Antithrombotic Therapy After TAVR.
Transvascular Aortic Valve Replacement (TAVR) has emerged as a treatment option in patients with severe aortic stenosis who are inoperable and has recently been evaluated in patients with intermediate surgical risk. The number of procedures is increasing worldwide in parallel with the demographic changes in industrial countries. The risk for cerebral embolism is of main concern and represents a major determinant for prognosis and quality of live after TAVR. The empiric antithrombotic therapy consists of Dual Antiplatelet Therapy (DAPT); However the risk-benefit of this approach is lacking evidence from randomized, placebo-controlled trials regarding choice and duration of antithrombotic treatment. Although anticoagulation is generally not recommended in patients with aortic bioprosthesis without atrial fibrillation, there is current uncertainty whether combination of antiplatelet and anticoagulant therapy or anticoagulation alone might represent a more favorable antithrombotic regimen compared to the current empiric standard of DAPT. In addition, so far undetected atrial fibrillation is highly prevalent in the elderly population undergoing TAVR. In particular, the favorable safety profile of Non-Vitamin K Oral Anticoagulants (NOAC) offers an attractive option. A number of trials are currently underway to investigate the benefit of NOAC in patients with and without atrial fibrillation undergoing TAVR. The present article reviews the available evidence concerning stroke risk in TAVR patients and the current and future role of antithrombotic therapy during and after the procedure.


Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy.
Although ammonia is considered the main factor involved in the pathogenesis of hepatic encephalopathy (HE), it correlates well with the severity of HE in acute liver failure, but not in chronic liver disease. Oxidative stress is another factor believed to play a role in the pathogenesis of this syndrome; it represents an imbalance between the production and neutralization of reactive oxygen species, which leads to cellular dysfunction. In the setting of liver disease, oxidative stress represents a systemic phenomenon induced by several mechanisms: decreased antioxidant synthesis, increased systemic release of oxidant enzymes, generation of reactive oxygen species, and impaired neutrophil function. High ammonia concentrations induce cerebral oxidative stress, thus contributing to severe hepatic encephalopathy, as observed in acute liver failure. In chronic liver disease, significantly lower degrees of hyperammonemia (<500 μM) do not induce cerebral nor systemic oxidative stress. Data from both animal and human studies sustain that there is a synergistic effect between systemic oxidative stress, and ammonia that is implicated in the pathogenesis of hepatic encephalopathy.


The health-related quality of life of Indigenous populations: a global systematic review.
Indigenous conceptions of health have been shown to differ from that of their non-Indigenous counterparts. As a result, there remains uncertainty over the appropriateness and value of using existing health-related quality-of-life (HRQoL) instruments in Indigenous communities. The objective of this review was to identify studies that either measure the HRQoL of an Indigenous population or validated a measure used to elicit the HRQoL in an Indigenous population. A systematic review of the published literature was conducted to (1) investigate the extent to which HRQoL instruments are used in Indigenous populations; (2) to identify which instruments have been validated in which populations; and (3) to identify which instruments have been tailored for use with Indigenous populations. Forty-one studies were included in the review. Only three of the 41 studies utilised Indigenous-specific instruments. The remainder (38 studies) utilised generic population or disease-specific instruments. Four studies found specific HRQoL instruments to be valid in these populations and 32 estimated the HRQoL of an Indigenous population. The limited examples of Indigenous-specific instruments highlighted the potential importance to the HRQoL of these populations of domains that lie outside of traditional measures including social and community domains as well as domains relating to culture, diet and land use on top of more traditional HRQoL domains. Ensuring that the HRQoL of Indigenous populations is being appropriately measured is vital to prioritising available resources to the most effective interventions. HRQoL instruments present an opportunity to directly elicit and incorporate Indigenous preferences and conceptions of health into these decisions. Further work is required in the field to ensure that this potential is realised.


Transcriptional autoregulation controls pancreatic Ptf1a expression during development and adulthood.
The basic helix-loop-helix (bHLH) transcription factor PTF1a is critical to the development of the embryonic pancreas. It is required early for the formation of the undifferentiated tubular epithelium of the nascent pancreatic rudiment and then becomes restricted to the differentiating acinar cells, where it directs the transcriptional activation of the secretory digestive enzyme genes. Here we report that the complex temporal and spatial expression of Ptf1a is controlled by at least three separable gene-flanking regions. A 14.8-kb control domain immediately downstream of the last Ptf1a exon is highly conserved among mammals and directs expression in the dorsal part of the spinal cord but has very little activity in the embryonic or neonatal pancreas. A 13.4-kb proximal promoter domain initiates limited expression in cells that begin the acinar differentiation program. The activity of the proximal promoter domain is complemented by an adjacent 2.3-kb autoregulatory enhancer that is able to activate a heterologous minimal promoter with high-level penetrance in the pancreases of transgenic mice. During embryonic development, the enhancer initiates expression in the early precursor epithelium and then superinduces expression in acinar cells at the onset of their development. The enhancer contains two evolutionarily conserved binding sites for the active form of PTF1a, a trimeric complex composed of PTF1a, one of the common bHLH E proteins, and either RBPJ or RBPJL. The two sites are essential for acinar cell-specific transcription in transfected cell lines and mice. In mature acinar cells, the enhancer and PTF1a establish an autoregulatory loop that reinforces and maintains Ptf1a expression. Indeed, the trimeric PTF1 complex forms dual autoregulatory loops with the Ptf1a and Rbpjl genes that may maintain the stable phenotype of pancreatic acinar cells.


Seasonal effects of heat shock on bacterial populations, including artificial Vibrio parahaemolyticus exposure, in the Pacific oyster, Crassostrea gigas.
During the warmer summer months, oysters are conditioned to spawn, resulting in massive physiological efforts for gamete production. Moreover, the higher temperatures during the summer typically result in increased bacteria populations in oysters. We hypothesized that these animals are under multiple stresses that lead to possible immune system impairments during the summer months that can possibly lead to death. Here we show that in the summer and the fall animals exposed to a short heat stress respond similarly, resulting in a general trend of more bacteria being found in heat shocked animals than their non-heat shocked counterparts. We also show that naturally occurring bacterial populations are effected by a heat shock. In addition, oysters artificially contaminated with Vibrio parahaemolyticus were also affected by a heat shock. Heat shocked animals contained higher concentrations of V. parahaemolyticus in their tissues and hemolymph than control animals and this was consistent for animals examined during summer and fall. Finally, oyster hemocyte interactions with V. parahaemolyticus differed based on the time of the year. Overall, these findings demonstrate that seasonal changes and/or a short heat shock is sufficient to impact bacterial retention, particularly V. parahaemolyticus, in oysters and this line of research might lead to important considerations for animal harvesting procedures.


Disturbed patterns of immunocompetent cells in usual-type vulvar intraepithelial neoplasia.
Genital infection with human papillomavirus (HPV) is usually transient, as the immune system is capable of eliminating the virus. When immunity "fails" and the infection persists, vulvar intraepithelial neoplasia (VIN) may develop. In this study, we examined the distribution of inflammatory cells in 51 patients with HPV-associated usual-type VIN and in 19 healthy controls. Frozen vulvar tissue samples were tested for the presence of HPV-DNA, and immunohistochemical staining for the markers CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8, and CD25/HLA-DR was performed. Cells were counted in both the epidermis and dermis over at least 2 mm of basal membrane length. In the epidermis of VIN patients, CD1a(+) and CD207(+) (Langerin) dendritic cells (DC) and CD8(+) T cells were significantly lower than in controls, whereas the number of CD123(+)/CD11c(-) plasmacytoid DCs (pDC) was significantly increased. No significant changes were observed for CD208(+) DCs, CD94(+) natural killer (NK) cells, CD4(+) T cells, and CD25(+)/HLA-DR(+) regulatory T cells. In the dermis of VIN patients, elevated numbers of CD208(+), CD123(+)/CD11c(-), CD94(+), CD4(+), CD8(+), and CD25(+)/HLA-DR(+) cells were observed when compared with healthy controls. The numbers of CD1a(+) and CD207(+) DCs were not different between groups. In summary, high-risk HPV-related usual-type VIN lesions are characterized by an immunosuppressive state in the epidermis, showing a reduction of immature myeloid DCs (mDC) and CD8(+) T cells. In the dermis, inflammatory activation is reflected by the influx of mature mDCs and pDCs, NK cells, and T cells, suggesting that the cellular immune response on viral HPV infection occurs in the dermis of VIN patients.


Naringin promotes osteoblast differentiation and effectively reverses ovariectomy-associated osteoporosis.
Osteoporosis is a common pathological condition that influences 20 % of women over 50 years of age. This condition decreases bone strength and increases the risk of bone fracture. Naringin is a major flavonoid found in grapefruit and an active compound extracted from a Chinese herbal medicine (Rhizoma Drynariae). Studies have shown that naringin possesses many pharmacological effects. The current study evaluated the influence of naringin on osteoblastic cell differentiation and proliferation, and assessed its therapeutic effects on a rat osteoporosis model. The proliferation, differentiation, and function of rat bone marrow stromal cells (BMSCs) were determined following treatment with various concentrations of naringin. Ovariectomy (OVX)-induced osteoporotic rats were orally administered naringin daily at low, medium, and high dosages, while a control group received PBS for 2 months. Femoral X-ray images and microCT scans were used for bone mineral density (BMD) and BV/TV (bone volume/total volume) analyses, and histological assessments of left tibiae were employed to check for changes in trabecular thickness (Tb.Th) and trabecular space (Tb.Sp) in the groups. Naringin was effective at enhancing the proliferation and osteogenic differentiation of BMSCs, and a concentration of 10 μg/ml prompted the highest levels of osteocalcin expression among the in vitro study groups. There appeared to be a delayed response pattern of BMSCs to the naringin treatment. Naringin also effectively reversed OVX-induced bone loss via increasing BMD, bone volume, and trabecular thickness. The medium dose (300 mg/kg) appeared to be the optimal dosage for delivering satisfactory therapeutic effects. Naringin promotes the proliferation and differentiation of BMSCs, and increases osteocalcin expression. Naringin also effectively reverses ovariectomy-induced osteoporosis in rats. The study suggests that naringin administration may represent an effective treatment for osteoporosis.


