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Brain edema; Intracranial hemorrhage; Serum biomarker Edema cerebral; Hemorragia intracraneal; Biomarcador sérico Edema cerebral; Hemorràgia intracranial; Biomarcador sèric Background: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications. Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4. Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log10S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7–6.9, p = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3–7.1, p

Despite the recognised need for education and training in laboratory animal science (LAS) and ethics in Africa, access to such opportunities has historically been limited. To address this, the Pan-African Network for Laboratory Animal Science and Ethics (PAN-LASE) was established to pioneer a support network for the development of education and training in LAS and ethics across the African continent. In the 4.5 years since the establishment of PAN-LASE, 3635 individuals from 28 African countries have participated in our educational activities. Returning to their home institutions, they have both established and strengthened institutional and regional hubs of knowledge and competence across the continent. Additionally, PAN-LASE supported the development of guidelines for establishment of institutional Animal Ethics Committees, a critical step in the implementation of ethical review processes across the continent, and in enhancing animal welfare and scientific research standards. Key challenges and opportunities for PAN-LASE going forward include the formalisation of the network; the sustainability of education and training programmes; implementation of effective hub-and-spoke models of educational provision; strengthening governance frameworks at institutional, national and regional levels; and the availability of Africa-centric open access educational resources. Our activities are enhancing animal welfare and the quality of animal research undertaken across Africa, enabling African researchers to undertake world-leading research to offer solutions to the challenges facing the continent. The challenges, successes and the lessons learnt from PAN-LASE’s journey are applicable to other low- and middle-income countries across the world seeking to enhance animal welfare, research ethics and ethical review in their own country or region.

Anthropogenic carbon emissions have the potential to trigger changes in climate and ecosystems that would be catastrophic for the well-being of humans and other species. Widespread shifts in production and consumption patterns are urgently needed to address climate change. Although transnational agreements and national policy are necessary for a transition to a fully decarbonized global economy, fluctuating political priorities and lobbying by vested interests have slowed these efforts. Against this backdrop, bottom-up pressure from social movements and shifting social norms may offer a complementary path to a more sustainable economy. Furthermore, norm change may be an important component of decarbonization policies by accelerating or strengthening the impacts of other demand-side measures. Individual actions and policy support are social processes—they are intimately linked to expectations about the actions and beliefs of others. Although prevailing social norms often reinforce the status quo and unsustainable development pathways, social dynamics can also create widespread and rapid shifts in cultural values and practices, including increasing pressure on politicians to enact ambitious policy. We synthesize literature on social-norm influence, measurement, and change from the perspectives of psychology, anthropology, sociology, and economics. We discuss the opportunities and challenges for the use of social-norm and social-tipping interventions to promote climate action. Social-norm interventions aimed at addressing climate change or other social dilemmas are promising but no panacea. They require in-depth contextual knowledge, ethical consideration, and situation-specific tailoring and testing to understand whether they can be effectively implemented at scale. Our review aims to provide practitioners with insights and tools to reflect on the promises and pitfalls of such interventions in diverse contexts.

Foraging and feeding are indispensable for survival and their timing depends not only on the metabolic state of the animal but also on the availability of food resources in their environment. Since both these aspects are subject to change over time, these behaviours exhibit rhythmicity in occurrence. As the locomotor activity of an organism is related to its disposition to acquire food, and peak feeding in fruit flies has been shown to occur at a particular time of the day, we asked if cyclic food availability can entrain their rhythmic activity. By subjecting flies to cyclic food availability i.e., feeding/starvation (FS) cycles, we provided food cues contrasting to the preferred activity times and observed if this imposed cycling in food availability could entrain the activity/rest rhythm. We found that phase control, which is a property integral to entrainment, was not achieved despite increasing starvation duration of FS cycles (FS12:12, FS10:14 and FS8:16). We also found that flies subjected to T21 and T26 FS cycles were unable to match period of the activity rhythm to short or long T-cycles. Taken together these results show that external food availability cycles do not entrain the activity/rest rhythm of fruit flies. However, we find that starvation induced hyperactivity causes masking which results in phase changes. Additionally, T-cycle experiments resulted in minor period changes during FS treatment. These findings highlight that food cyclicity by itself may not be a potent zeitgeber but may act in unison with other abiotic factors like light and temperature to help flies time their activity appropriately.

Seaweed fibre is usually discarded as biomass waste after extraction of useful ingredients from seaweed. However this seaweed fibre, a natural abundant cellulose material with uniform dimensions 10 times smaller than other plant-based fibre can be utilized as electrode material for energy storage. In this work, we converted seaweed fibre into conductive carbon electrodes by a thermal carbonisation method. The morphology, chemical composition and conductivity are highly influenced by the carbonisation temperature. In comparison to other biomass sources such as cotton pulp, seaweed fibre is finer, smoother and more conductive at low carbonisation temperature. These carbonized seaweeds were then used as a supercapacitor, giving a high supercapacitance (226.3 Fg−1) at the carbonisation temperature of 900°C, and good stability within 2400 cycles. This specific capacitance is significantly higher than values obtained from filter paper or cotton pulp.

Nodding Syndrome (NS) occurs within a wide spectrum of epilepsies seen in onchocerciasis endemic areas of sub-Saharan Africa. It has debilitating consequences on affected individuals and increases the socio-economic, physical and psychological burden on care-givers and their households, diminishing their standing within the community. Social science research on the disproportionate burden of the disease on females is limited. Based on ethnographic research over 3 years in northern Uganda, we explored the burden of being ill and care-giving for persons with NS from a gendered perspective. We found that NS-affected females were at greater risk of physical and psychological abuse, sexual violence, unwanted pregnancies, sexually transmitted infections and stigma, in a context of deteriorating socio-economic conditions. Primary care-givers of the NS-affected, mostly women, struggled to make ends meet and were subjected to stigma and abandonment. Targeted interventions, including legal protection for affected females, stigma reduction, and psycho-social and financial support are needed.

Animal dissection remains a common practice in American biology classrooms, despite the availability of dissection alternatives to study anatomy and physiology. Indeed, there is a growing body of evidence in the literature suggesting that the use of alternatives leads to the greater achievement of learning objectives, as compared to dissection. To better understand the current use of and attitudes toward dissection and alternatives, a nationwide survey of (mainly high-school) biology teachers ( n = 2687) was conducted. Most educators believed that learning objectives related to biology subject content could be met through the use of alternatives, yet they preferred the hands-on experience of dissection. Most educators allow their students to use alternatives if requested, although few teachers ask students about their preference for using an animal specimen versus an alternative. Educators cited student engagement as the main factor driving their decision to choose between dissection specimens and alternatives, and felt that cost is the biggest barrier to implementing alternatives at their schools. Additional perspectives on dissection and alternatives were shared by survey participants. Since alternatives can be used to meet learning objectives associated with dissection, we recommend their use as replacements for traditional animal specimens, in line with the replacement, reduction and refinement of animal use in education, according to the Three Rs principles.

