Therapeutic Ultrasound Alone and Associated with Lymphatic Drainage in Women with Breast Engorgement: A Clinical Trial.

Introduction: Breast engorgement (BE) is a problem that affects many women, especially in the first days of breastfeeding, producing inflammatory symptoms. Nonpharmacological therapies are inexpensive, safe, and can produce symptom relief. Objective: This study aims to analyze the safety of therapeutic ultrasound regarding possible risks of overheating and the effects of its use alone and associated with lymphatic drainage (LD) in women. Material and Methods: Effectiveness is measured through thermography, visual analog scale, and six-point scale of BE. This is a nonrandomized clinical trial with a sample of 34 in the ultrasound group (G1), 28 in the ultrasound and LD group (G2), and 37 in the control group (G3). Results: The mean reduction for engorgement was 1.3 ± 0.8 to G1, 1.4 ± 1.0 to G2, and 1.2 ± 0.9 to G3 according to the six-point scale. The mean reduction for pain level was 3.6 ± 2.1 to G1, 4.0 ± 3.1 to G2, and 4.0 ± 2.2 to G3 according to the visual analogue scale. Conclusion: It was observed that all therapies were effective in reducing the level of engorgement, according to the six-point scale. However, combined ultrasound and LD therapy has been shown to be more effective in reducing the level of pain. Brazilian Registry of Clinical Trials (RBR-6btb6zz).

A new case of platelet-type von Willebrand disease supports the recent findings of gain-of-function GP1BA variants outside the C-terminal disulphide loop enhances affinity for von Willebrand factor.

Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant bleeding disorder characterized by an increased ristocetin-induced platelet aggregation (RIPA) and enhanced affinity of platelet glycoprotein Ibα (GPIbα) to von Willebrand factor (VWF). To date, only seven variants have been described with this gain-of-function effect, most of them located in the C-terminal disulphide loop of the VWF-binding domain of GPIbα. We herein describe a patient with moderate bleeding symptoms, mild thrombocytopenia and increased RIPA. By direct sequencing of GP1BA, a novel leucine-rich repeat heterozygous variant was identified (c.580C>T; predictably p.Leu194Phe), strongly suggestive as being the underlying cause for the PT-VWD phenotype of our patient.

A coumarin based Schiff Base: An effective colorimetric sensor for selective detection of F- ion in real samples and DFT studies.

Chemosensors are molecular devices which react with target and give a visible signal, which is a degree of its sensitivity. Herein, a novel coumarin based Schiff Base has been synthesized for F- ions detection. The chemosensor showed an intense color change upon the addition of F- ions (light yellow to purple). The chemosensor has fewer effects of competing anions. The limit of detection is calculated as low as 1.1 × 10-6 and the binding constant was determined as 1.61 × 104. The job's plot confirmed 1:1 stoichiometry between chemosensor and F- ion. The reverse reaction of chemosensor with MeOH is useful to construct a combinatorial logic circuit gates. The interaction mechanism of chemosensor was deliberated by 1H NMR, FTIR, and DFT studies. Finally, the chemosensor was useful to detect F- ions in tooth-paste sample and test strip is prepared for F- ions detection.

Drain use can be avoided in reverse shoulder arthroplasty.

