BACKGROUND & AIMS: OBJECTIVE:Patients with severe traumatic or burn injury and a mouse model of burn injury were studied early after injury to determine the relation of plasma endotoxin (lipopolysaccharide [LPS]) to the production of proinflammatory cytokines and subsequent resistance to infection.

SUMMARY BACKGROUND DATA:Elevated levels of plasma LPS have been reported in patients after serious injury. It has been suggested that circulating LPS may be a trigger for increased proinflammatory cytokine production and may play a role in the septic syndromes seen in a substantial portion of such patients. Yet, despite multiple reports of leakage of LPS from the gut and bacterial translocation after injury in animal models, there is little direct evidence linking circulating LPS with production of inflammatory mediators.

METHODS:The authors studied serial samples of peripheral blood from 10 patients with 25% to 50% surface area burns and 8 trauma patients (injury Severity Score, 25-57). Patients were compared with 18 healthy volunteers. The study was focused on the first 10 days after injury before the onset of sepsis or the systemic inflammatory response syndrome. Plasma samples were assayed for LPS, and adherent cells from the blood were studied for basal and LPS-stimulated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). The correlation of increased plasma LPS with TNF-alpha production was studied as was the association of increased plasma LPS and increased TNF-alpha production with subsequent septic complications. We also studied a mouse model of 25% burn injury. Burn mice were compared with sham burn control subjects. Plasma samples were assayed at serial intervals for LPS, and adherent cells from the spleens were studied for basal- and LPS-stimulated production of TNF-alpha, IL-1 beta, and IL-6. Expression of the messenger RNAs for IL-1 beta and TNF-alpha also was measured. The relation of increased TNF-alpha production with mortality from a septic challenge, cecal ligation and puncture (CLP), was determined. Finally, the effect of administration of LPS to normal mice on subsequent mortality after CLP and on TNF-alpha production was studied.

RESULTS:Elevated plasma LPS (> 1 pg/mL) was seen in 11 of the 18 patients within 10 days of injury and in no normal control subjects. In this period, patients as compared with control subjects showed increased stimulated production of TNF-alpha, IL-1 beta, and IL-6. Increased TNF-alpha production was not correlated with elevated plasma LPS in the same patients. Neither increased plasma LPS nor increased TNF-alpha production early after injury was correlated with subsequent development of systemic inflammatory response syndrome or sepsis in the patients. Burn mice, as compared with sham burn control subjects, showed elevated plasma LPS levels chiefly in the first 3 days after injury. Increased stimulated production of proinflammatory cytokines by adherent splenocytes from the burn mice also was seen at multiple intervals after injury and did not correlate with mortality from CLP. Increased production of TNF-alpha and IL-1 beta was associated with increased expression of messenger RNAs for these cytokines. Finally, two doses of 1 ng LPS administered 24 hours apart to normal mice had no effect on mortality from CLP performed 7 days later nor on the production of TNF-alpha at the time of CLP.

CONCLUSIONS:These findings call into question the idea that circulating LPS is the trigger for increased proinflammatory cytokine production, systemic inflammatory response syndrome, and septic complications in injured patients.

