Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Cardiac Amyloidosis in Venezuela: A Pending Issue.

Cardiac amyloidosis (CA) is an infiltrative disease characterized by the deposition of misfolded proteins in cardiac interstitial tissue. Interest towards studying this pathology has been growing in the last decade, as new epidemiological insights have revealed that it is not as uncommon as previously believed. Likewise, advances in non-invasive diagnostic approaches and the identification of molecules that modify its long-term progression, even in terms of mortality, have also bolstered interest in CA. Despite this global panorama, in Venezuela, limitations remain regarding the diagnosis of CA, partly associated with a lack of knowledge of the disease. Therefore, additional efforts are necessary for clinical cardiologists to hone their diagnostic skills regarding this disease, as opportune identification is an essential step for its effective management.

Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte-endothelial interactions.

AIMS/HYPOTHESIS: Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population. METHODS: This is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte-endothelial interaction assays were performed by perfusing participants' leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system. RESULTS: Participants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA1c, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte-endothelial interactions. CONCLUSIONS/INTERPRETATION: Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.

Assessing the prevalence and severity of cisplatin-induced nephrotoxicity in a minority- low socioeconomic population in the Bronx, New York.

Studies evaluating Cisplatin-induced nephrotoxicity in minorities are limited. We conducted a retrospective review of adult patients receiving cisplatin from 2019 to 2023 at an inner-city hospital. Renal indices were obtained at baseline and after cycles 1, 2, and 3 of Cisplatin. A total of 93 patients were included, 46% were male. Median age was 57 years. About 40% were Black, 13% White, and 42% Hispanic. About 54% were uninsured. About 16% of the patients developed AKI after cycle 1 of cisplatin, 5% after cycle 2%, and 17% after cycle 3. There was no statistically significant correlation between race, sex, BMI and development of cisplatin-induced AKI. Repeated measures ANOVA test indicated a statistically significant and cumulative rise in creatinine level following cisplatin therapy [Wilks' Lambda = 0.003, F(1,26)=13.7, η2 = 0.44]. Our study in a minority, low socioeconomic population highlights the progressive kidney injury following each cycle of cisplatin therapy. Further studies targeting this specific population are warranted to develop tailored interventions.

Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring.

BACKGROUND: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). METHODS: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. FINDINGS: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: -15.0%, (SD = 19.1); Mogen clamp Prevotella: -3.6% (11.2); ShangRing Veillonella: -11.3% (17.2); Mogen clamp Veillonella: -2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. INTERPRETATION: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. FUNDING: Bill and Melinda Gates Foundation.

Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.

Evolution of the Antigenic Landscape in Children and Young Adults with COVID-19 and MIS-C.

There is minimal knowledge regarding the durability of neutralization capacity and level of binding antibody generated against the highly transmissible circulating Omicron subvariants following SARS-CoV-2 infection in children with acute COVID-19 and those diagnosed with multisystem inflammatory syndrome in children (MIS-C) in the absence of vaccination. In this study, SARS-CoV-2 neutralization titers against the ancestral strain (WA1) and Omicron sublineages were evaluated in unvaccinated children admitted for COVID-19 (n = 32) and MIS-C (n = 32) at the time of hospitalization (baseline) and at six to eight weeks post-discharge (follow-up) between 1 April 2020, and 1 September 2022. In addition, antibody binding to the spike receptor binding domain (RBD) from WA1, BA.1, BA.2.75, and BA.4/BA.5 was determined using surface plasmon resonance (SPR). At baseline, the children with MIS-C demonstrated two-fold to three-fold higher binding and neutralizing antibodies against ancestral WA1 compared to those with COVID-19. Importantly, in children with COVID-19, the virus neutralization titers against the Omicron subvariants at six to eight weeks post-discharge reached the same level as those with MIS-C had at baseline but were higher than titers at 6-8 weeks post-discharge for MIS-C cases. Cross-neutralization capacity against recently emerged Omicron BQ.1, BQ.1.1, and XBB.1 variants was very low in children with either COVID-19 or MIS-C at all time points. These findings about post-infection immunity in children with either COVID-19 or MIS-C suggest the need for vaccinations in children with prior COVID-19 or MIS-C to provide effective protection from emerging and circulating SARS-CoV-2 variants.

Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

Mitochondrial bioenergetics as a cell fate rheostat for responsive to Bcl-2 drugs: New cues for cancer chemotherapy.

Pro-survival BCL-2 proteins prevent the initiation of intrinsic apoptosis (mitochondria-dependent pathway) by inhibiting the pro-apoptotic proteins BAX and BAK, while BH3-only proteins promote apoptosis by blocking pro-survival BCL-2 proteins. Disruptions in this delicate balance contribute to cancer cell survival and chemoresistance. Recent advances in cancer therapeutics involve a new generation of drugs known as BH3-mimetics, which are small molecules designed to mimic the action of BH3-only proteins. Promising effects have been observed in patients with hematological and solid tumors undergoing treatment with these agents. However, the rapid emergence of mitochondria-dependent resistance to BH3-mimetics has been reported. This resistance involves increased mitochondrial respiration, altered mitophagy, and mitochondria with higher and tighter cristae. Conversely, mutations in isocitrate dehydrogenase 1 and 2, catalyzing R-2-hydroxyglutarate production, promote sensitivity to venetoclax. This evidence underscores the urgency for comprehensive studies on bioenergetics-based adaptive responses in both BH3 mimetics-sensitive and -resistant cancer cells. Ongoing clinical trials are evaluating BH3-mimetics in combination with standard chemotherapeutics. In this article, we discuss the role of mitochondrial bioenergetics in response to BH3-mimetics and explore potential therapeutic opportunities through metabolism-targeting strategies.

Paxlovid™ reduces the incidence of pneumonia, hospitalization, and death in a cohort of COVID-19 patients from northeast Mexico.

BACKGROUND: Information on Paxlovid™ effectiveness must be monitored and updated in real world scenarios. Our research question was what is the effectiveness of Paxlovid™ in adult patients with COVID-19? Therefore, we investigated the effectiveness of Paxlovid™ on reducing the incidence of pneumonia, hospitalization, and mortality in a cohort of COVID-19 positive adult patients from northeast Mexico. METHODS: A retrospective cohort study of COVID-19 positive adult patients from Nuevo Leon, Mexico from December 2020 to May 2023 (after Omicron BA-5 circulation) was performed. Paxlovid™ use was authorized in September 2022. Therefore, we analyzed effectiveness in patients with confirmed diagnosis who met selection criteria between September 2022 and May 2023 (n = 20,799; 5,673 with and 15,126 without Paxlovid™). RESULTS: The pneumonia (0.1% vs. 0.4%, p < 0.0001), hospitalization (0.1% vs. 1.2%, p < 0.0001), and death rates (0.04% vs. 0.2%, p < 0.0001) were lower in patients with Paxlovid™ treatment independently of age, sex, comorbidity, and COVID-19 and pneumococcal vaccination history. Effectiveness was 88.2%, 95.9% y 91.9% for pneumonia, hospitalization, and death, respectively. CONCLUSIONS: Paxlovid™ reduces the presentation of pneumonia, hospitalization, and death secondary to COVID-19. It is recommended to continue monitoring Paxlovid™ effectiveness, as other SARS-CoV-2 variants continue to emerge.

Going Viral: Assessing the Impact of Social Media on Enrollment in a Coronavirus Disease 2019 (COVID-19) Cohort Study.

