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Summary Background Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. Methods This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18–50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. Findings Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene–placebo difference 0·16 pu, 95% CI –0·39 to 0·71; p=0·55). Interpretation We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. Funding Multiple Sclerosis Society of the United Kingdom.

Objetivo: revisar artigos disponí­veis em periódicos cientí­ficos que exemplificassem o papel do profissional de odontologia no atendimento de manifestações bucais em pacientes com Leucemia. Metódo: tratou-se de uma revisão bibliográfica narrativa utilizando artigos selecionados datados dos anos de 2008 a 2018. Resultados: As manifestações bucais das leucemias são mais frequentes nas formas agudas, do que nas formas crônicas. O profissional da saúde deve estar sempre atento a qualquer tipo de sinal ou sintoma, assim como í constante atualização da história médica. Com o surgimento de novas técnicas que propiciem a manutenção da saúde bucal nos pacientes com algum tipo de neoplasia, hoje é possí­vel prevenir uma doença sem que ela já esteja instalada. Conclusão: Conclui-se que a presença do profissional de odontologia na equipe oncológica pode diminuir a morbidade e a mortalidade relacionadas a complicações bucais, assim como aumentar o conforto e qualidade de vida dos pacientes durante a terapia.

Objetivo: Revisar artigos disponí­veis em periódicos cientí­ficos que retratassem os aspectos odontológicos de pacientes com Sí­ndrome de Down. Métodos: Trata-se de um estudo de revisão bibliográfica realizado em 2020, o limite temporal estabelecido para a pesquisa foi entre 2008 a 2018, elegí­veis as bases da Biblioteca Digital Brasileira de Teses e Dissertações (BDTD), Coordenação de Aperfeiçoamento de Pessoal de Ní­vel Superior (CAPES) e Google Acadêmico. Conclusão: A partir das informações obtidas podemos concluir que A higiene bucal supervisionada é fundamental nesses indiví­duos, devido í s limitações motoras e í alta prevalência de doenças periodontais. O cirurgião-dentista deve estar preparado para o atendimento de pacientes com necessidades especiais por meio da capacitação técnica e cultivo de valores humanos, minimizando os diversos problemas que esses pacientes já estão condicionados a enfrentar devido ao seu estado de deficiência.

Background and objectives: Osteoarthritis (OA) is a degenerative articular disease that affects approximately 240 million people worldwide, with knee OA accounting for 80% of this burden. One of the aims of pharmacological treatment in OA is to reduce pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for pain relief in OA but have considerable renal, hepatic, cardiovascular, and gastrointestinal adverse effects, with the resultant increase in morbidity and mortality. Naltrexone is an orally activated opioid antagonist that has varied dose-dependent pharmacodynamic effects: Analgesic and anti-inflammatory effects are exhibited only at low dosage ranges of 0.5mg to 4.5mg (Low Dose Naltrexone LDN) while retaining a favorable adverse effect profile. This study aims to test the non-inferiority of LDN against Naproxen. Methodology: This is a prospective phase II triple-blinded, two-arm, parallel-group, non-inferiority randomized controlled trial. The intervention group will receive low dose naltrexone 4.5 mg once daily, and the control group will receive extended-release naproxen 1000 mg once daily during the 12 week trial duration. Our sample size will be 118 patients recruited from a single Orthopedic referral center in the USA. Discussion: The use of LDN for pain relief in osteoarthritis (OA) may be beneficial due to its favorable adverse effect profile. To the best of our knowledge, there is no published data on LDN use in OA even though preliminary evidence has documented its safety and tolerability in a variety of chronic pain conditions.

Aortic injury is a frequently encountered condition that can present as a life-threatening emergency. When this injury occurs in the retroperitoneal portion of the aorta, it can be difficult to diagnose and treat because of the location. Although surgical repair remains the mainstay of treatment, surgery might not be an option for some patients. We have presented a case of a 54-year-old nonoperative candidate who had experienced iatrogenic retroperitoneal abdominal aortic rupture with pseudoaneurysm formation. The patient was successfully treated with the novel use of a proven technique: direct percutaneous embolization of the pseudoaneurysm sac via a translumbar approach under image guidance.

Background Low back pain (LBP) and knee osteoarthritis (OA) are major contributors to disability worldwide. These conditions result in a significant burden at both individual and societal levels. Engagement in regular physical activity and exercise programs are known to improve physical function in both chronic LBP and knee OA populations. For people residing in rural areas, musculoskeletal conditions are often more frequent and disabling compared to urban populations, which could be the result of reduced access to appropriate health services and resources in rural settings. EHealth is an innovative solution to help provide equitable access to treatment for people with musculoskeletal pain living in rural settings. Methods/design We will conduct a randomised clinical trial investigating the effects of an eHealth intervention compared to usual care, for people with chronic non-specific LBP or knee OA in rural Australia. We will recruit 156 participants with non-specific chronic LBP or knee OA. Following the completion of baseline questionnaires, participants will be randomly allocated to either the eHealth intervention group, involving a tailored physical activity and progressive resistance exercise program remotely delivered by a physiotherapist (n = 78), or usual care (n = 78) involving referral to a range of care practices in the community. Outcomes will be measured at baseline, 3 and 6 months post-randomisation. The primary outcome will be physical function assessed by the Patient-Specific Functional Scale (PSFS). Secondary outcomes include pain intensity, physical activity levels, activity limitations, quality of life, pain coping. We will also collect process evaluation data such as recruitment rate, attendance and adherence, follow-up rate, participants’ opinions and any barriers encountered throughout the trial. Discussion The findings from this trial will establish the effectiveness of eHealth-delivered interventions that are known to be beneficial for people with LBP and knee OA when delivered in person. As a result, this trial will help to inform health care policy and clinical practice in Australia and beyond for those living in non-urban areas. Trial registration This study was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12618001494224) registered 09.05.2018.

Infantile pyknocytosis is a rare, self-limited, hemolytic condition of unknown pathogenesis. It is diagnosed when a neonate with Coombs-negative hemolytic anemia has abundant pyknocytes and a characteristic clinical course after other hemolytic disorders has been excluded. Previous reports suggest that transfusions might be avoidable in this condition by administering recombinant erythropoietin. We cared for a patient with this disorder where we employed novel diagnostics and therapeutics. Despite these, and a good outcome free of transfusions, we continue to consider the condition to be idiopathic.

Severe asthma is characterized by steroid insensitivity and poor symptom control and is responsible for most asthma-related hospital costs. Therapeutic options remain limited, in part due to limited understanding of mechanisms driving severe asthma. Increased arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is increased in human asthmatic lungs. In this study, we show that PRMT5 drives allergic airway inflammation in a mouse model reproducing multiple aspects of human severe asthma. We find that PRMT5 is required in CD4+ T cells for chronic steroid-insensitive severe lung inflammation, with selective T cell deletion of PRMT5 robustly suppressing eosinophilic and neutrophilic lung inflammation, pathology, airway remodeling, and hyperresponsiveness. Mechanistically, we observed high pulmonary sterol metabolic activity, retinoic acid-related orphan receptor γt (RORγt), and Th17 responses, with PRMT5-dependent increases in RORγt’s agonist desmosterol. Our work demonstrates that T cell PRMT5 drives severe allergic lung inflammation and has potential implications for the pathogenesis and therapeutic targeting of severe asthma.