Recurrent aphthous stomatitis (RAS) is a common recurrent ulcerative disease of the oral mucosa which is closely related to oral microbial composition. However, the specific effect and the mechanism of smoking in RAS are unclear. In this study, 16S rRNA sequencing technology was used to compare the differences in saliva microbial community between 28 non-smoking healthy controls (NSctrl), 31 non-smoking RAS patients (NSras), and 19 smoking RAS patients (Sras). The results showed that the bacterial community diversity in patients with RAS (NSras and Sras) was lower than that of NSctrl. The microbial community in smoking-associated RAS is less diverse and distinct from that of non-smokers. The RAS groups have higher abundance of Veillonella, Rothia, and Sneathia and lower abundance of Bacteroidales, Bacteroides, Wolinella, Moryella, Pyramidobacter, and Christensenellaceae at the genera level. A significantly different abundance of Anaerovorax, Candidatus Endomicrobium, Lactococcus, Sneathia, Veillonella, and Cloacibacterium was observed between the Sras and the NSras group. Notably, there was a significant difference in many species from the genus Prevotella and Treponema between the NSras and the Sras group. Further, the relative abundance of several taxa is correlated with smoking age or frequency, including Megasphaera, Haemophilus, Leptotrichia, and Rothia at the genera level, and Prevotella melaninogenica, Prevotella salivae, Megasphaera micronuciformis, Haemophilus parainfluenzae, Alloprevotella tannerae, Actinomyces naeslundii, Lautropia mirabilis, and Capnocytophaga sputigena at the species level. Among patients with RAS, smoking aggravated the pathways of respiration and human pathogens. Our results suggest that smoking is closely related to changes in the oral microbiota, which may contribute an opposite effect to the pathogenesis of RAS. This study provides new insight and theoretical basis for the cause and pathogenesis of RAS and better prevention and treatment.

Renal transplant patients are immunosuppressed and are at increased risk of opportunistic infections, including Nocardia infection. In renal transplant patients, information on the incidence and risk factors associated with nocardiosis is limited. To address the incidence and risk factors associated with nocardiosis in a large renal transplant population, we used the US Renal Data System (USRDS). Sequelae of allograft failure or rejection after infection were also examined. Demographics, clinical risk factors, Nocardia diagnosis, and allograft failure following Nocardia infection were queried in USRDS renal transplant patients using International Classification of Diseases, Ninth Revision (ICD-9) codes in billing claims and Centers for Medicare and Medicaid Services Form 2728. Generalized linear models were used to determine the risk factors associated with nocardiosis, and Cox proportional hazards models were used to examine the association of risk factors with graft failure among patients with Nocardia infection. Of 203,233 renal transplant recipients identified from 2001 to 2011, 657 (0.32%) were diagnosed with Nocardia infection. Pneumonia was the most frequent presentation (15.2%), followed by brain abscess (8.4%). Numerous factors associated with increased Nocardia infection included age >65 years (OR=2.10, 95% CI 1.71 to 2.59), history of transplant failure (OR=1.28, CI 1.02 to 1.60) or history of rejection (OR=4.83, CI 4.08 to 5.72), receipt of a deceased donor transplant (OR=1.23, CI 1.03 to 1.46), and treatment with basiliximab (OR=1.25, CI 1.00 to 1.55), cyclosporine (OR=1.30, CI 1.03 to 1.65), tacrolimus (OR=2.45, CI 2.00 to 3.00), or thymoglobulin (OR=1.89, CI 1.59 to 2.25). In patients with nocardiosis administration of antithymocyte globulin (HR=2.76), chronic obstructive pulmonary disease (HR=2.47), and presentation of Nocardia infection with brain abscess (HR=1.85) were associated with an increased risk of graft failure. This study provides new information to enhance early recognition and targeted treatment of nocardiosis in renal transplant patients.

In January of 2018, after decades of sexual abuse of hundreds of athletes under his medical care, USA Gymnastics team doctor Larry Nassar faced 156 of the women he victimized when they testified at his sentencing hearing and detailed the abuse. In the wake of the Nassar verdict, gymnastics and other youth sports organizations have come under fire for abusive practices that victimize young athletes. Scholars have recently argued for an approach to understanding sexual violence as an organizational, rather than individual, phenomenon. The power organizations possess to inflict violence on their members requires an understanding of the increased role of organizations in our decision-making and shaping our values and desires. Through an analysis of testimonies submitted by women who were victimized by Nassar as children, I argue that violence was intentionally deployed as an organizing strategy by USA Gymnastics. Abusive organizational practices traumatized girls, leading them to recalibrate their expectations for what was normal and acceptable, ultimately facilitating their abuse. I propose “high-stakes organizations” as contexts particularly vulnerable to violent organizational practices. I argue, in these high-stakes organizations, trauma is likely to be deployed as a strategy for organizational commitment, further fostering precarity in modern organizations.

Biliary fibrosis is an important pathological indicator of hepatobiliary damage. Cholangiocyte is the key cell type involved in this process. To reveal the pathogenesis of biliary fibrosis, it is essential to understand the normal development as well as the aberrant generation and proliferation of cholangiocytes. Numerous reports suggest that the Wnt signaling pathway is implicated in the physiological and pathological processes of cholangiocyte development and ductular reaction. In this review, we summarize the effects of Wnt pathway in cholangiocyte development from embryonic stem cells, as well as the underlying mechanisms of cholangiocyte responses to adult ductal damage. Wnt signaling pathway is regulated in a step-wise manner during each of the liver differentiation stages from embryonic stem cells to functional mature cholangiocytes. With the modulation of Wnt pathway, cholangiocytes can also be generated from adult liver progenitor cells and mature hepatocytes to repair liver damage. Non-canonical Wnt signaling is triggered in the active ductal cells during biliary fibrosis. Targeted control of the Wnt signaling may hold the great potential to reduce and/or reverse the biliary fibrogenic process.

PPM1A (magnesium-dependent phosphatase 1 A, also known as PP2Cα) is a member of the Ser/Thr protein phosphatase family. Protein phosphatases catalyze the removal of phosphate groups from proteins via hydrolysis, thus opposing the role of protein kinases. The PP2C family is generally considered a negative regulator in the eukaryotic stress response pathway. PPM1A can bind and dephosphorylate various proteins and is therefore involved in the regulation of a wide range of physiological processes. It plays a crucial role in transcriptional regulation, cell proliferation, and apoptosis and has been suggested to be closely related to the occurrence and development of cancers of the lung, bladder, and breast, amongst others. Moreover, it is closely related to certain autoimmune diseases and neurodegenerative diseases. In this review, we provide an insight into currently available knowledge of PPM1A, including its structure, biological function, involvement in signaling pathways, and association with diseases. Lastly, we discuss whether PPM1A could be targeted for therapy of certain human conditions.

The bacterium Listeria monocytogenes ( Lm) is widely distributed in the environment as a saprophyte, but may turn into a lethal intracellular pathogen upon ingestion. Invasive infections occur in numerous species worldwide, but most commonly in humans and farmed ruminants, and manifest as distinct forms. Of those, neuroinfection is remarkably threatening due to its high mortality. Lm is widely studied not only as a pathogen but also as an essential model for intracellular infections and host-pathogen interactions. Many aspects of its ecology and pathogenesis, however, remain unclear and are rarely addressed in its natural hosts. This review highlights the heterogeneity and adaptability of Lm by summarizing its association with the environment, farm animals, and disease. It also provides current knowledge on key features of the pathology and (molecular) pathogenesis of various listeriosis forms in naturally susceptible species with a special focus on ruminants and on the neuroinvasive form of the disease. Moreover, knowledge gaps on pathomechanisms of listerial infections and relevant unexplored topics in Lm pathogenesis research are highlighted.

The ability to distinguish among the subspecies of Pasteurella multocida isolates is important epidemiologically; however, classification at the subspecies level based on the results of conventional biochemical tests (fermentation of sorbitol and dulcitol) is reportedly not accurate in all cases. Therefore, we developed a rapid, multiplex PCR assay to differentiate among the 3 subspecies of P. multocida. The PCR assay includes the P. multocida species–specific primers KMT1SP6 and KMT1T7 as an internal amplification control, with a newly designed gatD (galactitol-1-phosphate-5-dehydrogenase)-specific primer pair (unique for subsp. gallicida), and primers targeting a 16S rRNA gene region specific for subsp. septica. The subspecies specificity of the PCR was demonstrated by applying the test to a collection of 70 P. multocida isolates, including the Heddleston serovar reference strains; all isolates and strains were assigned correctly. The PCR assay is a sensitive, specific, and highly effective method for the identification of P. multocida subspecies, and an alternative to biochemical test–based differentiation. A possible relationship was noticed between P. multocida subspecies and lipopolysaccharide (LPS) genotype; all but one of the subsp. gallicida strains were isolated only from avian hosts and represented L1 LPS genotype. Subsp. multocida and subsp. septica isolates were classified into 5 and 4 different LPS genotypes, respectively, of which L3 was the only LPS genotype shared between these 2 subspecies.