Intra-saccadic motion streaks as cues to linking object locations across saccades.
When visual objects shift rapidly across the retina, they produce motion blur. Intra-saccadic visual signals, caused incessantly by our own saccades, are thought to be eliminated at early stages of visual processing. Here we investigate whether they are still available to the visual system and could-in principle-be used as cues for localizing objects as they change locations on the retina. Using a high-speed projection system, we developed a trans-saccadic identification task in which brief but continuous intra-saccadic object motion was key to successful performance. Observers made a saccade to a target stimulus that moved rapidly either up or down, strictly during the eye movement. Just as the target reached its final position, an identical distractor stimulus appeared on the opposite side, resulting in a display of two identical stimuli upon saccade landing. Observers had to identify the original target using the only available clue: the target's intra-saccadic movement. In an additional replay condition, we presented the observers' own intra-saccadic retinal stimulus trajectories during fixation. Compared to the replay condition, task performance was impaired during saccades but recovered fully when a post-saccadic blank was introduced. Reverse regression analyses and confirmatory experiments showed that performance increased markedly when targets had long movement durations, low spatial frequencies, and orientations parallel to their retinal trajectory-features that promote intra-saccadic motion streaks. Although the potential functional role of intra-saccadic visual signals is still unclear, our results suggest that they could provide cues to tracking objects that rapidly change locations across saccades.


Vacuum assisted closure therapy in the treatment of mesh infection after hernia repair.
Mesh related infection after prosthetic abdominal wall hernia repair is a difficult clinical problem, particularly in an era of evolving microbial resistance. Commonly advocated treatment for such infection involves complete mesh excision which usually leaves a complicated weak wound. We report the use ofVAC therapy for mesh infections that allows mesh preservation leaving a sound wound. From june 2002 to January 2007, four patients with mesh related infection after abdominal wall hernia repair were treated with VAC therapy. Patients' notes were reviewed to gather clinical details. Mesh infection was evident after a variable period (day three to eight years) following hernia repair. Of the four patients, one had infection with methicillin resistant Staphylococcus aureus (MRSA), while the bacteriological cultures from two confirmed Staphylococcus aureus in one and a mixture of Pseudomonas and enterococcus species in the other. One patient failed to show significant bacterial growth on pus swab culture, having had prior broad-spectrum antibiotic treatment for mesh infection. Three patients had complete mesh preservation and one had partial mesh excision. All patients were treated with VAC therapy, following the drainage of their operation sites, until the visible mesh was covered with granulation (one to seven weeks). No patient had a recurrent hernia after complete wound healing. VAC therapy allows salvage of infected exposed mesh by promoting granulation through the mesh. Judicious use of VAC therapy may prevent the need of mesh excision and its wound related complications.


Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Studies I to III.
To evaluate the outcome of patients with rhabdomyosarcoma (RMS) treated with complete surgical resection and multiagent chemotherapy, with or without local radiotherapy (RT). Four hundred thirty-nine patients with completely resected (ie, group I) RMS were further treated with chemotherapy (vincristine and actinomycin D +/- cyclophosphamide, doxorubicin, and cisplatin) on Intergroup Rhabdomyosarcoma Studies (IRS) I to III between 1972 and 1991. Eighty-three patients (19%) also received local RT as a component of initial treatment. Eighty-six patients relapsed (10-year failure-free survival [FFS] 79%, overall survival 89%). Six percent of failure sites were local, 6% were regional, and 7% were distant. Poor prognostic factors were tumor size greater than 5 cm, alveolar or undifferentiated histology, primary tumor sites other than genitourinary, and treatment on IRS-I or II. For patients with embryonal RMS who were treated with RT, there was a trend for improved FFS but no difference in overall survival. On IRS-I and II, patients with alveolar or undifferentiated sarcoma who received RT compared with those who did not receive RT had greater 10-year FFS rates (73% v 44%, respectively; P =.03) and overall survival rates (82% v 52%, respectively; (P =.02). Such patients who received RT on IRS III also benefited more than those who did not receive RT (10-year FFS, 95% v 69%; P =.01; overall survival, 95% v 86%; P =.23). Patients with group I embryonal RMS have an excellent prognosis when treated with adjuvant multiagent chemotherapy without RT. Patients with alveolar RMS or undifferentiated sarcoma fare worse; however, FFS and overall survival are substantially improved when RT is added to multiagent chemotherapy (IRS-I and II). The best outcome occurred in IRS-III, when RT was used in conjunction with intensified chemotherapy.


Hydroxyapatite Mineralization on the Calcium Chloride Blended Polyurethane Nanofiber via Biomimetic Method.
Polyurethane nanofibers containing calcium chloride (CaCl2) were prepared via an electrospinning technique for the biomedical applications. Polyurethane nanofibers with different concentration of CaCl2 were electrospun, and their bioactivity evaluation was conducted by incubating in biomimetic simulated body fluid (SBF) solution. The morphology, structure and thermal properties of the polyurethane/CaCl2 composite nanofibers were characterized by means of scanning electron microscopy (SEM), field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy and thermogravimetry. SEM images revealed that the CaCl2 salt incorporated homogeneously to form well-oriented nanofibers with smooth surface and uniform diameters along their lengths. The SBF incubation test confirmed the formation of apatite-like materials, exhibiting enhanced bioactive behavior of the polyurethane/CaCl2 composite nanofibers. This study demonstrated that the electrospun polyurethane containing CaCl2 composite nanofibers enhanced the in vitro bioactivity and supports the growth of apatite-like materials.


Secondhand Smoke Exposure and Subsequent Academic Performance Among U.S. Youth.
Previous research shows the associations between secondhand smoke exposure and health consequences among youth, but less is known about its effect on academic performance. This study examines a dose-response relationship between secondhand smoke exposure and subsequent academic performance among U.S. youth. Data were from a nationally representative sample of youth non-tobacco users (aged 12-16 years) in Wave 2 (2014-2015) who completed Wave 3 (2015-2016) of the Population Assessment of Tobacco and Health Study (n=9,020). Past-7-day number of hours exposed to secondhand smoke at Wave 2 and academic performance at Wave 3 (1=Mostly As to 9=Mostly Fs) were assessed. Weighted multivariable linear regression models were used to examine the association between hours of self-reported secondhand smoke exposure at Wave 2 and academic performance at Wave 3 (1=Mostly Fs, 9=Mostly As), adjusting for covariates including sociodemographics, prior academic performance, internalizing and externalizing problems, and substance use problems. Analyses were conducted in 2019. More than 30% of U.S. youth non-tobacco users were exposed to secondhand smoke in the past 7 days. Compared with unexposed youth at Wave 2, those who were exposed for 1-9 hours had poorer academic performance at Wave 3 (adjusted regression coefficient= -0.11, 95% CI= -0.18, -0.04), and those who were exposed for ≥10 hours at Wave 2 had even poorer academic performance (adjusted regression coefficient = -0.31, 95% CI= -0.45, -0.18). A dose-response relationship was observed between secondhand smoke exposure and academic performance among U.S. youth. Reducing youth secondhand smoke exposure may promote academic performance and subsequent educational attainment.


Cryptorchidectomy in equids: 604 cases (1977-2010).
To evaluate the management of equids undergoing cryptorchidectomy at a referral hospital. Retrospective case series. 604 client-owned equids. Medical records of all equids undergoing surgical treatment of cryptorchidism from 1977 to 2010 were retrospectively reviewed. Analyses of breed, location of retained testes, accuracy of palpation per rectum for determining the location of retained testes, surgical technique, and postoperative complications were performed. The most frequently affected breed was the Quarter Horse (282/604 [47%]), which was significantly overrepresented. Of the 604 equids, 90 (15%) had undergone previous surgical attempts at castration. Preoperative palpation per rectum was performed in 395/604 (65.4%) patients, and was accurate in predicting the location of the retained testes in 354/395 (89.6%). Surgeons were significantly more likely to be incorrect in determining the location of the retained testis by means of palpation per rectum in patients that had undergone a prior attempt at castration. For equids with abdominal cryptorchidism (360/604 [59.6%]), the most common surgical technique was noninvasive cryptorchidectomy (298/360 [82.8%]). In unilateral cryptorchids (521/604 [86.3%]), the 2 most common sites were left abdominal (184/521 [35.3%]) and right inguinal (148/521 [28.4%]). For bilateral retention (80/604 [13.2%]), abdominal cryptorchidism was most common (48/80 [60%]). Fever was present in 138/324 (43%) equids on the first day after surgery. Postoperative fever was not significantly associated with any variables evaluated. Including postoperative (≤ 24 hours) fever, 150 of 604 (25%) patients developed postoperative complications. Excluding postoperative fever, 18 of 604 (3%) patients developed major postoperative complications; complications in 10 of 604 patients were deemed surgically related, and 3 of 604 patients died. Results indicated that cryptorchidectomy in equids performed with a variety of surgical approaches was associated with minimal postoperative complications. A history of previous attempts at castration decreased the ability to accurately predict the location of the retained testis.