BACKGROUND: Drains have demonstrated no clear benefits and some potentially harmful effects in hip and knee replacements. There is little evidence about the effects of its use in shoulder arthroplasty. We hypothesized that drain use would increase postoperative blood loss without reducing wound complications. METHODS: We included 103 reverse shoulder arthroplasties (RSA), 71 were operated for degenerative pathology, 32 due to a fracture. All complications were recorded. Hemoglobin (Hb) and hematocrit (Htc.) level were collected and compared to postoperative data. Length of hospitalization and volume output were also noted. RESULTS: 45 patients received a closed-suction drain. Patients with coagulopathy had significant higher bleeding and were excluded (p = 0.03). Patients operated for a fracture were older (80.1y.o vs 72.1 p < 0.01) and had higher blood drop (∆Hb p = 0.01; ∆Htc p = 0.03). There were neither differences between drain and control group in ∆Hb or ∆Htc in the degenerative RSA group (1.84+/-0.89 vs 1.68+/-0.84, p = 0.36; 5.78+/-2.89 vs 5.53+/-2.87 p = 0.50) nor in the fracture RSA group (2.65+/-0.94 vs 2.65+/-1.01, p = 0.90; 7.91+/-2.99 vs. 7.09+/-4.21, p = 0.56). There were neither differences in complications (degenerative p = 0.33; fracture p = 0.21). Drain use was related to a longer hospital stay in elective surgery (2.6 vs 1.8 days; p < 0.01). DISCUSSION: The rate of complication is similar between patients with and without drain use. Drain use after shoulder arthroplasty does not affect postoperative bleeding but increases the length of hospital stay. Drains seems to be an unnecessary intervention after RSA that may increase associated costs and can be safely abandoned. LEVEL OF EVIDENCE: Level III retrospective comparative study.

Inflammatory and Hemostatic Markers in COVID-19 Patients with Arterial Thrombosis Are Significantly Lower at Hospital Admission than in COVID-19 Patients without Thrombosis.

Patients with Coronavirus disease 2019 (COVID-19) are at increased risk of venous thromboembolism (VTE); however, data on arterial thromboembolism (ATE) is still limited. We report a case series of thromboembolic events (TE) in 290 COVID-19 patients admitted between October and December 2020 to a Portuguese hospital. Admission levels of various laboratory parameters were evaluated and compared between COVID-19 patients with (TE) and without thrombotic events (non-TE). The overall incidence of isolated ATE was 5.52%, isolated VTE was 2.41% and multiple mixed events was 0.7%. A total of 68% events were detected upon admission to the hospital with 76% corresponding to ATE. Admissions to the Intensive Care Unit were higher in patients with TE, when comparing with the non-TE group (44% vs. 27.2%; p = 0.003). Patients with ATE presented significantly lower levels of CRP (p = 0.007), ferritin (p = 0.045), LDH (p = 0.037), fibrinogen (p = 0.010) and higher monocyte counts (p = 0.033) comparatively to the non-TE patients. These results point to an early occurrence of TE and an increased incidence of ATE over VTE. The less prominent inflammation markers in patients with TE and the early presence of TE in patients with otherwise no reason for hospitalization, may suggest a direct role of SARS-CoV-2 in the thrombotic process.

[Intrahospital Protocol for the Management of COVID-19 Disease in Adults]. / Protocolo Intra-Hospitalar para Abordagem da Doença COVID-19 no Adulto.

The COVID-19 pandemic is currently responsible for over 526 million infections and over 6.3 million deaths. As a new disease, the number of papers on the subject is extensive, motivating considerable heterogeneity in its approach. Despite some medicines having sound evidence of benefit, new interventions and strategies continue to be proposed, and some still lack scientific evidence, which hinders a uniform and consensual approach. This article aims to standardize healthcare to adult patients with moderate-to-critical COVID-19, from the emergency department to hospitalization, either in a general ward or in level 2 or level 3 intensive care units, based on the best and most updated scientific evidence available. This protocol presents recommendations for the stratification of adult patients with COVID-19 disease, adequate workup at admission and during hospitalization, inpatient treatment criteria, general treatment measures, pharmacological treatment, management of complications such as organizing pneumonia and bacterial superinfection, thromboprophylaxis, special considerations on pregnancy and breastfeeding and possible future therapies.