Purpose: Hepatoblastoma is the most common primary neoplasm of the liver in the pediatric population, usually diagnosed during the first 5 years of life. Patients with large or peripheral hepatoblastomas are at risk for rupture and peritoneal hemorrhage. Image-guided, minimally invasive interventions are offered for controlling hemorrhage. Case presentation: We present a 2-year-old female with an 11.8 cm hepatoblastoma in the right hepatic lobe involving segment 4A, who developed hemodynamic instability on day 8 of induction chemotherapy. Imaging revealed intraperitoneal hemorrhage secondary to her ruptured hepatoblastoma. The patient was successfully treated by celiac artery angiogram and transarterial bland embolization. Conclusion: Transarterial bland embolization of large hepatoblastomas may control and even prevent intraperitoneal/intracapsular hemorrhage, and may also enhance the efficacy of systematic chemotherapy in the pediatric patients with advanced hepatoblastoma.

The physical processes of incision, traction and hemostasis used for craniotomy, stimulate nerve fibers and specific nociceptors, resulting in postoperative pain. During the first 24 h after craniotomy, 87% of patients have postoperatory pain. The rate of suffering pain after craniotomy falls 3% for every year of life. The objective of this study is to review the available therapeutic options to help physicians treating this pain, and discuss pain mechanisms, pathophysiology, plasticity, risk factors and psychological factors. This is a narrative review of the literature from 1970 to June 2019. Data were collected by doing a search in PubMed, EMBASE, Cochrane Reviews and a manual search of all relevant literature references. The literature includes some drugs treatment: Opioids, codeine, morphine, and tramadol, anti-inflammatory non-steroids such as cyclooxygenase-2 inhibitors, gabapentin. It discusses: side effects, pharmacodynamics and indications of each drug, anatomy and Inervation of Skull and its Linigs, pathogenesis of pain Post-craniotomy, scalp nerve block, surgical nerve injury, neuronal plasticity, surgical factors and chronic post-surgical pain.

O objetivo deste trabalho é estimar a frequência de estresse entre professores e verificar sua associação com variáveis sociodemográficas, características de trabalho e estado nutricional. Trata-se de estudo transversal com 84 professores da área de Ciências Humanas e Naturais, através dos instrumentos: IPAQ abreviado, escala demanda-controle de Karasek e Theorel e Job Stress Scale. O estado nutricional foi definido pelo Índice de Massa Corporal (IMC), o estado de saúde e as características de trabalho foram autorreferidas. Observou-se que 64,3% dos docentes apresentaram baixos níveis de estresse. Embora a prevalência encontrada seja menor do que em outros estudos, 35,7% mostraram alto estresse e trabalho passivo (n = 30). Dentre os estressores, destacam-se os deveres administrativos (p = 0,012) e o tempo exercendo o cargo administrativo (p = 0,024). O excesso de peso predominou na amostra. Diante disso, é fundamental repensar o modelo de gestão dessas instituições de modo a não prejudicar a saúde e atuação do profissional do ensino superior.

Although several studies have attempted to deduce by theoretical calculations the reaction mechanism of carmustine with DNA, no study has presented data on the reaction sites and the behavior of the electrons of the participating molecules. Thus, the objective of this paper is to apply the NBO (Natural Bond Orbital) model from the donor-acceptor point of view and the QTAIM (Quantum Theory: Atoms in Molecules) theory from the Laplacian of electronic density and the energy partition formalism IQA (Interacting Quantum Atoms) to quantify the interactions present in the alkylation between carmustine and DNA. The results showed that the decomposition of carmustine forms the chloroethyl ion and the 2-chloroethyldiazene hydroxide molecule, which subsequently breaks down to form 2-chloroethanol and N2. The NBO, QTAIM, and IQA data demonstrated that the ionic carbon of the chloroethyl ion suffers a nucleophilic attack from the O6-guanine. In the alkylation between intermediate 1,O6-ethanoguanine and cytosine, the bond between the CO of the intermediate ring breaks with a subsequent nucleophilic attack of the N of the cytosine with the C of the ring of the molecule 1,O6-ethanoguanine, forming a bridge of ethane between the guanine and cytosine bases.

An excluded calyx is a rare, acquired urologic condition where there is discontinuity between a portion of the renal collecting system with the remainder of the collecting system. Re-establishment of reliable long-term communication between the excluded calyx and the remaining collecting system is crucial for preservation of renal function and possible relief of symptoms. In this manuscript, we discuss two such cases where a previously undescribed novel procedure is used for treatment of this uncommon condition, where percutaneous antegrade transcatheter techniques were used to establish long-term urinary drainage. The first case discusses an excluded calyx in a 17-year-old male who suffered left renal injury after a high speed motor vehicle accident, where the kidney was divided by the injury and subsequently required creation of a neoinfundibulum in order to maintain continuity of the collecting system. The second case involves a 39-year-old female who underwent resection of a renal cell carcinoma, later developing an excluded calyx where radiofrequency wire recanalization was performed and the neoinfundibular track underwent serial retrograde balloon dilation, resulting in a continuous collecting system. Both patients have done well for more than 2 years after neoinfundibulum creation, showing that this novel technique should be considered a viable and safe procedure in the treatment of this rare condition.

Introduction: Although Brazil has complete legislation that establishes guidelines and recommendations for companies regarding Occupational Health and Safety, according to data from the Ministry of Labor and Social Security, indices of absenteeism and absences from work functions increase with each year. Objective: To identify the association of the level of physical activity on absenteeism by diseases in workers, through a systematic review. Methods: Four databases (Lilacs, SciELO, Medline via Pubmed and Cochrane Library) were consulted from November 10 to 23, 2017. Results: The selection process of the articles were included after screening 25 articles: (08) articles did not mention workers, only school children, (05) articles were systematically reviewed, and (12) articles had randomized clinical trials. The systematic relationship included a bias analysis, data extraction and important discussions of the characteristics of the articles selected so that we had breadth of knowledge produced in this theme. Conclusion: We evidenced the need for more research in the area of physical activity and less number of absenteeism due to diseases in workers.