Objective This study aimed to quantify the effect of social media posts on study enrollment among children with mild coronavirus disease 2019 (COVID-19). Methods The primary outcome was weekly study enrollments analyzed using a run chart. A secondary analysis used linear regression to assess study enrollments two days before and after a social media post, adjusted for the statewide pediatric seven-day-average severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case rate, social media posting day, and the interaction of these two variables. Results In seven months before social media posting, only eight patients were enrolled. One week after social media posting began, the median weekly enrollment increased (0 to 3). In the regression model, neither social media post day nor the pediatric SARS-CoV-2 case rate was significantly associated with enrollment rate. However, the interaction of a post day and the pediatric case rate was significant. Conclusion Social media posts significantly increased enrollment among children with mild COVID-19 in a prospective study. This effect was amplified by the presence of high community case rates during the Omicron wave.

OCT Imaging in Murine Models of Alzheimer's Disease in a Systematic Review: Findings, Methodology and Future Perspectives.

The murine models of Alzheimer's disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

New complementary alternatives in third molar autotransplantation: A systematic review

Background: Dental autotransplantation (DAT) is defined as the replacement or direct transfer of an impacted, semi-impacted or erupted tooth to a donor site, either to a post-extraction socket or to a surgically created socket within the same individual. The use of new technological advances, such as 3-D dental models based on computer-aided design, among others, have been reported to improve the success rate of DAT. Therefore, we aimed to perform a systematic review to explore the possible benefits that the use of these innovative techniques can provide when applied to DAT. Material and Methods: The literature search was conducted in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. The research question was: "Are computerized technological advancements a useful tool for improving the success of third molar autotransplantation technique? Results: The initial literature search identified 195 articles, of which only 11 were included for qualitative analysis. All studies used 3D dental models based on computer-aided design data. Surgical guides and stereolithographic models were used by 4 and 1 study respectively. A total of 91 transplanted teeth were evaluated, out of which only 88 were considered within the parameters of clinical success (96.7%). Only 7 out of the 11 articles reported the specific autotransplanted tooth, being mandibular third molars the most prevalent autotransplanted teeth. Conclusions: Although the application of new technologies for DAT increases the success rate of this technique, further primary studies are still needed to address long-term teeth survival rates and complications. The cost and availability to implement the integration of these techniques to DAT may be a variable to consider, as this can be a limitation for some patients or for low-income countries. (AU)

Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage.

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma.

Weight Regain after Metabolic Surgery: Beyond the Surgical Failure.

Patients undergoing metabolic surgery have factors ranging from anatomo-surgical, endocrine metabolic, eating patterns and physical activity, mental health and psychological factors. Some of the latter can explain the possible pathophysiological neuroendocrine, metabolic, and adaptive mechanisms that cause the high prevalence of weight regain in postbariatric patients. Even metabolic surgery has proven to be effective in reducing excess weight in patients with obesity; some of them regain weight after this intervention. In this vein, several studies have been conducted to search factors and mechanisms involved in weight regain, to stablish strategies to manage this complication by combining metabolic surgery with either lifestyle changes, behavioral therapies, pharmacotherapy, endoscopic interventions, or finally, surgical revision. The aim of this revision is to describe certain aspects and mechanisms behind weight regain after metabolic surgery, along with preventive and therapeutic strategies for this complication.

Learning-oriented motivation: Examining the impact of teaching practices with motivational potential.

This study compares the predictive ability of nine different types of motivational practices on the motivational orientation toward learning. Given the nature of undergraduate studies, identifying the most predictive motivational variables on learning orientation allows us to focus our efforts on those motivational practices to guide students to deploy their cognitive resources by focusing on learning and not only on obtaining good grades. The study included Chilean university students from health (n = 398) and education (n = 365) programs. A Bayesian multiple regression was carried out in both groups. The results show strong evidence of a specific effect of motivational practices on motivational orientation towards learning. Although the impact on motivational orientation toward learning may vary slightly across different fields of study, the primary predictors consistently are practices that emphasize importance and foster autonomy. The effect of utility-focused motivational practices is observed only within the predictive model for the group of health students.

Olivary body exposure through far lateral and lower retrosigmoid approaches. Comparative analysis of the exposed surface and angle of attack.

