Glucocorticoid receptor controls atopic dermatitis inflammation via functional interactions with P63 and autocrine signaling in epidermal keratinocytes.

Atopic dermatitis (AD), a prevalent chronic inflammatory disease with multifactorial etiology, features epidermal barrier defects and immune overactivation. Synthetic glucocorticoids (GCs) are widely prescribed for treating AD due to their anti-inflammatory actions; however, mechanisms are incompletely understood. Defective local GC signaling due to decreased production of endogenous ligand and/or GC receptor (GR) levels was reported in prevalent inflammatory skin disorders; whether this is a consequence or contributing factor to AD pathology is unclear. To identify the chromatin-bound cell-type-specific GR protein interactome in keratinocytes, we used rapid immunoprecipitation of endogenous proteins and mass spectrometry identifying 145 interactors that increased upon dexamethasone treatment. GR-interacting proteins were enriched in p53/p63 signaling, including epidermal transcription factors with critical roles in AD pathology. Previous analyses indicating mirrored AD-like phenotypes between P63 overexpression and GR loss in epidermis, and our data show an intricate relationship between these transcription factors in human keratinocytes, identifying TP63 as a direct GR target. Dexamethasone treatment counteracted transcriptional up-regulation of inflammatory markers by IL4/IL13, known to mimic AD, causing opposite shifts in GR and P63 genomic binding. Indeed, IL4/IL13 decreased GR and increased P63 levels in cultured keratinocytes and human epidermal equivalents (HEE), consistent with GR down-regulation and increased P63 expression in AD lesions vs normal skin. Moreover, GR knockdown (GRKD) resulted in constitutive increases in P63, phospho-P38 and S100A9, IL6, and IL33. Also, GRKD culture supernatants showed increased autocrine production of TH2-/TH1-/TH17-TH22-associated factors including IL4, CXCL10, CXCL11, and CXCL8. GRKD HEEs showed AD-like features including hyperplasia and abnormal differentiation, resembling phenotypes observed with GR antagonist or IL4/IL13 treatment. The simultaneous GR/P63 knockdown partially reversed constitutive up-regulation of inflammatory genes in GRKD. In summary, our data support a causative role for GR loss in AD pathogenesis via functional interactions with P63 and autocrine signaling in epidermal keratinocytes.

Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.

BACKGROUND: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. OBJECTIVES: This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. METHODS: We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. RESULTS: Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. CONCLUSIONS: DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.

Nasal Airway Evaluation.

The nose has several important functions including inspiration, humidification of air, and filtering of allergens. The nose also has a major role in facial harmony as the central focal point. Patients will present to the rhinoplasty surgeon in an effort to fix the inability to breathe through the nose or correct a perceived nasal deformity in the shape of the nose. Choosing the optimal techniques to effectively change the nose requires a thorough understanding of nasal anatomy and nasal mechanics. Ultimately, a complete nasal evaluation is essential in identifying what corresponds to a patient's complaints and how those issues can be addressed surgically or perhaps nonsurgically. When the nose is divided into subunits, and a systematic nasal analysis is performed, one can be confident that all components of the nasal skeleton have been assessed.

Individuals with psychosis present a reduced lung diffusion capacity and early spirometry alterations: Results from a cross-sectional study.

OBJECTIVE: Individuals with psychosis present a greater prevalence of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). These chronic respiratory diseases are preceded by early lung function alterations; such as preserved ratio impaired spirometry (PRISm) or normal spirometry but low diffusion capacity of the lung for carbon monoxide (DLCO). However, there is no previous evidence on these lung function alterations in psychosis. The aim of this study is to evaluate the risk of having spirometry and DLCO alterations in subjects with psychosis compared with a control group. METHODS: Cross-sectional study on a cohort of 170 individuals including 96 subjects with psychosis and 74 sex-age-and smoking habit matched healthy controls. All subjects were under 60 years-old, and without COPD or asthma. Respiratory function was evaluated through spirometry. Clinical characteristics and DLCO values were recorded. RESULTS: Patients with psychosis showed lower spirometry results, both in terms of absolute and percentage of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Absolute and percentage levels of diffusion were also lower in patients with psychosis. The percentage of individuals with DLCO<80% was higher among patients with psychosis (75% vs. 40%, p < 0.001). And the prevalence of PRISm was higher among patients with psychosis (10.4% vs. 1.4%, p < 0.001). Multivariate logistic regression analysis indicated that psychosis was an independent predictor of DLCO<80% (OR 5.67, CI95% 1.86-17.27). CONCLUSION: Patients with psychosis and females had early alterations in lung function. These results suggest that early screening for lung disease should be encouraged in psychosis.

