Phenotypic diversity of cytomegalovirus DNA polymerase gene variants observed after antiviral therapy

BackgroundCytomegalovirus UL54 DNA polymerase mutations observed in clinical specimens are of diagnostic significance if confirmed to affect antiviral drug susceptibility.ObjectivesValidate an updated recombinant phenotyping method to determine the degree of drug resistance conferred by previously uncharacterized UL54 sequence variants, in comparison with known resistance-related mutations.Study designBacterial artificial chromosome clones of viral DNA were mutagenized by recombination, transfected to produce live virus and phenotyped by standardized reporter-based yield reduction assays.ResultsSixteen recombinant viruses were constructed, representing baseline sequences, known resistance-related mutations and amino acid changes of unproven significance from clinical specimens. Phenotypes of baseline strains and known mutants were comparable to results from prior methods and helped to resolve some published inconsistencies. Mutations F412L, F412S, L545W were newly confirmed to confer ganciclovir and cidofovir resistance, while Q578H conferred ganciclovir and foscarnet resistance with borderline cidofovir resistance. Some foscarnet-resistant mutants were appreciably growth-retarded.ConclusionsResults add to known exonuclease domain mutations that confer ganciclovir-cidofovir cross-resistance, polymerase domain mutations that confer foscarnet resistance with variably decreased ganciclovir/cidofovir susceptibility, and increase the list of sequence variants with no measurable impact on drug susceptibility. The phenotypic diversity of similar UL54 genotypic variants complicates the interpretation of genotypic resistance testing. Technical improvements are facilitating the phenotyping of remaining unknown sequence variants.     

Muscle power training in the institutionalized frail: a new approach to counteracting functional declines and very late-life disability

Skeletal muscle power decreases earlier than muscle strength with advancing age and is more strongly associated with functional test performance than muscle strength in elderly populations. In addition, some studies have shown that resistance training designed to improve muscle power output (high speed of movement) enhances several functional outcomes in the healthy elderly. Therefore, muscle power has emerged as a factor that is also potentially associated with functional limitations in frail elderly adults. The purpose of this review was to provide recent evidence regarding the association between skeletal muscle power and functional capacity in physically frail individuals. Scielo, Science Citation Index, MEDLINE, Scopus, Sport Discus and ScienceDirect databases were searched from 1990 to 2014. Recently, it has been shown that functional capacity among frail elderly adults could be improved by performing resistance training at a high speed of movement with a loading stimulus that optimizes muscle power output. Routine multicomponent interventions that include muscle power training should be prescribed to institutionalized oldest old because such interventions improve the overall physical status of frail elderly individuals and prevent disability and other adverse outcomes. This result is especially important in frail subjects, who urgently need to improve their functional capacities to prevent adverse outcomes such as falls, hospitalizations, disability, or even death.     

Preserving the efficacy of front-line fluoroquinolones through selective use to optimise clinical outcomes

As antibiotic resistance is increasing worldwide, it is important to prescribe fluoroquinolone (FQ) antibiotics appropriately for a given infection to preserve class efficacy. Clinical studies reveal good efficacy and tolerability of the currently approved FQs (ciprofloxacin, levofloxacin and moxifloxacin) in a wide range of community- and hospital-acquired infections. However, certain features supporting their clinical efficacy suggest a rationale for inclusion of moxifloxacin and ciprofloxacin with complementary clinical benefit on a formulary rather than levofloxacin alone; it may also be more cost-effective. Ciprofloxacin has advantages over levofloxacin in the treatment of Gram-negative infections, whilst moxifloxacin has certain efficacy and ease of use advantages over levofloxacin in respiratory tract infections. To preserve the potential of FQs and to minimise the risk of resistance selection, agents with the highest in vitro activity and supportive pharmacokinetic/pharmacodynamic profiles should be used first-line, as appropriate for local guidelines and prescribing information.     

Acquisition of the mcr-1 gene by a high-risk clone of KPC-2-producing Klebsiella pneumoniae ST437/CC258, Brazil

We identified one clinical isolate of K. pneumoniae harboring the mcr 1 (plasmid of IncX4 family) and bla_KPC-2 (plasmid of IncFIB family) genes in southern Brazil. These findings highlight that K. pneumoniae isolates carrying both mcr-1 and bla_KPC-2 may emergence as a serious threat to antimicrobial therapy.     