Creating a positive perception of childbirth experience: systematic review and meta-analysis of prenatal and intrapartum interventions.
A negative experience in childbirth is associated with chronic maternal morbidities. The aim of this systematic review and meta-analysis was to identify currently available successful interventions to create a positive perception of childbirth experience which can prevent psychological birth trauma. Randomized controlled trials of interventions in pregnancy or labour which aimed to improve childbirth experience versus usual care were identified from 1994 to September 2016. Low risk pregnant or childbearing women were chosen as the study population. PEDRO scale and Cochrane risk of bias tool were used for quality assessment. Pooled effect estimates were calculated when more than two studies had similar intervention. If it was not possible to include a study in the meta-analysis, its data were summarized narratively. After screening of 7832 titles/abstracts, 20 trials including 22,800 participants from 12 countries were included. Successful strategies to create a positive perception of childbirth experience were supporting women during birth (Risk Ratio = 1.35, 95% Confidence Interval: 1.07 to 1.71), intrapartum care with minimal intervention (Risk Ratio = 1.29, 95% Confidence Interval:1.15 to 1.45) and birth preparedness and readiness for complications (Mean Difference = 3.27, 95% Confidence Interval: 0.66 to 5.88). Most of the relaxation and pain relief strategies were not successful to create a positive birth experience (Mean Difference = - 2.64, 95% Confidence Intervention: - 6.80 to 1.52). The most effective strategies to create a positive birth experience are supporting women during birth, intrapartum care with minimal intervention and birth preparedness. This study might be helpful in clinical approaches and designing future studies about prevention of the negative and traumatic birth experiences.


Antidepressant-like effects of Perilla frutescens seed oil during a forced swimming test.
Unipolar depressive disorder may become one of the major leading causes of disease burden by 2030 according to the World Health Organization (WHO). Thus, the discovery of antidepressive foods is attractive and could have considerable impacts worldwide. We investigated the antidepressant-like effects of Perilla frutescens seed oil on adult male rats subjected to a forced swimming test (FST). Forty Sprague-Dawley rats were housed and fed various diets, including soybean oil-rich, eicosapentaenoic acid (EPA)-rich, and P. frutescens seed oil-rich diets for 6 weeks. After the dietary intervention, animals were tested using an FST and were sacrificed after the test. We analyzed the fatty acid profiles of red blood cells (RBCs) and the brain prefrontal cortex (PFC). Levels of brain-derived neurotrophic factor (BDNF), serotonin, and dopamine in the PFC were also determined. After the FST, the imipramine, EPA-rich, and P. frutescens seed oil-rich groups showed significant shorter immobility time and longer struggling time than the control group (p < 0.05). Levels of BDNF in the P. frutescens seed oil-rich group and levels of serotonin in the EPA-rich group were significantly (p < 0.05) higher than those of the control group. Moreover, the BDNF concentration in the PFC was significantly positively correlated with the struggling time. However, there were no significant differences in dopamine levels between the intervention groups and the control group. In conclusion, a P. frutescens seed oil-rich diet exhibited antidepressant-like properties through modulation of fatty acid profiles and BDNF expression in the brain during an FST.


Immunolocalization of Aspergillus fumigatus mycelial antigens.
Specific immunoglobulin from the sera of patients with antibodies to Aspergillus and from antisera raised in rabbits to Aspergillus fumigatus fractions bound almost exclusively to the mycelial wall, as shown by immunogold labelling of ultra-thin sections. Different layers of the wall were labelled, depending on the source of the antigen used to produce antibody. Internal, cytoplasmic components were generally not labelled, except with antisera raised to crude wall material and to a Concanavalin A (ConA)-binding fraction of a water-soluble preparation.


Gender-related differences in the prevalence of cardiovascular disease risk factors and their correlates in urban Tanzania.
Urban areas in Africa suffer a serious problem with dual burden of infectious diseases and emerging chronic diseases such as cardiovascular diseases (CVD) and diabetes which pose a serious threat to population health and health care resources. However in East Africa, there is limited literature in this research area. The objective of this study was to examine the prevalence of cardiovascular disease risk factors and their correlates among adults in Temeke, Dar es Salaam, Tanzania. Results of this study will help inform future research and potential preventive and therapeutic interventions against such chronic diseases. The study design was a cross sectional epidemiological study. A total of 209 participants aged between 44 and 66 years were included in the study. A structured questionnaire was used to evaluate socioeconomic and lifestyle characteristics. Blood samples were collected and analyzed to measure lipid profile and fasting glucose levels. Cardiovascular risk factors were defined using World Health Organization criteria. The age-adjusted prevalence of obesity (BMI > or = 30) was 13% and 35%, among men and women (p = 0.0003), respectively. The prevalence of abdominal obesity was 11% and 58% (p < 0.0001), and high WHR (men: >0.9, women: >0.85) was 51% and 73% (p = 0.002) for men and women respectively. Women had 4.3 times greater odds of obesity (95% CI: 1.9-10.1), 14.2-fold increased odds for abdominal adiposity (95% CI: 5.8-34.6), and 2.8 times greater odds of high waist-hip-ratio (95% CI: 1.4-5.7), compared to men. Women had more than three-fold greater odds of having metabolic syndrome (p = 0.001) compared to male counterparts, including abdominal obesity, low HDL-cholesterol, and high fasting blood glucose components. In contrast, female participants had 50% lower odds of having hypertension, compared to men (95%CI: 0.3-1.0). Among men, BMI and waist circumference were significantly correlated with blood pressure, triglycerides, total, LDL-, and HDL-cholesterol (BMI only), and fasting glucose; in contrast, only blood pressure was positively associated with BMI and waist circumference in women. The prevalence of CVD risk factors was high in this population, particularly among women. Health promotion, primary prevention, and health screening strategies are needed to reduce the burden of cardiovascular disease in Tanzania.


Latissimus dorsi tendon transfer for irreparable rotator cuff tears: a systematic review.
Massive and irreparable posterior-superior rotator cuff tears present a difficult treatment problem. The purpose of this systematic review was to critically examine the outcomes of latissimus dorsi tendon transfers for the treatment of irreparable rotator cuff tears. A systematic review of the literature was performed via a search of electronic databases. Two reviewers independently assessed the methodological quality of, and extracted relevant data from, each included study. In cases in which the outcomes data were similar between studies, data were pooled for the purposes of generating summary outcomes through the use of frequency-weighted values. Ten studies that fulfilled all inclusion and exclusion criteria were included. The frequency-weighted mean age was 58.7 years. Patients were followed for a frequency-weighted mean of 45.5 months (range, twenty-four to 126 months). Patients had a frequency-weighted mean adjusted Constant score of 45.9 preoperatively compared with 73.2 postoperatively (p < 0.001). The frequency-weighted mean active forward elevation improved from 101.9° preoperatively to 137.4° postoperatively (p < 0.001), and the frequency-weighted mean active external rotation improved from 16.8° to 26.7° (p < 0.001). Subscapularis muscle insufficiency, advanced teres minor muscle atrophy, and the need for revision surgery were correlated with poor functional outcomes in some studies. Compiled data and frequency-weighted means demonstrated improvement in shoulder function, range of motion, strength, and pain relief after latissimus dorsi tendon transfer for irreparable rotator cuff tears. Patients and physicians should not expect an outcome of "normal" function or complete pain relief.


Dental topography and the diet of Homo naledi.
Though late Middle Pleistocene in age, Homo naledi is characterized by a mosaic of Australopithecus-like (e.g., curved fingers, small brains) and Homo-like (e.g., elongated lower limbs) traits, which may suggest it occupied a unique ecological niche. Ecological reconstructions inform on niche occupation, and are particularly successful when using dental material. Tooth shape (via dental topography) and size were quantified for four groups of South African Plio-Pleistocene hominins (specimens of Australopithecus africanus, Paranthropus robustus, H. naledi, and Homo sp.) on relatively unworn M2s to investigate possible ecological differentiation in H. naledi relative to taxa with similar known geographical ranges. H. naledi has smaller, but higher-crowned and more wear resistant teeth than Australopithecus and Paranthropus. These results are found in both lightly and moderately worn teeth. There are no differences in tooth sharpness or complexity. Combined with the high level of dental chipping in H. naledi, this suggests that, relative to Australopithecus and Paranthropus, H. naledi consumed foods with similar fracture mechanics properties but more abrasive particles (e.g., dust, grit), which could be due to a dietary and/or environmental shift(s). The same factors that differentiate H. naledi from Australopithecus and Paranthropus may also differentiate it from Homo sp., which geologically predates it, in the same way. Compared to the great apes, all hominins have sharper teeth, indicating they consumed foods requiring higher shear forces during mastication. Despite some anatomical similarities, H. naledi likely occupied a distinct ecological niche from the South African hominins that predate it.


Clinical effects of Garcinia kola in knee osteoarthritis.
Over the past years, there has been a growing number of knee osteoarthritis (KOA) patients who are not willing to comply with long-term non-steroidal anti-inflammatory drugs (NSAID) treatment and wish to use herbal anti- rheumatic medicine. This study assessed the clinical effects of Garcinia kola (GK) in KOA patients. Prospective randomized, placebo controlled, double blind, clinical trial approved by the institutional medical ethics review board and written informed consent obtained from each patient. All KOA patients presenting at the Obafemi Awolowo University Teaching Hospital complex were recruited into the study. The patients were grouped into four (A = Placebo, B = Naproxen, C = Garcinia kola, D = Celebrex). The drugs and placebo were given twice a day per oral route. Each dose consisted of 200 mg of G. kola, Naproxen (500 mg), Celebrex (200 mg) and Ascorbic acid (100 mg). The primary outcome measure over six weeks study period was the change in mean WOMAC pain visual analogue scales (VAS). Secondary outcome measures included the mean change in joint stiffness and physical function (mobility/walking). 143 patients were recruited, 84 (58.7%, males--24, females--60) satisfied the selection criteria and completed the study. The effect of knee osteoarthritis bilateralism among the subjects was not significant on their outcome (p > 0.05). The change in the mean WOMAC pain VAS after six weeks of G. kola was significantly reduced compared to the placebo (p < 0.001). Multiple comparisons of the mean VAS pain change of G. kola group was not lowered significantly against the naproxen and celebrex groups (p > 0.05). The onset of G. kola symptomatic pain relief was faster than the placebo (p < 0.001). However, it was slower than the active comparators (p > 0.05). The duration of therapeutic effect of Garcinia kola was longer than the placebo (p > 0.001). G. kola period of effect was less than naproxen and celebrex (p < 0.001). G. kola subjects had improved mean change mobility/walking after six weeks better than the control group(p < 0.001). The mean change in mobility of the G. kola group when compared to the active comparators was not significantly better (p < 0.05). The mean change of knee joint stiffness (p < 0.001) and the change of mean WOMAC score (p < 0.001) were improved on Garcinia kola as compared to the placebo. The mid term outcome of eleven Garcinia kola subjects after cessation of use had a mean pain relief period of 17.27 +/- 5.15 days (range: 9-26 days). There was no significant cardiovascular, renal or drug induced adverse reaction to Garcinia kola. Garcinia kola appeared to have clinically significant analgesic/anti-inflammatory effects in knee osteoarthritis patients. Garcinia kola is a potential osteoarthritis disease activity modifier with good mid term outcome. Further studies are required for standardization of dosages and to determine long-term effects.


