Association of anatomical features of the petrotympanic fissure and presence of foramen of Huschke with otalgia and tinnitus.

The petrotympanic fissure (PTF) and foramen of Huschke (FH) are anatomical structures in the temporal bone that can connect the temporomandibular joint (TMJ) and the ear. The purpose of this retrospective study was to investigate the association between PTF morphology and otalgia and tinnitus, as well as the prevalence of the FH and otological symptoms, using cone beam computed tomography (CBCT). CBCT images from 114 patients presenting with symptoms of a temporomandibular disorder were examined retrospectively. The PTF was classified into three subtypes (open, semi-open, closed) and the presence of the FH was identified. Symptoms of otalgia and tinnitus were obtained from the patient files. The FH was observed in 12.3% of patients examined, and in 12.0% of those with otalgia and 18.9% of those with tinnitus. There was no significant association between the PTF subtypes or the presence of the FH and otalgia or tinnitus (all P > 0.05). The PTF subtype and presence of the FH alone do not appear to contribute to otalgia or tinnitus in patients with temporomandibular disorders.

Trapping Microparticles in a Structured Dark Focus.

We experimentally demonstrate stable trapping and controlled manipulation of silica microspheres in a structured optical beam consisting of a dark focus surrounded by light in all directions-the dark focus tweezer. Results from power spectrum and potential analysis demonstrate the nonharmonicity of the trapping potential landscape, which is reconstructed from experimental data in agreement to Lorentz-Mie numerical simulations. Applications of the dark tweezer in levitated optomechanics and biophysics are discussed.

Sex-Specific Patterns of Cerebral Atrophy and Enlarged Perivascular Spaces in Patients with Cerebral Amyloid Angiopathy and Dementia.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy is characterized by amyloid ß deposition in leptomeningeal and superficial cortical vessels. Cognitive impairment is common and may occur independent of concomitant Alzheimer disease neuropathology. It is still unknown which neuroimaging findings are associated with dementia in cerebral amyloid angiopathy and whether they are modulated by sex. This study compared MR imaging markers in patients with cerebral amyloid angiopathy with dementia or mild cognitive impairment or who are cognitively unimpaired and explored sex-specific differences. MATERIALS AND METHODS: We studied 58 patients with cerebral amyloid angiopathy selected from the cerebrovascular and memory outpatient clinics. Clinical characteristics were collected from clinical records. Cerebral amyloid angiopathy was diagnosed on MR imaging on the basis of the Boston criteria. Visual rating scores for atrophy and other imaging features were independently assessed by 2 senior neuroradiologists. RESULTS: Medial temporal lobe atrophy was higher for those with cerebral amyloid angiopathy with dementia versus those cognitively unimpaired (P = .015), but not for those with mild cognitive impairment. This effect was mainly driven by higher atrophy in men with dementia, compared with women with and without dementia (P = .034, P = .012; respectively) and with men without dementia (P = .012). Enlarged perivascular spaces in the centrum semiovale were more frequent in women with dementia versus men with and without dementia (P = .021, P = .011; respectively) and women without dementia (P = .011). CONCLUSIONS: Medial temporal lobe atrophy was more prominent in men with dementia, whereas women showed a higher number of enlarged perivascular spaces in the centrum semiovale. Overall, this finding suggests differential pathophysiologic mechanisms with sex-specific neuroimaging patterns in cerebral amyloid angiopathy.

Airway Phenotypes and Nocturnal Wearing of Dentures in Elders with Sleep Apnea.

The objective of this study was to examine to what extent the anatomic characteristics of the upper airway can influence the effect of nocturnal wearing of dentures on the sleep of edentulous elders with untreated sleep apnea. This study used the data from a randomized crossover clinical trial and an exploratory approach to address its objectives. Cone beam computed tomography scans of 65 edentulous individuals (female, n = 37; male, n = 28; mean ± SD age, 74.54 ± 6.42 y) with untreated obstructive sleep apnea (OSA) were used to identify anatomic variables. Polysomnography data were collected by means of one portable overnight recording. The respiratory variable values, including apnea-hypopnea index (AHI), with and without denture worn during sleep were used to calculate the change. Statistical analyses included multiple linear regressions, cluster analysis, and binary logistic regressions. A receiver operator characteristic curve was used to illustrate the accuracy of the statistical model. The regression model explained 15.8% (R2) of AHI change. An increase in the lateral dimension of the minimum cross-sectional area was associated with a decrease in AHI, oxygen desaturation index, and respiratory arousal index changes (P ≤ 0.041). Furthermore, an increase in the length of the hypopharynx was associated with an increase in AHI and oxygen desaturation index changes (P ≤ 0.027). An increase in the lateral dimension of the minimum cross-sectional area of the upper airway was associated with a decreased likelihood of being in the group having a worsened AHI (odds ratio = 0.85; 95% CI, 0.76 to 0.95; P = 0.006). An increase in the length of the oropharynx was associated with an increased likelihood of having increased AHI (odds ratio = 1.10; 95% CI, 1.01 to 1.20; P = 0.026). The nocturnal aggravation of respiratory variables in edentulous individuals with OSA who wear dentures at night can be linked to certain anatomic characteristics of the upper airway. Replication of these findings may open novel avenues for personalized advice regarding nocturnal wearing of dentures in edentulous individuals with OSA (ClinicalTrials.gov: NCT01868295).

