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PURPOSE: To evaluate the incidence and risk factors for inflammatory conditions among patients with primary acquired nasolacrimal duct obstruction (PANDO). METHODS: A retrospective case-control study was conducted among patients of Clalit Health Services (CHS) in Israel from 2001 to 2022. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Differences in demographic characteristics, ocular surface, eyelid, upper airway, and systemic diseases were assessed between the groups, and odds ratios (OR) were calculated. RESULTS: A total of 60,726 patients diagnosed with PANDO were included. The average age of PANDO patients was 63 ± 18 years, 63% were female. Significant associations were found between PANDO and various ocular surface and eyelid conditions, including chronic conjunctivitis (OR 2.96, 95% CI [2.73-3.20]), vernal keratoconjunctivitis (OR 2.89, 95% CI [2.45-3.29]), and blepharitis (OR 2.75, 95% CI [2.68-2.83]). There was a significant association with various upper airway conditions, including rhinitis (OR 1.62, 95% CI [1.58-1.66]), chronic sinusitis (OR 1.71, 95% CI [1.62-1.80]), and deviated nasal septum (OR 1.76, 95% CI [1.69-1.84]). Association was also observed with systemic conditions, including asthma (OR 1.34, 95% CI [1.27-1.41]) and atopic dermatitis (OR 1.36, 95% CI [1.32-1.41]). CONCLUSION: Ocular surface, eyelid, upper airway, and systemic inflammatory-related diseases were found to be associated with PANDO, supporting the theory that inflammation has a prominent role in the pathophysiology of PANDO.
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Obstrucción del Conducto Lagrimal , Conducto Nasolagrimal , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Blefaritis/epidemiología , Blefaritis/diagnóstico , Estudios de Casos y Controles , Conjuntivitis/epidemiología , Conjuntivitis/diagnóstico , Incidencia , Inflamación/epidemiología , Israel/epidemiología , Obstrucción del Conducto Lagrimal/epidemiología , Obstrucción del Conducto Lagrimal/diagnóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
While functional endoscopic evaluation of swallowing (FEES) is the most useful diagnostic test for the evaluation of dysphagia, it cannot evaluate the esophageal phase of swallowing. To evaluate if a modification for the FEES exam by swallowing an empty capsule and screening of the upper esophagus could be used for early detection of esophageal dysphagia. A prospective, single-center, pilot study. At the end of a standard FEES exam, the patients were asked to swallow an empty capsule. Fifteen seconds later, the endoscope was inserted into the upper esophagus. A pathological capsule test was defined when the capsule was seen in the esophagus. In such cases, the patient was advised to undergo a gastroscopy, MBS, or esophageal manometry, which were compared to the results of the capsule test. The capsule test was utilized in 109 patients. A pathological capsule test was found in 55 patients (57.8%). In 48 patients (87.3%), an isolated or combined esophageal dysphagia was seen. The accuracy value of the capsule test compared to gastroenterology tests was 83.3%, sensitivity 88.46%, specificity 75%, PPV 85%, and NPV 80%. A modification of the standard FEES exam by including an empty capsule swallow test with an upper esophagus examination may provide a useful screening tool for esophageal dysphagia.
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INTRODUCTION: The definition of thyroid goiter remains ambiguous, yet size may impact both malignancy rate and surgical complications' rate. METHODS: All patients with thyroid goiter who underwent thyroidectomy between 1/2015-1/2023 were included. Goiter was defined as lobe ≥4 cm. For analysis purpose, goiters measuring 4-8 cm and ≥8 cm were defined as large and extremely large goiters, respectively. For malignancy definition, tumor<1 cm in their largest diameter were excluded from study. Collected data included demographics, cytology, histology and postoperative complication. RESULTS: 144 goiters from 111 patients were included. The most common indication for surgery was symptoms (55 %). Compared with large goiter, extremely large goiters demonstrated a trend for tracheal narrowing on pre-operative CT findings (23 % vs. 45 %, p = 0.07 respectively). Overall differentiated thyroid carcinoma (DTC) rate was 17 % (25/144) without statistical difference between groups (p = 0.89). Within goiters with pre-operative benign cytology, the DTC rate was 17 % (7/43). Follicular variant of papillary thyroid cancer was the most common type for both groups. Nodular hyperplasia was significantly associated with extremely large goiters (53 % vs. 73 %, p = 0.03). No significant difference was found in transient hypocalcemia (48 % [15/31] vs. 41 % [5/12], p = 0.6) and other complications' rate between extremely large goiters and the control group. CONCLUSION: When discussing management options for patients with goiters, the size of the goiter should not regarded as a higher risk for complications or malignancy, yet the relatively high malignancy rate found should be taken under consideration for resection.
