Association between Intracellular Calcium Signaling and Tumor Recurrence in Human Non-Functioning Pituitary Adenomas.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

Chronic Cardiac Herniation: A Peculiar Diagnosis.

The presented case describes a 56-year-old male with adult-onset Still's disease, exhibiting polyserositis in 2019, who underwent pleurectomy and pericardiectomy. Despite treatment with tocilizumab and methylprednisolone, the patient developed deep vein thrombosis and pulmonary embolism in 2022, managed with apixaban. A contrast-enhanced chest tomography revealed no recurrent thromboembolic events. Over a year, the patient experienced progressive dyspnea, correlating with signs of constriction on transthoracic echocardiogram. Cardiac magnetic resonance imaging confirmed cardiac herniation, prompting pericardiectomy. Surgery led to complete resolution of anatomical alterations without heart failure or new abnormalities, although exertional dyspnea persists post-discharge. The pathophysiology of cardiac herniation involves complex mechanisms influenced by congenital or acquired factors, resulting in abnormal heart protrusion. Medical literature highlights varied presentations, with acute cases typically post-thoracic surgeries, while late-onset cases are less common. Imaging modalities like computed tomography (CT) and cardiac magnetic resonance (CMR) aid diagnosis, emphasizing interdisciplinary collaboration. Despite challenges posed by its rarity, timely diagnosis and treatment are crucial for favourable outcomes, demonstrating the importance of considering this entity in clinical practice.

The "peel-away" technique for a ventriculoatrial shunt in a 6-month-old patient: A case report.

Background: A ventriculoatrial shunt (VAS) proves to be an excellent alternative in the treatment of hydrocephalus. Its usage is a viable option when ventriculoperitoneal shunt (VPS) is contraindicated in any age of patients. Case Description: This report highlights a successful case involving a 6-month-old patient who underwent VAS catheter positioning. The child presented with hydrocephalus and biliary atresia, making him a candidate for a liver transplant. Notably, a VPS was considered a relative contraindication in this scenario. Conclusion: The VAS emerges as a viable option for patients in whom a VPS might be contraindicated. This case demonstrates the successful application of a VAS in a pediatric patient.

Risk of progression of early-stage mycosis fungoides, 10-year experience.

BACKGROUND: Mycosis fungoides is the most frequent form of cutaneous T-cell lymphoma. It is characterized by a chronic, slow, and progressive course, and is associated with mortality rates that depend on several factors, such as clinical staging. A median survival time of up to 13 months is found in patients with advanced stages that require more aggressive treatments, with greater toxicity and higher costs. In Latin America, few prognostic studies of the disease are available. OBJECTIVE: To determine the rate of progression from early stages (IA, IB, IIA) to more advanced stages (> IIB) in patients older than 18 years with mycosis fungoides treated at two medical centers in Colombia between January 1, 2010, and December 31, 2019. METHODS: Retrospective cohort study with a longitudinal design. RESULTS: 112 patients diagnosed with early mycosis fungoides were included. 56.2% were male (n = 63), with a median age of 53 years (IQR 43‒67). The most frequent clinical variant was classic (67.9%; n = 76), followed by folliculotropic (16%; n = 18), and hypopigmented (10.7%; n = 12). The most common first-line treatment was NB-UVB phototherapy (27.7%; n = 31), followed by PUVA phototherapy (25.8%; n = 29%), and topical corticosteroids (25%; n = 28). The global rate of disease progression was 8% (n = 9), with an overall mortality of 12.5% (n = 14). STUDY LIMITATIONS: Its retrospective design and the lack of molecular studies for case characterization. CONCLUSIONS: Early mycosis fungoides is a disease with a good prognosis in most patients, with a progression rate of 8% (n = 9).

Production of the PET radionuclide 61Cu via the 62Ni(p,2n)61Cu nuclear reaction.

