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Outbreaks linked to inadequate endoscope drying have infected numerous patients, and current standards and guidelines recommend at least 10 minutes of forced air for drying channels. This study evaluated a new forced-air drying system (FADS) for endoscopes. Drying was assessed using droplet detection cards; visual inspection of air/water connectors, suction connectors, and distal ends; and borescope examinations of endoscope interiors. Assessments were performed after automated endoscope reprocessor (AER) alcohol flush and air purge cycles and after 10-minute FADS cycles. Researchers evaluated drying during encounters with 22 gastroscopes and 20 colonoscopes. After default AER alcohol and air purge cycles, 100% (42/42) of endoscopes were still wet. Substantial fluid emerged from distal ends during the first 15 seconds of the FADS cycle, and droplets also emerged from air/water and suction connectors. Following FADS cycle completion, 100% (42/42) were dry, with no retained fluid detected by any of the assessment methods. Multiple endoscope ports and channels remained wet after AER cycles intended to aid in drying but were dry after the FADS cycle. This study reinforced the need to evaluate the effectiveness of current drying practices and illustrated the use of practical tools in a real-world setting. • A forced-air drying system with multiple channel connections was evaluated. • Assessments included droplet detection paper and visual inspection with borescopes. • Endoscopes were wet after automated reprocessor alcohol flush and air purge cycles. • Fluid emerged from multiple ports and channels during forced air drying. • No residual fluid was detected following a 10-minute forced air drying cycle. [ABSTRACT FROM AUTHOR]

Multitarget stool DNA (mt-sDNA) testing is a stool-based screening test for colorectal cancer (CRC). In a single instance of testing, the pivotal Food and Drug Administration–approval study (NCT01397747) found that 16% of mt-sDNA tests were positive, and the positive predictive value (PPV) for CRC or advanced precursor lesions (APL) was 27.3%. We aimed to examine real-world longitudinal performance by determining the test-positive rate and PPV of mt-sDNA on the second round of testing. Colonoscopy and pathology reports were reviewed retrospectively for patients with a negative mt-sDNA on the first round of screening and a positive mt-sDNA on the second round. The test-positivity rate and PPV for CRC, APL, and any colorectal neoplasia were calculated for the second mt-sDNA and compared with baseline PPVs from a previously published cohort of patients from our institution who tested positive on the first round of screening. A total of 2758 patients completed a second test at a median of 3.2 years after the first test. Of these, 422 (15%) had a positive second mt-sDNA. The PPV was 0.25% for CRC, 24% for APL, and 67% for any colorectal neoplasia. There was no significant difference in PPV on the second mt-sDNA test compared with the first round (24% vs 28% for APL; P =.12). mt-sDNA test positive rate and PPV were similar between the first and second rounds of screening. These observations confirm the utility of a second round of mt-sDNA screening and may inform estimates of mt-sDNA effectiveness for CRC screening. [Display omitted] [ABSTRACT FROM AUTHOR]

Diverse neuron classes in hippocampal CA1 have been identified through the heterogeneity of their cellular/molecular composition. How these classes relate to hippocampal function and the network dynamics that support cognition in primates remains unclear. Here, we report inhibitory functional cell groups in CA1 of freely moving macaques whose diverse response profiles to network states and each other suggest distinct and specific roles in the functional microcircuit of CA1. In addition, pyramidal cells that were grouped by their superficial or deep layer position differed in firing rate, burstiness, and sharp-wave ripple-associated firing. They also showed strata-specific spike-timing interactions with inhibitory cell groups, suggestive of segregated neural populations. Furthermore, ensemble recordings revealed that cell assemblies were preferentially organized according to these strata. These results suggest that hippocampal CA1 in freely moving macaques bears a sublayer-specific circuit organization that may shape its role in cognition. [Display omitted] • Oscillatory modulation of spike timing varies as a function of frequency and cell group • Sharp-wave ripple participation differs among cell groups • Spike-time interactions with inhibitory groups depend on the layer depth of pyramidal cells • Macaque hippocampal CA1 consists of functionally distinct superficial-deep cell assemblies Abbaspoor et al. report that, in macaque CA1, superficial and deep pyramidal cells form subcircuits through differing interactions with local inhibitory cell groups. Segregation into superficial and deep cell assemblies during post-learning sleep suggests recruitment into distinct circuits during replay and memory consolidation. [ABSTRACT FROM AUTHOR]

