Exploring Post-treatment Weight Changes in Overweight and Obese Patients With Graves' Disease: A Retrospective Analysis.

INTRODUCTION: Graves' disease (GD) is associated with primary hyperthyroidism, leading to weight loss before treatment. During the treatment, weight gain is frequently observed, often surpassing the initial weight loss. This study aimed to analyze weight fluctuations in GD patients, focusing on the subset of overweight and obese (OAO) individuals, considering the significant metabolic implications and heightened cardiovascular risk of these weight changes. METHODS: A retrospective cohort study included 122 GD patients with biochemical primary hyperthyroidism and at least 12 months of clinical follow-up after treatment for analysis. The OAO cohort comprised individuals with a body mass index (BMI) ≥25 kg/m². Data on laboratory, demographic, and weight variables were collected longitudinally. RESULTS: During the hyperthyroidism state, 34.4% (n=42) of patients presented with weight loss, a phenomenon linked to lower serum thyroid-stimulating hormone levels at diagnosis (p=0.010) and an extended need for anti-thyroid drug treatment (p<0.001). Following treatment, around 60% (n=73) of individuals encountered weight gain, exhibiting a higher prevalence among women (p<0.001) and those undergoing definitive treatment modalities (p=0.024). Notably, 26.2% (n=32) experienced excessive weight gain, which was correlated with higher premorbid BMI and diminished weight loss induced by hyperthyroidism (p<0.001). Within the OAO cohort, 66.7% (n=26) observed an increase in weight post-treatment, and in 28.2% (n=11), excessive weight gain was reported. Weight gain and excessive weight gain were noted in patients with higher initial BMIs. CONCLUSIONS: This study highlights that post-treatment weight gain is common, emphasizing the need for careful weight management in GD. In OAO GD patients, the association between initial BMI and increased weight underscores potential cardiovascular risks, warranting vigilant monitoring and early intervention.

Pharmacogenetic Approaches in Personalized Medicine for Postoperative Pain Management.

Despite technical and pharmacological advancements in recent years, including optimized therapies and personalized medicine, postoperative pain management remains challenging and sometimes undertreated. This review aims to summarize and update how genotype-guided therapeutics within personalized medicine can enhance postoperative pain management. Several studies in the area have demonstrated that genotype-guided therapy has the ability to lower opioid consumption and improve postoperative pain. Gene mutations, primarily OPRM1, CYP2D6, CYP2C9, COMT and ABCB1, have been shown to exert nuanced influences on analgesic response and related pharmacological outcomes. This review underscores the integration of pharmacogenetic-guided personalized medicine into perioperative care, particularly when there is uncertainty regarding opioid prescriptions. This approach leads to superior outcomes in terms of postoperative pain relief and reduced morbidity for numerous patients.

Chemical Characterization and Biological Properties Assessment of Euphorbia resinifera and Euphorbia officinarum Moroccan Propolis.

Although the plants of the genus Euphorbia are largely exploited by therapists in Morocco, the composition and antibacterial activities of propolis from these plants are still unknown. To address this gap, this study aimed to characterize the pollen type, the volatile compounds, and the phenolic and mineral profiles of three Euphorbia propolis samples collected in Morocco and evaluate their antimicrobial activities. The minimum inhibitory concentration of the propolis samples was determined by the microdilution method, and the anti-adherence activity was evaluated by the crystal violet assay. The examination of anti-quorum-sensing proprieties was performed using the biosensor Chromobacterium violaceum CV026. Pollen analysis revealed that Euphorbia resinifera pollen dominated in the P1 sample (58%), while E. officinarum pollen dominated in the P2 and P3 samples (44%). The volatile compounds were primarily composed of monoterpene hydrocarbons, constituting 35% in P1 and 31% in P2, with α-pinene being the major component in both cases, at 16% in P1 and 15% in P2. Calcium (Ca) was the predominant mineral element in both E. resinifera (P1) and E. officinarum (P2 and P3) propolis samples. Higher levels of phenols, flavonoids and dihydroflavonoids were detected in the E. officinarum P2 sample. The minimum inhibitory concentration (MIC) value ranged from 50 to 450 µL/mL against Gram-positive and Gram-negative bacteria. Euphorbia propolis displayed the ability to inhibit quorum sensing in the biosensor C. violaceum CV026 and disrupted bacterial biofilm formation, including that of resistant bacterial pathogens. In summary, the current study evidences the potential use of E. officinarum propolis (P2 and P3) to combat important features of resistant pathogenic bacteria, such as quorum sensing and biofilm formation.

Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress.

OBJECTIVE: The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. METHODS: DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). RESULTS: DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. SIGNIFICANCE: DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions. PLAIN LANGUAGE SUMMARY: Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.

Epidemiological Data and Antimicrobial Resistance of Campylobacter spp. in Portugal from 13 Years of Surveillance.

This study extensively analyzed campylobacteriosis surveillance in Portugal from 2009 to 2021, aiming to investigate demographic shifts, seasonal variations, and antimicrobial resistance (AMR) within Campylobacter isolates. Surveillance network and sentinel laboratory-based system data revealed a substantial under-notification of campylobacteriosis cases, suggesting an underestimated disease burden. Notification rates exhibited a paradigm shift, with a notable prevalence among the pediatric population, particularly in children aged 1-4 years, diverging from European reports. Additionally, an emerging trend of Campylobacter infections in younger adults (15-44 years) was observed. The study unveiled a unique seasonal distribution of cases, defying typical summer peaks seen elsewhere. AMR analysis revealed high resistance to ciprofloxacin and tetracycline, in both C. jejuni (93.7% and 79.2%, respectively) and C. coli (96.5% and 93.2%, respectively), stable throughout the studied period (2013-2021). C. coli exhibited significantly higher resistance to erythromycin, gentamicin, ampicillin and ertapenem compared to C. jejuni (p < 0.001). Multilocus Sequence Typing (MLST) data demonstrated the distribution of resistance markers across diverse sequence types, challenging the notion of a clonal origin for multidrug-resistant isolates. In conclusion, the study highlights the need for enhanced surveillance and raises concerns about alarming AMR levels, recommending the implementation of whole-genome sequencing (WGS)-based surveillance for a deeper comprehension of disease patterns and an evolving AMR landscape.

Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

Whipple’s disease-A typical endoscopic finding of a rare disease

A 49-year-old female presented with a 5-month course of diarrhoea, nocturn abdominal pain, asthenia, and weight loss of 30% of her body mass in three months. The patient had also a four-year medical history of bilateral mechanic gonalgy and arthralgias of the metacarpophalangeal and interphalangeal joints, despite treatment with prednisolone. On examination the patient had hyperpigmentation of the face and thorax, low-grade fever, and a BMI of 15,8 Kg/m2. Diarrhoea was documented with watery stools seven times per day despite loperamide, brownish, with no visible blood or mucous. Since the upper GI endoscopy and colonoscopy had no macroscopic abnormalities, the patient underwent a capsule endoscopy, which revealed continuous mucosal lesion with lymphangiectasia, oedema, villous atrophy and areas of denudation with hematinic punctate from the duodenum to the ileum. Diagnosis of Whipple’s Disease was made with typical histology findings in duodenum material and a positive PCR for Tropheryma whipplei. (AU)

Simultaneous stoma closure and type IV parastomal hernia repair after botulinum toxin and progressive pneumoperitoneum.

Surgery is the only treatment for parastomal hernia (PH). When possible, stoma closure is the best way to manage this type of hernia, however, whether to perform it in a single approach with abdominal wall reconstruction (AWR) is still debatable. A 58-year-old woman with a type IV PH with loss of domain was submitted to preoperative optimization [botulinum toxin type A and progressive pneumoperitoneum (PPP)], followed by simultaneous stoma closure and AWR. Hospital discharge was on the eighth day with no complications. Six months later, no clinical evidence of recurrence or other complication was observed. Large PHs are technically challenging. Stoma closure and simultaneous AWR increase surgical risk. Preoperative optimization with a combination of adjuvants (including PPP) is feasible in PH and may overcome technical complexity, even though patient selection remains the key when choosing a PH repair with synchronous stoma closure.

Virulence factors in carbapenem-resistant hypervirulent Klebsiella pneumoniae.

Hypervirulence and carbapenem-resistant have emerged as two distinct evolutionary pathotypes of Klebsiella pneumoniae, with both reaching their epidemic success and posing a great threat to public health. However, as the boundaries separating these two pathotypes fade, we assist a worrisome convergence in certain high-risk clones, causing hospital outbreaks and challenging every therapeutic option available. To better understand the basic biology of these pathogens, this review aimed to describe the virulence factors and their distribution worldwide among carbapenem-resistant highly virulent or hypervirulent K. pneumoniae strains, as well as to understand the interplay of these virulence strains with the carbapenemase produced and the sequence type of such strains. As we witness a shift in healthcare settings where carbapenem-resistant highly virulent or hypervirulent K. pneumoniae are beginning to emerge and replace classical K. pneumoniae strains, a better understanding of these strains is urgently needed for immediate and appropriate response.

