Antagonists of the stress and opioid systems restore the functional connectivity of the prefrontal cortex during alcohol withdrawal through divergent mechanisms.

Chronic alcohol consumption leads to dependence and withdrawal symptoms upon cessation, contributing to persistent use. However, the brain network mechanisms by which the brain orchestrates alcohol withdrawal and how these networks are affected by pharmacological treatments remain elusive. Recent work revealed that alcohol withdrawal produces a widespread increase in coordinated brain activity and a decrease in modularity of the whole-brain functional network using single-cell whole-brain imaging of immediate early genes. This decreased modularity and functional hyperconnectivity are hypothesized to be novel biomarkers of alcohol withdrawal in alcohol dependence, which could potentially be used to evaluate the efficacy of new medications for alcohol use disorder. However, there is no evidence that current FDA-approved medications or experimental treatments known to reduce alcohol drinking in animal models can normalize the changes in whole-brain functional connectivity. In this report, we tested the effect of R121919, a CRF1 antagonist, and naltrexone, an FDA-approved treatment for alcohol use disorder, on whole-brain functional connectivity using the cellular marker FOS combined with graph theory and advanced network analyses. Results show that both R121919 and naltrexone restored the functional connectivity of the prefrontal cortex during alcohol withdrawal, but through divergent mechanisms. Specifically, R121919 increased FOS activation in the prefrontal cortex, partially restored modularity, and normalized connectivity, particularly in CRF1-rich regions, including the prefrontal, pallidum, and extended amygdala circuits. On the other hand, naltrexone decreased FOS activation throughout the brain, decreased modularity, and increased connectivity overall except for the Mu opioid receptor-rich regions, including the thalamus. These results identify the brain networks underlying the pharmacological effects of R121919 and naltrexone and demonstrate that these drugs restored different aspects of functional connectivity of the prefrontal cortex, pallidum, amygdala, and thalamus during alcohol withdrawal. Notably, these effects were particularly prominent in CRF1- and Mu opioid receptors-rich regions highlighting the potential of whole-brain functional connectivity using FOS as a tool for identifying neuronal network mechanisms underlying the pharmacological effects of existing and new medications for alcohol use disorder.

Partial Thyroidectomy for Papillary Thyroid Microcarcinoma: Is Completion Total Thyroidectomy Indicated?

BACKGROUND: Total thyroidectomy is a well-established surgical approach for the management of papillary thyroid cancer (PTC). However, the best surgical approach for papillary microcarcinoma is nowadays still debated. Both total thyroidectomy and simple lobectomy are used. We report the experience of a single University center in the treatment of thyroid microcarcinoma. METHODS: A retrospective analysis on all patients who underwent thyroid surgery at our institution over a 24-year period (1991-2015) was performed. Patients were grouped according to whether they received total thyroidectomy (Group 1) or lobectomy (Group 2). Follow-up was made by routine clinical and ultrasound examination. Specific outcomes such as recurrence and need for reoperation as well as complications (transient vocal cord paralysis and hypocalcemia) were analyzed. RESULTS: During the study period 880 patients underwent surgery for PTC. Group 1 and 2 consisted, respectively, of 756 and 124 patients. A micro PTC (<10 mm) was present in 251 and 69 specimen of Group 1 and 2. No evidence of disease recurrence in the follow-up was reported in patients with microPTC in Group 1 and in 57 patients of Group 2. In the remaining 12 patients completion thyroidectomy was carried out due to ultrasound findings of contralateral nodules (10), lymphadenopathy (1), and capsular invasion (1). Five of these patients had a contralateral papillary carcinoma on final histopathologic examination. Thus recurrence rate for patients of Group 2 was 7.3%. Morbidity rates were, respectively, for Group 1 and 2: transient nerve palsy 81 and 5 (11 vs. 7.3%, p = ns), transient hypoparathyroidism (Calcium <2.00 mmol/L) 137 (18.6%) and 0 (p < 0.0001). Three of the 12 patients of Group 2 undergoing further surgery had a transient hypoparathyroidism. CONCLUSIONS: Thyroid lobectomy is an effective surgical strategy to manage papillary microcarcinomas with low complications. Routine completion thyroidectomy is not mandatory. Appropriate selection excluding high-risk patients is of paramount importance in order to achieve the best results.