Late adolescence is a period of dynamic change in the brain as humans learn to navigate increasingly complex environments. In particular, prefrontal cortical (PFC) regions undergo extensive remodeling as the brain is fine-tuned to orchestrate cognitive control over attention, reasoning, and emotions. Late adolescence also presents a uniquely vulnerable period as neurodevelopmental illnesses, such as schizophrenia, become evident and worsen into young adulthood. Challenges in early development, including prenatal exposure to infection, may set the stage for a cascade of maladaptive events that ultimately result in aberrant PFC connectivity and function before symptoms emerge. A growing body of research suggests that activation of the mother's immune system during pregnancy may act as a disease primer, in combination with other environmental and genetic factors, contributing to an increased risk of neurodevelopmental disorders, including schizophrenia. Animal models provide an invaluable opportunity to examine the course of brain and behavioral changes in offspring exposed to maternal immune activation (MIA). Although the vast majority of MIA research has been carried out in rodents, here we highlight the translational utility of the nonhuman primate (NHP) as a model species more closely related to humans in PFC structure and function. In this review, we consider the protracted period of brain and behavioral maturation in the NHP, describe emerging findings from MIA NHP offspring in the context of rodent preclinical models, and lastly explore the translational relevance of the NHP MIA model to expand understanding of the etiology and developmental course of PFC pathology in schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare lipid and blood pressure (BP) control before and after implementing a certified pharmacy technician (CPhT) protocol that optimized electronic health record (EHR) capabilities and shifted work from clinical pharmacy specialists (CPSs) to CPhT.Setting: Kaiser Permanente Colorado's pharmacist-managed cardiac risk reduction service (which manages dyslipidemia, hypertension, and diabetes for all patients with atherosclerotic cardiovascular disease).Practice Description: In 2019, a protocol that optimized EHR capabilities and allowed work to be offloaded from CPS to CPhT was implemented. Filtered views within the EHR were created that bucketed patients with specific lipid results criteria. The CPhT protocol provided guidance to CPhT on determining whether patients were at low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein (non-HDL) goals, on appropriate statin intensity, adherent to medications, and whether the most recent BP was controlled. The CPhT notified CPS of uncontrolled patients who would assess and manage these patients, as necessary. The CPhT notified controlled patients of their results.Practice Innovation: Data on the outcomes of incorporating pharmacy technicians to support CPS clinical activities in ambulatory clinical pharmacy are limited.Evaluation Dethods: This retrospective study compared a "Pharmacist-Driven" (index date: January 1, 2016) with a "Tech-Enhanced" (index date: January 1, 2019) group. The primary outcome was the proportion of patients at all goals defined as LDL-C < 70 mg/dL, non-HDL < 100 mg/dL, and BP < 140/90 mm Hg at 1 year after the index dates.Results: There were 6813 patients included (mean age: 70.2 ± 11.1 years, 71.4% male): 3130 and 3683 in the "Pharmacist-Driven" and "Tech-Enhanced" groups, respectively. The proportion of patients who attained LDL-C, non-HDL, and BP goals was higher in the "Tech-Enhanced" group (51.1% vs. 39.7%, P < 0.001) than the "Pharmacist-Driven" group.Conclusion: A protocol integrating EHR decision support and CPhTs enabled work to shift to from CPS to CPhT and improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Cardiogenic shock (CS) represents a spectrum of hemodynamic deficits in which the cardiac output is insufficient to provide adequate tissue perfusion. The Impella (Abiomed Inc, Danvers, MA) device, a contemporary percutaneous ventricular support, is most often indicated for classic, deteriorating, and extremis Society for Coronary Angiography and Intervention stages of CS, which describe CS that is not responsive to optimal medical management and conventional treatment measures. Impella devices are an evolving field of mechanical support that is used with increasing frequency. Critical care transport medicine crews are required to transport patient support by the Impella device with increasing frequency. It is important that critical care transport medicine crews are familiar with the Impella device and are able to troubleshoot complications that may arise in the transport environment. This article reviews many aspects of the Impella device critical to the transport of this complex patient population. [ABSTRACT FROM AUTHOR]

