Is hard physical work in the early working life associated with back pain later in life? A cross-sectional study among 5700 older workers.
Physically demanding work increases the risk of developing musculoskeletal disorders during working life, with low back pain (LBP) as the most prevalent and debilitating musculoskeletal disorder worldwide. However, a lack of knowledge exists about the role of early working years on musculoskeletal health later in life. This study investigated whether an exposure-response association exists between physical demands in early working life and risk of LBP in later working life. Cross-sectional study. In the SeniorWorkingLife study, 5909 wage earners aged ≥50 years with currently sedentary work replied to a questionnaire survey in 2018 about physical work demands during their first working years (exposure) and current LBP (outcome). Associations between physical work demands in the early working years and current LBP were modelled using general linear models controlling for various confounders, combined with model-assisted weights based on national registers. Hard physical work during early working life was associated with more intense LBP later in life among senior workers with currently sedentary jobs. In the fully adjusted model, workers with 'standing/walking work with lifting/carrying' and 'heavy or fast work that is physically strenuous' during the first years of working life reported higher LBP intensity than those with sedentary work during their first working years (0.2 (95% CI, 0.0 to 0.4) and 0.6 (95% CI, 0.4 to 0.9), respectively). Work involving lifting/carrying or work that is physically strenuous in early life is associated with higher intensity of LBP among older workers with currently sedentary employment. These findings suggest that early working life may have an impact on later working years and underscore the necessity for careful introduction and instruction to the working environment for retaining musculoskeletal health and prolonging working life. NCT03634410.


Unsupervised Neural Manifold Alignment for Stable Decoding of Movement from Cortical Signals.
The stable decoding of movement parameters using neural activity is crucial for the success of brain-machine interfaces (BMIs). However, neural activity can be unstable over time, leading to changes in the parameters used for decoding movement, which can hinder accurate movement decoding. To tackle this issue, one approach is to transfer neural activity to a stable, low-dimensional manifold using dimensionality reduction techniques and align manifolds across sessions by maximizing correlations of the manifolds. However, the practical use of manifold stabilization techniques requires knowledge of the true subject intentions such as target direction or behavioral state. To overcome this limitation, an automatic unsupervised algorithm is proposed that determines movement target intention before manifold alignment in the presence of manifold rotation and scaling across sessions. This unsupervised algorithm is combined with a dimensionality reduction and alignment method to overcome decoder instabilities. The effectiveness of the BMI stabilizer method is represented by decoding the two-dimensional (2D) hand velocity of two rhesus macaque monkeys during a center-out-reaching movement task. The performance of the proposed method is evaluated using correlation coefficient and R-squared measures, demonstrating higher decoding performance compared to a state-of-the-art unsupervised BMI stabilizer. The results offer benefits for the automatic determination of movement intents in long-term BMI decoding. Overall, the proposed method offers a promising automatic solution for achieving stable and accurate movement decoding in BMI applications.


Resistance of soybean vegetative storage proteins (S-VSPs) to proteolysis by rumen microorganisms.
Soybean vegetative storage proteins (S-VSPs) are lysine-rich and, hence, are potentially of high nutritive value for high productive ruminants. Using S-VSPs from wild-type soybean and from transgenic tobacco plants expressing either one of the two S-VSPs subunits (S-VSP alpha or S-VSP beta) or both, we tested their stability in cow rumen fluid under in situ conditions, using SDS-polyacrylamide gel electrophoresis. Proteolysis and degradation pattern of S-VSPs from transgenic tobacco leaves occurred relatively fast compared with that of wild-type (WT) soybean plants. Comparing the two S-VSPs subunits expressed in transgenic plants, we found that S-VSP alpha was degraded much faster than S-VSP beta. The degradation pattern of S-VSPs in transgenic tobacco plants expressing both subunits resembled that of WT soybean. In contrast, the degradation pattern of transgenic tobacco plants expressing a single subunit was different. These finding suggest that the quaternary structure of S-VSPs may be an important factor determining their resistance to rumen degradation. Our results also suggest that the stability to rumen proteolysis of a given protein, when expressed in a transgenic plant, may not always be predictable and has to be verified.


Assessing health status and health care utilization in adolescents with chronic kidney disease.
Few validated health status measures have been assessed in children with chronic kidney disease (CKD). The objective was to assess the validity of a generic health status measure, the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), in adolescents with CKD. A case-control study was performed (1) to assess scores on the CHIP-AE in adolescents with CKD compared with two control groups of age-, socioeconomic-, and gender-matched peers and (2) to compare health of patients who had chronic renal insufficiency (CRI), were on dialysis, and were posttransplantation. Seven pediatric nephrology centers recruited 113 patients (mean age, 14 yr; 39 CRI, 21 dialysis, 53 posttransplantation). Compared with 226 control subjects, patients with CKD had lower overall satisfaction with health and more restriction in activity. Positively, patients with CKD had more family involvement, better home safety and health practices, and better social problem-solving skills and were less likely to participate in risky social behaviors or socialize with peers who engaged in risky behavior. Patients who received dialysis were less physically active and experienced more physical discomfort and limitations in activities than did transplant or CRI patients. It is concluded that patients with CKD have poorer functional health status than age-matched peers. Among CKD patients, dialysis patients have the poorest functional health status. These results suggest that the CHIP-AE can be used to measure functional health status in adolescent patients with CKD.


The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells.
As a result of a viral infection, viral genomes are not only recognized by RIG-I, but also lead to the activation of RNase L, which cleaves cellular RNA to generate the endogenous RIG-I ligand (eRL). The eRL was previously identified as a specific sequence derived from the internal transcribed spacer region 2, which bears a 2'3' cyclic phosphate instead of the common 5' triphosphate. By now, the generation of the eRL and its immunostimulatory effect were shown both in vitro and in reporter systems. In this work, we aimed to elucidate whether the eRL is also generated in Influenza A (IAV) and vesicular stomatitis virus (VSV) infected cells. RNA was extracted from virus-infected cells and used for immunostimulations as well as specific PCR-strategies to detect eRL cleavage. We show that the eRL is generated in IAV infected HEK293 cells, but we could not detect specific eRL fragments in VSV infected cells. Further, RIG-I mediated IFN-response depends not only on viral genomes but also on the eRL, as immunostimulatory properties remain present under 5'triphosphate degrading conditions. In summary, we prove the IAV infection induced eRL generation in HEK293 cells, amplifying the innate immune response.


Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.
Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. Bayer.


Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation.
Upon antigen recognition, T-cell receptor (TCR/CD3) and other signaling molecules become enriched in a specialized contact site between the T cell and antigen-presenting cell, i.e. the immunological synapse (IS). Enrichment occurs via mechanisms that include polarized secretion from recycling endosomes, but the Rabs and RabGAPs that regulate this are unknown. EPI64C (TBC1D10C) is an uncharacterized candidate RabGAP we identified by mass spectrometry as abundant in human peripheral blood T cells that is preferentially expressed in hematopoietic cells. EPI64C is a Rab35-GAP based both on in vitro Rab35-specific GAP activity and findings in transfection assays. EPI64C and Rab35 dominant negative (DN) constructs each impaired transferrin export from a recycling pathway in Jurkat T-cells and induced large vacuoles marked by transferrin receptor, TCR, and SNAREs implicated in TCR-polarized secretion. Rab35 localized to the plasma membrane and to intracellular vesicles where it substantially colocalized with TfR and with TCR. Rab35 was strongly recruited to the IS. Conjugate formation was impaired by transfection with Rab35-DN or EPI64C and by EPI64C knock down. TCR enrichment at the IS was impaired by Rab35-DN. Thus, EPI64C and Rab35 regulate a recycling pathway in T cells and contribute to IS formation, most likely by participating in TCR transport to the IS.


Socioeconomic inequalities in survival and provision of neonatal care: population based study of very preterm infants.
To assess socioeconomic inequalities in survival and provision of neonatal care among very preterm infants. Prospective cohort study in a geographically defined population. Former Trent health region of the United Kingdom (covering about a twelfth of UK births). All infants born between 22+0 and 32+6 weeks' gestation from 1 January 1998 to 31 December 2007 who were alive at the onset of labour and followed until discharge from neonatal care. Survival to discharge from neonatal care per 1000 total births and per 1000 very preterm births. Neonatal care provision for very preterm infants surviving to discharge measured with length of stay, provision of ventilation, and respiratory support. Deprivation measured with the UK index of multiple deprivation 2004 score at super output area level. 7449 very preterm singleton infants were born in the 10 year period. The incidence of very preterm birth was nearly twice as high in the most deprived areas compared with the least deprived areas. Consequently rates of mortality due to very preterm birth per 1000 total births were almost twice as high in the most deprived areas compared with the least deprived (incidence rate ratio 1.94, 95% confidence interval 1.62 to 2.32). Mortality rates per 1000 very preterm births, however, showed little variation across all deprivation fifths (incidence rate ratio for most deprived fifth versus least deprived 1.02, 0.86 to 1.20). For infants surviving to discharge from neonatal care, measures of length of stay and provision of ventilation and respiratory support were similar across all deprivation fifths. The burden of mortality and morbidity is greater among babies born to women from deprived areas because of increased rates of very preterm birth. After very preterm birth, however, survival rates and neonatal care provision is similar for infants from all areas.