The effect of positional changes on intraocular pressure during sleep in patients with and without glaucoma.
To determine whether sleeping at a 20-degree head-up position decreases nocturnal intraocular pressure (IOP) compared with lying supine (flat) in patients with and without glaucoma. Prospective, nonrandomized comparative case series. Thirty patients were recruited based on self-reported disease status with 15 glaucoma and 15 nonglaucoma patients; a total of 60 eyes were tested. Patients were evaluated in a sleep laboratory on 2 separate nights, lying flat 1 night and lying on a wedge pillow at a 20-degree head-up position another night. Baseline IOP was measured during the awake period (10 PM), then measured at 2-hour intervals during the sleep period (12, 2, 4, and 6 AM). IOP measurements during the 10 PM awake period did not significantly differ between the 2 positions (P=0.55). During the sleep period (12 to 6 AM), the mean IOP was 1.51 mm Hg lower in the 20-degree head-up position when compared with the flat position (95% confidence interval, 0.99 to 2.04 mm Hg), with an average drop of 1.56 and 1.47 mm Hg in glaucoma and nonglaucoma patients, respectively. This corresponds to a 9.33% and 8.67% IOP reduction in glaucoma and nonglaucoma patients, respectively. Twenty-five of 30 patients (83.3%) had lower mean IOPs in the 20-degree head-up position. Mean IOP reduction was >10% for 11 of 30 patients (36.7%) when sleeping in the head-up position. The 20-degree head-up position correlates with lower nocturnal IOP as compared with the supine position in glaucoma and nonglaucoma patients. No significant difference in IOP reduction was observed in glaucoma patients when compared with nonglaucoma patients.


Pathways through which health influences early retirement: a qualitative study.
Due to the aging of the population, there is a societal need for workers to prolong their working lives. In the Netherlands, many employees still leave the workforce before the official retirement age of 65. Previous quantitative research showed that poor self-perceived health is a risk factor of (non-disability) early retirement. However, little is known on how poor health may lead to early retirement, and why poor health leads to early retirement in some employees, but not in others. Therefore, the present qualitative study aims to identify in which ways health influences early retirement. Face-to-face semi-structured interviews were conducted with 30 employees (60-64 years) who retired before the official retirement age of 65. Participants were selected from the Study on Transitions in Employment, Ability and Motivation. The interviews were transcribed verbatim, a summary was made including a timeline, and the interviews were open coded. In 15 of the 30 persons, health played a role in early retirement. Both poor and good health influenced early retirement. For poor health, four pathways were identified. First, employees felt unable to work at all due to health problems. Second, health problems resulted in a self-perceived (future) decline in the ability to work, and employees chose to retire early. Third, employees with health problems were afraid of a further decline in health, and chose to retire early. Fourth, employees with poor health retired early because they felt pushed out by their employer, although they themselves did not experience a reduced work ability. A good health influenced early retirement, since persons wanted to enjoy life while their health still allowed to do so. The financial opportunity to retire sometimes triggered the influence of poor health on early retirement, and often triggered the influence of good health. Employees and employers barely discussed opportunities to prolong working life. Poor and good health influence early retirement via several different pathways. To prolong working life, a dialogue between employers and employees and tailored work-related interventions may be helpful.


Successes and failures in modeling heart cell electrophysiology.
Mathematical models of the electrical activity of the heart using equations for protein ion channels and other transporters began with the Noble 1962 model. These models then developed over a period of about 50 years. Cell types in all regions have been modeled and now are available for download from the CellML website (www.cellml.org). Simulation is a necessary tool of analysis in attempting to understand biological complexity. We often learn as much from the failures as from the successes of mathematical models. It is the iterative interaction between experiment and simulation that is important.


Effects of Different Stain Removal Protocols on Bonding Orthodontic Brackets to Enamel.
To evaluate the effect of different stain removal protocols with or without topical fluoride application on the bond strength of orthodontic brackets to enamel. Eighty extracted premolars were randomly assigned into four groups according to the stain removal protocol. The stain removal protocols were (1) using rubber cup with prophylaxis paste in (G1, n = 20), (2) air-abrasion with prophy-jet polishing system (G2, n = 20), (3) micro-abrasion with opalusture polishing paste (G3, n = 20), and (4) macro-abrasion with ultrafine diamond finishing tips (G4, n = 20). Ten teeth in each group (SG1, n = 10) had no topical fluoride treatment after stain removal protocol, while the rest (SG2, n = 10) were subjected to topical fluoride application. After bonding the orthodontic brackets, all specimens were thermocycled before testing their bracket-enamel bond strength. The debonded bracket and enamel surfaces of each specimen were also assessed to determine the adhesive remnant index (ARI) for each subgroup. Specimens in G2, G3, and G4 recorded lower shear bond strength as compared with G1 (p < 0.05). For all groups, specimens in SG2 demonstrated lower bond strength than their counterpart in SG1 (p < 0.05). No significant differences were detected between the ARIs of different subgroups (p > 0.05). Bonding orthodontic brackets is affected by the protocol of removing enamel stains. The use of the rubber cup with prophylaxis paste provided the highest bracket-enamel bond strength. Topical fluoride application usually complicates the bonding process of orthodontic brackets to cleaned enamel surfaces. The results of the current study indicate higher bracket bond strength to enamel surfaces treated with different stain removal protocols than the clinically acceptable values (5.9-7.8 MPa). However, the more aggressive enamel pretreatment methods should not be considered unless the clinical situation necessitates such action. Postponing the topical fluoride application is advisable to follow the bracket bonding procedure. This action would prevent the negative effect of topical fluorides on bracket-enamel bond strength.


Sociodemographic and health-related risks for loneliness and outcome differences by loneliness status in a sample of U.S. older adults.
This study assesses sociodemographic and health-related factors associated with loneliness and outcome differences between loneliness groups using a sample of 13,812 older adults from the U.S Health and Retirement Study. Descriptive and bivariate analyses were followed by logistic regression to evaluate risks and analysis of covariance testing to determine outcome differences. Overall, prevalence of loneliness was 16.9%. Nonmarried status, poorer self-report of health, lower educational level, functional impairment, increasing number of chronic illnesses, younger age, lower income, and less people living in the household were all associated with loneliness. The chronically lonely group reported less exercise, more tobacco use, less alcohol use, a greater number of chronic illnesses, higher depression scores, and greater average number of nursing home stays. Future research evaluating the effectiveness of both prevention and treatment interventions for loneliness in older adults would provide empirical data to further guide gerontological nursing practice.


Review of bupropion for smoking cessation.
The advent of bupropion hydrochloride sustained release (Zyban) has heralded a major change in the options available for smoking cessation pharmacotherapy. Bupropion is a selective re-uptake inhibitor of dopamine and noradrenalin which prevents or reduces cravings and other features of nicotine withdrawal. Bupropion is a useful oral and non-nicotine form of pharmacotherapy for smoking cessation. For this review a total of 221 papers were reviewed plus poster presentations. This review examines in detail original clinical trials on efficacy, categorised according to whether they were acute treatment trials in healthy smokers; studies in specific populations such as people with depression, chronic obstructive pulmonary disease (COPD) or cardiovascular disease; or relapse prevention studies. Overall, these studies in varying populations comprising over four thousand subjects, showed bupropion consistently produces a positive effect on smoking cessation outcomes. The evidence highlights the major public health role that bupropion has in smoking cessation. The methodological issues of published clinical trials reporting one year outcomes were examined in detail including: completeness of follow-up; loss to follow-up; intention to treat analysis; blindness of assessment; and validation of smoking status. The review discusses contraindications, adverse effects, dose and overdose, addictive potential, and the role of bupropion in reducing cessation-related weight gain. Bupropion combined with or compared to other pharmacotherapies (nicotine patch; nortriptyline) is considered. Impressive evidence exists for the use of bupropion in smoking cessation among difficult patients who are hard-core smokers such as those with cardiovascular disease, chronic obstructive pulmonary disease (COPD) and depression. Bupropion reduces withdrawal symptoms as well as weight gain and is effective for smoking cessation for people with and without a history of depression or alcoholism. Serious side effects of bupropion use are rare. The major safety issue with bupropion is risk of seizures (estimated at approximately 0.1%) and it should not be prescribed to patients with a current seizure disorder or any history of seizures. In clinical trials of bupropion for smoking cessation no seizures were reported. Allergic reactions occur at a rate of approximately 3% and minor adverse effects are common including dry mouth and insomnia.


Plasma proteomic profiling: search for lung cancer diagnostic and early detection markers.
Environmental and occupational exposure to asbestos is among the established risk factors for lung cancer, the leading cause of cancer-related deaths in the United States. This link between exposure to asbestos and the excessive death rate from lung cancer was evident in a study of former workers of an asbestos pipe insulation manufacturing plant in Tyler, TX. We performed comparative proteomic profiling of plasma samples that were collected from nine patients within 12 months before death and their age-, race- and exposure-matched disease-free controls on strong anion exchange chips using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. A distance-dependent K-nearest neighbor (KNN) classification algorithm identified spectral features of m/z values 7558.9 and 15103.0 that were able to distinguish lung cancer patients from disease-free individuals with high sensitivity and specificity. The high correlation between the intensities of these two peaks (r=0.987) strongly suggests that they are the doubly and singly charged ions of the same protein product. Examination of these proteomic markers in the plasma samples of subjects from >5 years before death from lung cancer suggested that they are related to the early development of lung cancer. Validation of these biomarkers would have significant implications for the early detection of lung cancer and better management of high-risk patients.


