Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing.

Common genetic contributions to autism spectrum disorder (ASD) reside in risk gene variants that individually have minimal effect sizes. As environmental factors that perturb neurodevelopment also underlie idiopathic ASD, it is crucial to identify altered regulators that can orchestrate multiple ASD risk genes during neurodevelopment. Cytoplasmic polyadenylation element binding proteins 1-4 (CPEB1-4) regulate the translation of specific mRNAs by modulating their poly(A)-tails and thereby participate in embryonic development and synaptic plasticity. Here we find that CPEB4 binds transcripts of most high-confidence ASD risk genes. The brains of individuals with idiopathic ASD show imbalances in CPEB4 transcript isoforms that result from decreased inclusion of a neuron-specific microexon. In addition, 9% of the transcriptome shows reduced poly(A)-tail length. Notably, this percentage is much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of ASD risk genes. An equivalent imbalance in CPEB4 transcript isoforms in mice mimics the changes in mRNA polyadenylation and protein expression of ASD risk genes and induces ASD-like neuroanatomical, electrophysiological and behavioural phenotypes. Together, these data identify CPEB4 as a regulator of ASD risk genes.

High-risk human papillomavirus-18 uses an mRNA sequence to synthesize oncoprotein E6 in tumors.

Cervical cancer is the fourth most common cause of cancer in women worldwide in terms of both incidence and mortality. Persistent infection with high-risk types of human papillomavirus (HPV), namely 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, constitute a necessary cause for the development of cervical cancer. Viral oncoproteins E6 and E7 play central roles in the carcinogenic process by virtue of their interactions with cell master proteins such as p53, retinoblastoma (Rb), mammalian target of rapamycin (mTOR), and c-MYC. For the synthesis of E6 and E7, HPVs use a bicistronic messenger RNA (mRNA) that has been studied in cultured cells. Here, we report that in cervical tumors, HPV-18, -39, and -45 transcribe E6/E7 mRNAs with extremely short 5' untranslated regions (UTRs) or even lacking a 5' UTR (i.e., zero to three nucleotides long) to express E6. We show that the translation of HPV-18 E6 cistron is regulated by the motif ACCaugGCGCG(C/A)UUU surrounding the AUG start codon, which we term Translation Initiation of Leaderless mRNAs (TILM). This motif is conserved in all HPV types of the phylogenetically coherent group forming genus alpha, species 7, which infect mucosal epithelia. We further show that the translation of HPV-18 E6 largely relies on the cap structure and eIF4E and eIF4AI, two key translation initiation factors linking translation and cancer but does not involve scanning. Our results support the notion that E6 forms the center of the positive oncogenic feedback loop node involving eIF4E, the mTOR cascade, and p53.

Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α.

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

Radiofrequency ablation of supraventricular arrhythmias after orthotopic heart transplantation: Long-term follow-up of a single-center experience.

BACKGROUND: Supraventricular arrhythmias (SVAs), commonly managed with radiofrequency ablation (RFA), may occur after orthotopic heart transplantation (OHT). METHODS: We retrospectively assessed 514 consecutive patients (pts.) undergoing OHT between January 1990 and July 2016 in a single-center. Patients with SVAs managed with RFA were included. Mechanisms of genesis of SVAs, association with surgical techniques and outcomes, were analyzed. RESULTS: Of 514 pts undergoing OHT, 53% (272 pts.) were managed with bicaval (BC) technique and 47% (242 pts.) with biatrial (BA) technique. Mean follow-up 10 ± 8.4 years. Nine pts. (1.7%) developed SVA requiring RFA. The BC technique was performed in 4 pts., 3 pts. presented cavotricuspid isthmus-dependent atrial flutter (CTI AFL), and 1 pt. double loop AFL. Five pts. were managed with BA technique, 4 pts. presented CTI AFL, and 1 pt. atrial tachycardia (AT). Mean time between OHT and SVA occurrence was 6.6 ± 5.5 years. The procedure was successful in 89% (8 pts.). Arrhythmia recurrence was seen in 3 pts (37%), all with BA technique. CONCLUSION: Supraventricular arrhythmias in heart transplantation may be associated with the surgical scar. Identifying the mechanism is vital to choose the appropriate treatment with radiofrequency ablation.