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Bocio , Complicaciones Posoperatorias , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Femenino , Masculino , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Persona de Mediana Edad , Estudios de Casos y Controles , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Bocio/cirugía , Bocio/patología , Adulto , Anciano , Tomografía Computarizada por Rayos X , Factores de RiesgoRESUMEN
OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.
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Diabetes Gestacional , Microbiota , Embarazo , Femenino , Humanos , Diabetes Gestacional/diagnóstico , Tercer Trimestre del Embarazo , Inflamación , CitocinasRESUMEN
To examine the impact of pneumococcal conjugate vaccines (PCV) on the occurrence of recurrent acute otitis media (rAOM) among infants diagnosed with an early acute otitis media (AOM) episode. Retrospective cohort study of pediatric patients with a first episode of AOM at an age < 2 months. Data included clinical, demographic, and microbiological findings at the first AOM episode. In addition, a 5-year follow-up after the patient's first episode was completed from the medical records. This information included documentation of rAOM episodes and complications of AOM (hearing loss, speech disturbance, mastoiditis, and tympanic membrane perforation) and of ear-related surgical procedures (ventilation tube placement, adenoidectomies, and mastoid surgery). Two groups were studied: patients diagnosed between 2005 and 2009 (representing the unvaccinated group, group 1) and those diagnosed in 2010-2014 (the vaccinated group, group 2). A total of 170 infants were diagnosed with a first AOM episode at an age < 2 months; 81 of them belonged to group 1 and 89 to group 2. Streptococcus pneumoniae was isolated in the middle-ear fluid in the first AOM episode in 48.1% of the patients in group 1 and in 30.3% in group 2 (P = 0.0316). 49/81 (60.5%) infants in group 1 were diagnosed with rAOM versus 39/80 (43.8%) in group 2 (P = 0.0298). No statistical differences were found between the groups with respect to long-term complications or need for surgery later in life. Conclusion: Our study showed a significant decrease in the occurrence of rAOM in infants diagnosed with AOM during the first 2 months of life and timely immunized with PCVs following this initial AOM episode. What is Known: ⢠30% of children experience recurrent AOM (rAOM) at the first year of life. The earlier the age of the first AOM, the greater the risk for future complications. ⢠After the introduction of PCVs, the overall pneumococcal AOM incidence declined. We investigated the future effect of PCVs on rAOM occurrence, when administered after the first AOM episode. What is New: ⢠A retrospective cohort of 170 infants with a first AOM episode at an age <2 months and followed for 5 years, showed a significant decrease (28.0%) of rAOM in immunized infants following the initial AOM episode. ⢠Our findings supplement previous data suggesting that the widespread PCVs use prevents rAOM by preventing early AOM and emphasize the importance of timely administration of the PCVs.
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Otitis Media , Infecciones Neumocócicas , Niño , Lactante , Humanos , Vacunas Neumococicas , Estudios Retrospectivos , Streptococcus pneumoniae , Vacunas Conjugadas , Enfermedad Aguda , Otitis Media/prevención & control , Otitis Media/epidemiología , Enfermedad Crónica , Infecciones Neumocócicas/diagnóstico , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & controlRESUMEN
INTRODUCTION: The universal newborn hearing screening (UNHS) allows for early detection of hearing impairment (HI). The goal of this current study was to evaluate the impact of cultural background involving consanguineous marriage on newborn HI diagnosed using UNHS, and compliance with hearing rehabilitation. MATERIALS AND METHODS: This is a retrospective cohort study that included all children born at a single tertiary medical center between 2011 and 2017 who did not pass the UNHS (oto-acoustic emission and auditory brainstem response), and were diagnosed with HI. The study group included children from consanguineous marriage cultural background which were compared to a control group-all other children. Data were retrieved from the computerized medical charts and included epidemiological, audiological, and pregnancy/delivery-related data, and known risk factors for congenital HI. RESULTS: A total of 238 (196 study and 42 control) neonates were diagnosed with HI. Family history of HI was significantly more prevalent in the study group in mild-severe and profound HI subgroups (p = 0.03 and 0.01, respectively). Study group demonstrated lower rates of cochlear implantation (CI) compliance (p = 0.079), performed at a significantly older age (23 months (IQR 17-36.5) vs. 16 (IQR 12-26) months, p = 0.021). When recommended, bilateral CI compliance was significantly lower in the study group (94.1 vs.48.9%, p < 0.001). CONCLUSION: UNHS allows for early HI detection among minority populations at higher risk for CI, yet compliance rates remain lower compared with control. Familiarity of families with the importance of early detection and HI risk may result in higher compliance rates for cochlear implantation. Health providers should aim to improve education and communication with this unique group of patients and consider health promotion programs.
