The occurrence of thyroid focal lesions and a need for fine needle aspiration biopsy in patients with acromegaly due to an increased risk of thyroid cancer.
The high prevalence of goiter in acromegalic patients is well known. Several studies revealed increased frequency of thyroid carcinoma in these patients. The aim of the study was to evaluate the incidence of thyroid lesions, including thyroid cancer in acromegalic patients and to estimate possible factors influencing their occurrence, especially high IGF-1 level. 86 consecutive patients with acromegaly were retrospectively analyzed. 45 patients had been previously treated for acromegaly and 41 were newly diagnosed. In all subjects hGH, IGF-1, TSH, FT4 levels were determined. Thyroid gland was evaluated in ultrasound examination. Fine needle aspiration biopsy (FNAB) was performed in every solid or mixed thyroid nodule. Thyroid morphology abnormalities were found in 75 patients (87.2%). 10 patients (11.6%) had diffuse goiter and 65 patients (75.6%) had nodular goiter. There were 5 cases of thyroid carcinoma (5.8%): 3 papillary carcinomas and two follicular variants of papillary cancer. Out of five cancers three were multifocal, one infiltrated thyroid capsule and one was diagnosed at the stage of metastases to four lymph nodes. Our study confirmed common co-existence of acromegaly and thyroid lesions. Furthermore, it revealed considerably high occurrence of thyroid carcinoma in these patients. In view of this correlation, the potential role of IGF-1 in pathogenesis of benign and malignant thyroid neoplasms should be considered. Due to high frequency of thyroid cancer in acromegalic patients, we suggest to perform fine needle aspiration biopsy in each case of thyroid nodule.


Effects of Locomotion on Visual Responses in the Mouse Superior Colliculus.
Visual responses are extensively shaped by internal factors. This effect is drastic in the primary visual cortex (V1), where locomotion profoundly increases visually-evoked responses. Here we investigate whether a similar effect exists in another major visual structure, the superior colliculus (SC). By performing two-photon calcium imaging of head-fixed male and female mice running on a treadmill, we find that only a minority of neurons in the most superficial lamina of the SC display significant changes during locomotion. This modulation includes both increase and decrease in response amplitude and is similar between excitatory and inhibitory neurons. The overall change in the SC is small, whereas V1 responses almost double during locomotion. Additionally, SC neurons display lower response variability and less spontaneous activity than V1 neurons. Together, these experiments indicate that locomotion-dependent modulation is not a widespread phenomenon in the early visual system and that the SC and V1 use different strategies to encode visual information.SIGNIFICANCE STATEMENT Visual information captured by the retina is processed in parallel through two major pathways, one reaching the primary visual cortex through the thalamus, and the other projecting to the superior colliculus. The two pathways then merge in the higher areas of the visual cortex. Recent studies have shown that behavioral state such as locomotion is an essential component of vision and can strongly affect visual responses in the thalamocortical pathway. Here we demonstrate that neurons in the mouse superior colliculus and primary visual cortex display striking differences in their modulation by locomotion, as well as in response variability and spontaneous activity. Our results reveal an important "division of labor" in visual processing between these two evolutionarily distinct structures.


Wave turbulence in quantum fluids.
Wave turbulence (WT) occurs in systems of strongly interacting nonlinear waves and can lead to energy flows across length and frequency scales much like those that are well known in vortex turbulence. Typically, the energy passes although a nondissipative inertial range until it reaches a small enough scale that viscosity becomes important and terminates the cascade by dissipating the energy as heat. Wave turbulence in quantum fluids is of particular interest, partly because revealing experiments can be performed on a laboratory scale, and partly because WT among the Kelvin waves on quantized vortices is believed to play a crucial role in the final stages of the decay of (vortex) quantum turbulence. In this short review, we provide a perspective on recent work on WT in quantum fluids, setting it in context and discussing the outlook for the next few years. We outline the theory, review briefly the experiments carried out to date using liquid H2 and liquid (4)He, and discuss some nonequilibrium excitonic superfluids in which WT has been predicted but not yet observed experimentally. By way of conclusion, we consider the medium- and longer-term outlook for the field.


Persistent Risk-Related Worry as a Function of Recalled Exposure to the Deepwater Horizon Oil Spill and Prior Trauma.
Large oil spills are disasters associated with psychological effects for exposed communities. The amount of worry that individuals experience after a disaster may be influenced by many factors, such as the type and extent of exposure to disaster impacts, prior trauma, and sociodemographic characteristics. This study examined the nature and predictors of worry about ongoing impacts of the 2010 Deepwater Horizon (DH) oil spill reported by Gulf of Mexico coastal residents. A random sample of 2,520 adult residents of Gulf of Mexico coastal counties were administered a telephone survey in 2016, including items about persistent worry and exposure to DH impacts, prior trauma, residence at the time of the spill, and sociodemographic characteristics. Respondents varied in the amount of worry they reported about ongoing health, social, and economic impacts. Controlling for sociodemographic characteristics, higher exposure to the DH oil spill was related to higher levels of worry about ongoing impacts, with past traumatic events related specifically to worry about health impacts. Unexpectedly, those who moved into the region after the spill showed similar levels of worry to residents exposed to the spill, and higher levels than residents who did not recall being exposed to the DH oil spill. This study highlights the impact of the DH oil spill on coastal residents many years after the DH disaster. The findings underscore the need to examine multiple pathways by which individuals experience disasters and for risk researchers to close knowledge gaps about long-term impacts of oil spills within a multi-dimensional framework.


Effect of micronized progesterone on bone turnover in postmenopausal women on estrogen replacement therapy.
To determine whether daily oral micronized progesterone affects bone turnover, as estimated by serum and urine biochemical markers, in postmenopausal women on long-term estrogen replacement therapy (ERT). We recruited 14 women aged 65 or older to participate in a 9-week trial with micronized progesterone. Each woman had undergone a hysterectomy and was on unopposed ERT at time of study entry. Women received micronized progesterone 100 mg twice daily in the first week and then received 200 mg twice daily in weeks 2-9. We measured markers of bone turnover in serum and urine collected at baseline and at 3 weeks, 6 weeks, and 9 weeks on treatment. Markers of bone formation were serum bone alkaline phosphatase (BAP), N-terminal procollagen peptides (PINP), and osteocalcin (OC). Markers of bone resorption were urinary cross-linked N-terminal and C-terminal telopeptides of type I collagen. In addition, we measured serum progesterone, estradiol and sex hormone binding globulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL)-cholesterol levels at baseline and at 9 weeks on treatment. Mean serum progesterone levels increased from 1.6 +/- 1.1 to 15.2 +/- 3.9 ng/mL, which was within the luteal phase range (3-25 ng/mL). Crosslinked C-telopeptides of type I collagen and osteocalcin increased significantly (p < 0.05) with progesterone treatment, however, other bone markers did not change. Estradiol, estrone, and SHBG levels did not change with treatment. High-density lipoprotein-cholesterol levels decreased 19% (p < 0.001) at 9 weeks on treatment compared to baseline but total and low-density lipoprotein (LDL) cholesterol and triglycerides did not change with treatment. In postmenopausal women on long-term estrogen replacement therapy, micronized progesterone (400 mg/d) increased one marker each of bone resorption and bone formation. Other sensitive markers of bone turnover did not change with treatment. Further, micronized progesterone decreased HDL-cholesterol in these women. Our data do not support a beneficial effect of micronized progesterone on bone or cardiovascular risk factors in postmenopausal women.


Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age.
Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. However, estimates of the RSV hospitalization burden have varied, and precision has been limited by the use of age strata grouped in blocks of 6 to ≥ 12 months. We analyzed data from a 5-year, prospective, population-based surveillance for young children who were hospitalized with laboratory-confirmed (reverse-transcriptase polymerase chain reaction) RSV acute respiratory illness (ARI) during October through March 2000-2005. The total population at risk was stratified by month of age by birth certificate information to yield hospitalization rates. There were 559 (26%) RSV-infected children among the 2149 enrolled children hospitalized with ARI (85% of all eligible children with ARI). The average RSV hospitalization rate was 5.2 per 1000 children <24 months old. The highest age-specific rate was in infants 1 month old (25.9 per 1000 children). Infants ≤ 2 months of age, who comprised 44% of RSV-hospitalized children, had a hospitalization rate of 17.9 per 1000 children. Most children (79%) were previously healthy. Very preterm infants (<30 weeks' gestation) accounted for only 3% of RSV cases but had RSV hospitalization rates 3 times that of term infants. Young infants, especially those who were 1 month old, were at greatest risk of RSV hospitalization. Four-fifths of RSV-hospitalized infants were previously healthy. To substantially reduce the burden of RSV hospitalizations, effective general preventive strategies will be required for all young infants, not just those with risk factors.


Recurrence of carbamoyl phosphate synthetase 1 (CPS1) deficiency in Turkish patients: characterization of a founder mutation by use of recombinant CPS1 from insect cells expression.
Carbamoyl phosphate synthetase 1 (CPS1) deficiency due to CPS1 mutations is a rare autosomal-recessive urea cycle disorder causing hyperammonemia that can lead to death or severe neurological impairment. CPS1 catalyzes carbamoyl phosphate formation from ammonia, bicarbonate and two molecules of ATP, and requires the allosteric activator N-acetyl-L-glutamate. Clinical mutations occur in the entire CPS1 coding region, but mainly in single families, with little recurrence. We characterized here the only currently known recurrent CPS1 mutation, p.Val1013del, found in eleven unrelated patients of Turkish descent using recombinant His-tagged wild type or mutant CPS1 expressed in baculovirus/insect cell system. The global CPS1 reaction and the ATPase and ATP synthesis partial reactions that reflect, respectively, the bicarbonate and the carbamate phosphorylation steps, were assayed. We found that CPS1 wild type and V1013del mutant showed comparable expression levels and purity but the mutant CPS1 exhibited no significant residual activities. In the CPS1 structural model, V1013 belongs to a highly hydrophobic β-strand at the middle of the central β-sheet of the A subdomain of the carbamate phosphorylation domain and is close to the predicted carbamate tunnel that links both phosphorylation sites. Haplotype studies suggested that p.Val1013del is a founder mutation. In conclusion, the mutation p.V1013del inactivates CPS1 but does not render the enzyme grossly unstable or insoluble. Recurrence of this particular mutation in Turkish patients is likely due to a founder effect, which is consistent with the frequent consanguinity observed in the affected population.


Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein.
Usher syndrome type III (USH3) is characterized by progressive loss of hearing and vision, and varying degrees of vestibular dysfunction. It is caused by mutations that affect the human clarin-1 protein (hCLRN1), a member of the tetraspanin protein family. The missense mutation CLRN1(N48K), which affects a conserved N-glycosylation site in hCLRN1, is a common causative USH3 mutation among Ashkenazi Jews. The affected individuals hear at birth but lose that function over time. Here, we developed an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype. Immunolabeling demonstrated that Clrn1 localized to the hair cell bundles (hair bundles). The clrn1 mutants generated by zinc finger nucleases displayed aberrant hair bundle morphology with diminished function. Two transgenic zebrafish that express either hCLRN1 or hCLRN1(N48K) in hair cells were produced to examine the subcellular localization patterns of wild-type and mutant human proteins. hCLRN1 localized to the hair bundles similarly to zebrafish Clrn1; in contrast, hCLRN1(N48K) largely mislocalized to the cell body with a small amount reaching the hair bundle. We propose that this small amount of hCLRN1(N48K) in the hair bundle provides clarin-1-mediated function during the early stages of life; however, the presence of hCLRN1(N48K) in the hair bundle diminishes over time because of intracellular degradation of the mutant protein, leading to progressive loss of hair bundle integrity and hair cell function. These findings and genetic tools provide an understanding and path forward to identify therapies to mitigate hearing loss linked to the CLRN1 mutation. Mutations in the clarin-1 gene affect eye and ear function in humans. Individuals with the CLRN1(N48K) mutation are born able to hear but lose that function over time. Here, we develop an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype. This approach illuminates the role of clarin-1 and the molecular mechanism linked to the CLRN1(N48K) mutation in sensory hair cells of the inner ear. Additionally, the investigation provided an in vivo model to guide future drug discovery to rescue the hCLRN1(N48K) in hair cells.


Atypical Kawasaki Disease Presenting with Hemiparesis and Aphasia: A Case Report.
Kawasaki disease (KD) is an inflammatory vasculitis. KD is classified into two groups based on clinical characteristics criteria, namely classic and incomplete. Cerebral vascular abnormality, especially arterial ischemic stroke (AIS) is very rare and unusual in KD. Here, we report a 4-year-old boy who was referred to our tertiary pediatric center with abrupt right hemiparesis and aphasia. At admission time, he had febrile illness and was toxic. On physical examination, we found unilateral left submandibular lymphadenopathy. On neurologic examination, we obtained right sided hemiparesis with hemiparetic gait and aphasia. His deep tendon reflexes (DTRs) of right extremities were exaggerated and his sensory system was intact. Based on these features, some differential diagnoses were suggested, such as acute encephalitis with focal signs, brain abscess, cerebral vasculitis, hemorrhagic insults, and ischemic stroke, etc. After a complete evaluation, especially brain MRI and MRA, our diagnosis was arterial ischemic stroke (AIS) following atypical KD. Based on these findings, we administered intravenous immunoglobulin (IVIG 2 gm/kg) and oral high dose aspirin (100 mg/kg/d). He responded to these anti-inflammatory treatments dramatically.


Development and validation of the BRIGHTLIGHT Survey, a patient-reported experience measure for young people with cancer.
Patient experience is increasingly used as an indicator of high quality care in addition to more traditional clinical end-points. Surveys are generally accepted as appropriate methodology to capture patient experience. No validated patient experience surveys exist specifically for adolescents and young adults (AYA) aged 13-24 years at diagnosis with cancer. This paper describes early work undertaken to develop and validate a descriptive patient experience survey for AYA with cancer that encompasses both their cancer experience and age-related issues. We aimed to develop, with young people, an experience survey meaningful and relevant to AYA to be used in a longitudinal cohort study (BRIGHTLIGHT), ensuring high levels of acceptability to maximise study retention. A three-stage approach was employed: Stage 1 involved developing a conceptual framework, conducting literature/Internet searches and establishing content validity of the survey; Stage 2 confirmed the acceptability of methods of administration and consisted of four focus groups involving 11 young people (14-25 years), three parents and two siblings; and Stage 3 established survey comprehension through telephone-administered cognitive interviews with a convenience sample of 23 young people aged 14-24 years. Stage 1: Two-hundred and thirty eight questions were developed from qualitative reports of young people's cancer and treatment-related experience. Stage 2: The focus groups identified three core themes: (i) issues directly affecting young people, e.g. impact of treatment-related fatigue on ability to complete survey; (ii) issues relevant to the actual survey, e.g. ability to answer questions anonymously; (iii) administration issues, e.g. confusing format in some supporting documents. Stage 3: Cognitive interviews indicated high levels of comprehension requiring minor survey amendments. Collaborating with young people with cancer has enabled a survey of to be developed that is both meaningful to young people but also examines patient experience and outcomes associated with specialist cancer care. Engagement of young people throughout the survey development has ensured the content appropriately reflects their experience and is easily understood. The BRIGHTLIGHT survey was developed for a specific research project but has the potential to be used as a TYA cancer survey to assess patient experience and the care they receive.


Interaction between alcohol and exercise: physiological and haematological implications.
Alcohol use, particularly excessive alcohol consumption is one of the most serious health risks in the world. A relationship between sport, exercise and alcohol consumption is clear and long-standing. Alcohol continues to be the most frequently consumed drug among athletes and habitual exercisers and alcohol-related problems appear to be more common in these individuals. Alcohol use is directly linked to the rate of injury sustained in sport events and appears to evoke detrimental effects on exercise performance capacity. The model of alcohol consumption in human experimental studies has either been acute (single dose) or chronic (repeated doses over a period). These studies suggested that alcohol consumption decreases the use of glucose and amino acids by skeletal muscles, adversely affects energy supply and impairs the metabolic process during exercise. In addition, chronic alcohol use is associated with increased citrate synthase activity and decreased cross-sectional area of type I, IIa and IIb fibres. There is evidence to suggest that exercise may attenuate the ethanol-induced decline in hepatic mitochondria and accelerates ethanol metabolism by the liver. Exercise training seems to reduce the extent of the oxidative damage caused by ethanol. Evidence generated from in vitro experiments and animal studies have also suggested that ethanol administration decreased skeletal muscle capillarity and increased pyruvate kinase and lactate dehydrogenase activities. Substantial epidemiological evidence has been accrued showing that moderate ingestion of alcohol may reduce the incidence of cardiovascular diseases. Although the existing evidence is often confusing and disparate, one of the mechanisms by which alcohol may reduce the incidence of mortality of cardiovascular diseases is through raising levels of high-density lipoprotein cholesterol. Available evidence suggests that exercise and moderate alcohol consumption may have favourable effects on blood coagulation and fibrinolysis; however, compelling experimental evidence is lacking to endorse this notion. Occasional and chronic alcohol consumption is usually linked with unfavourable alterations in platelet aggregation and function and may be associated with platelet-related thrombus formation. Although the effects of alcohol consumption on the rheological properties of the blood are not known, recent experimental evidence suggests that alcohol use following exercise is associated with unfavourable changes in the main determinants of blood viscosity. It is well documented that alcohol use modulates the immune system and impairs host defence. Compelling evidence is also mounting to suggest that chronic alcohol use is linked with adverse effects on the body systems and organs including the brain, the cardiovascular system and the liver.


Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology.
Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer. This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of < = 32 ng/ml (n = 1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit. Of 1651 patients, 799 were available for follow up assessment. The mean serum 25(OH)D levels were compared in these 799 patients across the 2 time points (baseline and first follow-up) using paired sample t-test. We also investigated the factors associated with response to vitamin D supplementation. Of 2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean age at presentation was 55.4 years. The most common cancer types were breast (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and prostate (185, 8.4%). The mean time duration between baseline and first follow-up assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks). The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p < 0.001. Patients with prostate and lung cancer had the highest percentage of responders (70% and 69.2% respectively) while those with colorectal and pancreas had the lowest (46.7% each). Similarly, patients with serum levels 20-32 ng/ml at baseline were most likely to attain levels > 32 ng/ml compared to patients with baseline levels < 20 ng/ml. The response to supplementation from suboptimal to optimal levels was greatest in patients with prostate and lung cancer as well as those with baseline levels between 20-32 ng/ml. Characteristics of non-responders as well as those who take longer to respond to supplementation need to be further studied and defined. Additionally, the impact of improved serum 25(OH)D levels on patient survival and quality of life needs to be investigated.


Parkinson's disease and driving ability.
To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in-car driving test. The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all p<0.001). The level of drug treatment and the length of driving history were not correlated. Discriminant analysis revealed that the most important features in distinguishing safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction time, moderate disease associated with another medical condition and high score on car testing. Most individuals with PD are safe to drive, although many benefit from car modifications or from using an automatic transmission. A combination of clinical tests and in-car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on-road driving assessment.


