Mas receptor blockade impairs exercise-induced cardiac hypertrophy.

Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.

Chrysin attenuates epithelial prostatic hyperplasia in the ventral prostate of spontaneously hypertensive rats.

The aim of this study was to evaluate the effects of chrysin on the ventral prostate of spontaneously hypertensive rats (SHR). Ten-week-old male Wistar and SHR rats received 100 mg/kg/day of chrysin (TW and TSHR) or 200 µL/day of the dilution vehicle (CW and CSHR) for 70 days. After the treatment, the animals were euthanized and the prostates were dissected out, fixed, and processed for further morphological, immunohistochemical, and biochemical analyses. Blood was collected for serological analysis. Chrysin did not interfere with the blood pressure. Morphologically, the epithelial height increased in TW and decreased in TSHR. Stereology showed an increase in the epithelial and stromal relative frequency, and a decrease in the lumen of TW, whereas the epithelium in TSHR was reduced. Normal alveoli decreased, and hyperplastic alveoli had an increment in TW, whereas in TSHR normal alveoli increased and intense hyperplasia decreased. The secretion area was reduced in TW. Immunohistochemical analysis showed a smaller number of PCNA-positive cells in TW. Finally, the biochemical analysis showed a reduction in malondialdehyde, carbonylated proteins, superoxide dismutase, and catalase in TW and TSHR. We concluded that the chrysin effect is dependent on the context in which this flavonoid is employed. In normal conditions, the anabolic potential of the chrysin was favored, disrupting the morphology of the prostate. However, when used in animals predisposed to develop hyperplasia, this flavonoid attenuates the hyperplastic status, improving the morphology of the gland.

Comparison of P-glycoprotein gene expression of two Haemonchus contortus isolates from Yucatan, Mexico, with resistant or susceptible phenotype to ivermectin in relation to a susceptible reference strain.

The variability in the expression of different P-glycoprotein (P-gp) genes in parasitic nematodes of ruminants such as Haemonchus contortus (Hco-pgp) may be caused by different factors including nematode biology, geographical region and anthelmintic pressure. This study analysed the relative expression level of 10 P-gp genes in two H. contortus (Hco-pgp) field isolates from Yucatan, Mexico: 1) PARAISO (IVM-resistant) and 2) FMVZ-UADY (IVM-susceptible). These isolates were compared with a susceptible reference isolate from Puebla, Mexico, namely "CENID-SAI". In all cases H. contortus adult males were used. The Hco-pgp genes (1, 2, 3, 4, 9, 10, 11, 12, 14 and 16) were analysed for each isolate using the RT-qPCR technique. The Hco-pgp expressions were pairwise compared using the 2-ΔΔCt method and a t-test. The PARAISO isolate showed upregulation compared to the CENID-SAI isolate for Hco-pgp 1, 3, 9, 10 and 16 (P < 0.05), and the PARAISO isolate showed upregulation vs. FMVZ-UADY isolate for Hco-pgp 2 and 9 (P < 0.05), displaying 6.58- and 5.93-fold differences (P < 0.05), respectively. In contrast, similar Hco-pgp gene expression levels were recorded for FMVZ-UADY and CENID-SAI isolates except for Hco-pgp1 (P <0.1), which presented a significant upregulation (6.08-fold). The relative expression of Hco-pgp allowed confirming the IVM-resistant status of the PARAISO isolate and the IVM-susceptible status of the FMVZ-UADY isolate when compared to the CENID-SAI reference isolate. Therefore, understanding the association between the Hco-pgp genes expression of H. contortus and its IVM resistance status could help identifying the genes that could be used as molecular markers in the diagnosis of IVM resistance. However, it is important to consider the geographic origin of the nematode isolate and the deworming history at the farm of origin.

Sodium overload during postnatal phases impairs diastolic function and exacerbates reperfusion arrhythmias in adult rats.

Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood. Male 21-day-old Wistar rats were treated for 60 days with hypertonic saline solution (NaCl; 0.3M; experimental group) or tap water (control group). Subsequently, both groups were maintained on a normal sodium diet for 30 days. Subsequently, the rats were euthanized, and their hearts were isolated and perfused according to the Langendorff technique. After 30 min of the basal period, the hearts were subjected to 20 min of anoxia, followed by 20 min of reperfusion. The basal contractile function was unaffected by HSD. However, HSD elevated the left ventricular end-diastolic pressure during reperfusion (23.1 ± 5.2 mmHg vs. 11.6 ± 1.4 mmHg; p < 0.05) and increased ectopic incidence period during reperfusion (208.8 ± 32.9s vs. 75.0 ± 7.8s; p < 0.05). In conclusion, sodium overload compromises cardiac function after reperfusion events, diminishes ventricular relaxation, and increases the severity of arrhythmias, suggesting a possible arrhythmogenic effect of HSD in the postnatal phases.

Choosing Wisely in oncology in Latin America: what SLACOM does not recommend in the care of cancer patients in Latin America: Ten essential recommendations to avoid harmful onclogy procedures in Latin America.

Choosing Wisely is an initiative by the American Board of Internal Medicine (ABIM) and ABIM Foundation to deter unnecessary medical treatments and procedures. Faced with the burden of modern technologies and treatments, it is crucial to identify practices lacking value in daily care. The Latin American and Caribbean Society (SLACOM), comprising cancer control experts, deems it vital to tailor this initiative for enhancing cancer care in the region. Through a modified DELPHI methodology involving two rounds of electronic questionnaires and a hybrid meeting to discuss key points of contention, ten essential recommendations were identified and prioritised to avoid harmful oncology procedures in our region. These consensus-based recommendations, contextualised for Latin America, have been compiled and shared to benefit patients. The Scientific Committee, consisting of prominent oncologists and health experts, collaborates remotely to drive this project forward.

An N-terminal acidic ß-sheet domain is responsible for the metal-accumulation properties of amyloid-ß protofibrils: a molecular dynamics study.

The influence of metal ions on the structure of amyloid- ß (Aß) protofibril models was studied through molecular dynamics to explore the molecular mechanisms underlying metal-induced Aß aggregation relevant in Alzheimer's disease (AD). The models included 36-, 48-, and 188-mers of the Aß42 sequence and two disease-modifying variants. Primary structural effects were observed at the N-terminal domain, as it became susceptible to the presence of cations. Specially when ß-sheets predominate, this motif orients N-terminal acidic residues toward one single face of the ß-sheet, resulting in the formation of an acidic region that attracts cations from the media and promotes the folding of the N-terminal region, with implications in amyloid aggregation. The molecular phenotype of the protofibril models based on Aß variants shows that the AD-causative D7N mutation promotes the formation of N-terminal ß-sheets and accumulates more Zn2+, in contrast to the non-amyloidogenic rodent sequence that hinders the ß-sheets and is more selective for Na+ over Zn2+ cations. It is proposed that forming an acidic ß-sheet domain and accumulating cations is a plausible molecular mechanism connecting the elevated affinity and concentration of metals in Aß fibrils to their high content of ß-sheet structure at the N-terminal sequence.

The in vitro rumen exsheathment test for studying the effect of plant extracts on the exsheathment of Haemonchus contortus infective larvae.

This study applied the in vitro rumen exsheathment test (IVRET) to evaluate the exsheathment kinetics of Haemonchus contortus infective larvae (L3) incubated in ruminal liquor (RL) containing acetone:water extracts of Acacia pennatula (AP), Gymnopodium floribundum (GF), Havardia albicans (HA) or Lysiloma latisiliquum (LL). The role of polyphenols in the biological activity of the evaluated extracts was also determined. Larvae were incubated in RL either alone or added with a different plant extract (AP, GF, HA, or LL) at 1200 µg/mL. Polyethylene glycol (PEG) was added to block polyphenols in each treatment (RL+PEG, AP+PEG, GF+PEG, HA+PEG, and LL+PEG). After incubation times of 0, 1, 3, 6, 9, and 24 h, the exsheathment process was stopped to count the number of ensheathed and exsheathed L3. A Log-Logistic model was used to determine the L3 exsheathment kinetics in the different RL treatments. The inflection point of the respective kinetic curves, which indicates the time to reach 50 % exsheathed L3 (T50), was the only parameter that differed when comparing the exsheathment models (99 % probability of difference). The T50 values obtained for GF, HA, and LL treatments (T50 = 7.11 - 7.58 h) were higher in comparison to the T50 of RL (5.72 h) (≥ 70 % probability of difference). The L3 incubated in RL added with GF, HA, and LL extracts delayed their exsheathment at 3 and 6 h of incubation (28.71 - 48.06 % exsheathment reduction) compared to the RL treatment. The T50 value for AP, AP+PEG, GF+PEG, HA+PEG, and LL+PEG were similar to RL and RL+PEG (T50 = 5.34 - 6.97 h). In conclusion, the IVRET can be used to identify plants with the potential to delay the exsheathment of H. contortus L3 in the ruminal liquor. The acetone:water extracts of G. floribundum, H. albicans, and L. latisiliquum delayed the T50 of H. contortus exsheathment, which was evident at 3 and 6 h of incubation in ruminal liquor. The observed exsheathment delay was attributed to the polyphenol content of the extracts.