Extreme genetic structure in a social bird species despite high dispersal capacity.

Social barriers have been shown to reduce gene flow and contribute to genetic structure among populations in species with high cognitive capacity and complex societies, such as cetaceans, apes and humans. In birds, high dispersal capacity is thought to prevent population divergence unless major geographical or habitat barriers induce isolation patterns by dispersal, colonization or adaptation limitation. We report that Iberian populations of the red-billed chough, a social, gregarious corvid with high dispersal capacity, show a striking degree of genetic structure composed of at least 15 distinct genetic units. Monitoring of marked individuals over 30 years revealed that long-distance movements over hundreds of kilometres are common, yet recruitment into breeding populations is infrequent and highly philopatric. Genetic differentiation is weakly related to geographical distance, and habitat types used are overall qualitatively similar among regions and regularly shared by individuals of different populations, so that genetic structure is unlikely to be due solely to isolation by distance or isolation by adaptation. Moreover, most population nuclei showed relatively high levels of genetic diversity, suggesting a limited role for genetic drift in significantly differentiating populations. We propose that social mechanisms may underlie this unprecedented level of genetic structure in birds through a pattern of isolation by social barriers not yet described, which may have driven this remarkable population divergence in the absence of geographical and environmental barriers.

La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1).

The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of protein synthesis. The best studied targets of mTORC1 in translation are the eukaryotic initiation factor-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). In this study, we identify the La-related protein 1 (LARP1) as a key novel target of mTORC1 with a fundamental role in terminal oligopyrimidine (TOP) mRNA translation. Recent genome-wide studies indicate that TOP and TOP-like mRNAs compose a large portion of the mTORC1 translatome, but the mechanism by which mTORC1 controls TOP mRNA translation is incompletely understood. Here, we report that LARP1 functions as a key repressor of TOP mRNA translation downstream of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii) LARP1 binds the 5'TOP motif to repress TOP mRNA translation; and (iv) LARP1 competes with the eukaryotic initiation factor (eIF) 4G for TOP mRNA binding. Importantly, from a drug resistance standpoint, our data also show that reducing LARP1 protein levels by RNA interference attenuates the inhibitory effect of rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation. Collectively, our findings demonstrate that LARP1 functions as an important repressor of TOP mRNA translation downstream of mTORC1.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

KEY POINTS: Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. ABSTRACT: Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB.

Effectiveness of transcervical hysteroscopic endometrial resection based on the prevention of the recurrence of endometrial polyps in post-menopausal women.

BACKGROUND: The objectives of this study were to determine the effectiveness the effectiveness of post-polypectomy hysteroscopic endometrial resection in preventing the recurrence of endometrial polyps in post-menopausal patients and analyse the complications and necessity of additional surgery in patients, in addition to their degree of satisfaction. METHODS: A prospective longitudinal study of post-menopausal patients diagnosed with endometrial polyps was conducted including polypectomy and hysteroscopic endometrial resection following the therapeutic purposes (endometrial polyp removal) and prevention of recurrence of endometrial polyps. We evaluated the general condition and characteristics of the patients, including age, BMI, smoking habits, medical, surgical, and obstetrics history and menstrual status. The results were analysed at several time points, 6, 18, 42 and 60 months by hysteroscopy, including the presence of vaginal bleeding and/or possible intracavitary pathology. RESULTS: A total of 89.5% (n = 355) of our patients had profile factors associated with the increased incidence of endometrial polyps and hyperestrogenism (diabetes mellitus, hypertension and overweight); 89.5% (n = 355) of patients were overweight; 34% had grade I obesity. The surgical procedure was safe, with a 90% (n = 357) success rate without complications, which was higher than the 95-99.5% at the beginning and end time points of the study. Patient acceptance and satisfaction was 90 and 84%, respectively. CONCLUSIONS: Endometrial resection proved effective in preventing the recurrence of endometrial polyps. It is a safe and effective method. Post-menopausal bleeding reduces the presence of endometrial polyps. Patients reported satisfaction and acceptance of the procedure.