Determining the adaptive potential of maternal stress.
Ecological and medical researchers are investing great effort to determine the role of Maternally-Derived Stress (MDS) as an inducer of phenotypic plasticity in offspring. Many researchers have interpreted phenotypic responses as unavoidable negative outcomes (e.g., small birth weight, high anxiety); however, a biased underestimate of the adaptive potential of MDS-induced effects is possible if they are not viewed within an ecologically relevant or a life-history optimization framework. We review the ecological and environmental drivers of MDS, how MDS signals are transferred to offspring, and what responses MDS induces. Results from four free-living vertebrate systems reveals that although MDS induces seemingly negative investment trade-offs in offspring, these phenotypic adjustments can be adaptive if they better match the offspring to future environments; however, responses can prove maladaptive if they unreliably predict (i.e., are mismatched to) future environments. Furthermore, MDS-induced adjustments that may prove maladaptive for individual offspring can still prove adaptive to mothers by reducing current reproductive investment, and benefitting lifetime reproductive success. We suggest that to properly determine the adaptive potential of MDS, researchers must take a broader integrated life-history perspective, appreciate both the immediate and longer term environmental context, and examine lifetime offspring and maternal fitness.


Stroop interference is the result of comparable, not of differential processing speeds of two stimulus dimensions.
On a digit-counting Stroop task, processing of the slower, nonverbal, i.e., number, dimension was slowed further by a large-number set (6 to 9), as compared with a small-number set (1 to 4). In the task, neutral symbols or conflicting digits were arranged on a horizontal line (e.g.,@@, 444) and on two separate sheets. Each sheet contained 120 stimulus arrays. Subjects counted out loud the number of symbols or digits in each array, and their counting times for each sheet were recorded. 23 subjects received the small-number set while 21 received the large-number set. It was found that counting a large number of symbols took significantly longer time (by 162 sec. per 120 stimulus arrays) than counting a small number of symbols. Moreover, interference was nonexistent (2 msec. per stimulus array) when a large number of conflicting digits were counted but was of a typical magnitude (110 msec. per stimulus array) when a small number of conflicting digits were counted. This suggests that Stroop interference is better explained as the result of comparable, not of differential, processing speeds of the two stimulus dimensions. Implications for the cause and the locus of Stroop interference are discussed.


Corrections and clarifications.
Note 21 on page 1178 of the report "Mice lacking TdT: Mature animals with an immature lymphocyte repertoire" by S. Gilfillan et al. (27 Aug., p. 1175) should have included the information that the cDNA sequence of mouse TdT was initially obtained by the authors from the European Molecular Biology Laboratory (accession number X04123), given in a 1986 paper by O. Koiwai, T. Yokota, T. Kageyama, T. Hirose, S. Yoshida, and K. Arai [Nucleic Acids Res. 14, 5777 (1986)].


Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.
Promiscuous gene expression (PGE) by thymic epithelial cells (TEC) is essential for generating a diverse T cell antigen receptor repertoire tolerant to self-antigens, and thus for avoiding autoimmunity. Nevertheless, the extent and nature of this unusual expression program within TEC populations and single cells are unknown. Using deep transcriptome sequencing of carefully identified mouse TEC subpopulations, we discovered a program of PGE that is common between medullary (m) and cortical TEC, further elaborated in mTEC, and completed in mature mTEC expressing the autoimmune regulator gene (Aire). TEC populations are capable of expressing up to 19,293 protein-coding genes, the highest number of genes known to be expressed in any cell type. Remarkably, in mouse mTEC, Aire expression alone positively regulates 3980 tissue-restricted genes. Notably, the tissue specificities of these genes include known targets of autoimmunity in human AIRE deficiency. Led by the observation that genes induced by Aire expression are generally characterized by a repressive chromatin state in somatic tissues, we found these genes to be strongly associated with H3K27me3 marks in mTEC. Our findings are consistent with AIRE targeting and inducing the promiscuous expression of genes previously epigenetically silenced by Polycomb group proteins. Comparison of the transcriptomes of 174 single mTEC indicates that genes induced by Aire expression are transcribed stochastically at low cell frequency. Furthermore, when present, Aire expression-dependent transcript levels were 16-fold higher, on average, in individual TEC than in the mTEC population.


Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials.
Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell-material interactions and suggest alternative research routes for evaluating biomaterials to improve their design.


Look again: effects of brain images and mind-brain dualism on lay evaluations of research.
Brain scans have frequently been credited with uniquely seductive and persuasive qualities, leading to claims that fMRI research receives a disproportionate share of public attention and funding. It has been suggested that functional brain images are fascinating because they contradict dualist beliefs regarding the relationship between the body and the mind. Although previous research has indicated that brain images can increase judgments of an article's scientific reasoning, the hypotheses that brain scans make research appear more interesting, surprising, or worthy of funding have not been tested. Neither has the relation between the allure of brain imaging and dualism. In the following three studies, laypersons rated both fictional research descriptions and real science news articles accompanied by brain scans, bar charts, or photographs. Across 988 participants, we found little evidence of neuroimaging's seductive allure or of its relation to self-professed dualistic beliefs. These results, taken together with other recent null findings, suggest that brain images are less powerful than has been argued.


GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.
Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems. Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines. The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel. To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions. Not only does this combination of algorithms enable extremely long simulations of large systems but also it provides that simulation performance on quite modest numbers of standard cluster nodes.


Steady-state ab initio laser theory for complex gain media.
We derive and test a generalization of the steady-state ab initio laser theory (SALT) to treat complex gain media. The generalized theory (C-SALT) is able to treat atomic and molecular gain media with diffusion and multiple lasing transitions, and semiconductor gain media in the free carrier approximation including fully the effect of Pauli blocking. The key assumption of the theory is stationarity of the level populations, which leads to coupled self-consistent equations for the populations and the lasing modes that fully include the effects of openness and non-linear spatial hole-burning. These equations can be solved efficiently for the steady-state lasing properties by a similar iteration procedure as in SALT, where a static gain medium with a single transition is assumed. The theory is tested by comparison to much less efficient finite difference time domain (FDTD) methods and excellent agreement is found. Using C-SALT to analyze the effects of varying gain diffusion constant we demonstrate a cross-over between the regime of strong spatial hole burning with multimode lasing to a regime of negligible spatial hole burning, leading to gain-clamping, and single mode lasing. The effect of spatially inhomogeneous pumping combined with diffusion is also studied and a relevant length scale for spatial inhomogeneity to persist under these conditions is determined. For the semiconductor gain model, we demonstrate the frequency shift due to Pauli blocking as the pumping strength changes.


Insect Arylalkylamine N-Acetyltransferases as Potential Targets for Novel Insecticide Design.
Crop protection against destructive pests has been at the forefront of recent agricultural advancements. Rapid adaptive evolution has led to insects becoming immune to the chemicals employed to quell their damage. Insecticide resistance is a serious problem that negatively impacts food production, food storage, human health, and the environment. To make matters more complicated are the strict regulations in place on insecticide development, driven by rising public concern relating to the harmful effects these chemicals have on the environment and on society. A key component to solving the problem of insecticide resistance, while keeping public welfare in mind, is the identification of novel insect-specific protein targets. One unexplored target for the development of new targeted insecticides are the insect arylalkylamine N-acetyltransferases (iAANATs). This group of enzymes, shown to be intrinsic in the development of the insect cuticle, is an untapped well of potential for target-specific inhibition, while offering enough variety to ensure protection for non-target enzymes. In this review, we highlight kinetic, genetic and bioinformatic data showing that the iAANATs are intriguing insecticide targets that should be specific only for particular insect pests. Such a pest-specific insecticide would minimize environmental harm by eliminating such non-discriminate attacks which have made insecticides such a highly regulated industry, and would have negligible toxicity to humans and other mammals.


Surgical patterns of care in patients with invasive breast cancer treated with neoadjuvant systemic therapy and breast magnetic resonance imaging: results of a secondary analysis of TBCRC 017.
Neoadjuvant chemotherapy (NCT) downstages advanced primary tumors, with magnetic resonance imaging (MRI) being the most sensitive imaging predictor of response. However, the impact of MRI evaluation on surgical treatment decisions in the neoadjuvant setting has not been well described. We report surgical patterns of care across 8 National Cancer Institute comprehensive cancer centers in women receiving both NCT and MRI to evaluate the impact of MRI findings on surgical planning. Seven hundred seventy women from 8 institutions received NCT with MRI obtained both before and after systemic treatment. Univariate and multivariate analyses of imaging, patient-, and tumor-related covariates associated with choice of breast surgery were conducted. MRI and surgical data were available on 759 of 770 patients. A total of 345 of 759 (45 %) patients received breast-conserving surgery and 414 of 759 (55 %) received mastectomy. Mastectomy occurred more commonly in patients with incomplete MRI response versus complete (58 vs. 43 %) (p = 0.0003). On multivariate analysis, positive estrogen receptor status (p = 0.02), incomplete MRI response (p = 0.0003), higher baseline T classification (p < 0.0001), younger age (p < 0.0006), and institution (p = 0.003) were independent predictors of mastectomy. A statistically significant trend toward increasing use of mastectomy with increasing T stage at presentation (p < 0.0001) was observed in patients with incomplete response by MRI only. Among women with complete response on MRI, 43 % underwent mastectomy. Within a multi-institutional cohort of women undergoing neoadjuvant treatment for breast cancer, MRI findings were not clearly associated with extent of surgery. This study shows that receptor status, T stage at diagnosis, young age, and treating institution are more significant determinants of surgical treatment choice than MRI response data.


Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery.
This study sought to evaluate the safety and efficacy of the CoreValve transcatheter heart valve (THV) for the treatment of severe aortic stenosis in patients at extreme risk for surgery. Untreated severe aortic stenosis is a progressive disease with a poor prognosis. Transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis is a potentially effective therapy. We performed a prospective, multicenter, nonrandomized investigation evaluating the safety and efficacy of self-expanding TAVR in patients with symptomatic severe aortic stenosis with prohibitive risks for surgery. The primary endpoint was a composite of all-cause mortality or major stroke at 12 months, which was compared with a pre-specified objective performance goal (OPG). A total of 41 sites in the United States recruited 506 patients, of whom 489 underwent attempted treatment with the CoreValve THV. The rate of all-cause mortality or major stroke at 12 months was 26.0% (upper 2-sided 95% confidence bound: 29.9%) versus 43.0% with the OPG (p < 0.0001). Individual 30-day and 12-month events included all-cause mortality (8.4% and 24.3%, respectively) and major stroke (2.3% and 4.3%, respectively). Procedural events at 30 days included life-threatening/disabling bleeding (12.7%), major vascular complications (8.2%), and need for permanent pacemaker placement (21.6%). The frequency of moderate or severe paravalvular aortic regurgitation was lower 12 months after self-expanding TAVR (4.2%) than at discharge (10.7%; p = 0.004 for paired analysis). TAVR with a self-expanding bioprosthesis was safe and effective in patients with symptomatic severe aortic stenosis at prohibitive risk for surgical valve replacement. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).


A functional network module for Smith-Magenis syndrome.
Disorders with overlapping diagnostic features are grouped into a network module. Based on phenotypic similarities or differential diagnoses, it is possible to identify functional pathways leading to individual features. We generated a Smith-Magenis syndrome (SMS)-specific network module utilizing patient clinical data, text mining from the Online Mendelian Inheritance in Man database, and in vitro functional analysis. We tested our module by functional studies based on a hypothesis that RAI1 acts through phenotype-specific pathways involving several downstream genes, which are altered due to RAI1 haploinsufficiency. A preliminary genome-wide gene expression study was performed using microarrays on RAI1 haploinsufficient cells created by RNAi-based approximately 50% knockdown of RAI1 in HEK293T cells. The top dysregulated genes were involved in growth signaling and insulin sensitivity, neuronal differentiation, lipid biosynthesis and fat mobilization, circadian activity, behavior, renal, cardiovascular and skeletal development, gene expression, and cell-cycle regulation and recombination, reflecting the spectrum of clinical features observed in SMS. Validation using real-time quantitative reverse transcriptase polymerase chain reaction confirmed the gene expression profile of 75% of the selected genes analyzed in both HEK293T RAI1 knockdown cells and SMS lymphoblastoid cell lines. Overall, these data support a method for identifying genes and pathways responsible for individual clinical features in a complex disorder such as SMS.


Reconciling sectoral abatement strategies with global climate targets: the case of the Chinese passenger vehicle fleet.
The IPCC Forth Assessment Report postulates that global warming can be limited to 2 °C by deploying technologies that are currently available or expected to be commercialized in the coming decades. However, neither specific technological pathways nor internationally binding reduction targets for different sectors or countries have been established yet. Using the passenger car stock in China as example we compute direct CO(2) emissions until 2050 depending on population, car utilization, and fuel efficiency and compare them to benchmarks derived by assuming even contribution of all sectors and a unitary global per capita emission quota. Compared to present car utilization in industrialized countries, massive deployment of prototypes of fuel efficient cars could reduce emissions by about 45%, and moderately lower car use could contribute with another 33%. Still, emissions remain about five times higher than the benchmark for the 2 °C global warming target. Therefore an extended analysis, including in particular low-carbon fuels and the impact of urban and transport planning on annual distance traveled and car ownership, should be considered. A cross-sectoral comparison could reveal whether other sectors could bear an overproportional reduction quota instead. The proposed model offers direct interfaces to material industries, fuel production, and scrap vehicle supply.


Quantitative transcriptomics, and lipidomics in evaluating ovarian developmental effects in Atlantic cod (Gadus morhua) caged at a capped marine waste disposal site.
In the present study, a previously capped waste disposal site at Kollevåg (Norway) was selected to study the effects of contaminant leakage on biomarkers associated with Atlantic cod (Gadus morhua) reproductive endocrinology and development. Immature cod were caged for 6 weeks at 3 locations, selected to achieve a spatial gradient of contamination, and compared to a reference station. Quantitative transcriptomic, and lipidomic analysis was used to evaluate the effects of the potential complex contaminant mixture on ovarian developmental and endocrine physiology. The number of expressed transcripts, with 0.75 log2-fold differential expression or more, varied among stations and paralleled the severity of contamination. Particularly, significant bioaccumulation of ∑PCB-7, ∑DDTs and ∑PBDEs were observed at station 1, compared to the other station, including the reference station. Respectively 1416, 698 and 719 differentially expressed genes (DEGs), were observed at stations 1, 2 and 3, compared to the reference station, with transcripts belonging to steroid hormone synthesis pathway being significantly upregulation. Transcription factors such as esr2 and ahr2 were increased at all three stations, with highest fold-change at Station 1. MetaCore pathway maps identified affected pathways that are involved in ovarian physiology, where some unique pathways were significantly affected at each station. For the lipidomics, sphingolipid metabolism was particularly affected at station 1, and these effects paralleled the high contaminant burden at this station. Overall, our findings showed a novel and direct association between contaminant burden and ovarian toxicological and endocrine physiological responses in cod caged at the capped Kollevåg waste disposal site.


High-Resolution Monitoring of Antimicrobial Consumption in Vietnamese Small-Scale Chicken Farms Highlights Discrepancies Between Study Metrics.
Chicken is, among farmed species, the target of the highest levels of antimicrobial use (AMU). There are considerable knowledge gaps on how and when antimicrobials are used in commercial small-scale chicken farms. These shortcomings arise from cross-sectional study designs and poor record keeping practiced by many such farmers. Furthermore, there is a large diversity of AMU metrics, and it is not clear how these metrics relate to each other. We performed a longitudinal study on a cohort of small-scale chicken farms (n = 102) in the Mekong Delta (Vietnam), an area regarded as a hotspot of AMU, from October 2016 to May 2018. We collected data on all medicine products administered to 203 flocks with the following aims: (1) to describe types and quantities of antimicrobial active ingredients (AAIs) used; (2) to describe critical time points of AMU; and (3) to compare AMU using three quantitative metrics: (a) weight of AAIs related to bird weight at the time of treatment (mg/kg at treatment); (b) weight of AAIs related to weight of birds sold (mg/kg sold); and (c) "treatment incidence" (TI), or the number of daily doses per kilogram of live chicken [Vietnamese animal daily dose (ADDvetVN)] per 1,000 days. Antimicrobials contained in commercial feed, administered by injection (n = N = 6), or antimicrobials for human medicine (n = N = 16) were excluded. A total of 236 products were identified, containing 42 different AAIs. A total of 76.2% products contained AAIs of "critical importance" according to the World Health Organization (WHO). On average, chickens consumed 791.8 (SEM ±16.7) mg/kg at treatment, 323.4 (SEM ±11.3) mg/kg sold, and the TI was 382.6 (SEM ±5.5) per 1,000 days. AMU was more common early in the production cycle and was highly skewed, with the upper 25% quantile of flocks accounting for 60.7% of total AMU. The observed discrepancies between weight- and dose-based metrics were explained by differences in the strength of AAIs, mortality levels, and the timing of administration. Results suggest that in small-scale chicken production, AMU reduction efforts should preferentially target the early (brooding) period, which is when birds are most likely to be exposed to antimicrobials, whilst restricting access to antimicrobials of critical importance for human medicine.


Effects of upper-body sprint-interval training on strength and endurance capacities in female cross-country skiers.
This study compared the effects of adding upper-body sprint-intervals or continuous double poling endurance training to the normal training on maximal upper-body strength and endurance capacity in female cross-country skiers. In total, 17 female skiers (age: 18.1±0.8yr, body mass: 60±7 kg, maximal oxygen uptake (VO2max): 3.30±0.37 L.min-1) performed an 8-week training intervention. Here, either two weekly sessions of six to eight 30-s maximal upper-body double poling sprint-intervals (SIG, n = 8) or 45-75 min of continuous low-to-moderate intensity double poling on roller skis (CG, n = 9) were added to their training. Before and after the intervention, the participants were tested for physiological and kinematical responses during submaximal and maximal diagonal and double poling treadmill roller skiing. Additionally, we measured maximal upper-body strength (1RM) and average power at 40% 1RM in a poling-specific strength exercise. SIG improved absolute VO2max in diagonal skiing more than CG (8% vs 2%, p<0.05), and showed a tendency towards higher body-mass normalized VO2max (7% vs 2%, p = 0.07). Both groups had an overall improvement in double poling peak oxygen uptake (10% vs 6% for SIG and CG) (both p<0.01), but no group-difference was observed. SIG improved 1RM strength more than CG (18% vs 10%, p<0.05), while there was a tendency for difference in average power at 40% 1RM (20% vs 14%, p = 0.06). Oxygen cost and kinematics (cycle length and rate) in double poling and diagonal remained unchanged in both groups. In conclusion, our study demonstrates that adding upper-body sprint-interval training is more effective than continuous endurance training in improving upper-body maximal strength and VO2max.