Increased risk of early lung function alterations in people with psychosis: A cross-sectional case-control study.

BACKGROUND: Tobacco smoking has been described as the main cause of chronic obstructive pulmonary disease (COPD) and this habit is clearly more frequent among individuals with psychosis than in the general population, with rates reaching up to 60%. However, little attention has been focused on the association of COPD and psychosis. We aimed to explore the risk of presenting early lung function alterations in a group of individuals with psychosis. METHODS: Following an observational cross-sectional design we studied a cohort of individuals with established psychosis (N=128), and compared them with a sex, age, and smoking habit matched control group (N=79). We evaluated respiratory symptoms by means of mMRC, CAT and Dyspnea-12 scales. And lung function through spirometry tests. RESULTS: Individuals with psychosis presented more respiratory symptoms than controls. Similarly, we observed significant differences in the lung function tests between these two groups, where individuals with psychosis presented worse results in most of the spirometry mean values (FEV1 or forced expiratory volume in the first one second: 3.29L vs. 3.75L, p<0.001; forced vital capacity or FVC: 4.25L vs. 4.72L, p=0.002; and FEV1/FVC ratio: 0.78 vs. 0.80, p=0.052). Patients also presented worse values of lung diffusion, with lower diffusing capacity for carbon monoxide (DLCO) than controls (6.95 vs. 8.54mmol/min/kPa, p<0.001). CONCLUSIONS: The individuals with psychosis in our study presented greater respiratory symptoms and poorer lung function measured through spirometry. These signs have been described as early signs of COPD.

Cuidado espiritual y espiritualidad en la formación académica en enfermería: revisión de alcance / Cuidado espiritual e espiritualidade na formação acadêmica de enfermagem: revisão de escopo / Spiritual care and spirituality in academic nursing training: A scoping review

Objective: To map existing studies in scientific literature addressing spiritual care and spirituality in academic nursing training. Materials and method: This is a scoping review, whose article search was conducted in July 2023 in the databases Scopus, Medline/ PubMed, ScienceDirect, Google® Scholar, and through a manual search of entries in the list of references of selected papers. The following research question was formulated for this study: How are spiritual care and spirituality addressed in academic nursing training? After applying the inclusion and exclusion criteria, the final sample consisted of 45 papers. Results: The main findings highlight a deficit in academic training, the importance of teachers as facilitators of the teaching-learning process, the essential methodologies to address the issue of spirituality, and the specific competences required in spiritual care, such as communication, empathy, attitude towards the patient's spirituality, personal support, counseling, and the proper application of the nursing process in this type of care. Conclusions: This review made it possible to identify how spiritual care and spirituality are addressed in the academic training of nurses, where the insertion of educational resources for spiritual care and approaches based on competences were emphasized. Despite this, spiritual-related teaching is still deficient in academic formation. Studies recommend modifying the curriculum to strengthen competencies related to spirituality and spiritual care in the nursing academy