Salud mental en estudiantes de medicina: un reto más allá del estrés académico / Mental health in medical students: a challenge beyond academic stress

Resumen El proceso de enseñanza en medicina tiene desafíos que pueden inducir estrés académico y con ello afectaciones a la salud mental, por lo que es imprescindible el cuidado de la salud mental de los futuros médicos. Este estudio quiso identificar los factores asociados a la salud mental de estudiantes de medicina de una universidad privada en Colombia, ajustados por estrés académico. Mediante un diseño transversal, se reclutaron 443 estudiantes (68.4% mujeres, 31.6% hombres) quienes completaron un cuestionario con variables sociodemográficas, académicas, el Inventario Cognitivo Sistémico para el Estudio del Estrés Académico y el inventario Symptom Checklist-90-Revised. Los factores de riesgo se analizaron utilizando un Modelo Lineal Generalizado por la familia de Poisson y log link. El 38,3% de los estudiantes presentó un nivel de riesgo en salud mental. Los factores protectores incluyeron actividad física regular (RPa = 0.78) y actividades extracurriculares (RPa = 0.75), mientras que los factores de riesgo fueron uso de sustancias psicoactivas (RPa = 1.36), bebidas energéticas (RPa = 1.35) y tener una ocupación alternativa al estudio (RPa = 1.47). La salud mental de los estudiantes de medicina presenta riesgos más allá de la misma exigencia académica. Hay elementos del individuo y la institución formadora que pueden actuar como factores protectores, lo que se convierte en un insumo para la creación de programas de cuidado y mantenimiento de la salud mental.

Abstract The teaching process in medicine has challenges that can induce academic stress and thus affect mental health, so it is essential to take care of the mental health of future physicians. This study aimed to identify the factors associated with the mental health of medical students at a private university in Colombia, adjusted for academic stress. Using a cross-sectional design, 443 students were recruited (68.4% women, 31.6% men) who completed a questionnaire with sociodemographic and academic variables, the Systemic Cognitive Inventory for the Study of Academic Stress and the Symptom Checklist-90-Revised inventory. Risk factors were analyzed using a Generalized Linear Model by Poisson family and log link. Thirty-eight point three percent of the students presented a level of mental health risk. Protective factors included regular physical activity (RPa = 0.78) and extracurricular activities (RPa = 0.75), while risk factors were psychoactive substance use (RPa = 1.36), energy drinks (RPa = 1.35) and having an alternative occupation to studying (RPa = 1.47). The study provided information on the need for intervention in factors beyond academic stress, seeking to maintain the well-being of students and thus avoid academic dropout.

Angiotensin-(1-7) Treatment Early in Life Prevents Cardiac Hypertrophy in Adult Hypertensive Rats.

ABSTRACT: Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Prepuberty has been considered as a later susceptible window of development, and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the prepuberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHRs). SHRs were treated with Ang-(1-7) (24 µg/kg/h) from age 4 to 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography up to 17th week. Thereafter, echocardiography was performed, and the rats were euthanized for the collection of tissues and blood. Ang-(1-7) did not change the systolic blood pressure but reduced the septal and posterior wall thickness, and cardiomyocyte hypertrophy and fibrosis in SHR. In addition, Ang-(1-7) reduced the gene expression of atrial natriuretic peptide and brain natriuretic peptide, increased the metalloproteinase 9 expression, and reduced the extracellular signal-regulated kinases 1/2 phosphorylation. Ang-(1-7) also prevented the reduction of Mas receptor but did not change the protein expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, AT1, and AT2. The treatment with Ang-(1-7) decreased the malondialdehyde (MDA) levels and increased superoxide dismutase-1 and catalase activities and protein expression of catalase. Our findings demonstrate that the treatment of SHR with Ang-(1-7) for 3 weeks early in life promotes beneficial effects in the heart later in life, even without altering blood pressure, through mechanisms involving the reduction of oxidative stress and ERK1/2 phosphorylation. In addition, this study supports the prepuberty as an important programming window.

