Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging ...studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10
), left fusiform gyrus (d=-0.288; P=8.25 × 10
) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10
). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Exotic fruit consumption and processing is increasing worldwide due to the improvement in preservation techniques, transportation, marketing systems and consumer awareness of health benefits. The ...entire body of tropical exotic fruits is rich in bioactive compounds, such as phenolic constituents, carotenoids, vitamins and dietary fiber. However, the fruit processing industry deals with the large percentage of byproducts, such as peels, seeds and unused flesh, generated in the different steps of the processing chains. In most cases, the wasted byproducts can present similar or even higher contents of bioactive compounds than the final produce does. The aim of this review is to promote the production and processing of exotic fruits highlighting the possibility of the integral exploitation of byproducts rich in bioactive compounds. Amongst the possible uses for these compounds that can be found in the food industry are as antioxidants (avoiding browning and lipid oxidation and as functional food ingredients), antimicrobials, flavoring, colorants and texturizer additives. Finally, the importance of extraction techniques of bioactive compounds designated as food additives is also included.
Frailty is now a well-recognized and common syndrome among older persons. Frailty is a syndrome which increases the risk of an older person to develop disability or to die when exposed either to ...physical or psychosocial stressors . Although frailty, disability and multimorbidity often coexist and interact, they are distinct and separate concepts. Growing evidence suggests that each of these interrelated conditions is preventable and their associated complications manageable. However, early identification is imperative as once disability and multimorbidity occur, frailty in less likely to be prevented or reversed. As such it should be distinguished from persons with disability in their activities of daily living. The conditions leading to the frailty syndrome should have some degree of reversibility, thus distinguishing it from multimorbidity. Recently, the International Conference of Frailty and Sarcopenia Research (ICFSR) formulated evidence-based guidelines for the identification and management of physical frailty. Physical frailty was originally defined and validated by Fried et al. This definition included measurements of low activity level, slowness of walking, muscle weakness, exhaustion and weight loss. This approach differs from that of Rockwood and Mitnitski which used the number of “deficits” (signs, symptoms, clinical conditions) to determine a frailty index. Primary care represents the entry point into the health care system for many older adults who may be pre-frail and frail. A shortage of geriatricians and the higher frequency of frailty in community settings call for primary care clinicians (general practitioners, generalists, family physicians) to increasingly assess and manage older adults at risk for frailty or who are already frail.The purpose of this paper is to suggest practical frailty screening and management strategies in primary care settings. We will also discuss the characteristics of these instruments and their applicability to primary care. For the sake of consistency hereafter, we will refer to clinicians delivering primary care as primary care providers.
Neuroimaging studies have found evidence of altered brain structure and function in schizophrenia, but have had complex findings regarding the localization of abnormality. We applied multimodal ...imaging (voxel-based morphometry (VBM), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) combined with tractography) to 32 chronic schizophrenic patients and matched healthy controls. At a conservative threshold of P=0.01 corrected, structural and functional imaging revealed overlapping regions of abnormality in the medial frontal cortex. DTI found that white matter abnormality predominated in the anterior corpus callosum, and analysis of the anatomical connectivity of representative seed regions again implicated fibres projecting to the medial frontal cortex. There was also evidence of convergent abnormality in the dorsolateral prefrontal cortex, although here the laterality was less consistent across techniques. The medial frontal region identified by these three imaging techniques corresponds to the anterior midline node of the default mode network, a brain system which is believed to support internally directed thought, a state of watchfulness, and/or the maintenance of one's sense of self, and which is of considerable current interest in neuropsychiatric disorders.
Display omitted
•A state-of-the-art review of nanotechnology alternatives for transformers is shown.•Performance of materials used in transformers can be enhanced by nanoparticles.•Nanofluids, ...nano-insulation, nanostructured insulators are the main topics.•A general prospective of nanomaterials applications for transformers is proposed.