Periodontitis is a common complex inflammatory disease of the oral cavity. It is characterized by inflammation of gingival tissues and alveolar bone loss. Recently, a genome-wide association study and 2 genome-wide association study meta-analyses found 2 associated regions (haplotype blocks) at the inhibitory immune receptor gene SIGLEC5 to increase the risk for periodontitis. The aims of the current study were the identification of the putative causal variants underlying these associations, characterization of their molecular biological effects, and validation of SIGLEC5 as the target gene. We mapped the associated single-nucleotide polymorphisms to DNA elements with predictive features of regulatory functions and screened the associated alleles for transcription factor (TF) binding sites. Antibody electrophoretic mobility shift assays (EMSAs) with allele-specific probes were used to identify TF binding and to quantify allele-specific effects on binding affinities. Luciferase reporter assays were used to quantify the effect directions and allele-specific strength of the associated regulatory elements. We used CRISPR-dCas9 gene activation to validate SIGLEC5 as a target of the association. EMSA in peripheral blood mononuclear cells showed that E-26 transformation–specific TF-related gene (ERG) binds at rs11084095, with almost complete loss of binding at the minor A-allele. Allele-specific reporter genes showed enhancer function of the DNA sequence at rs11084095, which was abrogated in the background of the A-allele. EMSA in B lymphocytes showed that TF MAF bZIP (MAFB) binds at the common G-allele of rs4284742, whereas the minor A-allele reduced TF binding by 69%, corresponding to 9-fold reduction of luciferase reporter gene activity by the A-allele. Using CRISPR-dCas9, we showed that the enhancer at rs4284742 strongly activated SIGLEC5 expression, validating this gene as the target gene of the association. We conclude that rs11084095 and rs4284742 are putatively causal for the genome-wide significant associations with periodontitis at SIGLEC5 that impair ERG and MAFB binding, respectively.

Objectives This report aims to review the management and outcomes of Brucella-associated mycotic aortic aneurysms. Methods This is a retrospective chart review at a tertiary-level healthcare system. IRB approval was waived per policy. Results We describe a case of Brucella aortitis acquired from habitual contact with wild hogs. Clinical presentation included lower back pain and elevated white blood cell count. Diagnosis was confirmed with imaging showing an infrarenal abdominal aortic aneurysm and serology revealing elevated Brucella antibodies titers. The patient was initially managed with endovascular aortic repair and combined oral and intravenous antibiotics therapy. He then underwent explanation and extra-anatomical bypass due to symptomatic periaortic infection and interval development of type I endoleak. The patient was asymptomatic after his final operation at 24 months of follow-up and remained on suppressive oral antibiotic therapy. Conclusions An aortic aneurysm secondary to Brucella is a rare entity. A detailed history of long-term exposure to animals may be a clue to obtain serologic testing. Operative debridement and re-establishing of reliable blood flow combined with long-term antibiotic suppression are the mainstay of treatment.

Tic disorders (TD) are childhood-onset neurological disorders. Immune system dysregulation has been postulated to play a role in TD, and its mechanisms likely involve dysfunctional neural-immune cross-talk, which ultimately leads to altered maturation of the brain pathways that control different TD clinical manifestations and behavioral and emotional damages. Clinical studies have demonstrated an association between TD and allergies and overactive immune responses at a systemic level. In this study, the Yale Global Tic Severity Scale was taken as a global measure of tic severity. Compared with the control group, the group of children with TD plus allergic diseases displayed significantly increased Yale total scores (p

Background:During high tibial osteotomy (HTO), the superficial medial collateral ligament (sMCL) is cut or released at any degree to expose the osteotomy site and achieve the targeted alignment correction according to the surgeon’s preference. However, it is still unclear whether transection of sMCL increases valgus laxity.Purpose:We aimed to assess the outcomes and safety of sMCL transection, especially focusing on iatrogenic valgus instability.Study Design:Case series; Level of evidence, 4.Methods:Seventy-two patients (89 knees) who underwent medial open wedge HTO (MOWHTO) with transection of the sMCL between October 2013 and September 2018 were retrospectively investigated. Clinical evaluations, including the International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Tegner and Lysholm scores, were performed preoperatively and at 2 years postoperatively. The radiographic parameters hip-knee-ankle (HKA) angle, joint line convergence angle on standing radiographs (standing JLCA), and weightbearing line (WBL) ratio were assessed preoperatively and at 3 months, 6 months, 1 year, and 2 years postoperatively. To evaluate valgus laxity, we assessed the valgus JLCA and medial joint opening (MJO) at the aforementioned time points using valgus stress radiographs.Results:All clinical results at the 2-year follow-up were significantly improved compared with those obtained at the preoperative assessment ( P < .001). The postoperative HKA angle significantly differed from the preoperative one, and no significant valgus progression was observed during follow-up (preoperative, 8.5°± 2.7°; 3 months, –3.5°± 2.0°; 6 months, –3.2°± 2.3°; 1 year, –3.1°± 2.3°; 2 years, –2.9°± 2.5°; P < .001) The mean WBL ratio was 62.5% ± 9.0% at 2 years postoperatively. The postoperative valgus JLCA at all follow-up points did not significantly change compared with the preoperative valgus JLCA (preoperative, –0.1°± 2.1°; 3 months, –0.2°± 2.4°; 6 months, –0.1°± 2.5°; 1 year, 0.1°± 2.5°; 2 years, 0.2°± 2.2°) The postoperative MJO at all follow-up points did not significantly change compared with the preoperative MJO (preoperative, 7.1 ± 1.7 mm; 3 months, 7.0 ± 1.7 mm; 6 months, 6.9 ± 1.9 mm; 1 year, 6.7 ± 1.8 mm; 2 years, 6.8 ± 1.8 mm).Conclusion:Transection of the sMCL during MOWHTO does not increase valgus laxity and could yield desirable clinical and radiographic results.

Purpose Patellofemoral instability (PFI) in young athletes presents both diagnostic and management dilemmas for which consensus often does not exist. The purpose of this study was to identify trends in management of PFI in children and adolescents in the United States and nationwide. Methods A 27-question multiple choice survey was distributed in 2018 to the members of the Pediatric Research in Sports Medicine (PRiSM) Society regarding treatment of PFI in paediatric and adolescent patients. Results In all, 56 of the respondents who were orthopaedic surgeons that manage patellar instability in children and adolescents and had performed PFI surgery more than five times in the past year completed the entire survey. A total of 41% of respondents reported that surgery for fragment refixation or loose body removal was indicated when a loose body or osteochondral fragment was evident, regardless of fragment size. Overall, 74% reported that if surgery was performed for an osteochondral loose body, primary repair (36%) or reconstruction (38%) of medial patellofemoral ligament (MPFL) was also completed. A total of 89% of members reported MPFL reconstruction in the absence of alignment or rotational abnormalities, tibial tubercle lateralization or trochlear dysplasia in skeletally immature patients; 59% reported performing the MPFL reconstruction with hamstring allograft, while 30% prefer autograft (hamstring, quadriceps). For patients with significant trochlear dysplasia, 87% reported no surgical management of trochlea in first-time or in revision surgery. Conclusion There is a lack of consensus regarding optimal diagnostic and treatment algorithms in the management of PFI, however, consistent trends have emerged among paediatric sports medicine surgeons. Level of Evidence Level V – survey of expert opinion and experience

Background The pathogenesis and related factors of central nervous system abnormality in patients with type 2 diabetes mellitus (T2DM) have always been the focus of clinical research. Purpose To compare and analyze the area of white matter (WM) damage in patients with T2DM based on their level of hemoglobin A1C (HBA1c) and discuss any related factors. Material and Methods Based on their levels of HBA1c, 87 patients with T2DM were divided into three groups (Group B, C, or D), of which 29 non-diabetic volunteers served as the control group (Group A). DTI data analysis was based on tract-based spatial statistics (TBSS). The obtained parameters were compared among each group and the relevant clinical factors were analyzed. Results For age, sex, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MoCA) scores, there were no statistically significant differences among groups. For fractional anisotropy (FA) and radial diffusivity (RD) of WM, there were statistically significant differences ( P < 0.05, two-tailed, FWE corrected) in the local area of corpus callosum, corona radiate, superior longitudinal fasciculus, etc. Most of these were significantly correlated with body mass index (BMI), left systolic blood pressure (SBP_L), and β2 microglobulin. Conclusion Before the cognitive function was obviously impaired, abnormalities of FA and RD had been found in the corpus callosum, corona radiate, and upper fasciculus in patients with T2DM, which suggested that the damage mainly occurred in the myelin sheath of WM and may be related to systemic vascular damage.