Background: Self-rated health status is a subjective indicator that is based on the body’s perception of health status, covering personal components such as, physical aspects, aspects of general well-being and satisfaction with life. Objective: To analyze the self-rated health status and factors associated with the lifestyle of higher education educators. Material and methods: This is an observational study, consisting of 85 faculty members in the area of Human and Natural Sciences of a university. For the analysis of the sample, chi-square test and Fisher’s exact test were used. Results: 24.7% (n = 21) self-rated their health as regular/poor. (P = 0.022), the Waist/Stature ratio (p = 0.014), the level of physical activity (p = 0.050), the time in administrative positions (p = 0.026) and stress-related symptoms (p = 0.043). Conclusion: The time in administrative position and the large number of symptoms related to stress, high PW, inadequate W/S ratio and low level of physical activity were associated with negative self-rated health, recommending strategies for promotional health and prevention of stress-related diseases.

Most patients have a time limited indication for inferior vena cava filtration. When the indication has expired, a retrievable inferior vena cava filter should be removed percutaneously, unless the risks of retrieval outweigh the benefits. Over time, long term indwelling inferior vena cava filters may experience complications, such as strut penetration, migration, thrombosis, tilt, fracture, and inferior vena cava stenosis. Long term indwelling retrievable inferior vena cava filters may become embedded in the wall of the inferior vena cava, making percutaneous retrieval difficult. However, this is not always the case, and they also may be easily and safely removed using simple techniques. We present a case of a long term indwelling retrievable inferior vena cava filter that was easily removed using simple techniques, 16.5 years after placement.

Purpose: To evaluate the use of a dual-chambered venous access port for extracorporeal apheresis therapy. Methods: This was a single-center retrospective analysis of all patients who received a dual-chambered venous access port for apheresis therapy over a 36-month period. Clinical success was defined as successful completion of at least one round of apheresis via the venous access port. Major complications were defined as any event requiring elevation of patient care and/or venous access port removal or repositioning. Minor complications were defined as venous access port issues resolved with clinical intervention. Results: Forty-four patients had a venous access port placed at the time of this study. Patients underwent red cell exchange (n = 33), therapeutic plasma exchange (n = 6) or extracorporeal photopheresis (n = 5). Forty (90%) patients had autoimmune diseases and four (10%) had neoplastic processes. Clinical success was achieved in 42 (95.5%) patients. Average venous access port dwell time was 632 days (range = 42–1191 days). All therapies through the venous access ports were well tolerated and no patients reported pain or discomfort. Major complications were seen in nine (20.5%) patients–the majority (n = 7) of which were due to venous access port malfunction–and resolved with catheter revision. One (2.27%) major complication involved an infected venous access port, and one involved a large hematoma at the venous access port site. Minor complications were seen in eight (18.2%) patients, where simple flushing of the catheter with saline or tissue plasminogen activator resolved the issue. Conclusion: The dual-chambered venous access port was successfully used for sustained blood flow in apheresis therapy with a moderate, yet correctable complication rate.

Mit dem getesteten Modell wird ein Qualitatsmodell in den wissenschaftlichen Diskurs eingebracht, das zeigt, wie Ergebnisqualitat - verstanden als das direkte Ergebnis der Beratung aus Sicht der Klienten - abgebildet werden kann. Das Modell konnte bei der Evaluation von Beratungsangeboten in der Pflege eingesetzt werden und zu einer stringenten Weiterentwicklung von Beratungsangeboten im Sinne des SGB XI fuhren. Allerdings bedarf es weiterer Testungen und der konzeptionellen Erweiterung zur Abbildung zielgruppenspezifischer Beratungsansatze (Diversitat). Dieser Aspekt konnte nicht getestet werden, da ein entsprechendes Klientel in der Stichprobe weitgehend fehlte. Die erreichte Modellgute und die Signifikanzniveaus deuten jedoch an, dass die Grundkomponenten erhalten bleiben sollten.

Microgreens are an emerging functional food crop with promise for sustainably diversifying global food systems, facilitating adaptations to urbanization and global climate change, and promoting human health. Previous work suggests microgreens have high nutritional quality, low environmental impacts, and broad consumer acceptance. For better reception into the global food system and increased per capita consumption, research is needed to elucidate consumer acceptance of various microgreens species, including factors contributing to their acceptance or lack thereof. Using a consumer panel (n = 99), this study evaluated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens species received high mean liking scores for acceptability by consumers (means ranged from highly acceptable to slightly acceptable), with more distinct differences across microgreens species for flavor and overall acceptability, which appeared to be driven by specific sensory properties. Data from principal component analysis demonstrated that high acceptability scores were associated with higher intent to purchase microgreens and negatively associated with food neophobia. Participants indicated that factors such as knowledge and familiarity of microgreens, cost, access/availability, freshness/shelf life, among other factors, influence their intention to purchase microgreens. These findings suggest that further integration of microgreens into the global food system will be met with high consumer acceptability, but needs to be aligned with enhanced consumer education regarding microgreens, as well as considerations of cost, availability/access, and freshness/shelf life. PRACTICAL APPLICATION: Researchers investigated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens tested had high consumer acceptability, but certain factors such as sensory perception and food neophobia impacted their acceptability. Additionally, participants indicated that factors such as knowledge, access and availability, cost, freshness, and shelf life may impact the purchasing of microgreens and thus are important factors to consider for further integration of this emerging functional food crop into the global food system.

This review article presents a comprehensive literature review regarding extended trochanteric osteotomy (ETO). The history, rationale, biomechanical considerations as well as indications are discussed. The outcomes and complications as reported in the literature are presented, discussed and compared with our own practice. Based on the available evidence, we present our preferred technique for performing ETO, its fixation, as well as post-operative rehabilitation. The ETO aids implant removal and enhanced access. Reported union rate of ETO is high. The complications related to ETO are much less frequent than in cases when accidental intra-operative femoral fracture occurred that required fixation. Based on the literature and our own experience we recommend ETO as a useful adjunct in the arsenal of the revision hip specialist.Cite this article: EFORT Open Rev 2020;5:104-112. DOI: 10.1302/2058-5241.5.190005

We report a novel glucose-6-phosphate dehydrogenase (G6PD) variant (c.1375C>G) discovered in a 3-day-old Hispanic male child from Salt Lake City, UT, USA. This newborn presented with severe hyperbilirubinemia (29.8 mg/dL or 510 μmol/L) and marked hemolysis evidenced by elevated end-tidal carbon monoxide concentration (5.9 ppm, normal G6PD variant. His mother was heterozygous for this same variant, and she had a moderate decrease in G6PD enzyme activity (7.1 U/g Hb). On the basis of these findings, we propose this variant as a novel pathogenic mutation.

