Outbreak of Intermediate Species Leptospira venezuelensis Spread by Rodents to Cows and Humans in L. interrogans-Endemic Region, Venezuela.

Leptospirosis is a common but underdiagnosed zoonosis. We conducted a 1-year prospective study in La Guaira State, Venezuela, analyzing 71 hospitalized patients who had possible leptospirosis and sampling local rodents and dairy cows. Leptospira rrs gene PCR test results were positive in blood or urine samples from 37/71 patients. Leptospira spp. were isolated from cultured blood or urine samples of 36/71 patients; 29 had L. interrogans, 3 L. noguchii, and 4 L. venezuelensis. Conjunctival suffusion was the most distinguishing clinical sign, many patients had liver involvement, and 8/30 patients with L. interrogans infections died. The Leptospira spp. found in humans were also isolated from local rodents; L. interrogans and L. venezuelensis were isolated from cows on a nearby, rodent-infested farm. Phylogenetic clustering of L. venezuelensis isolates suggested a recently expanded outbreak strain spread by rodents. Increased awareness of leptospirosis prevalence and rapid diagnostic tests are needed to improve patient outcomes.

Antiplaque and antigingivitis efficacy of medicated and non-medicated sugar-free chewing gum as adjuncts to toothbrushing: systematic review and network meta-analysis.

OBJECTIVE: This network meta-analysis (NMA) assessed the antiplaque and anti-inflammatory efficacy of different sugar-free chewing gums (SFCG) as adjuncts to toothbrushing. MATERIAL AND METHODS: PubMed, Scopus, EMBASE, Web of Science, and CENTRAL databases were searched up to February 2021 to identify randomized controlled trials, involving adults, comparing antiplaque and anti-inflammatory effects of SFCG, with different active ingredients, as adjunctive to mechanical control of biofilm, with a minimum of 7-day of follow-up. Plaque and gingival indexes were assessed. The risk of bias assessment was performed with the RoB 2.0 tool. NMA, and pairwise meta-analyses were performed for both dental plaque and gingival indexes. RESULTS: Twelve studies were included, comprising 850 (antiplaque) and 1459 (gingival inflammation) subjects randomized into 9 interventions: (1) chlorhexidine; (2) chlorhexidine + xylitol (CHX+Xyl); (3) green tea + xylitol (GT+Xyl); (4) magnolia; (5) Lactobacillus reuteri; (6) vitamin C + xylitol; (7) vitamin + carbamide; (8) eucalyptus; and (9) negative control, sorbitol, gum base only, or no chewing gum. No statistically significant differences were detected among SFCG, with different active ingredients, for both antiplaque and anti-inflammatory efficacy (p > 0.05). However, SFCG with GT+XyL outperformed negative control gums regarding antiplaque efficacy (SMD, - 2.93; 95% CrI, - 0.45 to - 5.38). The SUCRA results showed that SFCG containing GT+Xyl was ranked first, for both antiplaque and anti-inflammatory outcomes. CONCLUSION: SFCG containing GT+Xyl showed better antiplaque effect over negative controls. However, cautious interpretation is required due to the low number of direct comparisons arms. These shortcomings underscore the need for RCTs with mostly head-to-head comparison that provide more conclusive evidence. CLINICAL RELEVANCE: There is no robust evidence for the clinical indications of sugar-free chewing gums as adjunct to toothbrushing for the control of biofilm or the treatment of gingivitis.

[Personal and familial features associated with organ donation in Chilean adults]. / Características sociales y familiares asociadas a la decisión de ser donante de órganos y tejidos en población adulta, Coquimbo, Chile 2019.

BACKGROUND: The rates of organ donation are alarmingly low in Chile. AIM: To determine the relationship between social and family characteristics that influence the decision to donate organs and tissues among adults. MATERIAL AND METHODS: The questionnaire developed in Spain by the international collaborative project on organ transplantation and donation, developed and validated in Chile was applied to 383 adults aged 40 ± 17 years (mostly women), living in Coquimbo, Chile. RESULTS: Seventy seven percent of respondents would agree to be a donor. The main features of eventual donors are: being young adult in 62% of respondents, single in 48%, with complete secondary education in 29%, non-practicing Catholic in 37% and being informed on television about transplantation in 66%. In a logistic regression model, the features significantly associated with being an eventual donor were the decision of donating organs of relatives (Odds Ratio [OR] 9.1 95% confidence intervals [CI] 4.8-17-2), commenting and knowing the opinion of relatives (OR 2.3 95%CI 1.2-4.1), especially parents and partner, and a lower age (OR 0.98 95% CI 0.96-0.99). CONCLUSIONS: The decision to donate organs is influenced by commenting and knowing the opinion of relatives, especially parents and partners. Also, a lower age is associated with a better attitude towards donation.