Predictive Accuracy of Mandibular Ramus Flexure as a Morphologic Indicator of Sex Dimorphism in Jordanians / Exactitud Predictiva de la Flexura de la Rama Mandibular como Indicador Morfológico de Dimorfismo Sexual en Jordanos

The present study investigated the validity of mandibular ramus flexure in sex differentiation among young Jordanian adults using Orthopantomographic images in a double blind study. A normative sample comprised of 419 images was selected, of which 126 belonged to male patients and 293 images to females. The exclusion criteria used in the selection involved excluding images that showed marked loss of mandibular molars, over erupted, tilted, anomalous molars and teeth or mandibles associated with pathology. Each image was examined for the presence of a flexure on the posterior margin of the ramus at the occlusal plane. The posterior margin of the ramus was carefully traced graphically and the occlusal plane level was delineated as guided by the height of cusp tips at the occlusal surfaces of the mandibular molars. The ramus flexure was more accurately diagnostic for females (94.6%), than for males (47.6%); this gave rise to an overall diagnostic accuracy of 70.9% which is far below the reported 90.6-99.0% by Loth & Henneberg. Our results, however, agreed with some reported findings of other researchers. In conclusion, ramus flexure provides a moderately acceptable predictive accuracy and could be considered as a supplementary rather than a definitive mean of sex determination. In sexing unknown skeletal remains, it is necessary to employ as many methods or traits as possible instead of relying on one morphological trait.

El presente estudio investigó la validez de flexura de la rama mandibular en la diferenciación sexual entre adultos jóvenes jordanos utilizando imágenes de ortopantomografías, en un estudio doble ciego. Se seleccionó una muestra normativa compuesta de 419 imágenes, de las cuales 126 pertenecían a hombres y 293 a mujeres. Se excluyeron imágenes que mostraron una pérdida marcada de los molares mandibulares, dientes sobre erupcionados o inclinados, molares anómalos y los dientes o mandíbulas con enfermedad. Cada imagen fue examinada para detectar la presencia de un ángulo en el margen posterior de la rama en el plano oclusal. El margen posterior de la rama mandibular fue trazado gráficamente y el plano oclusal se delineó estableciendo como guía la altura de las puntas cuspídeas en las superficies oclusales de los molares mandibulares. La flexura de la rama mandibular fue más precisa en el diagnóstico de las mujeres (94,6%) que para los hombres (47,6%); con una precisión diagnóstica global del 70,9%, la cual es inferior a la reportada por Loth & Henneberg entre 90,6­99,0%. Nuestros resultados, concuerdan con algunos hallazgos reportados por otros investigadores. En conclusión, la flexura de la rama mandibular proporciona una exactitud de predicción moderadamente aceptable y podría ser considerada como un complemento en lugar de un medio definitivo de la determinación del sexo. En restos óseos desconocidos, es necesario emplear la mayor cantidad de métodos o rasgos posibles que depender de un solo rasgo morfológico.

Inhibition of aspartate transcarbamylase by a phenobarbital derivative.

Mammalian and hepatic aspartate transcarbamylase is inhibited by phenobarbital p-nitrophenylhydrazone in a reversible and non-competitive type with Ki values 8.45 x 10(-5) and 9.64 x 10(-5) M in the reactions toward carbamyl phosphate and aspartate, respectively. In vivo inhibition occurred in a dose-dependent manner in which less than 50% of the activity was retained. These observations suggest that this inhibitor may interfere with the in vivo regulation of this enzyme and lead to an additional biological effect of phenobarbitals.