To meet the evolving role of today's pharmacist, student pharmacists need to be given independent responsibilities that increase in rigor as they advance through the curriculum and be able to practice both autonomously and as part of an interprofessional team. Quality improvement methods: The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) experiential programs office undertook a 20-year process of developing independence for students. Students faced increasing challenges and responsibilities as they moved through experiential practice settings, with constant, cyclic adjustments made in response to feedback. The continuous focus on developing independence in students has established a culture of trust in the Colorado pharmacy practice community. Students are allowed autonomy, and are challenged with increasing rigor as they advance. Graduates are well-prepared to perform both independently and as part of a team. The curricular framework based on trust and independent learning has helped the SSPPS train student pharmacists to meet the demands of current pharmacy practice, as well as expected roles in the future. Requiring increasing responsibilities from students as they move through the curriculum allows them to move along the spectrum set up through the entrustable professional activity (EPA) assessments to achieve high ratings for an individual skill. Continuous feedback and adjustments are necessary to identify what can be accomplished in pharmacy practice settings. This 20-year approach to curricular design and modifications within experiential education has produced independent pharmacy practitioners upon graduation. [ABSTRACT FROM AUTHOR]

Despite growing evidence that checkpoint inhibitor immunotherapy (IO) toxicity is associated with improved treatment response, the relationship between immune-related adverse events (irAEs) and overall survival (OS) among older adults [age ≥ 70 years (y)] remains unknown. The study goal was to determine differences in OS based on age and ≥ grade 3 (G3) irAEs. This was a retrospective cohort study of 673 patients with advanced cancer. Patients who received ≥1 dose of IO at our institution from 2011 to 2018 were eligible. The primary outcome was OS from the start of first line of IO treatment, compared between four patient groups stratified by age and ≥ G3 irAEs with adjustment for patient characteristics using a Cox proportional hazards model. Among all 673 patients, 35.4% were ≥ 70y, 39.8% had melanoma, and 45.6% received single-agent nivolumab. Incidence and types of ≥G3 irAEs did not differ by age. Median OS was significantly longer for all patients with ≥G3 irAEs (unadjusted 21.7 vs. 11.9 months, P = 0.007). There was no difference in OS among patients ≥70y with ≥G3 irAEs (HR 0.94, 95% CI 0.61–1.47, P = 0.79) in the multivariable analysis. Patients <70y with ≥G3 irAEs had significantly increased OS (HR 0.33, 95% CI 0.21–0.52, P < 0.001). Younger patients, but not older adults, with high-grade irAEs experience strong survival benefit. This difference may be due to the toll of irAEs themselves or the effects of treatments for irAEs, such as corticosteroids. Factors impacting OS of older adults after irAEs must be determined and optimized. [ABSTRACT FROM AUTHOR]

A bipartite patella usually presents as an incidental finding on radiographs because most cases are asymptomatic. However, some patients may present with pain and functional limitations. Conservative treatment is sufficient to resolve symptoms in most cases; however, a small minority of patients may require surgical management. Recent studies have reported excellent results with an arthroscopic approach. This Technical Note details our procedure for treating a symptomatic bipartite patella that has not resolved with conservative care. [Display omitted] [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis (ACD) is a prevalent condition associated with numerous potential allergen exposures. Tattoo ink is variable and may contain allergens that can be overlooked in patient education and diagnosis. We present a 27-year-old female with ACD following a new tattoo. The patient was repeatedly misdiagnosed with cellulitis by three different clinicians and treated with multiple antibiotics without improvement. The correct diagnosis was eventually made in the emergency department (ED). Although the patient was aware of her allergies to nickel and cobalt from patch testing, she was not aware of the potential for tattoo ink to contain these allergens because prior tattoos had not provoked an allergic reaction. Consequently, the appropriate care was delayed by a month, resulting in significant morbidity. This case demonstrates the potential for ACD to present similarly to cellulitis in an ED setting and the need for clinical vigilance in diagnosis of ACD. It also highlights the importance of detailed patient education on potential allergen sources particularly in the context of tattooing, which is performed with unregulated and variable ink products. [ABSTRACT FROM AUTHOR]

