The mevalonate pathway contributes to breast primary tumorigenesis and lung metastasis.

The mevalonate pathway plays an important role in breast cancer and other tumor types. However, many issues remain obscure as yet regarding its mechanism of regulation and action. In the present study, we report that the expression of mevalonate pathway enzymes is mediated by the RHO guanosine nucleotide exchange factors VAV2 and VAV3 in a RAC1- and sterol regulatory element-binding factor (SREBF)-dependent manner in breast cancer cells. Furthermore, in vivo tumorigenesis experiments indicated that the two most upstream steps of this metabolic pathway [3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)] are important for primary tumorigenesis, angiogenesis, and cell survival in breast cancer cells. HMGCR, but not HMGCS1, is also important for the extravasation and subsequent fitness of breast cancer cells in the lung parenchyma. Genome-wide expression analyses revealed that HMGCR influences the expression of gene signatures linked to proliferation, metabolism, and immune responses. The HMGCR-regulated gene signature predicts long-term tumor recurrence but not metastasis in cohorts of nonsegregated and chemotherapy-resistant breast cancer patients. These results reveal a hitherto unknown, VAV-catalysis-dependent mechanism involved in the regulation of the mevalonate pathway in breast cancer cells. They also identify specific mevalonate-pathway-dependent processes that contribute to the malignant features of breast cancer cells.

Restauração transcirúrgica: passo a passo / Transsurgical restoration: step by step

Sabe-se que para uma restauração ser considerada um sucesso clínico é preciso que haja uma concomitância saudável entre a estrutura dentária, o material restaurador e as estruturas biológicas periodontais. As restaurações transcirúrgicas caracterizam-se como procedimentos alternativos para possibilitar a restauração de dentes com cárie dentária extensa, restaurações subgengivais desadaptadas e fraturas. O presente estudo teve como objetivo realizar um relato de caso de um procedimento cirúrgico-restaurador, através de uma técnica de restauração transcirúrgica. Este estudo tem como justificativa relatar um caso clínico, colaborando com maiores informações sobre a escolha da técnica a ser empregada, mostrando em quais situações devemos escolher uma restauração transcirúrgica e quais seus benefícios. Também, salientar se devemos fazer a recuperação do espaço biológico do periodonto ou não(AU)

It is known that for a restoration to be considered a clinical success, there must be a healthy concomitance between the tooth structure, the restorative material and the periodontal biological structures. Transsurgical restorations are characterized as alternative procedures to enable the restoration of teeth with extensive dental caries, maladapted subgingival restorations and fractures. The present study aims to carry out a case report of a surgical-restorative procedure, using a transsurgical restoration technique. This study is justified by reporting a clinical case, providing more information on the choice of technique to be used, showing in which situations we should choose a transsurgical restoration and what its benefits are. Also, highlight whether we should recover the biological space of the periodontium or not(AU)

Restauração indireta em resina composta: um relato de prontuário / Indirect resin composite restoration: a dental record report

Restaurações diretas em resina composta são amplamente utilizadas em odontologia para restaurar dentes posteriores. Todavia, quando há grande destruição coronária, onde a distância do istmo excede dois terços da distância intercuspídea, as restaurações indiretas em resina composta são indicadas. O presente estudo teve como objetivo relatar a análise de um prontuário de um paciente que recebeu uma restauração indireta em resina composta em dente posterior amplamente destruído. Através da análise de prontuários de pacientes atendidos nas disciplinas de Estágios Supervisionados do Curso de Odontologia da FSG Centro Universitário no ano de 2023, foi selecionado um prontuário de um paciente que compareceu a clínica odontológica da FSG com uma restauração em amálgama fraturada com reparo em resina composta que apresentou sintomatologia dolorosa. O procedimento diagnóstico ocorreu através de exame clínico e radiográfico, que constatou a indicação de substituição da restauração insatisfatória e realização de uma restauração indireta em resina composta. Os resultados estéticos e funcionais apresentados demostraram a viabilidade da técnica restauradora indireta em resina composta para reabilitar dentes posteriores com ampla destruição coronária(AU)