Background The Streptococcus anginosus group is known for its pathogenicity and tendency for abscess formation. The S anginosus group also causes brain abscesses, yet few studies describe this presentation in the pediatric neurology literature. We describe 5 patients with central nervous system infection due to S anginosus group evaluated by child neurologists at the University of Iowa from 2014 to 2020. Methods We performed a retrospective case series review of electronic medical records detailing the clinical presentation and course of pediatric patients with S anginosus group–associated central nervous system infection. Results We identified 4 males and 1 female (8, 11, 14, 16, and 21 years). Brain imaging showed abscesses in 4 cases and empyema in 1. All underwent neurosurgical intervention and antibiotic treatment. Cultures obtained during the neurosurgical procedure grew S anginosus group (4 cases with Streptococcus intermedius and 1 with Streptococcus constellatus). An 8-year-old boy with a delayed diagnosis died from brain herniation. Conclusions Central nervous system infections due to the S anginosus group can be life-threatening. Neuroimaging plays a key role in the early identification of abscesses. Prompt surgical intervention and timely initiation of antibiotics are critical for optimal outcomes.

We examine the effects of foreign currency borrowings (FCBs) and domestic market constraints on the performance of the export of the micro, small and medium enterprises (MSMEs) during the period 1988–2019. Our results show that access to the FCBs improved the performance of the MSME exports, indicating the importance of credit accessibility. MSMEs effectively utilise the grants when accompanied by credit facilities such as FCBs. We find that the high cost of debt and lack of financial development adversely affect the exports, as MSMEs are unable to borrow. The rupee depreciation alone does not help the MSMEs reap such depreciation benefits due to the lack of domestic credit. The recent policy stance of emphasis on MSMEs is expected to improve export performance. This study calls for the specialised window for the MSMEs to meet low cost and easy credit. The findings suggest stepping up grants to the MSMEs to improve the export performance. JEL Codes: F14, F34, F2, F31

Severe malarial anemia (SMA) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions. To gain enhanced understanding of predisposing factors for SMA, we explored the relationship between complement component 3 (C3) missense mutations [rs2230199 (2307C>G, Arg>Gly102) and rs11569534 (34420G>A, Gly>Asp1224)], malaria, and SMA in a cohort of children (n = 1617 children) over 36 months of follow-up. Variants were selected based on their ability to impart amino acid substitutions that can alter the structure and function of C3. The 2307C>G mutation results in a basic to a polar residue change (Arg to Gly) at position 102 (β-chain) in the macroglobulin-1 (MG1) domain, while 34420G>A elicits a polar to acidic residue change (Gly to Asp) at position 1224 (α-chain) in the thioester-containing domain. After adjusting for multiple comparisons, longitudinal analyses revealed that inheritance of the homozygous mutant (GG) at 2307 enhanced the risk of SMA (RR = 2.142, 95%CI: 1.229–3.735, P = 0.007). The haplotype containing both wild-type alleles (CG) decreased the incident risk ratio of both malaria (RR = 0.897, 95%CI: 0.828–0.972, P = 0.008) and SMA (RR = 0.617, 95%CI: 0.448–0.848, P = 0.003). Malaria incident risk ratio was also reduced in carriers of the GG (Gly102Gly1224) haplotype (RR = 0.941, 95%CI: 0.888–0.997, P = 0.040). Collectively, inheritance of the missense mutations in MG1 and thioester-containing domain influence the longitudinal risk of malaria and SMA in children exposed to intense Plasmodium falciparum transmission.

The majority of patients with cancer experience clinically significant levels of distress (Dyson et al., 2012; Kwak et al., 2013; Yanez, Garcia, Victorson, & Salsman, 2013) that varies by age at diagnosis, cancer type, and psychosocial needs. Across multiple oncology studies, it has been reported that relationships with family and friends are important sources of support throughout the cancer experience (e.g., Goodall, King, Ewing, Smith, & Kenny, 2012; Miedema, Zebrack, 2011). However, a close relationship can also be a source of distress for patients with cancer, particularly those who are emotionally unavailable or unable to handle stress (Synder & Pearse, 2010; Zebrack, Chesler, & Kaplan, 2010). Contributors to the oncology literature suggested that distress levels between patients and their partners are interrelated (Gregorio et al., 2012; Juth et al., 2015; Kim & Given, 2008; Segrin et al., 2007). Dyadic research that includes patients and their partners is necessary for developing programs and interventions better targeted at meeting patients’ and their partners’ needs. Yet, these factors and the exploration of adaptive processes have not been examined among couples who are facing cancer. In light of these facts, several implications are provided for clinical practice, future research, policy, and the field of medical family therapy based on the above-mentioned studies (Rajaei & Jensen, 2020; Rajaei et al., 2021a).

An obituary for the Great Barrier Reef (the Reef) by travel and food writer Rowan Jacobsen (2016) commemorated its ‘lifetime accomplishments’ in Outside, the US outdoor recreational magazine. ‘News’ of the Reef's demise went viral and the economic and political furore that followed was immense. Tourism industries, especially reliant on international arrivals, were impacted as potential visitors accepted the Reef's passing as fact. Politicians scampered to reassure Australians and the globe that the Reef was indeed still alive and beautiful. In the Australian public sphere, climate science deniers, alongside those advocating for climate action, collided over the impacts of global warming to Reef health. Subsequent mass coral bleaching events in 2016, 2017 and 2020 sustained at the very least, the idea that the Reef was, or was soon to be, dead. Our paper follows the idea of a ‘dead Reef’ in the context of historical and recent debates about Reef protection. Using Google Trends, we identify Jacobsen's article as the source of increased Australian and global ideation of a ‘dead Reef’. As a site of local and global environmental communication – where human relations to nature are expressed and understood - the Reef holds extraordinary story telling power. At the current junction then, the way we communicate the Reef is critical to public understanding and political action on climate change. We conclude Jacobsen's article is an example of the problems of satirical communication, serving to amplify existing conflicts and undermine efforts to foster to climate action.

A frozen banana pulp with functional properties was developed and characterized in this work. For this, 0 g, 3 g, 5 g and 7 g of psyllium in 100 g of banana pulp were added. The use of this fiber in industrialized products can contribute to the nutritional enrichment of the products and provide functional benefits already acknowledged, such as lowering LDL cholesterol, lowering blood glucose, increasing satiety and relieving constipation. According to the World Health Organization, vegetable consumption should be increased, as it reduces the risk of chronic diseases. The main purpose of this work was to incorporate psyllium in frozen banana pulp to develop a healthy product. The samples were evaluated through chemical analyses, rheological properties and sensory testing with Check-All-That-Apply questions (CATA). The addition of psyllium had a significant effect not only on the viscosity but also on the sensory and nutritional properties of the frozen banana pulp. This study indicated that the production of frozen banana pulp with psyllium is viable, as it has desirable nutritional and sensory characteristics which can contribute to the maintenance of health.