Metabolic bone disorders and the promise of marine osteoactive compounds.

Metabolic bone disorders and associated fragility fractures are major causes of disability and mortality worldwide and place an important financial burden on the global health systems. These disorders result from an unbalance between bone anabolic and resorptive processes and are characterized by different pathophysiological mechanisms. Drugs are available to treat bone metabolic pathologies, but they are either poorly effective or associated with undesired side effects that limit their use. The molecular mechanism underlying the most common metabolic bone disorders, and the availability, efficacy, and limitations of therapeutic options currently available are discussed here. A source for the unmet need of novel drugs to treat metabolic bone disorders is marine organisms, which produce natural osteoactive compounds of high pharmaceutical potential. In this review, we have inventoried the marine osteoactive compounds (MOCs) currently identified and spotted the groups of marine organisms with potential for MOC production. Finally, we briefly examine the availability of in vivo screening and validation tools for the study of MOCs.

O contexto vivido pelo familiar e pessoa em tratamento hemodialítico / The context experienced by family members and people under hemodialytic treatment / El contexto vivido por familiares y personas en tratamiento de hemodiálisis

Objetivo: compreender o contexto vivido pelo familiar e pessoa em tratamento hemodialítico. Método: estudo descritivo exploratório, qualitativo e transversal, aprovado pelo comitê de ética em pesquisa, realizado com pacientes com doença renal crônica e seus familiares, em um munícipio do interior do estado do Rio Grande do Norte, entre junho e julho de 2019. Utilizada entrevista semiestruturada, com perguntas norteadoras para a composição estrutural do genograma e ecomapa. Posteriormente à transcrição das falas, seguiu-se a leitura e construção das categorias a partir das informações encontradas. Resultados: Foram realizadas 18 entrevistas, compondo nove famílias participantes, obtendo-se as categorias: Apoio da família, Apoio externo à família, Renúncia e Enfrentamento da doença. Conclusão: a maneira com que cada paciente e família irão vivenciar o estar doente e interpretar esse significado fará essa adaptação particular e pessoal, assim como o seu enfrentamento, particularmente ao considerar que, no núcleo familiar, ocorre uma reestruturação em meio às demandas de cuidado.

Objective: to understand the context experienced by the family member and person undergoing hemodialysis treatment. Method: exploratory, qualitative and cross-sectional descriptive study, approved by the research ethics committee, carried out with patients with chronic kidney disease and their families, in a municipality in the interior of the state of Rio Grande do Norte, between June and July 2019. Used semi-structured interview, with guiding questions for the structural composition of the genogram and ecomap. After transcribing the speeches, the categories were read and constructed based on the information found. Results: comprising nine participating families, 18 interviews were carried out, obtaining the categories: Family support, External support to the family, Resignation and Coping with the disease. Conclusion: the way in which each patient and family will experience being sick and interpret this meaning will make this particular and personal adaptation, as well as coping, particularly when considering that, within the family nucleus, a restructuring occurs amid the demands of care.

Objetivo: comprender el contexto vivido por el familiar y la persona en tratamiento de hemodiálisis. Método: estudio descriptivo exploratorio, cualitativo y transversal, aprobado por el comité de ética en investigación, realizado con pacientes con enfermedad renal crónica y sus familiares, en un municipio del interior del estado de Rio Grande do Norte, entre junio y julio de 2019. Se utilizó una entrevista semiestructurada, con preguntas orientadoras para la composición estructural del genograma y del ecomapa. Luego de transcribir las declaraciones, se leyó la construcción de las categorías a partir de las informaciones encontradas. Resultados: Se realizaron 18 entrevistas, comprendiendo nueve familias participantes, obteniendo las categorías: Apoyo familiar, Apoyo externo a la familia, Rendimiento y Enfrentamiento de la enfermedad. Conclusión: la forma en que cada paciente y familia vivirá el estar enfermo e interpretará este significado, condicionará esa adaptación particular y personal, así como su enfrentamiento, particularmente si se considera que, dentro del núcleo familiar, se produce una reestructuración en medio de las demandas del cuidado.

Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Background and aims: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. Methods: A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. Results: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. Conclusion: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

Melanoma: Multiple Presentations of an Invisible Illness.