Direct composite resin restoration are widely used in dentistry to restore posterior teeth. However, when there is large coronary destruction, that the distance from the isthmus exceeds two- thirds of the intercuspal distance, indirect composite resin restorations are indicated. This study aimed to report the analysis of a dental record of a patient who received an indirect restoration in composite resin in a badly destroyed posterior tooth. Through the analysis of dental records of patients seen in the disciplines of Supervised Internship of the Dentistry Course at FSG Centro Universitário in the year 2023, the dental record of a patient who attended the FSG dental clinic with fractured amalgam restoration with composite resin repair was selected who had painful symptoms. The diagnostic procedure took place through clinical and radiographic examination, which revealed the indication of replacing the unsatisfactory restoration and carrying out an indirect restoration in composite resin.The aesthetic and functional results presented demonstrated the viability of the indirect composite resin restoration technique for rehabilitating posterior teeth with extensive coronal destruction(AU)

Termo de consentimento livre e esclarecido e sua relação com os procedimentos de preenchimento labial / Free and informed consent terms and its relationship with lip filling procedures

Introdução: Na medida em que envelhecemos os lábios estreitam-se, ocasionando perda de volume e contorno e como forma de minimizar este efeito fisiológico o preenchimento labial de escolha utilizado é o ácido hialurônico. É possível perceber efeitos adversos advindos do emprego deste material, e pelo fato da informação ao paciente ser assegurada pelo Código de Defesa do Consumidor e pelo fato da necessidade dos Cirurgiões-Dentistas terem de esclarecer seus pacientes, o Termo de Consentimento Livre e Esclarecido tornase necessário. Objetivo: identificar, por meio de aplicação de questionário, a percepção de profissionais que trabalham com Harmonização Orofacial em relação a necessidade do emprego do Termo de Consentimento Livre e Esclarecido (TCLE). O questionário apresentou 6 perguntas objetivas, que foram disponibilizadas na plataforma Google Forms®. Material e Método: os dados obtidos foram tabulados em uma planilha eletrônica do programa Microsoft Excel e após analisados descritivamente através de tabelas de frequência, porcentagens e gráficos estatísticos. Resultados: dentre os entrevistados foi constatado que a maioria, 87,5% dos especialistas em Harmonização Orofacial realizam o procedimento de preenchimento labial em sua rotina clínica, e 12,5% não. Conclusão: no presente estudo identificamos que os especialistas realizam o emprego do TCLE, em sua maioria, porém, alguns destes ainda negligenciam o seu uso(AU)

Introduction: As we age, the lips become thinner and to minimize this effect, the lip filler used is hyaluronic acid. It is possible to notice adverse effects arising from the use of this material, and it is extremely important that Dental Surgeons have to clarify their patients, the Free and Informed Consent Form becomes necessary. Objective: to identify, through the application of a questionnaire, the perception of professionals who work with Orofacial Harmonization in relation to the need to use the Free and Informed Consent Form (TCLE). The questionnaire presented 6 objective questions, which were made available on the Google Forms® platform. Materials and Methods: the data obtained were tabulated in a Microsoft Excel spreadsheet and then analyzed descriptively using frequency tables, percentages and graphs. Results: among those interviewed, it was found that the majority, 87.5% of specialists in Orofacial Harmonization perform the lip filling procedure in their clinical routine, and 12.5% do not. With the high percentage of 59.4%, it was possible to verify that the majority of professionals perform 1 to 3 procedures per month; 31.3% perform 4 to 9 procedures per month; and 9.4% of 10 or more monthly procedures. Conclusion: in the present study it was possible to identify that the majority of specialists in Orofacial Harmonization use the informed consent form, however, some of them still neglect its use(AU)

Restauração em resina composta semidireta em dente posterior: relato de caso / Semi-direct composite restoration in posterior toth: a case report