Cardiorespiratory fitness as a mediator in the relationship between lung function and blood pressure in adults.

It is unclear whether physical activity and cardiorespiratory fitness (CRF) are pathways that link low pulmonary function (LPF) to increased blood pressure (BP). Therefore, we investigated the extent to which CRF and moderate-to-vigorous physical activity (MVPA) mediate the relationship between LPF and high BP in adults. We conducted a cross-sectional study with 1,362 participants that underwent cardiopulmonary exercise testing (CPET), spirometry, and wore an accelerometer to determine physical activity patterns. We performed mediation analyses using structural equations considering peak oxygen uptake (V̇O2) and MVPA as mediators, forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) as independent variables, and systolic and diastolic blood pressure (SBP, DBP) as dependent variables. The probability of alpha error was set at 5%. We found a significant total effect of FVC on SBP and DBP considering V̇O2 as mediator (P<0.01). Indirect effects were also significant, with 42.6% of the total effect of FVC on SBP and 77% on DBP mediated by V̇O2 (P<0.01). We did not observe a direct effect of FVC on SBP and DBP. Considering FEV1 as an independent variable, the total effect on SBP was also significant, as were the indirect effects, mediated by V̇O2 at 14.8% for SBP and 7.6% for DBP (P<0.01). We did not find an indirect effect of FVC or FEV1 considering the MVPA as a mediator. CRF mediates the pathway that links LPF and elevated BP. Therefore, CRF is more sensitive to variations in FVC and FEV1 than MVPA.

Anti-Inflammatory and Antioxidant Effects of the Indole-Derived N-Salicyloyltryptamine on Peritonitis and Joint Disability Induced by Carrageenan in Rodents.

Purpose: To investigate the anti-inflammatory and antioxidant activities of N-salicyloyltryptamine (NST) in experimental models of carrageenan (Cg)-induced peritonitis in mice, and evaluation of the effects of NST on Cg-induced joint disability in rats. Methods: Female Swiss mice were submitted to Cg-induced peritonitis in mice or Cg-induced joint disability in rats after intraperitoneal injection of NST (100 or 200 mg/kg). Total leukocyte count, total protein concentration, myeloperoxidase (MPO) and catalase (CAT) activities, and nitrite (NO2 -) and thiobarbituric acid reactive species (TBARS) levels were determined. Results: NST significantly decrease the migration of leukocytes to peritoneal exudate. Cg induces inflammatory responses mediated by expression of reactive oxygen species (ROS). The results further showed that NST significantly decreased MPO and CAT activities, as well as reduced NO2 - and TBARS levels, compared with the vehicle group. Animals treated with NST significantly reduced paw elevation time (PET) on the first hour after induction of joint injury, and this effect was sustained throughout the analysis. Conclusion: NST presented anti-inflammatory and antioxidant effects in experimental models of carrageenan-induced peritonitis and joint disability in mice and rats, respectively, which may be related to the modulation of neutrophils migration as well as the involvement of antioxidant mechanisms.

Influence of breed and parasite challenge on the immune response to naturally acquired intestinal nematode infection in sheep.

