Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson's disease.

OBJECTIVE: The globus pallidus internus (GPI) has been demonstrated to be an effective surgical target for deep brain stimulation (DBS) treatment in patients with medication-refractory Parkinson's disease (PD). The ability of neurosurgeons to define the area of greatest therapeutic benefit within the globus pallidus (GP) may improve clinical outcomes in these patients. The objective of this study was to determine the best DBS therapeutic implantation site within the GP for effective treatment in PD patients. METHODS: The authors performed a retrospective review of 56 patients who underwent bilateral GP DBS implantation at their institution during the period from January 2015 to January 2020. Each implanted contact was anatomically localized. Patients were followed for stimulation programming for at least 6 months. The authors reviewed preoperative and 6-month postsurgery clinical outcomes based on data from the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), dyskinesia scores, and levodopa equivalent daily dose (LEDD). RESULTS: Of the 112 leads implanted, the therapeutic cathode was most frequently located in the lamina between the GPI external segment (GPIe) and the GP externus (GPE) (n = 40). Other common locations included the GPE (n = 24), the GPIe (n = 15), and the lamina between the GPI internal segment (GPIi) and the GPIe (n = 14). In the majority of patients (73%) a monopolar programming configuration was used. At 6 months postsurgery, UPDRS III off medications (OFF) and on stimulation (ON) scores significantly improved (z = -4.02, p < 0.001), as did postsurgery dyskinesia ON scores (z = -4.08, p < 0.001) and postsurgery LEDD (z = -4.7, p < 0.001). CONCLUSIONS: Though the ventral GP (pallidotomy target) has been a commonly used target for GP DBS, a more dorsolateral target may be more effective for neuromodulation strategies. The assessment of therapeutic contact locations performed in this study showed that the lamina between GPI and GPE used in most patients is the optimal central stimulation target. This information should improve preoperative GP targeting.

Understanding costs and benefits of thermal plasticity for pest management: insights from the integration of laboratory, semi-field and field assessments of Ceratitis capitata (Diptera: Tephritidae).

The relative costs and benefits of thermal acclimation for manipulating field performance of pest insects depend upon a number of factors including which traits are affected and how persistent any trait changes are in different environments. By assessing plastic trait responses of Ceratitis capitata (Mediterranean fruit fly) across three distinct operational environments (laboratory, semi-field, and field), we examined the influence of different thermal acclimation regimes (cool, intermediate [or handling control], and warm) on thermal tolerance traits (chill-coma recovery, heat-knockdown time, critical thermal minimum and critical thermal maximum) and flight performance (mark-release-recapture). Under laboratory conditions, thermal acclimation altered thermal limits in a relatively predictable manner and there was a generally positive effect across all traits assessed, although some traits responded more strongly. By contrast, dispersal-related performance yielded strongly contrasting results depending on the specific operational environment assessed. In semi-field conditions, warm- or cold-acclimated flies were recaptured more often than the control group at cooler ambient conditions suggesting an overall stimulatory influence of thermal variability on low-temperature dispersal. Under field conditions, a different pattern was identified: colder flies were recaptured more in warmer field conditions relative to other treatment groups. This study highlights the trait- and context-specific nature of how thermal acclimation influences traits of thermal performance and tolerance. Consequently, laboratory and semi-field assessments of dispersal may not provide results that extend into the field setting despite the apparent continuum of environmental complexity among them (laboratory < semi-field < field).

Mitochondrial mutations alter endurance exercise response and determinants in mice.

Primary mitochondrial diseases (PMDs) are a heterogeneous group of metabolic disorders that can be caused by hundreds of mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes. Current therapeutic approaches are limited, although one approach has been exercise training. Endurance exercise is known to improve mitochondrial function in heathy subjects and reduce risk for secondary metabolic disorders such as diabetes or neurodegenerative disorders. However, in PMDs the benefit of endurance exercise is unclear, and exercise might be beneficial for some mitochondrial disorders but contraindicated in others. Here we investigate the effect of an endurance exercise regimen in mouse models for PMDs harboring distinct mitochondrial mutations. We show that while an mtDNA ND6 mutation in complex I demonstrated improvement in response to exercise, mice with a CO1 mutation affecting complex IV showed significantly fewer positive effects, and mice with an ND5 complex I mutation did not respond to exercise at all. For mice deficient in the nDNA adenine nucleotide translocase 1 (Ant1), endurance exercise actually worsened the dilated cardiomyopathy. Correlating the gene expression profile of skeletal muscle and heart with the physiologic exercise response identified oxidative phosphorylation, amino acid metabolism, matrisome (extracellular matrix [ECM]) structure, and cell cycle regulation as key pathways in the exercise response. This emphasizes the crucial role of mitochondria in determining the exercise capacity and exercise response. Consequently, the benefit of endurance exercise in PMDs strongly depends on the underlying mutation, although our results suggest a general beneficial effect.

