male smokers. 74 of the smokers had developed COPD (62 ± 2 years; FEV₁ 44 ± 6 % reference) whereas the rest retained normal lung function (56 ± 2 yrs; FEV₁ 95 ± 3 % reference). In addition, we genotyped 159 males recruited randomly from the general population. The prevalence of the DD genotype was highest (p = 0.01) in the smokers that developed COPD and its presence was associated with a 2-fold increase in the risk for COPD (OR 2.2; IC95% 1.1 to 5.5). Surprisingly, the 151 individuals in the smoking population did not demonstrate Hardy-Weinberg equilibrium unlike the 159 recruited from the general population. Our results suggest that ACE polymorphisms are associated with both the smoking history of an individual and their risk of developing COPD.     

The Presentation and Outcome of HIV-related Disease in Nairobi

The range of clinical presentations of HIV-related disease inAfrica has not been adequately described, despite the fact thatmany hospitals have to rely heavily on clinical diagnosis. Sixhundred adult medical patients seen in the Casualty Departmentof the main Government hospital in Nairobi were enrolled ina study of the presentation and outcome of HIV-related disease:506 of these patients were admitted, of whom 19 per cent (95)were HIV seropositive. The remaining 94 were dealt with as outpatients:11 percent (10) of these were seropositive. A history of priortreatment for sexually transmitted disease and, if male, beinguncircumcised, were associated with being seropositive. Threepresentations were strongly associated with HIV infection: acutefever with no focus except the gastrointestinal tract (entericfever-like illness), acute cough with fever (community-acquiredpneumonia) and chronic diarrhoea with wasting. The WHO clinicalcase definition (CCD) for AIDS missed a substantial amount ofHIV-related morbidity (sensitivity 39 per cent) and misidentifiedmany seronegative patients (positive predictive value 59 percent). In comparison with the Centers for Disease Control surveillancedefinition for AIDS, the CCD was specific (91 per cent) andsensitive (79 per cent) but only had a positive predictive valuesof 30 per cent: the CCD may therefore be a poor surveillancetool for AIDS. Seropositive patients were much more likely todie than were seronegative patients (39 per cent vs. 15 percent mortality). Enteric fever-like illness was the presentationwhich most commonly proved fatal. A wider spectrum of diseaseis associated with underlying HIV immunosuppression than haspreviously been described in Africa.