Several studies have tested the Elevational Rapoport Rule (ERR) in arthropods, especially in the Neotropical mountains. Nonetheless, different approaches should be used for a more nuanced comprehension of ERR patterns and assemblage altitudinal distribution patterns, such as the biogeographical, ecological, and evolutionary contexts. This study aims to test the ERR for elevational gradients in Mexican mountains. For this study, dung beetle assemblages of the genus Onthophagus were used as a model organism, and their distribution was studied in several different mountain ranges of the Mexican tropics. Altitudinal distribution of Onthophagus species was analyzed, including ecological traits and biogeographical/phylogenetical contexts as covariables. The increase of altitude was positively correlated to the assemblage altitudinal range. Furthermore, altitudinal range, relative abundance, body size, and mountain’s topographic prominence were positively correlated to the mean altitudinal range of Onthophagus species. Nonetheless, different altitudinal relationships were observed, depending on the mountain. The results support the idea that species that inhabit higher altitudes appear to be more environmentally plastic and occur in wider altitudinal ranges than species from lower altitudes, thus supporting the ERR. The present findings stress that biogeographical, ecological, phylogenetical, and historical aspects, besides body size, are essential drivers of the altitudinal distribution of Onthophagus dung beetles.

This study investigated the effects of single nucleotide polymorphisms (SNPs) of the VEGF （vascular endothelial growth factor） gene, which are associated with susceptibility to age-related macular degeneration (AMD), on the expression of VEGF proteins (VEGF165 and VEGF165b) and their role in cell proliferation and apoptosis in human retinal vascular endothelial cells (hRVECs). Cell viability and VEGF165 and VEGF165b expressions were evaluated in hRVECs transfected with VEGF genes containing different SNPs (rs3025039, rs3025033, and rs10434). The Cell Counting Kit 8 assay, quantitative real-time PCR, western blotting, TUNEL assay, and enzyme-linked immunosorbent assay were used to examine the effects of VEGF gene SNPs on cell viability, VEGF165 and VEGF165b expressions, and cell apoptosis in hRVECs. The interaction and localization of the RNA-binding protein alternative splicing factor/splicing factor 2 (ASF/SF2) were assessed using RNA pull-down. Although VEGF165 expression decreased, VEGF165b levels increased significantly in hRVECs transfected with rs3025039, which decreased cell viability and induced apoptosis. The SNPs rs3025033 and rs10434 had no significant effects on VEGF165b protein production and apoptosis; however, they promoted cell proliferation. SNPs affected the interaction between RNA and ASF/SF2, a splicing factor for intron retention. Insulin-like growth factor-1 treatment induced the expression of VEGF165, but not VEGF165b, whereas SRPIN340 treatment, an inhibitor of ASF/SF2, increased VEGF165b protein levels. VEGF gene sequence variations affected hRVEC proliferation and apoptosis via alternative gene splicing. Thus, the regulation of splicing via ASF/SF2 could be a potential strategy in treating pathological neovascularization in patients with AMD.

The reappearance of VHS skateboarding movies produced during the 1990s on YouTube presents a timely opportunity to examine how the subcultural identities of former skateboarders are reassessed in later life. Drawing on subcultural studies and theories of mediated memory, this article analyses comments made by viewers of YouTube re-postings of 411 Video Magazine, an era-defining skateboard movie series of the 1990s. The analysis suggests that re-viewing content of once cherished VHS tapes affords former skaters a nostalgic moment of reconnection with their youth involving a combination of three forms of nostalgia: subcultural nostalgia, biographical nostalgia, and format nostalgia. For many viewers, re-viewing skate videos retrospectively recognizes the formative role skateboarding played in shaping their identity and also allows an appraisal of both the past subcultural formation and the media format through which its values were expressed and communicated.

Background Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide can provoke cluster headache attacks in up to half of cluster headache patients in their active phase. At present, it is unknown whether provoked attacks are mediated via calcitonin gene-related peptide or mast cell activation. Methods All enrolled patients with cluster headache were randomly allocated to receive a continuous infusion of either PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We collected clinical data and measured plasma levels of calcitonin gene-related peptide and markers of mast cell activation (tryptase and histamine) at fixed time points: at baseline (T0), at the end of the infusion (T20), 10 min after the infusion (T30), and 70 min after the infusion (T90). Results Blood was collected from episodic cluster headache patients in active phase (n = 14), episodic cluster headache patients in remission (n = 15), and chronic cluster headache patients (n = 15). At baseline, plasma levels of calcitonin gene-related peptide, tryptase, and histamine were not different among the three study groups. Plasma levels of calcitonin gene-related peptide ( p = 0.7074), tryptase ( p = 0.6673), or histamine ( p = 0.4792) remained unchanged during provoked attacks compared to attack-free patients. Conclusion Cluster headache attacks provoked by either PACAP38 or vasoactive intestinal polypeptide were not accompanied by alterations of plasma calcitonin gene-related peptide, tryptase or histamine. The provoked attacks may not be mediated by calcitonin gene-related peptide or mast cell activation. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03814226).

Introduction. Periductal stromal tumor (PST) of the breast is a rare fibroepithelial neoplasm with controversial pathogenesis. Methods. A retrospective search of our Pathology database from 2000 to 2021 identified 6 PST, all evaluated according to the Armed Forces Institute of Pathology (AFIP) criteria. Immunohistochemistry for CD10, CD34, KIT, GATA3, p63, SOX10, ER, PR, HER2, smooth muscle actin (SMA), beta-catenin, and myogenin was performed as well. Results. All 6 patients were female and age ranged from 29 to 55 years (mean 40 years). Tumor size ranged from 2.9 to 5.9 cm (mean 3.0 cm). Data showed absence of leaf-like architecture (0/6), at least moderate hypercellularity (6/6), lack of a circumscribed border (5/6), coalescing nodules with intermixed adipose tissue (4/6), at least moderate stromal atypia (4/6), and an elevated mitotic activity ≥3mitotic figures/10 HPF (6/6). The stromal cells were positive for CD10 (4/4), CD34 (4/4), KIT (3/4), and SMA (3/4), and negative for GATA3 (0/6), p63 (0/6), SOX10 (0/6), ER (0/4), PR (0/4), HER2 (0/4), nuclear beta-catenin (0/5), and myogenin (0/4). No patient had a PST recurrence or metastasis (average follow-up of 91 months). Conclusion. We confirm that PST shares morphologic and immunophenotypic similarities with phyllodes tumor (PT). However, PST can be reliably differentiated from PT using the AFIP criteria. Additionally, PST's immunoprofile of positive KIT and CD34 stromal expression alongside the negative GATA3, p63, and SOX10 reactivity can aid the pathologist in excluding metaplastic carcinoma. All 6 of our PST behaved as benign neoplasms akin to benign PT.

