Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of the inflammatory myopathies: update and practical recommendations

Background: The inflammatory myopathies are a heterogeneous group of diseases including dermatomyositis, polymyositis, and inclusion body myositis. Clinical trials in myositis are rare, making it difficult to make clear recommendations on the treatment of these rare disorders. Objective: To give an overview of treatment options and strategies and to provide the clinician with a framework that can be used in treating patients with myositis. Methods: Results of clinical trials in myositis, case series and important case reports are presented and discussed. Results/conclusion: Most patients with dermatomyositis or polymyositis require treatment with oral high-dose prednisone combined with azathioprine or methotrexate to facilitate early tapering of prednisone. In case of treatment failure, intravenous immunoglobulin can be tried, followed by rituximab, mycophenolate mofetil, or tacrolimus depending on the specific clinical situation. A treatment trial with oral prednisone combined with methotrexate is advised in a subgroup of patients with inclusion body myositis.
Clinical assessment of functional outcome in lateral epicondylitis managed by local infiltration of autologous blood

Lateral epicondylitis is a well known elbow disorder known to affect a variety of population. Though the disorder is expected to affect a lot of sports personnel, the incidence is not uncommon in persons of household activities. The management comprises of conservative to operative with a dilemma of what to be done in most of the affected population. A large number of interventions have been tried to delineate the best modality but none of them proved to be conclusive. The aim of the present study was to prove the efficacy of cheapest possible interventional modality autologous blood for treatment of Lateral Epicondylitis. Twenty five patients of Tennis elbow were included in this study who have attended the OPD of GSVM Medical College and associated LLR Hospital, Kanpur from November 2007 to April 2008 and fulfilled inclusion and exclusion criteria. 78% were females, mostly housewives involved in regular household activities. All the patients were infiltrated autologous blood with local anaesthetic infiltration. Patients were deprived of regular activities for 3 weeks after infiltration. Follow up was done at weekly interval for 2 weeks and then at 6th week and 12th week. Assessment was done using Visual Analogue Scale ( VAS) and Verhaar et al scoring system. Total follow up period was 3 months. We observed that the mean VAS score improved from preinfiltrative 6.40±1.22 to 0.48±1.53 with p value being showed good results as per Verhaar et al scoring system on 12 weeks follow up. One patient did not respond to this procedure and showed poor result as per Verhaar et al score. Therefore, autologous blood infiltration is a safe and effective modality in treatment of Lateral Epicondylitis. KEY WORD S : Lateral epicondylitis; Autologous blood infiltration
GLP-1 receptor agonists in the treatment of polycystic ovary syndrome

ABSTRACT Introduction: Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed. Literature was searched from PubMed using appropriate search terms up to November 2016. Expert commentary: The available studies of GLP-1 RA therapy in the treatment of excess body weight in women with PCOS demonstrate that exenatide and liraglutide are effective in weight reduction either as monotherapy or in combination with metformin. A few studies showed that androgens may be modestly decreased and menstrual frequency may be increased. Eating behavior may be improved with liraglutide therapy. Glucose parameters are generally improved. GLP-1RAs were well-tolerated, with nausea being the most significant adverse side effect. Barriers to utilization may be the short duration studies, lack of familiarity of the medication, the route of administration (injection) and the variable outcomes on ovulation and hyperandrogenism.
Sepse por Salmonella associada à deficiência do receptor da Interleucina-12 (IL-12Rbeta1)

OBJECTIVE: to present a case report of a child who developed sepsis by Salmonella enteritidis associated with the diagnosis of primary immunodeficiency. DESCRIPTION: a twenty-one months old boy presenting fever and skin lesions, bilateral pneumonia with pleural effusion and septic shock. Salmonella enteritidis was isolated in blood cultures and pleural fluid. The identification of the bacteria suggested the presence of the MIM syndrome. The diagnosis of IL-12Rb1 was confirmed after IL-12 and IFN-g levels were measured using patient cells in a culture medium. The results showed absence of IL-12 and the IFN-g post stimulation using BCG. COMMENTS: a severe infection by Salmonella enteritidis is strongly suggestive of an immune system dysfunction. Laboratory tests for humoral, cellular and innate immunity were performed. Interleukin 12 receptor b1 (IL-12 Rb1) deficiency was confirmed after specific laboratory evaluation. The use of INF-g is recommended in severe cases.
Optimizing pharmacologic management of inflammatory bowel disease