背景与目标： 目标 : 严重创伤或烧伤患者和烧伤小鼠模型在损伤后早期进行了研究，以确定血浆内毒素 (脂多糖 [LPS]) 与促炎细胞因子的产生以及随后对感染的抵抗力之间的关系。
摘要背景数据 : 据报道，严重损伤后患者血浆LPS水平升高。已经提出，循环LPS可能是促炎性细胞因子产生增加的触发因素，并且可能在此类患者的大部分脓毒症综合征中起作用。然而，尽管有多份动物模型中LPS从肠道泄漏和细菌移位的报道，但几乎没有直接证据将循环LPS与炎症介质的产生联系起来。
方法 : 作者研究了10例25% 至50% 表面积烧伤患者和8例创伤患者的外周血系列样本 (损伤严重程度评分，25-57)。将患者与18名健康志愿者进行比较。该研究的重点是败血症或全身性炎症反应综合征发作前的受伤后10天。测定血浆样品中的LPS，并研究血液中的贴壁细胞的基础和LPS刺激的肿瘤坏死因子-α (TNF-α)，interleukin-1 β (IL-1 β) 和interleukin-6 (IL-6) 的产生。研究了血浆LPS增加与TNF-α 产生的相关性，以及血浆LPS增加和TNF-α 产生增加与随后的败血症并发症的关联。我们还研究了25% 烧伤的小鼠模型。将烧伤小鼠与假烧伤对照组进行比较。以连续间隔测定血浆样品中的LPS，并研究来自脾脏的贴壁细胞的基础和LPS刺激的TNF-α，IL-1 β 和IL-6的产生。还测量了IL-1 β 和TNF-α 的信使rna的表达。确定了TNF-α 产生增加与败血性攻击，盲肠结扎和穿刺 (CLP) 造成的死亡率之间的关系。最后，研究了向正常小鼠施用LPS对CLP后后续死亡率和TNF-α 产生的影响。
结果 : 18例患者中有11例在受伤后10天内发现血浆LPS升高 (> 1 pg/mL)，而没有正常对照。在此期间，与对照组相比，患者表现出TNF-α，IL-1 β 和IL-6的刺激产生增加。在同一患者中，TNF-α 产生的增加与血浆LPS升高无关。损伤后早期血浆LPS的增加和TNF-α 的产生均与患者全身炎症反应综合征或败血症的后续发展无关。与假烧伤对照组相比，烧伤小鼠的血浆LPS水平主要在受伤后的前3天升高。烧伤小鼠的粘附脾细胞刺激促炎细胞的产生也在受伤后的多个间隔内增加，并且与CLP的死亡率无关。TNF-α 和IL-1 β 的产生增加与这些细胞因子的信使rna的表达增加有关。最后，对正常小鼠相隔24小时施用两次1 ng LPS对7天后进行的CLP的死亡率没有影响，也没有对CLP时TNF-α 的产生影响。
结论 : 这些发现使人们质疑循环LPS是导致受伤患者促炎性细胞因子产生增加，全身性炎症反应综合征和败血症并发症的诱因。

BACKGROUND & AIMS: Calcitriol has been widely used in the management of osteoporosis, but its efficiency is a matter of controversy. It is not known whether combinations of calcitriol and antiresorptive agents such as etidronate and calcitonin are superior to calcitriol alone in the treatment of postmenopausal osteoporosis. To make this determination, 30 Turkish women with postmenopausal osteoporosis between 45 and 68 years of age were randomized to receive either intermittent cyclical etidronate (400 mg/day, for 14 days) followed by 60 days of cyclical calcitriol therapy 0.25 microg twice daily (group 1; n = 10), or calcitriol 0.25 microg twice daily (group 2; n = 10), or calcitriol 0.25 microg/day in combination with 100 IU intranasal salmon calcitonin taken every other day (group 3; n = 10) through a 1-year period. Bone mineral density (BMD) of lumbar spine (L2 to L4) was determined for each patient by dual-photon absorptiometry (153Gd) at baseline, after 6 months, and at the end of the study. There was no significant difference among groups with respect to mean spinal BMD at baseline, after 6, and after 12 months. No significant spinal BMD changes occurred in any group from baseline, after 6 months, and after 12 months. Four patients in groups 1 and 2 and five patients in group 3 developed hypercalcemia at least once during therapy. Hypercalciuria occurred at least once in 9, 10, and 7 patients in groups 1, 2, and 3, respectively. One patient in group 2 developed a renal stone at the end of the study. Mean urine hydroxyproline levels did not change significantly in any group with respect to baseline. The data suggest that one-year treatment with calcitriol, given either alone or in combination with antiresorptive agents, does not improve spinal BMD in Turkish women with postmenopausal osteoporosis, and is associated with a high rate of adverse events.

背景与目标： 骨化三醇已广泛用于骨质疏松症的治疗，但其效率仍存在争议。尚不清楚骨化三醇和抗吸收剂 (如依替膦酸盐和降钙素) 的组合在绝经后骨质疏松症的治疗中是否优于单独的骨化三醇。为了做出这一决定，30名年龄在45至68岁之间的绝经后骨质疏松症土耳其妇女被随机分配接受间歇性周期性依替膦酸盐 (400毫克/天，持续14天)，然后接受60天的周期性骨化三醇治疗，0.25每天两次 (组1; n = 10)，或骨化三醇0.25 microg每天两次 (组2; n = 10)，或骨化三醇0.25 microg/天与100 IU鼻内鲑鱼降钙素组合，每隔一天服用 (组3; n = 10)，持续1年。在基线，6个月后和研究结束时，通过双光子吸收法 (153Gd) 测定每位患者的腰椎 (L2至L4) 的骨矿物质密度 (BMD)。在基线，6个月后和12个月后，各组之间的平均脊柱BMD没有显着差异。从基线，6个月后和12个月后，任何组均未发生明显的脊柱BMD变化。第1组和第2组中的4名患者和第3组中的5名患者在治疗期间至少出现一次高钙血症。高钙尿症分别在第1、2和3组的9、10和7名患者中至少发生一次。第2组中的一名患者在研究结束时出现了肾结石。任何组的平均尿羟脯氨酸水平相对于基线没有明显变化。数据表明，单独或与抗吸收剂联合使用骨化三醇治疗一年不会改善土耳其绝经后骨质疏松症妇女的脊柱BMD，并且与不良事件的发生率很高有关。

