Association Between Ocular Surface Temperature and Tear Film Stability in Soft Contact Lens Wearers.
To investigate the correlation between the changes in the ocular surface temperature (OST) and tear film stability over soft contact lenses (SCLs). We enrolled 20 eyes of 20 normal SCL wearers (20 men; 24.4 ± 4.1 years). We used four different daily disposable SCLs: one silicone hydrogel lens (delefilcon A) and three hydrogel lenses (etafilcon A with polyvinylpyrrolidone [PVP], etafilcon A, and polymacon). OST was measured every second during 10 seconds without blinking. We defined the difference in the OST from 0 to 10 seconds as ΔOST. To evaluate tear film stability, we measured noninvasive tear break-up time (NIBUT) and tear interference patterns on the contact lenses (TIPCL) using tear film interferometry. The parameters were measured before and 15 minutes after wearing each SCL. ΔOST was correlated significantly with NIBUT without (r = 0.411, P < 0.01) and with SCL (r = 0.642, P < 0.01). TIPCL grade was correlated significantly with ΔOST over SCLs (r = -0.636, P < 0.01). ΔOST was significantly smaller with silicone hydrogel delefilcon A than hydrogel etafilcon A and polymacon lenses (P < 0.05 and P < 0.01, respectively). Delefilcon A and etafilcon A with PVP lenses had significantly smaller NIBUT than etafilcon A (P < 0.05 for both comparisons). TIPCL grade of delefilcon A lens was significantly smaller than those of etafilcon A and polymacon (P < 0.01 for both comparisons). The changes in OST over SCLs are related to tear film stability. Measurements of OST can be used to evaluate tear film stability for SCL wearers.


Epidemiological profile and clinical associations of human bocavirus and other human parvoviruses.
Human bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom). Anonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction. HBoV infection was detected in 47 (8.2%) of 574 study subjects, ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6-24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4. In the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future.


Alloy and composition dependence of hydrogen embrittlement susceptibility in high-strength steel fasteners.
High-strength steel fasteners characterized by tensile strengths above 1100 MPa are often used in critical applications where a failure can have catastrophic consequences. Preventing hydrogen embrittlement (HE) failure is a fundamental concern implicating the entire fastener supply chain. Research is typically conducted under idealized conditions that cannot be translated into know-how prescribed in fastener industry standards and practices. Additionally, inconsistencies and even contradictions in fastener industry standards have led to much confusion and many preventable or misdiagnosed fastener failures. HE susceptibility is a function of the material condition, which is comprehensively described by the metallurgical and mechanical properties. Material strength has a first-order effect on HE susceptibility, which increases significantly above 1200 MPa and is characterized by a ductile--brittle transition. For a given concentration of hydrogen and at equal strength, the critical strength above which the ductile-brittle transition begins can vary due to second-order effects of chemistry, tempering temperature and sub-microstructure. Additionally, non-homogeneity of the metallurgical structure resulting from poorly controlled heat treatment, impurities and non-metallic inclusions can increase HE susceptibility of steel in ways that are measurable but unpredictable. Below 1200 MPa, non-conforming quality is often the root cause of real-life failures.This article is part of the themed issue 'The challenges of hydrogen and metals'.


The ingenious ULKs: expanding the repertoire of the ULK complex with phosphoproteomics.
The mammalian ULK kinase complex is the most upstream component in the macroautophagy/autophagy signaling pathway. ULK1 and homolog ULK2, the sole serine/threonine kinases in autophagy, transduce an array of autophagy-inducing stimuli to downstream autophagic machinery, regulating autophagy from autophagosome initiation to fusion of autophagosomes with lysosomes. ULK signaling is also implicated in a diverse array of non-canonical processes from necroptosis to ER-Golgi trafficking to stress granule clearance. However, the exact mechanisms by which ULK regulates these diverse processes remain largely unknown. Most notably, the number of validated ULK substrates is surprisingly low. Our study identifies new ULK substrates from a wide array of protein families and signaling pathways and supports an expanded range of physiological roles for the ULKs. We further characterize several new substrates, including the PIK3C3/VPS34-containing complex subunit PIK3R4/VPS15 and the AMPK component PRKAG2. Finally, by analyzing PIK3R4/VPS15-deficient models we discover novel aspects of ULK signaling with potential relevance in selective autophagy.


Learning disabilities: a survey of community nurses for people with prevalence of challenging behaviour and contact demands.
There is scant knowledge on the contacts community nurses for people with learning disabilities have with clients who display challenging behaviours, or the numbers of such people on these nurses' caseloads. This study was undertaken in a UK region with a population of 1.68 million people. In this region it is estimated that there are 8500 people with learning disabilities who are in contact with services, this includes around 500 people remaining in hospitals awaiting resettlement. The research aims were to identify the overall caseload sizes of the nurses, the prevalence of people with learning disabilities who have challenging behaviours on the nurses' caseloads and what contact demands these people required. An additional aim was to discover courses or training that helped the nurses to fulfill their roles. A postal survey was undertaken of the total population of community nurses for people with learning disabilities in the region. The method of data collection was a self-completion questionnaire. The study found that people with challenging behaviours accounted for over a quarter of the combined caseloads, and these clients required the most frequent visits from the nurses. There was a wide range in the number of clients on the caseloads of each nurse but overall these were higher than in other parts of the UK. It is concluded that community nurses for people with learning disabilities have large caseloads and people with learning disabilities who have challenging behaviours, who account for over one-quarter of the clients they visit, require much more frequent contact visits than other clients. The combination of high numbers of clients (or low numbers of these nurses) may impact on how such nurses are able to perform their role and functions. An increase in the numbers of community nurses for people with learning disabilities and skill development in caring for people with challenging behaviours is recommended. If this is not performed the clinical effectiveness of this group of nurses with respect to their work with people who challenge services may be unduly hampered.


Simultaneous segmentation and anatomical labeling of the cerebral vasculature.
We present a novel algorithm for the simultaneous segmentation and anatomical labeling of the cerebral vasculature. The method first constructs an overcomplete graph capturing the vasculature. It then selects and labels the subset of edges that most likely represents the true vasculature. Unlike existing approaches that first attempt to obtain a good segmentation and then perform labeling, we jointly optimize for both by simultaneously taking into account the image evidence and the prior knowledge about the geometry and connectivity of the vasculature. This results in an Integer Program (IP), which we solve optimally using a branch-and-cut algorithm. We evaluate our approach on a public dataset of 50 cerebral MRA images, and demonstrate that it compares favorably against state-of-the-art methods.


Probing the role of a secondary structure element at the 5'- and 3'-splice sites in group I intron self-splicing: the tetrahymena L-16 ScaI ribozyme reveals a new role of the G.U pair in self-splicing.
Several ribozyme constructs have been used to dissect aspects of the group I self-splicing reaction. The Tetrahymena L-21 ScaI ribozyme, the best studied of these intron analogues, catalyzes a reaction analogous to the first step of self-splicing, in which a 5'-splice site analogue (S) and guanosine (G) are converted into a 5'-exon analogue (P) and GA. This ribozyme preserves the active site but lacks a short 5'-terminal segment (called the IGS extension herein) that forms dynamic helices, called the P1 extension and P10 helix. The P1 extension forms at the 5'-splice site in the first step of self-splicing, and P10 forms at the 3'-splice site in the second step of self-splicing. To dissect the contributions from the IGS extension and the helices it forms, we have investigated the effects of each of these elements at each reaction step. These experiments were performed with the L-16 ScaI ribozyme, which retains the IGS extension, and with 5'- and 3'-splice site analogues that differ in their ability to form the helices. The presence of the IGS extension strengthens binding of P by 40-fold, even when no new base pairs are formed. This large effect was especially surprising, as binding of S is essentially unaffected for S analogues that do not form additional base pairs with the IGS extension. Analysis of a U.U pair immediately 3' to the cleavage site suggests that a previously identified deleterious effect from a dangling U residue on the L-21 ScaI ribozyme arises from a fortuitous active site interaction and has implications for RNA tertiary structure specificity. Comparisons of the affinities of 5'-splice site analogues that form only a subset of base pairs reveal that inclusion of the conserved G.U base pair at the cleavage site of group I introns destabilizes the P1 extension >100-fold relative to the stability of a helix with all Watson-Crick base pairs. Previous structural data with model duplexes and the recent intron structures suggest that this effect can be attributed to partial unstacking of the P1 extension at the G.U step. These results suggest a previously unrecognized role of the G.U wobble pair in self-splicing: breaking cooperativity in base pair formation between P1 and the P1 extensions. This effect may facilitate replacement of the P1 extension with P10 after the first chemical step of self-splicing and release of the ligated exons after the second step of self-splicing.