BACKGROUND: There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio 61Cu, 64Cu and 67Cu, for diagnosis and therapy respectively, is a very attractive candidate. In fact, the alternative of two imaging radionuclides with different half-lives is a clear advantage over other theranostic pairs, since it offers a better matching for the tracer biological and radionuclide physical half-lives. Due to the high availability of 64Cu, its translation into the clinic is being successfully carried out, giving the example of the FDA approved radiopharmaceutical Detectnet (copper Cu 64 dotatate injection). However, a shorter-lived PET radionuclide such as 61Cu may as well be beneficial. RESULTS: Proton irradiation of enriched 62Ni electrodeposited targets with a compact cyclotron produced the desired radionuclide via the 62Ni(p,2n)61Cu nuclear reaction, leading to 61Cu activities of up to 20 GBq at end of bombardment and 8 GBq at end of purification. Furthermore, two purification methods are compared leading to comparable results regarding separation yield and product purity. Following the radiochemical separation, quality assessment of this product [61Cu]CuCl2 solution proved radionuclidic purities (RNP) over 99.6% and apparent molar activities (AMA) of 260 GBq/µmol with the 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA) chelator, end of purification corrected. CONCLUSIONS: In the current article a comprehensive novel production method for the PET radionuclide 61Cu is presented, providing an alternative to the most popular production routes. Characterization of the [61Cu]CuCl2 product showed both high RNP as well as high AMA, proving that the produced activity presented high quality regarding radiolabeling up to 9 h after end of purification. Furthermore, production scalability could be easily achieved by increasing the irradiation time.

Single Nucleotide Polymorphisms Associated with Prostate Cancer Progression: A Systematic Review.

BACKGROUND: New biomarkers of progression in patients with prostate cancer (PCa) are needed to improve their classification and clinical management. This systematic review investigated the relationship between single nucleotide polymorphisms (SNPs) and PCa progression. METHODS: A keyword search was performed in Pubmed, EMBASE, Scopus, Web of Science, and Cochrane for publications between 2007 and 2022. We included articles with adjusted and significant associations, a median follow-up greater than or equal to 24 months, patients taken to radical prostatectomy (RP) as a first therapeutic option, and results presented based on biochemical recurrence (BCR). RESULTS: In the 27 articles selected, 73 SNPs were identified in 39 genes, organized in seven functional groups. Of these, 50 and 23 SNPs were significantly associated with a higher and lower risk of PCa progression, respectively. Likewise, four haplotypes were found to have a significant association with PCa progression. CONCLUSION: This article highlights the importance of SNPs as potential markers of PCa progression and their possible functional relationship with some genes relevant to its development and progression. However, most variants were identified only in cohorts from two countries; no additional studies reproduce these findings.

Bispidine Chelators for Radiopharmaceutical Applications with Lanthanide, Actinide, and Main Group Metal Ions.

Octadentate and specifically nonadentate ligands with a bispidine scaffold (3,7-diazabicyclo[3.3.1]nonane) are known to be efficiently coordinated to a range of metal ions of interest in radiopharmaceutical chemistry and lead to exceedingly stable and inert complexes. Nonadentate bispidine L2 (with a tridentate bipyridine acetate appended to N3 and a picolinate at N7) has been shown before to be an ideal chelator for 111In3+, 177Lu3+, and 225Ac3+, nuclides of interest for diagnosis and therapy, and a proof-of-principle study with an SSTR2-specific octreotate has shown potential for theranostic applications. We now have extended these studies in two directions. First, we present ligand derivative L3, in which the bipyridine acetate is substituted with terpyridine, a softer donor for metal ions with a preference for more covalency. L3 did not fulfill the hopes because complexation is much less efficient. While for Bi3+ and Pb2+ the ligand is an excellent chelator with properties similar to those of L2, Lu3+ and La3+ show very slow and inefficient complexation with L3 in contrast to L2, and 225Ac3+ is not fully coordinated, even at an increased temperature (92% radiochemical yield at 80 °C, 60 min, [L3] = 10-4 M). These observations have led to a hypothesis for the complexation pathway that is in line with all of the experimental data and supported by a preliminary density functional theory analysis, which is important for the design of further optimized bispidine chelators. Second, the coordination chemistry of L2 has been extended to Bi3+, La3+, and Pb2+, including solid state and solution structural work, complex stabilities, radiolabeling, and radiostability studies. All complexes of this ligand (La3+, Ac3+, Lu3+, Bi3+, In3+, and Pb2+), including nuclides for targeted α therapy (TAT), single-photon emission computed tomography, and positron emission tomography, are formed efficiently under physiological conditions, i.e., suitable for the labeling of delicate biological vectors such as antibodies, and the complexes are very stable and inert. Importantly, for TAT with 225Ac, the daughter nuclides 213Bi and 209Pb also form stable complexes, and this is important for reducing damage to healthy tissue.

Cyclotron-Based Production of 67Cu for Radionuclide Theranostics via the 70Zn(p,α)67Cu Reaction.

