Dissociable Contributions of Basolateral Amygdala and Ventrolateral Orbitofrontal Cortex to Flexible Learning Under Uncertainty.

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

Modulated Arc Therapy for hippocampal-avoidance whole brain radiation therapy: planning comparison with intensity modulated Radiation Therapy.

This study aimed to evaluate the modulated arc therapy (mARC) technique as a planning and treatment option for hippocampal sparing whole brain radiotherapy (HS-WBRT) following the Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) were selected retrospectively for 15 patients. Two types of plans were created for each patient, namely an intensity-modulated radiation therapy (IMRT) and a mARC plan. IMRT and mARC plans were compared in terms of plan quality indices, absorbed dose to organs at risk (OARs), number of monitor units (MUs), and treatment time. All plans in both techniques were considered clinically acceptable for treatment. However, IMRT plans presented a higher conformity (p = 0.01) as well as a higher homogeneity as compared to mARC plans, but this difference was not statistically significant (p > 0.05). In terms of the preservation of the hippocampus, it was observed that the IMRT plans achieved significantly lower doses for both 100% of its volume and for its maximum dose (p < 0.001). The evaluation of the remaining OARs showed that the IMRT technique resulted in lower doses, and significant differences were observed for the following organs: left cochlea (p < 0.001), left eye (p < 0.001), right eye (p = 0.03), both lenses of the eye (p < 0.001), and right optic nerve (p = 0.02). Despite these differences, the absolute differences in all dosimetric parameters were low enough to bear any clinical relevance. A drastic (close to 65%) and significant (p < 0.001) decrease was observed in the number of MUs for the mARC plans. This resulted in a substantial decrease in treatment time (60.45%, p < 0.001). It is concluded that the mARC technique is a feasible planning and treatment solution for HS-WBRT that meets the RTOG 0933 criteria. The main advantage of using mARC over IMRT for HS-WBRT is the considerable reduction in MUs and treatment time.

Brief Telephonic Motivational Interviewing for People Living with HIV with Follow-up Problems.

Motivational interviewing (MI)-based interventions can be effective for people living with HIV (PLWHIV) with medical follow-up problems. This study aimed to assess the stage of motivation to attend medical appointments of PLWHIV with medical follow-up problems and to evaluate a single telephone session MI intervention directed to engage them in care. The change in stage was evaluated before and after the intervention, and attending medical appointments was monitored for six months. Thirty-nine PLWHIV participated; 51.3% were in precontemplation/contemplation and 49.7% in preparation/action stage. Most (excluding those in the action stage from the beginning) (n = 22, 71.0%) advanced to another stage after the intervention (z = - 4.235, p < .001), and most did not miss the following appointments. Brief and remote MI interventions could be useful in low-resource settings, especially for those in the early stages of change, to explore motivations related with missing medical appointments.

The role of minimally invasive gynecologic surgeons in the era of subspecialties: when to refer and consult.

PURPOSE OF REVIEW: Minimally invasive gynecologic surgery (MIGS) is a subspecialty focus of obstetrics and gynecology with focused expertise on complex benign gynecologic disorders. To date, no formal recommendations have been made in defining a referral system for MIGS. This article reviews the evidence regarding common disorders and procedures and their outcomes, and posits a basis for MIGS referral. RECENT FINDINGS: In instances where intraoperative and perioperative features may pose clinical challenges to the surgeon and ultimately the patient, the literature suggests the following scenarios may have adverse outcomes, and therefore, benefit from the skills of MIGS subspecialists: fibroids - at least five myomas, myoma size at least 9 cm, and suspected myoma weight at least 500 g; endometriosis - presence of endometrioma(s), suspected stage III/IV endometriosis, and requirement for advanced adjunct procedures; hysterectomy - uteri at least 250 g or 12 weeks estimated size, at least three prior laparotomies, obesity, and complex surgical history with suspected adhesive disease. SUMMARY: A referral system for MIGS subspecialists has proven benefits for both the gynecologic surgical community as well as the patients and their outcomes. This article provides evidence for collaboration with MIGS especially as it relates to leiomyomatous uteri, endometriosis, and complex hysterectomies.

Predicting recurrence of papillary thyroid cancer using the eighth edition of the AJCC/UICC staging system.

