Altered nucleus accumbens functional connectivity precedes apathy in Parkinson's disease.

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson's disease with a syndrome of reduced goal-directed behaviour-apathy. Building on this work, we investigated whether the neural regions implementing effort-based decision-making were associated with apathy in Parkinson's disease, and more importantly, whether changes to these regions were evident prior to apathy development. We performed a large, multimodal neuroimaging analysis in a cohort of people with Parkinson's disease (n = 199) with and without apathy at baseline. All participants had ∼2-year follow-up apathy scores, enabling examination of brain structure and function specifically in those with normal motivation who converted to apathy by ∼2-year follow-up. In addition, of the people with normal motivation, a subset (n = 56) had follow-up neuroimaging data, allowing for examination of the 'rate of change' in key nodes over time in those who did, and did not, convert to apathy. Healthy control (n = 54) data were also included to aid interpretation of findings. Functional connectivity between the nucleus accumbens and dorsal anterior cingulate cortex was higher in people with normal motivation who later converted to apathy compared to those who did not, whereas no structural differences were evident between these groups. In contrast, grey matter volume in these regions was reduced in the group with existing apathy. Furthermore, of those with normal motivation who had undergone longitudinal neuroimaging, converters to apathy showed a higher rate of change in grey matter volume within the nucleus accumbens. Overall, we show that changes in functional connectivity between nucleus accumbens and anterior cingulate cortex precedes apathy in people with Parkinson's disease, with conversion to apathy associated with higher rate of grey matter volume loss in nucleus accumbens, despite no baseline differences. These findings significantly add to an accumulating body of transdiagnostic evidence that apathy arises from disruption to key nodes within a network in which normal goal-directed behaviour is instantiated, and raise the possibility of identifying those at risk for developing apathy before overt motivational deficits have arisen.

Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease.

A caregiver's all-too-familiar narrative - "He doesn't think through what he does, but mostly he does nothing." Apathy and impulsivity, debilitating and poorly understood, commonly co-occur in Huntington's disease (HD). HD is a neurodegenerative disease with manifestations bridging clinical neurology and psychiatry. In addition to movement and cognitive symptoms, neurobehavioral disturbances, particularly apathy and impulsivity, are prevalent features of HD, occurring early in the disease course, often worsening with disease progression, and substantially reducing quality of life. Treatments remain limited, in part because of limited mechanistic understanding of these behavioral disturbances. However, emerging work within the field of decision-making neuroscience and beyond points to common neurobiological mechanisms underpinning these seemingly disparate problems. These insights bridge the gap between underlying disease pathology and clinical phenotype, offering new treatment strategies, novel behavioral and physiological biomarkers of HD, and deeper understanding of human behavior. In this review, we apply the neurobiological framework of cost-benefit decision making to the problems of apathy and impulsivity in HD. Through this decision-making lens, we develop a mechanistic model that elucidates the occurrence of these behavioral disturbances and points to potential treatment strategies and crucial research priorities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Postoperative bleeding and leaks in sleeve gastrectomy are independent of both staple height and staple line oversewing.

BACKGROUND: Over 100,000 sleeve gastrectomy procedures are performed annually in the USA. Despite technological advances, postoperative bleeding and gastric staple line leak are complications of this procedure. We analyzed patient-specific and perioperative factors to determine their association with these complications. METHODS: We performed a retrospective cohort analysis of patients who underwent sleeve gastrectomy between 2005 and 2019 at our institution. Patient demographics, comorbidities, and procedure details including type of energy device, staple type, staple height, staple line oversewing, and staple line clipping were compared using multiple logistic regression for combined postoperative complications (blood transfusion, bleeding, and staple line leak). Postoperative bleeding was defined by requiring blood transfusion and/or re-operation to control bleeding. Staple line leak was confirmed radiographically. RESULTS: There were 1213 patients who underwent sleeve gastrectomy. Fifty-two high-risk patients were excluded due to cirrhosis, end-stage renal disease, and anticoagulation use for left ventricular assist device. Of the remaining 1161 patients, twenty-five (2.2%) received postoperative blood transfusion, nine (0.8%) had postoperative bleeding, two (0.2%) had staple line leak, and twenty-eight patients (2.4%) had combined postoperative complications. The median age was significantly higher for patients with combined postoperative complications (43 vs 49; p = 0.02). There was no difference in postoperative blood transfusion, bleeding, staple line leak, or combined postoperative complication with different energy devices (p = 0.92), staple types (p = 0.21), staple heights (p = 0.50), or staple line suturing/clipping (p = 0.95). In addition, there was no difference in bleeding when comparing staple line sewing techniques (p = 0.44). Predictably, patients with combined postoperative complications had increased length of stay (3 days vs 1 day; p < 0.001). CONCLUSION: Sleeve gastrectomy procedure has tremendous variability in technique and devices used. We observed no difference in the combined postoperative complications of bleeding or staple line leak with respect to different energy devices, staple height, or oversewing of the gastric staple line. Patient selection is crucial, as patient age and coagulopathic comorbidities were found to lead to higher combined postoperative complications.