Theranostic matched pairs of radionuclides have aroused interest during the last couple of years, and in that sense, copper is one element that has a lot to offer, and although 61Cu and 64Cu are slowly being established as diagnostic radionuclides for PET, the availability of the therapeutic counterpart 67Cu plays a key role for further radiopharmaceutical development in the future. Until now, the 67Cu shortage has not been solved; however, different production routes are being explored. This project aims at the production of no-carrier-added 67Cu with high radionuclidic purity with a medical 30MeV compact cyclotron via the 70Zn(p,α)67Cu reaction. With this purpose, proton irradiation of electrodeposited 70Zn targets was performed followed by two-step radiochemical separation based on solid-phase extraction. Activities of up to 600MBq 67Cu at end of bombardment, with radionuclidic purities over 99.5% and apparent molar activities of up to 80MBq/nmol, were quantified.

Chronic circadian desynchronization of feeding-fasting rhythm generates alterations in daily glycemia, LDL cholesterolemia and microbiota composition in mice.

Introduction: The circadian system synchronizes behavior and physiology to the 24-h light- dark (LD) cycle. Timing of food intake and fasting periods provide strong signals for peripheral circadian clocks regulating nutrient assimilation, glucose, and lipid metabolism. Mice under 12 h light:12 h dark (LD) cycles exhibit behavioral activity and feeding during the dark period, while fasting occurs at rest during light. Disruption of energy metabolism, leading to an increase in body mass, was reported in experimental models of circadian desynchronization. In this work, the effects of chronic advances of the LD cycles (chronic jet-lag protocol, CJL) were studied on the daily homeostasis of energy metabolism and weight gain. Methods: Male C57 mice were subjected to a CJL or LD schedule, measuring IPGTT, insulinemia, microbiome composition and lipidemia. Results: Mice under CJL show behavioral desynchronization and feeding activity distributed similarly at the light and dark hours and, although feeding a similar daily amount of food as compared to controls, show an increase in weight gain. In addition, ad libitum glycemia rhythm was abolished in CJL-subjected mice, showing similar blood glucose values at light and dark. CJL also generated glucose intolerance at dark in an intraperitoneal glucose tolerance test (IPGTT), with increased insulin release at both light and dark periods. Low-density lipoprotein (LDL) cholesterolemia was increased under this condition, but no changes in HDL cholesterolemia were observed. Firmicutes/Bacteroidetes ratio was analyzed as a marker of circadian disruption of microbiota composition, showing opposite phases at the light and dark when comparing LD vs. CJL. Discussion: Chronic misalignment of feeding/fasting rhythm leads to metabolic disturbances generating nocturnal hyperglycemia, glucose intolerance and hyperinsulinemia in a IPGTT, increased LDL cholesterolemia, and increased weight gain, underscoring the importance of the timing of food consumption with respect to the circadian system for metabolic health.

Development and validation of an infrared-artificial intelligence software for breast cancer detection.

Aim: In countries where access to mammography equipment and skilled personnel is limited, most breast cancer (BC) cases are detected in locally advanced stages. Infrared breast thermography is recognized as an adjunctive technique for the detection of BC due to its advantages such as safety (by not emitting ionizing radiation nor applying any stress to the breast), portability, and low cost. Improved by advanced computational analytics techniques, infrared thermography could be a valuable complementary screening technique to detect BC at early stages. In this work, an infrared-artificial intelligence (AI) software was developed and evaluated to help physicians to identify potential BC cases. Methods: Several AI algorithms were developed and evaluated, which were learned from a proprietary database of 2,700 patients, with BC cases that were confirmed through mammography, ultrasound, and biopsy. Following by evaluation of the algorithms, the best AI algorithm (infrared-AI software) was submitted to a clinic validation process in which its ability to detect BC was compared to mammography evaluations in a double-blind test. Results: The infrared-AI software demonstrated efficiency values of 94.87% sensitivity, 72.26% specificity, 30.08% positive predictive value (PPV), and 99.12% negative predictive value (NPV), whereas the reference mammography evaluation reached 100% sensitivity, 97.10% specificity, 81.25% PPV, and 100% NPV. Conclusions: The infrared-AI software here developed shows high BC sensitivity (94.87%) and high NPV (99.12%). Therefore, it is proposed as a complementary screening tool for BC.