Dual coupling of the alpha-thrombin receptor to signal-transduction pathways involving phosphatidylinositol and phosphatidylcholine metabolism.
Addition of alpha-thrombin to quiescent IIC9 cells results in the activation of lipid-metabolizing enzymes associated with signal-transduction cascades. These enzymes include phosphatidylinositol (PI)-specific phospholipase C (PI-PLC), phosphatidylcholine (PC)-specific phospholipases C and D and phospholipase A2 (PLA2). Whereas the alpha-thrombin receptor has been shown to couple with PI-PLCs, it is not clear whether this receptor, or a putative second receptor, couples to one or more of the other phospholipases. In this report we determine whether the cloned receptor couples to all or a subset of these enzymes. We show that (i) an alpha-thrombin-receptor-activating peptide also elicits the above responses and (ii) addition of enterokinase to IIC9 cells, stably transfected with an alpha-thrombin receptor (enterokinase- responsive alpha-thrombin receptor, EKTR) containing an enterokinase cleavage site in place of an alpha-thrombin cleavage site, stimulates both PI and PC hydrolysis, including PLA2. Enterokinase also induces mitogenesis in the IIC9s transfected with EKTR. These results indicate that, in addition to initiating a mitogenic signalling cascade, the cloned alpha-thrombin receptor couples to enzymes involved in generating PC-derived, as well as PI-derived, second-messenger molecules in IIC9s. Additionally, using the cells transfected with EKTR, we further demonstrate that only activated, i. e. cleaved, receptors are desensitized.


The Yield of Upper Gastrointestinal Endoscopy at a Pediatric Tertiary Care Center.
The number of investigative esophagogastroduodenoscopies (EGD) in children has increased over several decades, despite their unclear diagnostic yields. To evaluate the indications for performing EGD, their diagnostic yields, and consequences on pediatric patient management. A retrospective chart review was performed of consecutive pediatric patients aged 0-18 years, who underwent EGD between January and August 2014. During the study period, 547 EGD were performed on 478 children. The most frequent indications were suspected celiac disease, chronic non-specific abdominal pain, persistent Helicobacter pylori infection, and gastrointestinal hemorrhage. The yield of the diagnostic EGD was 59.2%, and the most common new diagnoses were celiac disease (28%), Helicobacter pylori-positive gastritis (16.5%), and Crohn's disease (5.4%). Of the patients with documented follow-up, 74.1% reported improved symptoms. Procedures performed for chronic unexplained abdominal pain had significantly lower yields (26.2%) and only 39.3% improved at follow-up. Our findings suggest a general high diagnostic yield for EGD in pediatric patients, stemming mainly from patients in whom a specific condition was suspected a priori. However, the role of the procedure in the diagnosis and management of non-specific gastrointestinal complaints was minor suggesting that EGD may be superfluous for some of these patients.


Experiences with transconjunctival upper blepharoplasty.
Upper blepharoplasty remains a valuable procedure in rejuvenating the upper eyelid. An innovative technique was recently reported whereby medial fat is removed through a transconjunctival approach. This is a preliminary report of our experience with 60 patients treated over the past 10 months using this technique. The technique will be described in detail and cases will be reported. There were no perioperative or postoperative complications. All of the patients are satisfied with the results of their surgical procedure. The technique has the advantage of avoiding an incision of the medial upper eyelid and the inherent risks of excessive scarring in this area. We have found the technique especially useful in secondary blepharoplasty with an isolated prominence of residual medial fat. Other advantages include the following: primary cases in which the surgeon is able to avoid medial extension of the cutaneous incision, patients who possess deep tarsal folds with prominent medial fat, or as an adjunct to eyebrow lifting techniques where in both cases cutaneous excision is unnecessary. No disadvantages have been noted.


Multidimensional apathy and executive dysfunction in amyotrophic lateral sclerosis.
Apathy and cognitive dysfunction are prominent symptoms of Amyotrophic lateral sclerosis (ALS). More specifically ALS patients show increased Initiation apathy-a lack of motivation for self-generation of thoughts as assessed by the Dimensional Apathy Scale. This study aimed to investigate the cognitive underpinnings of apathy subtypes in ALS. We hypothesized that increased Initiation apathy would be associated deficits on tests of intrinsic response generation, such as verbal fluency. We also explored the relationship of other apathy subtypes to cognitive processes, in particular emotional apathy with emotional and social cognition deficits and executive apathy with planning and goal management deficits. ALS patients, and their carers (N = 30), and healthy matched controls, and their informants (N = 29) were recruited. All participants completed self- and informant/carer-rated Dimensional Apathy Scale, to quantify apathy subtypes (Executive, Emotional and Initiation), along with standard apathy and depression measures. Patients and controls completed the Edinburgh Cognitive and behavioural ALS Screen, and a comprehensive neuropsychological battery including emotional recognition, social cognition, intrinsic response generation tasks (verbal fluency and random number generation) and a new ecologically valid, computerised measure of planning and goal management. The results demonstrated that increased Initiation apathy was the only significantly elevated subtype in ALS (self-rated p < .05, informant/carer-rated p < .01). Initiation apathy was found to be significantly associated with verbal fluency deficit, while Emotional apathy was significantly associated with emotional recognition deficits. No associations were found between apathy subtypes and depression or in controls. This is the first study to show specific associations between apathy subtypes (Emotional and Initiation) and executive and emotional cognitive dysfunction, indicating possible distinct underlying mechanisms to these demotivational symptoms.


Dual secured nano-melittin for the safe and effective eradication of cancer cells.
The clinical application of natural and synthetic amphipathic peptides (e.g., melittin) for cancer therapy is hindered by their notorious side effect, lysing red blood cells. To safely deliver a therapeutic peptide to the tumor tissue and kill cancer cells, we developed an environment-sensitive peptide delivery system, dual secured nano-sting (DSNS), through the combination of a zwitterionic glycol chitosan and disulfide bonds. Melittin loaded DSNS could kill almost 100% of MCF-7, HCT-116, SKOV-3, and NCI/ADR-RES (multidrug resistant) cancer cells at the concentration of 5 μM, while not showing any hemolytic effect.


[An evaluation of a nutrient medium for isolating and cultivating Helicobacter pylori].
Selective Helicobacter agar containing the selective supplement and blood, adding ex tempore, for the isolation and cultivation of H. pylori was developed. The Helicobacter agar was studied with the use of 5 newly isolated H. pylori strains, 13 bacterial associated cultures, as well as 21 inoculated biopsy specimens of the gastric and duodenal mucosa of patients with peptic ulcer. The study revealed that Helicobacter agar ensured the growth of H. pylori and their isolation from clinical material. The positive results after the inoculation of the specimens of biopsy material on Helicobacter agar and control media was 85%. In addition, the study of Helicobacter agar showed that it also exhibited pronounced selective properties with respect to bacterial associations, not inhibiting the growth of Helicobacter organisms and retaining their main biological properties. It is possible to recommend Helicobacter agar for use in laboratory practice in diagnosing Helicobacter-associated diseases.


Acute pancreatitis in the paediatric age group: a personal experience.
Although relatively rare, acute pancreatitis is the most common disease complex involving the pancreas in the paediatric age group. The etiology of the disease is often unknown, and Italian epidemiological data on the paediatric population and, in particular, on the etiology of the disease are not available (except for studies of prevalence). Within the field of the most frequently encountered pancreatitis in the age range of our interest (i.e. 0-18 years), not only the commonly observed forms whose etiopathogenesis is ascribable to cholelithiasis must be mentioned but also those forms due to proteic-caloric malnutrition that are becoming increasingly common. The presenting clinical symptoms and signs may not be typical and the laboratory tests may not always be sensitive enough. In such age range chronic recurrent pancreatitis plays a very important epidemiologic role. Approximately 40% of children and teenagers admitted to the hospital with a diagnosis of pancreatitis report a previous episode of the disease. Irreversible changes in pancreatic parenchyma develop in those patients in whom the disease progresses, leading to pancreatic insufficiency. Such a morbid condition (chronic pancreatitis) is more often observed in adolescents, in whom the disease manifests itself with a vague repetitive dyspeptic symptomatology, after alternating remissions and recrudescences, not always clinically evident. In children, the clinical picture most commonly encountered is represented by recurrent abdominal pains, in view of the fact that the patients are frequently affected by thalassaemia. The pseudocystic evolution of the disease is the most common organic damage resulting from the chronic progression of the pancreatic impairment. A few differences have been found with respect to severity, etiology, and mortality of pancreatitis in the paediatric age group as compared with older age groups. Both the general practitioner with a paediatric practice and the paediatrician encounter a large number of difficulties in this field of pathology. Therefore, an adequate and correct "management" of children with acute or chronic pancreatitis seems to be mandatory.


Utility of Big Data in Predicting Short-Term Blood Glucose Levels in Type 1 Diabetes Mellitus Through Machine Learning Techniques.
Machine learning techniques combined with wearable electronics can deliver accurate short-term blood glucose level prediction models. These models can learn personalized glucose-insulin dynamics based on the sensor data collected by monitoring several aspects of the physiological condition and daily activity of an individual. Until now, the prevalent approach for developing data-driven prediction models was to collect as much data as possible to help physicians and patients optimally adjust therapy. The objective of this work was to investigate the minimum data variety, volume, and velocity required to create accurate person-centric short-term prediction models. We developed a series of these models using different machine learning time series forecasting techniques suitable for execution within a wearable processor. We conducted an extensive passive patient monitoring study in real-world conditions to build an appropriate data set. The study involved a subset of type 1 diabetic subjects wearing a flash glucose monitoring system. We comparatively and quantitatively evaluated the performance of the developed data-driven prediction models and the corresponding machine learning techniques. Our results indicate that very accurate short-term prediction can be achieved by only monitoring interstitial glucose data over a very short time period and using a low sampling frequency. The models developed can predict glucose levels within a 15-min horizon with an average error as low as 15.43 mg/dL using only 24 historic values collected within a period of sex hours, and by increasing the sampling frequency to include 72 values, the average error is reduced to 10.15 mg/dL. Our prediction models are suitable for execution within a wearable device, requiring the minimum hardware requirements while at simultaneously achieving very high prediction accuracy.