BACKGROUND & AIMS: :Sjögren's syndrome is an autoimmune disease of the exocrine glands characterized by the leading symptoms of keratoconjunctivitis and stomatitis sicca based on a complex pathogenesis. The prevalence is about 0.5-1%; primary Sjögren's syndrome is differentiated from secondary Sjögren's syndrome associated with other autoimmune disorders. The diagnosis is established by the presence of subjective complaints and objective evidence of sicca symptoms, anti-Ro(SSA)/La(SSB) antibodies, and/or focal lymphocytic infiltration of the glandular tissue. In addition to the typical sicca symptomatology, which is managed symptomatically by substitution and stimulation therapy, some patients exhibit extraglandular manifestations. Complaints involving the musculoskeletal system and inner ear dominate and are treated by the rheumatologist. The indication for base therapy is tailored to individual needs, but the efficacy of this approach has not been established in studies. About 5-10% of the patients with primary Sjögren's syndrome develop a B-cell non-Hodgkin's lymphoma. The disease requires interdisciplinary management including, among others, ophthalmologists, dentists, and otorhinolaryngologists, depending on the clinical picture.

背景与目标： : 干燥综合征是一种外分泌腺的自身免疫性疾病，其特征是角结膜炎和口炎的主要症状基于复杂的发病机理。患病率约为0.5-1%; 原发性干燥综合征与与其他自身免疫性疾病相关的继发性干燥综合征不同。诊断是通过主观主诉和sicca症状，抗Ro(SSA)/La(SSB) 抗体和/或腺组织的局灶性淋巴细胞浸润的客观证据来确定的。除了通过替代和刺激疗法对症治疗的典型sicca症状外，一些患者还表现出结肠外表现。涉及肌肉骨骼系统和内耳的主诉，由风湿病专家治疗。基础治疗的适应症是根据个人需求量身定制的，但是这种方法的疗效尚未在研究中确定。约5-10% 的原发性干燥综合征患者发展为b细胞非霍奇金淋巴瘤。该疾病需要跨学科的管理，其中包括眼科医生，牙医和耳鼻喉科医生，具体取决于临床情况。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS:We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS:Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION:Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.

背景与目标：

BACKGROUND & AIMS: :We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.

背景与目标： : 我们报告了一名具有独特特征组合的患者，包括小头畸形; 智力低下; 额叶发育不良; 垂体发育不良; 甲状腺功能减退; 普遍脱发; 单个上颌中切牙; 牛角牙症; 正中腭嵴; 纵向开槽的指甲; 和脊柱侧弯。发现他的不平衡核型为45，XY，der(15;18)(q10;q10)。异常星座似乎代表了一个连续的基因综合征，至少部分是由TGIF和负责遗传性低毛丝菌病的基因缺失引起的。我们患者的表型不同于其他报告的del患者 (18p)。可能的解释包括 (1) 不同缺失区域的影响，(2) 由接近的基因引起的位置效应，或 (3) 由染色体易位引起的不同基因的中断。

BACKGROUND & AIMS: PURPOSE OF REVIEW:Postthrombotic syndrome (PTS) is the most common complication of deep venous thrombosis (DVT). Identifying which patients are at high risk of developing PTS would help improve the management of patients with DVT and allow physicians to provide patients with individualized information on their expected prognosis. This review discusses the knowledge gained from key studies over the last decade on the incidence and determinants of PTS, with special emphasis on published studies from the last 2 years. RECENT FINDINGS:About a third to half of DVT patients will develop PTS, in most cases within 1-2 years of acute DVT. Important risk factors for PTS appear to be ipsilateral recurrence of DVT, poor quality of initial anticoagulation for the treatment of DVT and increased body mass index. SUMMARY:Preventing DVT recurrence by providing adequate intensity and duration of anticoagulation for the initial DVT and using effective thromboprophylaxis in high-risk settings is likely to reduce the frequency of PTS. Despite some advances in identifying risk factors for PTS, however, it is still not possible to reliably predict an individual patient's risk of developing PTS after an episode of DVT. Further studies of clinical determinants and biological markers of increased risk of PTS are needed to ultimately improve long-term prognosis after DVT.