Relevance of Individual Data When Assessing the Gastrointestinal Nematode Infection Level, Nutritional and Productive Variables in a Tropical Farm Context: The Median Isn't the Message.

We evaluated the relationship between individual and herd GIN infection level, nutrition, production performance and anemia parameters in a tropical farm context. Fifty-four female goats were monitored to assess their body condition score (BCS, nutritional status indicator), live weight (LW) and LW gain (LWG, both used as production level indicators), FAMACHA© and hematocrit (HT, both used as anemia indicators). Goats browsed for 4 h in a tropical forest and received balanced feed and chopped grass. The eggs per gram of feces (EPG) indicated the GIN burden, with fecal samples obtained at 7:00 (AM) and 15:00 h (PM.) from each goat at six sampling points during the study. The variables and their relationship with GIN burdens were analyzed using Kruskall-Wallis, ANOVA and Friedman tests and Spearman correlations. The fecal samples obtained in the AM and PM can be equally representative of parasitic burdens (similar and highly correlated). However, the EPG of individual goats from periods of 30 days apart can be considered independent. The BCS and LWG varied between sampling times (p < 0.05), whereas EPG, LW and HT did not (p > 0.05). The GIN burden was negatively correlated with HT and BCS (-0.21, p = 0.01 for each one). The individual pattern of infection demonstrates the true impact of GINs on their hosts. Additionally, feeding and nutritional status may present important variations influencing the performance of the goats more than the impact of GINs under the farm conditions of the present study. However, GIN infection contributed to the variation in goat health and productivity in this tropical farm.

Adapting the in vitro rumen incubation method to evaluate the effect of a plant extract on the exsheathment inhibition of Haemonchus contortus infective larvae.

This study adapted the in vitro rumen incubation (IVRI) method to evaluate the biological activity of a Gymnopodium floribundum leaves extract against the exsheathment of Haemonchus contortus infective larvae (L3), and to determine the role of plant polyphenols on the biological activity. The incubation protocol followed the IVRI method, adding polyethylene glycol (PEG) as a polyphenol-blocking agent. The L3 were incubated in ruminal liquor (RL), ruminal liquor with PEG (RL+PEG), ruminal liquor with G. floribundum extract (RLE), and ruminal liquor with G. floribundum extract and PEG (RLE+PEG). Incubation condition controls included phosphate buffered saline (PBS), PBS with PEG (PBS+PEG), incubation medium (without ruminal liquor) (IM), and incubation medium with PEG (IM+PEG). The L3 were recovered after incubation times of 0, 1, 3, 6, 9, and 24 h (39 °C). The respective L3 exsheathment kinetics were estimated for the different treatments (RL, RL+PEG, RLE, and RLE+PEG) using Log-Logistic models. The parameters of the different models were compared to determine the impact of the extract, with or without PEG, on the L3 exsheathment kinetics. The exsheathment in PBS and PBS+PEG remained < 2.71% at each incubation time. The exsheathment in IM and IM+PEG reached 13.58% and 17.18% at 24 h, respectively. The exsheathment percentages for RLE were lower than those for RL at 3, 6 and 9 h of incubation. The inflection point, indicating the time required to reach 50% of the maximal exsheathment (T50), was the only parameter that differed between the ruminal liquor models. The T50 in RLE (7.106 h) was higher than the values obtained for RL (5.385 h) and RL+PEG (4.923 h) (99.99% probability of being different). Such delay resulted in a reduction of exsheathment in RLE of 62% at 3 h, 38% at 6 h, and 12% at 9 h, relative to RL values. When PEG was added with the extract (RLE+PEG), the T50 (5.045 h) was similar to that of RL and RL+PEG. The IVRI method was adapted as an in vitro rumen exsheathment test (IVRET). The IVRET showed that H. contortus L3 exposed to G. floribundum extract delayed their exsheathment kinetics at different time points. The exsheathment delay was attributed to the polyphenol content of the extract.