Successful treatment of lichen planus with sulfasalazine in 20 patients.
Lichen planus (LP) is a disturbing pruritic cutaneous disease that may have an spontaneous resolution or exhibit a more chronic course during some weeks or months. Our objective was to demonstrate that sulfasalazine is effective in the treatment of LP. Twenty patients were diagnosed in our department with LP of the skin and/or mucosa between 1985 and 2001 on the basis of clinical and histologic findings. All patients were treated with sulfasalzine at initial doses of 1.5 g/day, increasing by 0.5 g/week to 3 g/day for 4-16 weeks. Some patients also received descendent doses for 2-12 months. Complete responses were observed in 13 patients and partial responses in seven patients. All patients reported an early resolution of the pruritus. No changes were detected in mucosal LP. Most of the patients tolerated the treatment well and only eight patients presented some minor side-effects. Sulfasalazine is a successful therapeutic option for cutaneous LP, constituting an alternative to corticosteroids and retinoids.


Hadza sleep biology: Evidence for flexible sleep-wake patterns in hunter-gatherers.
Cross-cultural sleep research is critical to deciphering whether modern sleep expression is the product of recent selective pressures, or an example of evolutionary mismatch to ancestral sleep ecology. We worked with the Hadza, an equatorial, hunter-gatherer community in Tanzania, to better understand ancestral sleep patterns and to test hypotheses related to sleep segmentation. We used actigraphy to analyze sleep-wake patterns in thirty-three volunteers for a total of 393 days. Linear mixed effects modeling was performed to assess ecological predictors of sleep duration and quality. Additionally, functional linear modeling (FLM) was used to characterize 24-hr time averaged circadian patterns. Compared with post-industrialized western populations, the Hadza were characterized by shorter (6.25 hr), poorer quality sleep (sleep efficiency = 68.9%), yet had stronger circadian rhythms. Sleep duration time was negatively influenced by greater activity, age, light (lux) exposure, and moon phase, and positively influenced by increased day length and mean nighttime temperature. The average daily nap ratio (i.e., the proportion of days where a nap was present) was 0.54 (SE = 0.05), with an average nap duration of 47.5 min (SE = 2.71; n = 139). This study showed that circadian rhythms in small-scale foraging populations are more entrained to their ecological environments than Western populations. Additionally, Hadza sleep is characterized as flexible, with a consistent early morning sleep period yet reliance upon opportunistic daytime napping. We propose that plasticity in sleep-wake patterns has been a target of natural selection in human evolution.


Best practice in psychological activities in cardiovascular prevention and rehabilitation: Position Paper.
Recent guidelines on cardiovascular disease prevention suggest multimodal behavioral interventions for psychosocial risk factors and referral for psychotherapy in the case of clinically significant symptoms of depression and anxiety overall. Accordingly, psychologists of the Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiology (GICR-IACPR) have reviewed the key components of psychological activities in cardiovascular prevention and rehabilitation (CPR). The aim of this study was to elaborate a position paper on the best practice in routine psychological activities in CPR based on efficacy, effectiveness and sustainability. The steps followed were: i) a review of the latest international guidelines and position papers; ii) analysis of the evidence-based literature; iii) a qualitative analysis of the psychological services operating in some reference Italian cardiac rehabilitation facilities; iv) classification of the psychological activities in CPR as low or high intensity based on the NICE Guidelines on psychological interventions on anxiety and depression. We confirm the existence of an association between depression, anxiety, social factors, stress, personality and illness onset/outcome and coronary heart disease. Evidence for an association between depression, social factors and disease outcome emerges particularly for chronic heart failure. Some positive psychological variables (e.g., optimism) are associated to illness outcome. Evidence is reported on the impact of psychological activities on 'new' conditions which are now indicated for cardiac rehabilitation: pulmonary hypertension, grown-up congenital heart, end-stage heart failure, implantable cardioverter-defribrillator and mechanical ventricular assist devices, frail and oldest-old patients, and end-of-life care. We also report evidence related to caregivers. The Panel divided evidence-based psychological interventions into: i) low intensity (counseling, psycho-education, self-care, self-management, telemedicine, self-help); or ii) high intensity (individual, couples and/or family and group psychotherapy, such as stress management). The results show that psychotherapy is mainly consisting of cognitive-behavior therapy, interpersonal therapy, and short-term psycho-dynamic therapy. The current data further refine the working tools available for psychological activities in CPR, giving clear directions about the choice of interventions, which should be evidence-based and have at least a minimum standard. This document provides a comprehensive update on new knowledge and new paths for psychologists working in the CPR settings.


Risk factors for radial artery harvest site infection following coronary artery bypass graft surgery.
Radial arteries increasingly are used during coronary artery bypass graft (CABG) surgery. Although risk factors for saphenous vein harvest site infection (HSI) have been reported, rates of and risk factors for radial artery HSI are not well established. We compared rates of radial artery HSI that were detected by 2 surveillance methods, regular and heightened. Risk factors were determined by a case-control study. We identified 35 radial artery HSIs ("case sites") in 26 case patients. The radial artery HSI rate was significantly higher during heightened surveillance than during routine surveillance (12.3% vs. 3.1%, respectively; P=.002). Multivariate analysis showed that diabetes mellitus with a preoperative glucose level >/=200 mg/dL (odds ratio [OR], 4.4; P=. 01) and duration of surgery >/=5 h (OR, 3.1; P=.02) were independent risk factors for radial artery HSI. Infection is a common complication of radial artery harvesting for CABG surgery, and infection rates are dependent on the intensity of surveillance. We identified preoperative hyperglycemia and surgery duration as independent risk factors for radial artery HSI.


Suicide.
Suicide receives increasing attention worldwide, with many countries developing national strategies for prevention. Rates of suicide vary greatly between countries, with the greatest burdens in developing countries. Many more men than women die by suicide. Although suicide rates in elderly people have fallen in many countries, those in young people have risen. Rates also vary with ethnic origin, employment status, and occupation. Most people who die by suicide have psychiatric disorders, notably mood, substance-related, anxiety, psychotic, and personality disorders, with comorbidity being common. Previous self-harm is a major risk factor. Suicide is also associated with physical characteristics and disorders and smoking. Family history of suicidal behaviour is important, as are upbringing, exposure to suicidal behaviour by others and in the media, and availability of means. Approaches to suicide prevention include those targeting high-risk groups and population strategies. There are, however, many challenges to large-scale prevention, especially in developing countries.


Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells.
Human (h) induced pluripotent stem cells (iPSCs) are a potentially abundant source of blood cells, but how best to select iPSC clones suitable for this purpose from among the many clones that can be simultaneously established from an identical source is not clear. Using an in vitro culture system yielding a hematopoietic niche that concentrates hematopoietic progenitors, we show that the pattern of c-MYC reactivation after reprogramming influences platelet generation from hiPSCs. During differentiation, reduction of c-MYC expression after initial reactivation of c-MYC expression in selected hiPSC clones was associated with more efficient in vitro generation of CD41a(+)CD42b(+) platelets. This effect was recapitulated in virus integration-free hiPSCs using a doxycycline-controlled c-MYC expression vector. In vivo imaging revealed that these CD42b(+) platelets were present in thrombi after laser-induced vessel wall injury. In contrast, sustained and excessive c-MYC expression in megakaryocytes was accompanied by increased p14 (ARF) and p16 (INK4A) expression, decreased GATA1 expression, and impaired production of functional platelets. These findings suggest that the pattern of c-MYC expression, particularly its later decline, is key to producing functional platelets from selected iPSC clones.


False Labor at Term in Singleton Pregnancies: Discharge After a Standardized Assessment and Perinatal Outcomes.
To evaluate perinatal outcomes in women sent home with a diagnosis of false labor at term and assess the time interval to return for delivery. This was a prospective observational cohort study of women at 37 0/7 to 41 6/7 weeks of gestation without pre-existing medical complications who presented to our hospital-based triage unit with symptoms of labor and underwent a standardized evaluation. Women diagnosed as having false labor with a live singleton fetus in cephalic presentation without a prior cesarean delivery and sent home were compared with a group of similar women diagnosed to be in spontaneous labor. Women with hypertension, diabetes, and known fetal malformations were excluded. Using a perinatal composite outcome of respiratory insufficiency, intraventricular hemorrhage, culture-proven sepsis, Apgar score 3 or less at 5 minutes, phototherapy, and perinatal death, we tested the noninferiority of being sent home compared with being admitted for labor. The relationship of cervical dilatation to the time interval from discharge home to delivery was also analyzed. Between October 2012 and March 2016, a total of 3,949 women met inclusion criteria and were diagnosed with false labor, discharged, and returned to deliver, whereas 2,592 similar women were admitted in early labor. The mean interval from discharge to return was 4.9 days. Cesarean delivery rates were not different between the study groups-11% for both (P=.69), and the perinatal composite outcome rates were not significantly different between those sent home and those admitted-3.2% compared with 3.1% (P=.79). Women with more advanced cervical dilatation at discharge returned and delivered significantly earlier than those with less dilatation regardless of parity. Discharge with false labor at term after a standardized assessment in a triage unit was not associated with increased rates of adverse perinatal composite outcomes or cesarean delivery. The time interval to return for delivery was significantly associated with the cervical dilatation at discharge.