Endometriosis node in gynaecologic scars: a study of 17 patients and the diagnostic considerations in clinical experience in tertiary care center.

BACKGROUND: Endometriosis nodes are observed in extra pelvic locations, particularly in gynaecological scars, with the abdominal wall being one of the most frequent locations. The main objective of the study is to review patient characteristics of cases of endometriosis nodes in gynaecological scars. METHODS: A retrospective, observational and descriptive study with a cohort of patients from Hospital 12 de Octubre was conducted from January 2000 to January 2012. We analysed all of the patients who presented with an endometriosis node in a gynaecological scar presentation who had undergone surgery in that period. Descriptive data were collected and analysed. RESULTS: A total of 17 patients with an anatomopathological diagnosis of an endometriosis node in a gynaecological scar were found. The following variables were studied: the age at diagnosis (32.5 years +/- 5.5 years), personal and obstetric history, time from surgery to diagnosis (4.2 years +/- 3.4 years), symptoms (a painful mass that grows during menstruation is the most frequent symptom in our patients), technical analyses by computed tomography (CT), magnetic resonance (MR) or fine needle aspiration (FNA) (77% of the patients), node size (2.5 cm +/- 1.1 cm) and location (caesarean scar, 82%; episiotomy scar, 11.7%; and laparoscopic surgery port, 5.8%), involvement of adjacent structures (29% of the patients), treatment (exeresis with a security margin in all the patients) and other endometriosis locations (14% of the patients). CONCLUSIONS: A high level of suspicion is required to diagnose gynaecological scar endometriosis, which should be suspected in the differential diagnosis of scar masses in reproductive-aged women. Several theories have been proposed to explain the formation of endometriosis nodes in extrauterine localizations. The two of them that seem to be more plausible are the metaplasia and transport theories. Imaging with ultrasound, CT and MR facilitate the diagnosis. FNA could be used for preoperative diagnosis. Treatment must be by node resection with a security margin. In some cases, surgery could be combined with hormonal treatment.

Trunnion-Head Stresses in THA: Are Big Heads Trouble?

The effects of large heads on stresses at the THA trunnion-head junction and their impact on tribocorrosion/metal ion release remain controversial. A 12/14 3D-model of a stem with different head sizes was investigated. Material properties of titanium were assigned to the trunnion and cobalt-chrome/alumina to the heads. A load simulating walking single-leg stand phase was applied to the head. A total contact head-trunnion interface was assumed. The area underneath the junction underwent significant elevations in stresses as head size increased from 28- to 40-mm. Maximum principal stress doubled between 28 and 40-mm heads, regardless of head material. Stress levels had a direct correlation to head diameter. Stress increases observed using increasingly larger heads will probably contribute to head-trunnion tribocorrosion and ion release.

Pain and symptoms of depression in older adults living in community and in nursing homes: the role of activity restriction as a potential mediator and moderator.

BACKGROUND: Chronic pain is likely to lead to depressive symptoms, but the nature of this relationship is not completely clear. The aim of the present study is to analyze the role of activity restriction in the pain-depression relationship in older people, and to test the hypothesis that this role is more relevant in community-dwelling older people than in nursing home residents. METHOD: Depressive symptoms, pain intensity, and activity restriction were measured in a sample of 208 older adults with osteoarthritis, 102 living in nursing homes (NH), and 106 in the community. Analyses were carried out using moderation and moderated mediation analyses approach, treating activity restriction as a confounder. RESULTS: RESULTS showed a significant confounding effect of activity restriction, interaction effect between pain intensity and activity restriction on depression, and modifying effect of pain intensity on depression by adding activity restriction into the model. These results suggest a potential mediating and moderating effects of activity restriction. Moreover, analyses suggest that, surprisingly, the strength of the mediation could be higher in nursing homes. CONCLUSIONS: Overall, it may be that what is really important to emotional well-being is not so much pain itself, but rather the way in which the pain alters older people's lives. The greater strength of the mediation in NH might be understood within the scope of self-determination theory. Generally speaking, the NH context has been considered as a coercive setting, promoting non-autonomous orientation. In this context, when events are objectively coercive, people may lack perceived autonomy and hence be at greater risk of depression.

