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Objective: To describe the clinical characteristics of male adolescents and young adults hospitalized for medical complications of atypical anorexia nervosa (atypical AN) and to compare their clinical characteristics with females with atypical AN and males with anorexia nervosa (AN). Method: A retrospective review of electronic medical records for patients with atypical AN and AN aged 9–25 admitted to the UCSF Eating Disorders Program from May 2012 to August 2020 was conducted. Results: Among 21 males with atypical AN (mean age 15.1 ± 2.7, mean %mBMI 102.0 ± 11.8), medical complications evidenced by admission laboratory values included anemia (52.9%), vitamin D insufficiency/deficiency (52.6%), and zinc deficiency (31.6%). Compared with females with atypical AN (n = 69), males with atypical AN had longer length of stay (11.4 vs 8.4 days, p =.004), higher prescribed kcal at discharge (4114 vs 3045 kcal, p <.001), lower heart rate nadir (40.0 vs 45.8, p =.038), higher aspartate transaminase (AST, 37.9 vs 26.2 U/L, p =.032), higher alanine transaminase (ALT, 30.6 vs 18.3 U/L, p =.005), and higher rates of anemia (52.9% vs 19.4%, p =.005), with no differences in vitamin D, zinc, and vital signs. Compared with males with AN (n = 40), males with atypical AN had no significant differences in vital signs or laboratory assessments during the hospitalization. Discussion: Atypical AN in males leads to significant medical comorbidity, and males with atypical AN require longer hospital stays compared to females with atypical AN. Rates of abnormal vital signs and abnormal serum laboratory values during hospital admissions do not differ in males with atypical AN compared to AN. Public Significance: Adolescent and young adult males with atypical anorexia nervosa experience significant medical complications. Males with atypical anorexia nervosa had longer hospitalizations and higher prescribed nutrition at discharge than females. Medical complications of atypical anorexia nervosa in male adolescents and young adults were generally equal to those of male adolescents and young adults with anorexia nervosa. Clinicians should be aware of unique medical complications of males with atypical anorexia nervosa. [ABSTRACT FROM AUTHOR]

The article discusses a 2021 study on the design, delivery and evaluation of community-based physical activity prescription in Great Britain. It states that limited data has not clarified what works, under what circumstances, and for whom, that is reflected in conservative policy recommendations. Also noted is the call for a more nuanced approach to future commissioning and evaluation.

Progressive neurodegenerative diseases represent some of the largest growing treatment challenges for public health in modern society. These diseases mainly progress due to aging and are driven by microglial surveillance and activation in response to changes occurring in the aging brain. The lack of efficacious treatment options for Alzheimer's disease (AD), as the focus of this review, and other neurodegenerative disorders has encouraged new approaches to address neuroinflammation for potential treatments. Here we will focus on the increasing evidence that dysbiosis of the gut microbiome is characterized by inflammation that may carry over to the central nervous system and into the brain. Neuroinflammation is the common thread associated with neurodegenerative diseases, but it is yet unknown at what point and how innate immune function turns pathogenic for an individual. This review will address extensive efforts to identify constituents of the gut microbiome and their neuroactive metabolites as a peripheral path to treatment. This approach is still in its infancy in substantive clinical trials and requires thorough human studies to elucidate the metabolic microbiome profile to design appropriate treatment strategies for early stages of neurodegenerative disease. We view that in order to address neurodegenerative mechanisms of the gut, microbiome and metabolite profiles must be determined to pre-screen AD subjects prior to the design of specific, chronic titrations of gut microbiota with low-dose antibiotics. This represents an exciting treatment strategy designed to balance inflammatory microglial involvement in disease progression with an individual's manifestation of AD as influenced by a coercive inflammatory gut. [ABSTRACT FROM AUTHOR]

Background: It is not clear whether use of specialty palliative care consults and "comfort measures only" (CMO) order sets differ by type of intensive care unit (ICU). A better understanding of palliative care provided to these patients may help address heterogeneity of care across ICU types. Objectives: Examine utilization of specialty palliative care consultation and CMO order sets across several different ICU types in a multihospital academic health care system. Design: Retrospective cohort study using Washington State death certificates and data from the electronic health record. Setting/Subjects: Adults with a chronic medical illness who died in an ICU at one of two hospitals from July 2013 through December 2018. Five ICU types were identified by patient population and attending physician specialty. Measurements: Documentation of a specialty palliative care consult during a patient's terminal ICU stay and a CMO order set at time of death. Results: For 2706 eligible decedents, ICU type was significantly associated with odds of palliative care consultation (p < 0.001) as well as presence of CMO order set at time of death (p < 0.001). Compared with medical ICUs, odds of palliative care consultation were highest in the cardiothoracic ICU and trauma ICU. Odds of CMO order set in place at time of death were highest in the neurology/neurosurgical ICU. Conclusion: Utilization of specialty palliative care consultations and CMO order sets varies across types of ICUs. Examining this variability within institutions may provide an opportunity to improve end-of-life care for patients with chronic, life-limiting illnesses who die in the ICU. [ABSTRACT FROM AUTHOR]

Background: Acute flaccid myelitis is characterized by acute-onset flaccid limb weakness with predominantly gray matter lesions in the spinal cord spanning one or more segments. Rates of full recovery are poor, and there is no standard treatment or definitive cause.Methods: This is a retrospective review of children diagnosed with acute flaccid myelitis in Texas during 2016. Patients were identified through a Texas collaborative of six hospitals in four major metropolitan areas. Data abstraction included health history, illness presentation, medical treatments, laboratory studies, imaging data, recovery, and ability to perform activities of daily living up to approximately two years from illness onset.Results: Among all sites, 21 patients met inclusion criteria. Treatments varied with the most common being intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. No differences were seen in response to medical treatments. A potential etiology was found in 12 (57%) cases, including four with enterovirus D68. Five cases recovered fully. Of the 16 patients without full recovery, abilities ranged from (1) able to perform all activities of daily living for age independently (n = 5), (2) mild deficits (n = 5), and (3) substantial reliance on caregivers for activities of daily living (n = 6).Conclusion: Many reports describe symptoms and outcomes of acute flaccid myelitis, but limited data are available on long-term functional outcomes. We were unable to make a strong case for any single cause or treatment modality. Fortunately, the majority of patients (15, 71%) were able to perform activities of daily living with complete independence or only mild deficits. [ABSTRACT FROM AUTHOR]