BACKGROUND: The AJCC/UICC classification is widely used for predicting survival in papillary thyroid cancer (PTC), but has not been evaluated as a predictor of recurrence. The hypothesis of this study was that the eighth edition of the AJCC system can be used in this novel way. METHODS: All patients in the study underwent surgery for PTC at a high-volume endocrine surgery centre in France between 1985 and 2015. The seventh and eighth editions of the AJCC/UICC staging system for PTC were employed to predict recurrence and disease-specific survival using the Kaplan-Meier and log rank tests. RESULTS: Among 4124 patients (79·7 per cent female), median age was 50 (i.q.r. 38-60) years; 3906 patients (94·7 per cent) underwent total thyroidectomy, with lymph node dissection in 2495 (60·5 per cent). The eighth edition of the AJCC/UICC staging system placed 91·8, 7·1, 0·4 and 0·7 per cent of patients in stages I-IV respectively. After reclassifying patients from the seventh to the eighth AJCC/UICC edition, the disease was downstaged in 23·8 per cent. Over a median follow-up of 7 years, 260 patients (6·4 per cent) developed recurrent disease, including 5·2 per cent of patients with stage I, 19·6 per cent with stage II, 59 per cent with stage III and 50 per cent with stage IV disease, according to the eighth edition. The eighth edition was a better predictor of recurrence than the seventh edition. CONCLUSION: The eighth edition of the AJCC/UICC staging system appears to be a novel tool for predicting PTC recurrence, which is a meaningful outcome for this indolent disease. The eighth edition can be used to risk-stratify patients, keeping in mind that other molecular and pathological predictive factors must be integrated into the assessment of recurrence risk.

Gene expression of growth factors with angiogenic potential in human dental pulp tissue from teeth with complete and incomplete root development.

AIM: To quantify the expression of angiogenic growth factors (ANG2, VEGFA, TGFß1) and their corresponding receptors (VEGFR1, VGFR2, NRP1 and TGFßR1) in human dental pulps from extracted third molars with complete and incomplete root development. METHODOLOGY: Fifty-six dental pulp samples obtained from freshly extracted human third molars were divided equally into two groups according to their stage of root development; 28 third molars with complete root development and 28 third molars with incomplete root development. All samples were processed and total RNA was extracted, cDNA was then synthetized for each sample and the target genes expression profiles for ANG2, VEGFA, VEGFR1, VEGFR2, NRP1, TGFß1 and TGFßR1 were obtained by RT2-PCR. The data was analysed with a Student's t-test to compare the replicate ∆∆Ct values for each gene. RESULTS: Teeth with incomplete root development were associated with a significantly greater gene expression of TGFßR1 (P = 0.03), whereas in teeth with complete root development the genes that had significantly greater expression were VEGFA (P = 0.04). CONCLUSION: The angiogenic growth factors (ANG2, VEGFA, TGFß1) and their receptors (NRP1, VEGFR1, VEGFR2 and TGFßR1) were expressed in pulps of teeth with complete and incomplete root development measured by RT2-PCR, with TGFBR1 genes being significantly different in teeth with incomplete root development and VEGFA genes in teeth with complete root development.

Encapsulation of Lactobacillus plantarum ATCC 8014 and Pediococcus acidilactici ATCC 8042 in a freeze-dried alginate-gum arabic system and its in vitro testing under gastrointestinal conditions.

The aim of this study was to investigate the viability of Pediococcus acidilactici ATCC 8042 and Lactobacillus plantarum ATCC 8014 in a freeze-dried capsules system prepared with sodium alginate and gum arabic using the extrusion technique. The capsules made with alginate 2% (w/v)/gum arabic 2% (w/v) showed higher hardness (7.12 ± 0.71 N), with highly cohesive (0.81 ± 0.02) and elastic (0.99 ± 0.00) features on the Texture Profile Analysis (TPA), as well as higher sphericity with 1.75 ± 0.12 mm y 1.73 ± 0.13 mm diameter axes and regularity in their surface by Scanning Electron Microscopy (SEM). The use of skimmed milk at 10% as a cryoprotector in the freeze-drying process allowed the obtention of high viability percentages (88% a 96%) for both strains. Best results of viability for P. acidilactici encapsulated was with the use of alginate 2% (w/v)/gum arabic 2% (w/v) (92%±2.65), and L. plantarum with the use of alginate 2% (w/v) (84.71%±10.33) during the gastrointestinal environment challenge.