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BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 µIU/mL vs placebo, 1.64 ± 4.7 µIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05). CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.
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Trasplante de Microbiota Fecal , Obesidad/dietoterapia , Aumento de Peso , Adulto , Animales , Dieta Mediterránea , Modelos Animales de Enfermedad , Ejercicio Físico , Femenino , Humanos , Israel , Estilo de Vida , Masculino , Ratones , Persona de Mediana Edad , Circunferencia de la Cintura , Pérdida de PesoRESUMEN
PURPOSE: To determine the immediate post-operative course and outcome of pediatric patients with complicated acute mastoiditis (CAM) following surgical treatment. METHODS: A retrospective chart review of children diagnosed with CAM who underwent mastoid surgery during 2012-2019 in a tertiary care university hospital. 33 patients, divided into 2 groups: 17 patients with sub-periosteal abscess (SPA) alone-single complication group (SCG) and 16 patients with SPA and additional complications: sigmoid sinus thrombosis (SST), peri-sinus fluid/abscess, epidural/subdural abscess, and acute meningitis-multiple complications group (MCG). RESULTS: 33 patients belong to the SCG 17(51%) and 16(49%) belonged to the MCG, respectively. 6/17(35.3%) SCG patients experienced POF vs. 12/16(75%) in the MCG (P = 0.012). At post-operative day 2 (POD2), 10/13(77%) febrile patients belonged to MCG and 3/13(23%) to SCG (P = 0.013). POF was recorded until POD6 in both groups. Seven patients, all from MCG with POF, underwent second imaging with no new findings; a total of 18 positive cultures were reported. Fusobacterium necrophorum counted for 8/18(44.5%) of all positive cultures, 7/9(77.8%) in the MCG vs. 1/9(11.1%) in the SCG, P = 0.004. Streptococcus pneumoniae was reported only in SCG (5/9, 55.5%, vs. 0/9, P = 0.008). CONCLUSION: Post-mastoidectomy fever due to CAM is not unusual and seems to be a benign condition for the first 5-6 days, following surgery. MCG patients are more prone to develop POF. F. necrophorum is more likely to be associated with MCG, and S. pneumoniae is common in SCG patients.
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Absceso Epidural , Mastoiditis , Enfermedad Aguda , Antibacterianos/uso terapéutico , Niño , Absceso Epidural/etiología , Absceso Epidural/cirugía , Humanos , Lactante , Mastoidectomía/efectos adversos , Mastoiditis/complicaciones , Mastoiditis/diagnóstico , Mastoiditis/cirugía , Estudios Retrospectivos , Streptococcus pneumoniaeRESUMEN
BACKGROUND: Adjuvant chemotherapy induces weight gain, glucose intolerance, and hypertension in about a third of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers. METHODS: Patients were recruited before starting adjuvant therapy. Weight and height were measured before treatment and 4-6 weeks after treatment completion. Weight gain was defined as an increase of 3% or more in body weight. A stool sample was collected before treatment, and 16S rRNA gene sequencing was performed. Data regarding oncological therapy, menopausal status, and antibiotic use was prospectively collected. Patients were excluded if they were treated by antibiotics during the study. Fecal transplant experiments from patients were conducted using Swiss Webster germ-free mice. RESULTS: Thirty-three patients were recruited; of them, 9 gained 3.5-10.6% of baseline weight. The pretreatment microbiome of women who gained weight following treatment was significantly different in diversity and taxonomy from that of control women. Fecal microbiota transplantation from pretreatment samples of patients that gained weight induced metabolic changes in germ-free mice compared to mice transplanted with pretreatment fecal samples from the control women. CONCLUSION: The microbiome composition is predictive of weight gain following adjuvant chemotherapy and induces adverse metabolic changes in germ-free mice, suggesting it contributes to adverse metabolic changes seen in patients. Confirmation of these results in a larger patient cohort is warranted.
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Neoplasias de la Mama/complicaciones , Quimioterapia Adyuvante/efectos adversos , Microbioma Gastrointestinal/genética , Neoplasias de los Genitales Femeninos/complicaciones , Aumento de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Animales , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Humanos , Ratones , Persona de Mediana Edad , Adulto JovenRESUMEN
Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3+ regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.