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Background/aim Wire-guided localisation (WGL) has been the mainstay for localisation of clinically occult breast lesions before excision. However, it has restrictive scheduling requirements, and causes patient discomfort. This has prompted the development of various wireless alternatives. In this prospective study we shall evaluate the role of radiation-free wireless localisation using a radiofrequency identification (RFID) tag and a hand-held reader (LOCalizer™) in the management of occult breast lesions. Patients and methods This technique was evaluated in a prospective cohort of 10 patients. The evaluation focused on: i) successful deployment, ii) identification and retrieval, iii) the status of surgical margins and need for re-operation, iv) resected specimen weight, v) marker migration rates (>5mm), and vi) acceptance by patients, radiologists and surgeons. Results RFID tags (n=11) were deployed under ultrasound guidance pre-operatively to localise occult breast lesions in 10 patients. The mean time for deployment of the RFID tag was 5.4 min (range=2-20). The mean distance from the lesion was 0.45 mm (range=0-3). The mean duration for retrieval was 10.2 min (range=6-20). Mean specimen weight was 19.6 g for malignant lesions (range=4.5-42). All tags were identified, and none had migrated. There were no positive margins, re-operations, nor complications. Patient feedback was highly positive. Both radiologists and surgeons rated the LOCalizer™ technique as better than WGL. Conclusion Our study demonstrates that wireless localisation using RFID is an effective and time-efficient alternative to WGL, with low margin positivity and re-operation rates, and high patient, radiologist and surgeon acceptance.

BackgroundProstate cancer (PC) is the most common non-cutaneous diagnosed cancer among men in USA.1 Although clinical outcomes are favorable for patients with localized disease, 20–30% of patients will develop metastatic prostate cancer (mPC) and have poor prognosis. Immunotherapy, as a single agent, provides benefit to a small subset of PC patients, which is thought to be partially due to its known cold tumor immune microenvironment (TIME). Combination studies are needed to enhance benefit.2 Prostvac is a therapeutic cancer vaccine engineered to activate an immune response against prostate-specific Antigen (PSA).3 Prostvac alone could induce systemic immune response by increasing immune-cell infiltrates in and around the tumor.4 In this study, we are exploring the effect of Prostvac in combination with nivolumab in TIME in prostate cancer.MethodsWe treated locally advanced prostate cancer patients (n=6) undergoing radical prostatectomy (RP) with neoadjuvant Prostvac in combination with nivolumab, an immune checkpoint PD-1 inhibitor. Dynamic changes in TIME before and after treatment were studied using multiplex immunofluorescence (Opal Method). Formalin fixed paraffin-embedded sections from matched pre-treated prostate biopsies and post-treated RP samples were stained with a validated T cell panel (DAPI, CD4, CD8, FOXP3, Ki67, Pan CK and PD-L1). To analyze the data, TIME was segmented into 3 compartments: intratumoral, invasive margin and benign.ResultsCombination immunotherapy significantly increased CD4+ T cell density in the invasive margin (mean 211.5 cells/mm2 vs 592.2 cells/mm2, pConclusionsThe combination of Neoadjuvant Prostvac and nivolumab was associated with increased immune cell infiltration in a cohort of early prostate cancer patients. A broader examination of the TIME and the role immune cells undertake to control tumor growth is on-going.Trial RegistrationNCT02933255ReferencesSiegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin (Internet) 2020;70:7–3Zhao SG, Lehrer J, Chang SL, et al. The immune landscape of prostate cancer and nomination of PD-L2 as a potential therapeutic target. J Natl Cancer Inst 2018;111:301–10.Madan RA, Arlen PM, Mohebtash M, et al. Prostvac-VF: a vectorbased vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs 2009;18:1001–11Abdul Sater H, Marté JL, Donahue RN, et al. Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer. J Immunother Cancer 2020;8(1):655–64Ethics ApprovalThis study was performed in compliance with ethical standard and was approved by the NIH IRB, 17C-0007. All patients participating in this study gave an informed consent before taking part.

Kehrer et al.1 categorized different onset forms of metachromatic leukodystrophies based on first symptoms at onset and disease progression. The genotypes associated with each of these categories seem to indicate that earlier symptom onset is associated with more severe arylsulfatase A (ARSA) deficiency.

Subacute Sclerosing panencephalitis (SSPE), also known as Dawson’s disease or measles encephalitis, is an extremely rare and fatal subacute infection caused by a persistent defective measles virus (MV). It mostly develops 7-10 years after initial MV infection and is fatal within 3 years from onset of symptoms.1 Measles virus infection before 2 years of age has 16 times higher risk of developing SSPE as compared to infection occurring after five years of age.2 SSPE is a progressive, degenerative disease of the central nervous system that occurs several years after measles infection. Saha et al reported an annual incidence of 21 per million population in India3 as compared to 2.4 per million population in the middle east.4-5 By this case report, we aim to stress on the certitude that the only definitive prevention against SSPE is timely measles vaccination. Keywords: SSPE, Measles, Vaccination.

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B- cell malignancies leading to durable responses in patients with relapsed/refractory disease. 1,2 One of the most severe toxicities associated with this treatment is immune effector cell-associated neurotoxicity syndrome (ICANS), which was seen in 65-75% of patients treated with axicabtagene ciloleucel (axi-cel) in initial clinical trials. ICANS can range from mild headache to coma, and can occur with or without cytokine release syndrome (CRS). Due to the recent development of CAR T-cell therapy, the long-term effects of ICANS are unknown. This study sought to determine the long-term outcomes in patients with neurotoxicity from axi-cel. Methods We conducted a retrospective chart review of patients who received CAR T-cell therapy with axi-cel between June 2018 and June 2021. Neurotoxicity was graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) ICANS grading system. 3 The primary outcome was percentage of patients who had neurotoxicity defined as ICANS grade ≥ 1 as well as the percentage of patients with neurotoxicity lasting ≥ 1 month. We captured descriptive data such as age, sex, ethnicity, comorbidities, IPI score, stage, baseline neurologic dysfunction, performance status, and number of prior treatments. Secondary outcomes included progression free survival (PFS) and overall survival (OS). Results Thirty-four patients received axi-cel between June 2018 and June 2021 at our institution. Median age of patients was 65. Twenty patients (59%) were male and 14 (41%) were female. The majority of patients received axi-cel for diffuse large B-cell lymphoma (97%). Study population was predominantly hispanic (35%), white (32%), African american (29%) and asian (3%). (Sixteen patients (47%) developed neurotoxicity of any grade, with 7 patients (21%) ≥ grade 3. Of note, 4 patients (12%) died during admission for CAR T-cell therapy and 3/4 deaths were in patients with ICANS ≥ grade 3. Median follow up time was 8 months. Of the 12 patients with neurotoxicity who survived initial admission for CAR-T, 9 (75%) patients recovered from neurotoxicity and mental status was at baseline at discharge without recurrence during follow up. Three (25%) of patients had prolonged neurotoxicity lasting > 1 month. Long-term neurotoxicity included confusion, disorientation, and mild cognitive impairment in the three patients. One patient recovered 15 months after CAR T-cell infusion. 2 patients had prolonged neurotoxicity resulting in deterioration of functional status and death in 1 patient, and 1 patient transitioning to hospice and being lost to follow up. Conclusions Neurotoxicity from axicabtagene ciloleucel is a common adverse event, with half of patients in our cohort having neurotoxicity of some degree, and 20% ≥ grade 3. Twenty-five percent of patients that developed neurotoxicity had long-term effects lasting > 1 month, which resulted in deterioration of functional status in 2 patients. Long-term neurotoxicity included disorientation, confusion, and memory impairment. Our study is limited by a small sample size. Larger studies with longer follow-up times are needed to further characterize the long-term outcomes of neurotoxicity associated with CAR T-cell therapy. Neurotoxicity can be confounded by other causes of neurological dysfunction in these patients such as hospital delirium, chemotherapy toxicity, encephalopathy from infection, and subtle baseline neurologic dysfunction that may not be apparent at presentation. Next steps include prospective evaluation of patients with formal neurology evaluation prior to CAR T-cell therapy and periodically after treatment, in order to objectively monitor late neurologic effects of CAR T-cell therapy. 1. Fl, L. et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 20, (2019). 2. Jacobson, C. Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). in (ASH, 2020). 3. Dw, L. et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 25, (2019). Disclosures Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; Guidepoint: Consultancy; GLC: Consultancy; Kymera Therapeutics: Research Funding. Verma: Celgene: Consultancy; BMS: Research Funding; Stelexis: Current equity holder in publicly-traded company; Curis: Research Funding; Eli Lilly: Research Funding; Medpacto: Research Funding; Novartis: Consultancy; Acceleron: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; Throws Exception: Current equity holder in publicly-traded company.