Helicobacter himalayensis sp. nov. isolated from gastric mucosa of Marmota himalayana.
A Gram-stain-negative, microaerophilic strain, 80(YS1)T, with a spiral-shaped morphology and 1-2 sheathed flagella at each end of the cells was isolated from the gastric mucosa of Marmota himalayana, the animal reservoir of Yersinia pestis in China, on the Qinghai-Tibet Plateau. The strain grew at 30, 35 and 42 °C, but not at 25 °C. Growth was in the form of a thinly spreading film on brain heart infusion agar containing 8 % sheep blood under microaerobic conditions. The strain did not hydrolyse urea or hippurate, and did not grow on media containing 1 % glycine. It reduced nitrate to nitrite, and was catalase- and alkaline-phosphatase-positive, susceptible to nalidixic acid and resistant to cefalotin. It was positive for genus-specific PCR for the genus Helicobacter, but could not be classified to any recognized species according biochemical tests results. Therefore, a phylogenetic study based on 16S rRNA, 23S rRNA, 60 kDa heat-shock protein (hsp60) and gyrase subunit B (gyrB) genes was conducted. The 16S rRNA gene sequence (1468 bp) analysis showed that strain 80(YS1)T was most closely related to Helicobacter marmotae (96.7 % similarity). The 23S rRNA gene sequence (2879 bp) analysis showed that the strain was most closely related to Helicobacter canis (96 % similarity). The complete gyrB gene sequence (2325 bp) analysis showed that it was related phylogenetically to Helicobacter cinaedi (79.4 % similarity) and H. marmotae (79.1 % similarity). Analysis of the partial sequence of the hsp60 gene of strain 80(YS1)T showed closest similarity to the sequences of Helicobacter equorum (82 %) and H. cinaedi (81 %), respectively. However, there was no hsp60 sequence of H. marmotae available for analysis. The data of morphological, biochemical and phylogenetic characteristics all supported that this strain represents a novel species. The name Helicobacter himalayensis sp. nov. is proposed for this novel species with the type strain 80(YS1)T ( = CGMCC 1.12864T = DSM 28742T).


How you provide corrective feedback makes a difference: the motivating role of communicating in an autonomy-supporting way.
We relied on self-determination theory (SDT; Deci & Ryan, 2000) to investigate to what extent autonomy-supporting corrective feedback (i.e., feedback that coaches communicate to their athletes after poor performance or mistakes) is associated with athletes' optimal motivation and well-being. To test this hypothesis, we conducted a cross-sectional study with 337 (67.1% males) Greek adolescent athletes (age M = 15.59, SD = 2.37) from various sports. Aligned with SDT, we found through path analysis that an autonomy-supporting versus controlling communication style was positively related to future intentions to persist and well-being and negatively related to ill-being. These relations were partially mediated by the perceived legitimacy of the corrective feedback (i.e., the degree of acceptance of corrective feedback), and, in turn, by intrinsic motivation, identified regulation, and external regulation for doing sports. Results indicate that autonomy-supporting feedback can be still motivating even in cases in which such feedback conveys messages of still too low competence.


Maintenance of cohesin at centromeres after meiosis I in budding yeast requires a kinetochore-associated protein related to MEI-S332.
The halving of chromosome number that occurs during meiosis depends on three factors. First, homologs must pair and recombine. Second, sister centromeres must attach to microtubules that emanate from the same spindle pole, which ensures that homologous maternal and paternal pairs can be pulled in opposite directions (called homolog biorientation). Third, cohesion between sister centromeres must persist after the first meiotic division to enable their biorientation at the second. A screen performed in fission yeast to identify meiotic chromosome missegregation mutants has identified a conserved protein called Sgo1 that is required to maintain sister chromatid cohesion after the first meiotic division. We describe here an orthologous protein in the budding yeast S. cerevisiae (Sc), which has not only meiotic but also mitotic chromosome segregation functions. Deletion of Sc SGO1 not only causes frequent homolog nondisjunction at meiosis I but also random segregation of sister centromeres at meiosis II. Meiotic cohesion fails to persist at centromeres after the first meiotic division, and sister centromeres frequently separate precociously. Sgo1 is a kinetochore-associated protein whose abundance declines at anaphase I but, nevertheless, persists on chromatin until anaphase II. The finding that Sgo1 is localized to the centromere at the time of the first division suggests that it may play a direct role in preventing the removal of centromeric cohesin. The similarity in sequence composition, chromosomal location, and mutant phenotypes of sgo1 mutants in two distant yeasts with that of MEI-S332 in Drosophila suggests that these proteins define an orthologous family conserved in most eukaryotic lineages.


Comparison of the effects of sevoflurane, isoflurane, and desflurane on microcirculation in coronary artery bypass graft surgery.
This investigation was performed to compare the effects of inhalation agents on microcirculation in coronary artery bypass grafting (CABG) using orthogonal polarization spectral imaging. This prospective and randomized study was performed in patients scheduled for CABG surgery from March through September 2010. Tertiary care university hospital. Thirty patients undergoing elective CABG. Patients were assigned to sevoflurane, desflurane, or isoflurane. Orthogonal polarization spectral imaging was used to evaluate the sublingual microcirculation. Hemodynamic variables (heart rate, mean arterial pressure, central venous pressure, cardiac output, and pulmonary capillary wedge pressure), laboratory parameters (hematocrit, lactate, and potassium), and microcirculatory variables (total vascular density [TVD] [mm/mm(2)], microvascular flow index [MFI] [arbitrary units], perfused vessel density [PVD] [mm/mm(2)], and proportion of perfused vessels [PPV] [percentage] were obtained before induction, after induction, during cardiopulmonary bypass, at the end of surgery, and 24 hours after surgery. The greatest alterations in microcirculation parameters were found during cardiopulmonary bypass. In the sevoflurane group, TVD (14.7%), PVD (22%), PPV (5.97%, p < 0.05), and MFI (7.69%, p > 0.05) were decreased. In the isoflurane group, TVD (14.7%) and PVD (20.3%) were decreased, whereas PPV (1.69%) and MFI (17.99%) were increased (p < 0.05). In the desflurane group, there were no changes in TVD and PVD, but MFI (8.99%, p > 0.05) and PPV (1.48%, p < 0.05) were increased in the small vessels. These changes returned to their initial values 24 hours postoperatively. Sevoflurane had a negative effect on the microcirculation. Isoflurane decreased vascular density and increased flow. Desflurane produced stable effects on the microcirculation. These inhalation agents induced transient alterations in microvascular perfusion.


Burden and Prevention of HPV. Knowledge, Practices and Attitude Assessment Among Pre-Adolescents and their Parents in Italy.
Despite infections due to HPV nowadays represent the most common sexually transmitted diseases worldwide with recognized effective and safe preventive strategies, knowledge, attitudes; however, awareness on HPV is considerably low. The present study has two main objectives: 1. To conduct a literature review to analyze the evolution of preventive tools, the complexity of the vaccine choice process, and the challenges posed by HPV vaccine hesitancy and refusal among pre-adolescents and their parents; 2. To assess knowledge, practices and attitudes toward HPV infection and vaccination in a sample of Italian pre-adolescents and their parents. The observational study was carried out through the use of two anonymous and self-administered pre- and postintervention questionnaires dedicated to the target populations. Between the administrations of the pre- and postintervention questionnaires, an educational intervention on HPV infection and related diseases, and prevention strategies was conducted. All participants demonstrated suboptimal knowledge and positive attitudes in the preintervention questionnaire. Higher levels of knowledge and attitudes were observed among pre-adolescents thatused social networks and had heard of sexually transmitted diseases at home/school/physician and from parents and also who had heard of HPV from General Practitioners, Gynecologists, family members and newspapers. A significant increase in HPV vaccination awareness was observed among pre-adolescents after the educational sessions. Health education programs aimed at increasing knowledge, attitudes and awareness on HPV are needed to implement the outcomes of HPV immunization programs, especially if supported by the physicians involved in counselling and recommendation processes.


2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases.
The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. The total diabetic population is expected to increase from 415 million in 2015 to 642 million by 2040. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of patients with type 2 diabetes died of ASCVD. The association between hyperglycemia and elevated cardiovascular (CV) risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction by conventional antidiabetic agents did not significantly reduce macrovascular outcomes.In December 2008, U.S. Food and Drug Administration issued a mandate that every new antidiabetic agent requires rigorous assessments of its CV safety. Thereafter, more than 200,000 patients have been enrolled in a number of randomized controlled trials (RCTs). These trials were initially designed to prove noninferiority. It turned out that some of these trials demonstrated superiority of some new antidiabetic agents versus placebo in reducing CV endpoints, including macrovascular events, renal events, and heart failure. These results are important in clinical practice and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases.In 2018, the Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC) published the first joint consensus on the "Pharmacological Management of Patients with Type 2 Diabetes and Cardiovascular Diseases." In 2020, TSOC appointed a new consensus group to revise the previous version. The updated 2020 consensus was comprised of 5 major parts: (1) treatment of diabetes in patients with multiple risk factors, (2) treatment of diabetes in patients with coronary heart disease, (3) treatment of diabetes in patients with stage 3 chronic kidney disease, (4) treatment of diabetes in patients with a history of stroke, and (5) treatment of diabetes in patients with heart failure. The members of the consensus group thoroughly reviewed all the evidence, mainly RCTs, and also included meta-analyses and real-world evidence. The treatment targets of HbA1c were finalized. The antidiabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.


