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al ubiquitin ligase activator of NFKB1; NAC N-acetylcysteine; NEK2 NIMA (never in mitosis gene a)-related expressed kinase 2; NH4Cl ammonium chloride; PARP1 poly(ADP-ribose) polymerase family, member 1; PI proteasome inhibitor; R-HSPA5 arginylated HSPA5; ROS reactive oxygen species; SQSTM1 sequestome 1; Ub ubiquitin; USP7 ubiquitin specific peptidase 7.Triple-negative breast cancer (TNBC) displays an aggressive clinical course, heightened metastatic potential, and is linked to poor survival rates. Through its lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), this subtype remains unresponsive to traditional targeted therapies. Undesirable and sometimes life-threatening side effects associated with current chemotherapeutic agents warrant the development of more targeted treatment options. Targeting signal transducer and activator of transcription 3 (STAT3), a transcription factor implicated in breast cancer (BCa) progression, has proven to be an efficient approach to halt cancer growth in vitro and in vivo. Currently, there are no FDA-approved STAT3 inhibitors for TNBC. Although pimozide, a FDA-approved antipsychotic drug, has been attributed a role as a STAT3 inhibitor in several cancers, its role on this pathway remains unexplored in TNBC. As a "one size fits all" approach canntion.Recent single center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intra-cranial (IC) injury and worse cerebrovascular reactivity. The goal of this study is to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution data set (HR ICU). Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher), and the presence of a digital admission CT scan. Physiologic signals were processed for pressure reactivity index (PRx) and both the % time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH) and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteovide preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern. Keywords autoregulation, computed tomography, CT, image segmentation, injury patterns, PRx.BACKGROUND Double origin of the posterior inferior cerebellar artery (DOPICA) is a rare cranial imaging finding with an incidence of 0.36-6% reported in various retrospective studies. Aneurysms on a DOPICA are even rarer. CASE DESCRIPTION A 34-year-old women hospitalised for subarachnoid haemorrhage showed a ruptured aneurysm arising from the caudal channel of the DOPICA. Endovascular treatment was selected, and the aneurysm was successfully and completely embolised using two coils. CONCLUSIONS To date, a total of three previous saccular aneurysms of the DOPICA itself have been reported, all of which were treated using endovascular methods. Our case is the first report of a ruptured saccular aneurysm arising from the non-branching segment of the caudal channel of the DOPICA.BACKGROUND AND PURPOSE Preoperative embolization of carotid paragangliomas is a common procedure in interventional neuroradiology. Direct puncture embolization has shown less morbidity and mortality than endovascular embolization and a higher percentage of devascularization. selleck We describe our experience using Squid® as the only embolic agent in direct puncture glomus embolization. METHODS We retrospectively reviewed pre-embolization imaging tests, emphasizing the volume of the lesion, clinical history data, technical aspects of the procedure, as well as the approximate amount of blood lost during the surgical procedure in all patients with preoperative embolization of carotid paragangliomas performed at our tertiary care hospital. RESULTS Six patients met our criteria from May 2017 to August 2018. The volume of the mass ranged from 1.4-18.5 mL and the quantity of Squid® injected varied from 1.1-15 mL. Total devascularization was achieved in almost all cases (>90%), with one puncture needed in all but one patient, who was punctured two times. No hemorrhagic complications were described in surgery, no blood transfusions were needed, and the mean decrease of hemoglobin after surgery was 1.04 g/dL. CONCLUSIONS Direct puncture embolization of carotid paragangliomas only using Squid® is a safe and relatively simple procedure that facilitates the subsequent surgery with minimal blood loss.Objectives To evaluate the reproducibility of ultrasound cervical length (CL) measurement at the second trimester.Methods A set of 565 cervical ultrasound images were collected at 19 + 0-24 + 6 weeks' gestation. Two senior maternal-fetal specialists measured CL in each image on three occasions 2 weeks apart. In the interval between the first and following two measures, the clinicians reviewed 20 images together to agree on the criteria for measurement. Measurements were analyzed for intra- and inter-observer disagreement. The robustness of patient classification when CL measure was used with different cutoff thresholds was analyzed.Results Average intra-observer deviation was 2.8 mm for clinician 1 and 3.7 mm for clinician 2. Inter-observer deviation among the two clinicians was 5.2 and 3.2 mm before and after reviewing measurement criteria together. When cutoffs were used to classify as "short" cervix, disagreement ranged from 22 to 70% depending on operator and threshold used.Conclusion Ultrasound CL measurements by experts showed moderate intra- and inter-observer reproducibility. The use of specific cutoffs to classify patients as high or low risk resulted in wide disagreements. The results stress the importance of training and quality assessments on considering universal screening