A escolha da técnica restauradora desempenha papel fundamental na eficácia e duração de um tratamento reabilitador. O objetivo deste relato de caso foi descrever a utilização da técnica semidireta para a confecção de uma restauração em resina composta em um primeiro molar inferior. A paciente apresentava uma restauração insatisfatória no dente 36, que necessitava ser substituída devido à infiltração por cárie. Optou-se pela técnica semidireta devido à amplitude da cavidade, que envolvia estruturas de suporte, e pela combinação das vantagens das abordagens direta e indireta. O procedimento envolveu a remoção de tecido cariado, a aplicação de hidróxido de cálcio pasta, seguida da aplicação de uma fina camada de ionômero de vidro e, posteriormente, resina fluída para realizar o selamento dentinário. O preparo foi realizado seguindo os princípios necessários. O elemento em questão foi moldado com silicone de adição e o arco antagonista, com alginato. Ambos modelos foram vertidos com silicone para modelos semirrígidos e montados em oclusor de peças de brinquedo. A restauração semidireta foi confeccionada em resina composta Filtek Z350 XT, respeitando a anatomia do dente 36. Pigmentos foram utilizados para aprimorar detalhes estéticos. Após acabamento e polimento, a peça foi condicionada e cimentada com cimento dual Relyx Ultimate. Pode-se concluir que a abordagem restauradora por meio da técnica semidireta construída em modelo semirrígido é uma opção terapêutica conservadora e vantajosa para dentes com extensa destruição coronária. Essa técnica possibilita a restauração de forma eficaz, garantindo tanto a estética quanto a função adequada do dente afetado(AU)

The choice of restorative technique plays a fundamental role in the effectiveness and duration of rehabilitation treatment. The objective of this case report was to describe the use of the semi-direct technique to create a composite resin restoration in a lower first molar. The patient had an unsatisfactory restoration on tooth 36, which needed to be replaced due to cavity infiltration. The semi-direct technique was chosen due to the amplitude of the cavity, which involved support structures, and the combination of advantages of the direct and indirect approaches. The procedure involved the removal of carious tissue, and the application of calcium hydroxide paste, followed by the application of a thin layer of glass ionomer and, subsequently, fluid resin to seal the dentin. The preparation was carried out following the necessary principles. The element in question was molded with addition silicone and the antagonist arch was molded with alginate. Both models were poured with silicone for semi-rigid models and mounted on toy parts occluders. The semi-direct restoration was made in Filtek Z350 XT composite resin, respecting the anatomy of tooth 36. Pigments were used to improve aesthetic details. After finishing and polishing, the piece was conditioned and cemented with Relyx Ultimate dual cement. It can be concluded that the restorative approach using the semi-direct technique built on a semi-rigid model is a conservative and advantageous therapeutic option for teeth with extensive coronal destruction. This technique allows for effective restoration, ensuring both the aesthetics and adequate function of the affected tooth(AU)

Age-dependent Powassan virus lethality is linked to glial cell activation and divergent neuroinflammatory cytokine responses in a murine model.

Powassan virus (POWV) is an emergent tick-borne flavivirus that causes fatal encephalitis in the elderly and long-term neurologic sequelae in survivors. How age contributes to severe POWV encephalitis remains an enigma, and no animal models have assessed age-dependent POWV neuropathology. Inoculating C57BL/6 mice with a POWV strain (LI9) currently circulating in Ixodes ticks resulted in age-dependent POWV lethality 10-20 dpi. POWV infection of 50-week-old mice was 82% fatal with lethality sequentially reduced by age to 7.1% in 10-week-old mice. POWV LI9 was neuroinvasive in mice of all ages, causing acute spongiform CNS pathology and reactive gliosis 5-15 dpi that persisted in survivors 30 dpi. High CNS viral loads were found in all mice 10 dpi. However, by 15 dpi, viral loads decreased by 2-4 logs in 10- to 40-week-old mice, while remaining at high levels in 50-week-old mice. Age-dependent differences in CNS viral loads 15 dpi occurred concomitantly with striking changes in CNS cytokine responses. In the CNS of 50-week-old mice, POWV induced Th1-type cytokines (IFNγ, IL-2, IL-12, IL-4, TNFα, IL-6), suggesting a neurodegenerative pro-inflammatory M1 microglial program. By contrast, in 10-week-old mice, POWV-induced Th2-type cytokines (IL-10, TGFß, IL-4) were consistent with a neuroprotective M2 microglial phenotype. These findings correlate age-dependent CNS cytokine responses and viral loads with POWV lethality and suggest potential neuroinflammatory therapeutic targets. Our results establish the age-dependent lethality of POWV in a murine model that mirrors human POWV severity and long-term CNS pathology in the elderly. IMPORTANCE: Powassan virus is an emerging tick-borne flavivirus causing lethal encephalitis in aged individuals. We reveal an age-dependent POWV murine model that mirrors human POWV encephalitis and long-term CNS damage in the elderly. We found that POWV is neuroinvasive and directs reactive gliosis in all age mice, but at acute stages selectively induces pro-inflammatory Th1 cytokine responses in 50-week-old mice and neuroprotective Th2 cytokine responses in 10-week-old mice. Our findings associate CNS viral loads and divergent cytokine responses with age-dependent POWV lethality and survival outcomes. Responses of young mice suggest potential therapeutic targets and approaches for preventing severe POWV encephalitis that may be broadly applicable to other neurodegenerative diseases. Our age-dependent murine POWV model permits analysis of vaccines that prevent POWV lethality, and therapeutics that resolve severe POWV encephalitis.