Dexmedetomidine is used in the intensive care unit (ICU) as a short‐term sedative. The data included in the manufacturer's product information is controversial, and there is little consensus to guide initial dosing and titration. This observational study surveyed the practice of dexmedetomidine use in Australian ICUs. An expression of interest (EOI) for a multisite observational study was sent to members of the ICU email group of the Society of Hospital Pharmacists Australia (SHPA). Participating members collected treatment‐related data for patients meeting inclusion criteria between January 2013 and July 2014. Six of 14 sites that responded positively to the EOI returned complete datasets, and 232 patients met the inclusion criteria. The main reported indications for dexmedetomidine use across the six sites were to manage agitation (33.2%), to aid extubation (32.8%) and to sedate (34.0%). The median duration of therapy was 42 h (range 1–672 h). Only nine patients (3.9%) received loading doses. The median maximum dose used for maintenance therapy in patients ranged from 1.2 to 4.0 microgram/kg per h. There was a significant disparity of practice across sites, as evidenced by differences in reported indication, off‐label use, rates of loading doses and doses used for maintenance therapy. Consensus prescribing guidelines are required to guide more consistent and evidence‐based prescribing of dexmedetomidine. [ABSTRACT FROM AUTHOR]

Mucosal‐associated invariant T (MAIT) cells are a subset of T cells that perform innate‐like immunity functions upon recognition of small molecule vitamin B metabolites presented by the MHC, class I‐related protein‐1 (MR1). MAIT cells are profuse in humans, but especially abundant in blood, liver, lungs, and mucosal layers. The mucosa is a common site of carcinogenesis and MAIT cells have been found in both primary and metastatic tumors. MAIT cells target a host of microbes including Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica, Legionella longbeachae, Escherichia coli, and Candida albicans, and are highly activated in viral infections. Cytokines produced by MAIT cells are both anticancerous and antibacterial, but also have proinflammatory and possibly tumorigenic properties. In addition, it is believed that MAIT cells play a protective role in viral infections in an MR1‐independent fashion. Based on our summary of recent advances concerning both MR1‐mediated and MR1‐independent MAIT cell immune responses, we weigh the strengths and weaknesses of these cells for vaccine development. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: Ivacaftor is a novel potentiator of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, which corrects the gating defect and increases ion‐function of activated cell‐surface CFTR. Bacteria also regulate their physiology through ion channels. However, little is known about the potential effects of ivacaftor on bacterial ion channels, which, in turn, may have a potential effect on transport across the bacterial cell membrane. Therefore, any change in the ability to transport molecules across cell membranes in bacteria could have an important impact on bacterial transport physiology. One area where this could be particularly important is in the movement of antibiotics, both into and out of the bacterial cell. An in vitro study was therefore performed to examine the influence of ivacaftor at therapeutic concentration on antibiotic susceptibility of 11 commonly used anti‐pseudomonal antibiotics against a population of clinical Pseudomonas aeruginosa [PA], from CF and non‐CF sources. Method: Pseudomonas aeruginosa (n = 80; including 70 ivacaftor‐naïve clinical PA from sputa from adult CF patients and 10 control PA from non‐CF clinical blood culture sources) were examined. Antibiotic susceptibility was determined by standard disc diffusion assay using CLSI criteria and measuring zone size (mm), against four classes of anti‐pseudomonal antibiotics, including beta‐lactams (temocillin, ceftazidime, piperacillin/tazobactam, imipenem, meropenem and aztreonam), aminoglycosides (gentamicin, tobramycin, amikacin), fluoroquinolone (ciprofloxacin) and polymyxin (colistin), in the absence and presence of ivacaftor (5 μmol/L), as previously determined. In addition, all CF and non‐CF PA were examined phenotypically in vitro, as previously described, for changes linked to bacterial virulence, including (i) growth density (ii) pigmentation, (iii) presence of adhesins and (iv) change to mucoidy, in the presence/absence of ivacaftor at therapeutic concentration. Results and discussion: Antibiotic susceptibility did not decrease significantly with any of the antibiotics examined with CF PA isolates or with non‐CF PA control organisms. There was a statistically significant increase in zone size (CF PA and amikacin, gentamicin, temocillin and ciprofloxacin; Non‐CF PA and amikacin, gentamicin and aztreonam). However, at a population level, this did not translate into a shift in CLSI category to a more susceptible phenotype. None of the PA isolates examined were susceptible to ivacaftor alone, and additionally, no changes were noted with the four phenotypic parameters examined in the presence of ivacaftor. What is new and conclusion: This study showed that antibiotic susceptibility of commonly used anti‐pseudomonal antibiotics was not negatively affected by ivacaftor, in a population of ivacaftor‐naive P. aeruginosa. Antibiotic susceptibility as determined by standard disc diffusion assay using CLSI criteria in the presence and absence of ivacaftor (mean zone size expressed in mm ± SEM [standard error of mean]) in relation to ivacaftor‐naïve clinical Pseudomonas aeruginosa isolates from sputa from adult cystic fibrosis patients. [ABSTRACT FROM AUTHOR]