Objetivo: mapear los estudios existentes en la literatura científica relacionados con el cuidado espiritual y la espiritualidad en la formación académica en enfermería. Materiales y método: revisión de alcance cuya búsqueda se realizó en julio de 2023 en las bases de datos Scopus, Medline/PubMed, ScienceDirect, Google® Scholar y por medio de una búsqueda manual en las listas de referencia de documentos seleccionados. Se delimitó la siguiente pregunta de investigación: ¿cómo se aborda el cuidado espiritual y la espiritualidad en la formación académica de enfermería? Tras la aplicación de los criterios de inclusión y exclusión, la muestra final estuvo conformada por 45 estudios. Resultados: los principales resultados señalan un déficit en la formación académica, la importancia de los docentes como facilitadores del proceso de enseñanza-aprendizaje, las metodologías esenciales para abordar el asunto de la espiritualidad y las competencias específicas en el cuidado espiritual, entre las que se cuentan la comunicación, la empatía, la actitud frente a la espiritualidad del paciente, el apoyo personal, el asesoramiento y la correcta aplicación del proceso de enfermería en este tipo de cuidado. Conclusiones: esta revisión permitió identificar la manera en que el cuidado espiritual y la espiritualidad son abordados en la formación académica de los profesionales en enfermería, donde destaca la adopción de recursos educativos para el cuidado espiritual y el enfoque basado en competencias. No obstante, este tipo de enseñanza aún es deficiente en la formación académica en enfermería. Por ello, algunas investigaciones recomiendan modificar el plan de estudios de los programas en enfermería con el fin de fortalecer las competencias relacionadas con la espiritualidad y el cuidado espiritual.

Objetivo: mapear os estudos existentes na literatura científica relacionados ao cuidado espiritual e à espiritualidade na formação acadêmica de enfermagem. Materiais e método: trata-se de uma revisão de escopo em que a busca foi realizada em julho de 2023 nas seguintes fontes de dados: Scopus, Medline/PubMed, ScienceDirect, Google® Scholar e busca manual de documentos em listas de referências dos artigos selecionados. Delimitou-se a seguinte questão de pesquisa: "como o cuidado espiritual e a espiritualidade são abordados na formação acadêmica de enfermagem?". Após a aplicação dos critérios de inclusão e exclusão, a amostra final foi composta de 45 estudos. Resultados: os principais resultados encontrados foram o déficit na formação acadêmica; a importância do professor como facilitador do processo ensino-aprendizagem; as metodologias essenciais para abordar o tema, bem como as competências específicas no cuidado espiritual, como a comunicação, a empatia, a atitude perante a espiritualidade do paciente, o apoio pessoal, o aconselhamento e a aplicação adequada do processo de enfermagem nesse tipo de cuidado. Conclusões: os resultados desta revisão permitem identificar como o cuidado espiritual e a espiritualidade são abordados na formação acadêmica de enfermagem, em que se destaca a inserção de recursos educacionais para o cuidado espiritual e abordagens baseadas em competências. No entanto, esse ensino ainda é deficiente na formação acadêmica. Por isso, alguns estudos recomendam modificar o currículo acadêmico de enfermagem a fim de fortalecer competências relacionadas à espiritualidade e ao cuidado espiritual.

Cancer and Myotonic Dystrophy.

Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Dominantly inherited CTG and CCTG repeat expansions in DMPK and CNBP genes cause DM type 1 (DM1) and 2 (DM2), respectively. These genetic defects lead to the abnormal splicing of different mRNA transcripts, which are thought to be responsible for the multiorgan involvement of these diseases. In ours and others' experience, cancer frequency in patients with DM appears to be higher than in the general population or non-DM muscular dystrophy cohorts. There are no specific guidelines regarding malignancy screening in these patients, and the general consensus is that they should undergo the same cancer screening as the general population. Here, we review the main studies that investigated cancer risk (and cancer type) in DM cohorts and those that researched potential molecular mechanisms accounting for DM carcinogenesis. We propose some evaluations to be considered as malignancy screening in patients with DM, and we discuss DM susceptibility to general anesthesia and sedatives, which are often needed for the management of cancer. This review underscores the importance of monitoring the adherence of patients with DM to malignancy screenings and the need to design studies that determine whether they would benefit from a more intensified cancer screening than the general population.