Guided Endodontic Treatment of Mandibular Incisor with Pulp Canal Obliteration following Dental Trauma: A Case Report.

Root canal obliteration is caused by hard tissue apposition and is often associated with teeth with a history of trauma, orthodontic movement, caries reaction, restorative procedures near the pulp chamber, and teeth of elderly patients. Preoperative planning of root canal treatment should be thorough and include an assessment of the patient's signs and symptoms in addition to the evaluation of complementary examinations. In a 27-year-old patient with dyschromia of the lower central incisor, a history of dental trauma, and a positive response to vertical percussion, an initial periapical radiograph was obtained that showed calcification of the canal and presence of a periapical lesion. The patient presented with pain on chewing, a positive response to palpation and a vertical percussion test. The diagnosis was symptomatic apical periodontitis. A cone-beam computed tomography scan was requested and a surface scan was performed to establish a static guide. The root canal was accessed in the middle third of the root and the canal was located using a minimally invasive approach. The root canal was treated conventionally. Results obtained showed the success of the treatment after a 3-year clinical and radiographic follow-up. Therefore, the use of an endodontic guide in cases of calcified canals significantly reduces the clinician's working time and offers a more predictable approach to the treatment of these pathologies.

A single center, inter-observer evaluation of vestibular schwannoma stereotactic radiosurgery and its dosimetric impact.

The aim of this work was to evaluate the inter- and intra-observer variation in contouring vestibular schwannoma (VS) and the organs-at-risk (OAR), and its dosimetric impact in Volumetric Modulated Arc Therapy (VMAT). Three VS typical cases were contoured by four clinicians. The Agreement Volume Index (AVI) appeared to be notably higher in VS than in OARs, such that the dose coverage of VS is fairly robust. In OARs, the largest variation was +1.02Gy in dmax for the brainstem, +0.78Gy in dmean for the cochlea and +1.05Gy in dmax of the trigeminal nerve. Accordingly, it was decided that all VS delineations for stereotactic radiosurgery (SRS), and all frame-based SRS contouring in general, should always be reviewed by a second physician. In addition, the retrospective presentation of VS cases at daily peer review meetings has also been adopted to ensure that the consensus is constantly updated, as well as for training purposes.

Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease: A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of inclisiran in participants with atherosclerotic cardiovascular disease (ASCVD) from ORION-10 and ORION-11 stratified by key patient characteristics. PATIENTS AND METHODS: Participants were randomized 1:1 to receive 300 mg inclisiran sodium (284 mg inclisiran) or placebo on days 1, 90, 270, and 450, alongside background lipid-lowering therapy. This pooled, post hoc analysis stratified participants with ASCVD by sex, age, race, kidney function, body mass index, and glycemic status. Co-primary endpoints were percentage changes in low-density lipoprotein cholesterol (LDL-C) from baseline to day 510, and after day 90 and up to day 540 (time-adjusted). LDL-C goal attainment and safety were also assessed. RESULTS: This analysis of 2975 participants included: female, n=827; Black, n=213; 75 years of age or older, n=458; obese, n=1474; diabetes, n=1182; and moderate-to-severe chronic kidney disease, n=538. Mean baseline LDL-C levels in the total ASCVD population were balanced between treatment arms (inclisiran, 103.4 mg/dL; placebo, 102.0 mg/dL). With inclisiran, mean placebo-corrected percentage changes in LDL-C from baseline were -51.5% (95% CI, -54.0% to -49.0%) and -52.1% (95% CI, -53.9% to -50.4%) to day 510 and day 540 (time-adjusted), respectively; this was consistent across subgroups. LDL-C less than 55 mg/dL at 1 or more visits was reached by 87.6% of participants receiving inclisiran. The inclisiran safety profile was consistent across subgroups. CONCLUSION: Twice-yearly inclisiran (after initial and 3-month doses) was well-tolerated and provided significant, consistent LDL-C reductions for up to 18 months in participants with ASCVD independent of key patient characteristics (ORION-10 [Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol]; NCT03399370 and ORION-11 [Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol]; NCT03400800).