application of CL measurement.Nerve tissue regeneration continues to represent an intractable obstacle to realizing the promise of tissue engineering. While neurobiology works to shed light on the mechanisms governing neuronal growth and repair, considerable technical gaps remain that hinder progress. Chief among these is the absence of an appropriate culture environment to faithfully reproduce the neuronal niche ex vivo. We propose that the various multipotent cells found in the oral cavity may represent an important, yet underutilized resource for preparing such neurogenic microenvironments. Like those of nerve tissue, these cell populations are of ectodermal origin and have clinically demonstrated neurogenic potential. While there is a lack of consensus on whether putative types of oral and craniofacial stem cells constitute distinct populations, their contribution to neural tissue engineering may be two-fold as a cellular feedstock for neoneurogenesis and for the production of specialized in vitro environments for neurogenic differentiation, phenotype maintenance, and use in therapeutic applications.Aim To evaluate the initial adhesion and formation of Streptococcus mutans biofilm in vitro in the presence of saliva, human colostrum and 3'-sialyllactose. Methods Human colostrum and salivas were collected from 30 mothers and newborn postpartum. Eighteen hours culture of S. mutans was treated with colostrum or 3'-sialyllactose in three different moments before, during, and after 24 h from the microbial inoculation. Salivas were also tested in conjunction with colostrum. The assays were realized in sterile 96-well flat-bottom microtiter plates for 24 h. The biofilms were fixed, washed, stained with crystal violet, and extracted. Absorbance was measured to evaluate biofilm growth mass. Results Colostrum applied after and during the inoculation decreased biofilm formation when compared with the control (p  less then  .05). The presence of saliva increased the biofilm biomass (p  less then  .05). The application of 3'-sialyllactose reduced biofilm formation independently of moments of application (p  less then  .05). Conclusion Saliva contributed to the proliferation of biofilm and colostrum did not prevent the initial adhesion, but interfered in the accumulation and development of microorganisms in biofilms. 3'-sialyllactose significantly decreased biofilm formation. This information expands the importance of colostrum as a potent oral antimicrobial biofluid.Introduction Antiretroviral treatment (ART) has led to improved control of HIV infection, giving the opportunity of exploring therapeutic alternatives as new long-acting (LA) regimens, that might improve the quality of life of people living with HIV (PLWH).Areas covered This article overviews the pharmacokinetic and pharmacodynamic properties of LA cabotegravir and rilpivirine (CR), two nanoformulated drugs of intramuscular administration and focuses on assessing its role on the treatment of HIV infection.Expert opinion In addition to the advantage of treatment simplification, which could be especially beneficial for population subgroups with significant HIV-related stigma, it also reduces the number of drugs, and probably, the risk of treatment-related toxicity. The similar efficacy when compared to oral triple therapies in clinical trials and the high satisfaction rates among both professionals and patients make LA CR a suitable alternative for the control of HIV infection in the modern era.Introduction Testicular germ cell tumors (TGCTs) are the most common neoplasia in the young male population, and the incidence has been constantly increasing in many parts of the world. These tumors are classified into seminomas and non-seminomas, and those divided, in turn, into yolk sac tumors, embryonal cell carcinomas, choriocarcinomas, and teratomas. Although therapeutic approaches have improved, approximately 25% of the patients relapse or, in a small number of cases, show platinum-resistant disease.Areas covered We review several molecular targets that have recently emerged as powerful tools for both diagnosis and therapy of TGCTs. Moreover, we reviewed the most frequent deregulated pathways involved in TGCT tumorigenesis, reporting drugs that may emerge as novel therapeutic agents.Expert opinion TGCT treatment is mainly based on platinum-derivative therapy with high cure rates. However, in the refractory patients, there are few alternative treatments. Thus, different pharmacological approaches have to be thoroughly investigated to shed new light on TGCT pathogenesis and treatment.Mucosal malignant melanoma of the head and neck (HN) is a rare and aggressive neoplasm which constitutes only 1% of all melanomas. Neuroendocrine differentiation is an extremely unusual phenomenon in mucosal melanomas, of which five cases have been reported. We report a rare case of a 63-year-old female who developed sinonasal amelanotic melanoma with immunohistochemical expression of neuroendocrine markers, presenting a diagnostic dilemma. Ultrastructural evidence of melanosomes and neurosecretory granules aided in arriving at the diagnosis. Aberrant immunoexpression of neuroendocrine markers, particularly in an amelanotic melanoma, has critical diagnostic implications, as various malignancies with undifferentiated histomorphology occur at this site, many of which stain positively with neuroendocrine markers. We discuss the differential diagnoses and recommend a high index of suspicion so as not to miss the diagnosis of mucosal melanoma at this location.