Self-Organization of Large Alumina Platelets and Silica Nanoparticles by Heteroaggregation and Sedimentation: Toward an Alternative Shaping of Nacre-Like Ceramic Composites.

Nacre-like ceramic composites are of importance in a wide range of applications, because of their mechanical properties, combining high mechanical strength and high fracture toughness. Those mechanical properties are the result of strongly aligned platelets glued in a matrix. Different methods exist to shape such a "brick-and-mortar" hierarchical structure. In this paper, we propose to use the phenomenon of heteroaggregation between silica nanoparticles and large alumina platelets. Experimental and numerical results show that silica nanoparticles can adsorb on alumina platelets with good distribution. This adsorption promotes the deagglomeration of alumina that can self-organize in layers by sedimentation. This phenomenon can be exploited to shape alumina-silica nacre-like composites.

Influence of the genetic background on the reproductive phenotype of mice lacking Cysteine-Rich Secretory Protein 1 (CRISP1).

Epididymal sperm protein CRISP1 has the ability to both regulate murine CatSper, a key sperm calcium channel, and interact with egg-binding sites during fertilization. In spite of its relevance for sperm function, Crisp1-/-mice are fertile. Considering that phenotypes can be influenced by the genetic background, in the present work mice from the original mixed Crisp1-/- colony (129/SvEv*C57BL/6) were backcrossed onto the C57BL/6 strain for subsequent analysis of their reproductive phenotype. Whereas fertility and fertilization rates of C57BL/6 Crisp1-/- males did not differ from those reported for mice from the mixed background, several sperm functional parameters were clearly affected by the genetic background. Crisp1-/- sperm from the homogeneous background exhibited defects in both the progesterone-induced acrosome reaction and motility not observed in the mixed background, and normal rather than reduced protein tyrosine phosphorylation. Additional studies revealed a significant decrease in sperm hyperactivation as well as in cAMP and protein kinase A (PKA) substrate phosphorylation levels in sperm from both colonies. The finding that exposure of mutant sperm to a cAMP analog and phosphodiesterase inhibitor overcame the sperm functional defects observed in each colony indicated that a common cAMP-PKA signaling defect led to different phenotypes depending on the genetic background. Altogether, our observations indicate that the phenotype of CRISP1 null males is modulated by the genetic context and reveal new roles for the protein in both the functional events and signaling pathways associated to capacitation.

The EP3 receptor regulates water excretion in response to high salt intake.

The mechanisms by which prostanoids contribute to the maintenance of whole body water homeostasis are complex and not fully understood. The present study demonstrates that an EP3-dependent feedback mechanism contributes to the regulation of water homeostasis under high-salt conditions. Rats on a normal diet and tap water were placed in metabolic cages and given either sulprostone (20 µg·kg-1·day-1) or vehicle for 3 days to activate EP3 receptors in the thick ascending limb (TAL). Treatment was continued for another 3 days in rats given either 1% NaCl in the drinking water or tap water. Sulprostone decreased expression of cyclooxygenase 2 (COX-2) expression by ∼75% in TAL tubules from rats given 1% NaCl concomitant with a ∼60% inhibition of COX-2-dependent PGE2 levels in the kidney. Urine volume increased after ingestion of 1% NaCl but was reduced ∼40% by sulprostone. In contrast, the highly selective EP3 receptor antagonist L-798106 (100 µg·kg-1·day-1), which increased COX-2 expression and renal PGE2 production, increased urine volume in rats given 1% NaCl. Sulprostone increased expression of aquaporin-2 (AQP2) in the inner medullary collecting duct plasma membrane in association with an increase in phosphorylation at Ser269 and decrease in Ser261 phosphorylation; antagonism of EP3 with L-798106 reduced AQP2 expression. Thus, although acute activation of EP3 by PGE2 in the TAL and collecting duct inhibits the Na-K-2Cl cotransporter and AQP2 activity, respectively, chronic activation of EP3 in vivo limits the extent of COX-2-derived PGE2 synthesis, thereby mitigating the inhibitory effects of PGE2 on these transporters and decreasing urine volume.