Pharyngeal mucosal closure in total laryngectomy: comparison between vertical and T-shaped closure.

Objective: The objective of this study was to compare the outcomes vertical and T-shaped pharyngoplasty closure techniques after total laryngectomy (TL) and to evaluate the factors associated with the development of pharyngocutaneous fistula. Materials and methods: We performed a retrospective study that included patients with a histopathological diagnosis of laryngeal cancer that underwent TL between 2009 and 2021. Results: Fifty-seven patients were included in the study. A total of 14 patients underwent a vertical closure of the neopharynx (24.6%), while 43 patients underwent a T-shaped closure (74.4%). Pharyngocutaneous fistula was the most common complication, observed in 40.4% of cases (n = 23). No difference in the rate of complications was observed between groups, with the exception of tracheal dehiscence which was reduced in patients with T-shaped closure (n = 2, 4.7% vs. n = 5, 35.7%, p = 0.002). Diabetes mellitus was more frequently observed in patients withthe development of pharyngocutaneous fistula (n = 7, 30.4% vs. n = 3, 8.8%, p = 0.03). Conclusions: Although complicationswere lower in the T-shaped closure group, we could not establish the superiority of either technique.

Objetivo: Evaluar los desenlaces de la técnica vertical en comparación con la técnica en T para el cierre de faringoplastia posterior a una laringectomía total, y evaluar los factores asociados con el desarrollo de fístula faringocutánea. Método: Estudio retrospectivo de pacientes con diagnóstico de cancer de laringe a quienes se realizó laringectomía total como tratamiento, de 2009 a 2021. Resultados: Se incluyeron 57 pacientes. A 14 (24.6%) se les realizó una faringoplastia con cierre en T y a 43 (74.4%) un cierre vertical. La fístula faringocutánea fue la complicación más frecuente, presente en el 40.4% de los casos (n = 23). No se observaron diferencias en el desarrollo de complicaciones entre grupos, con excepción de la dehiscencia traqueal, la cual fue menos frecuente en el grupo de cierre en T (n = 2, 4.7% vs. n = 5, 35.7%; p = 0.002). La diabetes mellitus se asoció con el desarrollo de fístula faringocutánea (n = 7, 30.4% vs. n = 3, 8.8%; p = 0.03). Conclusiones: Aunque se observó una tendencia a una disminución de las complicaciones en el grupo de cierre en T, no se encontró superioridad de una técnica sobre otra.

Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality.

Primary mitochondrial diseases (PMDs) are associated with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients with PMD show gliosis, and pharmacological depletion of microglia, the innate immune cells of the brain, ameliorates multiple symptoms in a mouse model. Given that microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated with microglia stimulation in vitro (via IL-33 or TAU treatment) was partially changed by complex I (CI) inhibition (via rotenone treatment). In vivo, we generated a mouse model deficient for CI activity in microglia (MGcCI). MGcCI microglia showed metabolic rewiring and gradual transcriptional activation, which led to hypertrophy and dysfunction in juvenile (1-month-old) and adult (3-month-old) stages, respectively. MGcCI mice presented widespread reactive astrocytes, a decrease of synaptic markers accompanied by an increased number of parvalbumin neurons, a behavioral deficit characterized by prolonged periods of immobility, loss of weight and premature death that was partially rescued by pharmacologic depletion of microglia. Our data demonstrate that microglia development depends on mitochondrial CI and suggest a direct microglial contribution to PMDs.

Conditioned Cooperative training for semi-supervised weapon detection.