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Conducta Animal/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Inmunidad/efectos de los fármacos , Penicilinas/administración & dosificación , Penicilinas/farmacología , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Caracteres Sexuales , Conducta Social , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Femenino , Masculino , Ratones , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/microbiologíaRESUMEN
OBJECTIVE: Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. DESIGN: We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1ß correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. RESULTS: A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology. Increased colonic tumor necrosis factor (TNF)α, IL-1ß and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial-epithelial co-cultures, postradiation microbiota enhanced IL-1ß and TNFα expression compared with naïve microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury. CONCLUSIONS: The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1ß. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.
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Colitis/etiología , Citocinas/biosíntesis , Disbiosis/etiología , Microbioma Gastrointestinal/efectos de la radiación , Traumatismos por Radiación/microbiología , Animales , Técnicas de Cocultivo , Colitis/inmunología , Colitis/microbiología , Susceptibilidad a Enfermedades , Disbiosis/inmunología , Disbiosis/microbiología , Trasplante de Microbiota Fecal , Heces/microbiología , Femenino , Vida Libre de Gérmenes , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Ratones Endogámicos C57BL , Proctitis/etiología , Proctitis/inmunología , Proctitis/microbiología , Traumatismos por Radiación/inmunología , Recto/inmunología , Recto/microbiología , Recto/efectos de la radiaciónRESUMEN
Recent studies have determined that the microbiome has direct effects on behavior, and may be dysregulated in neurodevelopmental conditions. Considering that neurodevelopmental conditions, such as autism, have a strong genetic etiology, it is necessary to understand if genes associated with neurodevelopmental disorders, such as Shank3, can influence the gut microbiome, and if probiotics can be a therapeutic tool. In this study, we have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 KO mice. L. reuteri, a species with decreased relative abundance in the Shank3 KO mice, positively correlated with the expression of gamma-Aminobutyric acid (GABA) receptor subunits in the brain. Treatment of Shank3 KO mice with L. reuteri induced an attenuation of unsocial behavior specifically in male Shank3 mice, and a decrease in repetitive behaviors in both male and female Shank3 KO mice. In addition, L. reuteri treatment affected GABA receptor gene expression and protein levels in multiple brain regions. This study identifies bacterial species that are sensitive to an autism-related mutation, and further suggests a therapeutic potential for probiotic treatment.
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Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/microbiología , Microbioma Gastrointestinal/genética , Animales , Trastorno del Espectro Autista/metabolismo , Conducta Animal/fisiología , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Disbiosis/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Limosilactobacillus reuteri/genética , Masculino , Ratones , Ratones Noqueados , Proteínas de Microfilamentos , Modelos Genéticos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/fisiología , Probióticos/metabolismo , Probióticos/farmacología , Probióticos/uso terapéutico , Receptores de GABA/metabolismoRESUMEN
BMP-dependent patterning in the Drosophila melanogaster wing imaginal disc serves as a paradigm to understand how morphogens specify cell fates. The observed profile of the transcriptional response to the graded signal of BMP relies upon two counter-active gradients of pMad and Brinker (Brk). This patterning model is inadequate to explain the expression of target genes, like vestigial and spalt, in lateral regions of the wing disc where BMP signals decline and Brk levels peak. Here, we show that in contrast to the reciprocal repressor gradient mechanism, where Brk represses BMP targets in medial regions, target expression in lateral regions is downregulated by BMP signalling and activated by Brk. Brk induces lateral expression indirectly, apparently through repression of a negative regulator. Our findings provide a model explaining how the expression of an established BMP target is differentially and inversely regulated along the anterior-posterior axis of the wing disc.
