2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus.

BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

Utilização da pele de tilápia-do-Nilo (Oreochromis niloticus) como xenoenxerto em um equino com ferimento traumático / Treatment of a traumatic equine wound using Nile tilapia (Oreochromis niloticus) skin as a xenograft

Background: Wounds are disruptions of the normal continuity of anatomic structures, generally due to local trauma. Theyare extremely prevalent in animals, especially horses, and a common reason for seeking veterinary attention. Their management aims to restore the function and integrity of the affected area in the shortest possible time and cost, while providingsatisfactory cosmetic results. This task becomes challenging when working with horses, considering the contact betweenwounds and contaminated environment is common. Thus, the present study aims to report the case of a traumatic equinewound treated with Nile Tilapia Fish Skin (NTFS).Case: A male 27-year-old horse previously castrated, with no defined breed (NDB), and weighing 400 kg presented a 6.0 x5.5 cm superficial wound in the distal left anterior limb (LAL) due to skin laceration. The animal belonged to the cavalry ofthe Military Police of Ceará, a public institution in Fortaleza, Brazil. Although in excellent general health, with no previouscomorbidities or restriction of movement, the animal was removed from its role in equine-assisted therapy (EAT) until completewound healing, aiming adequate evaluation of the novel biomaterial via lower influence of external factors. After informedconsent from the owner was obtained, Nile Tilapia Fish Skin was applied to the lesion. The Ethics Committee on the use ofanimals of the Drug Research and Development Center of the Federal University of Ceará, Fortaleza, Brazil, approved the studyprotocol. Compliance with regulations on the ethical treatment of animals was performed. Nile Tilapia Fish Skin applicationfollowed a protocol similar to that established in human clinical studies. Initially, the horse was submitted to wound cleaningwith tap water and 2% chlorhexidine gluconate, with no requirement of pre-treatment surgical...(AU)

Utilização da pele de tilápia-do-Nilo (Oreochromis niloticus) como xenoenxerto em um equino com ferimento traumático / Treatment of a traumatic equine wound using Nile tilapia (Oreochromis niloticus) skin as a xenograft

Background: Wounds are disruptions of the normal continuity of anatomic structures, generally due to local trauma. Theyare extremely prevalent in animals, especially horses, and a common reason for seeking veterinary attention. Their management aims to restore the function and integrity of the affected area in the shortest possible time and cost, while providingsatisfactory cosmetic results. This task becomes challenging when working with horses, considering the contact betweenwounds and contaminated environment is common. Thus, the present study aims to report the case of a traumatic equinewound treated with Nile Tilapia Fish Skin (NTFS).Case: A male 27-year-old horse previously castrated, with no defined breed (NDB), and weighing 400 kg presented a 6.0 x5.5 cm superficial wound in the distal left anterior limb (LAL) due to skin laceration. The animal belonged to the cavalry ofthe Military Police of Ceará, a public institution in Fortaleza, Brazil. Although in excellent general health, with no previouscomorbidities or restriction of movement, the animal was removed from its role in equine-assisted therapy (EAT) until completewound healing, aiming adequate evaluation of the novel biomaterial via lower influence of external factors. After informedconsent from the owner was obtained, Nile Tilapia Fish Skin was applied to the lesion. The Ethics Committee on the use ofanimals of the Drug Research and Development Center of the Federal University of Ceará, Fortaleza, Brazil, approved the studyprotocol. Compliance with regulations on the ethical treatment of animals was performed. Nile Tilapia Fish Skin applicationfollowed a protocol similar to that established in human clinical studies. Initially, the horse was submitted to wound cleaningwith tap water and 2% chlorhexidine gluconate, with no requirement of pre-treatment surgical...

Outcome and long-term follow-up of adrenal lesions in multiple endocrine neoplasia type 1

ABSTRACT Objective To describe the prevalence, clinical characteristics and outcome of adrenal lesions in long-term follow-up of Multiple endocrine neoplasia type 1 (MEN1) patients. Subjects and methods We retrospectively studied sixteen patients from six families of individuals with MEN1. Adrenal involvement was evaluated using clinical, biochemical and imaging data. Results Adrenal lesions were identified in nine of sixteen (56.3%) patients: seven women and two men (mean age: 52.2 years). Adrenal involvement was detected at MEN1 diagnosis in more than half of the patients. Eighteen adrenal nodules were founded (median of two nodules per patient) with mean adrenal lesion diameter of 17.4 mm. Three patients had unilateral adrenal involvement. Hormonal hypersecretion (autonomous cortisol secretion) was found in two patients. None of the patients was submitted to adrenalectomy, presented an aldosterone-secreting lesion, a pheochromocytoma, an adrenal carcinoma or metastatic disease during the follow-up. A predominance of stable adrenal disease, in terms of size and hormonal secretion, was observed. Adrenal lesions were evenly distributed between the germline mutations. Conclusion Adrenal tumours are a common feature of MEN1 that can affect more than half of the patients. Most of the tumours are bilateral non-functional lesions, but hormonal secretion may occur and should be promptly identified to reduce the morbidity/mortality of the syndrome. Periodic surveillance of these patients should be performed.