Analysis of Cephalometric Points in Male and Female Mandibles: An Application to Gender-Affirming Facial Surgery.

Gender-affirming facial surgery is a common intervention for transgender patients because of its ability to decrease the frequency of misgendering. Many anatomic targets can be addressed, but the mandible is the primary aspect of the lower third of the face that is manipulated during these procedures. This study's objective is to quantify the differences in cephalometric measurements between male and female mandibles on maxillofacial imaging, with the goal of identifying surgical targets for gender affirmation. A nonrandomized, retrospective, single-institution, case-control study of 387 patients who underwent maxillofacial computed tomography during 2017-2020 was performed. After excluding patients with imaging that did not capture the entire head or had deforming pathology of the face, a total of 113 patients were included. Cephalometric measurements that corresponded to areas reported by patients as sources of dysphoria were selected for analysis. These included mandibular width, ramus height, lateral flare, masseter volume, total face height, and the values of the mandibular angles in degrees. The relationship of masseter volume to the other measurements was also characterized. Significantly greater masseter volume was seen in males compared with females, and a greater masseter thickness was also seen in males. The mandibular angle was more acute in males than females. Aggregate analysis of muscle volume and thickness was positively correlated with ramus height, lateral flare, and mandibular width. Ramus, mental, and total facial height correlated directly with patient height in males but not in females. These data provide a normative baseline for planning lower facial gender-affirming surgery.

Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study.

INTRODUCTION/AIMS: Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem involvement. Cancer risk and cancer-related deaths are increased in DM patients relative to the general population. We aimed at determining the frequency and type of cancers in both DM1 and DM2 vs a non-DM muscular dystrophy cohort. METHODS: A retrospective, cross-sectional study was carried out on patients with genetically confirmed DM1, DM2, facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) at our institutions from 2000 to 2020. RESULTS: One hundred eighty-five DM1, 67 DM2, 187 FSHD, and 109 OPMD patients were included. Relative to non-DM, DM patients had an increased cancer risk that was independent of age and sex. Specifically, an increased risk of sex-related (ovarian) and non-sex-related (non-melanoma skin, urological, and hematological) cancers was observed in DM1 and DM2, respectively. The length of CTG repeat expansion was not associated with cancer occurrence in the DM1 group. DISCUSSION: In addition to current consensus-based care recommendations, our findings prompt consideration of screening for skin, urological, and hematological cancers in DM2 patients, and screening of ovarian malignancies in DM1 female patients.

Agenesis of Pectoralis Major Muscle in Late-Onset GFPT1-Related Congenital Myasthenic Syndrome: A Case Report.

Objectives: The objective of this study was to expand the phenotypic spectrum of glutamine-fructose-6-phosphate transaminase 1 (GFPT1)-related congenital myasthenia syndrome (CMS). Methods: A 61-year-old man with agenesis of the left pectoralis major muscle presented with progressive muscle weakness for a decade that transiently improved after exertion. Results: His examination revealed proximal and distal muscle weakness in upper extremities and proximal muscle weakness in lower extremities. Muscle enzymes were elevated. An electromyogram revealed a myopathic pattern; however, a muscle biopsy of deltoid muscle and genetic testing for limb-girdle muscular dystrophies were nondiagnostic. A 3-Hz repetitive nerve stimulation of the spinal accessory nerve recording from trapezius muscle demonstrated a >20% drop in amplitude of the 5th compound motor action potential relative to 1st at both baseline and after 45-second exercise. Acetylcholine receptor binding, lipoprotein-related protein 4, muscle-specific kinase, and voltage-gated calcium channel P/Q antibodies were negative. Genetic testing targeting CMS revealed 2 likely pathogenic variants within GFPT1: novel c.7+2T>G (intron 1) that was predicted to result in a null allele and known c*22 C>A (exon 19) associated with reduced GFPT1 expression. His muscle strength dramatically improved after pyridostigmine initiation. Discussion: In addition to other reported neurodevelopmental abnormalities, pectoralis major muscle agenesis (or Poland syndrome) may be a clinical manifestation of GFPT1-related CMS.

