Combination of Neovestitol and Vestitol Modifies the Profile of Periodontitis-Related Subgingival Multispecies Biofilm.

The aim of this study was to evaluate the effect of the combination of neovestitol-vestitol (CNV) compounds obtained from Brazilian red propolis on the microbiological profile of a mature multispecies subgingival biofilm. The biofilm with 32 bacterial species associated with periodontitis was formed for seven days using a Calgary device. Treatment with CNV (1600, 800, 400, and 200 µg/mL), amoxicillin (54 µg/mL), and vehicle control was performed for 24 h on the last day of biofilm formation. Biofilm metabolic activity and DNA-DNA hybridization (checkerboard) assays were performed. The groups treated with CNV 1600 and amoxicillin reduced 25 and 13 species, respectively, compared to the control vehicle treatment (p ≤ 0.05); both reduced P. gingivalis, while only CNV reduced T. forsythia. When the data from the two treatments (CNV and AMOXI) were compared, a statistically significant difference was observed in 13 species, particularly members of Socransky's orange complex. Our results showed that CNV at 1600 µg/mL showed the best results regarding the metabolic activity of mature biofilms and obtained a reduction in species associated with the disease, such as T. forsythia, showing a better reduction than amoxicillin. Therefore, CNV seems to be a promising alternative to eradicate biofilms and reduce their pathogenicity.

Parametric magnon transduction to spin qubits.

The integration of heterogeneous modular units for building large-scale quantum networks requires engineering mechanisms that allow suitable transduction of quantum information. Magnon-based transducers are especially attractive due to their wide range of interactions and rich nonlinear dynamics, but most of the work to date has focused on linear magnon transduction in the traditional system composed of yttrium iron garnet and diamond, two materials with difficult integrability into wafer-scale quantum circuits. In this work, we present a different approach by using wafer-compatible materials to engineer a hybrid transducer that exploits magnon nonlinearities in a magnetic microdisc to address quantum spin defects in silicon carbide. The resulting interaction scheme points to the unique transduction behavior that can be obtained when complementing quantum systems with nonlinear magnonics.

Recurrent IgA Nephropathy or Subclinical Chronic Humoral Rejection With Predominance of Plasma Cells: A Case Report.

Both antibody-mediated rejection and recurrence of kidney disease are major causes of allograft loss. A possible strategy to address the former is donor-specific antibody (DSA) monitoring. In this patient with IgA nephropathy, DSA detection triggered biopsy 10 years after transplant despite preserved graft function and normal urinary examination. Biopsy showed mild glomerulitis, mild capillaritis, and transplant glomerulopathy with no C4d peritubular capillary staining, along with IgA-dominant mesangial immunofluorescence staining. Interstitial inflammation had a notable predominance of plasma cells, a finding that has been variably attributed to rejection and worse prognosis. Immunosuppression was optimized with the working diagnosis of recurrent IgA nephropathy and/or chronic active humoral rejection with predominance of plasma cells, with favorable response at follow-up. This case illustrates the conflicting role of DSA monitoring and allograft biopsy to optimize immunosuppression management. Despite imperfect correlation with each other and clinical outcomes, they are key to tailor therapy. In the future, characterization of the role of plasma cell infiltrates in rejection might further enable prognosis and treatment individualization.

Digital flashcards and medical physiology performance: a dose-dependent effect.