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Proteínas Morfogenéticas Óseas/metabolismo , Proteínas de Drosophila/metabolismo , Animales , Tipificación del Cuerpo/genética , Tipificación del Cuerpo/fisiología , Proteínas Morfogenéticas Óseas/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Alas de Animales/embriología , Alas de Animales/metabolismoRESUMEN
How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
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Vasos Sanguíneos/fisiología , Diferenciación Celular/fisiología , Organogénesis/fisiología , Páncreas/anatomía & histología , Páncreas/irrigación sanguínea , Páncreas/embriología , Animales , Vasos Sanguíneos/anatomía & histología , Células Epiteliales/citología , Células Epiteliales/fisiología , Epitelio/embriología , Ratones , Ratones Transgénicos , Técnicas de Cultivo de Órganos , Páncreas/crecimiento & desarrollo , Fenotipo , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: Otitis media with effusion (OME) is a common finding in pediatric cochlear implant(CI) candidates and may be managed by inserting ventilation tubes. This study aimed to compare postoperative complication rates in children who underwent CI without and with OME, including patients who were treated without and with ventilation tube insertion. METHODS: A population-based retrospective cohort study was conducted, including all CI patients, under ten years of age, at our institution, between 2007 and 2020. The study's population was divided into three groups based on their middle ear status at CI: 1) OME previously treated with VT, 2) untreated OME, and 3) normal-aerated ears. Postoperative complications of the groups were reviewed and served as our primary outcome measure. RESULTS: Of the 257 implanted ears included, 53, 42, and 162 ears belonged to the VT-treated OME, untreated OME, and aerated groups, respectively. Acute mastoiditis (AM) rate was significantly higher in the OME group compared to the aerated groups (9.5 % vs. 2.5 %, p = 0.0134) and in the VT-treated compared to the untreated OME groups (15.1 % vs. 2.3 %, p = 0.0356). Similarly, the rate of developing chronic suppurative otitis media without cholesteatoma (CSOMWC) was significantly higher in the OME compared to the aerated groups (12.6 % vs. 2.5 %, p = 0.0011) and in the VT-treated compared to the untreated OME groups (18.8 % vs. 4.7 %, p = 0.0366). Other complications rated were very low and similar between the groups. No other statistical difference was found between the groups. CONCLUSION: VT insertion in pediatric CI candidates with OME increased postoperative AM and CSOMWC. We believe that, at least in our population, VT introduction prior to CI, for OME, surgery should be avoided.
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Implantación Coclear , Mastoiditis , Otitis Media con Derrame , Otitis Media , Niño , Humanos , Implantación Coclear/efectos adversos , Otitis Media con Derrame/complicaciones , Otitis Media con Derrame/cirugía , Estudios Retrospectivos , Otitis Media/complicaciones , Mastoiditis/terapia , Ventilación del Oído Medio/efectos adversos , Complicaciones Posoperatorias/etiologíaRESUMEN
A 13-month-old boy presented with bilateral periorbital swelling accompanied by rhinorrhea and fever. Nasal endoscopy revealed middle meatus edema and purulent discharge. He was diagnosed with bilateral preseptal cellulitis and treated with intravenous antibiotics. Continuous fever and new-onset proptosis with extraocular muscle restriction the next day prompted imaging, which revealed sinusitis with bilateral subperiosteal abscesses. He underwent endoscopic sinus surgery with bilateral abscess drainage and recovered uneventfully. Bilateral orbital complications of acute sinusitis are exceedingly rare occurrences and nearly always require surgical treatment.
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INTRODUCTION: Voice therapy (VT), a cornerstone in dysphonia treatment, relies on patient adherence for efficacy. Despite its positive outcomes, adherence rates remain consistently low. This study investigates the impact of cultural background on adherence to VT. METHODS: This is a retrospective cohort study that included all adult patients referred to our institution's Speech and Hearing unit, in 2018 for VT related to dysphonia. The study group included a distinct adult minority group (Bedouin Arabs) which was compared to a control group. Adherence rates, demographic factors, and therapy outcomes were analyzed. RESULTS: A total of 137 adult patients with dysphonia (20 in the study group and 117 in the control group) were included. There were no significant differences in adherence rates between the study and control groups (75% vs 74.3%, P = 1), with an overall nonadherence rate of 74.4%. The median leg of time for VT was 239days, and the median number of visits was 3.0. Logistic regression analysis, adjusting for age and visits, indicated lower odds of dysphonia improvement in the study group (odds ratios [OR]: 0.12, P = 0.05). However, visits showed a significant positive impact on improvement (OR: 2.58, P < 0.001). CONCLUSION: While cultural background does not impact adherence rate, it is associated with different attendance patterns and lower voice outcomes following VT. Future efforts should concentrate on investigating aspects of adherence such as home exercises, accessibility of treatment, and the frequency of follow-up sessions to facilitate customized interventions for specific populations.