Outcome and long-term follow-up of adrenal lesions in multiple endocrine neoplasia type 1.

OBJECTIVE: To describe the prevalence, clinical characteristics and outcome of adrenal lesions in long-term follow-up of Multiple endocrine neoplasia type 1 (MEN1) patients. SUBJECTS AND METHODS: We retrospectively studied sixteen patients from six families of individuals with MEN1. Adrenal involvement was evaluated using clinical, biochemical and imaging data. RESULTS: Adrenal lesions were identified in nine of sixteen (56.3%) patients: seven women and two men (mean age: 52.2 years). Adrenal involvement was detected at MEN1 diagnosis in more than half of the patients. Eighteen adrenal nodules were founded (median of two nodules per patient) with mean adrenal lesion diameter of 17.4 mm. Three patients had unilateral adrenal involvement. Hormonal hypersecretion (autonomous cortisol secretion) was found in two patients. None of the patients was submitted to adrenalectomy, presented an aldosterone-secreting lesion, a pheochromocytoma, an adrenal carcinoma or metastatic disease during the follow-up. A predominance of stable adrenal disease, in terms of size and hormonal secretion, was observed. Adrenal lesions were evenly distributed between the germline mutations. CONCLUSION: Adrenal tumours are a common feature of MEN1 that can affect more than half of the patients. Most of the tumours are bilateral non-functional lesions, but hormonal secretion may occur and should be promptly identified to reduce the morbidity/mortality of the syndrome. Periodic surveillance of these patients should be performed.

Remoção cirúrgica de melanoma de terceira pálpebra em equino / Surgical removal of melanoma in the third eyelid in equine

O melanoma é uma neoplasia maligna de melanócitos, os quais produzem a melanina responsável pela pigmentação da pele, descrito em várias espécies animais e em seres humanos. Em equinos, esse tipo tumoral representa grande parte dos comprometimentos cutâneos, principalmente em animais de pelagem tordilha; porém não se observa predileção racial e sexual, sendo a idade considerada um agravante na malignidade. Esta afecção acomete principalmente as regiões de cauda, períneo, orelhas e olhos, e ocasionalmente se desenvolvem em órgãos genitais; sendo que o curso clínico varia desde a invasão de órgãos até a disseminação metastática. Caracterizam-se por lesões firmes, nodulares, únicas ou múltiplas, de tamanhos e coloração variados, infiltrativas, podendo ocorrer ulcerações. Os sinais clínicos demonstrados pelos pacientes acometidos são variáveis, dependendo da localização tumoral. Em animais, o diagnóstico de melanoma está relacionado a um prognóstico desfavorável, pois, em geral, o tumor é detectado tardiamente, quando já houve infiltração local ou formação de metástases. Este trabalho tem como objetivo relatar um caso relacionado a melanoma de terceira pálpebra em um equino macho, com 13 anos de idade, raça Puro Sangue Lusitano (PSL), pelagem tordilha. O animal apresentava nódulos de tamanhos consideráveis na terceira pálpebra do olho direito, de coloração enegrecida, sendo submetido a procedimento cirúrgico para a remoção total do mesmo. O animal foi submetido a um protocolo pós-cirúrgico com antibioticoterapia local na forma de colírio (Ciprofloxacina 0,3mg ou 02 gotas), quatro vezes ao dia, durante dez dias e também sistêmica (Benzilpenicilina G Procaína 4000UI/Kg/PV) por via intramuscular, uma vez ao dia, durante cinco dias...

Melanoma is a malignant neoplasm of melanocytes which produce melanin, responsible for skin pigmentation, described in various animal species and in humans. In equines, this tumor type represents a large part of the mainly in fur animals; but there is no racial and sexual predilection, and age is considered an aggravating factor in malignancy. This condition mainly affects the tail, perineum, auricular and ocular regions and occasionally develops in the genital organs; and the clinical course varies from invasion of organs to metastatic dissemination. It is characterized by firm, nodular, single or multiple lesions of varying infiltrative sizes and staining, and ulcerations may occur. The clinical signs demonstrated by the affected patients are variable, depending on the tumor location. In animals, the diagnosis of melanoma is related to an unfavorable prognosis, since, in general, the tumor is detected late, when there has been local infiltration or formation of metastases. The aim of this study is to report a case related to third eyelid melanoma in a 13 year - old male Purebred Lusitano (PSL) equine breed. The animal presented nodules of considerable size in the third eyelid of the right eye, of blackened color, being submitted to surgical procedure for the total removal of the same one. The animal was submitted to a post-surgical protocol with local antibiotic therapy in the form of eye drops (Ciprofloxacin 0.3mg or 2 drops), four times a day for ten days and also systemic (Benzylpenicillin G Procaine 4000UI/Kg/PV) intramuscularly once daily for five days. As an anti-inflammatory protocol, it was used topically, eye drops (Flurbiprofen Sodium 0.03mg or 2 drops), four times a day for ten days and intravenously (Fenilbutazone 4.0mg/Kg/PV), once a day during five days, responding satisfactorily to the treatment.