Use of digital flashcards promotes active recall, spaced repetition, and self-assessment academic principles. This work explores the association and dose-dependent effect of this study method and locomotor (LP) and cardiovascular physiology (CP) grades. A single-faculty cohort study of medical LP and CP students was conducted, and 155 and 676 flashcards, respectively, were created through Moodle. An exploratory analysis examined three exam results (2019), and a confirmatory study used a fourth exam (2021) in another CP cohort. Of 685 students enrolled, 558 participated in the exploratory analysis: 319 (69%) for LP and 311 (84%) for CP, of which 203 LP and 267 CP students were flashcard users. Median grades were higher among flashcard users, and the number of cards reviewed was positively correlated with grades (r = 0.275 to 0.388 for LP and r = 0.239 to 0.432 for CP, P < 0.001). Multiple linear regression models confirmed a positive dose-dependent association between results and the number of flashcards studied: for every 100 LP cards reviewed, exam grades increased 0.44-0.75 on a 0-20 scale range (P < 0.001), and for every 1,000 CP flashcards, results raised 0.81-1.08 values (P < 0.05). These findings were confirmed in the 2021 CP cohort of 269 participants, of whom 67% were flashcard users. Digital flashcard revision has a consistent positive dose-dependent association on LP and CP grades.NEW & NOTEWORTHY Implementing flashcard-based strategies is a feasible way to promote active recall, spaced repetition, and self-assessment, and students are highly adherent to these initiatives. There is a positive dose-dependent association between the number of flashcards reviewed and physiology grades. These results are consistent across different physiology subjects, under different cohorts, over short and medium terms.

Nursing technicians' proxemic behaviors during transfusions in hospitalized clients / Comportamientos proxémicos de técnicos de enfermería durante transfusiones en clientes internados / Comportamentos proxêmicos de técnicos de enfermagem durante o ato transfusional em clientes hospitalizados

ABSTRACT Objective: to describe nursing technicians' proxemic behaviors during transfusions in hospitalized clients. Method: a qualitative, descriptive and exploratory study based on non-participant observation, recorded in an instrument prepared from the Theory of Proxemic Behavior. The participants were 18 nursing technicians from a reference hospital for Hematology and Hemotherapy in the Brazilian Southeast Region, from April to December 2022. Data analysis prioritized thematic content. Results: the following stood out: eye contact; instrumental touch; normal tone of voice; and intimate and personal distances. These indicate welcoming, attention and technical vigilance when carrying out the transfusions. Conclusion: there is a need to raise nursing technicians' awareness regarding proxemic behaviors when welcoming clients. That is: expanding listening, bonding and effective interpersonal coexistence, and favoring the reach of comprehensive health care in Hematology and Hemotherapy.

RESUMEN Objetivo: describir los comportamientos proxémicos de técnicos de Enfermería durante transfusiones en clientes internados. Método: estudio cualitativo, descriptivo y exploratorio, basado en la observación no participante y registrado en un instrumento elaborado a partir de la Teoría del Comportamiento Proxémico. Los participantes fueron 18 técnicos de Enfermería de un hospital que es referencia en Hematología y Hemoterapia de la Región Sudeste de Brasil, entre abril y diciembre de 2022. En el análisis de los datos se priorizó el contenido temático. Resultados: se destacó lo siguiente: contacto visual; toque instrumental; tono de voz normal; y distancias íntima y personal; los cuales indican buen recibimiento, atención y vigilancia técnica al realizar las transfusiones. Conclusión: es necesario generar conciencia en los técnicos de Enfermería con respecto a los comportamientos proxémicos al recibir a los clientes. Eso implica: prestar más atención al escuchar y ampliar los vínculos y la convivencia interpersonal efectiva, además de favorecer el alcance de las medidas de atención en integrales en Hematología y Hemoterapia.

RESUMO Objetivo: descrever os comportamentos proxêmicos de técnicos de enfermagem durante o ato transfusional em clientes hospitalizados. Método: estudo qualitativo, descritivo e exploratório, pautado em observação não participante, registrado em instrumento elaborado a partir da teoria do comportamento proxêmico. Participaram 18 técnicos de enfermagem de um hospital referência em hematologia e hemoterapia da Região Sudeste do Brasil, de abril a dezembro de 2022. A análise de dados priorizou o conteúdo temático. Resultados: destacaram-se o contato visual; o toque instrumental; o tom de voz normal e as distâncias íntima e pessoal. Estes, indicativos de acolhimento, atenção e vigilância técnica à realização do ato transfusional. Conclusão: há necessidade de despertar a consciência dos técnicos de enfermagem em relação aos comportamentos proxêmicos durante o acolhimento aos clientes. Isto é: ampliar a escuta, o vínculo, a efetiva convivência interpessoal e favorecer o alcance dos cuidados em saúde integral na hematologia e hemoterapia.