Physical Activity Among Urban Children with Asthma: Does Sleep Matter?

The present study examined associations between sleep and physical activity among a diverse sample of 97 urban children (ages 7-9) with persistent asthma. Differences in associations were evaluated by race/ethnicity and weight status. The extent to which sleep moderated the association between lung function and physical activity was also evaluated. Generalized linear models were utilized to examine associations. Findings indicated that, among the aggregate sample, more frequent nighttime awakenings were associated with less time spent engaging in moderate-to-vigorous physical activity (MVPA). Important differences in these associations were identified by both race/ethnicity and weight status. Better lung function was associated with, (a) higher levels of MVPA for children with better sleep efficiency and fewer nighttime awakenings, and (b) lower levels of MVPA for children with poorer sleep efficiency and more frequent nighttime awakenings. In short, sleep mattered with respect to children's physical activity levels in this sample.

Are oral rehydration solutions optimized for treating diarrhea?

BACKGROUND: A historical turning point occurred in the treatment of diarrhea when it was discovered that glucose could enhance intestinal sodium and water absorption. Adding glucose to salt water (oral rehydration solution, ORS) more efficiently replaced intestinal water and salt losses. AIM: Provide a novel hypothesis to explain why mainstream use of ORS has been strongly recommended, but weakly adopted. METHODS: Traditional (absorptive) and novel (secretory) physiological functions of glucose in an ORS were reviewed. RESULTS: Small amounts of glucose can stimulate both intestinal absorption and secretion. Glucose can exacerbate a net secretory state and may aggravate pathogen-induced diarrhea, particularly for pathogens that affect glucose transport. CONCLUSION: A hypothesis is made to explain why glucose-based ORS does not appreciably reduce diarrheal stool volume and why modern food science initiatives should focus on ORS formulations that replace water and electrolytes while also reducing stool volume and duration of diarrhea.

Randomized Study of enterade® to Reduce Diarrhea in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation.

High-dose chemotherapy frequently causes injury to the gastrointestinal mucosa, resulting in diarrhea. The purpose of the current study was to assess the tolerability and efficacy of enterade® in reducing ≥ grade 2 diarrhea (G2D) in association with high-dose melphalan followed by autologous stem cell transplantation (ASCT). We conducted a prospective, double blinded, multi-center trial in which 114 subjects were randomized to receive enterade® or placebo twice daily during the transplant hospitalization. Gastrointestinal toxicities (nausea, vomiting, oral mucositis and dysphagia) resulted in poor study compliance in both arms. Among subjects who were able to complete planned therapy (13%), the incidence of G2D was lower for those receiving enterade® as compared to placebo (16% vs 86%, p <0.03). Twice daily oral administration of enterade® and placebo following high-dose chemotherapy and ASCT was not feasible due to significant gastrointestinal toxicities.  Future explorations of enterade® should be conducted in populations capable of reasonable oral intake.
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Heat Acclimation Improves Heat Tolerance Test Specificity in a Criteria-dependent Manner.

PURPOSE: This study aimed to characterize HTT specificity and to determine any effect of HA on the outcome. METHODS: Thirteen unacclimatized, healthy men (V˙O2peak, 43.0 ± 4.8 mL·kg-1⋅min-1) with no previous history of heat illness completed 8 d of HA using the HTT protocol (40°C/40% RH; 120 min; 5 km·h-1 and 2% grade). Heart rate (HR) and core temperature (Tcore) recorded every 5 min during exercise and at the end of 120 min (terminal value) were compared between days 1 and 8. Test specificity (given no previous history of heat illness, the probability of being heat tolerant) was calculated on days 1 and 8. RESULTS: There was a significant reduction in HR and Tcore between days 1 and 8, indicating successful HA. All volunteers successfully completed 120 min of walking on all days. HTT specificity ranged between 54% and 85% on day 1 and between 77% and 92% on day 8, depending on the HTT criteria used. CONCLUSION: Young healthy men without any previous heat illness experienced a 15% to 46% false-positive fail rate for the HTT without HA. After HA, the false-positive fail rate decreased to between 8% and 13%. Outcomes of the HTT are significantly affected by the criteria used and by HA status. The use of HTT for RTA decisions should be done with the recognition of these effects.