Background: Sedative-hypnotic (SH) medications are often used to treat chronic insomnia, with potentially serious long-term side effects. The objective of this study is to evaluate an interprofessional SH deprescribing program within a community team-based, primary care practice, with or without cognitive behavioural therapy for insomnia (CBT-I). Methods: Retrospective chart review for patients referred to the team pharmacist for SH deprescribing from February 2016 to June 2019. Results: A total of 121 patients were referred for SH deprescribing, with 111 (92%) patients who attempted deprescribing (average age 69, range 29-97 years) and 22 patients who also received CBT-I. Overall, 36 patients (32%) achieved complete abstinence, and another 36 patients (32%) reduced their dosage by ≥50%. For the 36 patients who achieved complete abstinence, 26 (72%) patients remained abstinent at 6 months (9 patients resumed using SH and 1 patient was lost to follow-up). The proportion of patients achieving complete abstinence or reduced dosage of ≥50% (successful tapering) was higher with CBT-I than without CBT-I but did not reach statistical significance (77% vs 62%, p = 0.22). There were also no statistically significant differences detected in the success between those who took a benzodiazepine and those who took a Z-drug (67% vs 61%, p = 0.55) or for those who took SH daily and those who took them intermittently (67% vs 44%, p = 0.09). Conclusion: Almost two-thirds of patients participating in our pharmacist-led program were able to stop or taper their SH medications by ≥50%. The role of CBT-I in SH deprescribing remains to be further elucidated. Can Pharm J (Ott) 2021;154:xx-xx.

Objetivo: Sintetizar el efecto de la suplementación con ácidos grasos omega-3 sobre los componentes del Síndrome Metabólico (SM) en adultos con infección por el Virus de la Inmunodeficiencia Humana (VIH) en Tratamiento Antirretroviral de Gran Actividad (TARGA). Métodos: Llevamos a cabo una revisión sistemática y metaanálisis de ensayos clínicos aleatorizados. Definimos el SM según los criterios del ATP III basado en cinco componentes: triglicéridos, HDL, glucosa, circunferencia abdominal y presión arterial. Nuestra búsqueda primaria fue realizada en PubMed-MEDLINE, EMBASE, SCOPUS, Web of Science, CENTRAL, LILACS, SciELO hasta diciembre del 2019. Evaluamos el riesgo de sesgo con la herramienta Cochrane para ensayos clínicos. Estimamos el efecto conjunto mediante metaanálisis de efectos fijos y aleatorios en función a la heterogeneidad estadística. Calculamos diferencias de medias no estandarizadas (ΔMNE) y diferencia de medias estandarizadas (ΔME) con el estadístico d de Cohen (d-Cohen) para estimar el tamaño de efecto. Registramos el estudio en PROSPERO (CRD42019115749). Resultados: Encontramos un total de 13125 registros, a partir de los cuales incluimos 15 artículos en nuestro análisis: triglicéridos (15), HDL (5), glucosa (4), circunferencia abdominal (2) y presión arterial (1). Ocho artículos tuvieron alto riesgo de sesgo. Realizamos metaanálisis con nueve estudios para triglicéridos, observamos reducción significativa de los niveles [ΔMNE: -77,50 mg/dL (IC95% -117,72 a -37,28; I2: 27,2%)] con un efecto pequeño [Cohen-d: -0,43 (IC95% -0,62 a -0,25; I2:0,0%)]. Este efecto se acentúa cuando se acompaña de dieta y ejercicio [Cohen-d: -0,62 (IC95% -1,17 a -0,06; I2:0,0%)] o cuando se utiliza dosis mayores a 4 gr al día [Cohen-d: -0,58 (IC95% -0,93 a -0,23; I2:0,0%)]. No encontramos variación de acuerdo con los niveles basales de triglicéridos [Cohen-d: -0,43 (IC95% -0,62 a -0,25; I2:0,0%)]. Asimismo, efectuamos metaanálisis con cinco estudios para HDL, notamos que no hubo incremento significativo [ΔMNE:1,01 mg/dL (IC95% -1,35 a 3,37; I2: 0,0%)] con Cohen-d: 0,11 (IC95% -0,11 a 0,32; I2:0,0%). Al evaluar los otros componentes del SM detectamos alta heterogeneidad clínica y metodológica, por lo que no realizamos metaanálisis; no obstante, la totalidad de los estudios reportaron que no había efecto significativo de la suplementación sobre los niveles de glucosa sérica, circunferencia abdominal y presión arterial. Del mismo modo, no realizamos síntesis cuantitativa de los eventos adversos por la heterogeneidad y falta de reporte en los artículos individuales; sin embargo, la mayoría de los estudios informaron baja frecuencia de eventos adversos y sin diferencias con los producidos en los grupos de control. Conclusiones: En pacientes con infección por el VIH en TARGA la suplementación con ácidos grasos omega-3 reduce los niveles séricos de triglicéridos. No se observa efecto sobre los niveles séricos de HDL. La evidencia referente a los otros componentes del SM es escasa y apunta a que no habría efecto. Hubo baja frecuencia de eventos adversos fundamentalmente leves.

Increasing coronavirus disease 2019 (COVID-19) vaccination rates has been identified by the U.S. Centers of Disease Control and Prevention as critical to ending the COVID-19 pandemic.1 On May 10, 2021, the Pfizer-BioNTech COVID-19 vaccine (BNT162b2; Pfizer, Inc., New York, New York, and BioNTech SE, Mainz, Germany) was approved for emergency use authorization by the U.S. Food and Drug Administration for patients 12 years of age or older. Here we report a retrospective study describing the implementation of a COVID-19 vaccination program at our child and adolescent psychiatric hospital. To our knowledge, this is the first report detailing the administration of the COVID-19 vaccination in this setting.