背景与目标：

BACKGROUND & AIMS: :In 1969, the United States established its national rubella vaccination program. With the success of the program, 32 years later, reports of rubella reached record low numbers. To assess the achievement of elimination of rubella and congenital rubella syndrome (CRS) in the United States, 7 epidemiological criteria were used. Rubella cases reported to the National Notifiable Diseases Surveillance System from 1998 through 2004 and CRS cases reported to the National Congenital Rubella Syndrome Registry from 1998 through 2004 were analyzed. During 1998-2000, the median number of reported rubella cases was 272, whereas, during 2001-2004, the median number reported was 13. The incidence of rubella decreased significantly, from 0.1/100,000 population in 1998 to 0.005/100,000 population in 2004. Since 2001, 5 infants with CRS have been reported--3 were born in 2001, 1 was born in 2003, and 1 was born in 2004. The epidemiological evidence strongly supports the claim that rubella is no longer endemic in the United States. To prevent future rubella outbreaks and CRS cases, current strategies must be maintained.

背景与目标： : 1969年，美国建立了国家风疹疫苗接种计划。随着该计划的成功，32年后，风疹的报道达到了历史新低。为了评估在美国消除风疹和先天性风疹综合征 (CRS) 的成就，使用了7个流行病学标准。分析了向国家法定疾病监测系统报告的风疹病例1998年2004年和向国家先天性风疹综合征登记1998年2004年报告的CRS病例。在1998-2000年期间，报告的风疹病例的中位数为272，而在2001-2004年期间，报告的中位数为13。风疹的发病率从0.1/100,000人口1998年下降到0.005/100,000人口2004年。自2001年以来，已报告5例CRS婴儿-3例2001年出生，1例2003年出生，1例2004年出生。流行病学证据强烈支持风疹在美国不再流行的说法。为了防止未来的风疹暴发和CRS病例，必须维持当前的策略。

BACKGROUND & AIMS: :There is strong evidence for an association between overgrowth disorders such as Beckwith-Wiedemann syndrome and the development of neoplasia. An increased cancer risk has also been observed in individuals with isolated hemihyperplasia. We critically review the evidence for tumour surveillance in Beckwith-Wiedemann syndrome and isolated hemihyperplasia and suggest local practice guidelines.

背景与目标： : 有强有力的证据表明，Beckwith-Wiedemann综合征等过度生长性疾病与肿瘤的发展之间存在关联。在孤立的半增生个体中也观察到癌症风险增加。我们严格审查了Beckwith-Wiedemann综合征和孤立性半增生中肿瘤监测的证据，并提出了当地实践指南。

BACKGROUND & AIMS: OBJECTIVE:To assess the prevalence of night eating syndrome (NES) and binge eating disorder (BED) and their related behavioral and psychological correlates in persons who sought bariatric surgery. RESEARCH METHODS AND PROCEDURES:A consecutive series of 215 persons with extreme obesity (82% women, 70% European American) completed the Weight and Lifestyle Inventory and a semistructured interview as part of a pre-surgery behavioral/psychological assessment. Diagnoses for NES and BED were based on graded diagnostic criteria. RESULTS:Percentages of participants who met diagnostic criteria for NES by interview were 1.9% for the strictest definition and 8.9% across all definitions of NES. After interview, full DSM-TR criteria for BED were met by 4.2%; an additional 1.4% reported binge eating at least once per week. Self-reported prevalence of NES and BED were higher. Those with NES or BED had significantly more symptoms of depression and a greater history of psychological complications than the remaining sample. DISCUSSION:The prevalence rates of NES and BED among this population of bariatric surgery candidates were lower than expected based on previous reports. Findings and hypotheses regarding lowered prevalence rates are discussed.