Calcium Channel Blocker Use and Risk of Prostate Cancer by TMPRSS2:ERG Gene Fusion Status.
Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. Participants were residents of King County, Washington, recruited for population-based case-control studies (1993-1996 or 2002-2005). Tumor T2E status was determined by fluorescence in situ hybridization using tumor tissue specimens from radical prostatectomy. Detailed information on use of CCBs and other variables was obtained through in-person interviews. Binomial and polytomous logistic regression were used to generate odds ratios (ORs) and 95% confidence intervals (CIs). The study included 1,747 PCa patients and 1,635 age-matched controls. A subset of 563 patients treated with radical prostatectomy had T2E status determined, of which 295 were T2E positive (52%). Use of CCBs (ever vs. never) was not associated with overall PCa risk. However, among European-American men, users had a reduced risk of higher-grade PCa (Gleason scores ≥7: adjusted OR = 0.64; 95% CI: 0.44-0.95). Further, use of CCBs was associated with a reduced risk of T2E positive PCa (adjusted OR = 0.38; 95% CI: 0.19-0.78), but was not associated with T2E negative PCa. This study found suggestive evidence that use of CCBs is associated with reduced relative risks for higher Gleason score and T2E positive PCa. Future studies of PCa etiology should consider etiologic heterogeneity as PCa subtypes may develop through different causal pathways. Prostate 77:282-290, 2017. © 2016 Wiley Periodicals, Inc.


Medical yoga: another way of being in the world-a phenomenological study from the perspective of persons suffering from stress-related symptoms.
The prevalence of stress-related illness has grown in recent years. Many of these patients seek help in primary health care. Yoga can reduce stress and thus complements pharmacological therapy in medical practice. To our knowledge, no studies have investigated patients' experiences of yoga treatment in a primary health care setting or, specifically, the experiences of yoga when suffering from stress-related illness. Thus, the aim of the present study was to explore the meaning of participating in medical yoga as a complementary treatment for stress-related symptoms and diagnosis in a primary health care setting. This study has a descriptive phenomenological design and took place at a primary health care centre in Sweden during 2011. Five women and one man (43-51 years) participated. They were recruited from the intervention group (n=18) in a randomized control trial, in which they had participated in a medical yoga group in addition to standard care for 12 weeks. Data were collected by means of qualitative interviews, and a phenomenological data analysis was conducted. The essential meaning of the medical yoga experience was that the medical yoga was not an endpoint of recovery but the start of a process towards an increased sense of wholeness. It was described as a way of alleviating suffering, and it provided the participants with a tool for dealing with their stress and current situation on a practical level. It led to greater self-awareness and self-esteem, which in turn had an implicit impact on their lifeworld. In phenomenological terms, this can be summarized as Another way of being in the world, encompassing a perception of deepened identity. From a philosophical perspective, due to using the body in a new way (yoga), the participants had learnt to see things differently, which enriched and recast their perception of themselves and their lives.


Input-driven components of spike-frequency adaptation can be unmasked in vivo.
Spike-frequency adaptation affects the response characteristics of many sensory neurons, and different biophysical processes contribute to this phenomenon. Many cellular mechanisms underlying adaptation are triggered by the spike output of the neuron in a feedback manner (e.g., specific potassium currents that are primarily activated by the spiking activity). In contrast, other components of adaptation may be caused by, in a feedforward way, the sensory or synaptic input, which the neuron receives. Examples include viscoelasticity of mechanoreceptors, transducer adaptation in hair cells, and short-term synaptic depression. For a functional characterization of spike-frequency adaptation, it is essential to understand the dependence of adaptation on the input and output of the neuron. Here, we demonstrate how an input-driven component of adaptation can be uncovered in vivo from recordings of spike trains in an insect auditory receptor neuron, even if the total adaptation is dominated by output-driven components. Our method is based on the identification of different inputs that yield the same output and sudden switches between these inputs. In particular, we determined for different sound frequencies those intensities that are required to yield a predefined steady-state firing rate of the neuron. We then found that switching between these sound frequencies causes transient deviations of the firing rate. These firing-rate deflections are evidence of input-driven adaptation and can be used to quantify how this adaptation component affects the neural activity. Based on previous knowledge of the processes in auditory transduction, we conclude that for the investigated auditory receptor neurons, this adaptation phenomenon is of mechanical origin.


Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why.
The endometrium maintains complex controls on proliferation and apoptosis as part of repetitive menstrual cycles that prepare the endometrium for the window of implantation and pregnancy. The reliance on inflammatory mechanisms for both implantation and menstruation creates the opportunity in the setting of endometriosis for establishment of chronic inflammation that is disruptive to endometrial receptivity, causing both infertility and abnormal bleeding. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation, and strong evidence exists to suggest that endometrial changes are associated with decreased cycle fecundity as a result of this disease. Here we provide unifying concepts regarding those changes and how they are coordinated to promote progesterone resistance and estrogen dominance through aberrant cell signaling pathways and reduced expression of key homeostatic proteins in eutopic endometrium of women with endometriosis.


Association of Slow Graft Function with Long-Term Outcomes in Kidney Transplant Recipients.
BACKGROUND Whether slow graft function (SGF) represents an intermediate phenotype between immediate graft function (IGF) and delayed graft function (DGF) in kidney transplant recipients is unknown. MATERIAL AND METHODS In a retrospective cohort analysis of 1,222 kidney transplant recipients, we classified patients as having IGF, SGF, and DGF using two different schemas. SGF was defined as serum creatinine (Cr) ≥3.0 mg/dL by postoperative day 5 in Schema 1, and in Schema 2, SGF was defined as Cr >1.5 mg/dL plus a creatinine reduction ratio <20% between postoperative days 1 and 3. A complementary log-log model was used to examine the association of graft function with graft survival and patient survival. RESULTS Mean age of study patients was 51.5±13.3 years, 59.9% were male, and 66.7% were white. In Schema 1, SGF and DGF were associated with comparable increases in risk of graft failure compared to IGF (hazard ratio (HR) 1.46, 95% confidence intervals (CI) 1.02-2.10 for SGF and HR 1.56, CI 1.11-2.22 for IGF); estimates were similar for Schema 2 (HR 1.52, CI 1.05-2.20 for SGF and HR 1.54, CI 1.10-2.17 for IGF). However, for mortality, outcomes for SGF were similarly to IGF, both SGF and IGF were associated with lower risk relative to DGF (HR 0.54, CI 0.36-0.80 for SGF in Schema 1; HR 0.58, CI 0.39-0.85 for SGF in Schema 2). CONCLUSIONS These findings suggest that SGF may be a marker for graft failure but not for mortality, and SGF may therefore represent a phenotype separate from IGF and DGF.


Suppression of Biofouling on a Permeable Membrane for Dissolved Oxygen Sensing Using a Lubricant-Infused Coating.
Specific ranges of dissolved oxygen (DO) concentrations must be maintained in a waterbody for it to be hospitable for aquatic animals. DO sensor designs can employ selectively permeable membranes to isolate DO from untargeted compounds or organisms in waterbodies. Hence, the DO concentration can be monitored and the health of the water can be evaluated over time. However, the presence of bacteria in natural waterbodies can lead to the formation of biofilms that can block pores and prevent analyte from permeating the membrane, resulting in inaccurate readings. In this work, we demonstrate the implementation of a fluorosilane-based omniphobic lubricant-infused (OLI) coating on a selectively permeable membrane and investigate the rate of biofilm formation for a commercially available DO sensor. Coated and unmodified membranes were incubated in an environment undergoing accelerated bacterial growth, and the change in sensitivity was evaluated after 40, 100, 250, and 500 h. Our findings show that the OLI membranes attenuate biofouling by 70% and maintain sensitivity after 3 weeks of incubation, further demonstrating that oxygen transfer through the OLI coating is achievable. Meanwhile, unmodified membranes exhibit significant biofouling that results in a 3.35 higher rate of decay in oxygen measurement sensitivity and an over 70% decrease in static contact angle. These results show that the OLI coating can be applied on commercially available membranes to prevent biofouling. Therefore, OLI coatings are a suitable candidate to suppress biofilm formation in the widespread use of selectively permeable membranes for environmental, medical, and fluid separation applications.


Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells.
Essential oils from various aromatic plants have been reported to exert chemopreventive and/or antitumor effects. In addition, a number of studies have shown the ability of chemopreventive phytochemicals to increase the sensitivity of cancer cells to conventional anticancer drugs. The success of chemotherapeutic agents is often hindered by the development of drug resistance, with multidrug resistant (MDR) phenotypes reported in a number of tumors, generally involving reduced intracellular drug accumulation due to increased drug efflux by membrane transporters. In the present study, the effects of linalool (LIN), a monoterpene alcohol found in the essential oils from many aromatic plants, on the growth of two human breast adenocarcinoma cell lines, MCF7 WT and multidrug resistant MCF7 AdrR, were investigated, both as a single agent and in combination with doxorubicin (DOX). The results reported here show that LIN only moderately inhibits cell proliferation; interestingly, however, subtoxic concentrations of LIN potentiate DOX-induced cytotoxicity and pro-apoptotic effects in both cell lines. A significant synergism can be observed in MCF7 AdrR cells, which may be due, at least in part, to the ability of LIN to increase DOX accumulation and to induce a decrease in Bcl-xL levels. In summary, the results of the present study suggest that LIN may improve the therapeutic index of anthracyclines in the management of breast cancer, especially in MDR tumors.


Neurturin influences inflammatory responses and airway remodeling in different mouse asthma models.
Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild-type and NTN(-/-) mice after sensitization with two different allergens, OVA and house dust mite. We showed that NTN(-/-) dendritic cells and T cells had a stronger tendency to activate the Th2 pathway in vitro than similar wild-type cells. Furthermore, NTN(-/-) mice had significantly increased markers of airway remodeling like collagen deposition. NTN(-/-) lung tissues showed higher levels of neutrophils, cytokine-induced neutrophil chemoattractant, matrix metalloproteinase 9, TNF-α, and IL-6. Finally, NTN had the capacity to decrease IL-6 and TNF-α production by immune and epithelial cells, showing a direct anti-inflammatory activity on these cells. Our findings support the hypothesis that NTN could modulate the allergic inflammation in different mouse asthma models.


Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases.
The extent of renal fibrosis in chronic kidney disease (CKD) is the best predictor for progression of most renal diseases. To date, no established biomarkers of renal fibrosis exist. We measured circulating and urinary-specific matrix metalloproteinase (MMP)-generated collagen type I and III degradation fragments (C1M and C3M) and an N-terminal propeptide of collagen III (Pro-C3), as markers of collagen type III production, in three rat models of CKD and fibrosis: renal mass reduction (5/6 nephrectomy), progressive glomerulonephritis (chronic anti-Thy1.1 nephritis) and adenine crystal-induced nephropathy. Healthy rats served as controls. In all three models, the animals developed significant CKD and renal fibrosis. Compared with healthy rats, serum C1M and C3M significantly increased in rats with 5/6 nephrectomy and adenine nephropathy (2- to 3-fold), but not with chronic anti-Thy1.1 nephritis. Urinary C1M and C3M levels increased 9- to 100-fold in all three models compared with controls. Urinary degradation markers correlated closely with renal deposition of collagen type I and type III. Pro-C3 was significantly increased only in the urine of 5/6 nephrectomy rats. In particular, urinary markers of MMP-driven collagen degradation, rather than collagen production markers, may represent a novel, specific and non-invasive diagnostic approach to assess kidney fibrosis.


Land application of hydrofracturing fluids damages a deciduous forest stand in West Virginia.
In June 2008, 303,000 L of hydrofracturing fluid from a natural gas well were applied to a 0.20-ha area of mixed hardwood forest on the Fernow Experimental Forest, West Virginia. During application, severe damage and mortality of ground vegetation was observed, followed about 10 d later by premature leaf drop by the overstory trees. Two years after fluid application, 56% of the trees within the fluid application area were dead. Ehrh. was the tree species with the highest mortality, and L. was the least affected, although all tree species present on the site showed damage symptoms and mortality. Surface soils (0-10 cm) were sampled in July and October 2008, June and October 2009, and May 2010 on the fluid application area and an adjacent reference area to evaluate the effects of the hydrofracturing fluid on soil chemistry and to attempt to identify the main chemical constituents of the hydrofracturing fluid. Surface soil concentrations of sodium and chloride increased 50-fold as a result of the land application of hydrofracturing fluids and declined over time. Soil acidity in the fluid application area declined with time, perhaps from altered organic matter cycling. This case study identifies the need for further research to help understand the nature and the environmental impacts of hydrofracturing fluids to devise optimal, safe disposal strategies.


Effects of Timing of Copper Sprays, Defoliation, Rainfall, and Inoculum Concentration on Incidence of Olive Knot Disease.
The olive knot pathogen, Pseudomonas savastanoi, causes galls on shoots, branches, fruit, and leaves. Shoots girdled by galls die. Any fresh wound is susceptible to infection, but the most common entry sites are leaf scars. Leaf scars are most susceptible to infection during the first 2 days after leaf fall and remain susceptible for 7 more days. Simulated leaf scars on 'Manzanillo' olive trees were created by removing leaves from healthy shoots at approximately monthly intervals from December through June 1997-98, 1998-99, and 1999-2000. Trees were treated with a water suspension of cupric hydroxide (Kocide DF40) at 3 g/liter one, two, or three times in 1998-99 and 1999-2000 with a hand-gun sprayer. Generally, disease control improved with more applications (P = 0.008 and 0.032 in 1999 and 2000, respectively). Disease incidence was greatest on shoots that were defoliated in March 1998, April and June 1999, and March and May 2000. Cumulative rainfall 2 and 9 days after each defoliation was recorded. Disease incidence was positively correlated (P = 0.031 and 0.023 for 2 and 9 days, respectively) with spring (March through June) but not winter (December through February) rainfall. Comparable simulated leaf scars were inoculated in December and April 1997-98 and 1998-99 with 104, 106, and 108 CFU/ml of the pathogen and treated with a water suspension of cupric hydroxide at 3 g/liter using a handheld pump sprayer. Inoculated and noninoculated, nontreated shoots were included. More disease developed in April than in December inoculations (P = <0.0001) in both years. Disease incidence increased with increasing inoculum concentration (P = <0.0001) in both years and was lower in shoots treated with Kocide DF40 (P = <0.0001). Our work demonstrated that the common grower practice of one post-harvest application of copper bactericide provides only minimal protection against olive knot, and that additional sprays in spring are needed to substantially improve disease control.


Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists.
Medical tourism is a global health practice where patients travel abroad to receive health care. Voluntourism is a practice where physicians travel abroad to deliver health care. Both of these practices often entail travel from high income to low and middle income countries and both have been associated with possible negative impacts. In this paper, we explore the social responsibilities of medical tourists and voluntourists to identify commonalities and distinctions that can be used to develop a wider understanding of social responsibility in global health care practices. Social responsibility is a responsibility to promote the welfare of the communities to which one belongs or with which one interacts. Physicians stress their social responsibility to care for the welfare of their patients and their domestic communities. When physicians choose to travel to another county to provide medical care, this social responsibility is expanded to this new community. Patients too have a social responsibility to use their community's health resources efficiently and to promote the health of their community. When these patients choose to go abroad to receive medical care, this social responsibility applies to the new community as well. While voluntourists and medical tourists both see the scope of their social responsibilities expand by engaging in these global practices, the social responsibilities of physician voluntourists are much better defined than those of medical tourists. Guidelines for engaging in ethical voluntourism and training for voluntourists still need better development, but medical tourism as a practice should follow the lead of voluntourism by developing clearer norms for ethical medical tourism. Much can be learned by examining the social responsibilities of medical tourists and voluntourists when they engage in global health practices. While each group needs better guidance for engaging in responsible forms of these practices, patients are at a disadvantage in understanding the effects of medical tourism and organizing responses to these impacts. Members of the medical professions and the medical tourism industry must take responsibility for providing better guidance for medical tourists.


A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo.
Although amyloid beta (Abeta) oligomers are presumed to cause synaptic and cognitive dysfunction in Alzheimer's disease (AD), their contribution to other pathological features of AD remains unclear. To address the latter, we generated APP transgenic mice expressing the E693Delta mutation, which causes AD by enhanced Abeta oligomerization without fibrillization. The mice displayed age-dependent accumulation of intraneuronal Abeta oligomers from 8 months but no extracellular amyloid deposits even at 24 months. Hippocampal synaptic plasticity and memory were impaired at 8 months, at which time the presynaptic marker synaptophysin began to decrease. Furthermore, we detected abnormal tau phosphorylation from 8 months, microglial activation from 12 months, astrocyte activation from 18 months, and neuronal loss at 24 months. These findings suggest that Abeta oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of Abeta oligomer-induced pathology in the absence of amyloid plaques.


2019 Outstanding Manuscript Awards.
Congratulations to the winners of the 2019 Outstanding Manuscript Awards, as determined by the Editorial Board and the Editors of the Journal of Athletic Training.


Vertical cultural transmission effects on demic front propagation: theory and application to the Neolithic transition in Europe.
It is shown that Lotka-Volterra interaction terms are not appropriate to describe vertical cultural transmission. Appropriate interaction terms are derived and used to compute the effect of vertical cultural transmission on demic front propagation. They are also applied to a specific example, the Neolithic transition in Europe. In this example, it is found that the effect of vertical cultural transmission can be important (about 30%). On the other hand, simple models based on differential equations can lead to large errors (above 50%). Further physical, biophysical, and cross-disciplinary applications are outlined.


Cell guidance by alterations in monomolecular films.
Monolayers of stearic and behenic acids were transferred to quartz slides by the Blodgett technique. Troughs of different depths were cut into these multilayers (substrata), and additional monolayers were superimposed. When cultured and fresh embryonic cells were grown on these substrata, the cells were entrapped within troughs whose depths were as small as 60 angstroms. The results demonstrate cellular responses to molecular changes in contact surfaces.


Automatic Detection of Epileptic Seizures in EEG Using Sparse CSP and Fisher Linear Discrimination Analysis Algorithm.
In order to realize the automatic epileptic seizure detection, feature extraction and classification of electroencephalogram (EEG) signals are performed on the interictal, the pre-ictal, and the ictal status of epilepsy patients. There is no effective strategy for selecting the number of channels and spatial filters in feature extraction of multichannel EEG data. Therefore, this paper combined sparse idea and greedy search algorithm to improve the feature extraction of common space pattern. The feature extraction can effectively overcome the repeating selection problem of feature pattern in the eigenvector space by the traditional method. Then we used the Fisher linear discriminant analysis to realize the classification. The results show that the proposed method can get high classification accuracy using fewer data. For 10 subjects, the averaged accuracy of epilepsy detection is more than 99%. So, the detection of an epileptic seizure based on sparse features using Fisher linear discriminant analysis classifiers is more suitable for a reliable, automatic epileptic seizure detection system to enhance the patient's care and the quality of life.