Diffusion in tight confinement: a lattice-gas cellular automaton approach. I. Structural equilibrium properties.
The thermodynamic and transport properties of diffusing species in microporous materials are strongly influenced by their interactions with the confining framework, which provide the energy landscape for the transport process. The simple topology and the cellular nature of the alpha cages of a ZK4 zeolite suggest that it is appropriate to apply to the study of the problem of diffusion in tight confinement a time-space discrete model such as a lattice-gas cellular automaton (LGCA). In this paper we investigate the properties of an equilibrium LGCA constituted by a constant number of noninteracting identical particles, distributed among a fixed number of identical cells arranged in a three-dimensional cubic network and performing a synchronous random walk at constant temperature. Each cell of this network is characterized by a finite number of two types of adsorption sites: the exit sites available to particle transfer and the inner sites not available to such transfers. We represent the particle-framework interactions by assuming a differentiation in binding energy of the two types of sites. This leads to a strong dependence of equilibrium and transport properties on loading and temperature. The evolution rule of our LGCA model is constituted by two operations (randomization, in which the number of particles which will be able to try a jump to neighboring cells is determined, and propagation, in which the allowed jumps are performed), each one applied synchronously to all of the cells. The authors study the equilibrium distribution of states and the adsorption isotherm of the model under various conditions of loading and temperature. In connection with the differentiation in energy between exit and inner sites, the adsorption isotherm is described by a conventional Langmuir isotherm at high temperature and by a dual-site Langmuir isotherm at low temperature, while a first order diffuse phase transition takes place at very low temperature.


Plasmodium falciparum var gene expression is modified by host immunity.
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of immune targets, which play a central role in the host-parasite interaction by binding to various host molecules. They are encoded by a diverse family of genes called var, of which there are approximately 60 copies in each parasite genome. In sub-Saharan Africa, although P. falciparum infection occurs throughout life, severe malarial disease tends to occur only in childhood. This could potentially be explained if (i) PfEMP1 variants differ in their capacity to support pathogenesis of severe malaria and (ii) this capacity is linked to the likelihood of each molecule being recognized and cleared by naturally acquired antibodies. Here, in a study of 217 Kenyan children with malaria, we show that expression of a group of var genes "cys2," containing a distinct pattern of cysteine residues, is associated with low host immunity. Expression of cys2 genes was associated with parasites from young children, those with severe malaria, and those with a poorly developed antibody response to parasite-infected erythrocyte surface antigens. Cys-2 var genes form a minor component of all genomic var repertoires analyzed to date. Therefore, the results are compatible with the hypothesis that the genomic var gene repertoire is organized such that PfEMP1 molecules that confer the most virulence to the parasite tend also to be those that are most susceptible to the development of host immunity. This may help the parasite to adapt effectively to the development of host antibodies through modification of the host-parasite relationship.


Hydrate Nucleation, Growth, and Induction.
The first stage of any phase transition is a dynamic coupling of transport processes and thermodynamic changes. The free energy change of the phase transition must be negative and large enough to also overcome the penalty work needed for giving space to the new phase. The transition from an unstable situation over to a stable growth is called nucleation. Hydrate formation nucleation can occur along a variety of different routes. Heterogeneous formation on the interface between gas (or liquid) and water is the most commonly studied. A hydrate can also form homogeneously from dissolved hydrate formers in water, and the hydrate can nucleate toward mineral surfaces in natural sediments or a pipeline (rust). A hydrate particle's critical size is the particle size needed to enter a region of stable growth. These critical sizes and the associated nucleation times are nanoscale processes. The dynamics of the subsequent stable growth can be very slow due to transport limitations of hydrate-forming molecules and water across hydrate films. Induction times can be defined as the time needed to reach a visible hydrate. In the open literature, these induction times are frequently misinterpreted as nucleation times. Additional misunderstandings relate to the first and second laws of thermodynamics and the number of independent thermodynamics variables. It is not possible to reach thermodynamic equilibrium in systems where hydrates form in a pipeline or in sediments. Finally, there are common misconceptions that only one type of hydrate will form. In a non-equilibrium situation, several hydrates will form, depending on which phases the hydrate formers and water come from. In this paper, we utilize a simple nucleation theory to illustrate nucleation and growth of some simple hydrates in order to illustrate the non-equilibrium nature of hydrates and the fast nucleation times. To illustrate this, we apply thermodynamic conditions for a real pipeline transporting natural gas from Norway to Germany. This specific example also serves as a case for illustration of the possible impact of rusty pipeline surfaces in kicking out water from the gas. Specifically, we argue that the tolerance limit for water concentration according to current industrial hydrate risk practice might overestimate the tolerance by a factor of 20 as compared to tolerance concentration based on adsorption on rust.


Medial ganglionic eminence-derived neural stem cell grafts ease spontaneous seizures and restore GDNF expression in a rat model of chronic temporal lobe epilepsy.
Nearly 30% of patients with mesial temporal lobe epilepsy (TLE) are resistant to treatment with antiepileptic drugs. Neural stem cell (NSC) grafting into the hippocampus could offer an alternative therapy to hippocampal resection in these patients. As TLE is associated with reduced numbers of inhibitory gamma-amino butyric acid (GABA)-ergic interneurons and astrocytes expressing the anticonvulsant glial-derived neurotrophic factor (GDNF) in the hippocampus, we tested the hypothesis that grafting of NSCs that are capable of adding new GABA-ergic interneurons and GDNF-expressing astrocytes into the epileptic hippocampus restrains spontaneous recurrent motor seizures (SRMS) in chronic TLE. We grafted NSCs expanded in vitro from embryonic medial ganglionic eminence (MGE) into hippocampi of adult rats exhibiting chronic TLE with cognitive impairments. NSC grafting reduced frequencies of SRMS by 43% and stage V seizures by 90%. The duration of individual SRMS and the total time spent in seizures were reduced by 51 and 74%, respectively. Grafting did not improve the cognitive function however. Graft-derived cells (equivalent to approximately 28% of injected cells) were observed in various layers of the epileptic hippocampus where they differentiated into NeuN+ neurons (13%), S-100beta+ astrocytes (57%), and NG2+ oligodendrocyte-progenitors (3%). Furthermore, among graft-derived cells, 10% expressed GABA and 50% expressed GDNF. Additionally, NSC grafting restored GDNF in a vast majority of the hippocampal astrocytes but had no effect on neurogenesis. Thus, MGE-NSC therapy is efficacious for diminishing SRMS in chronic TLE. Addition of new GABA-ergic neurons and GDNF+ cells, and restoration of GDNF in the hippocampal astrocytes may underlie the therapeutic effect of MGE-NSC grafts.


Long-term Surveillance of Physical Activity Habits of Latinas Enrolled in a 12-Month Physical Activity Intervention.
Long-term physical activity surveillance has not been conducted among Latinas. This study explored the variability of daily physical activity habits of inactive adult Latinas participating in a 12-month physical activity intervention. We collected objective physical activity data (pedometer) from 139 Spanish speaking Latinas (age = 41.6 ± 10.1 years; BMI = 29.6 ± 4.3 kg/m2) enrolled in a 12-month physical activity intervention. Total and aerobic steps (>100 steps/minute) were computed by year, season, month, day of week, time of day, and hour. Participants walked an average of 6509 steps/day of which 1303 (20%) were aerobic steps. Significant physical activity differences were observed for subgroups including generational status, education, employment, income, marital status and health literacy. Significant and similar differences were observed for both total steps and aerobic steps for day of the week (weekdays > weekends) and season (summer > spring > fall > winter). Opposing trends were observed over the course of the day for total steps (early afternoon > late morning > late afternoon > early morning > evening) and aerobic steps (early morning > evening > late morning > late afternoon > early afternoon). Both seasonality and week day predicted physical activity habits of Latinas. This is the first long-term study to track daily physical activity habits of Latinas. These data have potential to inform the design of future physical activity interventions targeting Latinas.


Development and validation of diabetes empowerment questionnaire in Iranian people with type 2 diabetes.
Diabetes self-management education programmes which have been reported to improve the self-efficacy of diabetic people can lead to their empowerment. Specialized diabetes nurses also play a fundamental role in empowering patients with diabetes through improving their knowledge and self-care. The purpose of this study was to develop a valid and reliable questionnaire to measure empowerment in Iranian people with type 2 diabetes. Important subscales of patient empowerment were identified by an expert panel. The subscales included active self-care, coping with personal and social concerns, basic knowledge related to diabetes management and patient-physician communication. Questions related to each subscale were generated and the expert panel renewed the questionnaire to ensure relevance and clarity of the items. Patient focus groups were conducted to establish the face validity of the questionnaire. The final questionnaire consisted of 15 items organized in three subscales. In a population-based study, a sample of 378 people with type 2 diabetes was recruited. Reliability coefficient (Cronbach's α) was calculated for all of the subscales. Convergent validity was assessed by Pearson's product moment correlation. The scree test was used to select significant subscales. Two hundred forty-seven female and 131 male subjects with type 2 diabetes filled out the questionnaire. Three subscales were derived from factor analysis considering item-component loading of 0.4 as significant: 'active self-care' (Cronbach's α: 0.78), 'basic knowledge related to diabetes management' (Cronbach's α: 0.72) and 'coping with personal and social concerns' (Cronbach's α: 0.51). The scree plot of the eigenvalues of 15 items proposed three subscale solutions. Internal consistency reliabilities for the three subscales were acceptable (α: 0.51-0.78). The Diabetes Empowerment Questionnaire is a reliable and valid tool to assess patient empowerment in Iranian people with type 2 diabetes.