EFisioTrack System for Monitoring Therapeutic Exercises in Patients with Shoulder Orthopedic Injuries in a Hospital Setting: A Pilot Feasibility Study.

To assess the effects of the eFisioTrack monitoring system on clinical variables in patients with prescribed physiotherapy for shoulder injuries, twenty-four adult patients with shoulder orthopaedic injuries who underwent physical therapy treatment in a hospital setting participated in the study (twelve in the experimental group and twelve as controls). Clinical outcome measures were shoulder function and pain (Constant-Murley Score and Disabilities of the Arm, Shoulder, and Hand or DASH score). Each variable was measured by a blinded physiotherapist at baseline and at one month follow-up. Patients performed the prescribed exercises either supervised by the physiotherapist (control group) or in a separate room without therapist supervision (experimental group). There were no statistically significant differences between groups before treatment or at follow-up for any outcomes (p ≥ 0.05). There was a statistically significant decrease (p ≤ 0.05) of at least 10 points in both groups for the DASH score at follow-up. Differences in the total score and subjective components of the Constant-Murley were also evidenced within groups. The use of the eFisioTrack system showed similar results in clinical measures compared to those performed under the direct supervision of the physiotherapist. This approach might be suitable for providing an effective shoulder exercise program at home.

Morbidity burden of imported chronic schistosomiasis among West African migrants.

BACKGROUND: Past exposure to schistosomiasis is frequent among migrants from endemic countries, and chronic untreated infection may lead to long-term morbidities. METHODS: We carried out a prospective population-based cross-sectional study among migrants from endemic Sub-Saharan countries living in Barcelona, Spain. Participants had not been previously diagnosed or treated for schistosomiasis. Clinical signs and symptoms were scrutinised through a systematic revision of electronic medical records and an on-site standardised questionnaire, and blood and urine samples were screened for Schistosoma. FINDINGS: We recruited 522 eligible participants, 74.3% males, mean age 42.7 years (SD=11.5, range 18-76), Overall, 46.4% were from Senegal and 23.6% from Gambia. They had lived in the European Union for a median of 16 years (IQR 10-21). The prevalence of a Schistosoma-positive serology was 35.8%. S. haematobium eggs were observed in urine samples in 6 (1.2%) participants. The most prevalent symptoms among Schistosoma-positive participants were chronic abdominal pain (68.8%, OR=1.79; 95%CI 1.2-2.6), eosinophilia (44.9%, OR=2.69; 95%CI 1.8-4.0) and specific symptoms associated with urinary schistosomiasis, like self-reported episodes of haematuria (37.2%; OR=2.47; 95%CI 1.6-3.8), dysuria (47.9%, OR=1.84; 95%CI=1.3-2.7) and current renal insufficiency (13.4%; OR=2.35; 95%CI=1.3-4.3). We found a significant prevalence of gender-specific genital signs and symptoms among females (mainly menstrual disorders) and males (erectile dysfunction and pelvic pain). Individuals typically presented with a multitude of interconnected symptoms, most commonly chronic abdominal pain, which are often disregarded. CONCLUSIONS: Despite the lack of urine parasite identification, the high incidence of clinical signs and symptoms strongly correlated with a positive schistosomiasis serology suggests the existence of a heavy clinical burden among long-term West African migrants living for years/decades in the study region. More research is urgently required to determine whether these symptoms are the result of long-term sequelae or a persistent active Schistosoma infection.

A crayfish chitosan-based bioactive film to treat vaginal infections: A sustainable approach.