Ultrasonography of the urinary tract of female sheep.
We determined the position, dimensions, and structure of the kidneys, ureters, bladder, and urethra of 62 female sheep by use of ultrasonography. A 5.0-MHz convex transducer was placed over the right flank to examine the kidneys, and a 5.0 MHz-linear transducer was used to examine the bladder and urethra transrectally. All examinations were performed on sheep in standing position. The left kidney was 7.1 to 8.9 cm long, 3.4 to 5.5 cm wide, and 3.3 to 4.7 cm deep. Diameter of the parenchyma and renal sinus of the left kidney ranged between 1.1 and 1.9 cm and 1.1 and 2.0 cm, respectively. Circumference of the medullary pyramids varied between 2.1 and 3.3 cm. Similar ultrasonographic measurements were obtained for the right kidney. The diameter of the bladder varied between 0.3 and 6.9 cm in 96.8% of the sheep. The diameter of the bladder could not be determined in 32% of the sheep because it was > 10 cm, and, therefore, was beyond the penetration depth of the scanner. The only part of the urethra that could be ultrasonographically visualized was the internal urethral orifice. It had diameter between 0.1 and 0.2 cm. The ureters could not be ultrasonographically visualized in any of the sheep examined. The urinary tract of 8 sheep was examined 10 times within 2 weeks to examine whether measurements were reproducible. The interassay variation coefficient determined ranged from 3.1 to 31.8%, although for most variables, it ranged between 5 and 11%.(ABSTRACT TRUNCATED AT 250 WORDS)


Measuring, evaluating and improving the effectiveness of invasive predator control programs: Feral cat baiting as a case study.
Reducing the impacts of invasive predators is a key objective for conservation managers, livestock producers and human health agencies globally. The efficacy of invasive predator control programs, however, is highly variable. To improve control efficacy, managers require a fundamental understanding of the factors that contribute to the success or failure of a control program. Using a predator baiting program as a case study, we measured the efficacy of baiting as a control tool to significantly reduce feral cat (Felis catus) populations. We used camera traps and cat-borne GPS collars to monitor changes in feral cat populations at a baited site and an unbaited site, using a Before-After, Control-Impact (BACI) design. We also identified five key elements required for a successful baiting program (bait encounter rate, availability, attractiveness, palatability and lethality) and simultaneously measured these to identify areas for potential improvement. Baiting was ineffective at reducing feral cat populations; collared cat mortality was only 11% (1/9), with camera traps revealing negligible reductions in the number of cat detection events (9%), naïve occupancy (15%), and no significant change in the relative abundance of feral cats (F1,54 = 0.8641, P = 0.357). Several factors contributed to the poor control efficacy. Bait encounter rates were low, with cats active along tracks (where baits were laid) < 4% of the time. Cats encountered only 14% (7/50) of monitored baits, but none were eaten. Initially, baits appeared attractive to cats; however meat ants and desiccation rapidly decreased bait palatability. Bait availability to cats declined rapidly, with 36% of monitored baits (18/50) removed by non-target species within the first 48 h. The mortality of one collared cat and chemical assays confirmed that, on average, each bait contained sufficient 1080 to kill a large (>5 kg) feral cat. Our findings suggest that altering bait deployment patterns, increasing bait densities and improving bait palatability could potentially improve the efficacy of baiting programs to reduce feral cat populations. Our study provides a framework to measure and evaluate the key elements that contribute to efficacy of pest control programs, and to identify opportunities for improving outcomes of future control programs.


Predictors of discharge destination in a geriatric population after undergoing rehabilitation.
Patients undertaking inpatient rehabilitation comprise a diverse group, including patients with stroke and other neurological conditions, patients who have fallen with or without a resulting fracture, and patients with joint replacements, general debility, or various cardiopulmonary conditions. It is not clear whether diagnosis has an impact on discharge destination in a heterogeneous patient group. The purpose of this study was to determine whether diagnostic category matters or whether it is rehabilitation length of stay (LOS), ability on the 10-Meter Walk Test (10MWT), or Balance Outcome Measure for Elder Rehabilitation (BOOMER) at discharge that predicts discharge destination in elderly patients undergoing rehabilitation who had previously lived at home. A retrospective audit was undertaken at a single rehabilitation facility in South East Queensland, Australia, that serviced 4 local short-term care hospitals. Participants were admitted consecutively to the facility between June 2010 and March 2012 who met inclusion criteria. These included a primary diagnosis category of orthopedic conditions, debility, stroke, and other neurological conditions according to the Australasian Rehabilitation Outcomes Centre and older than 60 years (n = 248). Interventions while being a rehabilitation inpatient comprised usual care physiotherapy individually tailored and incorporating elements of balance, strengthening, and functional exercise. Main outcome measures were discharge to residential aged care facility (RACF) versus home, differences between diagnostic categories in terms of discharge destination, LOS, and performance on outcome measures. Prediction of discharge destination by LOS, 10MWT, and BOOMER performance at discharge was explored. A total of 28 patients (12.3%) were discharged to RACF. Diagnosis was not correlated with discharge destination (Pearson χ2 = 1.26, P = .74). The variables rehabilitation LOS, an inability to perform the 10MWT at discharge, and discharge BOOMER score of less than 4 can predict discharge destination with 86.4% accuracy (P = .002). This model had a sensitivity of 71.4% (discharge to RACF) and specificity of 93.3% (discharge home). To return home after rehabilitation, patients need to be able to walk at least 10 m and undertake tasks such as moving from sitting to standing, turning around, as well as managing steps. The study revealed that a standardized suite of measures of functional ability and balance may not be appropriate for patients in all diagnostic categories undergoing rehabilitation. Therefore, just as intervention needs to be tailored for the individual patient, the measure of their progress also should be unique.


Optical antennas with multiple plasmonic nanoparticles for tip-enhanced Raman microscopy.
Tip-enhanced Raman spectroscopy (TERS) has recently become one of the most important tools for analyzing advanced nano-devices and nano-materials, because it allows strong enhancement of weak Raman signal from the nanometric volume of a sample. However, consistent enhancement in TERS is still an issue and scientists have been struggling to fabricate good tips for reliable, strong and reproducible enhancement. There is a strong need to study the morphology and the arrangement of metal nanostructures near the tip apex for efficient plasmonic enhancement in TERS. Here, we present a study on the metal grains attached to the tip surface for producing higher and much consistent enhancement in TERS. Our study shows that the plasmonic enhancement strongly depends on the number of grains and on the their separations. We found through simulations that multiple grains arranged closely but discretely on a dielectric probe act as an efficient plasmonic antenna and that enhancement in TERS is maximum for an optimized number of grains. The number of grains and the nano-gap between them are crucial for reproducible enhancement. This promising result, which we also demonstrate and prove by experiments, will bring TERS to a new level, where it can be utilized with more confidence of large reproducible enhancement for those nano-sized samples that have extremely weak Raman scattering.


Mandarin Electrolaryngeal Speech Recognition Based on WaveNet-CTC.
Purpose The application of Chinese Mandarin electrolaryngeal (EL) speech for laryngectomees has been limited by its drawbacks such as single fundamental frequency, mechanical sound, and large radiation noise. To improve the intelligibility of Chinese Mandarin EL speech, a new perspective using the automatic speech recognition (ASR) system was proposed, which can convert EL speech into healthy speech, if combined with text-to-speech. Method An ASR system was designed to recognize EL speech based on a deep learning model WaveNet and the connectionist temporal classification (WaveNet-CTC). This system mainly consists of 3 parts: the acoustic model, the language model, and the decoding model. The acoustic features are extracted during speech preprocessing, and 3,230 utterances of EL speech mixed with 10,000 utterances of healthy speech are used to train the ASR system. Comparative experiment was designed to evaluate the performance of the proposed method. Results The results show that the proposed ASR system has higher stability and generalizability compared with the traditional methods, manifesting superiority in terms of Chinese characters, Chinese words, short sentences, and long sentences. Phoneme confusion occurs more easily in the stop and affricate of EL speech than the healthy speech. However, the highest accuracy of the ASR could reach 83.24% when 3,230 utterances of EL speech were used to train the ASR system. Conclusions This study indicates that EL speech could be recognized effectively by the ASR based on WaveNet-CTC. This proposed method has a higher generalization performance and better stability than the traditional methods. A higher accuracy of the ASR system based on WaveNet-CTC can be obtained, which means that EL speech can be converted into healthy speech. Supplemental Material https://doi.org/10.23641/asha.8250830.


On the use of antibodies in studies on glucocorticoid receptor structure.
Limited proteolysis of the glucocorticoid receptor has proven to be a valuable tool for a functional analysis of the receptor protein. With the help of these analyses, it has been possible to describe three functional domains of the receptor protein. The native glucocorticoid-receptor complex contains a steroid-binding domain (A), a DNA-binding domain (B) and an immunoactive domain (C). This form of the glucocorticoid receptor has a Stokes radius of 6.1 nm and a molecular weight of 94 K when purified. Two steroid-binding proteolytic receptor fragments can be found. The larger one has a Stokes radius of 3.3 - 3.6 nm and a molecular weight of 39 K and contains both the steroid- and DNA-binding sites (A + B). The smaller steroid-binding receptor fragment, with a Stokes radius of 1.9 nm and a molecular weight of 27 K, contains only the steroid-binding domain (A). Analysis of the proteolytic fragments of the glucocorticoid receptor using the specific anti-receptor antibodies revealed the occurrence of a fragment with Stokes radius 2.6 nm following limited proteolysis of the receptor by alpha-chymotrypsin. This fragment contains neither the steroid-binding nor the DNA-binding domains but consists only of the immunoactive domain (C). Further proteolysis of this fragment results in an even smaller form with Stokes radius 1.4 nm. The apparent identity of the larger of the two proteolytic forms of the glucocorticoid receptor (the 3.3 - 3.6 nm form) with the receptor isolated from certain corticosteroid-resistant cells, together with the lack of the immunoreactive domain in these cells appears to indicate an important function of this domain with regard to the biological activity of the receptor.