Characteristic spectra of energy absorption for dielectric solids.
A method has been developed of deriving the fundamental absorption spectra of solids directly from experimental infrared data without having to resort to computational evaluation. These characteristic lattice absorption spectra represent the true energy absorption spectra of solids. As opposed to the traditional absorption coefficient (k) vs frequency curve, which is regarded as the absorption spectrum for solids in the region of anomalous dispersion, the spectra, as derived by the proposed method, clearly resolve the transverse and longitudinal modes of vibration. They also exhibit the characteristics of anharmonicity and damping. The method uses the combined reflection and transmission data on single-crystal and thin-film specimens. Its validity has been verified on a wide variety of solids. The most recent data obtained from emission, laser-Raman, or cold neutron scattering techniques, is in complete agreement with the derived values. A method of calculating the various modes of vibration of solids, directly from elastic constants, is also advanced. It is simultaneously used to render further support for the developed characteristic energy absorption spectra. The importance of these spectra is discussed with regard to some problems in solid state physics.


A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.
Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67Ga, 77Br, 111In, 125I, 123I, 193mPt, 195mPt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.


Components that affect the Implementation of Health Services' Strategic Purchasing: A Comprehensive Review of the Literature.
Strategic purchasing is one of the mechanisms that can increase access, equity, and efficiency as well as the correct management of health resources. The aim of this study was to extract important and influential factors as necessary infrastructures to implement this method. In this comprehensive literature review, 13 databases and search engines were searched from 2000 to 2015 by applying appropriate keywords. From a total of 1403 titles and after ensuring the validity of the study by the Clinical Appraisal Skills Program (CASP) tool, 18 articles that contained title, abstract, and associated text were used in the study, and their related information was analyzed and extracted using an extraction form and LitAssist software. The findings showed six categories of intervention have been effective in the strategic purchasing of all health interventions in different countries. These six categories were "The target group of users of the service" (demand side), "purchased interventions," "providers and suppliers of interventions" (the supply side), "Methods and incentives" (payment method), "price," and "Structure and organization." Although the necessity of performing strategic purchasing in the health sector or developing countries is an indisputable fact, it is of great importance to use the experiences of developed countries while considering the factors extracted from the study for implementing this method. In this regard, it is suggested that studies be performed that can lead to assessing the feasibility of strategic purchasing for health services in developing countries and also in Iran to help health policy makers in these countries.


Nano-positioning system for structural analysis of functional homomeric proteins in multiple conformations.
Proteins may undergo multiple conformational changes required for their function. One strategy used to estimate target-site positions in unknown structural conformations involves single-pair resonance energy transfer (RET) distance measurements. However, interpretation of inter-residue distances is difficult when applied to three-dimensional structural rearrangements, especially in homomeric systems. We developed a positioning method using inverse trilateration/triangulation to map target sites within a homomeric protein in all defined states, with simultaneous functional recordings. The procedure accounts for probe diffusion to accurately determine the three-dimensional position and confidence region of lanthanide LRET donors attached to a target site (one per subunit), relative to a single fluorescent acceptor placed in a static site. As first application, the method is used to determine the position of a functional voltage-gated potassium channel's voltage sensor. Our results verify the crystal structure relaxed conformation and report on the resting and active conformations for which crystal structures are not available.


Cardiovascular risk factor trends and potential for reducing coronary heart disease mortality in the United States of America.
To examine the potential for reducing cardiovascular risk factors in the United States of America enough to cause age-adjusted coronary heart disease (CHD) mortality rates to drop by 20% (from 2000 baseline figures) by 2010, as targeted under the Healthy People 2010 initiative. Using a previously validated, comprehensive CHD mortality model known as IMPACT that integrates trends in all the major cardiovascular risk factors, stratified by age and sex, we calculated how much CHD mortality would drop between 2000 and 2010 in the projected population of the United States aged 25-84 years (198 million). We did this for three assumed scenarios: (i) if recent risk factor trends were to continue to 2010; (ii) success in reaching all the Healthy People 2010 risk factor targets, and (iii) further drops in risk factors, to the levels already seen in the low-risk stratum. If age-adjusted CHD mortality rates observed in 2000 remained unchanged, some 388,000 CHD deaths would occur in 2010. First scenario: if recent risk factor trends continued to 2010, there would be approximately 19,000 fewer deaths than in 2000. Although improved total cholesterol, lowered blood pressure in men, decreased smoking and increased physical activity would account for some 51,000 fewer deaths, these would be offset by approximately 32,000 additional deaths from adverse trends in obesity and diabetes and in blood pressure in women. Second scenario: If Healthy People 2010 cardiovascular risk factor targets were reached, approximately 188,000 CHD deaths would be prevented. Scenario three: If the cardiovascular risk levels of the low-risk stratum were reached, approximately 372,000 CHD deaths would be prevented. Achievement of the Healthy People 2010 cardiovascular risk factor targets would almost halve the predicted CHD death rates. Additional reductions in major risk factors could prevent or postpone substantially more deaths from CHD.


Timing and evolution of periventricular haemorrhage in infants weighing 1250 g or less at birth.
The brains of 50 consecutively admitted infants who weighed 1250 g or less at birth were examined with real time ultrasound. Of 30 (60%) who had periventricular haemorrhage (PVH), 19 (63%) bled on the first day and 17 (57%) showed extension of the initial haemorrhage on serial scans. The median age was 16 hours when PVH was first detected and 48 hours when PVH reached its maximum extent. Ventricular size at birth correlated with gestation. Progressive ventricular growth was seen after birth in infants both with and without PVH. Charts of normal ranges of ventricular size and head circumference were drawn up from birth to 10 weeks of age. All infants with PVH showed a transient increase in ventricular size at 2 weeks of age but most returned to normal by 6 weeks of age. Ventricular dilatation after PVH that was greater than the 95th centile for this population developed in 5 (31%) of 16 survivors, four of whom subsequently developed hydrocephalus, although none required ventriculo peritoneal shunting. The optimal timing for diagnosis with ultrasound is at the end of the first week for PVH and the second to third week for ventricular dilatation.


Zebrafish kidney development: basic science to translational research.
The zebrafish has become a significant model system for studying renal organogenesis and disease, as well as for the quest for new therapeutics, because of the structural and functional simplicity of the embryonic kidney. Inroads to the nature and disease states of kidney-related ciliopathies and acute kidney injury (AKI) have been advanced by zebrafish studies. This model organism has been instrumental in the analysis of mutant gene function for human disease with respect to ciliopathies. Additionally, in the AKI field, recent work in the zebrafish has identified a bona fide adult zebrafish renal progenitor (stem) cell that is required for neo-nephrogenesis, both during the normal lifespan and in response to renal injury. Taken together, these studies solidify the zebrafish as a successful model system for studying the broad spectrum of ciliopathies and AKI that affect millions of humans worldwide, and point to a very promising future of zebrafish drug discovery. The emphasis of this review will be on the role of the zebrafish as a model for human kidney-related ciliopathies and AKI, and how our understanding of these complex pathologies is being furthered by this tiny teleost.


Hypercarnivorous apex predator could provide ecosystem services by dispersing seeds.
Large "hypercarnivorous" felids are recognized for their role as apex predators and hence as key elements in food webs and ecosystem functioning through competition and depredation. Here we show that cougars (Puma concolor), one of the largest and the most widely ranging apex felid predators with a strictly carnivorous diet, could also be effective secondary long distance seed dispersers, potentially establishing direct and non-herbivore mediated interactions with plant species at the bottom of the food web. Cougars accidently ingest and disseminate large amounts of seeds (31,678 seeds in 123 scats) of plant species initially consumed by their main prey, the Eared Dove Zenaida auriculata. The germination potential of seeds for the three plant species most abundantly found in cougar scats (19,570 seeds) was not significantly different from that observed in seeds obtained from dove gizzards, indicating that seed passage through cougar guts did not affect seed germination. Considering the estimated cougar density in our study area, dispersal of seeds by cougars could allow a mean, annual seed spread of ~5,000 seeds per km(2). Our results demonstrate that strictly carnivorous, felid predators could have broad and overlooked ecological functions related to ecosystem structuring and functioning.