ABSTRACT Introduction: As our medical armamentarium for IBD continues to expand, it is essential that clinicians understand both optimizing and sequencing of individual and combination therapeutic approaches with available medications. Areas covered: This review summarizes dosing strategies and therapeutic drug monitoring for pharmacologic optimization in IBD. Aminosalicylates remain first-line therapies for mild-to-moderate UC but have limited evidence of efficacy in CD. Budesonide provides an alternative to aminosalicylates when targeted to appropriate sites in the distal small bowel and colon, as do conventional corticosteroids when applied rectally. Systemic steroids are highly efficacious but burdened by toxicity. Thiopurines or methotrexate can be utilized as steroid-sparing agents. Biologic agents targeting TNF remain important for steroid-sparing therapy in moderate-to-severe UC and CD. Newer biologics targeting lymphocyte trafficking and lymphocyte activation are also efficacious for moderate-to-severe IBD. Near future conventional drug options include oral agents such as tofacitinib and mongersen. Expert commentary: Positioning therapies according to the location, phenotypes, and severity, as well as the use of therapeutic and clinical targets, will improve outcomes and minimize toxicities and therapeutic futilities. Future IBD treatment should focus on personalized therapy plans based on genetic determinants, targeted mechanisms of action, and pharmacologic optimization.
THE ULTRAVIOLET COMPONENT OF THE SUNLIGHT OF PORTLAND, ORE.: MEASURED BY THE ACETONE-METHYLENE BLUE METHOD

In 1929 I reported on the amount of ultraviolet radiation in the sunshine of Portland, Ore.1The method used was the acetone-methylene blue method as described by Hill.2The observations were made from February 10 to Sept. 30, 1928, inclusive. Since that time, numerous investigators3have determined the amount of ultra-violet light in the sunshine as it was received in different parts of the world. In the United States alone about 23 different observations have been made. The methods employed included the oxalic acid method, the lithopone mixture method, the zinc sulfide method, the use of the I. G. Farbindustrie ultraviolet dosimeter, and the acetone-methylene blue method. A discussion of the relative merits of these various methods will not be undertaken here since this subject has recently been treated adequately by Mayerson3in an excellent review. My first report covered a period of somewhat less than
Mechanisms of Outside‐in Signaling at the Tight Junction by Junctional Adhesion Molecule A

Junctional adhesion molecule A (JAM‐A) is a tight junction–associated, PDZ binding domain containing transmembrane protein that forms cis‐homodimers in endothelial and epithelial cells. In vivo, the function of JAM‐A in colonic mucosa has been examined using JAM‐A knockout mice, which have increased intestinal permeability, inflammation and cellular proliferation compared to wild‐type controls. In vitro studies have revealed that downregulation of JAM‐A leads to altered cell migration secondary to diminished levels of β1 integrin on the cell surface. Similar findings have been observed after transfection of epithelial cells with mutant JAM‐A, which is defective in dimerization or lacks the PDZ binding domain. The dominant‐negative effects of these mutant JAM‐A proteins are most likely secondary to the inability of mutant JAM‐A to form signaling complexes, the lack of which results in decreases in active or GTP‐bound Rap1. This review highlights findings that support a hypothetical model for JAM‐A mediated outside‐in signaling. In this model, JAM‐A dimerization is required for close cytoplasmic apposition of complexes containing specific PDZ domain‐containing scaffold proteins that activate signaling molecules to serve as effectors for the regulation of cellular functions. The possibility of interactions of JAM‐A cis‐dimers between cells in trans is also discussed.
Etiology of pouchitis*