背景与目标：

BACKGROUND & AIMS: :Japanese people in both Japan and in Hawaii have a lower incidence of hip fractures than white people in Hawaii or on the mainland of the United States. Hip fractures usually occur after a fall, and differing incidence rates of falls might contribute to the observed differences in hip fracture rates. To investigate this possibility we undertook a prospective study of falls among elderly Japanese men and women living in Hawaii using intensive surveillance methods similar to those used in studies of predominantly white populations. For our Japanese participants, the incidence rates of total falls were 139 per 1000 person years for men and 276 per 1000 person years for women. Age adjusted rate ratios of falls for predominantly white populations compared with our Japanese participants ranged from 1.8 to 2.3 for women and from 2.6 to 4.7 for men. The risk of injuries when they did fall, however, was not lower for our Japanese participants than reported for white participants. For our Japanese population, past falls, female gender, and daytime hours were associated with an increased incidence of falls.

背景与目标： : 日本和夏威夷的日本人髋部骨折的发生率都比夏威夷或美国本土的白人低。髋部骨折通常发生在跌倒后，不同的跌倒发生率可能会导致观察到的髋部骨折发生率差异。为了调查这种可能性，我们使用了类似于以白人为主的研究中使用的强化监测方法，对居住在夏威夷的日本老年男性和女性的跌倒进行了前瞻性研究。对于我们的日本参与者，男性的总跌倒发生率为139/1000人年，女性为276/1000人年。与我们的日本参与者相比，以白人为主的年龄调整后的跌倒率比率为女性的1.8至2.3，男性的2.6至4.7。但是，我们的日本参与者跌倒时受伤的风险并不比白人参与者低。对于我们的日本人口，过去的跌倒，女性性别和白天的时间与跌倒的发生率增加有关。

BACKGROUND & AIMS: :Methicillin/oxacillin (Oxa) resistance in Staphylococcus aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself. We investigated the role of VraS/VraR in the phenotypic expression of oxacillin resistance by inactivating vraS in community-acquired MRSA clinical isolates that lack functional genes encoding the mecA regulatory sequences mecI and mecR1. Inactivation of vraS abrogated oxacillin resistance, and complementation with the vraS operon restored the resistance phenotype. mecA transcription increased in the vraS mutants; however, PBP2a abundance was similar to that of the wild type. Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance. These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient. Therefore, the vraS/vraR regulatory system plays a crucial role in allowing MRSA to respond to beta-lactams by regulation of a gene target other than the known effectors of methicillin resistance.

背景与目标： : 金黄色葡萄球菌对甲氧西林/苯唑西林 (Oxa) 的耐药性主要由mecA编码的获得性青霉素结合蛋白 (PBP2a) 介导。PBP2a与天然PBP2一起通过分别贡献互补的转肽酶和转糖基化酶活性来介导苯唑西林抗性。VraS/VraR两组分调节系统可由细胞壁抗菌剂 (β-内酰胺，糖肽) 诱导，并控制许多细胞壁基因 (包括pbp2及其自身) 的转录诱导。我们通过在缺乏编码mecA调节序列mecI和mecr1的功能基因的社区获得性MRSA临床分离株中灭活VraS，研究了vraS/VraR在苯唑西林抗性表型表达中的作用。vraS的失活消除了苯唑西林的抗性，并与vraS操纵子互补恢复了抗性表型。vraS突变体中的mecA转录增加; 然而，PBP2a的丰度与野生型相似。尽管vraS突变体中的pbp2转录降低，但pbp2操纵子的过表达并不能恢复抗性。这些数据表明，尽管mecA和pbp2的表达对于苯唑西林抗性是必需的，但它们还不够。因此，vraS/vraR调节系统在允许MRSA通过调节除甲氧西林抗性的已知效应子以外的基因靶标来响应 β-内酰胺方面起着至关重要的作用。

BACKGROUND & AIMS: :An inverse relationship between age and human papillomavirus (HPV) prevalence has been reported in many developed countries, but information on this relationship is scarce in many other parts of the world. We carried out a cross-sectional study of sexually active women from the general population of 15 areas in 4 continents. Similar standardised protocols for women's enrolment, cervical specimen collection and PCR-based assays for HPV testing were used. HPV prevalence in different age groups was compared by study area. 18,498 women aged 15-74 years were included. Age-standardised HPV prevalence varied more than 10-fold between populations, as did the shape of age-specific curves. HPV prevalence peaked below age 25 or 35, and declined with age in Italy, the Netherlands, Spain, Argentina, Korea and in Lampang, Thailand and Ho Chi Minh, Vietnam. This was not the case in Songkla, Thailand nor Hanoi, Vietnam, where HPV prevalence was low in all age groups. In Chile, Colombia and Mexico, a second peak of HPV prevalence was detected among older women. In the poorest study areas in Asia (Shanxi, China and Dindigul, India), and in Nigeria, HPV prevalence was high across all age groups. The substantial differences observed in age-specific curves of HPV prevalence between populations may have a variety of explanations. These differences, however, underline that great caution should be used in inferring the natural history of HPV from age-specific prevalences.