Characterising spoken responses to an intelligent virtual agent by persons with mild cognitive impairment.

The diagnosis of Mild Cognitive Impairment (MCI) characterises patients at risk of dementia and may provide an opportunity for disease-modifying interventions. Identifying persons with MCI (PwMCI) from adults of a similar age without cognitive complaints is a significant challenge. The main aims of this study were to determine whether generic speech differences were evident between PwMCI and healthy controls (HC), whether such differences were identifiable in responses to recent or remote memory questions, and to determine which speech variables showed the clearest between-group differences. This study analysed recordings of 8 PwMCI (5 females, 3 males) and 14 HC of a similar age (8 females, 6 males). Participants were recorded interacting with an intelligent virtual agent: a computer-generated talking head on a computer screen which asks pre-recorded questions when prompted by the interviewee through pressing the next key on a computer keyboard. Responses to recent and remote memory questions were analysed. Mann-Whitney U tests were used to test for statistically significant differences between PwMCI and HC on each of 12 speech variables, relating to temporal characteristics, number of words produced and pitch. It was found that compared to HC, PwMCI produce speech for less time and in shorter chunks, they pause more often and for longer, take longer to begin speaking and produce fewer words in their answers. It was also found that the PwMCI and HC were more alike when responding to remote memory questions than when responding to recent memory questions. These findings show great promise and suggest that detailed speech analysis can make an important contribution to diagnostic and stratification systems in patients with memory complaints.

Equine endometritis: a review of challenges and new approaches.

Endometritis in the mare begins as a normal physiological inflammatory response to breeding that involves both a mechanical and immunological response pathway activated to rid the uterus of semen and bacteria. With successful resolution of this inflammation, the mare's uterus will provide a hospitable environment for the development of the semi-allogenic conceptus. If the mare fails to resolve this inflammatory response within 48 h of breeding, she will become susceptible to persistent breeding-induced endometritis (PBIE) which will have detrimental effects on her fertility. This condition can then predispose the mare to bacterial or fungal endometritis leading to further degeneration of the endometrium. Optimisation of the mare's fertility requires a fine balance between allowing the natural immune response of the endometrium to its exposure to allogenic semen to run its course, and yet preventing its progression to PBIE or the involvement of infectious agents. This review discusses the challenges presented by PBIE, latent infections, biofilms, fungal infections and the need to utilise diagnostic methods available and implement targeted treatments to optimise fertility in the mare.

Fundamentals of Radiation Oncology for Neurologic Imaging.

Although the physical and biologic principles of radiation therapy have remained relatively unchanged, a technologic renaissance has led to continuous and ever-changing growth in the field of radiation oncology. As a result, medical devices, techniques, and indications have changed considerably during the past 20-30 years. For example, advances in CT and MRI have revolutionized the treatment planning process for a variety of central nervous system diseases, including primary and metastatic tumors, vascular malformations, and inflammatory diseases. The resultant improved ability to delineate normal from abnormal tissue has enabled radiation oncologists to achieve more precise targeting and helped to mitigate treatment-related complications. Nevertheless, posttreatment complications still occur and can pose a diagnostic challenge for radiologists. These complications can be divided into acute, early-delayed, and late-delayed complications on the basis of the time that they manifest after radiation therapy and include leukoencephalopathy, vascular complications, and secondary neoplasms. The different irradiation technologies and applications of these technologies in the brain, current concepts used in treatment planning, and essential roles of the radiation oncologist in the setting of brain disease are reviewed. In addition, relevant imaging findings that can be used to delineate the extent of disease before treatment, and the expected posttreatment imaging changes are described. Common and uncommon complications related to radiation therapy and the associated imaging manifestations also are discussed. Familiarity with these entities may aid the radiologist in making the diagnosis and help guide appropriate management. ©RSNA, 2020.