Nanoscience and nanotechnology applications have shown remarkable progress in several industrial fields, producing advance materials. Nowadays, there are a great number of technological developments and R&D projects regarding nanotechnology concepts to enhance performance and reliability of conventional materials. Electrical industry has taken advantage of these nanotechnology efforts looking for application in its components, such as in electrical transformers which are considered as key elements in the electricity network. This paper shows a comprehensive literature review on the applications of nanotechnology concepts for transformers, especially investigations related to insulating materials, dielectric fluids, outdoor insulators, monitoring systems and other components. Latest up to date literature on the applications regarding nanomaterials for transformers have been reviewed and reported. In addition, opportunities for future research and a general overview of nano-applications in electrical transformers are shown in this work.
Contents
Aquaporins (AQPs) play a vital role for the transport of water and solutes across cell membranes. Classification of these ubiquitous proteins into three categories (orthodox AQPs, ...aquaglyceroporins and superaquaporins) is based on their sequence similarity and substrate selectivity. In the male reproductive tract of mammals, most AQPs (except AQP6 and AQP12) are found in different organs (including testis, efferent ducts and epididymis). AQP1 and AQP9 are the most abundant AQPs in the efferent ducts and epididymis and play a crucial role for the secretion/reabsorption dynamics of luminal fluid during sperm transport and maturation. AQP3, AQP7, AQP8 and AQP11 are the most abundant AQPs in sperm and are involved in the regulation of their volume, which is required for the differentiation of spermatids into spermatozoa during spermatogenesis, as well as in sperm transit along environments of different osmolality (male and female reproductive tracts). While different studies conducted in oocytes and embryos have demonstrated that AQPs are important for cryotolerance, data in sperm are scarce. At present, mounting evidence indicates that AQP3, AQP7 and AQP11 are involved in the sperm response to variations of osmolality and to freeze‐thawing procedures. All these studies contribute to understand the physiology of both male reproductive tract and sperm, and open up new research ventures on the improvement of sperm cryopreservation protocols.
The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within ...clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although ...immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described.
Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n=51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.
Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 21%, 95% confidence interval (CI) 10% to 35% patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%,P<0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09–0.94;P = 0.04).
Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.
Introduction
The 2015 American Thyroid Association guidelines recommend to de-escalate treatment such as Thyroid lobectomy instead of total thyroidectomy for 1–4 cm papillary thyroid cancer (PTC). ...Dutch guidelines endorse restricted work-up for thyroid incidentalomas recommending only fine needle aspiration in case of a ‘palpable thyroid nodule’. This diagnostic work-up algorithm may result in the identification of less indolent PTCs and may lead to a patient population with relatively more aggressive PTCs. This study aims to retrospectively analyze recurrence rates of low-risk 1–4 cm PTC in the Netherlands.
Methods
From the national cancer registry, patients with low-risk 1–4 cm PTC between 2005 and 2015 were included for analysis. Disease free survival (DFS) and overall survival were compared between patients who underwent TT ± RAI and TL without RAI. Post-hoc propensity score analysis was performed correcting for age, sex, T-stage, and N-stage.
Results
In total 901 patients were included, of which 711 (78.9%) were females, with a median follow-up of 7.7 years. TT was performed in 893 (94.8%) patients. Recurrence occurred in 23 (2.6%) patients. Multivariable analysis showed no significant correlation between extent of surgery and DFS (
p
= 0.978), or overall survival (
p
= 0.590). After propensity score matching, multivariable analysis showed no significant difference on extent of surgery and recurrence.
Conclusion
Low-risk PTC patients with 1–4 cm tumor who underwent TL showed similar recurrence rates as those who underwent TT ± adjuvant RAI, which suggests that TL can be sufficient in treating low-risk 1–4 cm PTC, possibly reducing morbidity of these patients in the Netherlands.
Emission of bromine from sea‐salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO ...observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO “hotspots” during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short‐lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere.
PDF