A pandemia de COVID-19 é, atualmente, responsável por mais de 526 milhões de infeções e mais de 6,3 milhões de mortes. Como nova doença, é extenso o número de publicações sobre o tema, motivando uma considerável heterogeneidade na sua abordagem. Apesar de existirem terapêuticas com benefício comprovado, continuam a ser propostas novas intervenções e estratégias, algumas das quais carecendo ainda de suporte científico, dificultando assim uma abordagem uniforme e consensual. Este documento tem como objetivo uniformizar, baseando-se na melhor e mais atualizada evidência científica disponível, a prestação de cuidados aos doentes adultos com COVID-19 moderada a crítica, desde o serviço de urgência até à hospitalização, quer em enfermarias gerais, quer em enfermarias de cuidados intensivos de nível 2 e 3. Este protocolo apresenta recomendações para a estratificação da doença COVID-19, critérios de hospitalização, meios complementares de diagnóstico adequados à admissão e durante a hospitalização, medidas terapêuticas gerais e terapêutica farmacológica dirigida, gestão de complicações como pneumonia organizativa e sobreinfeção bacteriana, tromboprofilaxia, considerações especiais na gravidez e amamentação, e possíveis opções terapêuticas futuras.

Thrombocytopenia-Absent Radius Syndrome: Descriptions of Three New Cases and a Novel Splicing Variant in RBM8A That Expands the Spectrum of Null Alleles.

Thrombocytopenia-absent radius (TAR) syndrome is a rare congenital disorder characterized by the bilateral absence of the radius and thrombocytopenia, and sometimes by other skeletal, gastrointestinal, cardiac, and renal abnormalities. The underlying genetic defect is usually the compound inheritance of a microdeletion in 1q21.1 (null allele) and a low-frequency, non-coding single nucleotide variant (SNV) in the RBM8A gene (hypomorphic allele). We report three new cases from two unrelated families. The two siblings presented the common genotype, namely the compound heterozygosity for a 1q21.1 microdeletion and the hypomorphic SNV c.-21G>A in RBM8A, whereas the third, unrelated patient presented a rare genotype comprised by two RBM8A variants: c.-21G>A (hypomorphic allele) and a novel pathogenic variant, c.343-2A>G (null allele). Of the eight documented RBM8A variants identified in TAR syndrome patients, four have hypomorphic expression and four behave as null alleles. The present report expands the RBM8A null allele spectrum and corroborates the particularities of RBM8A involvement in TAR syndrome pathogenesis.

Understanding the reaction mechanism of the CO2 and cyclohexene oxide copolymerization catalyzed by zinc(II) and magnesium(II) catalysts: a DFT approach.

The reaction mechanisms of carbon dioxide and cyclohexene oxide copolymerization catalyzed by four different zinc(II)-magnesium(II) (labeled as M1-M2) catalysts were computationally studied using density functional theory at the BP86-D3(BJ)/def2-TZVP/SMD//BP86-D3(BJ)/def2-SVP/SMD level of theory. The results showed that the most effective catalyst was the ZnMg system, in which poly(cyclohexene carbonate) was the preferred product, followed by the side product cis-cyclohexene carbonate. The QTAIM, NCI and ELF analysis performed to understand the role of metals in the reaction showed that ligands and substrates interact more strongly with zinc(II) centers compared to magnesium(II) centers. Furthermore, the Zn-I interaction at the M1 position was stronger than the Mg-I interaction at the same position. All these results indicate a synergism between the metals Zn and Mg, which makes Zn(II)Mg(II) the best combination for the reaction.

Intestinal Intussusception: A Shocking Diagnosis.

Intussusception is a rare condition diagnosed in adults, with few cases reported as idiopathic. It is defined as the invagination of an intestinal segment into another adjacent one, due to the presence of a lead point, or in some cases, without identifiable causative lesions. The presentation is non-specific, even with careful evaluation, and most of the time, the diagnosis is made during surgery. We hereby present the case of a 73-year-old woman with idiopathic intussusception who presented in the emergency room. She was taken to the operating theatre, where intestinal resection was performed. Few cases of true idiopathic intestinal intussusception in adults are seen, and literature on this topic remains scarce. We discuss diagnostic and therapeutic options and do a brief review of the literature.

Pediatric defibrillation shocks alone do not cause heart damage in a porcine model.