Acrosome Reaction as a Preparation for Gamete Fusion.

The acrosome reaction (AR) is a universal requisite for sperm-egg fusion. However, whereas through the animal kingdom fusion of spermatozoa with the egg plasma membrane occurs via the inner acrosomal membrane exposed after the AR, in eutherian mammals, gamete fusion takes place through a specialized region of the acrosome known as the equatorial segment (ES) which becomes fusogenic only after the AR is completed. This chapter focuses on the different molecular mechanisms involved in the acquisition of the fusogenicity of the ES after the AR. We provide an update of the knowledge about the proteins proposed to have a role in this process either by modifying cytoskeletal and/or membrane molecules or by relocalizing to the ES after the AR to subsequently participate in gamete fusion.

The galectin-1-glycan axis controls sperm fertilizing capacity by regulating sperm motility and membrane hyperpolarization.

Lectin-glycan recognition systems play central roles in many physiologic and pathologic processes. We identified a role for galectin-1 (Gal-1), a highly conserved glycan-binding protein, in the control of sperm function. We found that Gal-1 is expressed in the epididymis and associates with sperm during epididymal maturation. Exposure of sperm to Gal-1 resulted in glycan-dependent modulation of the acrosome reaction (AR), a key event in the fertilization process. Gal-1-deficient (Lgals1(-/-)) mice revealed the essential contribution of this lectin for full sperm fertilizing ability both in vitro and in vivo. Mechanistically, Lgals1(-/-) sperm exhibited defects in their ability to develop hyperactivation, a vigorous motility required for penetration of the egg vestments. Moreover, Lgals1(-/-) sperm showed a decreased ability to control cell volume and to undergo progesterone-induced AR, phenotypes that were rescued by exposure of the cells to recombinant Gal-1. Interestingly, the AR defect was associated with a deficiency in sperm membrane potential hyperpolarization. Our study highlights the relevance of the Gal-1-glycan axis in sperm function with critical implications in mammalian reproductive biology.

PGE(2) EP(3) receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl.

We tested the hypothesis that inhibition of EP3 receptors enhances cyclooxygenase (COX)-2 expression in the thick ascending limb (TAL) induced by hypertonic stimuli. COX-2 protein expression in the outer medulla increased approximately twofold in mice given free access to 1% NaCl in the drinking water for 3 days. The increase was associated with an approximate threefold elevation in COX-2 mRNA accumulation and an increase in PGE2 production by isolated medullary (m)TAL tubules from 77.3 ± 8.4 to 165.7 ± 10.8 pg/mg protein. Moreover, administration of NS-398 abolished the increase in PGE2 production induced by 1% NaCl. EP3 receptor mRNA levels also increased approximately twofold in the outer medulla of mice that ingested 1% NaCl. The selective EP3 receptor antagonist L-798106 increased COX-2 mRNA by twofold in mTAL tubules, and the elevation in COX-2 protein induced by 1% NaCl increased an additional 50% in mice given L-798106. COX-2 mRNA in primary mTAL cells increased twofold in response to media made hypertonic by the addition of NaCl (400 mosmol/kg H2O). L-798106 increased COX-2 mRNA twofold in isotonic media and fourfold in cells exposed to 400 mosmol/kg H2O. PGE2 production by mTAL cells increased from 79.3 ± 4.6 to 286.7 ± 6.3 pg/mg protein after challenge with 400 mosmol/kg H2O and was inhibited in cells transiently transfected with a lentivirus short hairpin RNA construct targeting exon 5 of COX-2 to silence COX-2. Collectively, the data suggest that local hypertonicity in the mTAL is associated with an increase in COX-2 expression concomitant with elevated EP3 receptor expression, which limits COX-2 activity in this segment of the nephron.

Crisp1 and alopecia areata in C3H/HeJ mice.