Knowledge and attitudes regarding contraceptive methods and sex education in students and parents of eight Colombian schools 2020-2021: a mixed methods study.

Background: In Colombia, the average age of first sexual intercourse is between 14 and 15, and it has one of the highest fertility rates among adolescents in Latin America, which reflects poor access to health services and a lack of knowledge about contraception. Some laws support comprehensive sex education as a learning process that families and schools should provide. The objective of this work was to assess the frequency of adequate knowledge and attitudes of acceptance towards contraception in students, their associated factors, sexual behaviours in sexually active students, and experiences with sex education. Methods: Mixed methods study consisting of an analytical cross-sectional study and a qualitative hermeneutic phenomenological study. The former included students who completed a questionnaire with sociodemographic variables, surveys on knowledge and attitudes toward contraception, and questions about sexual behaviour. Focus groups were used in the qualitative study to evaluate students' and parents' sex education experiences. Findings: 827 students were surveyed, of whom 52.3% had adequate knowledge about contraceptives and 80.1% had attitudes of acceptance. Talking with parents about sex education, receiving sex education, and being in the eleventh grade increased the likelihood of having adequate knowledge. Each year of age, being male, being a victim of forced displacement, and studying in a public school were associated with lower possibilities of attitudes of acceptance. Using condoms, compared to other contraceptives, was associated with less adequate knowledge and attitudes of acceptance (p < 0.05). Experiences with sex education, contraception, and sexual and reproductive rights were three emerging categories in the focus groups. Interpretation: In a group of Colombian high school students, half of them had adequate knowledge, eight out of 10 had attitudes of acceptance about contraception, and both were associated with having received sex education. Nevertheless, different types of barriers to sexual education were identified at home and in schools. The results will allow the generation of educational policies that modify the educational model as well as new strategies by health professionals to raise awareness about responsible sexuality. Funding: This project was financed by internal research of the Fundación Universitaria de Ciencias de la Salud-FUCS (DI-I-0392-20).

Neofunctionalization driven by positive selection led to the retention of the loqs2 gene encoding an Aedes specific dsRNA binding protein.

BACKGROUND: Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects. RESULTS: Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference. CONCLUSIONS: Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors.

Curcumin-PVP improves the in vitro efficacy of ivermectin against resistant and susceptible Haemonchus contortus.

Ivermectin (IVM) resistance in parasitic nematodes such as Haemonchus contortus has spurred a search for substances that help to recover its efficacy. One potential agent is the natural product curcumin (CUR). In this study, CUR was combined with polyvinylpyrrolidone (PVP) (CUR/PVP) to improve its solubility and biological applicability. This study determined the effect of CUR preincubation on the effective concentration 50% (EC50) of IVM in three H. contortus isolates with different susceptibilities to IVM. The IVM EC50 was determined for three H. contortus isolates with different IVM susceptibilities using the larval migration inhibition (LMI) test. The three isolates were (i) PARAISO (IVM resistant), (ii) FMVZ-UADY (IVM susceptible), and (iii) CENID-SAI INIFAP (reference IVM susceptible). The L3 of each isolate were preincubated for 3 h with one of three concentrations of CUR (µg curcumin/mL): CONC-1 (3.67), CONC-2 (5.67), or CONC-3 (8.48). Corresponding controls were performed without CUR. The EC50 of IVM was determined for each isolate after they were exposed to the different CUR concentrations. The EC50 of IVM differed between the isolates PARAISO > FMVZ-UADY > CENID-SAI INIFAP (P < 0.05). The CUR preincubation at CONC-1 did not decrease the EC50 of IVM for any of the three isolates, suggesting a hormetic effect. By contrast, CUR preincubation at CONC-2 or CONC-3 decreased the IVM EC50 for the PARAISO isolate (P < 0.05) compared with the reference isolate and reduced the EC50 of IVM for the FMVZ-UADY and CENID-SAI INIFAP isolates below the EC50 for the CENID-SAI INIFAP isolate without CUR preincubation. In conclusion, preincubation of H. contortus L3 with CUR reduced the EC50 of IVM for field isolates classified as resistant and susceptible to IVM. The CUR preincubation reduced the IVM resistance factor in the different isolates tested.