[PROPERTIES OF CHICKEN LIVER MEMBRANE-ASSOCIATED THIAMINE TRIPHOSPHATASE].
The enzymes involved in thiamine triphosphate (ThTP) metabolism in birds are not characterized so far. The aim of the present work was to study some properties of ThTPase in chicken liver. In liver homogenate, ThTPase activity has been found to display a bell-like pH-profile with a maximum of 5.5-6.0. Low activity was observed without divalent metal ions, while the addition of Mg2+ or Ca2+, each at 5 mM concentration, enhanced the rate of ThTP hydrolysis by a factor of 17-20. In the presence of 5 mM Mg2+ an apparent K(m) of the enzyme for ThTP was estimated by the method of non-linear regression as well as from the Hanes plot to be 1.7-2.2 mM. Monovalent anions such as I-, SCN-, NO3-, Br-, Cl- (at 150 mM concentration) showed inhibitory effect decreasing the rate of ThTPase reaction by 20-60%. After the homogenate was centrifuged, more than 85% of ThTPase activity was revealed in the fraction of insoluble particles indicating a membrane localization of the enzyme. The precipitate treatment with 1% sodium deoxycholate caused about 53% solubilization of the activity. During Toyopeal HW-55 chromatography, ThTPase activity was eluted simultaneously with ATPase and ITPase peaks in the void volume of the column. Thus, a non-specific high molecular mass protein complex seems to be involved in ThTP hydrolysis in the chicken liver. The chicken liver phosphatase is clearly distinguishable from all membrane-bound ThTPases reported previously.


Clinical factors associated with high-risk carotid plaque features as assessed by magnetic resonance imaging in patients with established vascular disease (from the AIM-HIGH Study).
Association between clinical factors and high-risk plaque features, such as, thin or ruptured cap, intraplaque hemorrhage, presence of lipid-rich necrotic core (LRNC), and increased LRNC volume as assessed by magnetic resonance imaging (MRI), was examined in patients with established vascular disease in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides (AIM-HIGH) trial. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents, and MRI-modified American Heart Association lesion type by a core laboratory. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced American Heart Association type-VI lesions with possible surface defect, intraplaque hemorrhage, or mural thrombus. Type-VI lesions were associated with older age (odds ratio [OR] = 2.6 per 5 years increase, p <0.001). After adjusting for age, these lesions were associated with history of cerebrovascular disease (OR = 4.1, p = 0.01), higher levels of lipoprotein(a) (OR = 2.0 per 1 SD increase, p = 0.02), and larger percent wall volume (PWV [OR = 4.6 per 1 SD increase, p <0.001]) but, were negatively associated with metabolic syndrome (OR = 0.2, p = 0.02). Presence of LRNC was associated with the male gender (OR = 3.2, p = 0.02) and PWV (OR = 3.8 per 1 SD, p <0.001); however, it was negatively associated with diabetes (OR = 0.4, p = 0.02) and high-density lipoprotein cholesterol levels (OR = 0.7 per 1 SD, p = 0.02). Increased percent LRNC was associated with PWV (regression coefficient = 0.36, p <0.001) and negatively associated with ApoA1 levels (regression coefficient = -0.20, p = 0.03). In conclusion, older age, male gender, history of cerebrovascular disease, larger plaque burden, higher lipoprotein(a), and lower high-density lipoprotein cholesterol or ApoA1 level have statistically significant associations with high-risk plaque features. Metabolic syndrome and diabetes showed negative associations in this population.


An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells.
Lymphoid tissue inducer (LTi) cells are associated with early development of lymph nodes and Peyer's patches. We show here that during fetal life the nuclear hormone receptor RORgamma(t) is expressed exclusively in and is required for the generation of LTi cells. RORgamma(t+) LTi cells provide essential factors, among which lymphotoxin-alpha1beta2 is necessary but not sufficient for activation of the mesenchyma in lymph node and Peyer's patch anlagen. This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues.


Mechanisms in the inhibition of neointimal hyperplasia with triflavin in a rat model of balloon angioplasty.
RGD-containing peptides are able to inhibit the binding of ligands to certain beta3 integrins, such as alpha(IIb)beta3 and alpha(v)beta3, both of which are involved in neointimal hyperplasia. The present study was designed to elucidate the detailed mechanisms involved in the inhibition of neointimal hyperplasia with triflavin in a rat model of balloon angioplasty. Triflavin (0.25 mg x kg(-1) x d(-1)), an RGD-containing disintegrin, time dependently inhibited both neointimal hyperplasia and lumen occlusion after angioplasty in carotid arteries of rats. Furthermore, electron micrographs highlighted that SMCs were phenotypically different from the typical contractile, spindle-shaped SMCs normally seen in uninjured vessel walls. PDGF-BB was strongly produced in thrombus formation and neointimal SMCs after angioplasty, and triflavin significantly reduced PDGF-BB expression in vessel lumens and neointimal SMCs after angioplasty. Balloon angioplasty caused a significant increase of nitrate and cyclic guanosine monophosphate levels compared with levels found in sham-operated rats, and these were not significantly changed with infusion of triflavin (0.25 mg x kg(-1) x d(-1)). Furthermore, the plasma level of TXB2 obviously increased after angioplasty, and triflavin markedly suppressed the elevation of plasma TXB2 concentration. The results indicate that triflavin effectively prevents neointimal hyperplasia, possibly through the following 2 mechanisms. First, triflavin binds to alpha(IIb)beta3 integrin on platelet membranes, resulting in inhibition of platelet adhesion, secretion, and aggregation in injured arteries, followed by inhibition of TXA2 formation and PDGF-BB release from platelets. Second, triflavin may also bind to alpha(v)beta3 integrin on SMCs, thus subsequently inhibiting cell migration and proliferation. These results provide new insights into the mechanisms of neointimal hyperplasia and have significant implications for disintegrin therapy for the treatment of restenosis and atherosclerosis.


Synthesis, structural characterization and transformation of an eight-electron superatomic alloy, [Au@Ag19{S2P(OPr)2}12].
Controlling the metal nanoclusters with atomic precision is highly difficult and further studies on their transformation reactions are even more challenging. Herein we report the controlled formation of a silver alloy nanocluster [AuAg19{S2P(OnPr)2}12] (1) from an Ag20 template via a galvanic exchange route. X-ray structural analysis reveals that the alloy structure comprises of a gold-centered Ag12 icosahedron, Au@Ag12, capped by seven silver atoms. Interestingly upon reacting with one equiv. of silver(i) salt, (1) can transform into a higher nuclearity nanocluster, [Au@Ag20{S2P(OnPr)2}12]+ (2). The conversion process is studied via ESI mass spectrometry and 31P NMR spectroscopy. This kind of size-structural transformation at the single atom level is quite remarkable. Furthermore, the compositions of all the doped nanoclusters (1, 2) were fully characterized with ESI-MS and EDS. The blue shift depicted in the UV-visible and emission spectra of the doped nanoclusters (1, 2) compared with the precursor, Ag20, demonstrates that the doping atoms have significant effects on the electronic structures.


Epidemiology of campylobacteriosis in Germany - insights from 10 years of surveillance.
Campylobacteriosis caused by Campylobacter spp. is the most common notifiable bacterial gastrointestinal disease in Germany and a major problem in many other European countries as well. In contrast to other infectious diseases, e.g., salmonellosis, the annual number of notified campylobacteriosis cases has increased in Germany and other European countries from 2001-2010. National surveillance data from 2001 through 2010 were the basis of a detailed description of the epidemiological pattern of Campylobacter infections in Germany. Special focus was placed on geographical distribution and time trends of Campylobacter infections as well as the identification of risk groups. In total, 588,308 cases of campylobacteriosis were recorded during the observed time period. The mean annual incidence increased from 67 cases/100,000 population in 2001 to 80/100,000 population in 2010. Almost 92% of the notified Campylobacter infections were acquired in Germany. A seasonal distribution was observed with a large peak in the summer months and a small peak in January. Incidence was highest in children ≤4 years and young adults 20-29 years of age. Especially young children living in rural regions in Germany seemed to be at high risk of Campylobacter infection. Campylobacter is the leading cause of bacterial gastroenteritis in Germany, and has been of rising public health concern. There is a need for enhanced prevention of Campylobacter infections and the data presented here may contribute to better target prevention measures with focus on identified risk groups such as children and young adults.


The influence of type of delivery, skin-to-skin contact and maternal nationality on breastfeeding rates at hospital discharge in a baby-friendly hospital in Italy.
The aim of this epidemiological study is to evaluate how type of delivery, skin-to-skin contact and maternal nationality influence breastfeeding practices of newborns at discharge in a large population of babies born in the Baby-Friendly Hospital of San Bonifacio, Verona, Italy. Data were collected for all healthy newborns consecutively born over a period of three years, regarding type of delivery, feeding at hospital discharge, skin-to-skin procedure, and for a smaller group maternal nationality was recorded as well. The rate of exclusive breastfeeding in a group of 6017 newborns was 82.1%, higher among babies born by vaginal delivery than in those born by cesarean section (84.9% vs 65%; P<0.001). It was higher in those who had skin-to-skin contact than in those who did not, in both vaginal delivery (85.3% vs 69.2%; P<0.001) and cesarean section (67.7% vs 55.1%; P=0.009). Also, it was found to be higher in babies born to immigrant mothers than in those born to Italian mothers (89.9% vs 79.5%). Vaginal delivery, skin-to-skin contact and maternal foreign nationality have a positive association with breastfeeding at hospital discharge.


Prediction of Antibiotic Interactions Using Descriptors Derived from Molecular Structure.
Combination antibiotic therapies are clinically important in the fight against bacterial infections. However, the search space of drug combinations is large, making the identification of effective combinations a challenging task. Here, we present a computational framework that uses substructure profiles derived from the molecular structures of drugs and predicts antibiotic interactions. Using a previously published data set of 153 drug pairs, we showed that substructure profiles are useful in predicting synergy. We experimentally measured the interaction of 123 new drug pairs, as a prospective validation set for our approach, and identified 37 new synergistic pairs. Of the 12 pairs predicted to be synergistic, 10 were experimentally validated, corresponding to a 2.8-fold enrichment. Having thus validated our methodology, we produced a compendium of interaction predictions for all pairwise combinations among 100 antibiotics. Our methodology can make reliable antibiotic interaction predictions for any antibiotic pair within the applicability domain of the model since it solely requires chemical structures as an input.