Melanoma can spread to any organ of the body. The most affected sites are the skin and subcutaneous tissue, lymph nodes, lungs, liver, brain, bone, and intestine. Early diagnosis is crucial to prompt treatment. Although the incidence of melanoma is rising, novel treatment options are being developed, enabling a better prognosis. The authors present a rare case of metastatic melanoma affecting the muscle, lymph nodes, and subcutaneous tissue. The patient complained of redness and swelling of the right thigh and inguinal region, red, painful lumps on her chest wall, and pain in the left upper abdominal quadrant. A CT of the thorax, abdomen, and pelvis was performed, and surgical excision of the left thoracic mass led to the diagnosis of metastatic melanoma. However, no primary lesion was found despite extensive investigation. The unusual presentation of muscular metastasis heralds a poor prognosis. This case highlights the difficulty of diagnosing patients with rare presentations of a rather frequent disease.

Thermography as an indicator of goat welfare in an intensive production system.

This study evaluated the welfare of Saanen, Moxoto, and Anglo-Nubian goats kept in collective or individual pens for a feedlot system, evaluated with infrared thermography. A total of twenty-four goats were used, eight for each breed. Animals were distributed in a completely randomized design, with a 2 × 3 factorial with two fixed effects: housing type (collective or individual pens) and breed (Moxoto, Saanen, and Anglo-Nubian). The surface temperature was evaluated using an infrared thermographic camera, and behavioral analysis was based on the qualitative behavior assessment using a fixed list of descriptors. The breed was not different for all behavior evaluations and surface temperature (p>0.05). There was a difference between the housing types, where the collective pens showed goats more agitated, frustrated, and sociable (p<0.05). There was an influence of agitated, apathetic, frustrated, attentive, and curious behaviors on surface temperatures, in which feet and body temperatures decreased in these goats. (p<0.05). Moxoto, Anglo-Nubian, and Saanen goats showed similar behavior even when kept in collective or individual pens. Individual pens can restrict the goats' social relationships but reduce negative behaviors such as irritation and frustration. The lower foot temperatures of feedlot goats are related to the attention behavior in 86.75% of the observations.

Effect of Diet Supplementation with Oat Hay and Whole Carrot on Rabbit Growth and Productive Efficiency.

Is it possible to reduce feeding costs in rabbit meat production without compromising rabbit health and productive yield? The study tested four feeding strategies: Control group (CC) fed exclusively with concentrate feed; group CT supplemented with whole carrot; group OH supplemented with oat hay; and Group CO supplemented with oat hay and whole carrot. Each feeding strategy was tested in 20 rabbits, randomly allocated in five cages with four rabbits each. The average daily weight gain (ADG), feed conversion ratio (FCR), and the amount of concentrated feed consumed daily were estimated in all experimental groups. Group CC displayed the best ADG (37.1 g/rabbit/day), carrot had no significant influence on ADG (34.2 g/rabbit/day), but oat hay had a negative impact (p < 0.05), either used alone or in combination with carrot (33.0 and 32.6 g/rabbit/day, respectively). Supplementation with carrot, oat hay, or both increased the FCR (p < 0.001). Nevertheless, there were no significant differences in final live weight or carcass weight between the rabbits in the different experimental groups. In conclusion, supplementation with oat hay, carrot, or both can be a valid approach to reducing production costs by decreasing concentrate feed without affecting rabbit's health and meat yield. The combined supplementation with oat hay and carrot proved to be the best option in reducing the amount of concentrate feed ingested by rabbits (less than 1107 g/animal), but at current market values, supplementation exclusively with oat hay was the less expensive feeding strategy (less 14% than fed exclusively with concentrate feeding).

Mézières Method as a practice of embodiment in patients with low back pain: a mixed study.

INTRODUCTION: The objectives of this study were to determine the effects of the Mézières Method (MM) on pain and disability related to low back pain (LBP), compared to a program of heat, massage and exercise, and to understand the meaning of the bodily experience with the MM. PATIENTS AND METHODS: Mixed methods convergent parallel design, combining an equivalent randomized clinical trial with a qualitative phenomenological approach. Sixty-one participants aged 18-65 years with chronic non-specific LBP lasting more than 3 months. Patients were randomized into two groups: the MM group (n = 29) and the comparison group (CG) who received heat, massage plus flexibility and strengthening exercises (n = 31). MM and CG participants underwent 10 one-hour physical therapy sessions over a 5-week period and were evaluated three times: pre-intervention, post-intervention and follow-up at 6 weeks after the end of treatment. RESULTS: Both groups reported positive effects on LBP . MM group showed superior effects in pain relief in the short term (Cohen's D 0.80; p = 0.004). Participants interpreted the interaction with the MM as a teaching-learning process that allowed body awareness. CONCLUSION: Both treatment were similarly beneficial but MM had superior effects on pain in the short term. MM is perceived by the participants as a teaching-learning process focused on body awareness that facilitate effective management of LBP.