Podocyte injury is important in development of diabetic nephropathy (DN). Although several studies have reported single cell-based RNA-seq of podocytes in type 1 DN (T1DN), the podocyte translating mRNA profile in type 2 DN (T2DN) has not been previously compared to that of T1DN. We analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26fsTRAP; eNOS-/-; db/db mice and compared it to streptozotocin-induced T1DN in podocin-Cre; Rosa26fsTRAP; eNOS-/- mice utilizing Translating Ribosome Affinity Purification (TRAP) and RNA-seq. Over 125 genes were highly enriched in the podocyte ribosome. More podocyte TRAP genes were differentially expressed in T2DN compared to T1DN. TGF-β signaling pathway genes were upregulated while MAPK pathway genes were downregulated only in T2DN while ATP binding and cAMP-mediated signaling genes were downregulated only in T1DN. Genes regulating actin filament organization and apoptosis increased while genes regulating VEGFR signaling and glomerular basement membrane components decreased in both type 1 and type 2 diabetic podocytes. A number diabetes-induced genes not previously been linked to podocyte injury were confirmed in both mouse and human DN. Differences and similarities in the podocyte translatome in T2DN and T1DN can identify factors underlying the pathophysiology of DN and novel therapeutic targets to treat diabetes-induced podocyte injury.

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted., Graphical abstract, Meng et al. report that the SARS-CoV-2 spike ΔH69/V70 has arisen multiple times. The deletion increases entry efficiency associated with increased cleaved spike in virions and can compensate for loss of infectivity. The B.1.1.7 spike requires ΔH69/V70 for efficient cell entry and cell-cell fusion activity.

Background: Attention processes may play a central role in shaping trajectories of socioemotional development. Individuals who are clinically anxious or have high levels of trait anxiety sometimes show attention biases to threat. There is emerging evidence that young children also demonstrate a link between attention bias to salient stimuli and broad socioemotional profiles. However, we do not have a systematic and comprehensive assessment of how attention biases, and associated neural and behavioral correlates, emerge and change from infancy through toddlerhood. This paper describes the Longitudinal Attention and Temperament study (LAnTs), which is designed to target these open questions.Method: The current study examines core components of attention across the first 2 years of life, as well as measures of temperament, parental psychosocial functioning, and biological markers of emotion regulation and anxiety risk. The demographically diverse sample (N = 357) was recruited from the area surrounding State College, PA, Harrisburg, PA, and Newark, NJ. Infants and parents are assessed at 4, 8, 12, 18, and 24 months. Assessments include repeated measures of attention bias (via eye-tracking) in both infants and parents, and measures of temperament (reactivity, negative affect), parental traits (e.g., anxiety and depression), biological markers (electrophysiology, EEG, and respiratory sinus arrythmia, RSA), and the environment (geocoding, neighborhood characteristics, perceived stress). Outcomes include temperamental behavioral inhibition, social behavior, early symptom profiles, and cellular aging (e.g., telomere length).Discussion: This multi-method study aims to identify biomarkers and behavioral indicators of attentional and socioemotional trajectories. The current study brought together innovative measurement techniques to capture the earliest mechanisms that may be causally linked to a pervasive set of problem behaviors. The analyses the emerge from the study will address important questions of socioemotional development and help shape future research. Analyses systematically assessing attention bias patterns, as well as socioemotional profiles, will allow us to delineate the time course of any emerging interrelations. Finally, this study is the first to directly assess competing models of the role attention may play in socioemotional development in the first years of life.

RTS,S/AS01 (GSK) is the world’s first malaria vaccine. However, despite initial efficacy of almost 70% over the first 6 months of follow-up, efficacy waned over time. A deeper understanding of the immune features that contribute to RTS,S/AS01-mediated protection could be beneficial for further vaccine development. In two recent controlled human malaria infection (CHMI) trials of the RTS,S/AS01 vaccine in malaria-naïve adults, MAL068 and MAL071, vaccine efficacy against patent parasitemia ranged from 44% to 87% across studies and arms (each study included a standard RTS,S/AS01 arm with three vaccine doses delivered in four-week-intervals, as well as an alternative arm with a modified version of this regimen). In each trial, RTS,S/AS01 immunogenicity was interrogated using a broad range of immunological assays, assessing cellular and humoral immune parameters as well as gene expression. Here, we used a predictive modeling framework to identify immune biomarkers measured at day-of-challenge that could predict sterile protection against malaria infection. Using cross-validation on MAL068 data (either the standard RTS,S/AS01 arm alone, or across both the standard RTS,S/AS01 arm and the alternative arm), top-performing univariate models identified variables related to Fc effector functions and titer of antibodies that bind to the central repeat region (NANP6) of CSP as the most predictive variables; all NANP6-related variables consistently associated with protection. In cross-study prediction analyses of MAL071 outcomes (the standard RTS,S/AS01 arm), top-performing univariate models again identified variables related to Fc effector functions of NANP6-targeting antibodies as highly predictive. We found little benefit–with this dataset–in terms of improved prediction accuracy in bivariate models vs. univariate models. These findings await validation in children living in malaria-endemic regions, and in vaccinees administered a fourth RTS,S/AS01 dose. Our findings support a “quality as well as quantity” hypothesis for RTS,S/AS01-elicited antibodies against NANP6, implying that malaria vaccine clinical trials should assess both titer and Fc effector functions of anti-NANP6 antibodies.

This issue of Essays in Biochemistry explores lipid mediators — biologically active metabolites formed by enzymic and non-enzymic oxidation of polyunsaturated fatty acids. These can be exported across the cell membrane into the extracellular space, where they activate cell surface receptors to stimulate the cells of origin (autocrine) or nearby cells (paracrine). Lipid mediators are involved in many physiological processes, which may become dysregulated during ageing and in lipid-related diseases such as diabetes, atherosclerosis, arthritis, cancer, Alzheimer’s disease and metabolic syndrome. Following the death in March 2020 of Professor Mike Wakelam, with the loss of his major input into the lipid signalling field, Portland Press and Guest Editors John Harwood and Emyr Lloyd-Evans decided to dedicate this issue to his memory. This Editorial briefly recalls his work and influence.

Median arcuate ligament syndrome (MALS) is the chronic symptomatic compression of the celiac artery by the median arcuate ligament. A known potential sequela of MALS is celiac artery aneurysm, which could predispose the diseased artery to dissection. However, the presence of celiac artery dissection and MALS is yet to be reported. Here, we present a case of MALS with a coincident celiac artery aneurysm and dissection.