Update on advanced semen-processing technologies and their application for in vitro embryo production in horses.

The increased commercialisation of intracytoplasmic sperm injection (ICSI) in horses creates more opportunities to incorporate advanced reproductive technologies, such as sex-sorted, refrozen and lyophilised spermatozoa, into a breeding program. This paper reviews the status of these semen-handling technologies in light of their use in equine ICSI programs. Pregnancies have been achieved from each of these advanced technologies when combined with ICSI in horses, but refinements in the semen-handling processes underpinning these technologies are currently being explored to produce more reliable and practical improvements in the results from equine ICSI.

Routine use of mesh during hiatal closure is safe with no increase in adverse sequelae.

BACKGROUND: Primary laparoscopic hiatal repair with fundoplication is associated with a high recurrence rate. We wanted to evaluate the potential risks posed by routine use of onlay-mesh during hiatal closure, when compared to primary repair. METHODS: Utilizing single-institutional database, we identified patients who underwent primary laparoscopic hiatal repair from January 2005 through December 2014. Retrospective chart review was performed to determine perioperative morbidity and mortality. Long-term results were assessed by sending out a questionnaire. Results were tabulated and patients were divided into 2 groups: fundoplication with hiatal closure + absorbable or non-absorbable mesh and fundoplication with hiatal closure alone. RESULTS: A total of 505 patients underwent primary laparoscopic fundoplication. Mesh reinforcement was used in 270 patients (53.5%). There was no significant difference in the 30-day perioperative outcomes between the 2 groups. No clinically apparent erosions were noted and no mesh required removal. Standard questionnaire was sent to 475 patients; 174 (36.6%) patients responded with a median follow-up of 4.29 years. Once again, no difference was noted between the 2 groups in terms of dysphagia, heartburn, long-term antacid use, or patient satisfaction. Of these, 15 patients (16.9%, 15/89) in the 'Mesh' cohort had symptomatic recurrence as compared to 19 patients (22.4%, 19/85) in the 'No Mesh' cohort (p = 0.362). A reoperation was necessary in 6 patients (6.7%) in the 'Mesh' cohort as compared to 3 patients (3.5%) in the 'No Mesh' cohort (p = 0.543). CONCLUSIONS: Onlay-mesh use in laparoscopic hiatal repair with fundoplication is safe and has similar short and long-term results as primary repair.

Factors associated with inconsistent condom use in adolescents with negative or unknown HIV status in Northwest Cameroon.

The purpose of this study is to evaluate the association between utilization of HIV testing and condom use amongst Cameroonian youths/adolescents who are not known to be HIV-infected. Worldwide, HIV is spreading most quickly amongst youths/adolescents. Between 44% and 82% of sexually active youths in Cameroon report inconsistent condom use. Data regarding utilization of HIV testing and condom use are lacking. A cross-sectional survey was administered to 431 youths ages 12-26 years in Cameroon from September 2011 to December 2011. Data on sociodemographics, sexual risk behaviors, self-reported HIV status, and condom use were collected. We compared rates of inconsistent condom use between those with known HIV negative status who utilized testing (HIV-N) and those with unknown status due to unutilized testing (HIV-U). Inconsistent condom use was defined as responding "never," "sometimes," or "usually," while consistent condom use was defined as responding "always" to questions regarding frequency of condom use. Generalized estimating equations were applied to assess the association between HIV testing and inconsistent condom use, adjusting for other confounders. Of 414 eligible respondents, 205 were HIV-U and 209 were HIV-N. HIV-U subjects were younger (mean age = 16.4 vs. 17.9, p < 0.001) and more likely to report living in an urban area (p = 0.002) than HIV-N subjects. Seventy-two percent (137/191) of sexually active youths reported inconsistent condom use. After adjusting for potential confounders, HIV-U status (odds ratio [OR] = 3.97, 95% confidence interval [CI] = 1.68-6.01) was associated with inconsistent condom use. Similarly, female gender (OR = 3.2, 95% CI = 1.29-7.89) was associated with inconsistent condom use, while older age at sexual debut was associated with a decreased risk for inconsistent condom use (OR = 0.67, 95% CI = 0.56-0.81). Cameroonian adolescents report high rates of inconsistent condom use which we found to be associated with self-reported unknown HIV status due to unutilized HIV testing. Successful HIV prevention programs among African youths/adolescents may benefit from expanded HIV testing programs.