Extracorporeal shock wave lithotripsy for urinary tract stones using MPL 9000 spark gap technology and ultrasound monitoring.
Between November 7, 1988 and December 31, 1989, 881 treatments were given with the MPL 9000 lithotriptor to 513 sites in 510 renal units in 464 patients. Of the stones 447 (87.1%) were in the kidney, 64 (12.5%) in the ureter and 2 (0.4%) in the bladder. Stone size was up to 2 cm. in 58.5% of the cases, greater than 2 to 3 cm. in 25.8% and more than 3 cm. in 15.7%, including complete or partial staghorn, or multiple stones. Of the patients 54.2% received only 1 treatment, 17.6% received 2 treatments and 28.2% received more than 2 treatments (re-treatment was necessary in 45.8%). The number of shocks used varied from 610 to 4,000 at 14 to 24 kv., the usual energy used being 18 kv. Of the stones 30.2% were treated after Double-J stents were inserted. A patient was declared stone-free only when no stone particle was visible on a plain abdominal x-ray (or ultrasound if the stone was radiolucent). X-rays 3 months after extracorporeal shock wave lithotripsy (ESWL) were available for review in 397 patients (79.9%) and 72.8% were stone-free (with the aforementioned criteria) at 6 months (61.5% without ancillary procedures and 11.3% after ancillary procedures). Of a subset of 106 patients 84% were stone-free within 3 months when ESWL was restricted to a smaller stone burden, the number of shock waves administered was increased and energy was restricted to 14 to 18 kv. Over-all, 9.1% of the patients needed ancillary measures, including percutaneous nephrostomy in 1.6%, push-back for ESWL in 1.9%, ureterorenoscopy in 5.4%, percutaneous nephrolithotomy in 0.6% and pyelolithotomy/ureterolithotomy in 2.8%. The MPL 9000 device has the unique combination of electrohydraulic shock wave generation and ultrasound monitoring. The latter attribute has the distinct advantage of avoiding radiation to allow for visualization of nonopaque renal and gallbladder calculi. In addition, because there is continuous stone visualization during fragmentation accurate stone targeting can be maintained. The combination of ultrasound monitoring and spark gap technology allows for effective stone fragmentation.


The balance between proteinases and inhibitors in a murine model of proliferative retinopathy.
To examine the expression of matrix metalloproteinases (MMPs) and their inhibitors during the development of retinal neovascularization (NV) in a mouse model. A well-characterized murine model of retinal NV was used to study the expression of specific MMPs (MMP-2, MMP-9, and MT1-MMP) and tissue inhibitor of metalloproteinases (TIMPs types 1, 2, and 3). NV of the retina was induced in mice by exposure to 75% O(2) from postnatal day (P)7 to P12, followed by return to room air from P12 to P17. Expression of MMP mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). In addition, retinal tissue removed from control (without NV) and experimental animals (with NV) was analyzed for the expression of TIMP-1, TIMP-2, and TIMP-3 mRNA and protein using RT-PCR and Western blot analysis. During the angiogenic period from P13 to P17, MMP-2 and -9, and MT1-MMP message expression increased in experimental retinas compared with control samples. The TIMP-2 message and protein levels increased steadily in the retina of control animals until P17. This was in contrast to that seen in the retinas of the experimental animals in which TIMP-2 message and protein remained low and significantly less than in control samples. There were no significant changes in TIMP-3 message levels in retinal tissues, and TIMP-1 message and protein were undetectable. Correlation was made at the mRNA and protein levels of TIMP expression compared with that of MMPs in a murine model of retinal NV, which suggests a temporal role for MMP-2 and -9, MT1-MMP, and TIMP-2 in new vessel formation in response to hypoxic stimulation.


Patterns of skin cancer and treatment outcomes for patients with albinism at Kisangani Clinic, Democratic Republic of Congo.
People with albinism (PWA) are at increased risk of photodamage and skin cancer. In many parts of Africa, there is a significant lack of knowledge regarding albinism which can lead to societal stigma, discrimination, and persecution from an early age. In the Democratic Republic of Congo (DRC), there is limited clinical data on PWA and skin cancer. We aim to better understand sociodemographics, risk factors, clinical features, and outcomes of this population. Patients with a diagnosis of albinism and skin cancer presenting to Kisangani Albino Clinic were enrolled. Of 205 PWA, 61 patients were diagnosed with skin cancer with a mean age of 26.5 years. Common occupations were student (45.6%) or unemployed (26.4%). Discrimination was experienced from close contacts (24.4%) and society (67.4%). A majority (88.5%) had never used sunscreen, only 4.9% used fully sun protective clothing, and 90.2% spent 4 or more hours in the sun daily. Skin cancers had a mean size of 3.8 cm and were most commonly located on the face (47.7%). Squamous cell carcinoma was the most common histopathological diagnosis. Most patients underwent excision, and 90.2% had clinical clearance of tumors at a mean follow-up of 5.7 months. People living with albinism in the DRC experience a high rate of nonmelanoma skin cancers at a young age and additionally face a number of psychosocial challenges. This study represents the first attempt to analyze a cohort of patients with albinism from the DRC and serves to increase awareness of this vulnerable population.


Risk factors for community-acquired pneumonia in adults: a population-based case-control study.
Although community-acquired pneumonia (CAP) remains a major cause of hospitalization and death, few studies on risk factors have been performed. A population-based case-control study of risk factors for CAP was carried out in a mixed residential-industrial urban area of 74,610 adult inhabitants in the Maresme (Barcelona, Spain) between 1993 and 1995. All patients living in the area and clinically suspected of having CAP at primary care facilities and hospitals were registered. In total, 205 patients with symptoms, signs and radiographic infiltrate compatible with acute CAP participated in the study. They were matched by municipality, sex and age with 475 controls randomly selected from the municipal census. Risk factors relating the subject's characteristics and habits, housing conditions, medical history and treatments were investigated by means of a questionnaire. In the univariate analysis, an increased risk of CAP was associated with low body mass index, smoking, respiratory infection, previous pneumonia, chronic lung disease, lung tuberculosis, asthma, treated diabetes, chronic liver disease, and treatments with aminophiline, aerosols and plastic pear-spacers. In multivariate models, the only statistically significant risk factors were current smoking of >20 cigarettes x day(-1) (odds ratio (OR)=2.77; 95% confidence interval (CI) 1.14-6.70 compared with never-smokers), previous respiratory infection (OR=2.73; 95% CI 1.75-4.26), and chronic bronchitis (OR=2.22; 95% CI 1.13-4.37). Benzodiazepines were found to be protective in univariate and multivariate analysis (OR=0.46; 95% CI 0.23-0.94). This population-based study provides new and better established evidence on the factors associated with the occurrence of pneumonia in the adult community.


Characterization, Genetic Analyses, and Identification of QTLs Conferring Metabolic Resistance to a 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor in Sorghum (Sorghum bicolor).
Postemergence grass weed control continues to be a major challenge in grain sorghum [Sorghum bicolor (L.) Moench], primarily due to lack of herbicide options registered for use in this crop. The development of herbicide-resistant sorghum technology to facilitate broad-spectrum postemergence weed control can be an economical and viable solution. The 4-hydroxyphenylpyruvate dioxygenase-inhibitor herbicides (e.g., mesotrione or tembotrione) can control a broad spectrum of weeds including grasses, which, however, are not registered for postemergence application in sorghum due to crop injury. In this study, we identified two tembotrione-resistant sorghum genotypes (G-200, G-350) and one susceptible genotype (S-1) by screening 317 sorghum lines from a sorghum association panel (SAP). These tembotrione-resistant and tembotrione-susceptible genotypes were evaluated in a tembotrione dose-response [0, 5.75, 11.5, 23, 46, 92 (label recommended dose), 184, 368, and 736 g ai ha-1] assay. Compared with S-1, the genotypes G-200 and G-350 exhibited 10- and seven fold more resistance to tembotrione, respectively. To understand the inheritance of tembotrione-resistant trait, crosses were performed using S-1 and G-200 or G-350 to generate F1 and F2 progeny. The F1 and F2 progeny were assessed for their response to tembotrione treatment. Genetic analyses of the F1 and F2 progeny demonstrated that the tembotrione resistance in G-200 and G-350 is a partially dominant polygenic trait. Furthermore, cytochrome P450 (CYP)-inhibitor assay using malathion and piperonyl butoxide suggested possible CYP-mediated metabolism of tembotrione in G-200 and G-350. Genotype-by-sequencing based quantitative trait loci (QTL) mapping revealed QTLs associated with tembotrione resistance in G-200 and G-350 genotypes. Overall, the genotypes G-200 and G-350 confer a high level of metabolic resistance to tembotrione and controlled by a polygenic trait. There is an enormous potential to introgress the tembotrione resistance into breeding lines to develop agronomically desirable sorghum hybrids.


Surf lifeguard rescues.
This study assessed the utility of lifeguard rescue data for providing information on person and situation factors to inform surf bather drowning prevention research. The dataset comprised 872 beach-days (daily lifeguard reports) obtained from 26 beaches over a 95-day period in Victoria, Australia. The rescue rate was 128 per 100,000 in-water bathers. One or more rescues were required on 125 beach-days (14%). Rescue on a beach-day was more likely for offshore wind conditions, relatively high daily air temperatures, and high bather numbers (P < .05). Compared to female bathers, males were more frequently rescued (65%) and more likely (P < .05) to be from a younger age group (30 years or less), although being older was associated with a relatively poorer condition on rescue. Although rescues are proportional to water exposure, frequencies are also influenced by situation and person factors. Bathers at relatively high risk of rescue are hypothesized to be overrepresented in amenable sea and weather conditions, and poor patient condition on rescue may be associated with exposure to a preexisting health condition.