Perceptions of Anal Cancer Risk Among HIV-Positive and High-Risk HIV-Negative Women.
Women living with HIV (WLWH) have a greater risk of anal cancer than women without HIV; however, there are limited studies that examine awareness of anal cancer risk among WLWH and "high-risk" HIV-negative women. This study examines risk factors for anal cancer, perceptions of risk for anal cancer, and perceptions of anal cancer screening among a cohort of WLWH and high-risk HIV-negative women. From the Atlanta, GA, and Bronx, NY, sites of the Women's Interagency HIV Study, 155 WLWH and HIV-negative women were enrolled and the Champion Health Belief Model Scale questionnaire measuring risk perceptions to anal cancer was administered to each participant. The WLWH perceived anal cancer to be less serious and perceived facing fewer barriers to anal cancer screening than HIV-negative women (both p = .01). Older women (≥50 years) felt that they had less barriers to anal cancer screening (p = .047). Moreover, women who had less than a high school education felt more susceptible to anal cancer (p = .001), as did women who reported a history of anal intercourse (p = .017). Despite being at an increased risk for anal cancer, perceptions of susceptibility to anal cancer and seriousness of anal cancer were low among WLWH. These findings highlight opportunities for provider and patient educational interventions to improve awareness of anal cancer risk among WLWH.


Yellow fever: the recurring plague.
Despite the availability of a safe and efficacious vaccine, yellow fever (YF) remains a disease of significant public health importance, with an estimated 200,000 cases and 30,000 deaths annually. The disease is endemic in tropical regions of Africa and South America; nearly 90% of YF cases and deaths occur in Africa. It is a significant hazard to unvaccinated travelers to these endemic areas. Virus transmission occurs between humans, mosquitoes, and monkeys. The mosquito, the true reservoir of YF, is infected throughout its life, and can transmit the virus transovarially through infected eggs. Man and monkeys, on the other hand, play the role of temporary amplifiers of the virus available for mosquito infection. Recent increases in the density and distribution of the urban mosquito vector, Aedes aegypti, as well as the rise in air travel increase the risk of introduction and spread of yellow fever to North and Central America, the Caribbean, the Middle East, Asia, Australia, and Oceania. It is an acute infectious disease characterized by sudden onset with a two-phase development, separated by a short period of remission. The clinical spectrum of yellow fever varies from very mild, nonspecific, febrile illness to a fulminating, sometimes fatal disease with pathognomic features. In severe cases, jaundice, bleeding diathesis, with hepatorenal involvement are common. The case fatality rate of severe yellow fever is 50% or higher. The pathogenesis and pathophysiology of the disease are poorly understood and have not been the subject of modern clinical research. There is no specific treatment for YF, making the management of YF patients extremely problematic. YF is a zoonotic disease that cannot be eradicated, therefore instituting preventive vaccination through routine childhood vaccination in endemic countries, can significantly reduce the burden of the disease. The distinctive properties of lifelong immunity after a single dose of yellow fever vaccination are the basis of the new applications of yellow fever 17D virus as a vector for foreign genes, "the chimeric vaccine,' and the promise of developing new vaccines against other viruses, and possibly against cancers.


"It's Time to Represent": shifting the paradigm to improve the quality of inputs into value assessment frameworks.
"It's Time to Represent" integrates 2 strategies that challenge the status quo to increase the diversity of populations that participate in research and address drivers of health disparities to better inform value assessment. The first, a community-engaged campaign, proposes to develop authentic, long-term partnerships with community members, their health care providers, and researchers to tailor recruitment and retention methods for underrepresented groups and hold researchers accountable for equitable selection of study participants. The second proposes to create an expectation for researchers to routinely collect patient-reported, actionable social determinants of health data to generate enhanced real-world evidence and thereby improve the quality of inputs utilized in value assessment frameworks. DISCLOSURE: No specific funding was received for this manuscript. The authors report no potential conflicts of interest.


Riding motorcycles: is it a lower limb hazard?
The morbidity and mortality among motorcyclists involved in road traffic accidents (RTA) in Singapore is high. Due to their relatively small size, they represent a vulnerable group of road-users. Many reports from studies performed overseas have shown that both lower limb and head injuries appear to be common among motorcyclists. To study the characteristics of lower limb injuries among motorcyclists involved in RTA, who present to the Department of Emergency Medicine of an urban, tertiary, teaching hospital for treatment. The study was conducted prospectively from 1 July 2000 to 30 June 2001. Demographic data was collected together with details of the type of injuries, mechanism involved, management and disposition. SPSS (Chicago, Inc.) was utilised for data management and statistical analysis. Of the 1,809 motorcyclists studied, 1,056 (58.3%) sustained lower limb injuries, 328 (18.1%) had head injuries and 256 (14.2%), sustained facial injuries. The mean age was 26.4 +/- 7.2 years and males made up the majority of the patients (1,733, 95.8%). Helmet usage was 100%. The commonest type of lower limb injury was fractures (531, 50.3%). The most common type of fracture was that of the shaft of the tibia and fibula (231, 43.5%), followed by fractures around the ankle (186, 35.0%). For those with more than one body region injured, head injury was noted to be not commonly associated with lower limb injuries. The commonest mechanism of injury was collision with another vehicle, while approaching a turn (769, 42.5%). There were 96 motorcyclists (5.3%) who had clinical evidence of alcohol consumption on their breath at presentation. There were 533 (29.5%) patients who were admitted for in-patient management and the mean duration of stay was 4.8 +/- 4.5 days. Amongst those with lower limb injuries, the admission rate was 30.5% (322 of 1,056) and the mean duration of hospitalisation was 5.3 +/- 3.9 days. Lower limb injuries represent the commonest form of injury among motorcyclists involved in RTA. Improved training via motorcycle rider education, better design of future motorcycles and protective footwear may help to reduce this problem.


Going through the motions: incorporating movement analyses into disease research.
Though epidemiology dates back to the 1700s, most mathematical representations of epidemics still use transmission rates averaged at the population scale, especially for wildlife diseases. In simplifying the contact process, we ignore the heterogeneities in host movements that complicate the real world, and overlook their impact on spatiotemporal patterns of disease burden. Movement ecology offers a set of tools that help unpack the transmission process, letting researchers more accurately model how animals within a population interact and spread pathogens. Analytical techniques from this growing field can also help expose the reverse process: how infection impacts movement behaviours, and therefore other ecological processes like feeding, reproduction, and dispersal. Here, we synthesise the contributions of movement ecology in disease research, with a particular focus on studies that have successfully used movement-based methods to quantify individual heterogeneity in exposure and transmission risk. Throughout, we highlight the rapid growth of both disease and movement ecology and comment on promising but unexplored avenues for research at their overlap. Ultimately, we suggest, including movement empowers ecologists to pose new questions, expanding our understanding of host-pathogen dynamics and improving our predictive capacity for wildlife and even human diseases.


Intellectual property: the control of scientific information.
Control of scientific information is increasingly at the center of legal and administrative disputes, raising questions of sovereignty and secrecy, of proprietary rights over research. Disputes originate from efforts to extend the right of access to data at an early stage of research, from demands for information that threaten confidentiality, from proprietary interests in competitive areas of research, and from government restrictions on the free exchange of scientific ideas. They reflect policy changes with respect to information disclosure, university-industry collaboration, patent rights, and national security. A review of diverse situations that have led to disputes and of efforts to negotiate principles for controlling intellectual property suggests the problems of establishing such principles in the context of the changing role of science.


Impact of guided reciprocal peer questioning on nursing students' self-esteem and learning.
Self-esteem is essential for clinical judgments. Nursing students in clinical environments should make a bridge between theoretical education and clinical function. This study was aimed to survey the effect of guided questioning in peer groups on nursing students' self-esteem and clinical learning. In this quasi-experimental study, all nursing students in semester 4 (60) were selected. The autumn semester students (n = 28) were chosen as the control group, and the spring semester students (n = 32) as the experimental group. The experimental group underwent the course of cardiac medical surgical training by the Guided Reciprocal Peer Questioning. The control group was trained by lecture. After confirmation of the validity and reliability of tools including Rosenberg Self-esteem Scale and the researcher-made questionnaire, data were collected and analyzed by SPSS version 17.0. There was no significant difference concerning demographic and educational characteristics between the two groups. Mean score differences of self-esteem and learning were not significant before teaching, while they were significantly promoted after teaching in the experimental (P < 0.001) and control (P < 0.05) groups. Promotion in the experimental group was more considerable than in the control group. As revealed by the results, inquiry method, due to its more positive impact on self-esteem and students' learning, can be applied alone or in combination with the other methods. Conducting this study for other students and for theoretical courses is suggested.


Three cases of multi-generational Pompe disease: Are current practices missing diagnostic and treatment opportunities?
Pompe disease (Glycogen storage disease type II, GSDII, or acid maltase deficiency) is an autosomal recessive metabolic myopathy with a broad clinical spectrum, ranging from infantile to late-onset presentations. In 2015, Pompe disease was added as a core condition to the Recommended Uniform Screening Panel for state newborn screening (NBS). The clinical importance of Pompe disease is evolving with the use of NBS, increasing awareness of the disease, and higher than previously reported disease prevalence; however, current practices miss additional diagnostic and potential treatment opportunities in close relatives of the family proband. In this report, we describe three families with multiple individuals in multiple generations affected by both infantile and late-onset clinical presentations of Pompe disease. The presence of multi-generational disease within these families highlights the importance of subsequent risk assessment through medical history and physical examination, with a low threshold for the screening of a proband's family members. We recommend enzymology (GAA activity assay) as the first screening method, as opposed to targeted mutation analysis, for at-risk family members. Given that the initial symptoms of the slowly progressive late-onset presentation of Pompe disease may be mild or non-specific, enzymatic testing of all parents of affected infants should be considered.