Background: Racial/ethnic minority patients with nonhematologic malignancies (non-HM) have lower rates of hospice care, advance directive use, and palliative care utilization than non-Hispanic white (NHW) patients. Less is known regarding racial/ethnic minority patients with hematologic malignancies (HM). Objectives: To study hospital utilization among racial/ethnic minority patients with HM and compare end-of-life outcome measures to patients with non-HM. Methods: We performed a retrospective cohort study (2010–2015) using electronic health records from an integrated academic health center to study differences in hospital utilization patterns and documentation of advance care planning between patients with HM and non-HM. In the subgroup with hematologic malignancy, we examined outcomes associated with racial/ethnic minority status. Results: Among all patients in the last 30 days of life, those with HM had higher rates of inpatient care (odds ratio [OR], 1.96; 95% CI: 1.74–2.20; p < 0.001) and intensive care unit (ICU) care (OR, 3.50; 95% CI: 3.05–4.03; p < 0.001). Patients with HM were more likely to die in a hospital (OR, 2.75; 95% CI: 2.49–3.04; p < 0.001) than those with non-HM. Furthermore, during the last 30 days of life, among patients with HM, racial/ethnic minority patients were more likely to have more than one emergency room visit (OR, 6.81; 95% CI: 1.34–33.91; p = 0.02), 14+ days of inpatient care (OR, 1.60; 95% CI: 1.08–2.35; p = 0.02), longer stays in the ICU (OR, 1.26; 95% CI: 1.04–1.52; p = 0.02), and lower rates of advance directive documentation (OR, 0.60; 95% CI: 0.44–0.82; p < 0.01) than NHWs. Conclusion: Our findings suggest that racial/ethnic minority patients with HM have higher utilization of care at the end-of-life and lower rates of advance directives compared with NHW patients. [ABSTRACT FROM AUTHOR]

Objectives. To assess a community health worker (CHW) program's impact on childhood illness treatment in rural Liberia. Methods. We deployed CHWs in half of Rivercess County in August 2015 with the other half constituting a comparison group until July 2016. All CHWs were provided cash incentives, supply chain support, and monthly clinical supervision. We conducted stratified cluster-sample population-based surveys at baseline (March-April 2015) and follow-up (April-June 2016) and performed a difference-in-differences analysis, adjusted by inverse probability of treatment weighting, to assess changes in treatment of fever, diarrhea, and acute respiratory infection by a qualified provider. Results. We estimated a childhood treatment difference-in-differences of 56.4 percentage points (95% confidence interval [CI] = 36.4, 76.3). At follow-up, CHWs provided 57.6% (95% CI = 42.8, 71.2) of treatment in the intervention group. The difference-in-differences diarrhea oral rehydration therapy was 22.4 percentage points (95% CI = -0.7, 45.5). Conclusions. Implementation of a CHW program in Rivercess County, Liberia, was associated with large, statistically significant improvements treatment by a qualified provider; however, improvements in correct diarrhea treatment were lower than improvements in coverage. Findings from this study offer support for expansion of Liberia's new National Community Health Assistant Program. [ABSTRACT FROM AUTHOR]

The calibrated application of limited-duration, cyclic, moderately intense hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion stress. These intermittent hypoxic conditioning (IHC) programs consistently produce striking reductions in myocardial infarction and ventricular tachyarrhythmias after coronary artery occlusion and reperfusion and, in many cases, improve contractile function and coronary blood flow. These IHC protocols are fundamentally different from those used to simulate sleep apnea, a recognized cardiovascular risk factor. In clinical studies, IHC improved exercise capacity and decreased arrhythmias in patients with coronary artery or pulmonary disease and produced robust, persistent, antihypertensive effects in patients with essential hypertension. The protection afforded by IHC develops gradually and depends on β-adrenergic, δ-opioidergic, and reactive oxygen-nitrogen signaling pathways that use protein kinases and adaptive transcription factors. In summary, adaptation to intermittent hypoxia offers a practical, largely unrecognized means of protecting myocardium from impending ischemia. The myocardial and perhaps broader systemic protection provided by IHC clearly merits further evaluation as a discrete intervention and as a potential complement to conventional pharmaceutical and surgical interventions. [ABSTRACT FROM AUTHOR]

What is known and objective The CFTR potentiator, ivacaftor ( IVA), has been widely used in the treatment of cystic fibrosis ( CF) patients with the G551D mutation. To date, there has been limited information on the microbiological status of patients on this therapy and no data on the effect (if any) on the in vivo antibiotic susceptibility of Pseudomonas aeruginosa isolated from patients on therapy. Although IVA intervention is not designed per se as anti-infective, the effect (if any) of this molecule to CF patients' microbiological status merits careful monitoring. Therefore, it was the aim of this observational study to examine the effect in patients, both before and after commencement of IVA therapy, on several commonly reported microbiological markers in CF patients, including (i) bacterial density, (ii) frequency (rate) of isolation of bacterial pathogens, particularly P. aeruginosa, and (iii) antimicrobial susceptibility of these isolates to commonly prescribed oral and iv antibiotics. In addition, we wished to examine the requirements for these antibiotics in CF patients, before and after commencement of IVA therapy. Methods Archived data from 15 adult cystic fibrosis patients with the c.1652G›A (G551D) mutation were followed from two years pre- IVA therapy to two years after commencement of IVA therapy. The microbiological parameters examined included (i) oral antibiotic courses taken, (ii) intravenous (iv) antibiotic courses taken, (iii) rate of isolation of non-mucoid Pseudomonas aeruginosa ( NM- PA) and mucoid P. aeruginosa (M- PA), (iv) density of NM- PA and M- PA and (v) antimicrobial susceptibility of NM- PA and M- PA to 11 antibiotics [aminoglycosides, beta-lactams, polymyxin and fluoroquinolone]. Results and discussion Following commencement of IVA therapy, patients required less iv antibiotic courses but no change in number of oral antibiotics courses. There was significant reduction in both the rate of isolation and density of M- PA ( P = .02; P = .006, respectively). In contrast, there was no significant reduction in both the rate of isolation and density of NM- PA ( P = .90; P = .07, respectively). Antimicrobial susceptibility in NM- PA and M- PA was not significantly reduced within any of the antibiotics classes or individual antibiotics examined. Increased susceptibility was noted in the beta-lactam class for NM- PA and M- PA, in particular with ceftazidime. What is new and conclusion Overall, (i) the requirement for less iv antibiotic therapy, (ii) a reduction in the rate and density of M- PA and (iii) no reduction in antibiotic susceptibility indicate that microbiological parameters with patients on IVA therapy were not detrimentally affected. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Recurrent congenital tracheoesophageal fistula (TEF) is well documented in infancy but may also present later in life. This study reviews our experience with the clinical presentation, diagnosis and management of 5 recurrent and 2 primary congenital tracheoesophageal fistulas (TEF) in adult patients. There are no literature series of late recurrence of TEF (repaired in childhood and recurring in adulthood) and relatively few reported cases of initial adult presentation of TEF. In this series, we aim to provide the first large series description of late recurrence of congenital TEF following repair in infancy or childhood. We also present management considerations for this unique group of patients. METHODS: We performed a computer-based search of the adult thoracic surgery departmental operative database at our institution from 2002 to 2014. Patients with iatrogenic TEF or malignant TEF were excluded. RESULTS: Seven patients are included in our series. Five patients (71%) had recurrent congenital TEF and 2 (29%) had initial diagnosis of congenital TEF. All presented with severe coughing symptoms, and most (86%) had a history of recurrent aspiration pneumonia. Repair technique was dictated by the location of the TEF and the specific tracheoesophageal pathology. Four patients underwent repair via cervical approach with or without a tracheal resection. Three patients with distal recurrence underwent repair via right thoracotomy with partial oesophagectomy for significant tissue compromise and cervical reconstruction. Patients were followed for at least 1 year. All 7 patients experienced full resolution of symptoms. One patient required postoperative placement of a retrievable tracheal stent for tracheomalacia. There were no mortalities. CONCLUSIONS: Adult presentation of congenital TEF is a rare but recognizable clinical entity. Recurrent TEF in adulthood is a possible late complication of TEF repair performed in childhood that has not previously been described. Adult patients experiencing symptoms of cough and recurrent aspiration pneumonia should be evaluated for congenital TEF. Surgical repair of congenital TEF in the adult is feasible and effective with acceptable morbidity. [ABSTRACT FROM AUTHOR]