Enhancing Osteoblastic Cell Cultures with Gelatin Methacryloyl, Bovine Lactoferrin, and Bioactive Mesoporous Glass Scaffolds Loaded with Distinct Parsley Extracts.

The increasing interest in innovative solutions for addressing bone defects has driven research into the use of Bioactive Mesoporous Glasses (MBGs). These materials, distinguished by their well-ordered mesoporous structure, possess the capability to accommodate plant extracts with well-established osteogenic properties, including bovine lactoferrin (bLF), as part of their 3D scaffold composition. This harmonizes seamlessly with the ongoing advancements in the field of biomedicine. In this study, we fabricated 3D scaffolds utilizing MBGs loaded with extracts from parsley leaves (PL) and embryogenic cultures (EC), rich in bioactive compounds such as apigenin and kaempferol, which hold potential benefits for bone metabolism. Gelatin Methacryloyl (GelMa) served as the polymer, and bLF was included in the formulation. Cytocompatibility, Runx2 gene expression, ALP enzyme activity, and biomineralization were assessed in preosteoblastic MC3T3-E1 cell cultures. MBGs effectively integrated PL and EC extracts with loadings between 22.6 ± 0.1 and 43.6 ± 0.3 µM for PL and 26.3 ± 0.3 and 46.8 ± 0.4 µM for EC, ensuring cell viability through a release percentage between 28.3% and 59.9%. The incorporation of bLF in the 3D scaffold formulation showed significant differences compared to the control in all assays, even at concentrations below 0.2 µM. Combinations, especially PL + bLF at 0.19 µM, demonstrated additive potential, with superior biomineralization compared to EC. In summary, this study highlights the effectiveness of MBGs in incorporating PL and EC extracts, along with bLF, into 3D scaffolds. The results underscore cytocompatibility, osteogenic activity, and biomineralization, offering exciting potential for future in vivo applications.

Desigualdades sociales urbano-rurales en la mortalidad por siniestros viales en Colombia, 1998-2019

Introducción: Anualmente se pierden 1,35 millones de vidas por causa de siniestros viales; su ocurrencia se ha relacionado, además de factores comportamentales, con desigualdades sociales. Objetivo: Analizar las desigualdades sociales urbano-rurales en la mortalidad por siniestros viales en Colombia para el periodo 1998-2019. Materiales y métodos: Estudio ecológico a partir del análisis de las tasas de mortalidad ajustadas de los grupos poblacionales urbanos y rurales estratificados por sexo. Se hicieron análisis con regresión de Joinpoint y se calcularon medidas de desigualdad simple absoluta y relativa. Resultados: Se registraron 139 323 muertes por siniestros viales, en Colombia la tasa de mortalidad por esta causa se ha venido reduciendo. En contraste con las áreas rurales, en las áreas urbanas esta reducción es más significativa. Existen desigualdades en la mortalidad entre las áreas urbanas y rurales que han venido estrechándose. No obstante, en el caso de hombres y mujeres ha venido incrementándose. Discusión: La reducción de la tasa de mortalidad por siniestros viales sugiere que las intervenciones en seguridad vial han sido efectivas. La mayor mortalidad en hombres puede explicarse a partir de factores comportamentales. Las desigualdades urbano-rurales pueden estar relacionadas con las dinámicas de desarrollo. Conclusiones: Se registra una reducción en la tasa de mortalidad por siniestros viales, la cual es más significativa en áreas urbanas. Existen desigualdades urbano-rurales en la mortalidad por esta causa. Las políticas de seguridad vial deben partir de un enfoque integrador vinculado con otras agendas políticas.