Low case fatality during 2017 cholera outbreak in Borno State, North Eastern Nigeria.
Cholera is endemic in sub-Saharan Africa, especially in areas affected by natural disaster and human conflict. Northeastern Nigeria is experiencing a health crisis due to the destruction of essential amenities such as health infrastructure, sanitation facilities, water supplies, and human resources by Boko Haram insurgents. In 2017, a cholera outbreak occurred in five local government areas (LGAs) hosting internally displaced persons. The Nigeria Center for Disease Control, World Health Organization, Mĕdecins Sans Frontiĕres International, and several other organizations supported disease containment. An emergency operating center (EOC) established by the State Ministry of Health (SMoH) then coordinated the outbreak response. We conducted a retrospective analysis of data extracted from the line list utilized by the SMoH to investigate outbreaks. We evaluated the outbreak by time, place, and person. Attack rate by LGA and age-specific case fatality rate (CFR) was calculated based on cases with complete records for age, sex, place of residence, date of symptom onset, and disease outcome. A total of 5889 cholera cases were reported from five LGAs with an overall attack rate of 395.3/100,000 population. Among 4956 cases with documented outcome, the overall CFR was 0.87%, with CFR ranging from 0% to 6.98% by LGA. The age-specific CFR was highest among those aged ≥60 years (1.92%) and least among those aged 20-29 years at 0.3%. The epidemiological curve revealed two peaks that coincided with periods of heavy rain and flooding. This study reports on the largest ever documented cholera outbreak in five LGAs in Borno State. The outbreak was focused in LGA hit hardest by the destructive activities of insurgents and then spread to neighboring LGAs. The low CFR recorded in this cholera outbreak was achieved through timely detection, reporting, and response by the coordinated efforts of the EOC established by the SMoH that harmonized the outbreak response.


Epigenetic regulation of interleukin-8 expression by class I HDAC and CBP in ovarian cancer cells.
Although inhibitors of epigenetic regulators have been effective in the treatment of cutaneous T cell lymphoma (CTCL) and other hematopoietic malignancies, they have been less effective in solid tumors, including ovarian cancer (OC). We have previously shown that inhibition of histone deacetylase (HDAC) activity induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (CXCL8, IL-8) in OC cells, resulting in their increased survival and proliferation. Here, we show that in addition to ovarian cancer SKOV3, OVCAR3, and CAOV3 cells, HDAC inhibition induces the CXCL8 expression in HeLa cells, but not in CTCL Hut-78 cells. In OC cells, the CXCL8 expression is induced by pharmacological inhibition of class I HDACs. Interestingly, while an individual suppression of HDAC1, HDAC2, or HDAC3 by corresponding siRNAs inhibits the CXCL8 expression, their simultaneous suppression induces the CXCL8 expression. The induced CXCL8 expression in OC cells is dependent on histone acetyltransferase (HAT) activity of CREB-binding protein (CBP), but not p300, and is associated with HAT-dependent p65 recruitment to CXCL8 promoter. Together, our results show that the CXCL8 expression in OC cells is induced by combined inhibition of HDAC1, -2, and -3, and silenced by suppression of HAT activity of CBP. In addition, our data indicate that the induced CXCL8 expression may be responsible for the limited effectiveness of HDAC inhibitors in OC and perhaps other solid cancers characterized by CXCL8 overexpression, and suggest that targeting class I HDACs and CBP may provide novel combination strategies by limiting the induced CXCL8 expression.


Trends in elective and ruptured abdominal aortic aneurysm repair by practice setting in Ontario, Canada, from 2003 to 2016: a population-based time-series analysis.
Recent years have seen centralization of vascular surgery services in Ontario. We sought to examine the trends in overall and approach-specific elective and ruptured abdominal aortic aneurysm repair by hospital type (teaching v. community). We conducted a population-based time-series analysis of elective and ruptured abdominal aortic aneurysm repairs in Ontario, Canada, from 2003 to 2016. Quarterly cumulative incidences of repairs per 100 000 Ontarians aged 40 years and older were calculated. We fit exponential smoothing models to the data stratified by approach and hospital type to examine repair trends. We identified 19 219 elective and 2722 ruptured repairs between 2003 and 2016. The cumulative incidences of overall elective repair and elective open surgical repair decreased by 1.15% (p = 0.008) and 67% (p < 0.001), respectively, in teaching hospitals and by 23% (p < 0.001) and 60% (p < 0.001), respectively, in community hospitals. The cumulative incidence of elective endovascular repair increased 667% in teaching hospitals (p < 0.001). Elective endovascular repair began in community centres after 2010 and increased to 0.98/100 000 (p < 0.001), resulting in a rebound in overall elective repair in the community. Overall ruptured repairs and ruptured open repairs decreased by 84% (p < 0.001) and 88% (p = 0.002), respectively, at community hospitals. Ruptured endovascular repairs at community hospitals increased from no procedures before 2006 to 0.03/100 000 in 2016 (p = 0.005). There has been substantial uptake of endovascular aortic repair in teaching and community hospitals in Ontario, and community hospital uptake of endovascular repair has begun decentralization of abdominal aortic aneurysm repair. Increased experience and training in endovascular repair and reduced specialized care requirements will probably lead to continued decentralization.


Can COVID-19 mark a tipping point for home-based telework? Conflict between untact technology and rigid institutions in Korea.
Previously, Korea showed a passive attitude toward home-based telework; however, this stance rapidly changed after the COVID-19 pandemic. Sustaining home-based telework entails adjusting productivity conditions, introducing performance-based evaluations, and modifying employment rules, as required by the Korean Labor Standards Act, which demand the consent of most workers. This study aims to explore the societal and institutional shifts necessary for ongoing home-based telework post-pandemic. This study discusses the sustainability of home-based work based on survey data and materials from institutions and previous research. It used data from the Workplace Panel Survey provided by the Korea Labor Institution for 3 years (2015, 2017, and 2019) to examine the status of home-based work and business responses. It also addresses legal issues related to changes in working conditions and worker-management agreements resulting from telework implementation. Legal aspects of telework are explained using relevant sections of Korea's labor laws. To establish home-based telework as a working method relevant to the Fourth Industrial Revolution after the pandemic, essential discussions are needed regarding its fundamental applicability to specific job sectors. Moreover, to activate home-based telework without deteriorating working conditions, achieving agreement between workers and management is imperative. However, legal complexities necessitate systemic changes for effective resolution. For the sustainable continuity of telework, a blend of societal awareness and institutional transformations is indispensable. The growth of home-based telework through untact technology expansion is hindered by inflexible Korean labor laws, judicial precedents, and worker-management relations. The absence of necessary legal and organizational changes could lead Korea to revert to pre-pandemic norms or slow implementation. Initially prevalent in IT, home-based telework has expanded across sectors due to the pandemic. Leading the "new normal," companies creatively enhance productivity through telework, but rigid systems and outdated cultures could impede post-pandemic progress. The study highlights the need for forward-looking institutional changes and adaptation to advancing technology. It provides valuable insights for organizations and policymakers to optimize work dynamics and enhance employee and employer well-being in the post-COVID-19 era.


Dietary Supplement with Tribulus terrestris L. Extract Exhibits Protective Effects on Ischemic Stroke Rats.
Among herbal dietary supplements, the extract of Tribulus terrestris L. (TT) has been used as a commercially registered product in multiple studies. The previous studies demonstrate the protective effect of gross saponins of TT (GSTTF) on ischemic stroke. However, the mechanism by which GSTTF protects against ischemic stroke is still unclear. The study applies molecular biology and unbiased transcriptomics to explore the pathways and targets underlying the therapeutic impact of GSTTF in treating ischemic stroke. The mRNA of brain tissues from different groups is analyzed using a transcriptomics method. The data reveal that treatment with GSTTF significantly reduces elevated CRP, IL-6, and Ca2+ levels induced by middle cerebral artery occlusion (MCAO). A total of 61 differentially expressed genes (DEGs) are identified, GSTTF is found to effectively reverse the abnormal mRNA expression levels in rat brain tissues affected by ischemic stroke models. These positive effects of GSTTF are likely achieved through the suppression of calcium ion and the MyD88/IKK/NF-κB signaling pathway. This study uncovers the mechanisms behind the efficacy of GSTTF in treating ischemic stroke, which not only expands its potential medicinal applications but also confirmed its potential as a dietary supplement.