Remoção cirúrgica de melanoma de terceira pálpebra em equino / Surgical removal of melanoma in the third eyelid in equine

O melanoma é uma neoplasia maligna de melanócitos, os quais produzem a melanina responsável pela pigmentação da pele, descrito em várias espécies animais e em seres humanos. Em equinos, esse tipo tumoral representa grande parte dos comprometimentos cutâneos, principalmente em animais de pelagem tordilha; porém não se observa predileção racial e sexual, sendo a idade considerada um agravante na malignidade. Esta afecção acomete principalmente as regiões de cauda, períneo, orelhas e olhos, e ocasionalmente se desenvolvem em órgãos genitais; sendo que o curso clínico varia desde a invasão de órgãos até a disseminação metastática. Caracterizam-se por lesões firmes, nodulares, únicas ou múltiplas, de tamanhos e coloração variados, infiltrativas, podendo ocorrer ulcerações. Os sinais clínicos demonstrados pelos pacientes acometidos são variáveis, dependendo da localização tumoral. Em animais, o diagnóstico de melanoma está relacionado a um prognóstico desfavorável, pois, em geral, o tumor é detectado tardiamente, quando já houve infiltração local ou formação de metástases. Este trabalho tem como objetivo relatar um caso relacionado a melanoma de terceira pálpebra em um equino macho, com 13 anos de idade, raça Puro Sangue Lusitano (PSL), pelagem tordilha. O animal apresentava nódulos de tamanhos consideráveis na terceira pálpebra do olho direito, de coloração enegrecida, sendo submetido a procedimento cirúrgico para a remoção total do mesmo. O animal foi submetido a um protocolo pós-cirúrgico com antibioticoterapia local na forma de colírio (Ciprofloxacina 0,3mg ou 02 gotas), quatro vezes ao dia, durante dez dias e também sistêmica (Benzilpenicilina G Procaína 4000UI/Kg/PV) por via intramuscular, uma vez ao dia, durante cinco dias...(AU)

Melanoma is a malignant neoplasm of melanocytes which produce melanin, responsible for skin pigmentation, described in various animal species and in humans. In equines, this tumor type represents a large part of the mainly in fur animals; but there is no racial and sexual predilection, and age is considered an aggravating factor in malignancy. This condition mainly affects the tail, perineum, auricular and ocular regions and occasionally develops in the genital organs; and the clinical course varies from invasion of organs to metastatic dissemination. It is characterized by firm, nodular, single or multiple lesions of varying infiltrative sizes and staining, and ulcerations may occur. The clinical signs demonstrated by the affected patients are variable, depending on the tumor location. In animals, the diagnosis of melanoma is related to an unfavorable prognosis, since, in general, the tumor is detected late, when there has been local infiltration or formation of metastases. The aim of this study is to report a case related to third eyelid melanoma in a 13 year - old male Purebred Lusitano (PSL) equine breed. The animal presented nodules of considerable size in the third eyelid of the right eye, of blackened color, being submitted to surgical procedure for the total removal of the same one. The animal was submitted to a post-surgical protocol with local antibiotic therapy in the form of eye drops (Ciprofloxacin 0.3mg or 2 drops), four times a day for ten days and also systemic (Benzylpenicillin G Procaine 4000UI/Kg/PV) intramuscularly once daily for five days. As an anti-inflammatory protocol, it was used topically, eye drops (Flurbiprofen Sodium 0.03mg or 2 drops), four times a day for ten days and intravenously (Fenilbutazone 4.0mg/Kg/PV), once a day during five days, responding satisfactorily to the treatment.(AU)

TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma.

PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

Analysis of mental workload of electrical power plant operators of control and operation centers.

Electrical systems can be categorized as critical systems where failure can result in significant financial loss, injury or threats to human life. The operators of the electric power control centers perform an activity in a specialized environment and have to carry it out by mobilizing knowledge and reasoning to which they have adequate training under the terms of the existing rules. To reach this there is a common mental request of personnel involved in these centers due the need to maintain attention, memory and reasoning request. In this sense, this study aims to evaluate the Mental Workload of technical workers of the Control Centers of Electrical Energy. It was undertaken a research on operators control centers of the electricity sector in Northeast Brazil. It was used for systematic observations, followed by interview and application of the instrument National Aeronautics and Space Administration Task Load Index known as NASA-TLX. As a result there will be subsidies for an assessment of mental workload of operators, and a contribution to improving the processes of managing the operation of electric utilities and the quality of workers.