Development of an Australian practice-based research network as a community of practice.
There are many aspects of the communities of practice (CoP) framework that are applicable to the development of a practice-based research network (PBRN), where the focus is upon building primary health-care workers' research capacity and research questions. However, there is limited literature focussed on the application of CoP principles applied to research capacity building in Australia. The purpose of this paper is to demonstrate, through a case study, how a developing PBRN, the Illawarra and Southern Practice Research Network, successfully applied the theoretical foundation of CoP to develop a PBRN in a time- and resource-limited context.


¹³C- and ¹H-detection under fast MAS for the study of poorly available proteins: application to sub-milligram quantities of a 7 trans-membrane protein.
We demonstrate that (13)C-detected spectra recorded using fast (60 kHz) magic angle spinning on sub-milligram (<10 μmol) quantities of a protonated 7 trans-membrane helix protein (bacteriorhodopsin) in its native lipid environment are comparable in sensitivity and resolution to those recorded using 15-fold larger sample volumes with conventional solid state NMR methodology. We demonstrate the utility of proton-detected measurements which yield narrow (1)H linewidths under these conditions, and that no structural alterations are observed. We propose that these methods will prove useful to gain structural information on membrane proteins with poor availability, which can be studied in their native lipid environments.


Viability of limbal epithelium after anterior lamellar harvesting using a microkeratome.
To determine the viability in cold eye bank storage of different layers of central and limbal corneal epithelium, including the limbal basal stem cell population, on days 0, 3, 6, and 9 after harvest using a large diameter microkeratome system. Twenty-two human whole globes not suitable for transplantation were obtained from an eye bank (San Diego Eye Bank, San Diego, California) and used for study. Large-diameter anterior corneal discs were prepared using a large diameter microkeratome and stained with calcein AM and an ethidium homodimer to differentiate live from dead cells, respectively. A laser confocal microscope and digital imaging were used to distinguish live (green) from dead (red) cells. Central and limbal epithelial regions were isolated and the middle and basal epithelial sections were cell counted by 3 independent observers. These sections were stored up to 9 days at 4 degrees C in an eye bank corneal storage medium. Differences were tested using nonparametric methods. The percentage of live cells in each of these epithelial layers was determined for up to 9 days in cold eye bank corneal storage medium. At all time points studied, the better protected basal epithelial layers displayed greater mean viability than the overlying middle epithelial layers. However, the difference was not statistically significant on all days. When comparing the basal epithelial viability of the limbal and central regions, after day 0 in 4 degrees C cold organ culture, the observed viability of the limbal basal epithelium, the purported location of the limbal epithelial stem cell region, was significantly greater than that of the central epithelium. On day 0, median limbal basal versus central basal epithelial viability were 100% (range, 71.7-100%) versus 98.4% (range, 88.9-100%) (P>0.05); on day 3, 100% (range, 64.3-100%) versus 63.4% (range, 13.6-95.5%) (P<0.0005); on day 6, 95.0% (range, 35.0-100%) versus 28.0% (range, 0-92.0%) (P<0.0005); and on day 9, 95.0% (range, 3.7-100%) versus 68.6% (range, 0-100%) (P<0.0005). After microkeratome harvesting, the limbal basal epithelium is significantly longer lived in cold eye bank storage than central basal epithelium and the middle layers of limbal and central epithelium. This longevity not only bodes well for organ storage of limbal grafts, but also confirms the hardiness of the stem cell region.


Short-Term Impact of FS-LASIK and SMILE on Dry Eye Metrics and Corneal Nerve Morphology.
To analyze the short-term (up to 1 month) clinical outcomes in patients undergoing corneal laser refractive surgery and the impact on dry eye disease (DED) metrics and corneal nerves using in vivo confocal microscopy (IVCM). The unaided distance visual acuity, corrected distance visual acuity, and spherical equivalent refraction (SEQ) were determined in 16 and 13 patients undergoing FS-LASIK and SMILE, respectively. DED metrics assessed were Ocular Surface Disease Index, Dry Eye Questionnaire 5-items (DEQ-5), tear film osmolarity, tear meniscus height, noninvasive keratograph breakup time (NIKBUT), ocular staining, and meibomian gland atrophy. An automated analysis of corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length (CNFL), and corneal nerve fiber fractal dimension were obtained from the IVCM scans using ACCMetrics software (University of Manchester). Both surgical techniques provided good refractive and visual outcomes. DED symptoms were found to be higher after FS-LASIK compared with SMILE (P < 0.05). A decrease in tear meniscus height (∼31%) and NIKBUT (∼40%) was reported after FS-LASIK (P = 0.005 and P = 0.001, respectively) but not after SMILE. Both procedures affected corneal nerve fiber density, corneal nerve branch density, CNFL, and corneal nerve fiber fractal dimension, but the impact was significantly greater with FS-LASIK (P = 0.001). Only CNFL correlated with the reported symptoms (DEQ-5) after FS-LASIK (r = -0.545, P = 0.029). FS-LASIK and SMILE provided good refractive and visual outcomes. There was an increased impact on DED symptoms after FS-LASIK compared with SMILE, although there were no significant differences between the procedures for most of the other ocular surface metrics assessed. The IVCM findings showed that SMILE had less impact on corneal nerves compared with FS-LASIK.


Achievable Benchmarks of Care for Pediatric Readmissions.
Most inpatient care for children occurs outside tertiary children's hospitals, yet these facilities often dictate quality metrics. Our objective was to calculate the mean readmission rates and the Achievable Benchmarks of Care (ABCs) for pediatric diagnoses by different hospital types: metropolitan teaching, metropolitan nonteaching, and nonmetropolitan hospitals. We used a cross-sectional retrospective study of 30-day, all-cause, same-hospital readmission of patients less than 18 years old using the 2014 Healthcare Utilization Project National Readmission Database. For each hospital type, we calculated the mean readmission rates and corresponding ABCs for the 17 most common readmission diagnoses. We define outlier as any hospital whose readmission rate fell outside the 95% CI for an ABC within their hospital type. We analyzed 690,949 discharges at 525 metropolitan teaching hospitals (550,039 discharges), 552 metropolitan nonteaching hospitals (97,207 discharges), and 587 nonmetropolitan hospitals (43,703 discharges). Variation in readmission rates existed among hospital types; however, sickle cell disease (SCD) had the highest readmission rate and ABC across all hospital types: metropolitan teaching hospitals 15.7% (ABC 7.0%), metropolitan nonteaching 14.7% (ABC 2.6%), and nonmetropolitan 12.8% (ABC not calculated). For diagnoses in which ABCs were available, outliers were prominent in bipolar disorders, major depressive disorders, and SCD. ABCs based on hospital type may serve as a better metric to explain case-mix variation among different hospital types in pediatric inpatient care. The mean rates and ABCs for SCD and mental health disorders were much higher and with more outlier hospitals, which indicate high-value targets for quality improvement.


Porous nanoarchitectures of spinel-type transition metal oxides for electrochemical energy storage systems.
Transition metal oxides possessing two kinds of metals (denoted as AxB3-xO4, which is generally defined as a spinel structure; A, B = Co, Ni, Zn, Mn, Fe, etc.), with stoichiometric or even non-stoichiometric compositions, have recently attracted great interest in electrochemical energy storage systems (ESSs). The spinel-type transition metal oxides exhibit outstanding electrochemical activity and stability, and thus, they can play a key role in realising cost-effective and environmentally friendly ESSs. Moreover, porous nanoarchitectures can offer a large number of electrochemically active sites and, at the same time, facilitate transport of charge carriers (electrons and ions) during energy storage reactions. In the design of spinel-type transition metal oxides for energy storage applications, therefore, nanostructural engineering is one of the most essential approaches to achieving high electrochemical performance in ESSs. In this perspective, we introduce spinel-type transition metal oxides with various transition metals and present recent research advances in material design of spinel-type transition metal oxides with tunable architectures (shape, porosity, and size) and compositions on the micro- and nano-scale. Furthermore, their technological applications as electrode materials for next-generation ESSs, including metal-air batteries, lithium-ion batteries, and supercapacitors, are discussed.


Preregistration rotation including general practice at St Mary's Hospital Medical School.
A rotation for the preregistration year which included medicine, surgery, and general practice started at St Mary's Hospital Medical School in August 1981. Initially approved by London University for an experimental period of three years, in 1984 it became an established rotation subject to normal review. Special arrangements were made for clinical work, supervision, prescribing, teaching, and other aspects of the general practice component. Data relating to the general practice consultations of the nine participating house officers show that they obtained wide experience, and their comments on the post itself were generally favourable. The four months spent in general practice were needed to allow time for the house officers to adapt to the new setting but did not seem to have an important effect on their experience in medicine and surgery.


Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.
Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.


The Effect of Hypnosis on Adherence to Antituberculosis Drugs Using the Health Belief Model.
An RCT on the efficacy of hypnosis in improving adherence to antituberculosis treatment using the Health Belief Model (HBM). Sixty study subjects were sampled at random from tuberculosis patients who visited the Center for Pulmonary Community Health in Solo, Indonesia. Hypnotherapy with posthypnotic suggestions was delivered once a week over 6 months. The data on pretested 7 HBM constructs were analyzed using t test and path analysis. Hypnotherapy had a positive effect on perceived susceptibility, seriousness, threat, benefit, and self-efficacy. It indirectly had a positive effect on adherence. Hypnotherapy had a negative effect on perceived barrier. This study supports the hypothesis that hypnotherapy effectively improves adherence to tuberculosis treatment, by enhancing health-related perception and beliefs in the HBM.