Reporting and methodologic quality of Cochrane Neonatal review group systematic reviews.
The Cochrane Neonatal Review Group (CNRG) has achieved a lot with limited resources in producing high quality systematic reviews to assist clinicians in evidence-based decision-making. A formal assessment of published CNRG systematic reviews has not been undertaken; we sought to provide a comprehensive assessment of the quality of systematic reviews (both methodologic and reporting quality) published in CNRG. We selected a random sample of published CNRG systematic reviews. Items of the QUOROM statement were utilized to assess quality of reporting, while items and total scores of the Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ) were used to assess methodologic quality. Two reviewers independently extracted data and assessed quality. A Student t-test was used to compare quality scores pre- and post-publication of the QUOROM statement. Sixty-one systematic reviews were assessed. Overall, the included reviews had good quality with minor flaws based on OQAQ total scores (mean, 4.5 [0.9]; 95% CI, 4.27-4.77). However, room for improvement was noted in some areas, such as the title, abstract reporting, a priori plan for heterogeneity assessment and how to handle heterogeneity in case it exists, and assessment of publication bias. In addition, reporting of agreement among reviewers, documentation of trials flow, and discussion of possible biases were addressed in the review process. Reviews published post the QUOROM statement had a significantly higher quality scores. The systematic reviews published in the CNRG are generally of good quality with minor flaws. However, efforts should be made to improve the quality of reports. Readers must continue to assess the quality of published reports on an individual basis prior to implementing the recommendations.


Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.
Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.


The Effects of Acupuncture on Chronic Knee Pain Due to Osteoarthritis: A Meta-Analysis.
Acupuncture reportedly relieves chronic knee pain and improves physical function in patients diagnosed with osteoarthritis, but the duration of these effects is controversial. The aim of this study was to evaluate the temporal effects of acupuncture on chronic knee pain due to knee osteoarthritis by means of a meta-analysis. The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published through March 2015. Ten randomized controlled trials of acupuncture compared with sham acupuncture, usual care, or no intervention for chronic knee pain in patients with clinically diagnosed or radiographically confirmed knee osteoarthritis were included. All of the studies were available in English. Weighted mean differences (WMDs), 95% confidence intervals (CIs), publication bias, and heterogeneity were calculated. The acupuncture groups showed superior pain improvement (p < 0.001; WMD = -1.24 [95% CI, -1.92 to -0.56]; I(2) > 50%) and physical function (p < 0.001; WMD = 4.61 [95% CI, 2.24 to 6.97]; I(2) > 50%) in the short term (up to 13 weeks). The acupuncture groups showed superior physical function (p = 0.016; WMD = 2.73 [95% CI, 0.51 to 4.94]; I(2) > 50%) but not superior pain improvement (p = 0.199; WMD = -0.55 [95% CI, -1.39 to 0.29]; I(2) > 50%) in the long term (up to 26 weeks). Subgroup analysis revealed that the acupuncture groups tended to have better outcomes compared with the controls. Significant publication bias was not detected (p > 0.05), but the heterogeneity of the studies was substantial. This meta-analysis demonstrates that acupuncture can improve short and long-term physical function, but it appears to provide only short-term pain relief in patients with chronic knee pain due to osteoarthritis. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Phase II Study of Preoperative Treatment with External Radiotherapy Plus Panitumumab in Low-Risk, Locally Advanced Rectal Cancer (RaP Study/STAR-03).
Treatment with fluoropyrimidines and concomitant long-course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR-03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti-epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low-risk LARC preoperative treatment. Patients had adenocarcinoma of the mid-low rectum, cT3N- or cT2-T3N+, KRAS wild-type status, and negative circumferential radial margin. Panitumumab was administered concomitant to RTE. Rectal surgery was performed 6-8 weeks after the end of preoperative treatment. The adjuvant chemotherapy regimen was FOLFOX. The primary endpoint was the pathologic complete response (pCR) rate. The sample size was calculated using Simon's two-stage design. A pCR of 16% was considered to qualify the experimental treatment for further testing. Ninety-eight patients were enrolled in 13 Italian centers from October 2012 to October 2015. Three panitumumab infusions were administered in 92 (93.4%) patients. The RTE compliance was median dose 50.4 Gy; ≥28 fractions in 82 (83.7%) patients. Surgical treatment was performed in 92 (93.9%) patients, and no severe intraoperative complications were observed. A pCR was observed in 10 (10.9%) patients (95% confidence interval, 4.72%-17.07%). Pathological downstaging occurred in 45 (45.9%) patients. Grade 3 toxicities were observed in 22 (22.3%) patients, and the common adverse events were skin rash in 16 (16.3%) patients. No grade 4 toxicities were reported. The pCR rate (our primary endpoint), at only 10.9%, did not reach the specified level considered suitable for further testing. However, the analysis showed a good toxicity profile and compliance to concomitant administration of panitumumab and RTE in preoperative treatment of LARC. The pCR evaluation in all wild-type RAS is ongoing. The aim of the RaP/STAR-03 study was to evaluate the activity and safety of monoclonal antibody anti-epidermal growth factor receptor (EGFR) panitumumab as a single agent without chemotherapy in low-risk, locally advanced rectal cancer (LARC) preoperative treatment. Nevertheless, the use of panitumumab in combination with radiotherapy in preoperative treatment in patients with KRAS wild type and low-risk LARC did not reach the pathologic complete response primary endpoint. This study showed a good toxicity profile and compliance to combination treatment. Further analysis of NRAS and BRAF on tissue and circulating levels of the EGFR ligands and vascular factors (soluble vascular endothelial growth factor, E-selectin) may provide insight on the potential molecular pathways involved in the anti-EGFR response.


Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype.
B cell CLL/lymphoma 11A (BCL11A) is a transcription factor and regulator of hemoglobin switching that has emerged as a promising therapeutic target for sickle cell disease and thalassemia. In the hematopoietic system, BCL11A is required for B lymphopoiesis, yet its role in other hematopoietic cells, especially hematopoietic stem cells (HSCs) remains elusive. The extensive expression of BCL11A in hematopoiesis implicates context-dependent roles, highlighting the importance of fully characterizing its function as part of ongoing efforts for stem cell therapy and regenerative medicine. Here, we demonstrate that BCL11A is indispensable for normal HSC function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. We find that downregulation of cyclin-dependent kinase 6 (Cdk6), and the ensuing cell-cycle delay, correlate with HSC dysfunction. Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A.


Sex and Gender Differences in Emotion Recognition and Theory of Mind After TBI: A Narrative Review and Directions for Future Research.
A growing body of literature has examined sex differences in a variety of outcomes from moderate-severe traumatic brain injury (TBI), including outcomes for social functioning. Social functioning is an area in which adults with TBI have significant long-term challenges (1-4), and a better understanding of sex and gender differences in this domain may have a significant clinical impact. This paper presents a brief narrative review of current evidence regarding sex differences in one aspect of social functioning in adults with TBI: social cognition, specifically affect recognition and Theory of Mind (ToM). Data from typical adults and adults with TBI are considered in the broader context of common stereotypes about social skills and behaviors in men vs. women. We then discuss considerations for future research on sex- and gender-based differences in social cognition in TBI, and in adults more generally.


Conserved glycine 232 in the ligand channel of ba3 cytochrome oxidase from Thermus thermophilus.
Knowing how the protein environment modulates ligand pathways and redox centers in the respiratory heme-copper oxidases is fundamental for understanding the relationship between the structure and function of these enzymes. In this study, we investigated the reactions of O2 and NO with the fully reduced G232V mutant of ba3 cytochrome c oxidase from Thermus thermophilus (Tt ba3) in which a conserved glycine residue in the O2 channel of the enzyme was replaced with a bulkier valine residue. Previous studies of the homologous mutant of Rhodobacter sphaeroides aa3 cytochrome c oxidase suggested that the valine completely blocked the access of O2 to the active site [Salomonsson, L., et al. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 11617-11621]. Using photolabile O2 and NO carriers, we find by using time-resolved optical absorption spectroscopy that the rates of O2 and NO binding are not significantly affected in the Tt ba3 G232V mutant. Classical molecular dynamics simulations of diffusion of O2 to the active site in the wild-type enzyme and G232V mutant show that the insertion of the larger valine residue in place of the glycine appears to open up other O2 and NO exit/entrance pathways that allow these ligands unhindered access to the active site, thus compensating for the larger valine residue.


Androgen receptor non-nuclear regulation of prostate cancer cell invasion mediated by Src and matriptase.
Castration-resistant prostate cancers still depend on nuclear androgen receptor (AR) function despite their lack of dependence on exogenous androgen. Second generation anti-androgen therapies are more efficient at blocking nuclear AR; however resistant tumors still develop. Recent studies indicate Src is highly active in these resistant tumors. By manipulating AR activity in several different prostate cancer cell lines through RNAi, drug treatment, and the use of a nuclear-deficient AR mutant, we demonstrate that androgen acting on cytoplasmic AR rapidly stimulates Src tyrosine kinase via a non-genomic mechanism. Cytoplasmic AR, acting through Src enhances laminin integrin-dependent invasion. Active Matriptase, which cleaves laminin, is elevated within minutes after androgen stimulation, and is subsequently shed into the medium. Matriptase activation and shedding induced by cytoplasmic AR is dependent on Src. Concomitantly, CDCP1/gp140, a Matriptase and Src substrate that controls integrin-based migration, is activated. However, only inhibition of Matriptase, but not CDCP1, suppresses the AR/Src-dependent increase in invasion. Matriptase, present in conditioned medium from AR-stimulated cells, is sufficient to enhance invasion in the absence of androgen. Thus, invasion is stimulated by a rapid but sustained increase in Src activity, mediated non-genomically by cytoplasmic AR, leading to rapid activation and shedding of the laminin protease Matriptase.