Robotic versus laparoscopic versus open major hepatectomy - an analysis of costs and postoperative outcomes in a single-center setting.

PURPOSE: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study. METHODS: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department. Patients were grouped according to the technical approach in RS, LS, and OS. For better comparability, only cases stratified to the Diagnosis Related Groups (DRG) H01A and H01B were included in this study. Financial expenses were compared between RS, LS, and OS. A binary logistic regression model was used to identify parameters associated with increased costs. RESULTS: RS, LS and OS accounted for median daily costs of 1,725 €, 1,633 € and 1,205 €, respectively (p < 0.0001). Median daily (p = 0.420) and total costs (16,648 € vs. 14,578 €, p = 0.076) were comparable between RS and LS. Increased financial expenses for RS were mainly caused by intraoperative costs (7,592 €, p < 0.0001). Length of procedure (hazard ratio [HR] = 5.4, 95% confidence interval [CI] = 1.7-16.9, p = 0.004), length of stay (HR [95% CI] = 8.8 [1.9-41.6], p = 0.006) and development of major complications (HR [95% CI] = 2.9 [1.7-5.1], p < 0.0001) were independently associated with higher costs. CONCLUSIONS: From an economic perspective, RS may be considered a valid alternative to LS for major liver resections.

Hypothalamic GnRH expression and pulsatility depends on a balance of prolactin receptors in the plains vizcacha, Lagostomus maximus.

In mammals, gestation is considered a physiological hyperprolactinemia status. Prolactin (PRL) is one of the modulators of gonadotropin-releasing hormone (GnRH) neurons function. The South American plains vizcacha (Lagostomus maximus) is a unique model to study the regulation of hypothalamic GnRH neurons by direct and indirect steroid-dependent pathways. The aim was to characterize the hypothalamic expression of endocrine markers in vizcacha during gestation as well as their response to experimental induced hyperprolactinemia. The possible involvement of PRL regulatory pathways on GnRH in the context of hypothalamic and pituitary reactivation in mid-gestating vizcachas was discussed. Using two in vivo approaches, we determined changes in the hypothalamic expression and distribution of prolactin receptor (PRLR), tyrosine hydroxylase (TH), and dopamine type 2 receptor. A significant increment in the number of tuberoinfundibular dopaminergic (TIDA) neurons was determined in the arcuate nucleus from early to term pregnancy. On the other hand, at preoptic area, the number of both TH+PRLR+ and GnRH+PRLR+ double-labeled neurons significantly decreased at mid-pregnancy probably allowing the recovery of GnRH expression indicating that both types of neurons may represent the key points of PRL indirect and direct pathways modulating GnRH. Moreover, in a model of induced hyperprolactinemic vizcachas, the inhibitory effect of PRL on GnRH at both expression and delivery levels were confirmed. These results suggest the concomitant participation of both PRL regulatory pathways on GnRH modulation and pinpoint the key role of PRL on GnRH expression enabling the recovery of the hypothalamic activity during the gestation in this species.

Resultados del tratamiento quirúrgico del cáncer de recto y ano en el Hospital Español / Results of the surgical treatment of rectal and anal cancer in the Hospital Español / Resultados do tratamento cirúrgico do câncer de reto e ânus no Hospital Español

La cirugía del cáncer de recto y ano se ha desarrollado considerablemente en las últimas décadas. En función de dichos avances, se ha observado una disminución en la morbimortalidad operatoria, así como también una mejoría en el pronóstico de estos pacientes. El objetivo del presente estudio es exponer y analizar los resultados del tratamiento quirúrgico del cáncer de recto y ano en un servicio universitario. Se realizó un estudio observacional, descriptivo y retrospectivo de todos los pacientes intervenidos por cáncer de recto y ano en el Hospital Español entre 2016 y 2020. Las variables registradas fueron: variables demográficas, clínico-oncológicas, relacionadas a la morbimortalidad operatoria y a la recidiva locorregional, y la sobrevida a 5 años. El procedimiento más realizado fue la resección anterior de recto (RAR) en 11 intervenciones (58%), mientras que las 8 restantes correspondieron a amputaciones abdominoperineales (AAP) (42%). Se diagnosticaron un total de 6 complicaciones intraoperatorias en 5 pacientes, siendo la perforación del tumor la más frecuente, y un total de 18 complicaciones postoperatorias en 11 pacientes, siendo la más frecuente la infección de la herida quirúrgica abdominal. La morbilidad operatoria mayor fue de 31,6% y la mortalidad operatoria a 90 días fue de 0%. La sobrevida global a 5 años fue de 63,2%. Los resultados quirúrgicos en la presente casuística fueron comparables con los de la bibliografía consultada. Destacamos la nula mortalidad a 90 días, con resultados oncológicos similares a los reportados en la literatura.