Background Studies are required that evaluate real-world outcomes of inhaled aztreonam lysine in patients with cystic fibrosis (CF). Methods Our treatment-evaluator tool assessed the effectiveness of inhaled aztreonam in routine practice in 117 CF patients across four time periods (6–12 (P2) and 0–6 months (P1) pre-initiation, and 0–6 (T1) and 6–12 months (T2) post-initiation). Outcomes were: changes in %-predicted forced expiratory volume in 1 s (FEV 1 ), body-mass index (BMI), hospitalisation days and intravenous antibiotic usage. Results Median FEV 1 % predicted for each 6-month period was 38.9%, 34.6%, 37.1% and 36.5%; median change was − 2.0% between P2 and P1, increasing to + 0.6% (p < 0.001) between P1 and T1. Annualised hospital bed-days was reduced (p = 0.05) post-initiation, as was intravenous antibiotics days (p = 0.001). BMI increased over 6 months post-initiation (p ≤ 0.001). Conclusions In patients with CF in routine practice, inhaled aztreonam lysine is associated with improved lung function and weight, and reduced hospitalisation and intravenous antibiotic use. [ABSTRACT FROM AUTHOR]

Introduction: Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study. Methods: Two cohorts, those switching from a PRN to a T&E regimen ('prior PRN') and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy ('anti-VEGF-naïve') were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site. Results: At the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and −67.7 μm (95% CI −106.5, −28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics. Conclusion: This is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. Funding: Novartis Pharmaceuticals UK Limited. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of this pilot study was to determine the feasibility and use accelerometers before, during, and after a campbased constraint-induced movement therapy (CIMT) program for children with hemiplegic cerebral palsy. METHODS: A pre-test post-test design was used for 12 children with CP (mean = 4.9 yrs) who completed a 30-hour campbased CIMT program. The accelerometer data were collected using ActiGraph GT9X Link. Children wore accelerometers on both wrists one day before and after the camp and on the affected limb during each camp day. Three developmental assessments were administered pre-post CIMT program. RESULTS: Accelerometers were successfully worn before, during, and directly after the CIMT program to collect upper limb data. Affected upper limb accelerometer activity significantly increased during the CIMT camp compared to baseline (p < 0.05). Significant improvements were seen in all twelve children on all assessments of affected upper limb function (p < 0.05) measuring capacity and quality of affected upper limb functioning. CONCLUSION: Accelerometers can be worn during high intensity pediatric CIMT programs to collect data about affected upper limb function. Further study is required to determine the relationship between accelerometer data, measure of motor capacity, and real-world performance post-CIMT. [ABSTRACT FROM AUTHOR]

Australian guidelines state "Following brief surgery or procedures with short acting anaesthetic drugs, the patient may be fit to drive after a normal night's sleep. After long surgery or procedures requiring longer lasting anaesthesia, it may not be safe to drive for 24 hours or more". The increasing use of the short-acting anaesthetic drug propofol as a solitary sedative medication for simple endoscopy procedures suggests a need to review this blanket policy. Thirty patients presenting for elective day surgery were recruited as volunteers for a pre-procedure driving simulation study and randomised to propofol or placebo arms. Driving ability was assessed at baseline and then, in the propofol group, at three effect-site concentrations. Driving impairment at these concentrations of propofol was compared to that of a third group of volunteers with a blood alcohol concentration of 0.05% (g/100 ml). Driving impairment at 0.2 µg/ml propofol effect-site concentration was not statistically different to placebo. Impairment increased with propofol effect-site concentration (P=0.002) and at 0.4 µg/ml it was similar to that found with a blood alcohol concentration of 50 mg/100 ml (0.05%). Plasma propofol concentrations of 0.2 µg/ml, as might be found approximately an hour after short (<1 hour duration) propofol-only sedation for endoscopy, were not associated with driving impairment in our young cohort of volunteers. [ABSTRACT FROM AUTHOR]

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials. We summarize relevant therapeutics that underwent clinical trials during the West Africa outbreak and highlight promising candidates under advanced development. [ABSTRACT FROM AUTHOR]

Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors. Cannabinoids are also involved in remote preconditioning of the heart. The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart. The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory. The adenosine triphosphate-sensitive K(+)channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na(+)/Ca(2+)exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids. The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia-reperfusion injury in the clinical setting. [ABSTRACT FROM AUTHOR]

Recently, Wong et al. have successfully developed a fluorescent biosensor based on the PenPC β-lactamase which changes its intrinsic fluorescence in presence of β-lactam antibiotics (BLAs). Here, we studied systematically this correlation among the fluorescence change of the biosensor and the concentration of different BLAs aimed at developing a novel method for estimating the concentration of a wide range of BLAs. This method showed high precision and specificity and very low interference from clinically relevant samples. We were able to monitor the pharmacokinetics of meropenem in healthy volunteers as well as in an ill animal model too, indicating that the implemented method could be suitable for clinical practice. [ABSTRACT FROM AUTHOR]

The study attempts to determine the prevalence of organisms associated with urethritis in men in rural southwestern Haiti and to determine the association with demographic, clinical and laboratory variables. A standardised verbal interview was conducted; genital examinations were done; urethral swabs were collected for nucleic acid amplification testing, and first void urine was obtained for urinalysis. The mean participant age was 54; 88.8% lived in a rural area. Swabs were positive for Trichomonas vaginalis in 13.7% (28/205), Mycoplasma genitalium in 6.3% (13/205), Chlamydia trachomatis in 4.4% (9/205) and Neisseria gonorrhoeae in 0% (0/205). Subjects who never reported using condoms were nearly 3.5 times more likely to have any positive swab result (OR: 3.46, 95% CI 1.31–9.14). Subjects who reported their partners had other sexual partners or were unsure were more than three times likely to have any positive swab result (OR: 3.44, 95% CI 1.33–8.92). Infections with Trichomonas vaginalis and Mycoplasma genitalium were the most common. [ABSTRACT FROM AUTHOR]

Background/aims To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy. Methods Multicentre national nAMD database study on patients treated 3-5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections. Results The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12-6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001-0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12. Conclusions All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients' funding. [ABSTRACT FROM AUTHOR]

Objectives The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. Methods The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Results Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Conclusions Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background This randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction. Methods Twelve HIV-1 + patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm 3 blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH ( n = 3); (2) vaccine alone ( n = 4); or (3) IL-2, GM-CSF and rhGH ( n = 5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured. Results Median baseline CD4 T-cell count was 757 cells/mm 3 (interquartile range [IQR] 567–886 cells/mm 3 ), median age 48 years (IQR 42–51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells ( p = 0.0083) and improved CD4/CD8 T-cell ratios ( p = 0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells ( p = 0.0194), significantly increased IFN-γ and IL-2 production in response to Gag ( p = 0.0122) and elevated IFN-γ production in response to Tat ( p = 0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA. Conclusions Multifarious immunotherapeutic approaches in the context of fully suppressive cART further reduce immune activation, and improve both CD4 T-lymphocyte counts and HIV-1-specific T-cell responses ( NCT01130376 ). [ABSTRACT FROM AUTHOR]

Since the P2Y12 receptor antagonists were first introduced, they have been extensively tested in patients with acute coronary syndrome and are now standard of care. These antiplatelet drugs are very effective in reducing subsequent cardiovascular events, stent thromboses, and mortality in patients with acute myocardial infarction undergoing reperfusion therapy. Although the prevailing view is that their benefit derives from their antithrombotic properties, other unrelated pleiotropic effects appear to be equally beneficial. Accumulating clinical and animal evidence indicates that, if present at the time of reperfusion, these drugs have a direct anti-infarct effect similar to that of ischemic postconditioning. Four oral antagonists have been developed in rapid succession: ticlopidine, clopidogrel, prasugrel, and ticagrelor. Each agent had a more consistent and rapid onset of action than the previous one, and this has correlated with improved clinical outcomes when given early in treatment. Unfortunately, gut absorption causes an appreciable delay in the onset of effect, especially when morphine is used, and the constant push to minimize the door-to-balloon time has made it difficult to achieve adequate platelet inhibition at the time of percutaneous coronary intervention with an oral agent. An intravenous P2Y12 antagonist such as cangrelor may optimize treatment because it produces nearly maximal inhibition of platelet aggregation within minutes. If antiplatelet agents do protect through postconditioning’s mechanism, then they would render any other intervention that protects through that mechanism redundant. Indeed, animals treated with cangrelor cannot be further protected by pre- or postconditioning. However, interventions that use a different mechanism such as mild hypothermia or cariporide, a Na+-H+ exchange blocker, do add to cangrelor’s protection. Future research should be directed toward identifying interventions that can augment the protection from antiplatelet therapy and finding a way to optimize P2Y12 inhibition at reperfusion in all patients. [ABSTRACT FROM PUBLISHER]

Background Electroconvulsive therapy (ECT) is a very commonly used treatment for patients with severe and treatment-resistant depression. Although effective, this treatment is complicated by a number of side effects including cognitive impairment motivating attempts to develop treatment alternatives. Magnetic seizure therapy (MST) is a brain stimulation technique using a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary research suggests that MST has antidepressant activity in the absence of cognitive side effects. The aim of this study was therefore to investigate the therapeutic efficacy and cognitive profile of MST provided at high frequency (100 Hz) and potentially longer stimulation trains and longer treatment courses than have been previously investigated. Methods Thirteen patients participated in an open-label clinical trial of up to 18 treatment sessions with 100-Hz MST. Assessments of depression severity and cognitive functioning were performed before and after treatment. Results Of the 13 patients who completed the study, five met clinical response criteria at study end. There was an overall group reduction in depression severity and no evidence of any impairment of orientation, memory, or other elements of cognition after MST treatment. The major limitation of the study was its lack of sham control. Conclusions In conclusion, MST shows antidepressant efficacy without apparent cognitive side effects. However, substantial research is required to understand the optimal conditions for stimulation and to compare MST to established treatments including ECT. [ABSTRACT FROM AUTHOR]

