【特刊综述】雄激素对骨骼肌的作用：对乏力的发展和治疗的意义

雄激素对骨骼肌合成有明显影响,随着年龄增大,雄激素的下降常伴随肌量和肌力的下降。这种肌量和肌功能的下降,被称为少肌症或肌体老化,是老年人体质弱化（男性化减退）进展的关键事项。也是导致快速机能衰退及其不良后果的关键。雄激素水平下降对老年男性体质弱化（男性化减退）的潜在影响和对躯体功能的促进治疗作用无疑已经引起了相当的关注。本综述概述了近期关于肌肉老化、少肌症、老年体质弱化的概念、定义,并评估了关于雄激素和老年体质弱化的研究进展。近期源于观测性和介入性研究的证据强烈支持雄激素对老年男性肌量的作用,但雄激素对肌力和特有的躯体功能的效用并不明确。研究显示,雄激素治疗在老年男性中通常有良好的耐受性,而近期的研究则关注于雄激素的高剂量治疗和对于心血管风险较高人群的治疗。雄激素受体调节剂（SARMs）的初期试验研究显示传统雄激素治疗对于老年患者在肌量和肌功能方面有相同的效用。将来的重要研究方向包括利用这类雄激素治疗并结合适用于不同老年患者群体促进躯体功能的运动训练,同时将更多地关注近期关于激素水平、身体成分及躯体功能间关系的观测性（回顾性）研究。     

Lead alters intracellular protein signaling and suppresses pro-inflammatory activation in TLR4 and IFNR-stimulated murine RAW 264.7 cells,in vitro

Lead (Pb) is a persistent environmental pollutant that has a structure and charge similar to many ions, such as calcium, that are essential for normal cellular function. Pb may compete with calcium for protein binding sites and inhibit signaling pathways within the cell affecting many organ systems including the immune system. The aim of the current study was to assess whether the calcium/calmodulin pathway is a principal target of environmentally relevant Pb during pro-inflammatory activation in a RAW 264.7 macrophage cell line. RAW 264.7 cells were cultured with 5 μM Pb(NO₃)₂, LPS, rIFNγ, or LPS+rIFNγ for 12, 24, or 48 hr. Intracellular protein signaling and multiple functional endpoints were investigated to determine Pb-mediated effects on macrophage function. Western blot analysis revealed that Pb initially modulated nuclear localization of NFκB p65 and cytoplasmic phosphorylation of CaMKIV accompanied by increased phosphorylation of STAT1β at 24 hr. Macrophage proliferation was significantly decreased at 12 hr in the presence of Pb, while nitric oxide (NO) was significantly reduced at 12 and 24 hr. Cells cultured with Pb for 12, 24, or 48 hr exhibited altered cytokine levels after specific stimuli activation. Our findings are in agreement with previous reports suggesting that macrophage pro-inflammatory responses are significantly modulated by Pb. Further, Pb-induced phosphorylation of CaMKIV (pCaMKIV), observed in the present study, may be a contributing factor in metal-induced autophagy noted in our previous study with this same cell line.     

Orofacial neuralgia associated with a middle cerebral artery aneurysm

Chronic orofacial pain of neuropathic origin can present diagnostic and management dilemmas to dental practitioners and also affects the patient's quality of life. Intracranial aneurysms are a potential cause of stroke (e.g. sub‐arachnoid haemorrhage) that is usually associated with, high rates of mortality and morbidity. A patient who had been previously managed for symptoms of temporomandibular joint disorder (TMD) presented with sharp, shooting pain of moderate intensity. It was precipitated by swallowing, and radiated to the right throat, posterior border of the mandible, ear and temporomandibular joint. Clinical and radiological investigations ruled out odontogenic pain, TMD and other more common types of facial pain. Magnetic resonance imaging revealed a 7 × 6 mm aneurysm in the right middle cerebral artery (MCA) which was subsequently surgically clipped. Interestingly, the facial pain resolved after this procedure. Compression of the insular region of the brain innervated by the trigeminal, glossopharyngeal and vagus nerves provides a plausible explanation for the pain reported. To our knowledge, this is the first case of facial neuralgia associated with an aneurysm in the MCA which emphasizes the importance of a multidisciplinary approach in the diagnosis and management of unusual cases of chronic orofacial pain.     

Seasonal variation in physical activity,sedentary behaviour and sleep in a sample of UK adults

Background: Physical activity (PA), sedentary behaviour (SB), sleep and diet have all been associated with increased risk for chronic disease. Seasonality is often overlooked as a determinant of these behaviours in adults. Currently, no study has simultaneously monitored these behaviours in UK adults to assess seasonal variation.

Aim: The present study investigated whether PA, SB, sleep and diet differed over season in UK adults.

Subjects and methods: Forty-six adults (72% female; age?=?41.7?±?14.4 years, BMI?=?24.9?±?4.4?kg/m²) completed four 7-day monitoring periods; one during each season of the year. The ActiGraph GT1M was used to monitor PA and SB. Daily sleep diaries monitored time spent in bed (TIB) and total sleep time (TST). The European Prospective Investigation of Cancer (EPIC) food frequency questionnaire (FFQ) assessed diet. Repeated measures ANOVAs were used to identify seasonal differences in behaviours.

Results: Light-intensity PA was significantly higher in summer and spring (p?p?p?>?0.05).

Conclusions: Findings support the concept that health promotion campaigns need to encourage year-round participation in light intensity PA, whilst limiting SB, particularly during the winter months.     