Alopecia areata (AA), a cell mediated autoimmune disease, is the second most common form of hair loss in humans. While the autoimmune disease is responsible for the underlying pathogenesis, the alopecia phenotype is ultimately due to hair shaft fragility and breakage associated with structural deficits. Quantitative trait genetic analyses using the C3H/HeJ mouse AA model identified cysteine-rich secretory protein 1 (Crisp1), a hair shaft structural protein, as a candidate gene within the major AA locus. Crisp1 transcripts in the skin at various times during disease development were barely detectable. In situ hybridization identified Crisp1 expression within the medulla of hair shafts from clinically normal strains of mice but not C3H/HeJ mice with AA. Follow-up work with 5-day-old C3H/HeJ mice with normal hair also had essentially no expression of Crisp1. Other non-inflammatory based follicular dystrophy mouse models with similar hair shaft abnormalities also have little or no Crisp1 expression. Shotgun proteomics, used to determine strain difference in hair proteins, confirmed that there was very little CRISP1 within normal C3H/HeJ mouse hair in comparison to 11 other strains. However, mutant mice with hair medulla defects also had undetectable levels of CRISP1 in their hair. Crisp1 null mice had normal skin, hair follicles, and hair shafts indicating that the lack of the CRISP1 protein does not translate directly into defects in the hair shaft or hair follicle. These results suggest that CRISP1 may be an important structural component of mouse hair and that its strain-specific dysregulation may indicate a predisposition to hair shaft disease such as AA.

Mycobacterium tuberculosis population structure and molecular epidemiological analysis in Sucre municipality, Miranda state, Venezuela.

Sucre municipality is a large, densely populated marginal area in the eastern part of Caracas, Venezuela that consistently has more cases of tuberculosis than other municipalities in the country. To identify the neighborhoods in the municipality with the highest prevalence of tuberculosis, and determine whether the Mycobacterium tuberculosis strain distribution in this municipality is different from that previously found in the western part of Caracas and the rest of Venezuela, we collected data on all tuberculosis cases in the municipality diagnosed in 2005-6. We performed two separate molecular epidemiological studies, spoligotyping 44 strains in a first study, and spoligotyping 131 strains, followed by MIRU-VNTR 15 on 21 clustered isolates in the second. With spoligotyping, the most common patterns were Shared International Type SIT17 (21%); SIT42 (15%); SIT93 (11%); SIT20 (7%); SIT53 (6%), a distribution similar to other parts of Venezuela, except that SIT42 and SIT20 were more common. MIRU-VNTR 15 showed that six of seven SIT17 strains examined belonged to a large cluster previously found circulating in Venezuela, but all of the SIT42 strains were related to a cluster centered in the neighborhoods of Unión and Maca, with a MIRU-VNTR pattern not previously seen in Venezuela. It appears that a large percentage of the tuberculosis in the Sucre municipality is caused by the active transmission of two strain families centered within distinct neighborhoods, one reflecting communication with the rest of the country, and the other suggesting the insular, isolated nature of some sectors.

Association between salivary flow and dental caries in institutionalized adolescents: Cross-sectional study.

Background: Brazil has a larger number of adolescent offenders, but studies evaluating their oral health are still limited. Objective: Assess the association between salivary flow and caries experience in youngsters deprived of liberty. Methodology: Sixty-eight male adolescents in conflict with the law, aged between 15 and 19 years, from a Socio-Educational Assistance Center in Brazil participated in the present study. They answered a structured questionnaire, and oral examination was performed by the Decayed, Missing, and Filled Teeth (DMFT) index. The salivary flow rate was obtained using the mechanically stimulated total saliva method. Adjusted Poisson regression was used for the association with total DMFT and its decayed component, using the salivary flow (continuous fashion) or the hyposalivation (≤1 ml/min) as independent variables. Results: Participants were divided into two groups, those who did not have any decayed teeth at the moment of the examination (n = 39) and those who had at least one decayed tooth (n = 29). Moreover, two groups were formed based on the DMFT: those who had DMFT = 0 (n = 20) and those who had DMFT≥1 (n = 48). In the multivariate analysis, hyposalivation was associated with DMFT≥1 (p = 0.048), but when the salivary flow was included, no significant association with DMFT index was identified (p = 0.178). Conversely, the presence of at least one decayed tooth was significantly associated with the salivary flow (p = 0.004), but not with hyposalivation (p = 0.091). Conclusions: Institutionalized adolescents who present hyposalivation or low salivary flow are associated with DMFT≥1 index or presence of at least one decayed tooth, respectively.