Abstract: Restorative proctocolectomy with ileal‐pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that may occur in up to 50% of patients after RPC for UC. It is rarely seen in FAP patients after RPC. The etiology of pouchitis remains unclear. An overlap with UC is suggested by the frequency with which pouchitis affects patients with UC compared with FAP patients. There is significant clinical evidence implicating bacteria in the pathogenesis of pouchitis. Studies using culture and molecular methods demonstrate a dysbiosis of the pouch microbiota in pouchitis. Risk factors, genetic associations, and serological markers of pouchitis suggest that the interactions between the host immune responses and the pouch microbiota underlie the etiology of this idiopathic inflammatory condition. Here we present a detailed review of the data focusing on the pouch microbiota and the immune responses that support this hypothesis. We also discuss the contribution of luminal metabolic factors and the epithelial membrane in the etiology of this inflammatory process. The ileoanal pouch offers a unique opportunity to study the inter‐relationships between the gut microbiota and host immune responses from before the onset of disease. For this reason the study of pouchitis could serve as a human model that significantly enhances our understanding of inflammatory bowel diseases in general. (Inflamm Bowel Dis 2012;)
Endogenous PPARγ mediates anti-inflammatory activity in murine ischemia-reperfusion injury

Abstract Background & Aims: Peroxisome proliferator–activated receptor γ (PPARγ) is a nuclear receptor whose activation has been linked to several physiologic pathways including those related to the regulation of intestinal inflammation. We sought to determine whether PPARγ could function as an endogenous anti-inflammatory pathway in a murine model of intestinal ischemia-reperfusion (I/R) injury. Methods: PPARγ-deficient and wild-type mice were examined for their response to I/R procedure. Treatment with a PPARγ-specific ligand was also performed. Results: In a murine model of intestinal I/R injury, we observed more severe injury in PPARγ-deficient mice and protection against local and remote tissue injury in mice treated with a PPARγ-activating ligand, BRL-49653. Activation of PPARγ resulted in down-regulation of intercellular adhesion molecule 1 expression by intestinal endothelium and tissue tumor necrosis factor α messenger RNA levels most likely by inhibition of the NF-κB pathway. Conclusions: These data strongly suggest that an endogenous PPARγ pathway exists in tissues that may be amenable to therapeutic manipulation in I/R-related injuries. GASTROENTEROLOGY 2001;120:460-469
Development and Clinical Validation of a Multiplex Real-time PCR Assay for Herpes Simplex and Varicella Zoster Virus

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are related members of the Herpesviridae family and are well-documented human pathogens causing a spectrum of diseases, from mucocutaneous disease to infections of the central nervous system. This study was carried out to evaluate and validate the performance of a multiplex real-time polymerase chain reaction (PCR) assay in detecting and differentiating HSV1, HSV2, and VZV from clinical samples. Consensus PCR primers for HSV were designed from the UL30 component of the DNA polymerase gene of HSV, with 2 separate hydrolysis probes designed to differentiate HSV1 and HSV2. Separate primers and a probe were also designed against the DNA polymerase gene of VZV. A total of 104 clinical samples were available for testing by real-time PCR, conventional PCR, and viral culture. The sensitivity and specificity of the real-time assay was calculated by comparing the multiplex PCR result with that of a combined standard of virus culture and conventional PCR. The sensitivity of the real-time assay was 100%, with specificity ranging from 98% to 100% depending on the target gene. Both PCR methods detected more positive samples for HSV or VZV, compared with conventional virus culture. This multiplex PCR assay provides accurate and rapid diagnostic capabilities for the diagnosis and differentiation of HSV1, HSV2, and VZV infections, with the presence of an internal control to monitor for inhibition of the PCR reaction.
WNT Proteins: Environmental Factors Regulating HSC Fate in the Niche