Genetic analysis of TP63 implicates ΔNp63 isoforms in preservation of replicative capacity and cellular lifespan within adult stem cells. ΔNp63α is also an oncogene and survival factor that mediates therapeutic resistance in squamous carcinomas. These diverse activities are the result of genetic and functional interactions between TP63 and an array of morphogenic and morphostatic signals that govern tissue and tumor stasis, mitotic polarity, and cell fate; however the cellular signals that account for specific functions of TP63 are incompletely understood. To address this we sought to identify signaling pathways that regulate expression, stability or activity of ΔNp63α. An siRNA-based screen of the human kinome identified the Type 1 TGFβ receptor, ALK5, as the kinase required for phosphorylation of ΔNp63α at Serine 66/68 (S66/68). This activity is TGFβ-dependent and sensitive to either ALK5-directed siRNA or the ALK5 kinase inhibitor A83-01. Mechanistic studies support a model in which ALK5 is proteolytically cleaved at the internal juxtamembrane region resulting in the translocation of the C-terminal ALK5-intracellular kinase domain (ALK5IKD). In this study, we demonstrate that ALK5-mediated phosphorylation of ΔNp63α is required for the anti-clonogenic effects of TGFB and ectopic expression of ALK5IKD mimics these effects. Finally, we present evidence that ultraviolet irradiation-mediated phosphorylation of ΔNp63α is sensitive to ALK5 inhibitors. These findings identify a non-canonical TGFβ-signaling pathway that mediates the anti-clonogenic effects of TGFβ and the effects of cellular stress via ΔNp63α phosphorylation. [ABSTRACT FROM AUTHOR]

Purpose: Reduced baroreceptor sensitivity (BRS) results in changes in autonomic modulation. Patients with chronic obstructive pulmonary disease (COPD) may have altered BRS. Therefore, we compared BRS between COPD patients and normal controls. Methods: We compared 14 COPD patients [mean (±SD) age, 62 ± 8 years] to 14 healthy controls [mean (±SD) age, 59 ± 6 years] for the loss of BRS. All patients received β-agonist therapy but were free from any other type of medication that would interfere with autonomic responses, all controls were free from cardiopulmonary disease, and none was taking medications. All participants were female, post-menopausal, had no known cardiac disease and were ex-smokers. Reduced baroreceptor sensitivity was determined using the slope of the magnitude of R-R widening over the increase in systolic blood pressure following Valsalva maneuver. Results: The mean BRS in controls versus COPD patients showed a mean value of 6.15 ± 2.26 versus 1.91 ± 2.92 ms/mmHg ( p < 0.001). Conclusions: These findings are consistent with other abnormalities of autonomic disruption as previously reported, and demonstrate a severe blunting of the baroreceptor response in individuals with COPD. The cause of this altered BRS response in COPD is not fully clear, we postulate that air trapping with persistent elevation of intrathoracic pressure may lead to a subsequent blunting of the sensitivity of the baroreceptors. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Increased amygdala response to negative emotions seen in functional MRI (fMRI) has been proposed as a biomarker for negative emotion processing bias underlying depressive symptoms and vulnerability to depressive relapse that are normalized by antidepressant drug treatment. The purpose of this study was to determine whether abnormal amygdala responses to face emotions in depression are related to specific emotions or change in response to antidepressant treatment and whether they are present as a stable trait in medication-free patients in remission. METHOD: Sixty-two medication-free unipolar depressed patients (38 were currently depressed, and 24 were in remission) and 54 healthy comparison subjects underwent an indirect face-emotion processing task during fMRI. Thirty-two currently depressed patients were treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring citalopram plasma concentrations. RESULTS: Patients with current depression had increased bilateral amygdala responses specific to sad faces relative to healthy comparison subjects and nonmedicated patients in stable remission. Treatment with citalopram abolished the abnormal amygdala responses to sad faces in currently depressed patients but did not alter responses to fearful faces. CONCLUSIONS: Aberrant amygdala activation in response to sad facial emotions is specific to the depressed state and is a potential biomarker for a negative affective bias during a depressive episode. [ABSTRACT FROM AUTHOR]

Mild hypothermia (32-35°C) salvages ischemic myocardium and reduces infarct size in hearts undergoing ischemia/reperfusion. It is clear that a cardioprotective effect is evident when the heart is cooled during ischemia, and the protection is greater as the duration of normothermic ischemia is increasingly limited. The effect of cooling just before and at reperfusion is more controversial. Multiple experimental studies have revealed no effect of mild hypothermia on myocardial infarction when cooling was initiated in the waning minutes of ischemia. But Götberg et al. have demonstrated a small effect in pigs cooled with cold intravenous saline and a venous thermode, although the effect of cooling during ischemia continued to be more prominent. Clinical studies have been disappointing, and possible explanations are offered. Götberg's new data are encouraging, but it is questioned whether this is the correct time to conduct a new large-scale clinical trial. [ABSTRACT FROM AUTHOR]

Objectives: The timely recruitment of study participants is a critical component of successful trials. Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Successful recruitment methods for a trial of medical therapy for BPH, Medical Therapy of Prostate Symptoms (MTOPS), were mass mailing and advertising. The Complementary and Alternative Medicines Trial for Urological Symptoms (CAMUS) was designed to evaluate a botanical therapy, saw palmetto, for the treatment of BPH. The objective of this study was to evaluate recruitment strategies for CAMUS and to contrast the baseline characteristics of CAMUS participants with those recruited to a similar trial using conventional medical therapy. Design: CAMUS is a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of saw palmetto given at escalating doses over an 18-month period on relief from LUTS. Subjects: The target enrollment goal was 350 men with LUTS from 11 clinical centers over a 12-month period. The recruitment techniques used and participants contacted, screened, and randomized through each technique were obtained from the clinical centers. Baseline characteristics of the CAMUS participants were compared with participants in the MTOPS trial who met the CAMUS eligibility criteria for LUTS. Results: The target enrollment goal was achieved in 11 months. The overall monthly recruitment rate per site was 3.7 and ranged from 2.4 to 8.0. The most successful recruitment methods were mass mailing and advertising, which accounted for 39% and 35% of the study participants, respectively. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, more diverse, and had less severe urinary symptoms. Conclusions: Successful recruitment methods for CAMUS were similar to those in MTOPS. The use of botanical therapy attracted a less symptomatic and more educated study population. [ABSTRACT FROM AUTHOR]

The article presents two case studies on multifocal spindle cell hemangioma. The first case involves a 10-year-old girl with history of multiple violaceous and reddish cutaneous nodules on the right ankle and foot, and was treated with sclerotherapy and etoxisclerol foam. The second case involves 18-year-old woman with multiple subcutaneous nodules on the left upper extremity. Both cases showed nodular proliferation of thin-walled vascular structures lined by a layer of endothelial cells.