Physiological and pathological aspects of epididymal sperm maturation.

In mammals, sperm that leave the testes are nonfunctional and require a complex post-testicular maturation process to acquire their ability to recognize and fertilize the egg. The crucial maturation changes that provide sperm their fertilizing capability occur while passing through the epididymis. Due to the widespread use of assisted reproductive technologies to address male infertility, there has been a significant decrease in research focusing on the mechanisms underlying the maturation process over the past decades. Considering that up to 40% of male infertility is idiopathic and could be reflecting sperm maturation defects, the study of post-testicular sperm maturation will clearly contribute to a better understanding of the causes of male infertility and to the development of both new approaches to maturing sperm in vitro and safer male contraceptive methods. Based on this, the present review focuses on the physiopathology of the epididymis as well as on current approaches under investigation to improve research in sperm maturation and as potential therapeutic options for male infertility.

Correlates of Theta and Gamma Activity during Visuospatial Incidental/Intentional Encoding and Retrieval Indicate Differences in Processing in Young and Elderly Healthy Participants.

Incidental visuospatial learning acquired under incidental conditions is more vulnerable to aging than in the intentional case. The theta and gamma correlates of the coding and retrieval of episodic memory change during aging. Based on the vulnerability of incidental coding to aging, different theta and gamma correlates could occur under the incidental versus intentional coding and retrieval of visuospatial information. Theta and gamma EEG was recorded from the frontotemporal regions, and incidental/intentional visuospatial learning was evaluated in young (25-60 years old) and elderly (60-85 years old) participants. The EEG recorded during encoding and retrieval was compared between incidental low-demand, incidental high-demand, and intentional conditions through an ANCOVA considering the patient's gender, IQ, and years of schooling as covariates. Older adults exhibited worse performances, especially in place-object associations. After the intentional study, older participants showed a further increase in false-positive errors. Higher power at the theta and gamma bands was observed for frontotemporal derivations in older participants for both encoding and retrieval. Under retrieval, only young participants had lower power in terms of errors compared with correct responses. In conclusion, the different patterns of power and coherence support incidental and intentional visuospatial encoding and retrieval in young and elderly individuals. The correlates of power with behavior are sensitive to age and performance.

Pressure control and treatment interact in the deterioration of incidental visuospatial memory in hypertensive patients.

BACKGROUND: Systemic hypertension (SH) is the main risk factor to cognitive deterioration, whereas visuospatial memory is more vulnerable to ageing. Some antihypertensive agents have a neuroprotector effect, however, such effects could be masked by comorbidities and/or the lack of effective control on the arterial pressure of patients. OBJECTIVE: To assess this, the evaluation of incidental visuospatial memory of SH patients and the relation to the treatment received and the effective control of pressure were made. METHOD: 80 patients (46 woman) were included grouped by the received medication: angiotensin 2 receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI). A multiple correlation analysis between visuospatial scores and clinical variables was made; also, a mixed model analysis (fixed factors: treatment, pressure control, diabetes comorbidity; aleatory factors: age, schooling, months from SH diagnoses). RESULTS: Half of the patients had a controlled pressure, from them the higher proportion received ARB, and a minor number of patients received ACEI. The normotensive patients receiving ACEI were inefficient whereas the hypertensive patients were more efficient. The systolic pressure was negatively related with the visuospatial scores in spite of no correlations occurred with MoCA and Raven tests. CONCLUSIONS: The visuospatial incidental/intentional scores were negatively correlated with systolic pressure. The efficiency in the visuospatial ability depends on the interaction of treatment and effective control of blood pressure. The interaction between treatment and effective pressure control must be taken in count when cognitive deterioration is studied.