The incidence of left atrial diverticula in coronary CT angiography.
The aim of this study was to characterize the frequency and location of left atrial diverticula by using multidetector computed tomography (MDCT). Cardiac imaging was performed for 454 patients using 64MDCT. Most patients were being examined for coronary artery disease. All images were interpreted by two radiologists on a three-dimensional workstation using multiplanar reformatting, maximum intensity projection, and volumerendering. Diverticula were characterized by localization and diameter. A total of 207 atrial diverticula were diagnosed in 186 (41%) of the 454 patients in this study. The diameters of left atrial diverticula ranged from 2 mm to 16 mm, with an average diameter of 5.2 mm. Left atrial diverticula were located anterosuperiorly in 166 patients (36.6%), anteriorly in four patients (0.9%), anteroinferiorly in three patients (0.7%), inferolaterally in one patient (0.2%), inferomedially in two patients (0.4%), laterally in two patients (0.4%), posterosuperiorly in one patient (0.2%), and superiorly in seven patients (1.5%). Left atrial diverticula are frequently detected during routine cardiac computed tomography angiography examinations. From the Departments of Radiology, and Cardiology, GATA Haydarpasa Teaching Hospital, İstanbul, Turkey.


Regenerative materials: an overview.
Periodontal reconstructive therapies have demonstrated the ability to reverse the destruction due to periodontitis provided that they are implemented according to their individual indications. By properly evaluating a site, one can employ an evidence-based approach to effectively and predictably treat intrabony defects and furcation involvements. It also should be emphasized that a thorough evaluation of the therapeutic outcome should be continuously performed on all sites in order to determine treatment success and the possible need for further intervention. This is based on the long-term follow-up of cases treated with regenerative therapies, which have shown maintenance of results if the patient had good oral hygiene and was enrolled in a proper maintenance program. With respect to the preceding discussion: 1. The main periodontal reconstructive therapies employed by periodontists are GTR, bone replacement grafts and biologic mediators. 2. It is possible to achieve regeneration when using barriers, autografts, allografts, bovine-derived xenografts and EMDs. 3. Currently, regenerative techniques can be used for the treatment of intrabony defects and furcation involvements given the proper evaluation of each individual site. 4. Various regenerative materials are capable of achieving similar results in intrabony defects and are very predictable when employing evidence-based treatment. 5. A combination of regenerative materials such as barriers and grafts in intrabony defects has not demonstrated any improvement over their use alone. 6. A combination of regenerative materials such as barriers and grafts in mandibular class II furcations has demonstrated improvement over the use of the graft or barrier alone. 7. A combination of regenerative materials such as barriers and grafts in maxillary class II furcations has some limited evidence to support improvement over the use of the graft or barrier alone, but the predictability should not be considered high. 8. A combination of regenerative materials such as barriers and grafts in class III furcations has very limited evidence to support improvement over the use of the graft or barrier alone and should not be considered predictable. 9. Beyond the initial healing phase postsurgically, maintenance and oral hygiene play the largest role in long-term therapeutic success.


A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.
Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH.


Supplementary cranial description of the types of Edmontosaurus regalis (Ornithischia: Hadrosauridae), with comments on the phylogenetics and biogeography of Hadrosaurinae.
The cranial anatomy of the flat-skulled hadrosaurine Edmontosaurus regalis (Ornithischia: Hadrosauridae) is extensively described here, based on the holotype and paratype collected from the middle part of the Horseshoe Canyon Formation in southern Alberta. Focus is given to previously undocumented features of ontogenetic and phylogenetic importance. This description facilitates overall osteological comparisons between E. regalis and other hadrosaurids (especially E. annectens), and revises the diagnosis of E. regalis, to which a new autapomorphy (the dorsal half of the jugal anterior process bearing a sharp posterolateral projection into the orbit) is added. We consider the recently named Ugrunaaluk kuukpikensis from the upper Campanian/lower Maastrichtian of Alaska a nomen dubium, and conservatively regard the Alaskan material as belonging to Edmontosaurus sp.. A phylogenetic analysis of Hadrosauroidea using maximum parsimony further corroborates the sister-taxon relationship between E. regalis and E. annectens. In the strict consensus tree, Hadrosaurus foulkii occurs firmly within the clade comprising all non-lambeosaurine hadrosaurids, supporting the taxonomic scheme that divides Hadrosauridae into Hadrosaurinae and Lambeosaurinae. Within Edmontosaurini, Kerberosaurus is posited as the sister taxon to the clade of Shantungosaurus + Edmontosaurus. The biogeographic reconstruction of Hadrosaurinae in light of the time-calibrated cladogram and probability calculation of ancestral areas for all internal nodes reveals a significantly high probability for the North American origin of the clade. However, the Laramidia-Appalachia dispersals around the Santonian-Campanian boundary, inferred from the biogeographic scenario for the North American origin of Hadrosaurinae, are in conflict with currently accepted paleogeographic models. By contrast, the Asian origin of Hadrosaurinae with its relatively low probability resulting from the biogeographic analysis is worth seriously considering, despite the lack of fossil material from the Santonian and lower Campanian of Asia. Extra fossil collecting in appropriate geographic locations and stratigraphic intervals of Asia and Europe will help to clarify the biogeographic dynamics of hadrosaurine dinosaurs in the near future.


Perceptions and practices of COVID-19 protective measures among the general public of North India.
India has a high COVID-19 burden. The Indian government responded to the pandemic by mandating its population to adhere to certain Protective Measures (PMs). Compliance to these PMs depends on their acceptability and adaptability among the general public. To explore the perceptions and practices of COVID-19 related PMs among the general public of North India. Qualitative study in four administrative districts (Lucknow, Etawah, Patna and Darbhanga) of North India. Two urban and two rural districts were purposefully selected. Audio in-depth interviews (IDIs) were conducted with healthy caregivers of children (2-59 months). Data was managed using Atlast Ti and analyzed using conventional content analysis. From July-Sep 2020, 60 IDIs were conducted; 36.6% (22/60) were females and 26.6% (16/60) had below primary education. Respondents concurred that most people in their society flouted the recommended PMs. The reasons for poor/non-compliance with PMs were: perceived poor susceptibility to illness, perceived less severity of COVID-19 and low perceived benefits of complying with the PMs. Respondents opined that COVID-19 is less prevalent in rural areas and among the educated population. Most respondents were aware of the recommended PMs and opined that these must be followed, however subjective norms, social norms and behavioral intentions negatively impacted compliance. Since there was poor community perception of susceptibility to COVID-19 as well as poor perceived severity, the community did not understand the benefits of adhering to the recommended PMs. Therefore, future health communication strategies must take these into account to increase the possibility of success.


Obesity and health expenditures: evidence from Australia.
Rising rates of obesity are a public health concern in every industrialized country. This study investigates the relationship between obesity and health care expenditure in Australia, where the rate of obesity has tripled in the last three decades. Now one in four Australians is considered obese, defined as having a body mass index (BMI, kg/m(2)) of 30 or over. The analysis is based on a random sample survey of over 240,000 adults aged 45 and over that is linked at the individual-level to comprehensive administrative health care claims for the period 2006-2009. This sub-population group has an obesity rate that is nearly 30% and is a major consumer of health services. Relative to the average annual health expenditures of those with normal weight, we find that the health expenditures of those with a BMI between 30 and 35 (obese type I) are 19% higher and expenditures of those with BMI greater than 35 (obese type II/III) are 51% higher. We find large and significant differences in all types of care: inpatient, emergency department, outpatient and prescription drugs. The obesity-related health expenditures are higher for obese type I women than men, but in the obese type II/III state, obesity-related expenditures are higher for men. When we stratify further by age groups, we find that obesity has the largest impact among men over age 75 and women aged 60-74 years old. In addition, we find that obesity impacts health expenditures not only through its link to chronic diseases, but also because it increases the cost of recovery from acute health shocks.


[Atrial standstill: a paralysis of cardiological relevance].
Atrial standstill is a rare arrhythmogenic condition characterized by the absence of electrical and mechanical activity in the atria, transient or persistent, and complete or partial. It can be "idiopathic", sporadic or familial, or secondary to Ebstein's anomaly, Emery-Dreifuss muscular dystrophy (X-linked), Kugelberg-Welander syndrome (autosomal recessive), and amyloidosis. Idiopathic familial atrial standstill is inherited as autosomal dominant trait with variable penetrance. To date, a few cases of familial forms of primary atrial standstill have been described. In each family, the number of affected members was small and limited to relatives of one generation. The genetic basis for familial atrial standstill is unknown. Recently a mutation in the cardiac sodium channel gene SCN5A associated with relatively rare genotypes for two connexin 40 polymorphisms has been reported. The diagnosis relies on the ECG demonstration of bradycardia, absence of P waves, and junctional narrow complex escape rhythm. Nearly 50% of patients suffer from Adams-Stokes attacks. In the primary persistent form, the atrial paralysis is paralleled by atrial dilation, mitral valve incompetence, and thrombotic complications, with high risk of thromboembolic complications. The treatment is addressed to the thromboembolic risk (anticoagulation), mitral incompetence (diuretics and vasodilators) and syncope (pacemaker implantation).


Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.
Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs) in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R) but not (H316Y) polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.


Dual-Source Linear Energy Prediction (LINE-P) Model in the Context of WSNs.
Energy harvesting technologies such as miniature power solar panels and micro wind turbines are increasingly used to help power wireless sensor network nodes. However, a major drawback of energy harvesting is its varying and intermittent characteristic, which can negatively affect the quality of service. This calls for careful design and operation of the nodes, possibly by means of, e.g., dynamic duty cycling and/or dynamic frequency and voltage scaling. In this context, various energy prediction models have been proposed in the literature; however, they are typically compute-intensive or only suitable for a single type of energy source. In this paper, we propose Linear Energy Prediction "LINE-P", a lightweight, yet relatively accurate model based on approximation and sampling theory; LINE-P is suitable for dual-source energy harvesting. Simulations and comparisons against existing similar models have been conducted with low and medium resolutions (i.e., 60 and 22 min intervals/24 h) for the solar energy source (low variations) and with high resolutions (15 min intervals/24 h) for the wind energy source. The results show that the accuracy of the solar-based and wind-based predictions is up to approximately 98% and 96%, respectively, while requiring a lower complexity and memory than the other models. For the cases where LINE-P's accuracy is lower than that of other approaches, it still has the advantage of lower computing requirements, making it more suitable for embedded implementation, e.g., in wireless sensor network coordinator nodes or gateways.