Pulmonary tuberculosis (PTB) continues to be a public health problem and is still the leading cause of morbidity and mortality in the Philippines despite the preventive and control strategies done by different agencies. This study aimed to explore PTB in the workplace particularly in the business process outsourcing (BPO) industry, an area with limited studies. Descriptive comparative and correlational methods were used to assess the employees' level of knowledge and level of agreement to myths about PTB. 243 employees were randomly selected to participate in this study. T-test of independence, one-way ANOVA and post hoc Tukey were used to test for the significant and specific differences among variables. Results showed educational attainment (p=0.007) and length of service (p=0.008) to affect the level of knowledge, while educational attainment (p

Introducción: el aumento de la esperanza de vida y del número de personas mayores de 65 años, suponen un cambio en los patrones sociodemográficos, por ello los servicios sanitarios están evolucionando, siendo un gran ejemplo el proyecto “En mi casa”. El objetivo de este trabajo consiste en indagar e investigar el proyecto “En mi casa”, así como determinar el papel de enfermería y las bases científicas de dicho proyecto. Material y métodos: de los 147 artículos encontrados en metabuscadores como Tripdatabase o fuentes de información secundaria como Pubmed, 12 fueron los seleccionados, además de la utilización de otros buscadores científicos para completar la investigación. Resultados: en torno el 90% de los ancianos manifiesta su deseo de residir en sus domicilios durante la plenitud desu viday 4 decada 5 mayoresrefieren que la atención domiciliaria posee una red de apoyo más estructurada que la atención residencial. El 14 % de los ancianos que viven solos refieren abandono familiar. En el 2031, el 33,2% de las personas mayores vivirán solas en su domicilio. Discusión: debido a la pérdida de contacto familiar, así como de toma de decisiones y cambios en el estilo de vida de los ancianos que conviven en residencias, surge el proyecto “En mi casa”, que se inspira y sigue las bases del modelo nórdico Housing, el cual pretende erradicar esos ítems negativos mencionados con anterioridad, favoreciendo la individualidad, autonomía e intimidad familiar de cada una de esas personas de avanzada edad. Conclusiones: tanto el proyecto “En mi casa” como “A gusto en mi casa” llevan a cabo una serie de actividades y ayudas para promover la independencia tanto si están institucionalizados o habitan en su propio domicilio.

Comparing techniques of general anesthesia and regional anesthesia in arthroscopic shoulder surgery, some studies have shown differences in the intensity of immediate postoperative pain and neuroendocrine response, but the inflammatory response when using balanced general anesthesia (BGA) vs. an ultrasound-guided (USG) single-dose interscalene block (SDIB) has not been compared.In a single-center, prospective, randomized clinical trial, the inflammatory response of 2 groups of 10 patients scheduled to undergo arthroscopic shoulder surgery was evaluated through measurement of a panel of cytokines that act on cells of the adaptive immune response to promote or inhibit inflammation, chemokines involved in chemotaxis, the erythrocyte sedimentation rate (ESR), the high-sensitivity C-reactive protein (CRP) level, and the white blood cell (WBC) count in 3 blood samples (before anesthesia, immediately postoperatively, and 24 hours postoperatively) with 2 types of anesthesia (BGA vs. USG SDIB). Postoperative pain intensity (immediately, at 12 hours, and at 24 hours) was also assessed.The ESR and CRP level increased significantly at 24 hours after surgery; however, the increase in ESR (P.0001) and CRP level (P.0001) was lower in the USG SDIB group. Significant increases in the levels of soluble interleukin 2 receptor α (P = .022) and interleukin 12p40 (P = .016) occurred in the immediate postoperative period in the USG SDIB group. Immediate postoperative pain showed a significant increase (P.001) in the BGA group.In arthroscopic shoulder surgery, the use of a USG SDIB compared with the use of BGA is possibly associated with improved pain control in the immediate postoperative period and lower immunosuppression, even at 24 hours after surgery.

Physical exercise has the ability to alter the measurements of the body related to esthetic. The objective of the present study was to compare the body image and body esthetic between two groups of women with different levels of physical activity. We evaluated 79 women who were divided into 2 groups: 39 women with low or moderate levels of physical activity, and 40 women with high levels of physical activity according to the International Physical Activity Questionnaire (IPAQ). Anthropometric and body composition measurements were taken using the InBody S10 multifrequency device (InBody Co., Eonju-ro, Gangnam-gu, Seoul, South Korea). The scale of silhouettes, which is composed of 9 engravings of body images, was used to verify the body image, as well as the Portuguese version of the Body Shape Questionnaire (BSQ) validated for university students. The group of evaluators was composed of twenty physical education professionals of both sexes, ten male and ten female. The group with low/moderate levels of physical activity, as expected, showed a lower amount (minutes per week) of physical activity of mild, moderate and vigorous intensity when compared with the group with high levels of physical activity (p 0.05). The overall body esthetic score, attributed only by the male and only by the female evaluators, did not differ significantly (p > 0.05). We concluded that the level of physical activity did not influence the body image and body esthetic of the women.

Clostridioides difficile is the primary cause of antibiotic-associated diarrhea and colitis, a healthcare-associated intestinal disease resulting in a significant fatality rate. Colonization of the gut is critical for C. difficile pathogenesis. The bacterial molecules essential for efficient colonization therefore offer great potential as vaccine candidates. Here we present findings demonstrating that the C. difficile immunogenic lipoprotein CD0873 plays a critical role in pathogen success in vivo. We found that in a dixenic colonization model, a CD0873-positive strain of C. difficile significantly outcompeted a CD0873-negative strain. Immunization of mice with recombinant CD0873 prevented long-term gut colonization and was correlated with a strong secretory IgA immune response. We further present high-resolution crystal structures of CD0873, at 1.35–2.50 A resolutions, offering a first view of the ligand-binding pocket of CD0873 and provide evidence that this lipoprotein adhesin is part of a tyrosine import system, an amino acid key in C. difficile infection. These findings suggest that CD0873 could serve as an effective component in a vaccine against C. difficile.

Purpose of review The purpose of the review is to discuss recent advances in microRNA (miRNA) regulation of lipid metabolism and highlight the importance of miRNA-mediated gene regulation in dyslipidemia and fatty liver disease. This article reviews examples of miRNAs that bridge disparate metabolic pathways in the liver. For example, we highlight miRNAs that are regulated by the sterol-sensing pathway in the liver that in turn regulate cellular or systemic cholesterol, fatty acid, and glucose levels. Recent findings The most widely studied of these miRNAs are miR-33a/b; however, we recently reported that miRNAs in the miR-183/96/182 cluster are also likely regulated by hepatic cholesterol content and mediate the observed glucose-lowering effects of the bile acid sequestrant colesevelam through the sterol-sensing pathway. In addition, several other hepatic and adipose miRNAs have been recently demonstrated to be key regulators of cellular lipid synthesis, storage, and catabolism, as well as systemic lipid metabolism. Moreover, many of these miRNAs are altered in fatty liver disease and dyslipidemia. Summary miRNAs are not just fine-tuners of lipid metabolism, but critical regulatory factors in lipid homeostasis and health. Loss of these miRNA regulatory modules very likely contributes to the underlying metabolic defects observed in lipid disorders.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubular disorder caused by mutations in genes that encode renal tight junction proteins claudin-16 or claudin-19, which are responsible for magnesium and calcium paracellular reabsorption in the thick ascending limb of Henle’s loop. Progressive renal failure is frequently present, and most of the patients require renal replacement therapy still during adolescence. In this case report, we describe a new homozygous missense mutation on CLDN16 gene (c.592G>C, Gly198Arg) in a 24-year-old male patient diagnosed with FHHNC after clinical investigation due to incidental detection of altered routine laboratorial tests, who was firstly misdiagnosed with primary hyperparathyroidism. In addition, it illustrates an atypical presentation of this disease, with late onset of chronic kidney disease, improving the phenotype-genotype knowledge of patients with FHHNC.