Arcobacter butzleri Induce Colonic, Extra-Intestinal and Systemic Inflammatory Responses in Gnotobiotic IL-10 Deficient Mice in a Strain-Dependent Manner.
The immunopathological impact of human Arcobacter (A.) infections is under current debate. Episodes of gastroenteritis with abdominal pain and acute or prolonged watery diarrhea were reported for A. butzleri infected patients. Whereas adhesive, invasive and cytotoxic capacities have been described for A. butzleri in vitro, only limited information is available about the immunopathogenic potential and mechanisms of infection in vivo. Gnotobiotic IL-10-/- mice were generated by broad-spectrum antibiotic treatment and perorally infected with the A. butzleri strains CCUG 30485 and C1 shown to be invasive in cell culture assays. Bacterial colonization capacities, clinical conditions, intestinal, extra-intestinal and systemic immune responses were monitored at day six and 16 postinfection (p.i.). Despite stable intestinal A. butzleri colonization at high loads, gnotobiotic IL-10-/- mice were virtually unaffected and did not display any overt symptoms at either time point. Notably, A. butzleri infection induced apoptosis of colonic epithelial cells which was paralleled by increased abundance of proliferating cells. Furthermore A. butzleri infection caused a significant increase of distinct immune cell populations such as T and B cells, regulatory T cells, macrophages and monocytes in the colon which was accompanied by elevated colonic TNF, IFN-γ, nitric oxide (NO), IL-6, IL-12p70 and MCP-1 concentrations. Strikingly, A. butzleri induced extra-intestinal and systemic immune responses as indicated by higher NO concentrations in kidney and increased TNF, IFN-γ, IL-12p70 and IL-6 levels in serum samples of infected as compared to naive mice. Overall, inflammatory responses could be observed earlier in the course of infection by the CCUG 30485 as compared to the C1 strain. Peroral A. butzleri infection induced not only intestinal but also extra-intestinal and systemic immune responses in gnotobiotic IL-10-/- mice in a strain-dependent manner. These findings point towards an immunopathogenic potential of A. butzleri in vertebrate hosts.


Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism?
In most countries, millions of people are relying on herbal medicines as remedy for numerous ailments. In South-East Asia, Eurycoma longifolia Jack, also known as 'Malaysian ginseng' or Tongkat ali, is used to combat stress and disease and to improve physical strength. Moreover, the compounds of the roots of this plant are reported to have aphrodisiac and testosterone enhancing effects in the rat. Considering that human studies are not available, 76 of 320 patients suffering from late-onset hypogonadism (LOH) were given 200 mg of a standardised water-soluble extract of Tongkat ali for 1 month. The Ageing Males' Symptoms (AMS) according to the standardised rating scale and the serum testosterone concentration were taken. Results show that treatment of LOH patients with this Tongkat ali extract significantly (P < 0.0001) improved the AMS score as well as the serum testosterone concentration. While before treatment only 10.5% of the patients did not show any complaint according to the AMS scale and 35.5% had normal testosterone levels, after the completed treatment 71.7% and 90.8% of the patients showed normal values, respectively. Thus, Tongkat ali extract appears to be useful as a supplement in overcoming the symptoms of LOH and for the management of hypogonadism.


Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism.
The cone cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. This channel is composed of two structurally related subunits, CNGA3 and CNGB3; CNGA3 is the ion-conducting subunit, whereas CNGB3 is a modulatory subunit. Mutations in both subunits are associated with achromatopsia and progressive cone dystrophy, with mutations in CNGB3 alone accounting for 50% of all known cases of achromatopsia. However, the molecular mechanisms underlying cone diseases that result from CNGB3 deficiency are unknown. This study investigated the role of CNGB3 in cones, using CNGB3(-/-) mice. Cone dysfunction was apparent at the earliest time point examined (post-natal day 30) in CNGB3(-/-) mice. When compared with wild-type (WT) controls: photopic electroretingraphic (ERG) responses were decreased by approximately 75%, whereas scotopic ERG responses were unchanged; visual acuity was decreased by approximately 20%, whereas contrast sensitivity was unchanged; cone density was reduced by approximately 40%; photoreceptor apoptosis was detected; and outer segment disorganization was observed in some cones. Notably, CNGA3 protein and mRNA levels were significantly decreased in CNGB3(-/-) mice; in contrast, mRNA levels of S-opsin, Gnat2 and Pde6c were unchanged, relative to WT mice. Hence, we show that loss of CNGB3 reduces biosynthesis of CNGA3 and impairs cone CNG channel function. We suggest that down-regulation of CNGA3 contributes to the pathogenic mechanism by which CNGB3 mutations lead to human cone disease.


The effect of massage therapy on occupational stress of Intensive Care Unit nurses.
One of the main causes of stress in the lives of people is their jobs. Occupational stress is causing a wide range of significant issues in health and community services. Nursing is the most stressful profession in the health services. Massage therapy is one way of coping with stress. This study was conducted to determine the effect of massage therapy on stress in nurses. This study was a clinical trial on 66 male and female nurses working in intensive care units (dialysis, ICU, and CCU) of Isfahan University of Medical Sciences, Iran, in 2013. Participants were selected according to the aims and inclusion criteria of the study. Then, they were randomly divided into experimental and control groups. The Occupational Stress Inventory (OSI) (Osipow and Spokane, 1987) was completed by participants of the two groups before, immediately after, and 2 weeks after the intervention. General Swedish massage was performed on participants of the experimental group for 25 min in each session, twice a week for 4 weeks. Data were analyzed by descriptive and inferential statistics [Chi-square, t-test, and repeated measures analysis of variance (ANOVA)] using SPSS software. Results showed that the difference in overall mean occupation stress scores between experimental and control groups 2 weeks after the intervention was significant (P < 0.001). According to the results, it is recommended that massage, as a valuable noninvasive method, be used for nurses in intensive care units to reduce their stress, promote mental health, and prevent the decrease in quality of nursing work life.


Characterisation of light responses in the retina of mice lacking principle components of rod, cone and melanopsin phototransduction signalling pathways.
Gnat(-/-), Cnga3(-/-), Opn4(-/-) triple knockout (TKO) mice lack essential components of phototransduction signalling pathways present in rods, cones and photosensitive retinal ganglion cells (pRGCs), and are therefore expected to lack all sensitivity to light. However, a number of studies have shown that light responses persist in these mice. In this study we use multielectrode array (MEA) recordings and light-induced c-fos expression to further characterise the light responses of the TKO retina. Small, but robust electroretinogram type responses are routinely detected during MEA recordings, with properties consistent with rod driven responses. Furthermore, a distinctive pattern of light-induced c-fos expression is evident in the TKO retina, with c-fos expression largely restricted to a small subset of amacrine cells that express disabled-1 (Dab1) but lack expression of glycine transporter-1 (GlyT-1). Collectively these data are consistent with the persistence of a novel light sensing pathway in the TKO retina that originates in rod photoreceptors, potentially a rare subset of rods with distinct functional properties, and which is propagated to an atypical subtype of AII amacrine cells. Furthermore, the minimal responses observed following UV light stimulation suggest only a limited role for the non-visual opsin OPN5 in driving excitatory light responses within the mouse retina.


Surgical Outcomes for Minimally Invasive vs Open Transforaminal Lumbar Interbody Fusion: An Updated Systematic Review and Meta-analysis.
Minimally invasive transforaminal lumbar interbody fusion (TLIF)-or MI-TLIF-has been increasing in prevalence compared with open TLIF (O-TLIF) procedures. The use of MI-TLIF is an evolving technique with conflicting reports in the literature about outcomes. To investigate the impact of MI-TLIF in comparison with O-TLIF for early and late outcomes by using the Visual Analog Scale for back pain (VAS-back) and the Oswestry Disability Index (ODI). Secondary end points include blood loss, operative time, radiation exposure, length of stay, fusion rates, and complications between the 2 procedures. During August 2014, a systematic literature search was performed identifying 987 articles. Of these, 30 met inclusion criteria. A random-effects meta-analysis was performed by using both pooled and subset analyses based on study type. Our meta-analysis demonstrated that MI-TLIF reduced blood loss (P < .001), length of stay (P < .001), and complications (P = .001) but increased radiation exposure (P < .001). No differences were found in fusion rate (P = .61) and operative time (P = .34). A decrease in late VAS-back scores was demonstrated for MI TLIF (P < .001), but no differences were found in early VAS-back, early ODI, and late ODI. MI-TLIF is associated with reduced blood loss, decreased length of stay, decreased complication rates, and increased radiation exposure. The rates of fusion and operative time are similar between MI-TLIF and O-TLIF. Differences in long-term outcomes in MI-TLIF vs O-TLIF are inconclusive and require more research, particularly in the form of large, multi-institutional prospective randomized controlled trials. CI, confidence intervalMCID, minimal clinically important differenceMI-TLIF, minimally invasive transforaminal lumbar interbody fusionODI, Oswestry Disability IndexO-TLIF, open transforaminal lumbar interbody fusionVAS, Visual Analog Scale.


Preterm Neuroimaging and School-Age Cognitive Outcomes.
Children born extremely preterm are at risk for cognitive difficulties and disability. The relative prognostic value of neonatal brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear. Our objectives were to relate near-term conventional brain MRI and early and late CUS to cognitive impairment and disability at 6 to 7 years among children born extremely preterm and assess prognostic value. A prospective study of adverse early and late CUS and near-term conventional MRI findings to predict outcomes at 6 to 7 years including a full-scale IQ (FSIQ) <70 and disability (FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated associations of neuroimaging with outcomes, adjusting for perinatal-neonatal factors. A total of 386 children had follow-up. In unadjusted analyses, severity of white matter abnormality and cerebellar lesions on MRI and adverse CUS findings were associated with outcomes. In full regression models, both adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0-129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1-6.7) remained associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI 3.6-111) were associated with FSIQ <70. Predictive accuracy of stepwise models was not substantially improved with the addition of neuroimaging. Severe but rare adverse late CUS findings were most strongly associated with cognitive impairment and disability at school age, and significant cerebellar lesions on MRI were associated with disability. Near-term conventional MRI did not substantively enhance prediction of severe early school-age outcomes.