Wearable device adoption among older adults: A mixed-methods study.
Recently, the popularity of smart wearable technologies, such as Fitbit, has significantly increased. There are numerous potential benefits in using these devices, especially among seniors. Yet, little is known about seniors' adoption behavior. Through a mixed-methods approach, this study investigates the factors that impact seniors' intention to use wearable devices. Results from an online survey and interviews showed that seniors' perception of the complexity of working with these devices is a barrier to their adoption decisions. Looking more deeply into the role of complexity revealed that seniors' concern about the complexity of reading and interpreting the output of wearable devices is the main deterring element. Furthermore, we explored the role of two important elements: seniors' cognitive age, and the influence of their subjective well-being on their adoption behavior. Results demonstrated that cognitive age does not significantly impact use intention by itself; nonetheless, subjective well-being moderates its effect. This result revealed an interesting finding, which is that the influence of cognitive age on seniors' use intention depends on seniors' level of subjective well-being. When seniors' subjective well-being is low, surprisingly, cognitive age increases seniors' intention to use the device. These findings provide interesting implications for practice and future research.


Lack in efficacy for imatinib mesylate as second-line treatment of recurrent or metastatic cervical cancer expressing platelet-derived growth factor receptor alpha.
Imatinib mesylate inhibits platelet-derived growth factor receptor (PDGFR), and there are evidences that the PDGFR participates in development and progression of cervical cancer. This pilot study was set to evaluate the efficacy in response rate and progression-free survival of imatinib. A secondary end point was to evaluate its safety as second-line treatment of recurrent or metastatic cervical cancer expressing PDGFRalpha. Imatinib mesylate was administered in daily dosages of 600 mg. Response was evaluated by positron emission tomography/computed tomography every two 28-day courses, and toxicity was evaluated weekly and thereafter. Twelve patients were included in the study. The median age was 49.8 years; all but 1 tumor were squamous cell carcinomas. First-line palliative chemotherapy with carboplatin-paclitaxel was the most frequently used scheme (75.0%). Ten (83.3%) had pelvic and systemic disease, whereas only 2 had systemic disease alone. All patients expressed the PDGFRalpha in more than 10% of malignant cells, whereas only 4 coexpressed the PDGFRbeta. No patient showed response. A single patient having metastatic disease in the lung showed stabilization for 6 months to then progressing in bone. No severe toxicities were seen except for the patient with worsening of bleeding from proctitis. Grades 1 and 2 gastrointestinal toxicities were common. Despite lack of activity of single-agent imatinib, further studies in cervical cancer are deserved to better define the status of imatinib targets in this tumor and to investigate its activity in combination with cytotoxic drugs.


Leaf-level gas-exchange uniformity and photosynthetic capacity among loblolly pine (Pinus taeda L.) genotypes of contrasting inherent genetic variation.
Variation in leaf-level gas exchange among widely planted genetically improved loblolly pine (Pinus taeda L.) genotypes could impact stand-level water use, carbon assimilation, biomass production, C allocation, ecosystem sustainability and biogeochemical cycling under changing environmental conditions. We examined uniformity in leaf-level light-saturated photosynthesis (A(sat)), stomatal conductance (g(s)), and intrinsic water-use efficiency (A(sat)/g(s) or δ) among nine loblolly pine genotypes (selected individuals): three clones, three full-sib families and three half-sib families, during the early years of stand development (first 3 years), with each genetic group possessing varying amounts of inherent genetic variation. We also compared light- and CO(2)-response parameters between genotypes and examined the relationship between genotype productivity, gas exchange and photosynthetic capacity. Within full-sib, half-sib and clonal genotypes, the coefficient of variation (CV) for gas exchange showed no consistent pattern; the CV for g(s) and δ was similar within clonal (44.3-46.9 and 35.5-38.6%) and half-sib (41.0-49.3 and 36.8-40.9%) genotypes, while full-sibs showed somewhat higher CVs (46.9-56.0 and 40.1-45.4%). In contrast, the CVs for A(sat) were generally higher within clones. With the exception of δ, differences in gas exchange among genotypes were generally insignificant. Tree volume showed a significant positive correlation with A(sat) and δ, but the relationship varied by season. Individual-tree volume and genotype volume were positively correlated with needle dark respiration (R(d)). Our results suggest that uniformity in leaf-level physiological rates is not consistently related to the amount of genetic variation within a given genotype, and δ, A(sat) and R(d) were the leaf-level physiological parameters that were most consistently related to individual-tree and genotype productivity. An enhanced understanding of molecular and environmental factors that influence physiological variation within and between loblolly pine genotypes may improve assessments of genotype growth potential and sensitivity to global climate change.


The prooxidant-induced and spontaneous mitochondrial calcium release: inhibition by meta-iodo-benzylguanidine (MIBG), a substrate for mono (ADP-ribosylation).
The norepinephrine analogue meta-iodo-benzylguanidine (MIBG), a substrate for mono(ADP-ribosylation) and inhibitor of eukaryotic ADP-ribosyltransferases, inhibits the prooxidant-induced and spontaneous calcium release from intact rat liver mitochondria without affecting pyridine nucleotide oxidation and hydrolysis. This finding strongly suggests regulation of calcium release by ADP-ribosylation in mitochondria, and may be relevant for the cellular and pharmacological effects of MIBG.


[Modification of Schmidt-Tannhauser's method of bacterial nucleic acid fractionation].
It was revealed that in fractionation of nucleic acids by Schmidt-Tannhauser's method up to 90% of the DNA of bacteria was destroyed in the course of alkaline hydrolysis changing into the RNA fraction (the alkali-labile fraction of the DNA). The authors suggest a modification of the method based on the precipitation of the alkali-labile DNA fraction from the RNA fraction with ethanol. This modified method permits to record over 96% of all the cell DNA of bacteria.


[Cytokine profile during experimental gastric and duodenal ulcers: the serotonin role].
We investigated the levels of proinflammatory and antiinflammatory cytokines in experimental gastric and duodenal ulcers. Precedence shown an increase of pro-inflammatory cytokine TNF-a level in the isolated simulation of gastric ulcers and duodenal ulcers and preferential increase in cytokine IL-4 level in a prior administration of serotonin. The development of chronic diseases of the gastrointestinal tract is largely mediated by immunological reactions and the activation of the serotonergic system. Diversion of functional activity of the immune system plays a big role in the pathogenesis of ulcer disease, particularly T-helper lymphocytes and cytokines produced by them. The formation of the ulcer was accompanied by massive apoptosis of epithelial cells, development of vascular reactions--a plethora of vessels, edema and development of fibrinoid necrosis and infiltration of the mucosa by neutrophils, plasma cells and proliferation of fibroblasts. These processes significantly induced and regulated by cytokines, particularly interleukin IL-1beta, TNF-alpha, IL-4, -6, -8, -12 [4-7]. The purpose of the study was to identify the role of serotonin in the development of immunological reactions during experimental gastric and duodenal ulcers.


Anorectal fistula is an early manifestation of Crohn's disease that occurs before bowel lesions advance: a study of 11 cases.
The diagnostic significance of single-balloon enteroscopy (SBE) in patients presenting with Crohn's disease (CD)-like anorectal fistula is unknown. We experienced 11 cases undergoing SBE due to CD-like fistulas between December 2007 and April 2013. The mean interval from fistula onset to SBE was 19.2 months with a range of 1.3-44.7. Prior to SBE, all patients underwent anorectal examination under anesthesia (EUA), and 9 patients underwent total colonoscopy with terminal ileal cannulation (TCS-I). One of 7 patients undergoing upper gastrointestinal endoscopy had CD-like gastritis. EUA revealed CD fissures in 7 patients, 1 of whom had no intestinal lesion. Primary TCS-I identified early lesions, such as aphthes and small ulcers, in 4 patients. Among the other 5 patients without any intestinal lesions with TCS-I, SBE indicated early lesions in 3 patients. One of 2 patients who initially underwent SBE without TCS-I showed multiple aphthes. Of the 11 patients, only 4 patients fulfilled the definitive Japanese diagnostic criteria for CD and 7 remained 'suspected CD' cases. Intrinsic anorectal fistulas as a presenting symptom of CD may be an early predictor of bowel lesions. SBE has the potential to reveal incipient disease because an early ileal lesion is not rare for patients with anorectal fistulas.


A rapid and simple RP-HPLC method for quantification of kirenol in rat plasma after oral administration and its application to pharmacokinetic study.
A rapid and simple reverse-phase high-performance liquid chromatography (RP-HPLC) was developed and validated for the quantification of kirenol in rat plasma after oral administration. Kirenol and darutoside (internal standard, IS) were extracted from rat plasma using Cleanert™ C(18) solid-phase extraction (SPE) cartridge. Analysis of the extraction was performed on a Thermo ODS-2 Hypersil C(18) reversed-phase column with a gradient eluent composed of acetonitrile and 0.1% phosphoric acid. The flow rate was 1.0 mL/min and the detection wavelength was set at 215 nm. The calibration curve was linear over the range of 9.756-133.333 µg/mL (r(2) = 0.9991) in rat plasma. The lower limits of detection and quantification were 2.857 and 9.756 µg/mL, respectively. The intra- and inter-day precisions (relative standard deviation, RSD) were between 2.24 and 4.46%, with accuracies ranging from 91.80 to 102.74%. The extraction recovery ranged from 98.16 to 107.62% with RSD less than 4.81%. Stability studies showed that kirenol was stable in preparation and analytical process. The present method was successfully applied to the pharmacokinetic study of kirenol in male Sprague-Dawley rats after oral administration at a dose of 50 mg/kg.