Pericarditis Due to Campylobacter fetus subsp. fetus: A Case Report of an Uncommon Infection.

Pericarditis is a common condition with numerous aetiologies. Bacteria other than the Mycobacterium tuberculosis complex are an exceptional cause. We present a case of subacute pericarditis highly probable due to Campylobacter fetus subsp. fetus in an immunosuppressed patient undergoing biologic therapy in relation to systemic lupus erythematosus (SLE). On admission, the patient presented with chest pain, dyspnea, and diaphoresis and has lately developed fever and a large pericardial effusion (PE) with a concomitant increase in the inflammatory parameters. The clinical presentation, along with the exclusion of a flare of the autoimmune disease and the isolation of Campylobacter fetus subsp. fetus on blood samples permitted the diagnosis. After therapy with antibiotics and colchicine, the patient showed full recovery.

New species of Asclepias (Apocynaceae), Baphia (Leguminosae), Cochlospermum (Bixaceae) and Endostemon (Lamiaceae) from the Kalahari sands of Angola and NW Zambia, with one new combination in Vangueria (Rubiaceae).

Four new species are described from central and eastern Angola and adjacent NW Zambia. All occur in Kalahari sand savannas rich in endemic and more widely distributed geoxylic suffrutices. Despite being known from very few collections, the conservation status of one of these new species is assessed as Least Concern, as these grasslands are nutrient-poor, are in remote sparsely populated areas, and are not threatened with conversion to agriculture. The remaining three are treated as Data Deficient. In addition, one new combination is provided for Ancylanthosrubiginosus Desf. under Vangueria as V.rubiginosa (Desf.) Lantz is an illegitimate later homonym. We also make orthographic corrections to specific epithets commemorating Ilse von Nolde, a collector who made important collections from Quela in Malange in the 1930s.

Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients. / Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos.

BACKGROUND: Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. OBJECTIVE: To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. METHODS: A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. RESULTS: A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. CONCLUSION: High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Antimicrobial activity of Desplac® oral gel in the subgingival multispecies biofilm formation.

Natural products are well-known due to their antimicrobial properties. This study aimed to evaluate the antimicrobial effect of Desplac® product (composed of Aloe Vera, Propolis Extract, Green Tea, Cranberry, and Calendula) on the subgingival biofilm. Two different protocols were used to treat the 33-species biofilms: (A) 2×/day (12/12 h) for 1 min with Desplac® or Noplak Toothpaste (Chlorhexidine + Cetylpyridinium Chloride) or Oral B ProGengiva (stannous Fluoride) or a placebo gel; (B) a 12-h use of the Desplac® product or 0.12% chlorhexidine gel or a placebo gel. After 7 days of biofilm formation, the metabolic activity (MA) and biofilm profile were determined by 2,3,5-triphenyltetrazolium chloride and Checker-board DNA-DNA hybridization, respectively. Statistical analysis used the Kruskal-Wallis test followed by Dunn's post-hoc. In protocol A, all treatments presented reduced MA compared to the placebo (p ≤ 0.05). The Desplac®-treated biofilm showed a similar microbial profile to other antimicrobials, although with higher bacterial total counts. In protocol B, MA of Desplac®-treated biofilms was lower than the placebo's MA but higher than chlorhexidine-treated biofilms (p ≤ 0.05). Pathogen levels in Desplac®-treated biofilms were lower than in placebo-treated biofilms and elevated compared to the chlorhexidine-treated biofilms (p ≤ 0.05). Desplac® inhibited the biofilm development and disrupted the mature subgingival biofilm, highlighting its effect on Tannerella forsythia counts.

Adenosine A2A Receptors Shut Down Adenosine A1 Receptor-Mediated Presynaptic Inhibition to Promote Implementation of Hippocampal Long-Term Potentiation.