Violent assaults and homicides occur daily, and the number of victims of mass shootings increases every year. However, this number can be reduced with the help of Closed Circuit Television (CCTV) and weapon detection models, as generic object detectors have become increasingly accurate with more data for training. We present a new semi-supervised learning methodology based on conditioned cooperative student-teacher training with optimal pseudo-label generation using a novel confidence threshold search method and improving both models by conditional knowledge transfer. Furthermore, a novel firearms image dataset of 458,599 images was collected using Instagram hashtags to evaluate our approach and compare the improvements obtained using a specific unsupervised dataset instead of a general one such as ImageNet. We compared our methodology with supervised, semi-supervised and self-supervised learning techniques, outperforming approaches such as YOLOv5 m (up to ＋19.86), YOLOv5l (up to ＋6.52) Unbiased Teacher (up to ＋10.5 AP), DETReg (up to ＋2.8 AP) and UP-DETR (up to ＋1.22 AP).

Drug Repurposing for Cancers With Limited Survival: Protocol for a Retrospective Cohort Study.

BACKGROUND: Only 5% of the molecules tested in oncology phase 1 trials reach the market after an average of 7.5 years of waiting and at a cost of tens of millions of dollars. To reduce the cost and shorten the time of discovery of new treatments, "drug repurposing" (research with molecules already approved for another indication) and the use of secondary data (not collected for the purpose of research) have been proposed. Due to advances in informatics in clinical care, secondary data can, in some cases, be of equal quality to primary data generated through prospective studies. OBJECTIVE: The objective of this study is to identify drugs currently marketed for other indications that may have an effect on the prognosis of patients with cancer. METHODS: We plan to monitor a cohort of patients with high-lethality cancers treated in the public health system of Catalonia between 2006 and 2012, retrospectively, for survival for 5 years after diagnosis or until death. A control cohort, comprising people without cancer, will also be retrospectively monitored for 5 years. The following study variables will be extracted from different population databases: type of cancer (patients with cancer cohort), date and cause of death, pharmacological treatment, sex, age, and place of residence. During the first stage of statistical analysis of the patients with cancer cohort, the drugs consumed by the long-term survivors (alive at 5 years) will be compared with those consumed by nonsurvivors. In the second stage, the survival associated with the consumption of each relevant drug will be analyzed. For the analyses, groups will be matched for potentially confounding variables, and multivariate analyses will be performed to adjust for residual confounding variables if necessary. The control cohort will be used to verify whether the associations found are exclusive to patients with cancer or whether they also occur in patients without cancer. RESULTS: We anticipate discovering multiple significant associations between commonly used drugs and the survival outcomes of patients with cancer. We expect to publish the initial results in the first half of 2024. CONCLUSIONS: This retrospective study may identify several commonly used drugs as candidates for repurposing in the treatment of various cancers. All analyses are considered exploratory; therefore, the results will have to be confirmed in subsequent clinical trials. However, the results of this study may accelerate drug discovery in oncology. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48925.

CrimeNet: Neural Structured Learning using Vision Transformer for violence detection.

The state of the art in violence detection in videos has improved in recent years thanks to deep learning models, but it is still below 90% of average precision in the most complex datasets, which may pose a problem of frequent false alarms in video surveillance environments and may cause security guards to disable the artificial intelligence system. In this study, we propose a new neural network based on Vision Transformer (ViT) and Neural Structured Learning (NSL) with adversarial training. This network, called CrimeNet, outperforms previous works by a large margin and reduces practically to zero the false positives. Our tests on the four most challenging violence-related datasets (binary and multi-class) show the effectiveness of CrimeNet, improving the state of the art from 9.4 to 22.17 percentage points in ROC AUC depending on the dataset. In addition, we present a generalisation study on our model by training and testing it on different datasets. The obtained results show that CrimeNet improves over competing methods with a gain of between 12.39 and 25.22 percentage points, showing remarkable robustness.

Anatomical Variants of the Uncinate Process: A Challenge in the Endoscopic Surgery of the Nose and Paranasal Sinuses.