2-Chlorophenol degradation by catalytic wet air oxidation using copper supported on TiO2-CeO2-ZrO2.

In this work, we describe the morphological, electronic and catalytic properties of support TiO2-CeO2-ZrO2, prepared by sol-gel method, which was impregnated with copper at 5 and 10% by weight, in order to obtain efficient catalysts in the catalytic wet air oxidation (CWAO) of 2-cp. The catalysts were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM-EDS), UV-Vis diffuse reflectance spectroscopy (DRS) and nitrogen physisorption by the Brunauer-Emmett-Teller (BET) method. The activity of the materials used in this study revealed that without the presence of Cu, the SCO2 is low and with a content of 10% this metal shows the best catalytic behaviour; conversely, a reaction mechanism is proposed that describes the complete oxidation of 2-cp in this case.

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens.

Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.

Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma.

Angiogenesis is the formation of new blood vessels based on a pre-existing vasculature. It comprises two processes, sprouting of endothelial cells and the division of vessels due to abnormal growth of the microvasculature. It has been demonstrated that substance P (SP) can induce angiogenesis either by modulating endothelial cell growth (direct mechanism) or by attracting cells with angiogenic potential to the injury site (indirect mechanism). Therefore, the purpose of this article is to review the angiogenic mechanisms that regulate mineralized tissue formation in human dental pulp tissue and their relationship with SP expression as a defence response to stimuli such as the masticatory function and occlusal trauma. Articles included in this review were searched in PubMed, Scopus and ISI Web of Science databases, combining the following keywords: human dentine pulp, angiogenesis, angiogenic growth factors, neuropeptides, substance P, neurogenic inflammation, dentine matrix, dentinogenesis, occlusal trauma and dental occlusion. It is concluded that human dental pulp tissue responds to occlusal trauma and masticatory function with a neurogenic inflammatory phenomenon in which SP plays an important role in the direct and indirect mechanisms of angiogenesis by the action evoked via NK1 receptors at different cells, such as fibroblasts, endothelial and inflammatory cells, leading to new blood vessel formation which are needed to stimulate mineralized tissue formation as a defence mechanism.

Reproductive strategy of the Patagonian catfish Hatcheria macraei.

This study describes the reproductive strategy of the stream-dwelling catfish Hatcheria macraei in the Pichileufu River, Argentina. Gonad maturity phases, classified on the basis of histological analysis, stages of gamete development and the frequency distribution of oocyte size, were correlated with macroscopic features of the gonads. Hatcheria macraei has a cystovarian ovary, asynchronous oocyte development and lobular testes. Five oocyte and four spermatogenic stages were identified and related to macroscopic gonad characteristics, making it possible to divide gonad development into five phases for females and males. Mature oocyte diameter ranged from 922 to 1935 µm. Absolute fecundity in mature females varied from 115 to 480 oocytes. Hatcheria macraei has multiple spawning during a protracted reproductive season that extends from December to April. This, together with its small size, is characteristic of an opportunistic reproductive strategy, commonly found in species that inhabit adverse and unpredictable environments, such as the low-order rivers of Patagonia.

Patterns of Use and Short-Term Outcomes of Minimally Invasive Surgery for Malignant Pheochromocytoma: A Population-Level Study.

BACKGROUND: Malignant pheochromocytoma is rare, and there is a scarcity of data on the use of minimally invasive surgery (MIS) for treatment. The aims of this study were to analyze patterns of use of MIS for malignant pheochromocytoma in the U.S. and compare short-term outcomes to those of open adrenalectomy. METHODS: Patients with malignant pheochromocytoma undergoing MIS, including laparoscopy, robotic assisted, laparoscopy converted to open, or open adrenalectomy, were culled from the National Cancer Database, from 1998 to 2011. Data were examined using simple summary statistics, Χ2 and student's t tests, Mann-Whitney test, and logistic regression. RESULTS: A total of 36 MIS and 67 open adrenalectomies were identified in 2010-2011. No significant differences were observed between the two treatment groups in demographic characteristics or comorbidities. Preoperative diagnosis of malignancy was made in 52.8% of MIS and 48.5% of open patients (p=NS). MIS and open adrenalectomies did not differ with respect to lymph node metastases, vascular invasion, extra-adrenal-extension, and distant metastases (all p=NS). MIS tended to more often be used to perform partial adrenalectomy (38.9 vs. 20.4% open, p=0.061); surgical margins, 30-day readmission and mortality rates were similar to open adrenalectomy (all p=NS). Tumors removed via MIS were smaller (48.7 vs. 73.3 mm open, p=0.003) and associated with a shorter length of stay. CONCLUSIONS: A significant proportion of patients with malignant pheochromocytomas underwent MIS, with short-term outcomes which are comparable to those of open surgery. Further studies focused on long-term survival and recurrence are needed to assess the role of MIS in the management of these rare tumors.