ANTECEDENTES: La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para el deterioro cognitivo; por otro lado, la memoria visuoespacial es más vulnerable al envejecimiento. Algunos fármacos antihipertensivos tienen un efecto neuroprotector, pero tal efecto puede enmascararse o bien no manifestarse por comorbilidad o por falta de control efectivo de la presión arterial. OBJETIVO: Evaluar las alteraciones en la memoria visuoespacial incidental de pacientes con HAS en relación con su tratamiento antihipertensivo y su control de la presión. MÉTODO: Se incluyeron 80 pacientes con HAS (46 mujeres), agrupados por su medicación en bloqueadores de los receptores de la angiotensina II (BRA) o inhibidores de la enzima convertidora de angiotensina (IECA). Se realizó un análisis de correlaciones múltiples para los puntajes obtenidos en la prueba de memoria visuoespacial incidental/intencional y un análisis de modelos mixtos (factores fijos: tratamiento, control de la presión y comorbilidad con diabetes; factores aleatorios: edad, escolaridad, meses desde el diagnóstico de HAS y coeficiente intelectual). RESULTADOS: De los pacientes controlados, la mayoría de los que recibían BRA fueron eficientes y los que recibían IECA fueron deficientes. De los que recibían IECA, los descontrolados hipertensos fueron más eficientes que los normotensos. La memoria visuoespacial se correlacionó negativamente con la presión sistólica a pesar de no haber diferencias en MoCA y Raven. CONCLUSIONES: La eficiencia en la memoria visuoespacial dependió de la interacción del tratamiento y el control de la presión. Ambos factores, tratamiento y control efectivo de la presión, deben considerarse en la evaluación del deterioro cognitivo asociado a la HAS.

Antimicrobial Effect of Copper Nanoparticles on Relevant Supragingival Oral Bacteria.

Copper nanoparticles (Cu NPs) show promise in dentistry for combating bacterial dysbiosis and tooth decay. Understanding their effects on commensal versus pathogenic bacteria is vital for maintaining oral health balance. While Cu NPs demonstrate antibacterial properties against various oral bacteria, including common pathogens associated with tooth decay, their impact on commensal bacteria requires careful examination. In our work, we analyzed three types of Cu NPs for their effects on the growth, viability, and biofilm formation of representative caries-associated and commensal oral bacteria. S. sanguinis showed high tolerance to all Cu NPs, while L. rhamnosus was highly sensitive. Oxide-Cu NPs exhibited a stronger inhibitory effect on pathobionts compared with commensal bacteria. Moreover, the biofilm formation of the key cariogenic bacteria S. mutans was reduced, with minimal negative effects on commensal species' biofilm formation. All our results showed that CuO nanoparticles (CuO NPs) exhibit reduced toxicity toward commensal bacteria growth and development but have a strong impact on pathogens. This suggests their potential for targeted treatments against pathogenic bacteria, which could help in maintaining the balance of the oral bacterial community.

Association between embB mutations and ethambutol resistance in Mycobacterium tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns and problems.

The relation of ethambutol resistance to embB mutations remains unclear, and there are no reports on ethambutol resistance from the caribbean. We examined the sequence of embB in 57 distinct Multi-Drug Resistant (MDR) and non-MDR strains of Mycobacterium tuberculosis, mostly from Cuba and the Dominican Republic. embB306 codon mutations were found exclusively in MDR-TB, but in both ethambutol sensitive and resistant strains. Valine substitutions predominated in ethambutol resistant strains, while isoleucine replacements were more common in sensitive strains. Three ethambutol resistant MDR strains without embB306 substitutions had replacements in embB406 or embB497, but these were also found in ethambutol sensitive MDR strains. The results confirm previous findings that amino acid substitutions in EmbB306, EmbB406 and EmbB497 are found only in MDR-TB strains but in both phenotypically resistant and sensitive strains. One ethambutol resistant non-MDR strain did not have any embB mutation suggesting that other undefined mutations can also confer ethambutol resistance.

Poor Quality of Sleep is Associated with Lower Academic Performance in Undergraduate Dental Students: A Cross-Sectional Study.