Negligible role for pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) in the nasopharyngeal colonization of mice with a serotype 6B pneumococcal strain.

Streptococcus pneumoniae colonizes the human nasopharynx asymptomatically, but it can also cause several diseases, including otitis media, pneumonia, bacteremia, and meningitis. The colonization of the nasopharynx by the bacteria is an essential step for the pneumococcus to invade other sites and cause diseases. Pneumococcal surface protein A (PspA) and Pneumococcal surface Protein C (PspC) are important virulence factors and have been described to play roles in adhesion and immune evasion. In this study, we immunized mice subcutaneously with the recombinant α-helical region of PspA and/or PspC combined with different adjuvants to assess protection against colonization with the serotype 6B strain BHN418. Though high serum levels of specific IgG were detected, none of the formulations led to reduction in the colonization of the nasopharynx. The negative result may be due to the poor induction of IgG2c, which has been previously correlated with protection against pneumococcal colonization in mice. Furthermore, BHN418 pspA and pspC single and double knockouts were evaluated in colonization experiments and no differences in bacterial load were observed. In competition assays with the wild-type strain, borderline to no reduction was observed in the loads of the knockouts. Our results contrast with data from the literature using other pneumococcal strains, showing that the role of PspA and PspC in colonization can vary depending on the background of the knockout strain studied. BHN418 has been selected for its capacity to colonize humans in experimental challenge studies and may have redundant factors that compensate for the lack of PspA and PspC during nasopharyngeal colonization of mice.

Multisystem Failure in Fatal Dengue: Associations between the Infectious Viral Serotype and Clinical and Histopathological Findings.

Dengue is the most important arthropod-borne viral infection of humans. However, its viral pathogenesis is still unknown. The information collected from dengue fatal cases is crucial for understanding the complex interactions between virulence and host factors. This study aimed to establish possible associations between the clinical characteristics, histopathological changes, replication, and tissue location of viral serotypes in dengue fatal cases. Clinical and histopathological characterizations, antigen localization in tissue, and detection of the infecting serotype and replication using real-time polymerase chain reaction were all performed on the dengue fatal cases. The majority of the cases involved people under the age of 20. Bleeding (48.3%), abdominal pain (44.8%), myalgia (52.9%), and headache (48.3%) were the most common clinical manifestations in the cases. There was multiorgan pathology, with histopathological changes primarily in the liver, spleen, and lung. Similarly, the viral antigen was found primarily in these organs; however, there were no associations between tissue changes, viral location, infecting serotypes, and replication processes. Dengue infection should be considered a multiorgan disease, the outcome of which is possibly not associated with the infecting viral serotype.

Web-based interventions to improve blood pressure control in patients with hypertension: a protocol for a systematic review.

INTRODUCTION: Hypertension is the major cause of cardiovascular disease and mortality in the world. Blood pressure control (BPC) is recognised as a key measure in the management of hypertension. Several studies have been conducted assessing the impact of specific web-based interventions in improving BPC. Our systematic review intends to identify all the available web-based interventions and determine if and which are more effective than usual care in improving BPC. METHODS AND ANALYSIS: We will include randomised control trials completed until April 2023 including patients diagnosed with hypertension comparing the effect of receiving usual care versus web-based interventions in BPC. No language restriction will be applied. We will start with an extensive electronic database search, in the Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, EU Clinical Trials Register, Pan-African Clinical Trials Registry and ClinicalTrials.gov. Eligibility criteria will be applied blindly and independently by two researchers to the title and abstract of the references, in the first stage, and to the full version of the ones selected. All divergences will be solved by a third researcher. We will conduct a narrative description and meta-analysis (if adequate) of the results of the included studies, structured according to the type of intervention, characteristics of the population and outcome measurement. We will extract features of the web-based interventions, selecting the ones with the best outcomes regarding BPC, to later propose an ideal web-based intervention to improve BPC in hypertensive patients and/or guide future research on this topic. The risk of bias will be assessed using Cochrane's RoB2 Tool. ETHICS AND DISSEMINATION: Ethical approval is not required since this is a protocol for a systematic review. The findings of this study will be disseminated through peer-reviewed publications and national or international conference presentations. Updates of the review will be conducted, as necessary. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020184166.