耐甲氧西林金黄色葡萄球菌感染的流行病学调查、耐药性监测与预后因素分析

肥目的探讨耐甲氧西林金黄色葡萄球菌（MRSA）的流行分布和多药耐药趋势及预后相关因素，采取有效的医院管理措施。方法采用回顾性调查方法，VITEK-60全自动微生物分析系统进行细菌鉴定，K—B法做体外药敏试验，采用Logistic回归分析危险因素。结果445株金黄色葡萄球菌中MRSA检出率为46．96，其分离率有逐年增长的趋势（P〈0．05）；MR—SA检出率以老年痛科最高，其次重症监护病房，神经外科；药敏结果显示MRSA对万古霉素、利奈唑胺、替考拉宁全部敏感之外，对另外10种抗生素均不同程度耐药；多器官功能衰竭、住院时间长、长期大剂量使用广谱抗菌药物、机械通气、高龄、MRSA未清除、近期手术史是MRSA的独立危险因素，万古霉素、替考拉宁、利奈唑胺是MRSA感染的保护性因素。结论金黄色葡萄球菌耐药严重，MRSA的高检出率给临床治疗及控制医院感染带来较大困难；糖肽类抗菌药物可作为多药耐药金黄色葡萄球菌感染的首选抗菌药；MRSA感染的危险因素较多，尽早进行痛原学监测，及时发现、隔离和治疗对疾病预后有重要影响。     

Effect of Exercise on Taxane Chemotherapy–Induced Peripheral Neuropathy in Women With Breast Cancer: A Randomized Controlled Trial

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse effect of taxanes. We sought to evaluate the effect of exercise on taxane CIPN in women with breast cancer.Patients and MethodsWomen (n = 27) were randomized to immediate exercise (IE, during taxane chemotherapy) or delayed exercise (DE, after chemotherapy). Supervised aerobic, resistance, and balance training was offered 3 days a week for 8-12 weeks. CIPN symptoms and quality of life were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and CIPN20 (scored from 0 to 100). The percentage of participants reporting moderate to severe sensory symptoms (‘3/4’ or ‘4/4’ for CIPN20 sensory items) was also evaluated, along with clinical sensory testing at the lower limb (vibration sense and pinprick). Taxane treatment adherence, including relative dose intensity, was extracted from patient medical records. Assessments occurred at: baseline (before taxane chemotherapy), pre-cycle 4 (before the final taxane cycle), the end of chemotherapy, and follow-up (10-15 weeks after chemotherapy).ResultsNo differences in the EORTC QLQ CIPN20 symptom scores were detected between groups at any time point. At pre-cycle 4, there was a significant difference between groups in patient-reported moderate to severe numbness in the toes or feet (IE: n = 1, 9%, DE: n = 7, 50%, P = .04) and impaired vibration sense in the feet (IE: n = 2, 18%, DE: n = 10, 83%, P < .01). Overall global health status/quality of life was higher in IE compared to DE at the end of chemotherapy (P = .05), yet both groups had worse CIPN20 sensory (Δ24.3 ± 4.6, P < .01) and motor symptom scores (Δ10.5 ± 1.9, P < .01) relative to baseline. By the end of chemotherapy, no differences between groups were found for moderate to severe numbness in the toes or feet (P = 1.0) or impaired vibration sense in the feet (P = .71). More IE participants received ≥ 85% relative dose intensity (IE: n = 12, 100%, DE: n = 10, 67%, P < .05).ConclusionExercise may attenuate CIPN over the course of taxane chemotherapy and possibly improve taxane adherence in women with breast cancer. These findings, as well as whether exercise can attenuate CIPN by the end of taxane chemotherapy, should be confirmed in larger trials.     

“Mad Scared” versus “I Was Sad”: Emotional expression and response in urban adolescent males

Decades of masculinity research have concluded that society places higher demands on males to adhere to norms for low emotional expression; yet, countless studies find that emotional expression is integral to well-being. Unfortunately, this contradiction places boys and men in a tenuous position as they must navigate a bombardment of societal messages about the importance of emotional stoicism and invincibility. For urban adolescents, the situation is more complicated as they encounter environmental stressors that place greater emphasis on projecting a tough façade. Thus, our primary aim was to assess to what degree dyads of close adolescent male friends from urban, low-income neighborhoods are able to engage in emotional expression and response and to explore some of the underlying mechanisms and interpersonal processes. Qualitative findings from our sample suggest that urban boys exhibit a wide range of behaviors when participating in dyadic emotional disclosure and response, including being highly emotionally expressive and supportive in the context of close male friendship.