Background: The effect of low body mass index (BMI) on outcomes in female athletes is unknown. Purpose: (1) To report minimum 2-year patient-reported outcomes and return to sports for high-level female athletes with low BMI undergoing hip arthroscopy for femoroacetabular impingement syndrome and (2) to compare results with those of a propensity-matched control group of high-level female athletes with a normal BMI. Study Design: Cohort study; Level of evidence, 3. Methods: Data were collected on all professional, collegiate, and high school female athletes who had a low BMI and underwent primary hip arthroscopy between September 2009 and March 2017 at our institute. Return-to-sports status and minimum 2-year patient-reported outcomes were collected for the modified Harris Hip Score (mHHS), Nonarthritic Hip Score, Hip Outcome Score–Sport Specific Subscale, and visual analog scale (VAS) for pain. The percentage of patients achieving the minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), and maximum outcome improvement satisfaction threshold (MOIST) was also recorded. These patients were propensity matched to high-level female athletes with a normal BMI for comparison. Results: A total of 21 high-level female athletes (25 hips) with a mean ± SD follow-up of 58.9 ± 31.5 months were included. They demonstrated significant improvement from preoperatively to latest follow-up for the mHHS, Nonarthritic Hip Score, Hip Outcome Score–Sport Specific Subscale, and VAS ( P < .001). When outcomes were compared with those of the control group, female athletes with low BMI demonstrated lower rates of achieving the MCID for the mHHS (54.5% vs 77.4%; P = .041), PASS for the International Hip Outcome Tool–12 (45.5% vs 72.6%; P = .022), and MOIST for the VAS (31.8% vs 56.5%; P = .047). There were no other significant differences in the rate of achieving the MCID, PASS, or MOIST between the groups ( P > .05). Female athletes with low BMI also had higher rates of revision when compared with the control group (27.2% vs 10.6%; P = .049), but there were comparable return-to-sports rates (75.0% vs 74.5%; P > .05). Conclusion: High-level female athletes with low BMI undergoing primary hip arthroscopy for femoroacetabular impingement syndrome demonstrated significant improvement in patient-reported outcomes and acceptable rates of return to play. When compared with a control group with normal BMI, they exhibited higher rates of revision and lower rates of achieving the MCID for the mHHS, PASS for the International Hip Outcome Tool–12, and MOIST for the VAS.

Introduction The present study was undertaken to investigate the prognostic value of the frontal QRS-T angle associated with adverse cardiac outcomes in patients with carbon monoxide (CO) poisoning in early stages in the emergency department. Materials and methods The data of 212 patients with CO poisoning who were admitted to the ED between January 2010 and May 2020 were retrospectively analyzed. The frontal QRS-T angle was obtained from the automatic reports of the EKG device. Results Compared to patients without myocardial damage, among patients with myocardial damage, statistically high creatinine, creatine kinase MB, cardiac troponin I, and frontal QRS-T angle values were found ( p < 0.001 for all parameters), while the saturation of arterial blood pH and arterial oxygen values were found to be lower ( p = 0.002 and p < 0.001, respectively). The frontal QRS-T angle values were correlated with creatine kinase, creatine kinase-MB, cardiac troponin I, and oxygen saturation (SpO2) in arterial blood (r = 0. 232, p = 0.001; r = 0. 253, p = < 0.001; r = 0. 389, p = < 0.001; r = −0. 198, p = 0.004, respectively). The optimum cut-off value of the frontal QRS-T angle was found to be 44.5 (area under the curve: 0.901, 95% confidence interval: 0.814–0.988, sensitivity: 87%, specificity: 84%). Conclusions The frontal QRS-T angle, a simple and inexpensive parameter that can be easily obtained from 12-lead surface electrocardiography, can be used as an early indicator in the detection of myocardial damage in patients with CO poisoning.

Identifying cancer driver genes is essential for understanding the mechanisms of carcinogenesis and designing therapeutic strategies. Although driver genes have been identified for many cancer types, it is still not clear whether the selection pressure of driver genes is homogeneous across cancer subtypes. We propose a statistical framework MutScot to improve the identification of driver genes and to investigate the heterogeneity of driver genes across cancer subtypes. Through simulation studies, we show that MutScot properly controls the type I error in detecting driver genes. In addition, we demonstrate that MutScot can identify subtype heterogeneity of driver genes. Applications to three studies in The Cancer Genome Atlas (TCGA) project showcase that MutScot has a desirable sensitivity for detecting driver genes and that MutScot identifies subtype heterogeneity of driver genes in breast cancer and lung cancer with regards to the status of hormone receptor and to the smoking status, respectively.

Background: Within the hip joint, the anatomy of the acetabulum and cotyloid fossa is well established. There is little literature describing the association between the size of the cotyloid fossa relative to the acetabulum and characteristics of patients with femoroacetabular impingement (FAI). Purpose/Hypothesis: The purpose was to calculate the cotyloid fossa coverage percentage in the acetabulum and determine its association with patient characteristics, radiographic parameters, intra-articular findings, and preoperative patient-reported outcomes in patients with FAI. We hypothesized there is an association between the cotyloid fossa coverage percentage of the acetabulum and characteristics of patients with FAI. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients were included who underwent standard clinical 3-T magnetic resonance imaging of the hip and primary arthroscopic FAI correction surgery during 2015 and 2016. Exclusion criteria were age 40 years, osteoarthritis, labral reconstruction, previous ipsilateral hip surgery, and hip dysplasia. Measurements of the cotyloid fossa and surrounding lunate cartilage were performed to calculate cotyloid fossa width (CFW) and cotyloid fossa height (CFH) coverage percentages. The relationships between coverage percentages and patient characteristics and intraoperative findings were assessed using independent t tests or Pearson correlations. Results: An overall 146 patients were included. Alpha angle negatively correlated with CFH coverage percentage ( r = −0.19; P = .03) and positively correlated with labral tear size ( r = 0.28; P < .01). CFH coverage percentage was negatively correlated with labral tear size ( r = −0.24; P < .01). Among patients with degenerative tears, CFH was negatively correlated with labral tear size ( r = −0.31; P < .01). However, this association was no longer significant after adjusting for sex (partial r = −0.10; P = .39). Cotyloid fossa coverage was not associated with the condition of the cotyloid fossa synovium (synovitis vs no synovitis). CFW coverage percentage was negatively correlated with the 12-Item Short Form Health Survey (SF-12) physical component summary score ( r = −0.23; P < .01). Conclusion: The CFW and CFH coverage percentages may be associated with alpha angle, labral tear size, and SF-12 physical component summary score in patients with FAI. We may be able to predict the labral condition based on preoperative measurements of CFH and CFW coverage percentages.

Although spindle cell lipoma (SCL) is a subtype of lipoma, the characteristics of SCL are observed in both lipomatous and non-lipomatous tumors. In this article, we present a case of SCL with ossification mimicking atypical lipomatous tumors/well-differentiated liposarcomas (ALTs/WDLs). Considering the findings of magnetic resonance imaging and needle biopsy, which exhibited ALTs/WDLs, marginal resection was performed. Histopathological findings demonstrated mature adipocytes and spindle cells without atypia and no malignant osteoid tissue in the ossified region. In addition, immunohistochemistry (IHC) showed positive staining for CD34, heterogeneous retinoblastoma protein deficiency, and negative staining for mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase. Fluorescence in-situ hybridization showed negative amplification of MDM2. The final diagnosis of the tumor was established using IHC as an extremely rare SCL with ossification.

A 3-y-old, intact female, American Pit Bull Terrier was presented because of acute onset of anorexia and a large subcutaneous submandibular mass that had been present for 3 wk. The submandibular mass, 2 engorged black-legged ticks on the dorsum of the neck, pyrexia, and icterus were seen on physical examination. Abnormal laboratory test results included a positive Anaplasma antibody test, severe thrombocytopenia, mild nonregenerative anemia, hyperbilirubinemia, and elevated liver enzyme activities. Cytology of the mass was interpreted as marked septic purulent inflammation with acute hemorrhage. Treatment with doxycycline for anaplasmosis was unsuccessful, and the patient died at an emergency follow-up visit 2 d after the initial presentation. Autopsy and histopathology revealed widespread metastasis of a presumptive histiocytic neoplasm with associated hemophagocytosis seen in lymph nodes (LNs), liver, and spleen. Immunohistochemistry yielded a definitive diagnosis of a CD3+/CD18+ T-cell lymphoma. In this case of canine lymphoma-associated hemophagocytic syndrome, hemophagocytes were observed as >2% of neoplastic cells in the liver, spleen, and LN histologically, a scarce or unreported finding, to our knowledge. The prognosis was grave, with a short survival time after the onset of clinical signs.