Importance To identify the anatomical variants of the uncinate process relevant to surgical intervention during the nose and paranasal sinus surgeries. Objective To evaluate the frequency of anatomical variants of the uncinate process in a population of northeast Mexico and compare it with another population. Methods Retrospective study, descriptive and analytical, randomly selected patients with radiological evaluation at Hospital Universitario Dr. José Eleuterio González, Monterrey, Mexico. Images were obtained from the Radiology Department. A total of 149 patients aged from 18 to 79 years with paranasal sinus-CT performed between January 2019 and December 2021 were analyzed. The variables evaluated were uncinate process anatomical variations by age group, radiological classification of the superior attachment of the uncinate process, and morphological variations. Main outcomes and measures The primary study outcome was the determination of the most frequent insertion of uncinate process in the northeast Mexican population. Results The 149 CT scans comprised 71 females with a mean age of 38.28 ± 16.7 years and 78 males, with a mean age of 41.8 ± 15.01 years. The most frequent uncinate process of superior attachment was type one, observed in 57.7% of males (n=45) and 50.7% of females (n=37) (p=0.494). Type one was most observed on the right side (57.7%). Type four was the second most common type, present in 12.8% of males (n=10) and 12.7% of females (n=9) (p=0.82). Conclusion Knowledge about the types of variations in the insertion of the uncinate process is fundamental prior to any endoscopic sinus surgery. The surgeon must be familiar with this detail when approaching patients with sinonasal pathology.

The potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: a call for research.

INTRODUCTION: Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients. AREAS COVERED: This clinical opinion provides a summary of recent studies exploring risk factors for the development of malignant endometrial pathology including obesity, PCOS, and T2DM. Studies assessing efficacy of fertility-sparing treatment of malignant endometrial pathology are reviewed, and a potential new adjunct treatment approach to LNG-IUD is explored. EXPERT OPINION: There is an unmet-need for a personalized treatment approach in cases of first-line progestin treatment failure. Glucagon-like peptide 1 receptor agonists are a class of anti-diabetic agents, but may have a role in fertility-sparing treatment of obese patients with malignant endometrial pathology by reducing weight, decreasing inflammation, and decreasing insulin resistance; these changes may also improve chances of subsequent pregnancy. This hypothesis warrants further exploration.

Frontal penetrating arrow injury: A case report.

BACKGROUND: Penetrating arrow injuries of the head and neck are exceedingly rare in pediatric patients. This pathology has high morbidity and mortality because of the presence of vital organs, the airway, and large vessels. Therefore, the treatment and removal of an arrow is a challenge that requires multidisciplinary management. CASE SUMMARY: A 13-year-old boy was brought to the emergency room after an arrow injury to the frontal region. The arrowhead was lodged in the oropharynx. Imaging studies showed a lesion of the paranasal sinuses without compromising vital structures. The arrow was successfully removed by retrograde nasoendoscopy without complications, and the patient was discharged. CONCLUSION: Although rare, maxillofacial arrow injuries have high morbidity and mortality and require multidisciplinary management to preserve function and aesthetics.

What do we know about Q fever in Mexico?

In Mexico, Q fever is considered a rare disease among humans and animals. From March to May of 2008, three patients were referred, from the state of Hidalgo to a tertiary-care center in Mexico City, with an acute febrile illness that was diagnosed as Q fever. We decided to undertake a cross sectional pilot study to identify cases of acute disease in this particular region and to determine the seroprevalence of Coxiella burnetii among healthy individuals with known risk factors for infection with this bacteria. Q fever was defined according to the Centers for Disease Control and Prevention criteria. All subjects were interviewed for signs and symptoms of the disease, demographic and household characteristics and occupational exposure to cattle. Blood samples were taken from hospitalized and outpatients with symptoms suggestive of Q fever, as well as from asymptomatic individuals with direct and daily exposure to cattle (slaughterers, butchers, farmers, shepherds and veterinarians) in the five municipalities. We report the occurrence of 17 cases with positive antibodies against C. burnetii in a rural area of central Mexico; eight cases had clinical criteria of acute Q fever disease. Results from this pilot study underscore the need for active surveillance programs and comprehensive studies to further define the prevalence and risk factors associated with the disease in Mexico, to know more about its clinical presentation and to characterize bacterial factors involved in its pathogenesis.