Activation of lipid-burning pathways in the fat-storing white adipose tissue (WAT) is a promising strategy to improve metabolic health and reduce obesity, insulin resistance, and type II diabetes. For unknown reasons, bilirubin levels are negatively associated with obesity and diabetes. Here, using mice and an array of approaches, including MRI to assess body composition, biochemical assays to measure bilirubin and fatty acids, MitoTracker-based mitochondrial analysis, immunofluorescence, and high-throughput coregulator analysis, we show that bilirubin functions as a molecular switch for the nuclear receptor transcription factor peroxisome proliferator–activated receptor α (PPARα). Bilirubin exerted its effects by recruiting and dissociating specific coregulators inWAT, driving the expression of PPARα target genes such as uncoupling protein 1 (Ucp1) and adrenoreceptor b 3 (Adrb3). We also found that bilirubin is a selective ligand for PPARα and does not affect the activities of the related proteins PPARγ and PPARδ. We further found that diet-induced obese mice with mild hyperbilirubinemia have reduced WAT size and an increased number of mitochondria, associated with a restructuring of PPARα-binding coregulators. We conclude that bilirubin strongly affects organismal body weight by reshaping the PPARa coregulator profile, remodeling WAT to improve metabolic function, and reducing fat accumulation. [ABSTRACT FROM AUTHOR]

Intrathecal baclofen (ITB) is a mainstay of treatment for patients with chronic spasticity. Up to 40% of all patients receiving ITB experience overdose or withdrawal symptoms, which in the most severe cases can lead to multisystem organ failure and death. There is currently no well-established treatment for ITB withdrawal. One previous case report details an intubated pediatric patient who underwent baclofen pump removal in which dexmedetomidine was used in combination with other medications to prevent baclofen withdrawal. We report a case of baclofen withdrawal where the decision was made to initiate a dexmedetomidine infusion, with subsequent improvement of the patient's hypertension and tachycardia. At no point during her stay did the patient require intubation for airway protection, and the patient was ultimately discharged to her previous nursing facility on hospital day 9 with no new neurologic deficits. Emergency physicians should be aware of dexmedetomidine as a promising option for the treatment of ITB withdrawal in the acute setting. Although little evidence is currently present, dexmedetomidine was used successfully in this case, and should be considered as a temporizing treatment for ITB withdrawal. Dexmedetomidine holds promise in the management of ITB withdrawal compared to other previously described treatments, including oral baclofen, cyproheptadine, and dantrolene. In addition, dexmedetomidine has a superior safety profile compared to propofol or large doses of benzodiazepines. Further research will be useful in supporting the use of dexmedetomidine for this purpose. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The purpose of this study is to explore how representational paintings of radiology encounters with patients may impact medical students' understanding and impression of both radiologists and the radiology profession.Methods: Participants included third year medical students at a single institution rotating through a one-week radiology elective. Three works of art were analyzed using the validated Visual Thinking Strategies technique. Data collected included a postsession questionnaire and transcriptions of audio-recorded sessions. Data analysis involved both qualitative and quantitative methodology.Results: Fifty students participated; all participants completed the postsession questionnaire and 10 participated in the audio recorded sessions. Total 82% found the experience "very enjoyable" and 86% agreed that the paintings positively affected their understanding of how radiologists provide care to patients; 96% would recommend this session to others. Exploring representational paintings of radiology encounters seemed to influence perception and understanding of radiology with students reporting "light bulb moments;" create a dissonance between the student experience and the experience depicted in the paintings; and address gaps in content specific knowledge.Conclusion: The findings of this study suggest that analyzing paintings depicting radiology encounters with patients can challenge negative stereotypes that medical students have of the radiology profession and radiologists. This arts-based learning module employing a learning strategy such as Visual Thinking Strategies, should be considered by the radiology profession as a strategy to positively inform and educate trainees about the specialty. [ABSTRACT FROM AUTHOR]