Adenosine operates a modulation system fine-tuning the efficiency of synaptic transmission and plasticity through A1 and A2A receptors (A1R, A2AR), respectively. Supramaximal activation of A1R can block hippocampal synaptic transmission, and the tonic engagement of A1R-mediated inhibition is increased with increased frequency of nerve stimulation. This is compatible with an activity-dependent increase in extracellular adenosine in hippocampal excitatory synapses, which can reach levels sufficient to block synaptic transmission. We now report that A2AR activation decreases A1R-medated inhibition of synaptic transmission, with particular relevance during high-frequency-induced long-term potentiation (LTP). Thus, whereas the A1R antagonist DPCPX (50 nM) was devoid of effects on LTP magnitude, the addition of an A2AR antagonist SCH58261 (50 nM) allowed a facilitatory effect of DPCPX on LTP to be revealed. Additionally, the activation of A2AR with CGS21680 (30 nM) decreased the potency of the A1R agonist CPA (6-60 nM) to inhibit hippocampal synaptic transmission in a manner prevented by SCH58261. These observations show that A2AR play a key role in dampening A1R during high-frequency induction of hippocampal LTP. This provides a new framework for understanding how the powerful adenosine A1R-mediated inhibition of excitatory transmission can be controlled to allow the implementation of hippocampal LTP.

Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.

Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.

Increased Synaptic ATP Release and CD73-Mediated Formation of Extracellular Adenosine in the Control of Behavioral and Electrophysiological Modifications Caused by Chronic Stress.

Increased ATP release and its extracellular catabolism through CD73 (ecto-5'-nucleotidase) lead to the overactivation of adenosine A2A receptors (A2AR), which occurs in different brain disorders. A2AR blockade blunts mood and memory dysfunction caused by repeated stress, but it is unknown if increased ATP release coupled to CD73-mediated formation of extracellular adenosine is responsible for A2AR overactivation upon repeated stress. This was now investigated in adult rats subject to repeated stress for 14 consecutive days. Frontocortical and hippocampal synaptosomes from stressed rats displayed an increased release of ATP upon depolarization, coupled to an increased density of vesicular nucleotide transporters and of CD73. The continuous intracerebroventricular delivery of the CD73 inhibitor α,ß-methylene ADP (AOPCP, 100 µM) during restraint stress attenuated mood and memory dysfunction. Slice electrophysiological recordings showed that restraint stress decreased long-term potentiation both in prefrontocortical layer II/III-layer V synapses and in hippocampal Schaffer fibers-CA1 pyramid synapses, which was prevented by AOPCP, an effect occluded by adenosine deaminase and by the A2AR antagonist SCH58261. These results indicate that increased synaptic ATP release coupled to CD73-mediated formation of extracellular adenosine contributes to mood and memory dysfunction triggered by repeated restraint stress. This prompts considering interventions decreasing ATP release and CD73 activity as novel strategies to mitigate the burden of repeated stress.

Feedback facilitation by adenosine A2A receptors of ATP release from mouse hippocampal nerve terminals.

The adenosine modulation system is mostly composed by inhibitory A1 receptors (A1R) and the less abundant facilitatory A2A receptors (A2AR), the latter selectively engaged at high frequency stimulation associated with synaptic plasticity processes in the hippocampus. A2AR are activated by adenosine originated from extracellular ATP through ecto-5'-nucleotidase or CD73-mediated catabolism. Using hippocampal synaptosomes, we now investigated how adenosine receptors modulate the synaptic release of ATP. The A2AR agonist CGS21680 (10-100 nM) enhanced the K+-evoked release of ATP, whereas both SCH58261 and the CD73 inhibitor α,ß-methylene ADP (100 µM) decreased ATP release; all these effects were abolished in forebrain A2AR knockout mice. The A1R agonist CPA (10-100 nM) inhibited ATP release, whereas the A1R antagonist DPCPX (100 nM) was devoid of effects. The presence of SCH58261 potentiated CPA-mediated ATP release and uncovered a facilitatory effect of DPCPX. Overall, these findings indicate that ATP release is predominantly controlled by A2AR, which are involved in an apparent feedback loop of A2AR-mediated increased ATP release together with dampening of A1R-mediated inhibition. This study is a tribute to María Teresa Miras-Portugal.

[Evaluation of the Manchester Triage System in Patients with Acute Primary Angle Closure Attack: A Retrospective Study]. / Avaliação do Sistema de Triagem de Manchester em Doentes com Crise de Encerramento Agudo Primário do Ângulo Iridocorneano: Um Estudo Retrospetivo.