Polymicrobial communities are seen to be a sign of health, but they can turn detrimental when an excess of pathogenic species leads to recurring vaginal infections. This microbiological imbalance may decrease women's fertility, increasing also the risk of infection by Human Papillomavirus (HPV) and/or other sexually transmitted infections (STIs). There is a worldwide need for smart/sustainable solutions to tackle these types of infections. Hereupon, we investigated, as a potential solution, the use of crayfish chitosan-based membrane as a mucoadhesive, antimicrobial, biocompatible and biodegradable material. Chitosan was chemically extracted with a process yield of ca. 63 % and a degree of deacetylation of ca. 65 %. Further chitosan was characterized by FTIR, DSC, XRD and zeta potential. Antimicrobial and antioxidant activities were tested by microbicide concentration and ABTS methods. The extracted chitosan was confirmed to be antioxidant and antimicrobial against Escherichia coli, Candida albicans, Staphylococcus aureus (methicillin resistant and susceptible strains). Vaginal films using chitosan extracted from crayfish shells were produced by solvent casting, and the biological profile was tested in simulated vaginal fluid as a proof of concept. The main data showed that the vaginal films prepared were active against several microorganisms responsible for vaginal infections, demonstrating their potential in the field.

Carotid body interoception in health and disease.

Interoception entails perceiving or being aware of the internal state of the body, playing a pivotal role in regulating processes such as heartbeat, digestion, glucose metabolism, and respiration. The carotid body (CB) serves as an interoceptive organ, transmitting information to the brain via its sensitive nerve, the carotid sinus nerve, to maintain homeostasis. While traditionally known for sensing oxygen, carbon dioxide, and pH levels, the CB is now recognized to possess additional interoceptive properties, detecting various mediators involved in blood pressure regulation, inflammation, and glucose homeostasis, among other physiological functions. Furthermore, in the last decades CB dysfunction has been linked to diseases like sleep apnea, essential hypertension, and diabetes. In this review manuscript, we make a concise overview of the traditional interoceptive functions of the CB, acting as a sensor for oxygen levels, carbon dioxide levels, and pH, and introduce the novel interoceptive properties of the CB related to vascular, glucose and energy regulation. Additionally, we revise the contribution of the CB to the onset and progression of metabolic diseases, delving into the potential dysfunction of its interoceptive metabolic functions as a contributing factor to pathophysiology. Finally, we postulate the use of therapeutic interventions targeting the metabolic interoceptive properties of the CB as a potential avenue for addressing metabolic diseases.

Successful Mycobacterium tuberculosis culture isolation from tongue swabs: Results from both experimentally infected and clinical swabs from pulmonary tuberculosis patients.

This study explored Mycobacterium tuberculosis (MTB) growth from tongue swabs, both experimentally infected after sampling from healthy controls, or sampled from patients with smear-microscopy confirmed pulmonary tuberculosis (PTB). For both, we evaluated the performance of NALC-NaOH/MGIT960 (MGIT), Kudoh-Ogawa (KO), and cetylpyridinium chloride-Löwenstein-Jensen (CPC/LJ) culture processing methods. Experimentally spiked swabs from 20 participants exhibited 94.4% MTB growth when inoculated within 7 days of CPC exposure, declining significantly after 14-21 days (p<0.00001). KO-processed specimens showed 100% MTB growth, with a non-significant reduction after storage (94.1%; p=0.21), and all spiked swabs yielded growth in MGIT. In the field evaluation on 99 PTB patients, MGIT isolated MTB from 89% of tongue swabs, with an 8% contamination rate, compared to 99% MGIT positivity from sputum. Solid media had lower positivity, 62% for KO and 49% for CPC/LJ, suggesting MGIT as optimal for growing MTB from tongue swabs. Further testing of presumptive PTB patients is recommended.

In-hospital initiation of sodium-glucose cotransporter-2 inhibitors in patients with heart failure and reduced ejection fraction: 90-day prescription patterns and clinical implications.