The Wnt signaling pathway has been implicated in regulation of hematopoiesis through a plethora of studies from many different laboratories. However, different inducible gain‐ and loss‐of‐function approaches retrieved controversial and sometimes contradictory results. Different levels of activation of the pathway, dosages of Wnt signaling required, and the interference by other signals in the context of Wnt activation collectively explain these controversies. Gain‐of‐function or in vitro exposure to WNT proteins and more specifically WNT3a was shown to enhance hematopoietic stem cell (HSC) activity, but its exact role was still not completely understood. In a recent study we analyzed the hematopoietic system of mice deficient for this specific Wnt gene. Wnt3a deficiency results in early embryonic lethality around embryonic day 12.5 (E12.5), precluding analysis in adult mice, but allowing hematopoiesis to be studied in fetal liver (FL) and in the just colonized thymic rudiment. Notably, we showed that long‐term HSCs and multipotent progenitors are reduced in FL and have severely reduced long‐term reconstitution capacity as observed in serial transplantation assays. Of interest, deficiency in Wnt3a leads to complete abolition of canonical Wnt signaling in FL hematopoietic stem and progenitor cells. This HSC deficiency is not explained by altered cell cycle or survival and is irreversible, since it cannot be restored by transplantation into Wnt3a‐competent mice. In addition, Wnt3a deficiency differentially affects myeloid and B‐lymphoid lineages, with myeloid cells being affected at the progenitor level, while B lymphopoiesis is apparently unaffected. Immature thymocytes, however, were reduced in cell numbers due to lack of Wnt3a production by the thymic microenvironment. Our results show that while in the thymus Wnt3a provides cytokine‐like, proliferative stimuli to developing thymocyte Wnt3a regulates cell fate decisions of FL HSC in a nonredundant way.
Use of the ecosystem services concept in ecological risk assessment of chemicals

The reason for expressing ecological protection goals in terms of ecosystem services is to make a connection between ecosystems and what people get out of them in terms of marketed goods and nonmarketed welfare. Here our focus will be on how the ecosystem services framework is and can be applied to the ecological risk assessment (ERA) of chemicals. We provide 2 contrasting examples of how the ecosystem services framework is currently being applied in regulatory risk assessment, and we discuss the challenges and knowledge gaps that need to be addressed if such a framework is to substantially improve ERAs and their ability to inform management decisions. We make the point that formulating protection goals in terms of ecosystem services only makes sense if they can be used in managing environmental impacts and if they are useful in informing the risk assessments behind these. Ecosystem services can make a contribution to management by connecting ecosystem structure and process to what is valued, and analyzing risk in this context is a way of making risk assessment more policy‐ and value‐relevant. Using an ecosystem services framework to its fullest potential to support ERA will require the successful development of a suite of coupled Valuation Methods, Ecological Production Functions, and Mechanistic Effect Models that will require the establishment of strong multidisciplinary collaborations among ecologists, computer scientists, social scientists, and possibly others. In addition, buy‐in from environmental decision makers and other stakeholders will be crucial. Some progress is being made on the research front, and the implementation of new legislation is providing incentives for developing risk assessment outputs that are much more directly related to environmental protection goals than those used currently. Integr Environ Assess Manag 2013; 9: 269–275. © 2012 SETAC
Parenting Stress in Mothers of Children With Autism Without Intellectual Disability. Mediation of Behavioral Problems and Coping Strategies

The present study investigated the mediating role of behavioral difficulties, coping strategies, and social functional support in the relationship between symptoms severity and parenting stress in mothers of children with ASD (autism spectrum disorder). The parenting stress questionnaire, coping orientation to problems experienced scale, strengths and difficulties questionnaire, and Duke-UNC social support questionnaire were administered to 52 mothers, who also estimated the ASD severity symptoms of their children. Correlation analyses revealed that parenting stress was positively correlated with the children’s ASD symptoms and behavioral problems. On the other hand, parenting stress was negatively correlated with the engagement coping and social functional support reported by the mothers. Multiple mediation analysis indicated that engagement coping and behavioral difficulties were significant mediators in the relationship between ASD symptoms and parenting stress, with the engagement variable having a larger effect. The findings illustrate the need to promote the mothers’ engagement coping orientation and the application of behavioral strategies with their children to help them to buffer the impact of stress.
Nicotiana benthamiana RanBP1-1 Is Involved in the Induction of Disease Resistance via Regulation of Nuclear-Cytoplasmic Transport of Small GTPase Ran