背景与目标： : 在许多发达国家，已经报道了年龄与人乳头瘤病毒 (HPV) 患病率之间的反比关系，但是在世界许多其他地区，有关这种关系的信息很少。我们对来自4大洲15个地区的普通人群的性活跃女性进行了横断面研究。使用了类似的标准化方案，用于女性入组，宫颈标本收集和基于PCR的HPV检测方法。按研究区域比较了不同年龄组的HPV患病率。包括18,498名15-74岁的妇女。年龄标准化的HPV患病率在人群之间的变化超过10倍，年龄特定曲线的形状也是如此。HPV的患病率在25岁或35岁以下达到峰值，在意大利，荷兰，西班牙，阿根廷，韩国以及泰国南邦和越南胡志明市，随着年龄的增长而下降。泰国宋卡和越南河内的情况都不是这样，那里所有年龄组的HPV患病率都很低。在智利，哥伦比亚和墨西哥，在老年妇女中发现了HPV患病率的第二个高峰。在亚洲最贫困的研究地区 (中国山西和印度Dindigul) 和尼日利亚，HPV的患病率在所有年龄组中都很高。在人群之间HPV患病率的年龄特异性曲线中观察到的实质性差异可能有多种解释。然而，这些差异强调，在从年龄特异性患病率推断HPV的自然史时应格外小心。

BACKGROUND & AIMS: :Obstructive sleep apnoea (OSA) is a complex disease entity strongly influenced by genetic factors, especially those that affect obesity and fat distribution, upper airway muscle tone, craniofacial morphology, ventilatory control and sleep, giving rise to the OSA phenotype. OSA can also be considered a metabolic syndrome which adversely affects multiple organ systems, especially the cardiovascular system and the brain. The most widely used clinical marker for the diagnosis of OSA is the apnoea-hypopnoea index, calculated by polysomnography. A percentage of 35 to 40% of its variance can be attributed to genetic factors. Therefore, the identification and elucidation of the genes implicated in the pathogenesis of OSA becomes a matter of extensive research and could lead to the development of therapeutic agents that can have a beneficial effect on the natural course of OSA.

背景与目标： 阻塞性睡眠呼吸暂停 (OSA) 是一种复杂的疾病，受到遗传因素的强烈影响，尤其是那些影响肥胖和脂肪分布，上呼吸道肌张力，颅面形态，通气控制和睡眠的因素，从而引起OSA表型。OSA也可以被认为是一种代谢综合征，会对多器官系统 (尤其是心血管系统和大脑) 产生不利影响。诊断OSA最广泛使用的临床标志物是通过多导睡眠图计算的呼吸暂停-低通气指数。其方差的35% 至40% 的百分比可归因于遗传因素。因此，鉴定和阐明与OSA发病机理有关的基因已成为广泛研究的问题，并可能导致开发可对OSA自然过程产生有益作用的治疗剂。

BACKGROUND & AIMS: :Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.

背景与目标： : 人类免疫缺陷病毒 (HIV) 通过CD4与病毒包膜糖蛋白gp120之间的相互作用与细胞结合。先前的研究已将gp120的高亲和力结合位点定位于CD4的第一个结构域，与该区域反应性的单克隆抗体 (mab) 与gp120结合竞争，从而阻止病毒的感染性和合胞体的形成。尽管对gp120与CD4的结合有详细的了解，但对导致膜融合和病毒进入的后续事件知之甚少。我们描述了两种与CD4的第三结构域反应的新mab，它们抑制了对HIV感染性和细胞融合至关重要的病毒结合之后的步骤。重组gp120或病毒与CD4的结合不受这些抗体的抑制，而许多HIV分离株的感染和合胞体形成被阻断。这些发现表明，除了病毒结合外，CD4可能在膜融合中起积极作用。

BACKGROUND & AIMS: PURPOSE:Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. METHODS:Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. RESULTS:A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). CONCLUSIONS:Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.

背景与目标：