INTRODUCTION: Acute primary angle closure attack is an ophthalmological emergency. The aim of this study was to describe the cases diagnosed in the Emergency Department, by correlating the initial complaint with the Manchester triage level and ultimately the time needed until ophthalmological evaluation and iridotomy. MATERIAL AND METHODS: Retrospective analysis of the electronic medical records of patients with acute primary angle closure attack that attended the Ophthalmology Emergency Department of our tertiary center between January 2010 and December 2020. Overall, 2228 Emergency Department episodes coded with the diagnoses glaucoma or ocular hypertension were retrieved, followed by screening of each episode for correct identification of true acute primary angle closure attacks. Clinical data was gathered, including Manchester triage level, presenting complaint, intraocular pressure at presentation, first medical specialty that observed the patient, time until observation by Ophthalmology and time until laser iridotomy. RESULTS: Among the 120 patients identified, 84 (70%) were female and the mean age was 68 ± 12 years. Mean intraocular pressure at admission was 53.4 ± 12.4 mmHg, and 9.2% of patients presented only non-ocular complaints, while 9.2% presented mixed complaints (ocular and non-ocular). Most patients (68.1%) with only non-ocular or mixed complaints were triaged to a non-ophthalmologist (p < 0.001). Concerning the triage system, at admission, most patients (66.7%) were labelled yellow (urgent), while 9.2% and none were labelled as orange (very urgent) or red (emergent), respectively. Most patients (83.3%) were directly sent to Ophthalmology (properly triaged), while the remaining were incorrectly assigned to a non-ophthalmologist. Median time until observation by Ophthalmology was 49 minutes in the properly triaged group (min. 15, max. 404), while it was 288 minutes (min. 45, max. 871) in those who were incorrectly triaged (p < 0.001). Likewise, median time until treatment with laser iridotomy was 203 minutes in the properly triaged group (min. 22, max. 1440) and 353 minutes in the incorrectly triaged group (min.112, max. 947) (p < 0.001). CONCLUSION: Most patients with acute primary angle closure attack were not properly triaged according to the level of the Manchester triage system. There was a significant delay in the diagnosis and treatment of those patients who were first assigned to non-ophthalmologists. There is a need to raise awareness regarding the presenting signs and symptoms of an acute primary angle closure attack in order to avoid preventable vision loss.

Introdução: A crise de encerramento agudo primário do ângulo iridocorneano é uma emergência oftalmológica. O objetivo deste estudo foi descrever os casos admitidos no Serviço de Urgência do Centro Hospitalar Universitário São João, correlacionando a queixa inicial com o nível de triagem de Manchester atribuído e o tempo até observação por Oftalmologia e realização de iridotomia. Material e Métodos: Análise retrospetiva dos registos clínicos dos doentes com encerramento agudo primário do ângulo, admitidos no Serviço de Urgência entre janeiro de 2010 e dezembro de 2020. Foram revistos 2228 episódios com diagnóstico de glaucoma ou hipertensão ocular para identificação correta dos casos de crise de encerramento do ângulo. Foram extraídas variáveis, nomeadamente o nível de triagem de Manchester atribuído, queixa principal, pressão intraocular à admissão, especialidade responsável pelo primeiro contacto médico e tempos até observação por Oftalmologia e até iridotomia. Resultados: Foram identificados 120 doentes, 84 (70%) do sexo feminino, com idade média de 68 ± 12 (desvio padrão) anos. A pressão intraocular média à admissão foi de 53,4 ± 12,4 mmHg. Em 9,2% dos doentes a queixa principal foi não-ocular, enquanto 9,2% apresentavam queixas não-oculares e oculares associadas. A maioria (68,1%) dos doentes com queixas não-oculares ou mistas foi triada para um não-oftalmologista. Segundo o sistema de triagem, a maioria (66,7%) dos doentes foi triada com nível amarelo (urgente), 9,2% foram triados com laranja (muito urgente) e nenhum vermelho (emergente). O primeiro especialista a observar os doentes após a triagem foi um oftalmologista em 83,3% dos casos (corretamente triados), enquanto os restantes foram inicialmente observados por outra especialidade. O tempo mediano até observação por Oftalmologia foi de 288 minutos (min. 45, máx. 871) num doente incorretamente triado e 49 minutos (min. 15, máx. 404) (p < 0,001) em doentes corretamente triados. O tempo mediano até realização de iridotomia laser foi de 353 minutos (min. 112, máx. 947) nos doentes incorretamente triados e 203 minutos (min. 22, máx. 1440) nos corretamente triados (p < 0,001). Conclusão: A maioria dos doentes com crise de encerramento agudo primário do ângulo iridocorneano não foi triada de acordo com o grau de prioridade apropriado segundo o sistema de triagem de Manchester. Nos doentes que não foram imediatamente seguidos por Oftalmologia verificou-se um atraso significativo no diagnóstico e início do tratamento. Torna-se premente a consciencialização dos profissionais de saúde sobre esta condição clínica e a otimização do processo de triagem para minimizar a perda de visão.