Urbanization in low and middle-income nations is characterized by economic and demographic shifts largely understood to be beneficial to women’s empowerment. These changes include increased education and wage-labor opportunities, a disruption of traditional patrilocal residence systems, and reductions in spousal age gap and fertility. However, such changes may drive a “violence backlash,” with men increasing intimate partner violence (IPV) in efforts to challenge women’s shifting status. To date, tests of this idea primarily relate to women’s changing economic status, with less known about the demographic correlates of IPV in urbanizing settings. Addressing this, we conducted a cross-sectional study of IPV behavior and attitudes in an urbanizing community in Mwanza, northern Tanzania ( n = 317). Consistent with a violence backlash, IPV was reported more often among women educated at higher levels than their husband, and women earning similar, rather than lower, wages to their husband were more likely to report that he condones IPV. These findings were independent of women’s absolute education and income. Furthermore, less frequent paternal kin contact, and relatively small spousal age gaps, generally understood to boost women’s empowerment, were associated with an increased risk of experiencing IPV. Less frequent paternal kin contact was also associated with an increased likelihood that a husband condones IPV. Contrary to our predictions, relatively lower fertility, generally linked to higher women’s empowerment, did not predict IPV behavior and women with high, rather than low, fertility were more likely to report that their husband condones IPV. Overall, our results support the notion of a violence backlash corresponding to economic changes for women that accompany urbanization. In contrast, demographic changes associated with urbanization have more variable relationships. Drawing on these results, we suggest future research avenues for better understanding the vulnerability of women to IPV in urbanizing settings.

Background: Nontraumatic fatalities occur on a regular basis in high school (HS) and college football athletes, primarily in obese linemen performing high-intensity exercise. One contributing factor to these deaths may be a mismatch between baseline aerobic (cardiorespiratory) fitness and exercise regimens. Hypothesis: There is a wide range of aerobic fitness in HS and college football players. Body mass index (BMI) is a safe and simple method for estimating baseline aerobic fitness. Study Design: Retrospective cohort study. Level of Evidence: Level 3. Methods: A retrospective review was performed on 79 HS football athletes who had VO2Peak (mL·kg−1·min−1) measured during the offseason. Multivariate regression analysis was used to determine if BMI (obese, overweight, and normal; kg/m2), position played (linemen vs other), year in school (freshmen vs other), and/or race (African American vs White) were risk factors for poor aerobic fitness. A separate cohort of 135 (48 HS; 87 college) football athletes performed a 6-minute run test to determine speed (miles/min), extrapolate VO2Max, and calculate reference values for suggested upper threshold safe starting speeds (85% of maximum) for aerobic training based on BMI. The relationship between BMI and VO2Peak was assessed. The exercise regimens (speeds) of 2 collegiate football fatalities from the public domain were used to predict their VO2Max values. Results: Mean VO2Peak (mL·kg−1·min−1) was 38.5 ± 8.6 (range 19.1-60.6); when grouped by BMI, low scores (2Peak was significantly lower in linemen (32.8 ± 6.4; P = 0.007) compared with nonlineman (41.8 ± 7.9), and in obese players (by BMI; 32.4; P = 0.019) compared with nonobese players (41.4 ± 7.6), but did not differ by age, year in school, or race. Means for speed (min/mile) and extrapolated VO2Max (mL·kg−1·min−1) for the 6-minute run test by BMI groups were both significantly different ( P = 0.001) for normal (7.0 ± 0.6; 51.1 ± 2.6), overweight (7.6 ± 0.8; 46.5 ± 3.2), and obese (8.9 ± 1.5; 36.8 ± 5.9) athletes. There was a significant negative correlation ( r = −0.551; P = 0.001; R2 = 0.304) between VO2Peak and BMI. Safe starting speed recommendations for running 1 mile range from 7.3 to 12.1 min/mile for BMIs 20 to 40 kg/m2 for HS and college athletes. For the 2 fatalities (mean, BMI of 36.5 kg/m2) repetitive sprint speeds were 49 and 89% higher than our safe starting speeds for their BMI. Conclusion: A large spectrum of baseline aerobic fitness was noted in HS and college football players. Obese players and linemen had statistically lower baseline aerobic fitness, a major risk factor for possible heat illness. BMI is an acceptable surrogate for VO2Peak and can be employed to develop safe training regimens without the need for a maximum fitness test, which can place the athlete at risk for a medical event. Clinical Relevance: Knowledge of BMI provides an estimate of baseline aerobic fitness and a foundation for prescribing safe, individualized exercise regimens.

Organ development is dictated by the regulation of genes preferentially expressed in tissues or cell types. Gene expression profiling and identification of specific genes in organs can provide insights into organogenesis. Therefore, genome-wide analysis is a powerful tool for clarifying the mechanisms of development during organogenesis as well as tooth development. Single-cell RNA sequencing (scRNA-seq) is a suitable tool for unraveling the gene expression profile of dental cells. Using scRNA-seq, we can obtain a large pool of information on gene expression; however, identification of functional genes, which are key molecules for tooth development, via this approach remains challenging. In the present study, we performed cap analysis of gene expression sequence (CAGE-seq) using mouse tooth germ to identify the genes preferentially expressed in teeth. The CAGE-seq counts short reads at the 5′-end of transcripts; therefore, this method can quantify the amount of transcripts without bias related to the transcript length. We hypothesized that this CAGE data set would be of great help for further understanding a gene expression profile through scRNA-seq. We aimed to identify the important genes involved in tooth development via bioinformatics analyses, using a combination of scRNA-seq and CAGE-seq. We obtained the scRNA-seq data set of 12,212 cells from postnatal day 1 mouse molars and the CAGE-seq data set from postnatal day 1 molars. scRNA-seq analysis revealed the spatiotemporal expression of cell type–specific genes, and CAGE-seq helped determine whether these genes are preferentially expressed in tooth or ubiquitously. Furthermore, we identified candidate genes as novel tooth-enriched and dental cell type–specific markers. Our results show that the integration of scRNA-seq and CAGE-seq highlights the genes important for tooth development among numerous gene expression profiles. These findings should contribute to resolving the mechanism of tooth development and establishing the basis for tooth regeneration in the future.

Objectives Poisoning from psychoactive drugs and substance use disorders (SUD) have been reported among non-medical cannabis users. However, little is known about medical cannabis users and their risk for poisoning and/or development of SUD. This study assessed the risk of emergency department (ED) visits or hospitalization for 1) poisoning by psychoactive drugs and 2) mental/behavioural disorders due to the use of psychoactive drugs and other substances, in medically authorized cannabis patients in Ontario, Canada from 2014–2017. Methods A cohort study of adult patients authorized for medical cannabis that were matched to population-based controls. ED visit/hospitalization were assessed with a main diagnostic code for: 1) poisoning by psychoactive drugs; 2) mental and behavioural disorder due to psychoactive drugs or other substance use. Conditional Cox proportional hazards regressions were conducted. Results 18,653 cannabis patients were matched to 51,243 controls. During a median follow-up of 243 days, the incidence rate for poisoning was 4.71 per 1,000 person-years (95%CI: 3.71–5.99) for cases and 1.73 per 1,000 person-years (95% CI: 1.36–2.19) for controls. The adjusted hazard ratio (aHR) was 2.45 (95%CI: 1.56–3.84). For mental/behavioural disorders, the incident rates were 8.89 (95% CI: 7.47–10.57) and 5.01 (95% CI: 4.36–5.76) in the cannabis and the controls group. The aHR was 2.27 (95%CI: 1.66–3.11). No difference was observed between males and females ( P-value for interaction > 0.05). Conclusions Our study observed a short-term increased risk of ED visit/hospitalization for poisoning or for mental/behavioural disorders (from use of psychoactive drugs and other substances)- in medically authorized cannabis patients.