Pregabalin in fibromyalgia--responder analysis from individual patient data.
Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores. We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (>or= 0%), minimal improvement (>or= 15%), moderate improvement (>or= 30%), substantial improvement (>or= 50%), and extensive improvement (>or= 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo. Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for >or= 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for >or= 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response. Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.


Harmonized benchmark labels of the hippocampus on magnetic resonance: the EADC-ADNI project.
A globally harmonized protocol (HarP) for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer's Disease Consortium (EADC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Our aim was to produce benchmark labels based on the HarP for manual segmentation. Five experts of manual hippocampal segmentation underwent specific training on the HarP and segmented 40 right and left hippocampi from 10 ADNI subjects on both 1.5 T and 3 T scans. An independent expert visually checked segmentations for compliance with the HarP. Descriptive measures of agreement between tracers were intraclass correlation coefficients (ICCs) of crude volumes and similarity coefficients of three-dimensional volumes. Two hundred labels have been provided for the 20 magnetic resonance images. Intra- and interrater ICCs were >0.94, and mean similarity coefficients were 1.5 T, 0.73 (95% confidence interval [CI], 0.71-0.75); 3 T, 0.75 (95% CI, 0.74-0.76). Certified benchmark labels have been produced based on the HarP to be used for tracers' training and qualification.


The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila.
During animal development cellular differentiation is often preceded by an asymmetric cell division whose polarity is determined by the orientation of the mitotic spindle. In the fruit fly, Drosophila melanogaster, the oocyte differentiates in a 16-cell syncytium that arises from a cystoblast which undergoes 4 synchronous divisions with incomplete cytokinesis. During these divisions, spindle orientation is highly ordered and is thought to impart a polarity to the cyst that is necessary for the subsequent differentiation of the oocyte. Using mutations in the Drosophila cytoplasmic dynein heavy chain gene, Dhc64C, we show that cytoplasmic dynein is required at two stages of oogenesis. Early in oogenesis, dynein mutations disrupt spindle orientation in dividing cysts and block oocyte determination. The localization of dynein in mitotic cysts suggests spindle orientation is mediated by the microtubule motor cytoplasmic dynein. Later in oogenesis, dynein function is necessary for proper differentiation, but does not appear to participate in morphogen localization within the oocyte. These results provide evidence for a novel developmental role for the cytoplasmic dynein motor in cellular determination and differentiation.


The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology.
Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct nosologic entity. Aetiology of SFN includes pre-diabetes status and immune-mediated diseases, though it remains frequently unknown. Due to their physiologic characteristics, small nerve fibres cannot be investigated by routine electrophysiological tests, making the diagnosis particularly difficult. Quantitative sensory testing (QST) to assess the psychophysical thresholds for cold and warm sensations and skin biopsy with quantification of somatic intraepidermal nerve fibres (IENF) have been used to determine the damage to small nerve fibres. Nevertheless, the diagnostic criteria for SFN have not been defined yet and a 'gold standard' for clinical practise and research is not available. We screened 486 patients referred to our institutions and collected 124 patients with sensory neuropathy. Among them, we identified 67 patients with pure SFN using a new diagnostic 'gold standard', based on the presence of at least two abnormal results at clinical, QST and skin biopsy examination. The diagnosis of SFN was achieved by abnormal clinical and skin biopsy findings in 43.3% of patients, abnormal skin biopsy and QST findings in 37.3% of patients, abnormal clinical and QST findings in 11.9% of patients, whereas 7.5% patients had abnormal results at all the examinations. Skin biopsy showed a diagnostic efficiency of 88.4%, clinical examination of 54.6% and QST of 46.9%. Receiver operating characteristic curve analysis confirmed the significantly higher performance of skin biopsy comparing with QST. However, we found a significant inverse correlation between IENF density and both cold and warm thresholds at the leg. Clinical examination revealed pinprick and thermal hypoesthesia in about 50% patients, and signs of peripheral vascular autonomic dysfunction in about 70% of patients. Spontaneous pain dominated the clinical picture in most SFN patients. Neuropathic pain intensity was more severe in patients with SFN than in patients with large or mixed fibre neuropathy, but there was no significant correlation with IENF density. The aetiology of SFN was initially unknown in 41.8% of patients and at 2-year follow-up a potential cause could be determined in 25% of them. Over the same period, 13% of SFN patients showed the involvement of large nerve fibres, whereas in 45.6% of them the clinical picture did not change. Spontaneous remission of neuropathic pain occurred in 10.9% of SFN patients, while it worsened in 30.4% of them.


Optimizing telemedicine to facilitate amyotrophic lateral sclerosis clinical trials.
Amyotrophic lateral sclerosis (ALS) has the largest drug pipeline among neuromuscular diseases, with over 160 companies actively involved in ALS research. There is a growing need to recruit trial participants, but ALS patients often have limited mobility and most ALS trials are conducted in a small number of major centers. These factors effectively limit patient participation, particularly for those in rural areas. The current coronavirus disease 2019 (COVID-19) pandemic has necessitated the more widespread use of telemedicine technology for clinical care, and has prompted consideration of its increased use for clinical trials. In this opinion piece, we describe the current state of telemedicine for recruitment, consenting, and screening of participants for clinical trials. We also summarize the available data on remote administration of outcome measures. Current challenges include validation of outcome measures for remote assessment, as well as technological, regulatory, and licensure barriers.


Efficacy of Three Different Prophylactic Treatments for Postoperative Nausea and Vomiting after Vitrectomy: A Randomized Clinical Trial.
Postoperative nausea and vomiting (PONV) after vitreoretinal surgery may potentially be associated with severe complications, such as suprachoroidal hemorrhage. The purpose of the present multicenter clinical trial (NCT02386059) was to assess the efficacy of three different prophylactic treatments for PONV after vitrectomy under local anesthesia. Patients undergoing primary vitrectomy were randomized to the control arm or to one of the treatment arms (4 mg ondansetron, 4 mg dexamethasone, combination of the two drugs). The primary outcome measure was the proportion of complete response (no nausea, no vomiting, no retching, and no use of antiemetic rescue medication) during 24 h after vitrectomy. Secondary outcomes included the severity standardized score of PONV, postoperative pain standardized score, and rate of ocular and non-ocular adverse events. Baseline demographics of the 1287 patients were comparable between the four arms. The combined therapy group showed a statistically significant lower incidence of PONV compared to the placebo and monotherapy (p < 0.001). PONV severity was also reduced in the combination group compared to the others (p < 0.001). Postoperative pain scores and adverse events were comparable among the four groups. Combined therapy with dexamethasone and ondansetron was the most effective treatment for reducing the incidence and severity of PONV in patients undergoing vitrectomy under local anesthesia.


Perceptual organization at attended and unattended locations.
This study examined the effects of attention on forming perceptual units by proximity grouping and by uniform connectedness (UC). In Experiment 1 a row of three global letters defined by either proximity or UC was presented at the center of the visual field. Participants were asked to identify the letter in the middle of stimulus arrays while ignoring the flankers. The stimulus onset asynchrony (SOA) between stimulus arrays and masks varied between 180 and 500 ms. We found that responses to targets defined by proximity grouping were slower than to those defined by UC at median SOAs but there were no differences at short or long SOAs. Incongruent flankers slowed responses to targets and this flanker compatibility effect was larger for UC than for proximity-defined flankers. Experiment 2 examined the effects of spatial precueing on discrimination responses to proximity- and UC-defined targets. The advantage for targets defined by UC over targets defined by proximity grouping was greater at uncued relative to cued locations. The results suggest that the advantage for UC over proximity grouping in forming perceptual units is contingent on the stimuli not being fully attended, and that paying attention to the stimuli differentially benefits proximity grouping.


Tb1, a Neurotoxin from Tityus bahiensis Scorpion Venom, Induces Epileptic Seizures by Increasing Glutamate Release.
Here, we report the neurotoxic effects aroused by the intracerebral injection (in rats) of Tb1, which is a neurotoxin isolated from Tityus bahiensis scorpion venom. Biochemical analyses have demonstrated that this toxin is similar to the gamma toxin from T. serrulatus, which is a β-scorpion toxin that acts on sodium channels, causing the activation process to occur at more hyperpolarized membrane voltages. Male Wistar rats were stereotaxically implanted with intrahippocampal electrodes and cannulas for electroencephalographic recording and the evaluation of amino acid neurotransmitters levels. Treated animals displayed behavioral and electroencephalographic alterations similar to epileptiform activities, such as myoclonus, wet dog shakes, convulsion, strong discharges, neuronal loss, and increased intracerebral levels of glutamate. Scorpion toxins are important pharmacological tools that are widely employed in ion channel dysregulation studies. The current work contributes to the understanding of channelopathies, particularly epilepsy, which may originate, among other events, from dysfunctional sodium channels, which are the main target of the Tb1 toxin.