AIM: Automated external defibrillators (AEDs) use various shock protocols with different characteristics when deployed in pediatric mode. The aim of this study is to assess and compare the safety and efficacy of different AED pediatric protocols using novel experimental approaches. METHODS: Two defibrillation protocols (A and B) were assessed across two studies: Protocol A: escalating (50-75-90 J) defibrillation waveform with higher voltage, shorter duration and equal phase durations. Protocol B; non-escalating (50-50-50 J) defibrillation waveform with lower voltage, longer duration and unequal phase durations.Experiment 1: Isolated shock damage was assessed following shocks to 12 anesthetized pigs. Animals were randomized into two groups, receiving three shocks from Protocol A (50-75-90 J) or B (50-50-50 J). Cardiac function, cardiac troponin I (cTnI), creatine phosphokinase (CPK) and histopathology were analyzed. Experiment 2: Defibrillation safety and efficacy were assessed through shock success, ROSC, ST-segment deviation and contractility following 16 randomized shocks from protocol A or B delivered to 10 anesthetized pigs in VF. RESULTS: Experiment 1: No clinically meaningful difference in cTnI, CPK, ST-segment deviation, ejection fraction or histopathological damage was observed following defibrillation with either protocol. No difference was observed between protocols at any timepoint. Experiment 2: all defibrillation types demonstrated shock success and ROSC ≥ 97.5%. Post-ROSC contractility was similar between protocols. CONCLUSIONS: There is no evidence that administration of clinically relevant shock sequences, without experimental confounders, result in significant myocardial damage in this model of pediatric resuscitation. Typical variations in AED pediatric mode settings do not affect defibrillation safety and efficacy.

Can increased load carriage affect lower limbs kinematics during military gait?

The aim of this study was to investigate if increased load carriage, in male military personnel, can affect the lower limbs kinematics. Twelve male military volunteers from the Portuguese Army were recruited and evaluated in an unloaded and loaded gait condition. Linear kinematics and lower limbs joint angle at heel strike, midstance and toe off were calculated. The stance, swing and double support times were found to be different between load conditions (p < 0.05). There was an interaction between load and limb (p < 0.05) for joint angles, during midstance, with limbs performing different movements in the frontal plane during loaded gait. Load increase had a different effect on the right knee, with a reduction in the abduction (valgus). This study may be beneficial in offering suggestion to improve the performance of gait with load and in an attempt to help prevent possible injuries. Practitioner summary: Increased load can affect lower limbs of male soldiers at the pelvic, hip and knee angles on the frontal plane, which can alter the joint force distribution. While these alterations may indicate protective mechanics, load management procedures should be implemented along with gait monitoring to avoid negative effects in performance.

CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2.

RASGRP2 encodes the calcium and diacylglycerol (DAG)-regulated guanine nucleotide exchange factor I (CalDAG-GEFI) identified as a Rap1-activating molecule. Pathogenic variants previously identified in RASGRP2 allowed the characterization of CalDAG-GEFI deficiency as a non-syndromic, autosomal recessive platelet function disease. We report on the clinical manifestations and laboratory features of a Portuguese family with a likely pathogenic variant in RASGRP2 (c.999G>C leading to a p.Lys333Asn change in the CDC25 catalytic domain of CalDAG-GEFI) and discuss the contribution of this variant to the disease manifestations. Based on the study of this family with one homozygous patient and five heterozygous carriers and on a critical analysis of the literature, we challenge previous knowledge that CalDAG-GEFI deficiency only manifests in homozygous patients. Our data suggest that at least for the RASGRP2 variant reported herein, there is a phenotypic expression, albeit milder, in heterozygous carriers.

2-Nitro- and 4-fluorocinnamaldehyde based receptors as naked-eye chemosensors to potential molecular keypad lock.