Rectal and anus surgery have been developed considerably in the last decades. Based on these advancements, it has been observed a decrease in the surgical morbidity and mortality, as well as an improved prognosis of these patients. The aim of the present study is to expose and analyze the results of the anus and rectal surgical treatment in a university service. An observational, descriptive and retrospective study was performed of all the intervened patients for rectum and anus cancer in the Hospital Español between 2016 and 2020. We recorded data about demographic, clinical-oncologic, related to the surgical morbidity and mortality, locoregional relapse and overall 5 year survival. The most performed procedure was the rectum anterior resection in 11 interventions (58%), while the 8 left corresponded to abdominoperineal resection (42%). There was a total of 6 intraoperative complications diagnosed in 5 patients, being the tumor perforation the most frequent one, and a total of 18 postoperative complications diagnosed in 11 patients, being the surgical wound infection the most frequent one. The serious surgical morbidity was 31,6%, while the surgical mortality rate at 90 days was 0%. Overall 5 year survival was 63,2%. The surgical results in the present study about the rectum and anal cancer were comparable with the results reported on the consulted bibliography. We highlight the null mortality within 90 days, with oncologic results similar to the ones reported in the literature.

A cirurgia do câncer retal e anal desenvolveu-se consideravelmente nas últimas décadas. Com base nesses avanços, observou-se diminuição da morbimortalidade operatória, bem como melhora no prognóstico desses pacientes. O objetivo deste estudo é apresentar e analisar os resultados do tratamento cirúrgico do câncer de reto e anal em um serviço universitário. Foi realizado um estudo observacional, descritivo e retrospectivo de todos os pacientes operados por câncer de reto e ânus no Hospital Espanhol entre 2016 e 2020. As variáveis ​​registradas foram: variáveis ​​demográficas, clínico-oncológicas, relacionadas à morbidade e mortalidade operatórias e recorrência locorregional. , e sobrevida em 5 anos. O procedimento mais realizado foi a ressecção anterior do reto (RAR) em 11 intervenções (58%) e as 8 restantes corresponderam a amputações abdominoperineais (AAP) (42%). Foram diagnosticadas 6 complicações intraoperatórias em 5 pacientes, sendo a perfuração tumoral a mais frequente, e um total de 18 complicações pós-operatórias em 11 pacientes, sendo a infecção da ferida operatória abdominal a mais frequente. A morbidade operatória maior foi de 31,6% e a mortalidade operatória em 90 dias foi de 0%. A sobrevida global em 5 anos foi de 63,2%. Os resultados cirúrgicos da presente casuística foram comparáveis ​​aos da bibliografia consultada. Destacamos a mortalidade nula em 90 dias, com resultados oncológicos semelhantes aos relatados na literatura.

Efficient Production of the PET Radionuclide 133La for Theranostic Purposes in Targeted Alpha Therapy Using the 134Ba(p,2n)133La Reaction.

Targeted Alpha Therapy is a research field of highest interest in specialized radionuclide therapy. Over the last decades, several alpha-emitting radionuclides have entered and left research topics towards their clinical translation. Especially, 225Ac provides all necessary physical and chemical properties for a successful clinical application, which has already been shown by [225Ac]Ac-PSMA-617. While PSMA-617 carries the DOTA moiety as the complexing agent, the chelator macropa as a macrocyclic alternative provides even more beneficial properties regarding labeling and complex stability in vivo. Lanthanum-133 is an excellent positron-emitting diagnostic lanthanide to radiolabel macropa-functionalized therapeutics since 133La forms a perfectly matched theranostic pair of radionuclides with the therapeutic radionuclide 225Ac, which itself can optimally be complexed by macropa as well. 133La was thus produced by cyclotron-based proton irradiation of an enriched 134Ba target. The target (30 mg of [134Ba]BaCO3) was irradiated for 60 min at 22 MeV and 10−15 µA beam current. Irradiation side products in the raw target solution were identified and quantified: 135La (0.4%), 135mBa (0.03%), 133mBa (0.01%), and 133Ba (0.0004%). The subsequent workup and anion-exchange-based product purification process took approx. 30 min and led to a total amount of (1.2−1.8) GBq (decay-corrected to end of bombardment) of 133La, formulated as [133La]LaCl3. After the complete decay of 133La, a remainder of ca. 4 kBq of long-lived 133Ba per 100 MBq of 133La was detected and rated as uncritical regarding personal dose and waste management. Subsequent radiolabeling was successfully performed with previously published macropa-derived PSMA inhibitors at a micromolar range (quantitative labeling at 1 µM) and evaluated by radio-TLC and radio-HPLC analyses. The scale-up to radioactivity amounts that are needed for clinical application purposes would be easy to achieve by increasing target mass, beam current, and irradiation time to produce 133La of high radionuclide purity (>99.5%) regarding labeling properties and side products.