A simplified fixed-time insemination protocol using frozen-thawed stallion spermatozoa stored at 17°C for up to 24 h before insemination.

BACKGROUND: Insemination of mares with frozen-thawed spermatozoa requires intensive management and results in 40%-60% per cycle pregnancy rates. OBJECTIVES: To determine if satisfactory fertility is possible for frozen-thawed semen after processing it through a microfluidic device, followed by storage at 17°C for up to 24 h before fixed-time insemination. STUDY DESIGN: Uncontrolled field trials. METHODS: A pilot study evaluated the motility of frozen-thawed spermatozoa after centrifugation and storage (17°C) in two different media for up to 48 h. Subsequently, the motility of frozen-thawed semen processed through a microfluidic device, resuspended in two different media during storage (17°C) for up to 24 h was evaluated. The fertility of frozen-thawed spermatozoa, after microfluidic sorting and storage at 17°C for up to 24 h, was evaluated after fixed-time insemination in a commercial embryo programme. Experiment 1: Frozen-thawed spermatozoa (N = 5 stallions) were centrifuged and resuspended in Botusemen Gold™ or SpermSafe™ and stored (17°C) for up to 48 h. Sperm motility was evaluated by CASA at 0, 6, 24 and 48 h. Experiment 2: Frozen-thawed spermatozoa (N = 4 stallions) underwent microfluidic sorting and storage (17°C) for up to 24 h in both media. Sperm concentration and motility were evaluated at 0, 16 and 24 h. Experiment 3: Fertility of frozen-thawed spermatozoa (N = 3 stallions) was evaluated after insemination of 42 mare cycles at 6, 16 and 24 h after thawing, microfluidic sorting and storage before fixed-time insemination. RESULTS: The stallion significantly influenced sperm motility, but there was no effect of media on motility parameters. Storage time significantly affected sperm motility after centrifugation but not after microfluidic sorting. Storage time had no effect on the overall embryo recovery rate (52%, n = 42). MAIN LIMITATIONS: Field trial with small mare numbers and no control at time = 0 h. CONCLUSIONS: Fixed-time insemination of frozen-thawed spermatozoa after microfluidic sorting and storage at 17°C for up to 24 h produced satisfactory embryo recovery rates.

Streptococcus pneumoniae purulent pericarditis in a neonate.

Purulent bacterial pericarditis is an uncommon infection that manifests during childhood, and in the post-antibiotic era Streptococcus pneumoniae is an unusual cause.We report a case of purulent bacterial pericarditis in a neonate caused by Streptococcus pneumoniae serotype 7F. Although cases of bacterial pericarditis caused by Streptococcus pneumoniae as a causative agent have been reported, their combination in a neonate is unique and this is, to our knowledge, the first case of this combination in the newborn period.

Brain on fire: an imaging-based review of autoimmune encephalitis.

Autoimmune encephalitis represents an increasingly recognized group of immune-mediated disorders the affect the central nervous system. The purpose of this article is to highlight the characteristic MR imaging findings associated with autoimmune encephalitis, describe the pathophysiology, review antibodies that have been identified and their patterns of CNS involvement, and discuss approaches to management. Familiarity with the imaging and clinical features of autoimmune encephalitis will prompt the radiologist to suggest the diagnosis which can facilitate appropriate management.

Massive thoracic lipoma: a case report.