Recurrent chylopericardium in a patient with history of left leg sarcoma.

Chylopericardium is a rare condition that is characterized by the presence of chyle in the pericardial space due to idiopathic (primary) or secondary causes. We present a 43-year-old female with hypothyroidism and left lower extremity sarcoma which were treated with resection and adjuvant chemoradiotherapy that was found with moderate pericardial effusion in surveillance tests. The patient was initially treated with tube thoracostomy and conservative management but presented with recurrence. Eventually, she was treated with left thoracotomy, ligation of the thoracic duct and pericardiectomy.

Glucocorticoid Resistance: Interference between the Glucocorticoid Receptor and the MAPK Signalling Pathways.

Endogenous glucocorticoids (GCs) are steroid hormones that signal in virtually all cell types to modulate tissue homeostasis throughout life. Also, synthetic GC derivatives (pharmacological GCs) constitute the first-line treatment in many chronic inflammatory conditions with unquestionable therapeutic benefits despite the associated adverse effects. GC actions are principally mediated through the GC receptor (GR), a ligand-dependent transcription factor. Despite the ubiquitous expression of GR, imbalances in GC signalling affect tissues differently, and with variable degrees of severity through mechanisms that are not completely deciphered. Congenital or acquired GC hypersensitivity or resistance syndromes can impact responsiveness to endogenous or pharmacological GCs, causing disease or inadequate therapeutic outcomes, respectively. Acquired GC resistance is defined as loss of efficacy or desensitization over time, and arises as a consequence of chronic inflammation, affecting around 30% of GC-treated patients. It represents an important limitation in the management of chronic inflammatory diseases and cancer, and can be due to impairment of multiple mechanisms along the GC signalling pathway. Among them, activation of the mitogen-activated protein kinases (MAPKs) and/or alterations in expression of their regulators, the dual-specific phosphatases (DUSPs), have been identified as common mechanisms of GC resistance. While many of the anti-inflammatory actions of GCs rely on GR-mediated inhibition of MAPKs and/or induction of DUSPs, the GC anti-inflammatory capacity is decreased or lost in conditions of excessive MAPK activation, contributing to disease susceptibility in tissue- and disease- specific manners. Here, we discuss potential strategies to modulate GC responsiveness, with the dual goal of overcoming GC resistance and minimizing the onset and severity of unwanted adverse effects while maintaining therapeutic potential.

[Impact of the duration of labor in the neonatal state measured by arterial blood gas at birth.] / Repercusión de la duración del parto en el estado neonatal medido a través de la gasometría arterial al nacimiento.

OBJECTIVE: The duration of labor has become a central axis of its clinical management, most of the studies that analyze its relationship with the neonatal state focus on indirect tests such as the Apgar test or admissions to the NICU. The aim of the study was to analyze the repercussions of the duration of labor on the condition of the neonates without added risk factors through a direct analysis test such as the umbilical artery blood gas test at birth. METHODS: An observational, analytical, retrospective, and prevalence study was conducted on a sample of 286 infants no previous risk factors obtained from the computerized clinical registry. For a confidence level of p<0.05, parametric tests such as Pearson's correlation coefficient and Chi-square were applied. RESULTS: Showed a significant negative correlation between umbilical artery pH values and delivery times (Dilation: R=-0.207; p=0.002 - Expulsive: R=-0.150; p=0.027 - Total delivery: R=-0.181; p=0.006). Presenting deliveries with times above the mean greater possibilities of fetal acidosis and hypercapnia in dilation (pH: OR=3.10; IC 1.64-5.51 - pCO2: OR=2.19; IC 1.23-3.89), the expulsive (pH: OR=2.24; IC 1.21-4.16 - pCO2: OR=1.77; IC 0.98-3.22) and the total duration (pH: OR=3.36, IC 1.84-6.13- pCO2: OR=2.53; IC 1.44-4.46). CONCLUSIONS: A significant association is was found between the prolongation of labor times and acidosis and neonatal hypercapnia.