Natural infection by intestinal nematodes was assessed in Santa Ines and Ile de France sheep breeds, over a five-month grazing period, with emphasis on the development of the immune response in lambs under two anthelmintic treatment regimens. Nineteen Santa Ines and 19 Ile de France male lambs were allocated into two treatment groups: animals under suppressive treatment with anthelmintics; and animals under targeted selective treatment (TST). The nematodes Trichostrongylus colubriformis and Strongyloides papillosus showed the highest infection intensity in the TST animals in both breeds. Parasite-specific immunoglobulin G levels were significantly higher and more rapidly induced in Santa Ines lambs. Additionally, these lambs had higher levels of parasite-specific immunoglobulin A in intestinal mucus. Animals under TST had higher means of mast cells and globule leukocytes in the intestinal mucosa due to longer and greater parasite challenge in comparison with the suppressive group. A breed effect (P < 0.05) was recorded for mast cells, with Santa Ines lambs presenting the highest counts. Although Santa Ines lambs had lower intestinal nematode counts than Ile de France lambs, they had shown a large variation in T. colubriformis burden, with most of them presenting a marked worm burden, despite showing an earlier and more intense immune response to intestinal nematode infection.

The combined coronal-transconjunctival approach: an innovative surgical access for orbital exenteration in craniofacial resection.

Malignant tumours arising in the paranasal sinuses or maxilla usually spread to the surrounding regions. The skull base and the anterior cranial fossa are frequently affected as well. When the resection of a tumour involves an orbital exenteration, a transconjunctival-perilimbic incision can be added to a coronal approach in order to preserve the eyelids and the conjunctiva, avoiding cutaneous midfacial incisions. Patients with a diagnosis of malignant tumour affecting the orbit, upper jaw, paranasal sinuses, and/or anterior skull base were eligible for this technique. Tumoural invasion of the eyelids, conjunctiva, lacrimal system, or surrounding skin was considered a contraindication for this technique. A retrospective study of the clinical records was performed and age, type of tumour, location, and reconstructive technique were evaluated. Eight patients referred to the study department between 2015 and 2019 were selected. All patients underwent craniofacial surgery and orbital exenteration. The transconjunctival-perilimbic approach was combined with a coronal incision in all cases. In our experience, the transconjunctival-perilimbic approach to orbital exenteration proposed in this paper can be used successfully in skull base surgery. Combined with a coronal and transmandibular approach, it allows wide access to the facial skeleton/anterior skull base while avoiding skin incisions in the midface.

Pregnancy in pigs: the journey of an early life.

Embryo mortality is responsible for greater losses in litter size in pigs. It is well known that pregnancy establishment is a complex process, and important changes occur continuously in both the corpora lutea and the endometrium, which varies depending on the pre-natal development phase: embryonic, pre-implantation or fetal stages. The placenta is a key organ responsible for the exchange of nutrients, metabolites and respiratory gases between mother and fetuses. The porcine placenta is diffuse, epitheliochorial, and placentation begins with implantation, which involves specialized cell adhesion and cell migration, leading to the attachment of the trophectoderm to the uterine endometrial lumen epithelium. The efficiency with which the placenta provides adequate amounts of nutrients and oxygen to the fetus is crucial for proper fetal growth and development. In the last decades, emphasis on selection for sow prolificacy has resulted in a substantial increase in the number of piglets born per litter, which had a direct effect on piglet quality, compromising birth weight and litter uniformity. Placental insufficiency will lead to fetal intrauterine growth restriction. This review addresses the main events of early embryo development, including preimplantation and implantation periods. In addition, placentation and its role on fetal development are covered, as well as intrauterine growth restriction, as it is a natural condition in the pig, with long lasting detrimental effects to the production chain.

Cardiorespiratory fitness as a mediator in the relationship between lung function and blood pressure in adults

It is unclear whether physical activity and cardiorespiratory fitness (CRF) are pathways that link low pulmonary function (LPF) to increased blood pressure (BP). Therefore, we investigated the extent to which CRF and moderate-to-vigorous physical activity (MVPA) mediate the relationship between LPF and high BP in adults. We conducted a cross-sectional study with 1,362 participants that underwent cardiopulmonary exercise testing (CPET), spirometry, and wore an accelerometer to determine physical activity patterns. We performed mediation analyses using structural equations considering peak oxygen uptake (V̇O2) and MVPA as mediators, forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) as independent variables, and systolic and diastolic blood pressure (SBP, DBP) as dependent variables. The probability of alpha error was set at 5%. We found a significant total effect of FVC on SBP and DBP considering V̇O2 as mediator (P<0.01). Indirect effects were also significant, with 42.6% of the total effect of FVC on SBP and 77% on DBP mediated by V̇O2 (P<0.01). We did not observe a direct effect of FVC on SBP and DBP. Considering FEV1 as an independent variable, the total effect on SBP was also significant, as were the indirect effects, mediated by V̇O2 at 14.8% for SBP and 7.6% for DBP (P<0.01). We did not find an indirect effect of FVC or FEV1 considering the MVPA as a mediator. CRF mediates the pathway that links LPF and elevated BP. Therefore, CRF is more sensitive to variations in FVC and FEV1 than MVPA.