A 60-year-old woman with a massive left intra-thoracic lipoma presented with worsening dyspnea. A computed tomographic scan revealed an 18 x 10 x 24 cm intra-thoracic mass, which was compressing the left lung and shifting the mediastinum to the right. At operative resection, a large, well-encapsulated, intrathoracic lipoma was discovered that weighed 2,556 grams. Histologic evaluation confirmed that the mass consisted of benign adipose tissue.

Development of the Association of Pediatric Program Directors Global Educator Scholarship-Expanding Bidirectional Efforts in Global Health Education.

BACKGROUND: The Board of the Association of Pediatric Program Directors (APPD) partnered with the APPD Global Health Learning Community (GHLC) to establish the APPD Global Pediatric Educator Scholarship. This award seeks to recognize pediatric educators who demonstrate leadership in improving pediatric education in low- and middle-income countries, and provide them with career development opportunities by attending the APPD Spring meeting. Two educators per year have been awarded the scholarship since 2017. AWARD EVALUATION: The authors sent survey questions via email and obtained responses from 6 (100%) of the scholarship awardees, 8 (75%) APPD GHLC leadership individuals, and 4 (67%) APPD Board members. Three authors analyzed the responses with consensus achieved on themes. RESULTS: Awardees noted learning about educational strategies, academic opportunities through networking, and context for stronger bilateral exchange with partners. APPD leaders noted an expansion of the organization's mission to include global presence. Challenges included program visibility, sustainable funding, and logistics. Suggestions included better incorporation of awardees into APPD membership, longitudinal mentorship, targeted conference navigation, and visits to local academic institutions. CONCLUSIONS: The APPD Global Educator Scholarship is a replicable model of organizational global outreach that expands the concept of bidirectional exchange to include career sponsorship for global partners.

Global Health Partnerships During the COVID-19 Pandemic: Perspectives and Insights from International Partners.

Global health partnerships (GHPs) have encountered many challenges during the coronavirus disease 2019 (COVID-19) pandemic. New perspectives and insights are needed to guide GHPs when navigating current and future collaborations. This study aimed to understand perspectives and insights of international partners regarding how the COVID-19 pandemic impacted their GHPs with institutions in the United States. We performed a cross-sectional qualitative study conducted through virtual semi-structured interviews performed between June 12, 2020 and July 22, 2020. We queried academic institutions based in the United States to refer individuals from their corresponding international GHP organizations. We invited these individuals to participate in virtual interviews that were audio-recorded and transcribed. We analyzed data qualitatively to identify themes. Eighty-four United States partners provided e-mail addresses for international partners. Ten individuals from these GHPs completed the interview. Participants reported overall positive experiences with their United States-based partners during the pandemic. The following themes emerged: imbalanced decision-making; worry about partnership continuity; opportunity to optimize communication within partnerships; interest in incorporating technology to facilitate engagement; and a desire for increased bilateral exchanges. Several challenges appeared to exist before COVID-19 and were highlighted by the pandemic. Most respondents were optimistic regarding the future of their GHPs. However, concerns were expressed regarding the implications of fewer in-person international experiences with United States trainees and the desire for stronger communication. Although our results do not represent the perspectives and insights of all GHPs, they provide considerations for the future. We urge institutions in the United States to re-examine and strive for equitable relationships with their international partners.

Characterization of endothelial progenitor cells mobilization following cutaneous wounding.

Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are known to play an important role in neovascularization and wound healing. We investigated the temporal effects of cutaneous wounding on EPC surface markers within the peripheral blood and BM, and to better understand the role of the stromal cell-derived factor-1 alpha (SDF-1alpha/CXCR4) axis on EPC mobilization after wounding. FVB/NJ mice were administered bilateral 8 mm circular full-thickness skin wounds. Peripheral blood and BM were isolated at daily intervals postwounding through day 7 and analyzed for EPC mobilization characteristics and levels of SDF-1alpha. Cutaneous wounding was found to cause a transient increase in EPC mobilization that peaked on day 3. In contrast, SDF-1alpha protein within blood plasma was observed to significantly decrease on days 3, 4, and 7 following cutaneous wounding. BM levels of SDF-1alpha protein decreased to a nadir on day 3, the same day as peak mobilization was observed to occur. The decrease in BM SDF-1alpha protein levels was also associated with a decrease in SDF-1alpha mRNA suggesting transcriptional down-regulation as a contributing factor. This study for the first time characterizes EPC mobilization following cutaneous wounding in mice and supports a major role for the SDF-1alpha/CXCR4 axis in regulating mobilization within the BM, without evidence for systemic increases in SDF-1alpha.