OBJETIVO: La duración del parto se ha convertido en un eje central de su manejo clínico, la mayoría de estudios que analizan su relación con el estado neonatal se centra en pruebas indirectas como el test de Apgar o los ingresos en UCIN. El objetivo del estudio fue analizar las repercusiones de la duración del parto en el estado de los neonatos sin factores de riesgo añadidos a través de una prueba de análisis directo como es la gasometría de arteria umbilical al nacimiento. METODOS: Se diseñó un estudio observacional analítico, retrospectivo y de prevalencia realizado sobre una muestra de 286 neonatos sin factores de riesgo previos obtenida del registro clínico informático. Para un nivel de confianza de p<0,05 se aplicaron pruebas paramétricas como el coeficiente de correlación de Pearson y la Chi cuadrado. RESULTADOS: Mostraron una correlación significativa negativa entre los valores de pH de arteria umbilical y los tiempos del parto (Dilatación: R=-0,207; p=0,002 ­ Expulsivo: R=-0,150; p=0,027 - Totales de parto: R=-0,181; p=0,006). Presentando los partos con tiempos superiores a la media mayores posibilidades de acidosis fetal e hipercapnia en la dilatación (pH: OR=3,10; IC 1,64-5,51 - pCO2: OR=2,19; IC 1,23-3,89), el expulsivo (pH: OR=2,24; IC 1,21-4,16 - pCO2: OR=1,77; IC 0,98-3,22) y la duración total (pH: OR=3,36, IC 1,84-6,13- pCO2: OR=2,53; IC 1,44-4,46). CONCLUSIONES: Se constató una asociación significativa entre la prolongación de los tiempos del parto y la acidosis e hipercapnia neonatal.

Investigating Long-Term Brow Stabilization by Endotine-Assisted Endoscopic Brow Lift with Concomitant Upper Lid Blepharoplasty.

OBJECTIVE: To determine whether Endotine-assisted endoscopic brow lift with concomitant upper lid blepharoplasty provides long-term brow elevation. METHODS: Pre- and post-operative photographs from 35 patients who underwent endoscopic brow lift using Endotine Forehead 3 mm implants with concomitant upper lid blepharoplasty were measured to determine changes in brow height with surgery and up to 55 months post-operatively. Photographs of 20 control subjects who did not undergo periorbital surgery and 11 control subjects who underwent upper blepharoplasty without brow lifting were also measured to provide a basis for comparison. Emotrics software was used to perform automated brow height measurements in order to determine elevation and longevity achieved with endoscopic brow lifting in conjunction with upper lid blepharoplasty. RESULTS: There was a statistically significant increase in brow height post-operatively, averaging 1.6 mm (P < .0001, 95% confidence interval 0.95-2.18 mm). Fifty-four percent of patients had follow-up beyond 6 months post-operatively and 40% had follow-up beyond 1 year. Elevation remained stable over time with no statistically significant change across all serial post-operative visits. There was no statistically significant difference in brow elevation based on gender or age, or between right and left sides. CONCLUSION: Endotine-assisted endoscopic brow lift in conjunction with upper lid blepharoplasty provides modest brow elevation and long-term brow fixation as demonstrated by stable post-operative brow height measurements for up to 55 months.

First Bite Syndrome Following Rhytidectomy: A Case Report.