Objectives: To assess the in vitro activity of the FDA-approved antihelminthic drug pyrvinium pamoate against Entamoeba histolytica and Giardia intestinalis. [ABSTRACT FROM PUBLISHER]

The article presents information on several papers discussed at the 2008 research poster session of the American Dance Therapy Association's 43rd annual conference. One of the papers explored the researcher's understanding of the experience and healing process of parents bereaved by the death of their child. Another paper focused on the survey of dance/movement therapy practice in Australia

OBJECTIVE To report a multicentre, community based open-label study designed to assess the efficacy and safety of intravesical sodium chondroitin sulphate in the treatment of patients with the clinical diagnosis of interstitial cystitis (IC). Chondroitin sulphate is a naturally occurring glycosaminoglycan (GAG) in the bladder mucus layer and changes in this GAG have been implicated in the pathogenesis of IC, and small single-centre studies have suggested that intravesical chondroitin sulphate may have efficacy in IC. PATIENTS AND METHODS Patients with IC were treated with sodium chondroitin sulphate (Uracyst®, Stellar Pharmaceuticals Inc., London ON, Canada) solution 2.0% via urinary catheter weekly for 6 weeks and then monthly for 16 weeks for a total of 10 treatments. The primary efficacy endpoint was the percentage of responders to treatment as indicated by a marked or moderate improvement on a seven-point patient Global Response Assessment (GRA) scale at week 10 (4 weeks after the initial six treatments) compared with baseline. A major secondary efficacy endpoint (durability) was the percentage of responders on the GRA scale after 10 treatments. Additional secondary efficacy objectives were differences from baseline in Patient Symptom/Problem Index scores over the course of the treatment compared with baseline. RESULTS In all, 47% of the 53 enrolled patients with long standing moderately severe IC (mean [sd, range] diagnosis of IC 3.0 [3.4, 0.1–16] years; duration of symptoms 9.2 [9.2, 1–39] years; baseline symptom score 14.2 [3.2]) were responders at week 10. At 24 weeks, 60% were responders. There was a statistically and clinically significant decrease in the mean (sd) symptom and bother scores from baseline at 10 weeks and 24 weeks, at 9.0 (4.3) and 8.1 (5.0), respectively ( P < 0.001). There were no significant safety issues during the study. CONCLUSIONS This multicentre community based real-life clinical practice study suggests that intravesical chondroitin sulphate may have an important role in the treatment of IC and validates the rationale for a randomized placebo-controlled trial. [ABSTRACT FROM AUTHOR]

The ideas of psychoanalytically-oriented psychotherapists about human sexuality have changed radically in recent years. During the past three decades we have worked toward revising traditional psychoanalytic ideas about sexual orientation in particular. This revision has contributed to changes in clinical theory and practice, and we review both our own work, and these changes, in this article. We have approached the many complex scientific and clinical problems in this field from a developmental, biopsychosocial perspective. We have also emphasized the importance of integrating psychoanalytic theories of sexuality with advances in neuroscience, descriptive psychiatry and sexology generally. In this article we draw on our experience as researchers and clinicians to discuss such common clinical problems in psychotherapeutic work with non-heterosexual patients as assessment of the patient, homophobia, internalized homophobia, gender differences among patients and therapists, the ageing patient, sexual orientation of the therapist, and transference and countertransference. [ABSTRACT FROM AUTHOR]

Background: The treatment of metastatic renal cell carcinoma (RCC) with high-dose interleukin-2 (HD IL-2) has resulted in durable tumor regression in a minority of patients. The current study presents the authors' 20-year experience administering this immunotherapeutic agent.Methods: Patients with metastatic RCC (n = 259) were treated with HD IL-2 alone from January 13, 1986 through December 31, 2006 at the Surgery Branch of the National Cancer Institute. Potential predictive factors for response and survival, both pretreatment and treatment-related, were first subjected to univariate analysis and then to multivariate logistic regression or a Cox proportional hazards model. Finally, the authors investigated Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic factors for survival to assess their predictive value in the patient population in the current study.Results: A total of 23 patients experienced a complete response and 30 patients achieved a partial response, for an overall objective response rate of 20%. All partial responders had developed disease recurrence at the time of last follow-up, but only 4 complete responders had experienced disease recurrence by that time. Despite toxicities, only 2 patients developed treatment-related mortalities over this same time period. A higher baseline weight (P = .05) and MSKCC prognostic factors (P = .02) were found to be the variables most associated with response. For survival >4 years and overall survival, several pretreatment and treatment-related factors maintained significance, but none more so than response (P < .0001).Conclusions: HD IL-2 can induce complete tumor regression in a small number of patients, and many patients have experienced extended disease-free intervals. Given its relative safety, HD IL-2 should still be considered a first-line therapy in patients with metastatic RCC who have an overall good performance status. [ABSTRACT FROM AUTHOR]