Cardiology co-management of rheumatoid arthritis patients with coronary artery disease as an intervention reduces hospitalization rates and adverse event occurrence.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease with important cardiovascular (CV) implications. CV disease represents over half of RA patient deaths and causes significant morbidity. CV manifestations in RA can be complex, raising concerns for adequate patient management and provider-dependent roles. METHODS: This is a retrospective study of patients diagnosed with RA and coronary artery disease (CAD). Patients were identified and filtered via EPIC Database search engine. Parameters were set from January 1, 2014, to December 31, 2020. Inclusion criteria consisted of patients who met diagnostic criteria for both RA and CAD. A total of 399 patients met criteria. RESULTS: Of the 399 identified patients, 272 were female (68.2%) and 127 were male (31.8%) with a median age of 73 (range 26-98). The population was further divided into two groups: those with established cardiology care versus those without. Patients without cardiology follow-up experienced significantly more hospitalizations (RR 1.63 95% CI 1.12, 2.38), higher rates of adverse events including myocardial infarction (MI) (RR 4.82 95% CI 1.94, 11.98), heart failure (HF) (OR 15.81 95% CI 3.54, 70.52), and stroke (RR 2.55 95% CI 1.29, 5.03). Patients not followed by cardiology also had numerical increases in CV death (4 deaths compared to none in those with cardiology follow) and all-cause mortality (HR 1.03 95% CI 0.63, 1.67). CONCLUSION: Patients with regular cardiology follow-up demonstrated fewer cardiac-related adverse events. This suggests that co-management may have a role in adverse cardiac event risk reduction and should therefore be an early consideration. Key Points • Rheumatoid arthritis patients demonstrate higher rates of coronary disease compared to the general population. Traditional cardiac risk factors may not be entirely responsible for this phenomenon • Hospitalization rates and adverse event occurrence are significantly higher in patients with single-provider care (rheumatology only) compared to dual provider care (rheumatology and cardiology) • Cardiology co-management should be an early consideration in the management of RA patients • Early screening, risk stratification of coronary disease, and utilization of appropriate treatment algorithms are important to decrease morbidity and mortality.

Effects of glyphosate on cladocera: A synthetic review.

Glyphosate [N-(phosphonomethyl) glycine] is currently the most widely used herbicide worldwide. Its application in agricultural and urban areas can lead to the dispersion and arrival to aquatic systems causing environmental deterioration with detrimental effects on the inhabiting biota. This is triggered not only by the herbicide per se but also its metabolite aminomethyl-phosphonic acid (AMPA), which can be highly toxic to many aquatic organisms. Water fleas are some of the key components in aquatic food webs, being one of the most sensitive groups to pollutants. Although being often used in standardized toxicity tests, they are comparatively less studied in relation to glyphosate exposition. Here we examine the current scientific literature regarding the acute and sublethal toxicity of glyphosate in the Cladocera taxonomic group, with special comparisons between the active ingredient (A.I) and formulations. Our results document a high variation in the lethal concentrations reported for different cladoceran species, due to the high diversity of products used in the toxicity tests. Most articles accounting for sublethal effects were performed on the standard Daphnia magna species. Reproduction, including decreased fecundity and delayed age of first reproduction, is usually one of the most severely affected individual traits. Although still scarce, studies documenting metabolic and genetic alterations might provide accurate information on the mechanisms of action of the herbicide.

Cysteine Oxidation Promotes Dimerization/Oligomerization of Circadian Protein Period 2.