Introduction: Annually, 1,35 million lives are lost due to road accidents; their occurrence has been related, in addition to behavioral factors, to social inequalities. Objective: To analyze urban-rural social inequalities in mortality from traffic accidents in Colombia from 1998-2019. Methods and materials: Ecological study based on the analysis of standardized mortality rates adjusted for age and sex of urban and rural population groups stratified by sex. Joinpoint regression analyses were performed, and absolute and relative simple inequality measures were calculated. Results: There were 139.323 deaths from road accidents; in Colombia mortality rates from this cause has been decreasing. In urban areas, the reduction is more significant than in rural areas. Disparities in mortality between urban and rural areas have been narrowing, however, in the case of men and women, they have been increasing. Discussion: Reducing the mortality rate from road accidents suggests that road safety interventions have been effective. Behavioral factors can explain the higher mortality in men. Urban-rural inequalities can be related to development dynamics. Conclusions: There is a significant reduction in the mortality rate due to road accidents in urban areas. There are urban-rural inequalities in mortality from this cause. Road safety policies must be based on an integrative approach linked to other political agendas.

Factores asociados con la intensidad de los síntomas ansiosos y depresivos en personal de salud de dos centros de referencia para la atención de pacientes con COVID-19 de Antioquia, Colombia. Un análisis de clases latentes / Factors Associated with the Intensity of Anxiety and Depression Symptoms in Health Workers of two Centres of Reference for COVID 19 Patient Care in Antioquia, Colombia-a Latent Class Analysis

RESUMEN Objetivo: Clasificar al personal de 2 instituciones de referencia para la atención de la COVID-19 en Antioquia según la intensidad de los síntomas ansiosos y depresivos y determinar los factores asociados con estas clases. Métodos: Estudio de corte transversal en el que se usaron las escalas GAD-7, PHQ-9, miedo a la COVID-19 y escala Burnout de Copenhague. Se hizo análisis de clases latentes para identificar las clases y se determinaron los factores asociados mediante regresión logística multinomial. Resultados: Participaron 486 personas. El modelo con mejor ajuste fue el de 3 clases. La I, con puntajes bajos en escalas; la II, con grados leves de ansiedad y depresión, e intermedios de miedo a la COVID-19 y estrés percibido; y la III, con grados moderados y graves de ansiedad, depresión y estrés percibido. Los factores asociados con pertenecer a la clase III fueron: edad (OR = 0,94; IC95%, 0,91-0,96), cambio de vivienda para no exponer a familiares (OR = 4,01; IC95%, 1,99-8,09), y antecedente de trastorno depresivo (OR = 3,10; IC95%, 1,27-7,56) y ansioso (OR = 5,5; IC95%, 2,36-12,90). Los factores asociados con la clase II fueron: edad (OR = 0,97; IC95%, 0,95-0,99), antecedente de trastorno depresivo (OR = 3,41; IC95%, 1,60-7,25), convivir con alguien con riesgo de muerte por COVID-19 (OR = 1,86; IC95%, 1,192,91), familiar personal de salud (OR = 1,58; IC95%, 1,01-2,47) y cambio de vivienda para no exponer a familiares (OR=1,99; IC95%, 1,11-3,59). 0034-7450/© 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados. Conclusiones: Se obtuvieron 3 clases de participantes, 2 de ellas con síntomas ansiosos y depresivos. La menor edad y el antecedente de un trastorno mental fueron factores asociados con las 2 clases de pacientes sintomáticos; otros factores pueden ser causa o consecuencia de los síntomas. © 2021 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

ABSTRACT Objective: To classify the staff of two reference institutions for COVID-19 care in Antioquia according to the intensity of anxiety and depression symptoms, and to determine the factors associated with these classes. Methods: Cross-sectional study in which the GAD-7, PHQ-9, fear of COVID-19, and the Copenhagen Burnout scale were used. Latent class analysis was performed to identify the classes, and the factors associated with these were determined using multinomial logistic regression. Results: 486 people participated. The three-class model had the best fit: class I with low scores on the scales; class II with mild degrees of anxiety and depression, and intermediate levels of fear of COVID-19 and perceived stress; and class III with moderate and severe degrees of anxiety, depression, and perceived stress. The factors associated with belonging to class III were age (OR = 0.94; 95%CI, 0.91-0.96), change of residence to avoid exposing relatives (OR = 4.01; 95%CI, 1.99-8.09), and a history of depressive disorder (OR = 3.10; 95%CI, 1.27-7.56), and anxiety (OR = 5.5; 95%CI, 2.36-12.90). Factors associated with class II were age (OR = 0.97; 95%CI, 0.95-0.99), history of depressive disorder (OR = 3.41; 95%CI, 1.60-7.25), living with someone at risk of death from COVID-19 (OR= 1.86; 95%CI, 1.19-2.91), family member being healthcare staff (OR = 1.58; 95%CI, 1.01-2.47), and change of residence to avoid exposing relatives (OR = 1.99; 95%CI, 1.11-3.59). Conclusions: Three classes of participants were obtained, two of them with anxiety and depression symptoms. Younger age and a history of mental disorder were factors associated with the two classes of symptomatic patients; other factors may be causes or consequences of the symptoms.