BACKGROUND: First bite syndrome (FBS) is a known complication of parotid gland resection, parapharyngeal space dissection, and cervical sympathetic chain injury. It can be described as severe cramping or spasms in the parotid region triggered by the first bite of a meal, with the pain lessening during each subsequent bite. Although dissection for a rhytidectomy is in the vicinity of the parotid parenchyma, face-lift is not typically characterized as a procedure that can lead to FBS. CASE DESCRIPTION: A 53-year-old female underwent a deep plane face-lift to address her goals of improving jowls, nasolabial folds, and cervicomental angle. Intraoperatively, the dissection proceeded without any complications. Initially, her postoperative course was uneventful; 3 weeks after surgery, she noticed pain at the start of mastication that would improve throughout the course of a meal. She elected to proceed with observation. At 6 months after surgery, she began to experience improvement in her symptoms, and shortly thereafter had complete resolution. DISCUSSION: First bite syndrome is a complication associated with deep lobe parotid resection, first described in 1998. The innervation of the parotid gland is complex and includes contributions from the auriculotemporal nerve, the great auricular nerve, and the cervical sympathetic chain. During rhytidectomy, dissection occurs along the parotidomasseteric fascia in order to elevate a flap of the superficial musculoaponeurotic system. Inadvertent injury to the parotid parenchyma can lead to damage to the postganglionic sympathetic fibers innervating the myoepithelial cells. Ultimately, expectant management is the mainstay of treatment and symptoms typically resolve within 6 months to 1 year. CONCLUSION: First bite syndrome is a complication that can be seen with a variety of facial surgeries. In the case of rhytidectomy, FBS should be considered a potential risk, as dissection into the parenchyma of the parotid gland can result in postoperative autonomic dysfunction.

Non-vascularized Fibular Cortex Grafts with Osteocutaneous Free Fibula Transfer: A Novel Technique in Midface Reconstruction.

OBJECTIVES: To present a method to reconstruct the midface using the fibula as both a microvascular free flap and as a free cortex graft. METHODS: 22-year-old male presented with bilateral maxillary odonotogenic myxoma. Bilateral total maxillectomy defects were reconstructed using an osteocutaneous fibula free flap. The nasomaxillary buttresses were augmented using free cortex grafts to provide additional soft tissue projection and lateral nasal support. RESULTS: The patient received dental implants at 10 months postoperatively and resumed a normal diet. His midface height, nasal and maxillary projection were adequate. At 36 months post-treatment he has no evidence of disease recurrence or resorption of the free bone grafts. CONCLUSION: The fibula free flap can be used to provide additional support to a patient's reconstruction by means of free cortex grafts. The patient has had successful restoration of pyriform aperture, nasal projection, mastication, and dental restoration using a single donor site.

Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development.

Nuclear receptors (NRs) are a superfamily of ligand-activated transcription factors that act as biological sensors and use a combination of mechanisms to modulate positively and negatively gene expression in a spatial and temporal manner. The highly orchestrated biological actions of several NRs influence the proliferation, differentiation, and apoptosis of many different cell types. Synthetic ligands for several NRs have been the focus of extensive drug discovery efforts for cancer intervention. This review summarizes the roles in tumour growth and metastasis of several relevant NR family members, namely androgen receptor (AR), estrogen receptor (ER), glucocorticoid receptor (GR), thyroid hormone receptor (TR), retinoic acid receptors (RARs), retinoid X receptors (RXRs), peroxisome proliferator-activated receptors (PPARs), and liver X receptors (LXRs). These studies are key to develop improved therapeutic agents based on novel modes of action with reduced side effects and overcoming resistance.

Tecnologias utilizadas para apoio ao processo de enfermagem: revisão de escopo / Tecnologías utilizadas para apoyar el proceso de enfermería: revisión de alcance / Technologies used to support the nursing process: scoping review

Resumo Objetivo: Identificar e mapear as tecnologias utilizadas para apoio ao processo de enfermagem. Métodos: Trata-se de uma scoping review, realizada em Novembro e Dezembro de 2019, em 15 bases de dados nacionais e internacionais. Os dados para análise foram extraídos a partir de indicadores para uma planilha do Microsoft Excell 2010®. Resultados: A amostra do estudo foi composta por 14 estudos, publicados principalmente no ano de 2017 e oriundos do Brasil. As tecnologias desenvolvidas são principalmente software, voltados para o ensino e como público alvo profissionais que já atuam na assistência à saúde. Conclusão: A pesquisa aponta que a inserção de tecnologias para apoio ao processo de enfermagem é crescente e está voltado principalmente para o ensino, com a finalidade de fortalecer a formação dos enfermeiros.