The molecular circadian clock is based on a transcriptional/translational feedback loop in which the stability and half-life of circadian proteins is of importance. Cysteine residues of proteins are subject to several redox reactions leading to S-thiolation and disulfide bond formation, altering protein stability and function. In this work, the ability of the circadian protein period 2 (PER2) to undergo oxidation of cysteine thiols was investigated in HEK-293T cells. PER2 includes accessible cysteines susceptible to oxidation by nitroso cysteine (CysNO), altering its stability by decreasing its monomer form and subsequently increasing PER2 homodimers and multimers. These changes were reversed by treatment with 2-mercaptoethanol and partially mimicked by hydrogen peroxide. These results suggest that cysteine oxidation can prompt PER2 homodimer and multimer formation in vitro, likely by S-nitrosation and disulphide bond formation. These kinds of post-translational modifications of PER2 could be part of the redox regulation of the molecular circadian clock.

Achieving full-term pregnancy in the vizcacha relies on a reboot of luteal steroidogenesis in mid-gestation (Lagostomus maximus, Rodentia).

Reactivation of the hypothalamic-pituitary-ovarian (HPO) axis triggered by the decline in serum progesterone in mid-gestation is an uncommon trait that distinguishes the vizcacha from most mammals. Accessory corpora lutea (aCL) developed upon this event have been proposed as guarantors of the restoration of the progesterone levels necessary to mantain gestation. Therefore, the steroidogenic input of primary CL (pCL) vs aCL was evaluated before and after HPO axis-reactivation (BP and AP respectively) and in term pregnancy (TP). Nonpregnant-ovulated females (NP) were considered as the pCL-starting point group. In BP, the ovaries mainly showed pCL, whose LH receptor (LHR), StAR, 3ß-HSD, 20α-HSD, and VEGF immunoexpressions were similar or lower than those of NP. In AP, luteal reactivity increased significantly compared to the previous stages, and the pool of aCL developed in this stage represented 20% of the ovarian structures, equaling the percentage of pCL. Both pCL and aCL luteal cells shared similar histological features consistent with secretory activity. Although pCL and aCL showed equivalent labeling intensity for the luteotropic markers, pCL were significantly larger than aCL. Towards TP, both showed structural disorganization and loss of secretory characteristics. No significant DNA fragmentation was detected in luteal cells throughout gestation. Our findings indicate that the LH surge derived from HPO axis-reactivation targets the pCL and boost luteal steroidogenesis and thus progesterone production. Because there are many LHR-expressing antral follicles in BP, they also respond to the LH stimuli and luteinize without extruding the oocyte. These aCL certainly contribute but it is the steroidogenic restart of the pCL that is the main force that restores progesterone levels, ensuring that gestation is carried to term. Most importantly, the results of this work propose luteal steroidogenesis reboot as a key event in the modulation of vizcacha pregnancy and depict yet another distinctive aspect of its reproductive endocrinology.

Evaluation of Telehealth Service for COVID-19 Outpatients: A Dashboard to Measure Healthcare Quality and Safety.

Due to the COVID-19 pandemic, changes and improvements regarding the organization have been made to adapt quickly at the Emergency Department (ED) of the Hospital Italiano de Buenos Aires, Argentina. This article describes the design, implementation, and use of an electronic dashboard which provided monitoring of patients discharged home, during follow-up with telehealth. It was useful to access essential information to organize and coordinate professional work and patients' surveillance, providing highly relevant data in real-time as proxy variables for quality and safety during home isolation. The implemented tool innovated in the integration of technologies within a real context. The information management was crucial to optimize services and decision-making, as well to guarantee safety for healthcare workers and patients.

Impact of COVID-19 Pandemic on Telehealth and In-Person Visits: Implications from an Emergency Department in Argentina.

Since Argentina's government declared a national emergency to combat the COVID-19 pandemic with a lockdown status, it has produced consequences on the healthcare system. We aimed to quantify the effect on the Emergency Department (ED) visits at Hospital Italiano de Buenos Aires. Our electronic health data showed that ED in-person visits declined 46% during the COVID-19 pandemic, from an overall of 176,370 visits during 2019 to 95,421 visits during 2020. Simultaneously, there was a telehealth visits boom when mandatory quarantine began (March 20, 2020): from a median of 12 daily in February 2020 to a median of 338 daily in April 2020; reaching a maximum daily peak of 1,132 on March 26 2020. For a while, teleconsultations replaced ED visits. Then, when face-to-face visits began to increase, teleconsultations began to decrease slowly, as the phenomenon reversed.