Art therapy masks reflect emotional changes in military personnel with PTSS.

Among disabling post-traumatic stress symptoms (PTSS) are irritability, aggressive behavior, distressing memories and general impaired cognition and negative mood. Art therapy interventions, including mask-making, can potentially alleviate these symptoms. We tested the hypothesis that art conveys emotions and predicted that blinded viewers would be able to perceive changes in theoretically derived emotional profiles expressed in art made by military personnel with PTSS from the onset to the end of therapy. Five service members and veterans exhibiting PTSS were enrolled in an 8-session art therapy protocol, during which they artistically transformed papier-mâché masks at the beginning and end of the protocol. We found that blinded viewers without knowledge of the masks' creation stage (onset or end of therapy) read initial masks as conveying more negative emotions (e.g., angry, upset, and challenged) and later masks as conveying more positive emotions (calm and pleasure). Based on the assessments from the blinded evaluators, we infer the emotional transition experienced by the participants was expressed in the masks. In an exploratory arm of the study, we also found that viewers were better able to empathize with the negative emotions experienced by participants with PTSS when asked to explicitly take their perspective.

Characteristics of US military personnel with atrial fibrillation and associated deployment and retention rates.

INTRODUCTION: Atrial fibrillation (AF) is an arrhythmia impacting military occupational performances. Despite being a recognised disqualifying condition, there is no literature describing US military service members with AF. This study aims to describe members with AF diagnoses, the distribution of treatment strategies and associated deployment and retention rates. METHODS: Active duty service members identified with AF from 2004 to 2019 were investigated. Cardiovascular profiles, AF management strategies and military dispositions were assessed by electronic medical record review. RESULTS: 386 service members (mean age 35.0±9.4 years; 94% paroxysmal AF) with AF diagnoses were identified. 91 (24%) had hypertension followed by 75 (19%) with sleep apnoea. Mean CHA2DS2-VASc scores were low (0.39±0.65). Rhythm treatments were used in 173 (45%) followed by rate control strategies in 155 (40%). 161 (42%) underwent pulmonary vein isolation (PVI). In subgroup analysis of 365 personnel, 147 (40%) deployed and 248 (68%) remained active duty after AF diagnosis. Deployment and retention rates did not differ between those who received no medical therapy, rate control or rhythm strategies (p=0.9039 and p=0.6192, respectively). PVI did not significantly impact deployment or retention rates (p=0.3903 and p=0.0929, respectively). CONCLUSION: Service members with AF are young with few AF risk factors. Rate and rhythm medical therapies were used evenly. Over two-thirds met retention standards and 40% deployed after diagnosis. There were no differences in deployment or retention between groups who receive rate therapy, rhythm medical therapy or PVI. Prospective evaluation of the efficacy of specific AF therapies on AF burden and symptomatology in service members is needed.

Solid-organ transplantation in older adults: current status and future research.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

Current management of medullary thyroid cancer.

Medullary thyroid carcinoma (MTC) is an uncommon malignancy of the parafollicular C cells of the thyroid, with a propensity for early lymph node spread and distant metastasis. It is hereditary in approximately 25% of cases, involving specific point mutations of the RET proto-oncogene inherited in an autosomal dominant fashion. While European professional organizations have put forth calcitonin screening guidelines for earlier detection of MTC, the American Thyroid Association, which has published recent guidelines for MTC treatment, have not had a position on routine screening in the USA. Surgical extirpation of the primary tumor and involved lymph node metastases is the mainstay of treatment and the only chance for cure. Conventional systemic chemotherapies for metastatic MTC have been disappointing; however, newer agents which affect specific RET proteins and tyrosine kinase growth factor receptors show promise in phase 1 and 2 clinical trials.

High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.