Background: Individuals with developmental dysplasia of the hip (DDH) often report hip pain and exhibit gait adaptations. Previous studies in this patient population have focused on average kinematic and acceleration measures during gait, but have not examined variability.Research Question: Do individuals with hip pain and DDH have altered kinematic variability or local dynamic stability (LDS) compared to individuals without hip pain?Methods: Twelve individuals with hip pain and DDH and 12 matched controls walked for two minutes on a treadmill at three speeds: preferred, fast (25% faster than preferred), and prescribed (1.25 m/s). Kinematic variability of spatiotemporal measures, joint and segment angles, and LDS of the trunk were calculated for each speed.Results: At the prescribed speed, individuals with hip pain and DDH had more kinematic variability than controls at the hip, pelvis, and trunk as well as greater variability in spatiotemporal measures. LDS was not different between groups. Kinematic variability of the joints decreased and LDS of the trunk increased (i.e., increased gait stability) with increased speed.Significance: Individuals with hip pain and DDH had greater kinematic variability compared to individuals without hip pain when walking at the same prescribed speed, indicating either an adaptation to pain or reduced neuromuscular control. LDS of the trunk was not different between groups, suggesting that hip pain does not affect overall gait stability. Kinematic variability and LDS were affected by walking speed, but in different ways, emphasizing that these measures quantify different aspects of walking behavior. [ABSTRACT FROM AUTHOR]

Background Autologous hepatocyte transplantation after ex vivo gene therapy is an alternative to liver transplantation for metabolic liver disease. Here we evaluate ex vivo gene therapy followed by transplantation of single-cell or spheroid hepatocytes. Methods Pig and mouse hepatocytes were isolated, labeled with zirconium-89 and returned to the liver as single cells or spheroids. Biodistribution was evaluated through positron emission tomography–computed tomography. Fumarylacetoacetate hydrolase–deficient pig hepatocytes were isolated and transduced with a lentiviral vector containing the Fah gene. Animals received portal vein infusion of single-cell or spheroid autologous hepatocytes after ex vivo gene delivery. Portal pressures were measured and ultrasound was used to evaluate for thrombus. Differences in engraftment and expansion of ex vivo corrected single-cell or spheroid hepatocytes were followed through histologic analysis and animals’ ability to thrive off 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione. Results Positron emission tomography–computed tomography imaging showed spheroid hepatocytes with increased heterogeneity in biodistribution as compared with single cells, which spread more uniformly throughout the liver. Animals receiving spheroids experienced higher mean changes in portal pressure than animals receiving single cells ( P < .01). Additionally, two animals from the spheroid group developed portal vein thrombi that required systemic anticoagulation. Immunohistochemical analysis of spheroid- and single-cell–transplanted animals showed similar engraftment and expansion rates of fumarylacetoacetate hydrolase–positive hepatocytes in the liver, correlating with similar weight stabilization curves. Conclusion Ex vivo gene correction of autologous hepatocytes in fumarylacetoacetate hydrolase–deficient pigs can be performed using hepatocyte spheroids or single-cell hepatocytes, with spheroids showing a more heterogeneous distribution within the liver and higher risks for portal vein thrombosis and increased portal pressures. [ABSTRACT FROM AUTHOR]

Background Although high-intensity statin therapy (HIST) is recommended for most patients between 21 and 75 years of age with atherosclerotic cardiovascular disease (ASCVD), several recent analyses examining contemporary statin use trends have identified a clinical care gap in the utilization of HIST. Objective The objective of this study was to assess secular trends in lipid management for patients with ASCVD enrolled in a clinical pharmacy program within an integrated health care delivery system. Methods We performed serial cross-sectional studies over time, comprising 18,006 adults with both acute and chronic ASCVD, to assess trends in statin use and low-density lipoprotein cholesterol (LDL-C) levels from 2007 to 2016. Results Although the use of statin therapy (any intensity) remained relatively consistent throughout the 10-year study period (89% in 2007, 87% in 2016), the proportion of patients receiving HIST increased over time (44% in 2007, 67% in 2016; P < .001 for trend). Population mean LDL-C levels ranged from 73 to 83 mg/dL with a downward trend over the 10-year study period ( P < .001 for trend). By 2016, the proportion of patients attaining an LDL-C <100 mg/dL and <70 mg/dL was 85% and 54%, respectively. Nonstatin lipid-lowering therapy use decreased over the study period, which was primarily driven by decreased use of ezetimibe (24% in 2007, 2% in 2016; P < .001 for trend). Conclusions Among adults with ASCVD enrolled in a clinical pharmacy cardiac risk reduction service, guideline-directed use of HIST significantly increased over the past 10 years and coincided with decreased population LDL-C levels. [ABSTRACT FROM AUTHOR]