[Opicapone for the treatment of Parkinson's disease: real-life data in Spain]. / Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.

Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of "real world or real clinical practice" studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.

TITLE: Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.Resumen. La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de 'vida real o práctica clínica real'. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.

Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España / Opicapone for the treatment of Parkinson's disease: real-life data in Spain

La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de ‘vida real o práctica clínica real’. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.(AU)

Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of “real world or real clinical practice” studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.(AU)

Asc-Seurat: analytical single-cell Seurat-based web application.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat's capabilities by analyzing a peripheral blood mononuclear cell dataset. CONCLUSIONS: Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

Mitogenomic analysis of extant condor species provides insight into the molecular evolution of vultures.

The evolution of large vultures linked to mountainous habitats was accompanied by extreme physiological and behavioral specializations for energetically efficient flights. However, little is known on the genetic traits associated with the evolution of these obligate soaring scavengers. Mitochondrial DNA plays a vital role in regulating oxidative stress and energy production, and hence may be an important target of selection for flight performance. Herein, we characterized the first mitogenomes of the Andean and California condors, the world's heaviest flying birds and the only living representatives of the Vultur and Gymnogyps genus. We reconstructed the phylogenetic relationships and evaluated possible footprints of convergent evolution associated to the life-history traits and distributional range of vultures. Our phylogenomic analyses supported the independent evolution of vultures, with the origin of Cathartidae in the early Paleogene (~ 61 Mya), and estimated the radiation of extant condors during the late Miocene (~ 11 Mya). Selection analyses indicated that vultures exhibit signals of relaxation of purifying selection relative to other accipitrimorph raptors, possibly indicating the degeneration of flapping flight ability. Overall, our results suggest that the extreme specialization of vultures for efficient soaring flight has compensated the evolution of large body sizes mitigating the selection pressure on mtDNA.

Intraoral anastomosis in maxillary microvascular reconstruction after oncological excision.

Microvascular anastomosis using an intraoral approach can avoid unnecessary external incisions thus improving patient satisfaction. Furthermore, in case of short pedicle flaps, the lack of proximity of the recipient vessels can be a problem in microvascular reconstruction of the midface. We present our experience in six patients treated for tumours affecting the midface and reconstructed with microvascular flaps through anastomosis to the intraoral aspect of the facial vessels, with the aim of reviewing the use of this technique. Our results showed that intraoral anastomosis is a feasible technique that can be used in the reconstruction after tumours resection, avoiding additional external incisions in patients with no previous cervicotomy incisions. In two cases, a vein graft was interposed to perform the intraoral arterial anastomosis in a tension-free situation without increasing morbidity. The technical features and advantages of intraoral anastomosis were reviewed.

Plane of nutrition during gestation affects reproductive performance and retention rate of hyperprolific sows under commercial conditions.

Defining a maternal plane of nutrition during gestation is pivotal for improving sow productivity and the cost-effectiveness of feeding. The benefits of increasing the amount of feed during late gestation have been controversial. The objective of this study was to investigate the effects of different planes of nutrition during gestation on reproductive performance of hyperprolific sows and pre-weaning litter performance. One hundred and thirty-five gestating sows were randomly assigned to one of three planes of nutrition throughout parities three and four (P4), as follows: Req - plane designed to meet requirements of prolific sows (2.3 kg per day from day 1 to 21; 1.8 kg per day from day 22 to 75; 2.3 kg per day from day 76 to farrowing); Bump - plane designed as the Req, with increased feed intake during late gestation (3.0 kg per day from day 91 to farrowing); and Maintenance - plane designed to closely meet maintenance requirements of sows (1.8 kg per day from day 1 to farrowing). All treatments were fed the same gestation diet (2.50MCal NE/kg; 0.67% SID Lysine; 15.17% CP). Sow biometrical parameters at farrowing and at weaning, and litter characteristics were recorded. Also, blood samples were collected for pre- and post-prandial serum glucose and plasma insulin, as well as triglycerides, calcium, and phosphorus analyses. Culling, stratified by cause, and retention rates were recorded in all treatments for each parity. Over two parities, Bump sows had higher weight gain and, at P4, had a higher number of piglets born alive (P < 0.05). Bump sows lost more weight between the end of gestation and weaning over two parities (P < 0.05). Maintenance sows showed reduced body condition score with a higher percentage of piglets removed throughout lactation (due to inappetence and inability to reach the udder) at P4 (P = 0.03). Pre- and post-prandial glucose levels were higher in Bump sows, as well as post-prandial insulin and phosphorus levels at P4 (P < 0.05). Bump sows also showed increased plasma triglycerides compared to the other treatments (P = 0.03). Retention rate was reduced in Maintenance compared to Bump and Req sows at parity 5 (P = 0.02). Taken together, our results indicate that higher feed intake allowance during late gestation may improve the sow's nutritional status triggering positive results on litter size of hyperprolific sows (e.g., more than 17 total born). However, body condition score must be carefully evaluated to prevent excessive weight gain during successive parities.