Plant cells enhance the tolerances to abiotic and biotic stresses via recognition of the stress, activation and nuclear import of signaling factors, up-regulation of defense genes, nuclear export of mRNA and translation of defense proteins. Nuclear pore-mediated transports should play critical roles in these processes, however, the regulatory mechanisms of nuclear-cytoplasmic transport during stress responses are largely unknown. In this study, a regulator of nuclear export of RNA and proteins, NbRanBP1-1 (Ran-binding protein1-1), was identified as an essential gene for the resistance of Nicotiana benthamiana to potato blight pathogen Phytophthora infestans. NbRanBP1-1-silenced plants showed delayed accumulation of capsidiol, a sesquiterpenoid phytoalexin, in response to elicitor treatment, and reduced resistance to P. infestans. Abnormal accumulation of mRNA was observed in NbRanBP1-1-silenced plants, indicating that NbRanBP1-1 is involved in the nuclear export of mRNA. In NbRanBP1-1-silenced plants, elicitor-induced expression of defense genes, NbEAS and NbWIPK, was not affected in the early stage of defense induction, but the accumulation of NbWIPK protein was reduced. Nuclear export of the small G-protein NbRan1a was activated during the induction of plant defense, whereas this process was compromised in NbRanBP1-1-silenced plants. Silencing of genes encoding the nuclear pore proteins, Nup75 and Nup160, also caused abnormal nuclear accumulation of mRNA, defects in the nuclear export of NbRan1a, and reduced production of capsidiol, resulting in decreased resistance to P. infestans. These results suggest that nuclear export of NbRan is a key event for defense induction in N. benthamiana, and both RanBP1-1 and nucleoporins play important roles in the process.
Carbon footprint of breton pâté production: A case study

This study targeted 9 different pork pâtés, produced with pork from different meat production systems (conventional, organic, and other quality certifications). Besides greenhouse gas (GHG) emissions, the study also included a detailed analysis of product nutrition. Results show that the GHG emissions range from 200 g CO2e per 100 g of product for conventional pork pâtés and 330 g CO2e per 100 g for organic pork pâtés. Results for organic pâtés are an indirect consequence of the lower productivity of swine feed ingredients. However, if the reference flow unit is nutritional indicator (e.g., calories, protein) instead of 100 g of product, results can be inverted. This fact highlights the difficulty of choosing a functional unit for studies on food products. The function of a food product is to provide quality nutrition, but because there are many different nutritional indicators, life cycle assessment practitioners normally use simple comparisons between amounts. This issue together with the choice of emissions allocation method between pork parts are the main sources of uncertainty. Also, the life cycle of pork production is the main hotspot in the C footprint, accounting for more than 80% of the total emissions. Energy spent for processing and packaging, the only life cycle step that the producer controls directly, accounts for less than 10% of the impact. Integr Environ Assess Manag 2013;9:645–651. © 2013 SETAC
Recognition and Successful Treatment of Priapism and Suspected Black Widow Spider Bite With Antivenin

AbstractPriapism, although uncommon in preadolescent children, is considered a true emergency. Envenomation by a black widow spider bite has been reported to induce priapism as a manifestation of its toxicity. Early recognition and timely administration of antivenin have been reported to be effective in relieving priapism. Clinicians who care for children need to be aware of this unusual presentation. The diagnosis is traditionally from either direct observation of a spider bite or capture of a spider. We report a case of a previously healthy 2-year-old boy who presented with severe irritability, leg cramps, and stomachache. The diagnosis of a likely black widow spider envenomation was made on the basis of clinical suspicion and suggestive physical findings in absence of demonstrated exposure. This case highlights the importance of early recognition and successful resolution of symptoms with administration of antivenin and supportive care.