In ischemic preconditioning (IPC) brief ischemia/reperfusion renders the heart resistant to infarction from any subsequent ischemic insult. Protection results from binding of surface receptors by ligands released during the preconditioning ischemia. The downstream pathway involves redox signaling as IPC will not protect in the presence of a free radical scavenger. To determine when in the IPC protocol the redox signaling occurs, seven groups of isolated rabbit hearts were studied. All hearts underwent 30 min of coronary branch occlusion and 2 h of reperfusion. IPC groups were subjected to 5 min of regional ischemia followed by 10 min of reperfusion prior to the 30-min coronary occlusion. The Control group had only the 30-min occlusion and 2-h reperfusion. In the second group IPC preceded the index coronary occlusion. The third group was also preconditioned, but the free radical scavenger N-2-mercaptopropionyl glycine (MPG 300 µM) was infused during the 10-min reperfusion and therefore was present in the myocardium in the distribution of the snared coronary artery during the entire reperfusion phase and also during the subsequent 30-min ischemia. In another preconditioned group MPG was added to the perfusate before the preconditioning ischemia and therefore was present in the tissue only during the preconditioning ischemia and then was washed out during reperfusion. In the fifth group MPG was added to the perfusate for only the last 5 min of the preconditioning reperfusion and therefore was present in the tissue during the last minutes of the reperfusion phase and the 30 min of ischemia. In an additional group of IPC hearts MPG was infused for only the initial 5 min of the preconditioning reperfusion and then allowed to wash out so that the scavenger was present for only the first half of the reperfusion phase. Infarct and risk zone sizes were measured by triphenyltetrazolium staining and fluorescent microspheres, resp. IPC reduced infarct size from 31.3 ± 2.7% of the ischemic zone in control hearts to only 8.4 ± 1.9%. MPG completely blocked IPC’s protection in the third (39.4 ± 2.8%) and sixth (36.1 ± 7.7%) groups but did not affect its protection in groups 4 (8.1 ± 1.5%) or 5 (7.8 ± 1.1%). When deoxygenated buffer was used during IPC’s reperfusion phase in the seventh group of hearts, protection was lost and infarct size was increased over that seen in control hearts (74.5 ± 9.0%). Hence redox signaling occurs during the reperfusion phase of IPC, and the critical component in that reperfusion phase appears to be molecular oxygen. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the relative efficacy of cryoablation (CRYO) versus external beam radiation (EBRT) for clinically locally advanced prostate cancer in a randomized clinical trial. Patients with histologically proven, clinically staged as T2C, T3A or T3B disease were randomized with 6 months of perioperative hormone therapy to one of the two procedures. Owing largely to a shift in practice to longer term adjuvant hormonal therapy and higher doses of radiation for T3 disease, only 64 out of the planned 150 patients were accrued. Twenty-one of 33 (64%) in the CRYO group and 14 of 31 (45%) in the EBRT-treated group who had met the ASTRO definition of failure were also classified as treatment failure. The mean biochemical disease-free survival (bDFS) was 41 months for the EBRT group compared to 28 months for the CRYO group. The 4-year bDFS for EBRT and CRYO groups were 47 and 13%, respectively. Disease-specific survival (DSS) and overall survival (OS) for both groups were very similar. Serious complications were uncommon in either group. EBRT patients exhibited gastrointestinal (GI) adverse effects more frequently. Taking into account the relative deficiency in numbers and the original trial design, this prospective randomized trial indicated that the results of CRYO were less favorable compared to those of EBRT, and was suboptimal primary therapy in locally advanced prostate cancer.Prostate Cancer and Prostatic Diseases (2008) 11, 40–45; doi:10.1038/sj.pcan.4500988; published online 19 June 2007 [ABSTRACT FROM AUTHOR]

Breast cancer is the most common nondermatological malignancy in women, and the incidence increases with age until the eighth decade. Breast cancer pathology and biology appear to be different in elderly patients than in younger ones, and therefore treatment recommendations cannot be generalized from one group to the other. Most elderly women can tolerate breast cancer surgery without significant complications and should be offered a definitive surgical procedure. Improved mechanisms to predict which patients will tolerate and benefit from various therapies are under development. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant and metastatic settings. Chemotherapy can be used in elderly women, but treatment decisions must be individualized based upon risk–benefit analyses. Elder-specific studies are underway to identify the most-efficacious and best-tolerated therapies for breast cancer in this population. Primary care physicians must be aware of these issues to provide adequate counseling and care to these patients. [ABSTRACT FROM AUTHOR]

[ABSTRACT FROM AUTHOR]

Background and Purpose. Pelvic-floor muscle (PFM) exercises are effective in reducing stress urinary incontinence (SUI), but few studies have investigated the effect of specific exercise variables on treatment outcomes. This study explored the effect of exercise position on treatment outcomes in women with SUI. Subjects and Methods. Forty-four women were randomly assigned to exercise in the supine position only or in both supine and upright positions. Bladder diary, pad test, urodynamic test, quality-of-life (Incontinence Impact Questionnaire [IIQ]), and PFM strength outcomes were obtained at baseline and after treatment. Results. Exercise position did not affect outcomes. After data from both groups were collapsed, statistically significant improvements with treatment were observed in bladder diary, IIQ, PFM strength, and urodynamic test results. Discussion and Conclusion. Exercise position did not differentially affect treatment outcomes. However, women in this study achieved a mean 67.9% reduction in the frequency of SUI episodes and improvements in other study outcomes. [ABSTRACT FROM AUTHOR]

Bone biology is a complex and vastly growing area of study. It brings together the traditional fields of anatomy, physiology, and biomechanics with the increasingly complex fields of developmental biology and molecular genetics. For clinicians who treat bone disorders such as osteoporosis, developing a working knowledge of this topic is essential. This article discusses bone from a structural, anatomical, and functional perspective. It reviews skeletogenesis as a developmental process and from a regulatory perspective and presents biomechanical principles and theories. Osteoporosis is reviewed, including recent literature related to the role of exercise in prevention and treatment of this disease. [ABSTRACT FROM AUTHOR]

This article presents the National Heart, Lung and Blood Institute (NHLBI) perspective on the status of cell-based therapies. A summary of current and future NHLBI/National Institutes of Health (NIH) programs is given along with a history of the development of NHLBI/NIH resources to aid the advancement of cell-based therapies. A brief discussion of clinical research programs to utilize cell-based therapies is also included. [ABSTRACT FROM AUTHOR]