To identify differences in perception on multi-drug-resistant (MDR) organisms and their management at intensive care units (ICU). A cross-sectional survey was conducted. A proposal addressing a pathogen priority list (PPL) for ICU, arising from the TOTEM study, was compared with a sample of global experts in infections in critically ill patients. The survey was responded by 129 experts. Globally, ESBL Enterobacteriaceae, followed by carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae, were the main concerns. Some differences in opinion were identified between 63 (49%) ICU physicians (ICU/anesthesiology) and 43 (33%) infectious disease consultants (ID physicians/microbiologists). The pathogens most concerning in the ICU for intensivists were ESBL Enterobacteriaceae (38%) versus carbapenem-resistant A. baumannii (48.3%) for ID consultants, (p 0.05). Increasing number of ID consultants over intensivists (26% vs 14%) reported difficulty in choosing initial therapy for carbapenem-resistant A. baumannii. For intensivists, the urgent measures to limit development of antibiotic resistance were headed by cohort measures (26.3%) versus increasing nurse/patient ratio (32.5%) for ID consultants, (p 0.05). Regarding effectiveness to prevent MDR development and spread, education programs (42.4%) were the priority for intensivists versus external consultation (35.7%) for ID consultants. Finally, both groups agreed that carbapenem resistance was the most pressing concern ( 70%) regarding emerging resistance. Differences in priorities regarding organisms, infection control practices, and educational priorities were visualized between ID/clinical microbiologists and ICU/anesthesiologists. Multi-disciplinary collaboration is required to achieve best care for ICU patients with severe infections.

Introducción: La Diabetes Mellitus (DM) es una enfermedad metabólica que se caracteriza por presentar valores elevados de glicemia debido a la disminución total o parcial de la insulina en el organismo o resistencia a la misma por los tejidos periféricos. Las complicaciones de la DM son frecuentes, por lo tanto se hace necesario incentivar la búsqueda de nuevos fármacos hipoglucemiantes que complementen el protocolo actual de tratamiento. Las complicaciones de la DM son cada vez más frecuentes, por ende se requiere incentivar la búsqueda de nuevas alternativas terapéuticas que complementen el protocolo actual de tratamiento de la DM. La planta medicinal Salvia amarissima Ortega es una planta abundante en el Estado de México, usada ampliamente en la medicina tradicional para el control de la DM. Objetivo: comprobar el efecto hipoglucemiante de Salvia amarissima Ortega, para lo cual se realizó un estudio experimental, tipo exploratorio, descriptivo y analítico. Material y Métodos: se determinó la DL50 empleando el método de Lorke y se realizó una curva de tolerancia a la glucosa con ratones macho de la cepa C57BL/6J con un peso de 25 g + 5 g, con dextrosa al 35% a dosis de una centésima parte de su peso, se dividieron en nueve grupos con una n:6 cada grupo. El extracto etanólico se administró vía intragástrica, se midió la glucosa a los 0, 30 y 60 y 90 minutos. Resultados: Las hojas de Salvia amarissima Ortega presenta dosis letal 50 a los 5,3 g/kg de peso y presenta actividad hipoglucemiante a dosis de 125, 250, 500 y 1000 mg/kg de peso. Introduction: Diabetes mellitus (DM) is a metabolic disease characterized by high blood glucose levels due to the total or partial decrease of insulin in the body or insulin resistance by peripheral tissues. Complications of DM are frequent, and as a consequence, it is necessary to encourage the search for new therapeutic alternatives that complement the current DM treatment protocol. The Salvia amarissima Ortega is an abundant medicinal plant in the State of Mexico, widely used in traditional medicine to control DM. General objective: To identify the hypoglycemic effect of Salvia amarissima Ortega. With this objective, an experimental, exploratory, descriptive, and analytical study was carried out. Materials and Methods: the LD50 was determined using Locke’s method, and glucose tolerance curve was performed with male mice of the C57BL/6J strain weighing 25 g + 5 g, with 35% of dextrose at doses of onehundredth of their weight, divided into nine groups with an n:6 each group. The ethanolic extract was administered intragastric route, and glucose was measured at 0, 30, and 60 and 90 minutes. Results: Salvia amarissima Ortega leaves have a lethal dose of 50 at 5,3 g/kg of weight and have a hypoglycemic activity at 125, 250, 500, and 1000 mg/kg of weight.

Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E-deficient background. When mice were placed on a western type diet for 16 weeks, we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms. With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the β-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.

Wire-guided localisation (WGL) has been the mainstay for localising non-palpable breast lesions before excision. Due to its limitations, various wireless alternatives have been developed. In this prospective study, we evaluate the role of radiation-free wireless localisation using the SAVI SCOUT® system at the London Breast Institute. A total of 72 reflectors were deployed in 67 consecutive patients undergoing breast conserving surgery for non-palpable breast lesions. The mean interval between deployment and surgery for the therapeutic cases was 18.8 days (range: 0–210). The median deployment duration was 5 min (range: 1–15 min). The mean distance from the lesion was 1.1 mm (median distance: 0, range: 0–20 mm). The rate of surgical localisation and retrieval of the reflector was 98.6% and 100%, respectively. The median operating time was 28 min (range: 15–55 min) for the therapeutic excision of malignancy and 17 min (range: 15–24) for diagnostic excision. The incidence of reflector migration was 0%. Radial margin positivity in malignant cases was 7%. The median weight for malignant lesions was 19.6 g (range: 3.5–70 g). Radiologists and surgeons rated the system higher than WGL (93.7% and 98.6%, respectively, 60/64 and 70/71). The patient mean satisfaction score was 9.7/10 (n = 47, median = 10, range: 7–10). One instance of signal failure was reported. In patients who had breast MRI after the deployment of the reflector, the MRI void signal was &lt, 5 mm (n = 6). There was no specific technique-related surgical complication. Our study demonstrates that wire-free localisation using SAVI SCOUT® is an effective and time-efficient alternative to WGL with excellent physician and patient acceptance.