Decreased dihydropyrimidine dehydrogenase enzyme activity is associated with severe fluoropyrimidine-associated toxicity. Four clinically relevant variants in the DPYD gene are associated with decreased dihydropyrimidine dehydrogenase activity. However, only ∼25% of DPYD variant carriers show a decreased dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells. Objective To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with DPYD genotyping in predicting fluoropyrimidine-related toxicity. Methods Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four DPYD variants and phenotyped using an ex vivo peripheral blood mononuclear cell assay. Results Severe toxicity occurred in 25% of patients with a variant and normal dihydropyrimidine dehydrogenase activity, in 21% of patients without a variant and with decreased dihydropyrimidine dehydrogenase activity, and in 29% of patients without a variant and with normal dihydropyrimidine dehydrogenase activity (controls). The majority of patients with a variant or a decreased dihydropyrimidine dehydrogenase activity received an initial dose reduction (68% and 53% vs 19% in controls) and had a lower mean dose intensity (75% and 81% vs 91% in controls). Fifty percent of patients with a variant and decreased enzyme activity experienced severe toxicity, despite the lowest initial dose and whole treatment dose intensity. They also experienced more grade 4/5 toxicities. Conclusions Our results indicate that a combined genotype–phenotype approach could be useful to identify patients at increased risk for fluoropyrimidine-associated toxicity (e.g. patients with a variant and decreased dihydropyrimidine dehydrogenase activity). Because the group sizes are too small to demonstrate statistically significant differences, this warrants further research in a prospective study in a larger cohort.

Background Since its legalization in Canada, cannabis use has expanded to include commercially available topical formations. Several scientifically unsupported claims regarding the therapeutic efficacy of topical cannabis are also being made. Developing an understanding of the consumer uses of topical cannabis is important for clinicians to provide appropriate counseling and inform potential areas of therapeutic development. We are examining the prevalence, purpose of use, and sources of information regarding topical cannabis in the Canadian population, with a focus on dermatologic uses. Method A cross-sectional, anonymous electronic, voluntary survey was developed to assess the use of topical cannabis amongst adults in Canada. Results Cannabis was used topically at least once by 24.3% of respondents who started the survey. The commonest form of topical cannabis were creams (26.2%). The most common dermatologic conditions being treated with topical cannabis included atopic dermatitis (25%), acne (19%), and anti-aging (16%); for non-dermatologic conditions, common uses were for joint stiffness or tendonitis (30%) and headaches and migraines (27%). Topical cannabis was reported to be most effective for joint stiffness and tendonitis, general muscular soreness, headaches, eczema, pruritus, acne, and psoriasis. Most respondents obtained and received information about topical cannabis from dispensaries. Conclusion Canadians use topical cannabis for a broad range of systemic and dermatologic purposes, most of which have limited evidence. Future clinical studies are required to elucidate the therapeutic efficacy and safety of topical cannabis. Dermatologists should screen their patients for topical cannabis use and be aware of the limited evidence of therapeutic potential.

Xanthogranulomatosis is an inflammatory lesion characterized by lipid-containing macrophages, extracellular lipid, hemorrhage, and necrosis. We describe disseminated intracoelomic xanthogranulomatosis in 5 eclectus parrots ( Eclectus roratus) and 2 budgerigars ( Melopsittacus undulatus). Postmortem, clinicopathologic, and historical case material was reviewed. Ages ranged from 3 to 24 years; there were 5 males and 2 females. Table food was included in the diet of 3/5 cases, and animal products were included in 2/3 cases. Common clinicopathologic abnormalities included leukocytosis (4/5 cases) and elevated concentrations of bile acids (3/4 cases) and cholesterol within 6 months prior to death (2/4 cases). At postmortem examination, all 7 birds had grossly visible, irregular, soft, tan to yellow, amorphous plaques distributed on the surfaces of the viscera and body wall. Histologic evaluation and oil red O stain revealed xanthogranulomatous inflammation with phagocytized and extracellular lipid, necrosis, cholesterol clefts, fibrosis, and mineralization. Infectious agents were not identified with special stains in all cases. Concurrent hepatobiliary disease was present in 6/7 cases, and 6/7 had lipid accumulation within the parenchyma of various visceral organs. Five cases had atherosclerosis of great vessels. We describe a unique form of disseminated coelomic xanthogranulomatosis in 2 psittacine species. This condition should be recognized as a differential diagnosis in cases of disseminated coelomic mass formation and coelomic distension in psittacine birds, particularly in eclectus parrots and budgerigars.

Allergic rhinitis (AR) is a common allergic inflammatory and chronic reactive disease caused by allergen-induced immunoglobulin E (IgE). Tanshinone IIA (Tan IIA) is one of the active ingredients in Salvia miltiorrhiza Bunge (Danshen) and plays a vital role in inhibiting inflammation. Thus, we hypothesized that Tan IIA has anti-allergic effects and studied the function of Tan IIA in mast cells and an AR animal model. We induced RBL-2H3 cell sensitization with monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA) and constructed an ovalbumin (OVA)-induced AR model in mice. The role of Tan IIA in AR progression was studied using the MTT assay, ELISA, western blot, toluidine blue staining, HE staining, and Alcian blue and safranin O (A&S) staining. Tan IIA treatment significantly increased IgE/HSA-induced cell viability. However, Tan IIA treatment markedly downregulated the expression levels of β-hexosaminidase, histamine, tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), IL-4, and IL-5 in IgE/HSA-induced cells. Furthermore, Tan IIA improved typical symptoms in the OVA-induced AR model mice by inhibiting the phospholipase Cγ1 (PLCγ1)/protein kinase C (PKC)/IP3R pathway. Additionally, Tan IIA effectively improved the degranulation of RBL-2H3 cells and OVA-induced AR in mice. Together, these results suggest that Tan IIA may be a potential drug for the treatment of AR in the future.

This paper focuses on the optimization and operation of the renewable energy power sources for electrification of isolated rural city in Algeria desert. For this purpose, a system composed by photovoltaic (PV), wind turbine (WT), diesel generator (DG), and battery bank (BB) as well as for storing the energy in the electrical form to meet the load. In the present paper we are interested in evolutionary algorithms for solving optimization problem of hybrid renewable energy system. A new meta-heuristic algorithm namely whale optimization algorithm (WOA) is used to solve optimization problem of cost of energy (COE) and total net present cost (TNPC) including reliability evaluation by using basic probabilistic concept in order to find Loss of Power Supply Probability (LPSP). The WOA mimics the social behavior of humpback whales. This algorithm is inspired by the bubble-net hunting strategy. Three recent algorithms, particle swarm optimization (PSO), grey wolf optimizer (GWO), and modified grey wolf optimizer (M-GWO) are also implemented in this work. For examining the accuracy, stability, and robustness of proposed optimization technique two case studies have been tested. The results of simulations and comparison with other methods exhibit high accuracy and validity of the proposed whale optimization algorithm to solve optimization problem of hybrid renewable energy system.

A juvenile, male tiger shark ( Galeocerdo cuvier) developed illness after capture in Florida waters and was euthanized. Gross lesions included mild skin abrasions, hepatic atrophy, and coelomic fluid. Histologically, gills contained multifocal lamellar epithelial cell necrosis and thromboses. Scattered gill and esophageal epithelial cells had large, basophilic, intracytoplasmic, and intranuclear inclusions. Ultrastructurally, lamellar epithelial cells contained arrays of intracytoplasmic viral particles and scattered intranuclear nucleocapsids. Capsulated virions were 148 ± 11 nm with an 84 ± 8 nm icosahedral nucleocapsid and an electron-dense core. Next-generation sequencing, quantitative polymerase chain reaction, and in situ hybridization performed on formalin-fixed tissue confirmed a herpes-like viral infection. The viral polymerase shared 24% to 31% protein homology with other alloherpesviruses of fish, indicating a divergent virus. This report documents the pathologic findings associated with a molecularly confirmed novel herpes-like virus in an elasmobranch.