The effect of estradiol and a combined estradiol/progestagen preparation on insulin sensitivity in healthy postmenopausal women.

Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result in an improvement in these parameters, although progestagens may antagonize these effects. We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause. After baseline measurements, subjects were randomized to receive either transdermal 17beta-estradiol (50 microg) or matching placebo patches for 6 weeks. The subjects were then further randomized to receive either estradiol in combination with oral norethisterone (1 mg) or a matching oral placebo preparation, crossing over after 6 weeks, with assessment of insulin sensitivity at the end of each treatment. No significant increase in insulin sensitivity was observed after 6 weeks of transdermal 17beta-estradiol treatment (95% confidence interval, -0.54, 1.86; P = 0.27). Addition of norethisterone for a further 6 weeks had no detectable effect on insulin sensitivity (95% confidence interval, -1.65, 1.10; P = 0.65). The results of this study using transdermal estradiol do not support previous reports that unopposed estrogens exert potentially beneficial effects on insulin sensitivity and suggest that the addition of an oral progestagen confers no clinically important risk or benefit. It is therefore unlikely that effects on insulin sensitivity contribute appreciably to the cardioprotective benefits attributed to hormone replacement therapy.     

Medical student perceptions of research and research-orientated careers: An international questionnaire study

Background: Engaging and inspiring the next generation of physician-scientists at an early stage is recognised as key to ensure the future of medical research. However, little is known about medical student perceptions of research.

Objectives: We attempted to ascertain perceptions of research and research-orientated careers from medical students studying in different countries.

Methods: An online questionnaire was developed, piloted, and promoted to medical students in various countries.

Results: 1625 responses were collected from 38 countries. Analysis was restricted to data collected from countries with >100 responses (n?=?890). Less than half the respondents felt their medical school provided adequate research training. Key perceived barriers to research participation as a student included lack of time and difficulty finding mentors or projects. A significant gender disparity existed in research ambitions of students with females desiring less research involvement. The importance of barriers and satisfaction with research training differed significantly between countries.

Conclusions: Students perceive a number of key barriers to research involvement and pursuit of research-orientated careers. Programmes designed to engage students with research should focus on overcoming identified barriers. Greater effort is needed to engage female students who report more significant barriers and less desire to follow research-orientated careers.     

Impact of Implementing the 2013 ACC/AHA Cholesterol Guidelines on Vascular Events in a Statewide Community‐Based Practice Registry

Electronic health record data were analyzed to estimate the number of statin‐eligible adults with the 2013 American College of Cardiology/American Heart Association cholesterol guidelines not taking statin therapy and the impact of recommended statin therapy on 10‐year atherosclerotic cardiovascular disease (ASCVD₁₀) events. Adults aged 21 to 80 years in an outpatient network with ≥1 clinic visit(s) from January 2011 to June 2014 with data to calculate ASCVD₁₀ were eligible. Moderate‐intensity statin therapy was assumed to lower low‐density lipoprotein cholesterol by 30% and high‐intensity therapy was assumed to reduce low‐density lipoprotein cholesterol by 50%. ASCVD events were assumed to decline 22% for each 39 mg/dL decline in low‐density lipoprotein cholesterol. Among 411,768 adults, 260,434 (63.2%) were not taking statins and 103,478 (39.7%) were eligible for a statin, including 79,069 (76.4%) patients with hypertension. Estimated ASCVD₁₀ events were 18,781 without and 13,328 with statin therapy, a 29.0% relative and 5.3% absolute risk reduction with a number needed to treat of 19. The 2013 cholesterol guidelines are a relatively efficient approach to reducing ASCVD in untreated, statin‐eligible adults who often have concomitant hypertension.     

The forehead lift: techniques to avoid complications and produce optimal results

This discussion of forehead lifting, based on modifications of Vinas, Caviglia, and Cortinas, shares the authors' methods of patient evaluation, diagnostic details, architectural planning, and surgical concepts for forehead rhytidectomy along with correction of malpositioned and ptosis of the eyebrows and also glabellar frown problems. In addition, the nasal deformities associated with the sagging of the skin and subcutaneous tissue onto the upper fourth of the nose may make the nose look too short for a pleasing balance of the face and the upper fourth may appear disagreeably wide. A contribution to this excessive width is made by a sometimes thick and wide procerus muscle along with bilateral thick depressor supercilii muscles. When this nasal deformity is corrected, glabellar frown problems are also corrected. Attention to the details of the above-mentioned factors results in very long-lasting, sometimes permanent, and almost complication-free results that please the surgeon and the patient. Complications such as adherence of the dermis to the underlying pericranium, lack of motion in a portion of or the entire forehead, hyperactivity around areas of immobility, muscle irregularities, and also surgically produced depressions which require grafting, skin sloughing, permanent nerve injury, persistent sensory nerve loss, and short-term improvement have been avoided by paying attention to diagnosis, surgical planning, and technique, and postoperative care. Most patients can return to work in four or five days with minimal discoloration and swelling if they have not had aspirin or vitamin E one month before surgery, and there is hemostasis and the use of drains when indicated. Minimizing detection of the surgical incisions is accomplished by detailed preoperative planning of their location, architectural design development and drawing at the time of surgery, special surgical techniques, and excision of the skin or scalp. For patients with male pattern baldness use of specially designed V-Y advancement flaps with the browlift procedure improve the appearance of the hair's thickness and distribution.