Phase I study of H5.020CMV.PDGF-beta to treat venous leg ulcer disease.

Venous leg ulcers are a prevalent nonhealing wound of the lower extremity. Although topically applied growth factors successfully improve wound repair in animal studies, similar studies on humans with venous leg ulcers have not been successful. This study was designed to evaluate the acute safety and biologic feasibility of peri-ulcer injection of a replication-incompetent adenoviral construct expressing platelet-derived growth factor-beta (PDGF-beta). In this phase I study, we demonstrate the initial safety, feasibility, and biologic plausibility of using H5.020CMV.PDGF-beta to treat venous leg ulcer disease.

Tuberculous peritonitis: a surgical dilemma.

This is a case report of tuberculous peritonitis (TB), an entity which is difficult to diagnose. When TB is found in extrapulmonary organs it is usually associated with an immunocompromised state, such as that caused by the human immunodeficiency virus (HIV). Medical therapy continues to be the treatment of choice and, if the correct diagnosis is made early, surgery is rarely required.

Congenital high airway obstruction syndrome due to complete tracheal agenesis: an accident of nature with clues for tracheal development and lessons in management.

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition characterized by complete blockage of the fetal airways associated with hydrops. We present a case of CHAOS due to the rare cause of complete tracheal agenesis. The ex utero intrapartum therapy (EXIT) strategy was employed to allow for neck and mediastinal exploration. Thymectomy allowed dissection to the level of the carina demonstrating the confluence of dilated mainstem bronchi but no trachea and no connection to the esophagus. A 2.5 endotracheal tube was inserted into the right mainstem bronchus and secured to the left clavicle. At 3 months of age, the infant succumbed to sepsis from Enterobacter mediastinitis due to friction between the tracheostomy tube and the nasogastric tube resulting in erosion of the esophagus. Complete tracheal agenesis, as seen in this case, is consistent with the failure of normal tracheal elongation as suggested by newer theories of foregut development. This case illustrates the most severe form of tracheal atresia causing CHAOS ever salvaged by the EXIT procedure at birth. The subsequent postnatal course highlights the need for early tracheal replacement in this particularly challenging form of CHAOS.

Severe micrognathia: indications for EXIT-to-Airway.

The ex utero intrapartum treatment (EXIT) procedure has become an important management option in cases of fetal airway obstruction. Select cases of severe micrognathia may be candidates for EXIT-to-Airway due to high-risk of airway obstruction at birth. Here we present three successful EXIT-to-Airway procedures for the management of congenital micrognathia in its most severe manifestations. CASE 1: A 23-year-old G3P1011 with a pregnancy complicated by severe micorgnathia, jaw index <5th percentile, as well as polyhydramnios. At 36 weeks EXIT-to-Airway was performed utilizing a bronchoscopically positioned laryngeal mask airway (LMA) during 23 min of uteroplacental support followed by tracheostomy. CASE 2: A 26-year-old G4P0120 with a pregnancy complicated by severe micrognathia, jaw index <5th percentile, and an obstructed oropharynx associated with polyhydramnios. At 37 weeks EXIT-to-Airway was performed with placement of tracheostomy. CASE 3: A 36-year-old G6P3023 with fetal magnetic resonance imaging (MRI) revealing esophageal atresia, polyhydramnios, and severe micrognathia with a jaw index <5th percentile. At 35 weeks the patient underwent EXIT-to-Airway with formal tracheostomy during 35 min of uteroplacental bypass. In the most severe cases of fetal micrognathia, EXIT-to-Airway provides time to evaluate and secure the fetal airway prior to delivery. We propose indications for EXIT-to-Airway in micrognathia to include a jaw index <5%, with indirect evidence of aerodigestive tract obstruction such as polyhydramnios, glossoptosis or an absent stomach bubble.