Purpose: This study aimed to assess the quality of sleep and associated factors among dental students. Methods: All dental students regularly enrolled at the Federal University of Pelotas, Brazil, were invited to participate. A structured online questionnaire was applied to collect the independent variables, including academic performance. Quality of sleep was assessed by the validated version of the Pittsburgh Sleep Quality Index. Sample was dichotomized as good sleep quality (total score: ≤ 4) and at least poor quality (total score: ≥ 5). Adjusted analyses were performed using Poisson regression with robust variance to detect the association between sleep quality and independent variables. Independent adjusted models were performed to the whole-sample, only undergraduate and only graduate dental students. Results: Poor quality of sleep was detected in 266 (65.2%) dental students, of which 228 (68.9%) and 38 (49.4%) were undergraduate and graduate dental students, respectively. Female students presented a prevalence ratio (PR) 19% higher compared to males (95% confidence interval [CI] 1.01-1.41). When only graduate students were considering, those that reported not being the head of the family presented a PR 4.39 higher for poor quality of sleep (95% CI 1.91-10.09). Poor quality of sleep was associated with lower academic performance among undergraduate students (PR: 0.94; 95% CI 0.89-0.99), but not significantly associated when graduate students are considered (PR: 0.99; 95% CI 0.96-1.03). Conclusion: It was concluded that dental students, mainly female ones, have high prevalence of poor quality of sleep, which is associated with undergraduate student's worst academic performance. Supplementary Information: The online version contains supplementary material available at 10.1007/s41782-022-00223-2.

A Novel Homozygous Mutation of AIRE Gene in a Patient With Autoimmune Polyglandular Syndrome Type I.

Autoimmune polyglandular syndrome type I (APS1) shows common features such as mucocutaneous candidiasis, hypoparathyroidism, and hypoadrenalism. The clinical manifestations and their onset are highly variable. Besides endocrine abnormalities, patients can present with dental problems, keratoconjunctivitis, fever, rash, chronic diarrhea, and autoimmune hepatitis. We discuss the case of a 5-year-old female who presented initially with a new-onset seizure due to severe hypocalcemia and was diagnosed with primary hypoparathyroidism. Because she also had a history of chronic mucocutaneous candidiasis, chronic diarrhea, and the presence of autoantibodies tested positive, the diagnosis of APS1 was suspected. Genetic testing detected a novel pathogenic homozygous AIRE mutation, which confirmed the diagnosis. She began multidisciplinary treatment with antifungals, calcium supplements, and parathyroid hormone analogs.

Prostaglandin E2 EP3 receptor regulates cyclooxygenase-2 expression in the kidney.

Cyclooxygenase-2 (COX-2) is constitutively expressed and highly regulated in the thick ascending limb (TAL). As COX-2 inhibitors (Coxibs) increase COX-2 expression, we tested the hypothesis that a negative feedback mechanism involving PGE(2) EP3 receptors regulates COX-2 expression in the TAL. Sprague-Dawley rats were treated with a Coxib [celecoxib (20 mg·kg(-1)·day(-1)) or rofecoxib (10 mg·kg(-1)·day(-1))], with or without sulprostone (20 µg·kg(-1)·day(-1)). Sulprostone was given using two protocols, namely, previous to Coxib treatment (prevention effect; Sulp7-Coxib5 group) and 5 days after initiation of Coxib treatment (regression effect; Coxib10-Sulp5 group). Immunohistochemical and morphometric analysis revealed that the stained area for COX-2-positive TAL cells (µm(2)/field) increased in Coxib-treated rats (Sham: 412 ± 56.3, Coxib: 794 ± 153.3). The Coxib effect was inhibited when sulprostone was used in either the prevention (285 ± 56.9) or regression (345 ± 51.1) protocols. Western blot analysis revealed a 2.1 ± 0.3-fold increase in COX-2 protein expression in the Coxib-treated group, an effect abolished by sulprostone using either the prevention (1.2 ± 0.3-fold) or regression (0.6 ± 0.4-fold vs. control, P < 0.05) protocols. Similarly, the 6.4 ± 0.6-fold increase in COX-2 mRNA abundance induced by Coxibs (P < 0.05) was inhibited by sulprostone; prevention: 0.9 ± 0.3-fold (P < 0.05) and regression: 0.6 ± 0.1 (P < 0.05). Administration of a selective EP3 receptor antagonist, L-798106, also increased the area for COX-2-stained cells, COX-2 mRNA accumulation, and protein expression in the TAL. Collectively, the data suggest that COX-2 levels are regulated by a novel negative feedback loop mediated by PGE(2) acting on its EP3 receptor in the TAL.