The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients. [ABSTRACT FROM AUTHOR]

Non-traditional learning (NTL), including aspects of self-directed learning (SDL), may address self-awareness development needs. Many factors can impact successful implementation of NTL. Objectives: To share our multi-year experience with modifications that aim to improve NTL sessions in a traditional curriculum. To improve understanding of applied implementation variables (some of which were based on successful SDL implementation components) that impact NTL. Methods: We delivered a single lesson in a traditional-delivery curriculum once annually for five years, varying delivery annually in response to student learning and reaction-to-learning results. At year 5, we compared student learning and reaction-to-learning to applied implementation factors using logistic regression. Results: Higher instructor involvement and overall NTL levels predicted correct exam responses (p=0.0007 and p<0.0001, respectively). Exam responses were statistically equivalent between the most traditional and highest overall NTL deliveries. Students rated instructor presentation skills and teaching methods higher when greater instructor involvement (p<0.0001, both) and lower overall NTL levels (P<0.0001, both) were used. Students perceived that teaching methods were most effective when lower student involvement and higher technology levels (p<0.0001, both) were used. Conclusion: When implementing NTL sessions as a single lesson in a traditional-delivery curriculum, instructor involvement appears essential, while the impact of student involvement and educational technology levels varies. [ABSTRACT FROM AUTHOR]

Spinetoram is a semi-synthetic, spinosyn class natural product derived from fermentation by the actinomycete, Saccharopolyspora spinosa . Based on LD 50 (50% lethal dose) values against adult cat fleas ( Ctenocephalides felis ) using an in vitro contact assay, spinetoram was approximately 4-fold more potent than spinosad. Subsequently, two parallel-arm, randomized block design laboratory studies were conducted to evaluate the effectiveness of orally administered spinetoram against experimental C. felis infestations on dogs, when administered as a single dose or multiple doses over a 6–12 h interval. In the first study, 16 mixed-breed dogs were allocated to two treatment groups of eight dogs each, based on pre-treatment flea retention rates: negative (placebo) control; and a single dose of spinetoram at 30 mg/kg. In the second study, 32 mixed- and pure-breed dogs were allocated to four treatments groups of eight dogs each, based on pre-treatment flea retention rates: negative (placebo) control; a single dose of 60 mg/kg; three sequential 20 mg/kg oral doses evenly administered over a 6 h period; and three sequential 20 mg/kg oral doses evenly administered over a 12 h period. In both studies, treatments were administered to dogs in a fed state in order to enhance absorption of spinetoram. Therapeutic efficacy was assessed 24 h after treatment and persistent efficacy was assessed 48 h after each subsequent flea infestation. The duration of effectiveness was assessed at approximate weekly intervals beginning on Day 5 through Day 56 in the first study, or through Day 105 in the second study. In both studies, treatment efficacy was ≥99% (geometric means) through 44 d, with ≥99% efficacy continuing through 72 d for all three treatments in the second study. Efficacy remained ≥90% for at least 8 weeks with a single 30 mg/kg dose; through 13 weeks with three sequential 20 mg/kg doses; and through 15 weeks with a single 60 mg/kg dose. For all time points and in both studies, spinetoram-treated groups had significantly fewer live fleas relative to their respective negative control group (p < 0.05). The pharmacokinetic profile in dogs revealed that the mean plasma concentration of spinetoram required for effectiveness against fleas was maintained for at least 3 months regardless of whether the 60 mg/kg total body dose was administered as a single bolus or in three sequential 20 mg/kg doses administered over a 6–12 h period of time. The results of preliminary in vitro and in vivo studies demonstrate that orally administered spinetoram was well tolerated, and provides long lasting effectiveness against C. felis infestations on dogs. [ABSTRACT FROM AUTHOR]