Inhibition of GCK-IV kinases dissociates cell death and axon regeneration in CNS neurons.

Axon injury is a hallmark of many neurodegenerative diseases, often resulting in neuronal cell death and functional impairment. Dual leucine zipper kinase (DLK) has emerged as a key mediator of this process. However, while DLK inhibition is robustly protective in a wide range of neurodegenerative disease models, it also inhibits axonal regeneration. Indeed, there are no genetic perturbations that are known to both improve long-term survival and promote regeneration. To identify such a neuroprotective target, we conducted a set of complementary high-throughput screens using a protein kinase inhibitor library in human stem cell-derived retinal ganglion cells (hRGCs). Overlapping compounds that promoted both neuroprotection and neurite outgrowth were bioinformatically deconvoluted to identify specific kinases that regulated neuronal death and axon regeneration. This work identified the role of germinal cell kinase four (GCK-IV) kinases in cell death and additionally revealed their unexpected activity in suppressing axon regeneration. Using an adeno-associated virus (AAV) approach, coupled with genome editing, we validated that GCK-IV kinase knockout improves neuronal survival, comparable to that of DLK knockout, while simultaneously promoting axon regeneration. Finally, we also found that GCK-IV kinase inhibition also prevented the attrition of RGCs in developing retinal organoid cultures without compromising axon outgrowth, addressing a major issue in the field of stem cell-derived retinas. Together, these results demonstrate a role for the GCK-IV kinases in dissociating the cell death and axonal outgrowth in neurons and their druggability provides for therapeutic options for neurodegenerative diseases.

Effect of 8 days of exercise-heat acclimation on aerobic exercise performance of men in hypobaric hypoxia.

Exercise-heat acclimation (EHA) induces adaptations that improve tolerance to heat exposure. Whether adaptations from EHA can also alter responses to hypobaric hypoxia (HH) conditions remains unclear. This study assessed whether EHA can alter time-trial performance and/or incidence of acute mountain sickness (AMS) during HH exposure. Thirteen sea-level (SL) resident men [SL peak oxygen consumption (V̇o2peak) 3.19 ± 0.43 L/min] completed steady-state exercise, followed by a 15-min cycle time trial and assessment of AMS before (HH1; 3,500 m) and after (HH2) an 8-day EHA protocol [120 min; 5 km/h; 2% incline; 40°C and 40% relative humidity (RH)]. EHA induced lower heart rate (HR) and core temperature and plasma volume expansion. Time-trial performance was not different between HH1 and HH2 after 2 h (106.3 ± 23.8 vs. 101.4 ± 23.0 kJ, P = 0.71) or 24 h (107.3 ± 23.4 vs. 106.3 ± 20.8 kJ, P > 0.9). From HH1 to HH2, HR and oxygen saturation, at the end of steady-state exercise and time-trial tests at 2 h and 24 h, were not different (P > 0.05). Three of 13 volunteers developed AMS during HH1 but not during HH2, whereas a fourth volunteer only developed AMS during HH2. Heat shock protein 70 was not different from HH1 to HH2 at SL [1.9 ± 0.7 vs. 1.8 ± 0.6 normalized integrated intensities (NII), P = 0.97] or after 23 h (1.8 ± 0.4 vs. 1.7 ± 0.5 NII, P = 0.78) at HH. Our results indicate that this EHA protocol had little to no effect-neither beneficial nor detrimental-on exercise performance in HH. EHA may reduce AMS in those who initially developed AMS; however, studies at higher elevations, having higher incidence rates, are needed to confirm our findings.

Hard palate defect repair by using haired angularis oris axial pattern flaps in dogs.