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INTRODUCTION: As the role of sinonasal anatomical variants as predisposing factors in determining the lateralization of acute rhinosinusitis-related orbital complications (ARS-OC) in pediatrics remains a topic of debate, this study further explores the potential association between anatomical variations and ARS-OC. METHODS: A retrospective study was conducted on children who had been admitted with ARS-OC using medical records and sinus CT scans to compare anatomical differences between the affected and contralateral sides. This study aimed to identify bony anatomical disparities that may impact OC laterality secondary to ARS. The anatomical features examined included septal deviation, concha bullosa, lamina papyracea dehiscence (LPD), and uncinate process abnormalities. RESULTS: The CT scans of 57 pediatric patients (114 sides) were reviewed. Our results indicated that bony anatomical variations were associated with ARS-OC laterality (63 % vs. 37 %, P = 0.006), yielding an odds ratio of 2.91. Additionally, our study revealed a significant association between ipsilateral LPD with the increased risk of ARS-OC (39 % vs. 1.8 %, P < 0.05), with an odds ratio of 34.3 compared to the opposite side. CONCLUSIONS: LPD might play a role in the pathophysiology of pediatric ARS-OC, as it is associated with a significantly higher risk of affecting the ipsilateral side. Further research is necessary to determine whether LPD is a causative factor or a result of ARS.
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Senos Paranasales , Rinosinusitis , Tomografía Computarizada por Rayos X , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Enfermedad Aguda , Variación Anatómica , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/etiología , Senos Paranasales/diagnóstico por imagen , Estudios Retrospectivos , Rinosinusitis/complicaciones , Rinosinusitis/diagnóstico por imagenRESUMEN
OBJECTIVES: To evaluate the impact of the pneumococcal conjugate vaccines (PCVs) introduction on the orbital complications of acute rhino-sinusitis (OC-ARS). METHODS: A retrospective cohort study of all pediatric patients with OC-ARS during the period 2002-2019. Data included clinical, demographic, laboratory, and microbiology findings. Patients were divided into three groups: before PCV7 introduction (group 1), after PCV7 and before PCV13 (group 2), and after PCV13 (group 3). RESULTS: Of 265 enrolled patients, 117, 39, and 109 were assigned to groups 1, 2, and 3. During the study period, a significant decrease was recorded in the percentages of patients in Chandler classification severity category 1, with an increase in patients in category 3 (P = 0.011). The yearly incidence of OC-ARS decreased from 12.64 cases per 100,000 population in 2002 to 5.56 per 100,000 in 2008, and 2.99 per 100,000 in 2019 (P < 0.001). Patients aged 0-4 years showed a dramatic decrease from 29 cases per 100,000 population in 2002 to 4.27 per 100,000 in 2019 (P < 0.001). The pathogens retrieved from all cultures performed were Streptococcus pneumoniae (32.5%), non-typeable Haemophilus influenzae (27.5%), Streptococcus Species, (12.5%), and Staphylococcus aureus (20%), with no changes in distribution during the study periods. Surgery was performed in 28 (10.6%) patients. CONCLUSIONS: A significant decrease was seen in the overall incidence of OC-ARS, mainly attributable to the decrease in patients aged 0-4 years. An increase was recorded in the severity of the disease following PCVs introduction.
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OBJECTIVE: To study national pediatric acute rhinosinusitis (ARS) burden fluctuations before and during the first 2 coronavirus-19 (COVID) years, characterized by alternating lockdown and relaxation periods, the introduction of COVID vaccines, and the emergence of nonalpha COVID variants. METHODS: This was a cross-sectional, population-based study covering the 3 pre-COVID years and the first 2 COVID years from a big database of the largest Israeli Health Maintenance Organization. For comparison purposes, we explored ARS burden trends with those of urinary tract infection (UTI), which is unrelated to viral diseases. We identified children <15 years presenting with ARS and UTI episodes and categorized them according to their age and presentation date. The average ARS and UTI episodes of the 3 pre-COVID years were used to calculate the incidence rate ratios (IRRs) of the 2 COVID years, analyzed separately. Seasonal variations were explored. RESULTS: We identified 44,483 ARS and 121,263 UTI episodes. There was a substantial reduction in ARS episodes during the COVID years (IRR 0.36, 95% CI: 0.24-0.56, P < 0.001). Although UTI episode rates also decreased during COVID (IRR 0.79, 95% CI: 0.72-0.86, P < 0.001), the reduction in ARS burden was 3-fold higher. The dominant pediatric ARS age group was between 5 and 15 years. The largest decrease in ARS burden was during the first COVID year. ARS episode distribution showed a seasonal fluctuation, with a peak during the summer months during the COVID years. CONCLUSIONS: Pediatric ARS burden decreased during the first 2 COVID years. Episode distribution was noted to be year-round.