Pertuzumab in Combination with Trastuzumab and Docetaxel in the Neoadjuvant Treatment for HER2-Positive Breast Cancer.

Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012-2015 and 2015-2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012-2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015-2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

Increased ATP Release and Higher Impact of Adenosine A2A Receptors on Corticostriatal Plasticity in a Rat Model of Presymptomatic Parkinson's Disease.

Extracellular ATP can be a danger signal, but its role in striatal circuits afflicted in Parkinson's disease (PD) is unclear and was now investigated. ATP was particularly released at high stimulation intensities from purified striatal nerve terminals of mice, which were endowed with different ATP-P2 receptors (P2R), although P2R antagonists did not alter corticostriatal transmission or plasticity. Instead, ATP was extracellularly catabolized into adenosine through CD73 to activate adenosine A2A receptors (A2AR) modulating corticostriatal long-term potentiation (LTP) in mice. In the presymptomatic phase of a 6-hydroxydopamine rat model of PD, ATP release from striatal nerve terminals was increased and was responsible for a greater impact of CD73 and A2AR on corticostriatal LTP. These observations identify increased ATP release and ATP-derived formation of extracellular adenosine bolstering A2AR activation as a key pathway responsible for abnormal synaptic plasticity in circuits involved in the onset of PD motor symptoms. The translation of these findings to humans prompts extending the use of A2AR antagonists from only co-adjuvants of motor control in Parkinsonian patients to neuroprotective drugs delaying the onset of motor symptoms.

Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos / Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients

Resumo Fundamento O aumento do peso frequentemente desencadeia mecanismos que elevam a pressão arterial. A obesidade causa mudanças estruturais no miocárdio, incluindo aumento da massa ventricular, dilatação atrial, bem como disfunções diastólicas e sistólicas. Além disso, variações pressóricas nos hipertensos obesos, como a ascensão matinal (AM), podem ter relevância clínica na prevenção dos eventos cardiovasculares. A AM da pressão arterial é um fenômeno fisiológico, que quando elevada pode ser considerada um fator de risco independente para eventos cardiovasculares. Objetivo Avaliar valores da elevação da AM e sua associação com a hipertrofia ventricular esquerda (HVE) e com o Descenso do Sono (DS) em obesos e não obesos hipertensos. Métodos Estudo transversal que avaliou medidas pressóricas à monitorização ambulatorial da pressão arterial (MAPA) e a presença de HVE, avaliada pela ecocardiografia, em 203 pacientes hipertensos em tratamento ambulatorial, separados em dois grupos: 109 não obesos e 94 hipertensos obesos. O nível de significância adotado foi de 0,05 em testes bicaudais. Resultados A AM acima de 20 mmHg à MAPA foi detectada em 59,2% dos pacientes do grupo "não obesos" e em 40,6% no grupo "obesos". A HVE foi encontrada em 18,1% no grupo dos não-obesos e em 39,3% no grupo de obesos, p<0,001. No grupo "obesos" foi observado que AM >16 mmHg esteve associada à HVE, com [razão de prevalência: 2,80; IC95% (1,12-6,98), p=0,03]. Para o grupo dos "não obesos", o ponto de corte da AM para essa associação foi >22 mmHg. Conclusão A AM elevada associou-se positivamente com HVE, com comportamento peculiar na população de hipertensos e obesos.