Influence of endometrial thickness on pregnancy rates in modified natural cycle frozen-thawed embryo transfer.
Pregnancy after frozen-thawed embryo transfer (FET) is a multifactorial process. Although embryo quality is a key factor in determining pregnancy, other factors, including maternal determinants, are also considered to be predictive. Even though an association between endometrial thickness measured by transvaginal ultrasound and pregnancy rates has been reported in patients undergoing various assisted reproductive technology treatments, whether endometrial thickness predicts achieving pregnancy after natural cycle FET (NC-FET) remains unclear. In this cohort study, 463 patients allocated to the modified NC-FET (mNC-FET) arm of a previously published randomized controlled trial were included. Monitoring in mNC-FET cycles consisted of regular ultrasound scans, measuring both dominant follicle and endometrial thickness. When the dominant follicle reached a size of 16-20 mm, an injection of human chorionic gonadotrophin was administered and embryo thawing and transfer planned. No minimal endometrial thickness was defined below which transfer was to be deferred. The primary endpoint was ongoing pregnancy rate. Overall, the ongoing pregnancy rate per started FET cycle was 12.5%. Multivariate regression analyses showed that embryo quality was the only significant predictor for ongoing pregnancy. Mean endometrial thickness did not differ between patients achieving ongoing pregnancy and those who did not (9.0 vs. 8.8 mm, p = 0.4). Comparable results were obtained with regard to clinical pregnancy, live birth and miscarriage rates. The area under the receiver operator curve was 0.5, indicating little discriminatory value of endometrial thickness. Given that endometrial thickness was not found to be predictive of pregnancy after mNC-FET, cancellation based on endometrial thickness alone may not be justified.


Evaluation of novel combined carbogen USPIO (CUSPIO) imaging biomarkers in assessing the antiangiogenic effects of cediranib (AZD2171) in rat C6 gliomas.
The recently described combined carbogen USPIO (CUSPIO) magnetic resonance imaging (MRI) method uses spatial correlations in independent imaging biomarkers to assess specific components of tumor vascular structure and function. Our study aimed to evaluate CUSPIO biomarkers for the assessment of tumor response to antiangiogenic therapy. CUSPIO imaging was performed in subcutaneous rat C6 gliomas before and 2 days after treatment with the potent VEGF-signaling inhibitor cediranib (n = 12), or vehicle (n = 12). Histological validation of Hoechst 33342 uptake (perfusion), smooth muscle actin staining (maturation), pimonidazole adduct formation (hypoxia) and necrosis were sought. Following treatment, there was a significant decrease in fractional blood volume (-43%, p < 0.01) and a significant increase in hemodynamic vascular functionality (treatment altered ΔR(2) *(carbogen) from 1.2 to -0.2 s(-1) , p < 0.05). CUSPIO imaging revealed an overall significant decrease in plasma perfusion (-27%, p < 0.05) following cediranib treatment, that was associated with selective effects on immature blood vessels. The CUSPIO responses were associated with a significant 15% reduction in Hoechst 33342 uptake (p < 0.05), but no significant difference in vascular maturation or necrosis. Additionally, treatment with cediranib resulted in a significant 40% increase in tumor hypoxia (p < 0.05). The CUSPIO imaging method provides novel and more specific biomarkers of tumor vessel maturity and vascular hemodynamics, and their response to VEGF-signaling inhibition, compared to current MR imaging biomarkers utilized in the clinic. Such biomarkers may prove effective in longitudinally monitoring tumor vascular remodeling and/or evasive resistance in response to antiangiogenic therapy.


Ischemia-like oxygen and glucose deprivation mediates down-regulation of cell surface γ-aminobutyric acidB receptors via the endoplasmic reticulum (ER) stress-induced transcription factor CCAAT/enhancer-binding protein (C/EBP)-homologous protein (CHOP).
Cerebral ischemia frequently leads to long-term disability and death. Excitotoxicity is believed to be the main cause for ischemia-induced neuronal death. Although a role of glutamate receptors in this process has been firmly established, the contribution of metabotropic GABAB receptors, which control excitatory neurotransmission, is less clear. A prominent characteristic of ischemic insults is endoplasmic reticulum (ER) stress associated with the up-regulation of the transcription factor CCAAT/enhancer-binding protein-homologous protein (CHOP). After inducing ER stress in cultured cortical neurons by sustained Ca(2+) release from intracellular stores or by a brief episode of oxygen and glucose deprivation (in vitro model of cerebral ischemia), we observed an increased expression of CHOP accompanied by a strong reduction of cell surface GABAB receptors. Our results indicate that down-regulation of cell surface GABAB receptors is caused by the interaction of the receptors with CHOP in the ER. Binding of CHOP prevented heterodimerization of the receptor subunits GABAB1 and GABAB2 and subsequent forward trafficking of the receptors to the cell surface. The reduced level of cell surface receptors diminished GABAB receptor signaling and, thus, neuronal inhibition. These findings indicate that ischemia-mediated up-regulation of CHOP down-regulates cell surface GABAB receptors by preventing their trafficking from the ER to the plasma membrane. This mechanism leads to diminished neuronal inhibition and may contribute to excitotoxicity in cerebral ischemia.


What can neuromorphic event-driven precise timing add to spike-based pattern recognition?
This letter introduces a study to precisely measure what an increase in spike timing precision can add to spike-driven pattern recognition algorithms. The concept of generating spikes from images by converting gray levels into spike timings is currently at the basis of almost every spike-based modeling of biological visual systems. The use of images naturally leads to generating incorrect artificial and redundant spike timings and, more important, also contradicts biological findings indicating that visual processing is massively parallel, asynchronous with high temporal resolution. A new concept for acquiring visual information through pixel-individual asynchronous level-crossing sampling has been proposed in a recent generation of asynchronous neuromorphic visual sensors. Unlike conventional cameras, these sensors acquire data not at fixed points in time for the entire array but at fixed amplitude changes of their input, resulting optimally sparse in space and time-pixel individually and precisely timed only if new, (previously unknown) information is available (event based). This letter uses the high temporal resolution spiking output of neuromorphic event-based visual sensors to show that lowering time precision degrades performance on several recognition tasks specifically when reaching the conventional range of machine vision acquisition frequencies (30-60 Hz). The use of information theory to characterize separability between classes for each temporal resolution shows that high temporal acquisition provides up to 70% more information that conventional spikes generated from frame-based acquisition as used in standard artificial vision, thus drastically increasing the separability between classes of objects. Experiments on real data show that the amount of information loss is correlated with temporal precision. Our information-theoretic study highlights the potentials of neuromorphic asynchronous visual sensors for both practical applications and theoretical investigations. Moreover, it suggests that representing visual information as a precise sequence of spike times as reported in the retina offers considerable advantages for neuro-inspired visual computations.


Quality of asthma management in an urban community in Delhi, India.
High prevalence and poor control of asthma make its management a major public health issue worldwide, especially in developing countries. Optimum review of asthma management in the community is essential to improve asthma control. This study was conducted to investigate the quality of asthma management, knowledge about asthma and quality of life of asthma patients referred to a public tertiary care chest hospital in Delhi. Diagnosis of asthma was confirmed by symptoms and reversible spirometry in 50 referred patients on their first visit. Patients were interviewed using three questionnaires on quality of asthma management before visiting referral hospital, asthma knowledge and asthma quality of life (AQLQ). Correlation amongst quality of treatment, asthma quality of life, and asthma knowledge was also determined. Findings revealed that only 60 per cent of patients were informed about their disease, and 10 per cent had undergone lung function tests previously. Only 44 per cent of patients were prescribed inhalers. None were provided with any educational material. Patients had poor knowledge of aetiology, pathophysiology, medication and how to assess the severity of their asthma. The mean scores in AQLQ indicated a moderate degree of impairment in quality of life. INTERPRETATIONS & CONCLUSIONS: This study provides evidence of unsatisfactory asthma management and patient-doctor interaction as patients had limited knowledge of asthma disease, its management and had poor quality of life as measured by a standardized questionnaire. Thus, there is need to implement suitable interventions to improve asthma management according to standard treatment guidelines in the community.


The Role of Nutrition in Degenerative Cervical Myelopathy: A Systematic Review.
Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord impairment worldwide, encompassing chronic compression of the spinal cord, neurological disability and diminished quality of life. Evidence on the contribution of environmental factors is sparse; in particular, the role of nutrition in DCM is unknown. The objective of this review was to assess the effect of nutrition on DCM susceptibility, severity and surgical outcome. A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English papers, focussing on cervical myelopathy and nutrition, published before January 2020 were considered eligible. Quality assessments were performed using the GRADE assessment tool. Patient demographics, nutritional factor and DCM outcomes measures were recorded. Relationships between nutritional factors, interventions and disease prognosis were assessed. In total, 5835 papers were identified of which 44 were included in the final analysis. DCM patients with pathological weight pre-operatively were more likely to see poorer improvements post-surgically. These patients experienced poorer physical and mental health improvements from surgery compared to normal weight patients and were more likely to suffer from post-operative complications such as infection, DVT, PE and hospital readmissions. Two trials reporting benefits of nutritional supplements were identified, with 1 suggesting Cerebrolysin to be significant in functional improvement. An unbalanced diet, history of alcohol abuse and malnourishment were associated with poorer post-operative outcome. Although the overall strength of recommendation is low, current evidence suggests nutrition may have a significant role in optimising surgical outcome in DCM patients. Although it may have a role in onset and severity of DCM, this is a preliminary suggestion. Further work needs to be done on how nutrition is defined and measured, however, the beneficial results from studies with nutritional interventions suggest nutrition could be a treatment target in DCM.