3-(Methoxycarbonylmethylene)isobenzofuran-1-imines as a new class of potential herbicides.
A novel class of potential herbicides, the 3-(methoxycarbonylmethylene) isobenzofuran-1-imines, has been discovered. The herbicidal activity has been tested on two particular molecules, (E)-methyl 2-[3-(butylimino)isobenzofuran-1(3H)-ylidene]acetate (1) and (E)-methyl 2-phenyl-2-[3-(phenylimino)isobenzofuran-1(3H)-ylidene]acetate (2), prepared by palladium-catalyzed oxidative carbonylation of 2-alkynylbenzamides. Both compounds 1 and 2 showed a strong phytotoxic effect on both shoot and root systems of Arabidopsis thaliana. The effects observed on the shoot were similar for both molecules, but while compound 1 showed a stronger effect on root parameters (such as primary root length, root hair and density, showing lower ED50 values), compound 2 caused important malformations in root morphology. Our results indicate that these molecules are very promising synthetic herbicides.


A Tellurium Oxide Microcavity Resonator Sensor Integrated On-Chip with a Silicon Waveguide.
We report on thermal and evanescent field sensing from a tellurium oxide optical microcavity resonator on a silicon photonics platform. The on-chip resonator structure is fabricated using silicon-photonics-compatible processing steps and consists of a silicon-on-insulator waveguide next to a circular trench that is coated in a tellurium oxide film. We characterize the device's sensitivity by both changing the temperature and coating water over the chip and measuring the corresponding shift in the cavity resonance wavelength for different tellurium oxide film thicknesses. We obtain a thermal sensitivity of up to 47 pm/°C and a limit of detection of 2.2 × 10-3 RIU for a device with an evanescent field sensitivity of 10.6 nm/RIU. These results demonstrate a promising approach to integrating tellurium oxide and other novel microcavity materials into silicon microphotonic circuits for new sensing applications.


Effects of positive end-expiratory pressure on mechanical ventilation duration after coronary artery bypass grafting: a randomized clinical trial.
Patients undergoing cardiac surgery remain on mechanical ventilation postoperatively until they regain consciousness. Positive end-expiratory pressure (PEEP) may influence the duration of mechanical ventilation after coronary artery bypass grafting (CABG). The aim of this study was to compare the effects of different levels of PEEP on the duration of mechanical ventilation after coronary artery bypass grafting. This was a randomized clinical trial with 136 patients undergoing CABG between January 2011 and March 2012. We divided the patients into three groups with different levels of PEEP at the onset of mechanical ventilation: Group A, PEEP=5 cmH2O (n=44); Group B, PEEP=8 cmH2O (n=47) and Group C, PEEP=10 cmH2O (n=45). Mechanical ventilation time was obtained from a Physical Therapy Evaluation Form. We excluded patients with chronic obstructive pulmonary disease and those requiring concomitant, emergency or off-pump surgeries. For statistical analysis, we used the Kruskal-Wallis, G and Chi-square tests, with p<0.05 considered significant. From the point of weaning from mechanical ventilation until 12 hours after intensive care unit (ICU) admission, we saw a statistically different duration of mechanical ventilation between groups (p=0.029). In Group A, the average mechanical ventilation time was 6.7±3.2 hours; it was 6.8±3.3 hours in Group B and 5.1±2.9 hours in Group C. The use of higher levels of PEEP was associated with shorter duration of mechanical ventilation in postoperative CABG patients.


A New Way of Evaluating Effectiveness of URM Summer Pipeline Programs.
Many academic medical centers fund educational opportunities (pipeline programs) for students who are underrepresented in medicine (URM). However, there is a sparsity of published literature on pipeline programs and an even smaller body of published literature that investigates program effectiveness. In a retrospective cohort study (n=12) of the Provost's Summer Mentorship Program-Medicine (SMPM), we evaluated students' rating of program effectiveness, students' rating of the program's impact on their mindsets, and SAT scores. Several program mindsets, including sense of belonging (inclusiveness) in the health professions and connection to mentors in the medical field, reflect common barriers that prevent URM students from pursuing careers in medicine as outlined in pipeline literature. We describe program effectiveness using mean and median ratings of SMPM effectiveness, ratings of mindsets, and SAT scores. We used Wilcoxon Rank Sum to assess pre and post program differences in ratings of mindsets and SAT scores. SMPM was effective for learners. The overall mean rating for SMPM effectiveness was 4.27. Mindsets for confidence, interest, sense of belonging, college mentorship, and physician mentorship were statistically different from the start to the end of SMPM (p<0.05), with mean improvement of about 34%, 41%, 44%, 180%, and 140% respectively. The mean pre and post SMPM SAT scores as well as 4-month follow-up SAT mean scores were 713 (SD:155), 813 (SD:83), and 1058 (SD:147), respectively. There was a statistically significant difference between all three SAT scores (p<0.05). In addition to providing educational support, our pipeline program effectively increased students' sense of belonging in the medical field and their connections to physician mentors, which are two common barriers for URM students who are interested in medicine.


Prenatal stress elicits regionally selective changes in basal FGF-2 gene expression in adulthood and alters the adult response to acute or chronic stress.
Exposure to stress during pregnancy influences the trajectory of brain development resulting in permanent alterations that may contribute to increased susceptibility to subsequent cognitive or neuropsychiatric disorders. In this manuscript, we examined the effects of prenatal stress on the expression of basic fibroblast growth factor (FGF-2), an important molecular regulator of development and plasticity, in adult male rats under basal conditions as well as in response to acute or chronic stress. Baseline FGF-2 mRNA levels were differentially influenced by gestational stress in a variety of brain regions, with significant decreases in prefrontal cortex and increases in entorhinal cortex and striatum. By itself, postnatal stress similarly decreased trophic factor expression in prefrontal cortex while evoking stimulation elsewhere. Gestational stress altered the pattern of FGF-2 expression in response to adult stress, completely reversing the pattern in the prefrontal cortex (stimulatory instead of inhibitory), blunting the response in the entorhinal cortex and desensitizing the response in the striatum. These effects point to a unique interference of chronic prenatal stress with both ongoing FGF-2 expression and its responses to subsequent stressors, lasting into adulthood. Given the multifaceted role of FGF-2 in synaptic development, maintenance and plasticity, these data provide detailed mechanistic evidence as to how prenatal stress elicits lifelong effects on synaptic function. The abnormal modulation of FGF-2 gene expression in specific brain regions in response to subsequent stress in adulthood may impair the normal adaptive responses of the cell to challenging situations.


Well-defined multibranched gold with surface plasmon resonance in near-infrared region from seeding growth approach using gyroid block copolymer template.
Well-defined multibranched gold (Au) in polymers, both as bulk or continuous thin films, can be fabricated by using a nanoporous polymer with gyroid nanochannels as a template. The nanoporous polymer template is obtained from the self-assembly of a degradable block copolymer, polystyrene-b-poly (L-lactide) (PS-PLLA), followed by the hydrolysis of PLLA blocks. Templated seeding growth approach can be conducted to create precisely controlled nanostructured Au giving remarkable surface plasmon resonance (SPR) in (branched Au with uniform distribution in PS matrix) near-infrared (NIR) region. Controlled growth conditions allow the fabrication of three-dimensionally ordered nanoporous Au particles that possess NIR SPR. Double gyroid Au with dual networks in the PS matrix is obtained after completing the seeding growth at which the NIR SPR diminishes resulting from the reduction in the density of nanostructured edge.


Blockade of CCL2/CCR2 signalling ameliorates diabetic nephropathy in db/db mice.
CCL2/C-C chemokine receptor 2 (CCR2) signalling is suggested to play a significant role in various kidney diseases including diabetic nephropathy. We investigated the renoprotective effect of a CCR2 antagonist, RS102895, on the development of diabetic nephropathy in a type 2 diabetic mouse model. Six-week-old diabetic db/db and non-diabetic db/m mice were fed either normal chow or chow mixed with 2 mg/kg/day of RS102895 for 9 weeks. We investigated the effects of CCR2 antagonism on blood glucose, blood pressure, albuminuria and the structure and ultrastructure of the kidney. Diabetes-induced albuminuria was significantly improved after CCR2 antagonist treatment, and glucose intolerance was improved in the RS102895-treated diabetic mice. RS102895 did not affect blood pressure, body weight or kidney weight. Mesangial expansion, glomerular basement membrane thickening and increased desmin staining in the diabetic kidney were significantly improved after RS102895 treatment. The up-regulation of vascular endothelial growth factor mRNA expression and the down-regulation of nephrin mRNA expression were markedly improved in the kidneys of RS102895-treated diabetic mice. Increased renal CD68 and arginase II and urinary malondialdehyde in diabetes were effectively attenuated by RS102895 treatment. Blockade of CCL2/CCR2 signalling by RS102895 ameliorates diabetic nephropathy not only by improving blood glucose levels but also by preventing CCL2/CCR2 signalling from altering renal nephrin and VEGF expressions through blocking macrophage infiltration, inflammation and oxidative stress in type 2 diabetic mice.