OBJECTIVE: To describe the repair of large hard palate defects with a haired angularis oris axial pattern flap (HAOF) and to report the postoperative outcome. STUDY DESIGN: Anatomical cadaver study and short case series. ANIMALS: One cadaver and three dogs with neoplasia of the caudal hard palate. METHODS: Large caudal and central hard palate defects were reconstructed by using the HAOF. The flap, composed of full-thickness skin and buccal mucosa, was rotated at the base of the angularis oris artery. The haired surface of the skin flap was placed facing into the oral cavity. RESULTS: Reconstruction of defects extending as far rostral as the maxillary canine tooth were feasible on the cadaver. The flap in dog 1 healed without complication and was intact at day 649 after surgery. Two minor areas of dehiscence were noted in dog 2, without further evidence of complications at 1331 days after surgery. Dog 3 had upper respiratory obstructive noise due to swelling immediately after surgery. These signs resolved, but local recurrence of the tumor prompted euthanasia at day 86. CONCLUSION: Anatomical studies provide evidence that the HAOF can be used to reconstruct caudal and central hard palate defects extending to the maxillary canine teeth. Its clinical use led to successful closure of such defects in three dogs. CLINICAL SIGNIFICANCE: HAOF provides an alternative for reconstruction of large defects of the caudal and central hard palate.

Potential for dehydration to impact the athlete biological passport.

In order to inform the Athlete Biological Passport (ABP), this study determined whether the elevation in hemoglobin (Hb) following intracellular or extracellular dehydration would trigger an atypical passport finding (ATPF). Seven male and three female volunteers (age: 23 ± 4 y; height: 170 ± 8 cm; body mass: 78 ± 12 kg) were carefully euhydrated (EUH) to determine baseline Hb levels. Volunteers then completed both an exercise-induced sweating dehydration (SW) protocol and a diuretic-induced dehydration (DI) protocol. Dehydration was assessed via body mass changes and Hb was measured via a bench-top automated hematology analyzer. Using the ABP module, the expected baseline range for each individual was determined using EUH trials, and the impact of each dehydration protocol was then assessed in comparison with these thresholds. Volunteers lost on average 3.1% and 3.7% body mass in the SW and DI trials, respectively. While only one subject exceeded the upper threshold following DI dehydration, six additional subjects demonstrated highly unusual ABP profiles; this was not the case for SW. Sweating is not a feasible explanation for elevated Hb during ABP testing; however, recent illness such as secretory diarrhea, which is mimicked by diuretic administration, may be capable of producing elevated Hb in athletes' biological passports.

Influence of Acetazolamide on Hand Strength and Manual Dexterity During a 30-h Simulated High Altitude Exposure.

INTRODUCTION: High altitude missions pose significant challenges to Warfighter medical readiness and performance. Decreased circulating oxygen levels cause a decrease in exercise performance and can cause debilitating symptoms associated with acute mountain sickness, especially with rapid ascent. Acetazolamide (AZ) is known to minimize symptoms of acute mountain sickness, but it is unknown whether this medication alters hand strength and manual dexterity during altitude exposure. MATERIALS AND METHODS: Ten male volunteers (22 ± 4 yr, 75.9 ± 13.7 kg, 174.9 ± 9.3 cm) participated in two separate 30 h simulated altitude exposures (496 mmHg, equivalent to 3,500 m, 20°C, 20% RH) in a hypobaric chamber. Participants were given either a placebo or 250 mg of AZ twice daily for 3.5 d (2 sea-level [SL] days + the 30 h altitude exposure) in a randomized, single-blind, crossover design. During SL and both altitude (ALT) exposures, hand function tests were performed, including hand grip and finger pinch strength tests, as well as the Purdue Pegboard (PP) and magazine loading tests to assess manual dexterity. Paired T tests and two-way repeated measure analysis of variance were used as appropriate to evaluate the effects of AZ and ALT. The value of p < 0.05 was accepted for statistical significance. RESULTS: There were no influences of acute ALT exposure or AZ treatment on hand strength (eg, grip strength; SL: 39.2 ± 5.5 kg vs. ALT: 41.5 ± 6.9 kg, p > 0.05) or dexterity (eg, PPassembly; placebo: 35.5 ± 5.3 vs. AZ: 34.3 ± 4.6, p > 0.05) in our volunteers. Two dexterity tests (PPsum and magazine loading) showed improvements over time at ALT, regardless of treatment, where scores were improved after 10 h of exposure compared to at 1 h (eg, magazine loading: 56 ± 12 vs. 48 ± 10, p < 0.001). This pattern was not seen in the PPassembly test or any strength measurements. CONCLUSIONS: Our results suggest that 500 mg/d of AZ does not influence hand strength or manual dexterity during a 30 h exposure to 3,500 m simulated ALT. Acute ALT exposure (1 h) did not influence dexterity or strength, although some measures of dexterity showed improvements as exposure time increased. We conclude that use of AZ to optimize medical readiness at ALT is unlikely to impair the Warfighter's ability to complete mission tasks that depend on hand function.