INTRODUCTION: Safety and early clinical benefit make sodium-glucose cotransporter-2 inhibitor (SGLT2-i) therapy suitable for in-hospital initiation in patients with heart failure and reduced ejection fraction (HFrEF). Despite randomized controlled trials and guideline recommendations, they are underused, and clinical inertia may play a role. OBJECTIVES PRIMARY: To assess the impact of initiating SGLT-2i at discharge on 90-day prescription rates in patients with HFrEF during hospitalization for acute heart failure (AHF). Secondary: To evaluate the presence of independent factors associated with prescription, and to explore clinical outcomes at 90 days. METHODS: Retrospective analysis of a consecutive prospective single-center cohort. Adult patients hospitalized between January 2021 and September 2022 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) <40% were included. The primary outcome was SGLT2-i prescription rate at 90 days, and the exploratory secondary endpoints was the composite of hospitalization or urgent visit for AHF or all-cause mortality at 90 days. RESULTS: 237 patients were included. Mean age was 76±11 years, and mean LVEF was 29±7%. In patients without contraindications, SGLT2 inhibitors (SGLT2-i) were prescribed during hospitalization in 52.3%. At 90 days, the SGLT2-i prescription rate was 94.2% in those with in-hospital initiation and 14.4% in those without. (p<0.001). Independent factor associated with inpatient prescription was lower LVEF, 0.83 (95% CI: 0.77-0.89) for each point. Patients with in-hospital SGLT2-i initiation showed a lower rate of the combined endpoint of all-cause death, HF rehospitalization, or unplanned HF visit at 90 days (44.4% versus 23.9%, p=0.005). CONCLUSIONS: In-hospital initiation of SGLT-2-i was associated with significantly higher prescription rates and lower prevalence in the secondary combined endpoint at 90 days. This study reflects the presence of medical inertia, particularly in patients with higher LVEF, and highlights the hospitalization period as an optimal time to start SGLT2-i.

Co-occurrence of oral pemphigus vulgaris and herpes simplex virus infection in a young patient with Crohn's disease: report of a rare case of oral lesions during anti-TFN alpha and immunomodulator therapy.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune disease that affects desmoglein-1 and desmoglein-3, leading to intraepithelial vesiculobullous lesions. In the oral mucosa, PV lesions can mimic other diseases such as mucous membrane pemphigoid, other forms of pemphigus, recurrent aphthous stomatitis, erythema multiforme, Stevens-Johnson syndrome, and virus-induced ulcers like herpes simplex virus (HSV), making diagnosis challenging. The co-occurrence of PV with Crohn's disease is rare and predominantly seen in younger patients. The therapeutic mainstay for both PV and Crohn's disease usually involves systemic corticosteroids combined with immunosuppressants and immunobiological drugs. Literature indicates that the use of these drugs, particularly TNF-alpha inhibitors, for managing autoimmune diseases like Crohn's can potentially induce other autoimmune diseases known as autoimmune-like syndromes, which include episodes of lupus-like syndrome and inflammatory neuropathies. There are few cases in the literature reporting the development of PV in individuals with CD undergoing infliximab therapy. CASE REPORT: A young female with severe Crohn's disease, treated with the TNF-alpha inhibitor infliximab, developed friable pseudomembranous oral ulcerations. Histopathological and immunofluorescence analyses confirmed these as PV. The treatment included clobetasol propionate and low-level photobiomodulation, which resulted in partial improvement. The patient later experienced severe intestinal bleeding, requiring intravenous hydrocortisone therapy, which improved both her systemic condition and oral lesions. Weeks later, new ulcerations caused by herpes virus and candidiasis were identified, leading to treatment with oral acyclovir, a 21-day regimen of oral nystatin rinse, and photodynamic therapy, ultimately healing the oral infections. To manage her condition, the gastroenterologists included methotrexate (25 mg) in her regimen to reduce the immunogenicity of infliximab and minimize corticosteroid use, as the patient was in remission for Crohn's disease, and the oral PV lesions were under control. CONCLUSION: Young patients with Crohn's disease should be referred to an oral medicine specialist for comorbidity investigation, as oral PV and opportunistic infections can arise during immunosuppressive therapy. The use of TNF-alpha inhibitors in patients treated for inflammatory bowel disease, such as Crohn's, should be carefully evaluated for potential side effects, including oral PV.

Distinct basal forebrain-originated neural circuits promote homoeostatic feeding and suppress hedonic feeding in male mice.

Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBBPenk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBBPenk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.