Resumen Objetivo: Identificar y mapear las tecnologías utilizadas para apoyar el proceso de enfermería. Métodos: Se trata de una scoping review, realizada en noviembre y diciembre de 2019, en 15 bases de datos nacionales e internacionales. Los datos para el análisis fueron extraídos a partir de indicadores a una planilla de Microsoft Excel 2010®. Resultados: La muestra estuvo compuesta por 14 estudios, publicados principalmente en 2017 y oriundos de Brasil. La principal tecnología desarrollada es software, utilizados para la enseñanza, cuyo público destinatario son profesionales que ya actúan en la atención a la salud. Conclusión: El estudio indica que la incorporación de tecnologías para apoyar el proceso de enfermería está creciendo y se orienta principalmente a la enseñanza, con la finalidad de fortalecer la formación de los enfermeros.

Abstract Objective: To identify and map the technologies used to support the nursing process. Methods: This is a scoping review carried out in November and December 2019, in 15 national and international databases. Data for analysis were extracted from indicators for a spreadsheet of Microsoft Excell 2010®. Results: The study sample consisted of 14 studies, published mainly in 2017 and from Brazil. The technologies developed are mainly software, aimed at teaching and as target audience professionals who already work in health care. Conclusion: The research points out that the insertion of technologies to support the nursing process is growing and is mainly focused on teaching, with the purpose of strengthening nursing training.

Glucocorticoids and Glucocorticoid-Induced-Leucine-Zipper (GILZ) in Psoriasis.

Psoriasis is a prevalent chronic inflammatory human disease initiated by impaired function of immune cells and epidermal keratinocytes, resulting in increased cytokine production and hyperproliferation, leading to skin lesions. Overproduction of Th1- and Th17-cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-23, IL-17, and IL-22, is a major driver of the disease. Glucocorticoids (GCs) represent the mainstay protocol for treating psoriasis as they modulate epidermal differentiation and are potent anti-inflammatory compounds. The development of safer GC-based therapies is a high priority due to potentially severe adverse effects associated with prolonged GC use. Specific efforts have focused on downstream anti-inflammatory effectors of GC-signaling such as GC-Induced-Leucine-Zipper (GILZ), which suppresses Th17 responses and antagonizes multiple pro-inflammatory signaling pathways involved in psoriasis, including AP-1, NF-κB, STAT3, and ROR-γt. Here we review evidence regarding defective GC signaling, GC receptor (GR) function, and GILZ in psoriasis. We discuss seemingly contradicting data on the loss- and gain-of-function of GILZ in the imiquimod-induced mouse model of psoriasis. We also present potential therapeutic strategies aimed to restore GC-related pathways.

Non-canonical dimerization of the androgen receptor and other nuclear receptors: implications for human disease.

Nuclear receptors are transcription factors that play critical roles in development, homeostasis and metabolism in all multicellular organisms. An important family of nuclear receptors comprises those members that respond to steroid hormones, and which is subdivided in turn into estrogen receptor (ER) isoforms α and ß (NR3A1 and A2, respectively), and a second subfamily of so-called oxosteroid receptors. The latter includes the androgen receptor (AR/NR3C4), the glucocorticoid receptor (GR/NR3C1), the mineralocorticoid receptor (MR/NR3C2) and the progesterone receptor (PR/NR3C3). Here we review recent advances in our understanding of the structure-and-function relationship of steroid nuclear receptors and discuss their implications for the etiology of human diseases. We focus in particular on the role played by AR dysregulation in both prostate cancer (PCa) and androgen insensitivity syndromes (AIS), but also discuss conditions linked to mutations of the GR gene as well as those in a non-steroidal receptor, the thyroid hormone receptor (TR). Finally, we explore how these recent results might be exploited for the development of novel and selective therapeutic strategies.