Acetazolamide does not alter endurance exercise performance at 3,500-m altitude.

Acetazolamide (AZ) is a medication commonly used to prevent acute mountain sickness (AMS) during rapid ascent to high altitude. However, it is unclear whether AZ use impairs exercise performance; previous literature regarding this topic is equivocal. The purpose of this study was to evaluate the impact of AZ on time-trial (TT) performance during a 30-h exposure to hypobaric hypoxia equivalent to 3,500-m altitude. Ten men [sea-level peak oxygen consumption (VO2peak): 50.8 ± 6.5 mL·kg-1·min-1; body fat %: 20.6 ± 5.2%] completed 2 30-h exposures at 3,500 m. In a crossover study design, subjects were given 500 mg/day of either AZ or a placebo. Exercise testing was completed 2 h and 24 h after ascent and consisted of 15-min steady-state treadmill walking at 40%-45% sea-level VO2peak, followed by a 2-mile self-paced treadmill TT. AMS was assessed after ~12 h and 22 h at 3,500 m. The incidence of AMS decreased from 40% with placebo to 0% with AZ. Oxygen saturation was higher (P < 0.05) in AZ versus placebo trials at the end of the TT after 2 h (85 ± 3% vs. 79 ± 3%) and 24 h (86 ± 3% vs. 81 ± 4%). There was no difference in time to complete 2 miles between AZ and PL after 2 h (20.7 ± 3.2 vs. 22.7 ± 5.0 min, P > 0.05) or 24 h (21.5 ± 3.4 vs. 21.1 ± 2.9 min, P > 0.05) of exposure to altitude. Our results suggest that AZ (500 mg/day) does not negatively impact endurance exercise performance at 3,500 m.NEW & NOTEWORTHY To our knowledge, this is the first study to examine the impact of acetazolamide (500 mg/day) versus placebo on self-paced, peak-effort exercise performance using a short-duration exercise test in a hypobaric hypoxic environment with a repeated-measures design. In the present study, acetazolamide did not impact exercise performance after 2-h or 24-h exposure to 3,500-m simulated altitude.

Influences of hypobaric hypoxia on skin blood flow and sweating responses during exercise in neutral and hot environments.

Exposure to hot environments augments cutaneous vasodilation and sweating during exercise compared with these responses in cooler environments. The effects of hypobaric hypoxia on these responses are less clear, as are the effects of heat and simulated altitude combined. We evaluated the individual and potential additive effects of environmental heat and hypobaric hypoxia on skin blood flow and sweating responses during exercise. Thirteen volunteers (11 M, 2 F; age 25.3 ± 6.1 yr; height 177 ± 9 cm; weight 81.2 ± 16.8 kg) completed 30 min of steady-state (SS) exercise on a cycle ergometer at 50% V̇o2peak during four separate conditions: 1) sea level thermoneutral (SLTN; 250 m, 20°C, 30-50% RH), 2) sea level hot (SLH; 250 m, 35°C, 30% RH), 3) simulated altitude thermoneutral (ATN; 3,000 m, 20°C, 30-50% RH), and 4) simulated altitude hot (AH; 3,000 m, 35°C, 30% RH). Skin blood flow and local sweating rate (LSR) were recorded on the ventral forearm. During exercise, SS cutaneous vascular conductance in AH (63 ± 31% peak) and SLH (52 ± 19% peak) were significantly higher than both SLTN (20 ± 9% peak, P < 0.001) and ATN (25 ± 12% peak, P < 0.05) but were not different from each other (P > 0.05). SS LSR was similarly increased in the hot environments but unaffected by simulated altitude. We propose that multiple antagonistic mechanisms during exposure to 3,000-m simulated altitude result in no net effect on skin blood flow or sweating responses during exercise in thermoneutral or hot environments.

Use of the heat tolerance test to assess recovery from exertional heat stroke.