New-generation chemosensors desire small organic molecules that are easy to synthesise and cost-effective. As a new interdisciplinary area of research, the integration of these chemosensors into keypad locks or other advanced communication protocols is becoming increasingly popular. Our lab has developed new chemosensor probes that contain 2-nitro- (1-3) and 4-fluoro-cinnamaldehyde (4-6) and applied them to the anion recognition and sensing process. Probes 1-6 are colorimetric sensors for naked-eye detection of AcO-/CN-/F-, while probes 4-6 could differentiate between F- and AcO-/CN- anions in acetonitrile. Using the density functional theory (DFT), it was found that probes 1-6 acted as effective chemosensors. By using Probe 5 as a chemosensor, we explored colorimetric recognition of multiple anions in more detail. Probe 5 was tested in combination with a combinatorial approach to demonstrate pattern-generation capability and its ability to distinguish among chemical inputs based on concentration. After pattern discrimination using principal component analysis (PCA), we examined anion selectivity using DFT computation. In our study, probe 5 demonstrates excellent performance as a chemosensor and shows promise as a future molecular-level keypad lock system.

[Guidelines on: COVID-19 Vaccine Induced Thrombosis, Bleeding, and Thrombocytopenia]. / Trombose, Hemorragia e Trombocitopenia Induzidas pelas Vacinas contra a COVID-19: Protocolo de Atuação.

After widespread vaccination with COVID-19 vaccines, there have been worldwide reports on thrombosis, bleeding, and thrombocytopenia. Recently, a rare syndrome with a high mortality rate consisting of an unusual combination of thrombocytopenia and thrombosis, in particular cerebral venous sinus thrombosis, which clinically resembles heparin-induced thrombocytopenia, was reported following vaccination. Different statements and recommendations were developed regarding the definition, diagnosis, and treatment of these rare complications. We present here a protocol with recommendations, based on current evidence.

Após a generalização da vacinação contra a COVID-19, foram relatados efeitos adversos como trombose, hemorragia e trombocitopenia. Recentemente, após vacinação, foi reconhecido um síndrome raro e com mortalidade elevada, caraterizado por uma combinação não usual de trombocitopenia e trombose, em particular trombose dos seios venosos cerebrais, com muitas semelhanças com a trombocitopenia induzida pela heparina. Foram desenvolvidas diferentes recomendações na definição, diagnóstico e tratamento destas raras complicações. Apresentamos aqui, um protocolo de atuação baseado na evidência atual.

Promoting health-enhancing physical activity in Europe: Surveillance, policy development and implementation 2015-2018.

In the European Union (EU), the low levels of health-enhancing physical activity (HEPA) and high levels of sedentary behaviour are a concerning public health issue common to all Member States. In 2013, the Council of the EU recognized the need for more data related to HEPA to support policymaking across the region and proposed a monitoring framework that included 23 indicators covering different themes relevant to HEPA promotion in the EU context. In 2014, the EU Physical Activity Focal Points Network was established to support the implementation of the monitoring framework and in 2015 and 2018 surveys were conducted to collect epidemiological and policy information related to HEPA for each Member State. This paper aims to provide an update on the status of HEPA policies and surveillance in the EU and describe the changes that have occurred since 2015. In 2018, all countries had implemented more than 10 indicators, 8/28 had implemented 20 or more indicators, and only one country had completed all 23 indicators. From 2015 to 2018, 19 indicators improved, one remained unchanged, and three regressed. From the country perspective, 17 improved the number of accomplished indicators, five maintained the indicators, and five worsened the number of indicators. Overall, there has been a clear increase in the number of countries implementing HEPA policies and strategies across the different sectors, although some heterogeneity between Members Sates was still observed. Implementation of regional physical activity strategies and the establishment of the EU-wide monitoring framework appears to have had an overall positive impact on HEPA policy development and implementation.

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection.

INTRODUCTION: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. METHODS: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. RESULTS: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. CONCLUSIONS: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.