A multiscale model of the role of microenvironmental factors in cell segregation and heterogeneity in breast cancer development.

We analyzed a quantitative multiscale model that describes the epigenetic dynamics during the growth and evolution of an avascular tumor. A gene regulatory network (GRN) formed by a set of ten genes that are believed to play an important role in breast cancer development was kinetically coupled to the microenvironmental agents: glucose, estrogens, and oxygen. The dynamics of spontaneous mutations was described by a Yule-Furry master equation whose solution represents the probability that a given cell in the tissue undergoes a certain number of mutations at a given time. We assumed that the mutation rate is modified by a spatial gradient of nutrients. The tumor mass was simulated by means of cellular automata supplemented with a set of reaction diffusion equations that described the transport of microenvironmental agents. By analyzing the epigenetic state space described by the GRN dynamics, we found three attractors that were identified with cellular epigenetic states: normal, precancer and cancer. For two-dimensional (2D) and three-dimensional (3D) tumors we calculated the spatial distribution of the following quantities: (i) number of mutations, (ii) mutation of each gene and, (iii) phenotypes. Using estrogen as the principal microenvironmental agent that regulates cell proliferation process, we obtained tumor shapes for different values of estrogen consumption and supply rates. It was found that he majority of mutations occurred in cells that were located close to the 2D tumor perimeter or close to the 3D tumor surface. Also, it was found that the occurrence of different phenotypes in the tumor are controlled by estrogen concentration levels since they can change the individual cell threshold and gene expression levels. All results were consistently observed for 2D and 3D tumors.

Factors associated with the intensity of anxiety and depression symptoms in health workers of two centres of reference for COVID 19 patient care in Antioquia, Colombia - A latent class analysis.

OBJECTIVE: To classify the staff of two reference institutions for COVID-19 care in Antioquia according to the intensity of anxiety and depression symptoms, and to determine the factors associated with these classes. METHODS: Cross-sectional study in which the GAD-7, PHQ-9, fear of COVID-19, and the Copenhagen Burnout scale were used. Latent class analysis was performed to identify the classes, and the factors associated with these were determined using multinomial logistic regression. RESULTS: 486 people participated. The three-class model had the best fit: class I with low scores on the scales; class II with mild degrees of anxiety and depression, and intermediate levels of fear of COVID-19 and perceived stress; and class III with moderate and severe degrees of anxiety, depression, and perceived stress. The factors associated with belonging to class III were age (OR = 0.94; 95%CI, 0.91-0.96), change of residence to avoid exposing relatives (OR = 4.01; 95%CI, 1.99-8.09), and a history of depressive disorder (OR = 3.10; 95%CI, 1.27-7.56), and anxiety (OR = 5.5; 95%CI, 2.36-12.90). Factors associated with class II were age (OR = 0.97; 95%CI, 0.95-0.99), history of depressive disorder (OR = 3.41; 95%CI, 1.60-7.25), living with someone at risk of death from COVID-19 (OR = 1.86; 95%CI, 1.19-2.91), family member being healthcare staff (OR = 1.58; 95%CI, 1.01-2.47), and change of residence to avoid exposing relatives (OR = 1.99; 95%CI, 1.11-3.59). CONCLUSIONS: Three classes of participants were obtained, two of them with anxiety and depression symptoms. Younger age and a history of mental disorder were factors associated with the two classes of symptomatic patients; other factors may be causes or consequences of the symptoms.

Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity.

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T. cruzi. Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major, for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T. cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L. major IPCS. However, disruption of the T. cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T. cruzi IPCS null mutants are unable to establish an infection in vivo, even in immune deficient mice.