Exercise or work in hot environments increases susceptibility to exertional heat illnesses such as exertional heat stroke (EHS). EHS occurs when body heat gain exceeds body heat dissipation, resulting in rapid body heat storage and potentially life-threatening consequences. EHS poses a dangerous threat for athletes, agriculture workers, and military personnel, as they are often exposed to hot environmental conditions that restrict body heat loss or contribute to body heat gain. Currently, there is limited guidance on return to activity (RTA) after an episode of EHS. While examining biomarkers in the blood is thought to be beneficial for determining RTA, they are not sensitive or specific enough to be a final determining factor as organ damage may persist despite blood biomarkers returning to baseline levels. As such, additional assessment tests to more accurately determine RTA are desired. One method used for determining RTA is the heat tolerance test (HTT, 120 minutes treadmill walking; 40°C, 40% relative humidity). Unfortunately, the HTT provides even less information about EHS recovery since it offers no test sensitivity or specificity even after years of implementation. We provide an overview of the HTT and the controversy of this test with respect to assessment criteria, applicability to tasks involving high metabolic workloads, and the lack of follow-up analyses to determine its accuracy for determining recovery in order to diminish the likelihood of a second EHS occurrence.

Separate and combined influences of heat and hypobaric hypoxia on self-paced aerobic exercise performance.

Heat and hypobaric hypoxia independently compromise exercise performance; however, their combined impact on exercise performance has yet to be quantified. This study examined the effects of heat, hypobaric hypoxia, and the combination of these environments on self-paced cycling time trial (TT) performance. Twelve subjects [2 female, 10 male; sea level (SL) peak oxygen consumption (V̇o2peak), 41.5 ± 4.4 mL·kg-1·min-1, mean ± SD] completed 30 min of steady-state cycling exercise (50% SL V̇o2peak), followed by a 15-min self-paced TT in four environmental conditions: SL thermoneutral [SLTN; 250 m, 20°C, 30-50% relative humidity (rh)], SL hot (SLH; 250 m, 35°C, 30% rh), hypobaric hypoxia thermoneutral (HTN; 3,000 m, 20°C, 30-50% rh), and hypobaric hypoxia hot (HH; 3,000 m, 35°C, 30% rh). Performance was assessed by the total work (kJ) completed. TT performance was lower (P < 0.05) in SLH, HTN, and HH relative to SLTN (-15.4 ± 9.7, -24.1 ± 16.2, and -33.1 ± 13.4 kJ, respectively). Additionally, the total work completed in HTN and HH was lower (P < 0.05) than that in SLH. In SLH, HTN, and HH, work rate was reduced versus SLTN (P < 0.05) within the first 3 min of exercise and was consistent for the remainder of the bout. No differences (P > 0.05) existed for heart rate or Ratings of Perceived Exertion at the end of exercise among conditions. The decrease in self-paced TT performance in the heat and/or hypobaric hypoxia conditions compared with SLTN conditions resulted from a nearly immediate reduction in work rate that may have been regulated by environmentally induced changes in physiological strain and perception of effort in response to TT exercise.NEW & NOTEWORTHY This is the first known study to examine the combined effects of heat and hypobaric hypoxia on short-duration self-paced cycling time trial performance. Regardless of environmental condition, subjects utilized an even work rate for the entire duration of the time trial. The presence of both environmental stressors led to a greater performance impairment than heat or hypobaric hypoxia alone, and the performance decrement stemmed from an early reduction of work rate.

Cool storage of Queensland fruit fly pupae for improved management of mass production schedules.

BACKGROUND: Cool storage is a valuable means of manipulating insect development time. The Queensland fruit fly (Q-fly) is Australia's most economically significant pest of fruit crops. The present study investigates cool storage of Q-fly pupae for increasing production flexibility for sterile insect technique programs. Development time, survival and fly quality were assessed following continuous storage of 1-day-old pupae at temperatures ranging from 13 to 25 °C. RESULTS: Survival was reduced almost to zero by pupal storage at 13 and 15 °C, was greatly reduced by storage at 17 °C, and was modestly reduced by storage at 19 °C. Pupal development time was extended by 16 days at 17 °C and by 9 days at 19 °C. Cool storage negatively affected flight ability and depleted lipid reserves. Cool storage at 19 °C enhanced the ability of 3-day-old adults to recover from chill-coma compared to control flies, indicating cold acclimation. CONCLUSION: There is potential for use of cool storage in Q-fly mass rearing, especially to improve alignment between production and field releases. For the purpose of delaying the development time of Q-fly pupae with minimal quality reduction, storage at 23 °C is recommended for 1-day-old pupae. © 2019 Society of Chemical Industry.