Exploring Ubiquinone Biosynthesis Inhibition as a Strategy for Improving Atovaquone Efficacy in Malaria.

Atovaquone (AV) acts on the malaria parasite by competing with ubiquinol (UQH2) for its union to the mitochondrial bc1 complex, preventing the ubiquinone-8 and ubiquinone-9 (UQ-8 and UQ-9) redox recycling, which is a necessary step in pyrimidine biosynthesis. This study focused on UQ biosynthesis in Plasmodium falciparum and adopted proof-of-concept research to better elucidate the mechanism of action of AV and improve its efficacy. Initially, UQ biosynthesis was evaluated using several radioactive precursors and chromatographic techniques. This methodology was suitable for studying the biosynthesis of both UQ homologs and its redox state. Additionally, the composition of UQ was investigated in parasites cultivated at different oxygen saturations or in the presence of AV. AV affected the redox states of both UQ-8 and UQ-9 homologs by increasing the levels of the respective reduced forms. Conversely, low-oxygen environments specifically inhibited UQ-9 biosynthesis and increased the antimalarial efficacy of AV. These findings encouraged us to investigate the biological importance and the potential of UQ biosynthesis as a drug target based on its inhibition by 4-nitrobenzoate (4-NB), a 4-hydroxybenzoate (4-HB) analog. 4-NB effectively inhibits UQ biosynthesis and enhances the effects of AV on parasitic growth and respiration rate. Although 4-NB itself exhibits poor antimalarial activity, its 50% inhibitory concentration (IC50) value increased significantly in the presence of a soluble UQ analog, p-aminobenzoic acid (pABA), or 4-HB. These results indicate the potential of AV combined with 4-NB as a novel therapy for malaria and other diseases caused by AV-sensitive pathogens.

Tooth survival following root canal treatment by general dental practitioners in a Swedish county - a 10-year follow-up study of a historical cohort.

AIM: To evaluate the 10-year survival rate of root filled teeth treated by general dental practitioners (GDPs), and to identify possible prognostic factors. METHODOLOGY: In 2006, 3676 individuals had at least one tooth root filled by a GDP within the Norrbotten Public Dental Service, Sweden. Over the next 10 years, 331 individuals died and were excluded. A random sample of 302 of the remaining individuals was included in the study, of whom 280 (n = 280 teeth) were included in the analysis. Dental records were reviewed retrospectively by a calibrated researcher to collect predetermined data regarding individual, pre-operative, intra-operative and post-operative factors. The outcome measure was tooth extraction over time, and cases with no events were censored, regardless of apical status or symptoms, until last known date of tooth survival. In case of missing data, individuals were recalled for a control visit. Kaplan-Meier survival tables and Cox regression models were used for analysis. P < 0.05 was considered statistically significant. RESULTS: The cumulative 10-year survival was 81.7% (standard error: 2.6%), and the mean incidence of tooth extraction during the 10 years was 1.8% per year. The univariate analysis identified three possible prognostic factors (P < 0.05) that were associated with extraction: molars, two or more emergency inter-appointment visits during the treatment, and root canal treatments consisting of five or more separate sessions. A multivariate regression analysis revealed no significant relationships for the variables gender, tooth type, number of contacts, any emergency visits during endodontic treatment, number of sessions to complete endodontic treatment, pulp diagnosis, or type of permanent restoration and extraction. CONCLUSIONS: The mean incidence of tooth loss over the first 10 years after completion of root canal treatment performed by a GDP was approximately 2% per year. No prognostic factors could be identified.