How canonical cytokinesis is altered during germ cell division to produce stable intercellular bridges, called "ring canals," is poorly understood. Here, using time-lapse imaging in Drosophila , we observe that ring canal formation occurs through extensive remodeling of the germ cell midbody, a structure classically associated with its function in recruiting abscission-regulating proteins in complete cytokinesis. Germ cell midbody cores reorganize and join the midbody ring rather than being discarded, and this transition is accompanied by changes in centralspindlin dynamics. The midbody-to-ring canal transformation is conserved in the Drosophila male and female germlines and during mouse and Hydra spermatogenesis. In Drosophila , ring canal formation depends on Citron kinase function to stabilize the midbody, similar to its role during somatic cell cytokinesis. Our results provide important insights into the broader functions of incomplete cytokinesis events across biological systems, such as those observed during development and disease states. [Display omitted] • Midbody core remodeling precedes formation of transient and stable germline ring canals • Ring canals originate from stabilized midbody rings • Aberrant midbody remodeling impacts ring canal formation and protein movement • Abscission inhibition stabilizes germ cell ring canals after they form Ring canals connect germ cells in syncytial groups and are necessary for gamete development. Price et al. show that ring canals form through the remodeling of germ cell midbodies in Drosophila , Hydra , and mouse. Perturbation of midbody formation and subsequent reorganization into ring canals affect communication between germ cells. [ABSTRACT FROM AUTHOR]

Background Hippocampal sharp-wave ripples (SWRs) arising from synchronous bursting in CA3 pyramidal cells and propagating to CA1 are thought to facilitate memory consolidation. Stimulation of the CA3 axon collaterals comprising the hippocampal commissure in rats interrupts sharp-wave ripples and leads to memory impairment. In primates, however, these commissural collaterals are limited. Other hippocampal fiber pathways, like the fornix, may be potential targets for modulating ongoing hippocampal activity, with the short latencies necessary to interrupt ripples. Objective The aim of this study is to determine the efficacy of closed-loop stimulation adjacent to the fornix for interrupting hippocampal ripples. Method Stimulating electrodes were implanted bilaterally alongside the fornix in the macaque, together with microelectrodes targeting the hippocampus for recording SWRs. We first verified that fornix stimulation reliably and selectively evoked a response in the hippocampus. We then implemented online detection and stimulation as hippocampal ripples occurred. Results The closed-loop interruption method was effective in interrupting ripples as well as the associated hippocampal multi-unit activity, demonstrating the feasibility of ripple interruption using fornix stimulation in primates. Conclusion Analogous to murine research, such an approach will likely be useful in understanding the role of SWRs in memory formation in macaques and other primates sharing these pathways, such as humans. More generally, closed-loop stimulation of the fornix may prove effective in interrogating hippocampal-dependent memory processes. Finally, this rapid, contingent-DBS approach may be a means for modifying pathological high-frequency events within the hippocampus, and potentially throughout the extended hippocampal circuit. [ABSTRACT FROM AUTHOR]

Assisted reproductive technologies (ARTs) utilize sperm sorting methods to select viable sperm from the semen samples. Conventional sperm sorting techniques in current use are density gradient centrifugation, direct swim-up, and conventional swim-up. These methods use multiple centrifugation steps, which have been shown to generate reactive oxygen species (ROS) that decrease DNA integrity and damage sperm. Newer technologies, such as microfluidics, electrophoresis, motile sperm organelle morphology examination (MSOME), and birefringence eliminate the centrifugation steps and can improve the selection of sperm with higher DNA integrity, normal morphology, and motility as well as improved artificial insemination outcomes. In this review, we discuss some recent research in centrifugation and non-centrifugation based techniques and their effect on sperm quality and ART outcomes. [ABSTRACT FROM AUTHOR]