Role of SARM1 and DR6 in retinal ganglion cell axonal and somal degeneration following axonal injury.

Optic neuropathies such as glaucoma are characterized by the degeneration of retinal ganglion cells (RGCs) and the irreversible loss of vision. In these diseases, focal axon injury triggers a propagating axon degeneration and, eventually, cell death. Previous work by us and others identified dual leucine zipper kinase (DLK) and JUN N-terminal kinase (JNK) as key mediators of somal cell death signaling in RGCs following axonal injury. Moreover, others have shown that activation of the DLK/JNK pathway contributes to distal axonal degeneration in some neuronal subtypes and that this activation is dependent on the adaptor protein, sterile alpha and TIR motif containing 1 (SARM1). Given that SARM1 acts upstream of DLK/JNK signaling in axon degeneration, we tested whether SARM1 plays a similar role in RGC somal apoptosis in response to optic nerve injury. Using the mouse optic nerve crush (ONC) model, our results show that SARM1 is critical for RGC axonal degeneration and that axons rescued by SARM1 deficiency are electrophysiologically active. Genetic deletion of SARM1 did not, however, prevent DLK/JNK pathway activation in RGC somas nor did it prevent or delay RGC cell death. These results highlight the importance of SARM1 in RGC axon degeneration and suggest that somal activation of the DLK/JNK pathway is activated by an as-yet-unidentified SARM1-independent signal.

Efficacy of Glucose or Amino Acid-Based Commercial Beverages in Meeting Oral Rehydration Therapy Goals After Acute Hypertonic and Isotonic Dehydration.

BACKGROUND: The efficacy of different commercial beverage compositions for meeting oral rehydration therapy (ORT) goals in the treatment of acute dehydration in healthy humans has not been systematically tested. The objective of the study was to compare fluid retention, plasma volume (PV), and interstitial fluid (ISF) volume restoration when using 1 popular glucose-based and 1 novel amino acid-based (AA) commercial ORT beverage following experimental hypertonic or isotonic dehydration. METHODS: Twenty-six healthy adults (21 males, 5 females) underwent either a controlled bout of hypertonic (n = 13) or isotonic (n = 13) dehydration (3%-4% body mass) via eccrine or renal body water and electrolyte losses induced using exercise-heat stress (EHS) or Lasix administration (LAS), respectively. Rehydration was achieved over 90 minutes by matching fluid intake to water losses (1:1) using a sports drink (SP) or AA commercial ORT beverage. Fluid retention (water and electrolytes), PV, and ISF volume changes were tracked for 180 minutes. RESULTS: AA produced significantly (P <0.05) greater fluid retention (75% vs 57%), ISF volume restoration, and tended (P = 0.06) to produce greater PV restoration in trial EHS. In trial LAS, neither beverage exceeded 65% retention, but AA replaced electrolytes and preserved ISF volume better than SP (P <0.05). CONCLUSION: The results of this study demonstrate superior rehydration when using AA compared with SP for both hypertonic and isotonic dehydration.

A systematic review of the state of the literature on sexually exploited boys internationally.

This systematic review assessed the current state of the literature on sexually exploited boys internationally. We aimed to describe what is known about sexual exploitation of boys, identify gaps in the literature, provide implications for practice, and make recommendations for future research. Multiple database searches were conducted using a combination of controlled vocabulary and keywords to capture child and adolescent sexual exploitation. Our search identified 11,099 unique references and excluded studies that did not include male participants less than 18 years old or disaggregate results by relevant age groups and/or by sex. This review identified 42 studies from 23 countries, providing evidence that sexual exploitation of boys is an issue in both high- and low-income countries. Seventeen articles had sexual exploitation as their primary variable of interest, the majority of which sampled boys who accessed services (i.e., shelters, health care, social, and justice services). Boys' experiences of sexual exploitation varied in terms of venue, exploiters, and compensation. Compared to their non-sexually exploited peers, sexually exploited boys more commonly reported experiences of child abuse, substance use, conduct problems, and mental health problems such as anxiety, depression, and self-harm. Despite increasing evidence that boys are sexually exploited around the world, the current literature provides limited data about the antecedents, sequelae, and the specific features of sexual exploitation experiences among boys. Further research is needed to inform, policy, social services and health care delivery specific to the needs of sexually exploited boys.