INTRODUÇÃO: A população de doentes com hemofilia (DCH) representa uma população com alta prevalência de infeção pelo virus da hepatite C (VHC), atendendo à utilização passada de derivados sanguíneos contaminados. Apesar de os objetivos terapêuticos nesta população serem semelhantes aos da população geral, estudos de vida real com follow-up de longa data são ainda escassos. O nosso objetivo consistiu em avaliar os outcomes infeção VHC, bem como, os resultados da terapéutica antivírica nos DCH. MÉTODOS: Foi avaliada retrospetivamente uma coorte unicêntrica de DCH com positividade para anti-VHC. Os outcomes registados foram a ocorrência de clearance espontêneo, resposta virológica sustentada (RVS), desenvolvimento de doença hepática terminal e mortalidade. RESULTADOS: De 131 DCH, 73 (55.7%) apresentavam positividade para o anticorpo VHC. Durante um follow-up médio de 22 anos, 46 doentes (63.9%) desenvolveram hepatite crónica C, 16 (34.8%) dos quais com desenvolvimento de cirrose. Trinta e quatro DCH foram tratados, a maioria (n = 32) exposta previamente a regimes baseados no interferão (IFN) com RVS de 40.6%. Antivíricos de ação direta foram utilizados em 14 doentes experimentados a IFN e 2 naïves com uma taxa de RVS geral de 100%. Morte foi observada em 17 doentes (23.3%), apenas 4 relacionadas à doença hepática. Destes nenhum tinha atingido RVS. CONCLUSÕES: Descrevemos os outcomes de uma coorte portuguesa de DCH e VHC após duas décadas de follow-up, mostrando uma mortalidade inferior à previamente descrita. As taxas de RVS mostradas foram comparáveis com as da população geral salientando a importancia do tratamento precoce.

Aggressive Neuroblastoma in a Pediatric Patient with Severe Hemophilia A.

Despite the extensive information regarding hemophilia's hemorrhagic complications, the literature on cancer in hemophilia is scarce, especially in pediatric patients. Many uncertainties remain concerning diagnosis and workup. We report a rare case of two severe diseases (neuroblastoma and hemophilia A (HA)) concomitantly present in the same pediatric patient. We highlight that the diagnosis of severe HA did not have a negative impact on the patient's oncologic course. This case also illustrates the significance of the cooperation among different specialties and hospitals when caring for the same patient.

DFT study of H2 adsorption at a Cu-SSZ-13 zeolite: a cluster approach.

In this work the H2 adsorption at a Cu(i)-SSZ-13 exchanged zeolite was theoretically investigated. A systematic cluster approach was used and different density functionals (B3LYP, B3LYP-D3(BJ), M06L, PBE, PBE-D3(BJ) and ωB97XD) and a def2-SVP basis set were benchmarked. In order to select the best approach to the H2 adsorption over a Cu(i)-SSZ-13 cluster with 78 atoms (16 T-sites), two main tasks were performed: (1) a comparison between theoretical and experimental structures and (2) a comparison between theoretical and experimental adsorption enthalpies. By employing the most suitable functional - the ωB97X-D - the H2 interaction with the zeolite structure was studied by means of NBO, NCI, AIM and DLPNO-CCSD(T)/LED analyses.

Congenital ataxia due to novel variant in ATP8A2.

Congenital ataxias are a heterogeneous group of disorders characterized by congenital or early-onset ataxia. Here, we describe two siblings with congenital ataxia, who acquired independent gait by age 4 years. After 16 years of follow-up they presented near normal cognition, cerebellar ataxia, mild pyramidal signs, and dystonia. On exome sequencing, a novel homozygous variant (c.1580-18C > G - intron 17) in ATP8A2 was identified. A new acceptor splice site was predicted by bioinformatics tools, and functionally characterized through a minigene assay. Minigene constructs were generated by PCR-amplification of genomic sequences surrounding the variant of interest and cloning into the pCMVdi vector. Altered splicing was evaluated by expressing these constructs in HEK293T cells. The construct with the c.1580-18C > G homozygous variant produced an aberrant transcript, leading to retention of 17 bp of intron 17, by the use of an alternative acceptor splice site, resulting in a premature stop codon by insertion of four amino acids. These results allowed us to establish this as a disease-causing variant and expand ATP8A2-related disorders to include less severe forms of congenital ataxia.