BNIP3 expression in follicular lymphoma.
To investigate the role of BNIP3, a 19-kDa interacting protein of the Bcl-2 family, alongside Bcl-2 in follicular lymphoma in comparison with reactive lymphoid hyperplasia. The results were compared with those from p53 and caspase-3 (apoptotic markers) and Ki67 (proliferation marker). Immunohistochemistry using monoclonal antibodies showed BNIP3 to be strongly expressed in most follicular lymphomas but to be weak to negative in all of the reactive cases. There was also an inverse relationship with Bcl-2 expression. There was no correlation of BNIP3 immunoreactivity with proliferation and caspase and p53 were virtually negative in all follicular lymphomas and reactive lymphoid cases. BNIP3 is strongly expressed in most follicular lymphomas, especially those that are Bcl-2 negative. BNIP3 may serve as a marker of more aggressive behaviour in follicular lymphoma and be useful diagnostically in the distinction from reactive lymphadenitis.


Physical human model eye and methods of its use to analyse optical performance of soft contact lenses.
A bench-top physical model eye that closely replicates both anatomical and optical properties of an average human eye was designed and constructed. The cornea was sourced from a flouro-polymer with refractive index (RI) of 1.376 and crystalline lenses were made of Boston RGP polymers, EO and Equalens II, with an equivalent RI of 1.429 and 1.423 respectively. These materials served to make crystalline lens components of different age groups and accommodative states. De-Ionized water, with RI of 1.334 represented both aqueous and vitreous humor. The complementary metal-oxide sensor of a PixelLink digital camera with a resolution of 5MP and a 2.2 microm pixel pitch, hosted on a motor-base, served as the 'acting' retina. The translation and rotary functions of the motor-base facilitated the simulation of different states of ametropia and assessment of peripheral visual function, respectively. We validated one of its configurations to suit normal viewing conditions and results from the on and off-axis optical quality measurements are presented. As a demonstration of potential practical uses, several corrective soft contact lenses were placed on the model eye and their optical performance evaluated.


Cohesin's DNA exit gate is distinct from its entrance gate and is regulated by acetylation.
Sister chromatid cohesion is mediated by entrapment of sister DNAs by a tripartite ring composed of cohesin's Smc1, Smc3, and α-kleisin subunits. Cohesion requires acetylation of Smc3 by Eco1, whose role is to counteract an inhibitory (antiestablishment) activity associated with cohesin's Wapl subunit. We show that mutations abrogating antiestablishment activity also reduce turnover of cohesin on pericentric chromatin. Our results reveal a "releasing" activity inherent to cohesin complexes transiently associated with Wapl that catalyzes their dissociation from chromosomes. Fusion of Smc3's nucleotide binding domain to α-kleisin's N-terminal domain also reduces cohesin turnover within pericentric chromatin and permits establishment of Wapl-resistant cohesion in the absence of Eco1. We suggest that releasing activity opens the Smc3/α-kleisin interface, creating a DNA exit gate distinct from its proposed entry gate at the Smc1/3 interface. According to this notion, the function of Smc3 acetylation is to block its dissociation from α-kleisin. The functional implications of regulated ring opening are discussed.


Self-assembly of nanosized 0D clusters: CdS quantum dot-polyoxotungstate nanohybrids with strongly coupled electronic structures and visible-light-active photofunctions.
Nanohybrids of CdS-polyoxotungstate with strongly coupled electronic structures and visible-light-active photofunctions can be synthesized by electrostatically derived self-assembly of very small CdS quantum dots, or QDs, (particle size ≈ 2.5 nm) and polyoxotungstate nanoclusters (cluster size ≈1 nm). The formation of CdS-polyoxotungstate nanohybrids is confirmed by high-resolution transmission electron microscopy, elemental mapping, and powder X-ray diffraction analysis. Due to the strong electronic coupling between two semiconductors, the CdS-polyoxotungstate nanohybrids show a narrow bandgap energy of around 1.9-2.7 eV, thus reflecting their ability to harvest visible light. Time-resolved photoluminescence experiments indicate that the self-assembly between nanosized CdS and polyoxotungstate is very effective in increasing the lifetime of holes and electrons, thus indicating an efficient electron transfer between two-component semiconductors. The hybridization results not only in a significant improvement in the photostability of CdS QD but also in the creation of visible-light-induced photochromism. Of particular importance is that the present nanohybrids show visible-light-driven photocatalytic activity to produce H(2) and O(2) , which is superior to those of the unhybridized CdS and polyoxotungstate. The self-assembly of nanometer-level semiconductor clusters can provide a powerful way of optimizing the photoinduced functionalities of each component (i.e., visible-induced photochromism and photocatalysis) by means of strong electronic coupling.


Is the 1254T>C polymorphism in the DMT1 gene associated with Parkinson's disease?
Parkinson's disease (PD) is a late-onset neurodegenerative disorder with both familial and sporadic presentation. The main pathological characteristic of PD is the death of dopaminergic neurons in the substantia nigra (SN) pars compacta. PD is the second most common neurodegenerative disease worldwide, after Alzheimer's disease. Recent studies have suggested increased levels of iron and iron-binding proteins in the brains of patients with PD. Divalent metal transporter 1 (DMT1) is one protein responsible for iron transport. Postmortem studies have shown an important increase in DMT1 levels in the SN of patients with PD. Our aim is to determine whether there is an association between DMT1 polymorphisms and PD. We analyzed two single nucleotide polymorphisms (1254T>C and IVS4+44C>A) in the DMT1 gene in patients with 97 Parkinson's disease and in 100 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No association was found between the IVS4+44C>A polymorphism and PD, but the TT genotype and T allele of the 1254T>C polymorphism in the DMT1 gene were associated with PD (P=0.002 and P=0.012, respectively). In contrast to a previous study, our results suggest that the TT genotype and T allele of the 1254T>C polymorphism may be a risk factor for PD.


Informing Estimates of Program Effects for Studies of Mathematics Professional Development Using Teacher Content Knowledge Outcomes.
Mathematics professional development is widely offered, typically with the goal of improving teachers' content knowledge, the quality of teaching, and ultimately students' achievement. Recently, new assessments focused on mathematical knowledge for teaching (MKT) have been developed to assist in the evaluation and improvement of mathematics professional development. This study presents empirical estimates of average program change in MKT and its variation with the goal of supporting the design of experimental trials that are adequately powered to detect a specified program effect. The study drew on a large database representing five different assessments of MKT and collectively 326 professional development programs and 9,365 teachers. Results from cross-classified hierarchical growth models found that standardized average change estimates across the five assessments ranged from a low of 0.16 standard deviations (SDs) to a high of 0.26 SDs. Power analyses using the estimated pre- and posttest change estimates indicated that hundreds of teachers are needed to detect changes in knowledge at the lower end of the distribution. Even studies powered to detect effects at the higher end of the distribution will require substantial resources to conduct rigorous experimental trials. Empirical benchmarks that describe average program change and its variation provide a useful preliminary resource for interpreting the relative magnitude of effect sizes associated with professional development programs and for designing adequately powered trials.


Water-based synthesis and characterisation of a new Zr-MOF with a unique inorganic building unit.
A new, microporous Zr-MOF was obtained using 2,5-pyrazinedicarboxylic acid (H2PzDC). The linker leads to the formation of a new 1D inorganic building unit composed of μ-OH bridged {Zr6O4(OH4)} clusters which are arranged in a hexagonal array and connected by the PzDC2- ions. The structure was determined from powder X-ray diffraction data.


Generating the Visual Biofeedback Signals Applicable to Reduction of Wrist Spasticity: A Pilot Study on Stroke Patients.
Application of biofeedback techniques in rehabilitation has turned into an exciting research area during the recent decade. Providing an appropriate visual or auditory biofeedback signal is the most critical requirement of a biofeedback technique. In this regard, changes in Surface Electromyography (SEMG) signals during wrist movement can be used to generate an indictable visual biofeedback signal for wrist movement rehabilitation via SEMG biofeedback. This paper proposes a novel methodology for selecting the most appropriate features out of wrist muscle SEMG signals. To this end, the surface EMG signals from flexor and extensor muscle groups during wrist joint movements were recorded and analyzed. Some linear and nonlinear features in frequency, time, and time-frequency domains were extracted from the recorded surface EMG signals of the flexor and extensor muscles. Experiments and analyses were performed on ten healthy subjects and four stroke patients with wrist muscle spasticity as the movement disorder subjects. Some heuristic feature selection measures were applied. The main motivation behind choosing applied heuristic feature selection measures was meeting. In the first step, the designed visual biofeedback signal should indicate a healthy wrist motion profile as its successful tracking by the patient guarantees rehabilitation. In addition, the visual biofeedback signal should be a smooth curve thus preventing the patient from discomfort while tracking it on a monitor during the biofeedback therapy. In this pilot study, after using the introduced feature selection measures, quantitative and qualitative analyses of the extracted features indicated that Shannon entropy is the most appropriate feature for generating a visual biofeedback signal as a healthy wrist motion profile to improve the ability of stroke patients in controlling wrist joint motion. In addition, it was shown that when the wrist joint moves between a flexed and rest position, the flexor muscle EMG signal should be used for generating a visual biofeedback signal. However when the wrist joint moves between a rest position and an extended position, the extensor muscle EMG signal is appropriate for providing a visual biofeedback signal. It is worth noting that the achieved pilot study results should be confirmed by the future studies with larger samples. According to the obtained results, it can be concluded that among the analyzed features, the Shannon entropy was the most appropriate feature. It can be employed for generating a visual biofeedback signal for reduction of spasticity in patients with stroke.