Observation inflation. Your actions become mine.
Imagining performing an action can induce false memories of having actually performed it-this is referred to as the imagination-inflation effect. Drawing on research suggesting that action observation-like imagination-involves action simulation, and thus creates matching motor representations in observers, we examined whether false memories of self-performance can also result from merely observing another person's actions. In three experiments, participants observed actions, some of which they had not performed earlier, and took a source-memory test. Action observation robustly produced false memories of self-performance relative to control conditions. The demonstration of this effect, which we refer to as observation inflation, reveals a previously unknown source of false memories that is ubiquitous in everyday life. The effect persisted despite warnings or instructions to focus on self-performance cues given immediately before the test, and despite elimination of sensory overlap between performance and observation. The findings are not easily reconciled with a source-monitoring account but appear to fit an account invoking interpersonal motor simulation.


Health in climate change research from 1990 to 2014: positive trend, but still underperforming.
Climate change has been recognized as both one of the biggest threats and the biggest opportunities for global health in the 21st century. This trend review seeks to assess and characterize the amount and type of scientific literature on the link between climate change and human health. We tracked the use of climate-related terms and their co-occurrence with health terms during the 25 years since the first Intergovernmental Panel on Climate Change (IPCC) report, from 1990 to 2014, in two scientific databases and in the IPCC reports. We investigated the trends in the number of publications about health and climate change through time, by nature of the health impact under study, and by geographic area. We compared the scientific production in the health field with that of other sectors on which climate change has an impact. The number of publications was extremely low in both databases from 1990 (325 and 1,004, respectively) until around 2006 (1,332 and 4,319, respectively), which has since then increased exponentially in recent years (6,079 and 17,395, respectively, in 2014). However, the number of climate change papers regarding health is still about half that of other sectors. Certain health impacts, particularly malnutrition and non-communicable diseases (NCDs), remain substantially understudied. Approximately two-thirds of all published studies were carried out in OECD countries (Organization for Economic Cooperation and Development), predominantly in Europe and North America. There is a clear need for further research on the links between climate change and health. This pertains particularly to research in and by those countries in which health will be mostly affected and capacity to adapt is least. Specific undertreated topics such as NCDs, malnutrition, and mental health should gain the priority they deserve. Funding agencies are invited to take note of and establish calls for proposals accordingly. Raising the interest in this research area in young scientists remains a challenge and should lead to innovative courses for large audiences, such as Massive Open Online Courses.


Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome.
Ekbom disease (EKD), formerly known as restless legs syndrome (RLS) has affected and bothered many people over the centuries. It is one of the most prevalent neurological disorders in Europe and North-America, affecting about 10% of the population. The main characteristics are the strong urge to move, accompanied or caused by uncomfortable, sometimes even distressing, paresthesia of the legs, described as a "creeping, tugging, pulling" feeling. The symptoms often become worse as the day progresses, leading to sleep disturbances or sleep deprivation, which leads to decreased alertness and daytime functions. Numerous studies have been conducted assessing the efficacy of dopaminergic drugs, opioids, and other pharmacologic agents in alleviating EKD symptoms. However, there is also a growing body of evidence demonstrating the effectiveness of nonpharmacologic treatments including life style changes, physical activity programs, pneumatic compression, massage, near-infrared light therapy, and complementary therapies. The working mechanisms behind these alternatives are diverse. Some increase blood flow to the legs, therefore reducing tissue hypoxia; some introduce an afferent counter stimulus to the cortex and with that "close the gate" for aberrant nerve stimulations; some increase dopamine and nitric oxide and therefore augment bio-available neurotransmitters; and some generate endorphins producing an analgesic effect. The advantages of these treatments compared with pharmacologic agents include less or no side effects, no danger of augmentation, and less cost.


Hidden treasures in "ancient" microarrays: gene-expression portrays biology and potential resistance pathways of major lung cancer subtypes and normal tissue.
Novel statistical methods and increasingly more accurate gene annotations can transform "old" biological data into a renewed source of knowledge with potential clinical relevance. Here, we provide an in silico proof-of-concept by extracting novel information from a high-quality mRNA expression dataset, originally published in 2001, using state-of-the-art bioinformatics approaches. The dataset consists of histologically defined cases of lung adenocarcinoma (AD), squamous (SQ) cell carcinoma, small-cell lung cancer, carcinoid, metastasis (breast and colon AD), and normal lung specimens (203 samples in total). A battery of statistical tests was used for identifying differential gene expressions, diagnostic and prognostic genes, enriched gene ontologies, and signaling pathways. Our results showed that gene expressions faithfully recapitulate immunohistochemical subtype markers, as chromogranin A in carcinoids, cytokeratin 5, p63 in SQ, and TTF1 in non-squamous types. Moreover, biological information with putative clinical relevance was revealed as potentially novel diagnostic genes for each subtype with specificity 93-100% (AUC = 0.93-1.00). Cancer subtypes were characterized by (a) differential expression of treatment target genes as TYMS, HER2, and HER3 and (b) overrepresentation of treatment-related pathways like cell cycle, DNA repair, and ERBB pathways. The vascular smooth muscle contraction, leukocyte trans-endothelial migration, and actin cytoskeleton pathways were overexpressed in normal tissue. Reanalysis of this public dataset displayed the known biological features of lung cancer subtypes and revealed novel pathways of potentially clinical importance. The findings also support our hypothesis that even old omics data of high quality can be a source of significant biological information when appropriate bioinformatics methods are used.


Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities.
The deep sea, the largest ocean's compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.


The Eurolight project: the impact of primary headache disorders in Europe. Description of methods.
The Eurolight project is the first at European Union level to assess the impact of headache disorders, and also the first of its scale performed by collaboration between professional and lay organizations and individuals. Here are reported the methods developed for it. The project took the form of surveys, by structured questionnaire, conducted in ten countries of Europe which together represented 60% of the adult population of the European Union. In Lithuania, the survey was population-based. Elsewhere, truly population-based studies were impractical for reasons of cost, and various compromises were developed. Closest to being population-based were the surveys in Germany, Luxembourg, the Netherlands, Italy and Spain. In Austria, France and UK, samples were taken from health-care settings. In addition in the Netherlands, Spain and Ireland, samples were drawn from members of national headache patient organizations and their relatives. Independent double data-entry was performed prior to analysis. Returned questionnaires from 9,269 respondents showed a moderate female bias (58%); of respondents from patients' organizations (n = 992), 61% were female. Mean age of all respondents was 44 years; samples from patients' organizations were slightly older (mean 47 years). The different sampling methods worked with differing degrees of effectiveness, as evidenced by the responder-rates, which varied from 10.8 to 90.7%. In the more population-based surveys, responder-rates varied from 11.3 to 58.8%. We conclude that the methodology, although with differences born of necessity in the ten countries, was sound overall, and will provide robust data on the public ill-health that results from headache in Europe.


Perianal nodule due to Enterobius vermicularis: Cytomorphological spectrum on fine needle aspiration cytology with a review of literature.
Enterobius vermicularis (EV), an intestinal nematode, causes lesions at ectopic sites also. Although lesions are fully curable with antihelminthic drugs, patients may require surgical intervention in clinically unsuspected cases to arrive at correct diagnosis and appropriate treatment. Accurate diagnosis of these lesions on fine needle aspiration cytology (FNAC) has an advantage of avoiding unwanted surgery. To the best of our literature search, there are few case reports of EV diagnosed on cytology, but none of them describes the various stages of development of eggs and hatching of larvae. Dealing cytopathologist should be cognizant of them as parasite can be present in any of these forms/stages. Recently, we came across an interesting case of young boy who presented with perineal nodule and on FNAC from the lesion showed EV larvae and its eggs in various stages of hatching and development. The patient responded to antihelminthic treatment (AHT). Morphological clues with a review of cytological literature are discussed.


Does Industry-Driven Alcohol Marketing Influence Adolescent Drinking Behaviour? A Systematic Review.
To systematically review evidence on the influence of specific marketing components (Price, Promotion, Product attributes and Place of sale/availability) on key drinking outcomes (initiation, continuation, frequency and intensity) in young people aged 9-17. MEDLINE, EMBASE, SCOPUS, PsychINFO, CINAHL and ProQuest were searched from inception to July 2015, supplemented with searches of Google Scholar, hand searches of key journals and backward and forward citation searches of reference lists of identified papers. Forty-eight papers covering 35 unique studies met inclusion criteria. Authors tended to report that greater exposure to alcohol marketing impacted on drinking initiation, continuation, frequency and intensity during adolescence. Nevertheless, 23 (66%) studies reported null results or negative associations, often in combination with positive associations, resulting in mixed findings within and across studies. Heterogeneity in study design, content and outcomes prevented estimation of effect sizes or exploration of variation between countries or age subgroups. The strength of the evidence base differed according to type of marketing exposure and drinking outcome studied, with support for an association between alcohol promotion (mainly advertising) and drinking outcomes in adolescence, whilst only two studies examined the relationship between alcohol price and the drinking behaviour of those under the age of 18. Despite the volume of work, evidence is inconclusive in all four areas of marketing but strongest for promotional activity. Future research with standardized measures is needed to build on this work and better inform interventions and policy responses.