OBJECTIVES: Throughout neurosurgical history, the treatment of intrinsic lesions located in the brainstem has been subject of much controversy. The brainstem is the anatomical structure of the central nervous system (CNS) that presents the highest concentration of nuclei and fibers, and its simple manipulation can lead to significant morbidity and mortality. Once one of the safe entry points at the medulla oblongata has been established, we wanted to evaluate the safest approach to the olivary body (the most used safe entry zone on the anterolateral surface of the medulla oblongata). The proposed objective was to evaluate the working channel from the surface of each of the far lateral and retrosigmoid approaches to the olivary body: distances, angles of attack and channel content. MATERIAL AND METHODS: To complete this work, a total of 10 heads injected with red/blue silicone were used. A total of 40 approaches were made in the 10 heads used (20 retrosigmoid and 20 far lateral). After completing the anatomical study and obtaining the data referring to all the approaches performed, it was decided to expand the sample of this research study by using 30 high-definition magnetic resonance imaging of anonymous patients without cranial or cerebral pathology. The reference points used were the same ones defined in the anatomical study. After defining the working channels in each of the approaches, the working distances, angle of attack, exposed surface, and the number of neurovascular structures present in the central trajectory were analyzed. RESULTS: The distances to the cranial and medial region of the olivary body were 52.71 mm (SD 3.59) from the retrosigmoid approach and 27.94 mm (SD 3.99) from the far lateral; to the most basal region of the olivary body, the distances were 49.93 (SD 3.72) from the retrosigmoid approach and 18.1 mm (SD 2.5) from the far lateral. The angle of attack to the caudal region was 19.44° (SD 1.3) for the retrosigmoid approach and 50.97° (SD 8.01) for the far lateral approach; the angle of attack to the cranial region was 20.3° (SD 1.22) for the retrosigmoid and 39.9° (SD 5.12) for the far lateral. Regarding neurovascular structures, the probability of finding an arterial structure is higher for the lateral far, whereas a neural structure will be more likely from a retrosigmoid approach. CONCLUSIONS: As conclusions of this work, we can say that far lateral approach presents more favorable conditions for the microsurgical treatment of intrinsic bulbar and bulbomedullary lesions approached through the caudal half of the olivary body. In those cases of bulbar and pontine-bulbar lesions approached through the cranial half of the olivary body, the retrosigmoid approach can be considered for selected cases.

Effectiveness of Omega-3 Fatty Acid Supplementation in Improving the Metabolic and Inflammatory Profiles of Mexican Adults Hospitalized with COVID-19.

BACKGROUND AND OBJECTIVES: The development of severe COVID-19 is related to the preexistence of comorbidities and an inadequate nutritional status. The latter is a critical factor for the development of infection and the progression of the disease. Notably, optimal nutrition impacts immune system function, as malnutrition is related to high cytokine levels in the late phase of the disease, correlating with a poor prognosis. In this sense, omega-3 fatty acids (O3FAs) have anti-inflammatory properties that may reduce morbidity and mortality from COVID-19 infection. O3FAs are linked to a better prognosis in COVID-19 patients. MATERIALS AND METHODS: In this randomized, double-blind clinical trial, we evaluate the administration of O3FAs to unvaccinated Mexican patients for two weeks starting after the first two hours of hospitalization. RESULTS: The findings support the notion that O3FAs (in a dose high enough to satisfy human physiological requirements in a short time, one capsule of 1.4 g O3FAs daily) exert a comprehensive multi-systemic modulatory influence, affecting inflammatory and metabolic pathways. Significant perturbations in biomarkers, including absolute neutrophil count, hematocrit, and platelet indices, underscore the compound's anti-inflammatory effect. Concurrently, the intervention modulates pivotal metabolic and hepatic parameters, attenuating cardiovascular risk profiles and expediting patient convalescence. These multifarious effects are likely orchestrated through intricate biochemical mechanisms and are subject to individual variations predicated on metabolic factors. CONCLUSIONS: The results of this trial support the notion that O3FA supplementation has beneficial effects on COVID-19 patients with moderate presentation by regulating metabolism and limiting inflammation.