Abstract Background Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. Objective To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. Methods A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. Results A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. Conclusion High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Laserterapia e tratamento medicamentoso tópico na onicomicose em pessoas com diabetes: série de casos* / Terapia láser y tratamiento con medicamento tópico para onicomicosis en personas con diabetes: serie de casos / Laser therapy and topical drug treatment for onychomycosis in people with diabetes: A case-series study

Objetivo: descrever os efeitos da laserterapia de baixa intensidade e do tratamento medicamentoso tópico da onicomicose em pessoas com diabetes. Método: estudo quantitativo, do tipo série de casos. Os participantes foram 21 pessoas com diabetes divididas em dois grupos, sendo o primeiro tratado com laser e o segundo com medicamento tópico no período de outubro de 2020 a agosto de 2021. Os dados foram coletados em histórico e exame clínico das lâminas ungueais e organizados em banco de dados, cuja análise ocorreu por meio de estatística descritiva. Resultados: identificou-se que no grupo I 30% das lâminas ungueais obtiveram cura clínica e no II 26%. Ao avaliar a resposta satisfatória o grupo I apresentou 63% e o II 53%. Conclusão: o tratamento da onicomicose com laserterapia apresentou maior prevalência de resposta satisfatória e cura clínica do que o tratamento medicamento tópico.

Objective: to describe the effects of low-level laser therapy and of topical drug treatment for onychomycosis in people with diabetes. Method: a qualitative study of the case-series type. The participants were 21 individuals with diabetes divided into two groups, the first treated with laser and the second with topical medication from October 2020 to August 2021. The data were collected in a clinical history and examination of the nail plates and organized in a database, whose analysis took place through descriptive statistics. Results: it was identified that 30% and 26% of the nail plates attained clinical cure in groups I and II, respectively. When assessing the satisfactory response, groups I and II presented 63% and 53%, respectively. Conclusion: the onychomycosis treatment with laser therapy presented higher prevalence of satisfactory response and clinical cure than the topical drug treatment.

Objetivo: describir los efectos de la Terapia Láser de Baja Intensidad y del tratamiento con medicamento tópico para la onicomicosis en personas con diabetes. Método: estudio cuantitativo del tipo serie de casos. Los participantes fueron 21 personas con diabetes divididas en dos grupos: el primero tratado con láser y el segundo con un medicamento tópico entre octubre de 2020 y agosto de 2021. Los datos se recolectaron de las historias y los exámenes clínicos de las placas ungueales y se los organizó en una base de datos, cuyo análisis se realizó por medio de estadística descriptiva. Resultados: se identificó que el 30% y el 26% de las placas ungueales alcanzaron cura clínica en los grupos I y II, respectivamente. Al evaluar la respuesta satisfactoria, los grupos I y II presentaron 63% y 53%. Conclusión: el tratamiento de la onicomicosis con terapia láser presentó mayor prevalencia de respuestas satisfactoria y cura clínica que el tratamiento con predicamento tópico.

C3 Glomerulonephritis Presenting With Nephritic and Nephrotic Syndromes: Spontaneous Remission After Six Months on Dialysis.

C3 glomerulopathy is a rare and complex renal disease driven by complement dysregulation, with variable presentation and pathophysiology. We report the case of a middle-aged male patient presenting with nephritic and nephrotic syndromes and low serum C3, whose biopsy established the diagnosis of C3 glomerulonephritis. He was found to be homozygous for the complement factor H-related protein (CFHR)3-CFHR1 deletion, which has been associated with the development of anti-factor H autoantibodies. However, the lack of consistent and accessible nephritic factor assays prevented full clarification of the mechanisms involved in the disease. Interestingly, despite not receiving treatment due to suspicion of malignancy and perceived poor renal prognosis, there was spontaneous recovery after six months on hemodialysis. This case reflects the enduring challenges in establishing the diagnosis and prognosis of C3 glomerulonephritis.