Fibrous Osteodystrophy,Chronic Renal Disease,and Uterine Adenocarcinoma in Aged Gray Mouse Lemurs (Microcebus murinus)

The gray mouse lemur (Microcebus murinus, GML) is a nocturnal, arboreal, prosimian primate that is native to Madagascar. Captive breeding colonies of GMLs have been established primarily for noninvasive studies on questions related to circadian rhythms and metabolism. GMLs are increasingly considered to be a strong translational model for neurocognitive aging due to overlapping histopathologic features shared with aged humans. However, little information is available describing the clinical presentations, naturally occurring diseases, and histopathology of aged GMLs. In our colony, a 9 y-old, male, GML was euthanized after sudden onset of weakness, lethargy, and tibial fracture. Evaluation of this animal revealed widespread fibrous osteodystrophy (FOD) of the mandible, maxilla, cranium, appendicular, and vertebral bones. FOD and systemic metastatic mineralization were attributed to underlying chronic renal disease. Findings in this GML prompted periodic colony-wide serum biochemical screenings for azotemia and electrolyte abnormalities. Subsequently, 3 additional GMLs (2 females and 1 male) were euthanized due to varying clinical and serum biochemical presentations. Common to all 4 animals were FOD, chronic renal disease, uterine adenocarcinoma (females only), cataracts, and osteoarthritis. This case study highlights the concurrent clinical and histopathologic abnormalities that are relevant to use of GMLs in the expanding field of aging research.

Within the past 5 y, recognition of the translational utility of the gray mouse lemur (Microcebus murinus, GML) has greatly expanded, in part due to the sequencing of its genome.²⁷ GMLs have been proposed as an animal model in the context of aging research,^14,35 most notably within the fields of Alzheimer disease and dementia^33,39 and circadian rhythms.^15,20 GMLs are nocturnal, arboreal, prosimian primates (family Cheirogaleidae) that are endemic to Madagascar. They are among the smallest primates, with a body weight of 49 to 80 g in the wild³⁷ (60 to 110 g in captivity) and have a life expectancy of approximately 8 to 10 y in captivity.¹⁴ A small number of captive breeding colonies have been established throughout Europe and the United States, many of which have arisen from a closed captive breeding colony at the Muséum National d''Histoire Naturelle (MNHN) in Brunoy, France.Despite an ever-growing interest in the GML as a model organism, clinical and pathologic case reports focusing on naturally occurring disease are rare for this species.^{1,4,10,16,17,20,28,31,34,38} Reports of spontaneous disease often focus on neoplasia^28,31,34 or on ocular abnormalities, which are accessible without invasive interventions.^1,4,12 Apart from age-related neurodegenerative disease and cognitive impairment,^{5,23,25,26,32,36} little is known about the natural disease predilection and histologic aging phenotypes of GMLs.In June 2017, a 9 y-old male GML was euthanized after the sudden onset of weakness, lethargy, and tibial fracture. Necropsy and histopathology revealed chronic renal disease, widespread fibrous osteodystrophy (FOD), and systemic metastatic mineralization. These findings prompted colony-wide serum biochemical screenings for potential underlying renal disease and subsequent metabolic bone disease within the population.Herein, we report the clinical, gross, and histologic multisystemic pathology of 4 aged GMLs. This is the first documentation of FOD secondary to chronic renal disease in GMLs in a captive research colony. In addition, we corroborate previous reports^31,34 of uterine adenocarcinoma in aged female GMLs. Together, these findings aid in providing appropriate clinical care to GMLs as their use in the field of aging research continues to expand.     

Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption

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Evidence for Exploitative Competition: Comparative Foraging Behavior and Roosting Ecology of Short-Tailed Fruit Bats (Phyllostomidae)

Chestnut short-tailed bats, Carollia castanea , and Seba's short-tailed bats, C. perspicillata (Phyllostomidae), were radio-tracked ( N = 1593 positions) in lowland rain forest at Tiputini Biodiversity Station, Orellana Province, Ecuador. For 11 C . castanea , mean home range was 6.8 ± 2.2 ha, mean core-use area was 1.7 ± 0.8 ha, and mean long axis across home range was 438 ± 106 m. For three C . perspicillata , mean home range was 5.5 ± 1.7 ha, mean core-use area was 1.3 ± 0.6 ha, and mean long axis was 493 ± 172 m. Groups of less than five C. castanea occupied day-roosts in earthen cavities that undercut banks the Tiputini River. Carollia perspicillata used tree hollows and buildings as day-roosts. Interspecific and intraspecific overlap among short-tailed bats occurred in core-use areas associated with clumps of fruiting Piper hispidum (peppers ) and Cecropia sciadophylla . Piper hispidum seeds were present in 80 percent of the fecal samples from C . castanea and 56 percent of samples from C . perspicillata . Carollia perspicillata handled pepper fruits significantly faster than C . castanea ; however, C . castanea commenced foraging before C . perspicillata emerged from day-roosts. Evidence for exploitative competition between C . castanea and C . perspicillata is suggested by our observations that 95 percent of ripe P . hispidum fruits available at sunset disappear before sunrise ( N = 74 marked fruits). Piper hispidum plants produced zero to 12 ripe infructescences per plant each night during peak production. Few ripe infructescences of P . hispidum were available during the dry season; however, ripe infructescences of C . sciadophylla , remained abundant.     

Energy charge regulation in photosynthetic bacteria

The “energy charge” concept suggests that the relative concentrations of adenylate nucleotides in cellular pools define a signal system that is important in the regulation, and integration, of energy conversion and biosynthesis in growing cells. The results of experiments in which photosynthetic bacteria are subjected to treatments that could be expected to disturb the “normal” energy charge can be reasonably interpreted in terms of “energy charge control.”     

Postoperative outcomes for Indigenous Peoples in Canada: a systematic review

Background:Substantial health inequities exist for Indigenous Peoples in Canada. The remote and distributed population of Canada presents unique challenges for access to and use of surgery. To date, the surgical outcome data for Indigenous Peoples in Canada have not been synthesized.Methods:We searched 4 databases to identify studies comparing surgical outcomes and utilization rates of adults of First Nations, Inuit or Métis identity with non-Indigenous people in Canada. Independent reviewers completed all stages in duplicate. Our primary outcome was mortality; secondary outcomes included utilization rates of surgical procedures, complications and hospital length of stay. We performed meta-analysis of the primary outcome using random effects models. We assessed risk of bias using the ROBINS-I tool.Results:Twenty-eight studies were reviewed involving 1 976 258 participants (10.2% Indigenous). No studies specifically addressed Inuit or Métis populations. Four studies, including 7 cohorts, contributed adjusted mortality data for 7135 participants (5.2% Indigenous); Indigenous Peoples had a 30% higher rate of death after surgery than non-Indigenous patients (pooled hazard ratio 1.30, 95% CI 1.09–1.54; I² = 81%). Complications were also higher for Indigenous Peoples, including infectious complications (adjusted OR 1.63, 95% CI 1.13–2.34) and pneumonia (OR 2.24, 95% CI 1.58–3.19). Rates of various surgical procedures were lower, including rates of renal transplant, joint replacement, cardiac surgery and cesarean delivery.Interpretation:The currently available data on postoperative outcomes and surgery utilization rates for Indigenous Peoples in Canada are limited and of poor quality. Available data suggest that Indigenous Peoples have higher rates of death and adverse events after surgery, while also encountering barriers accessing surgical procedures. These findings suggest a need for substantial re-evaluation of surgical care for Indigenous Peoples in Canada to ensure equitable access and to improve outcomes. Protocol registration:PROSPERO-CRD42018098757

Safe, timely and affordable access to surgical care is essential to overall population health, as conditions amenable to surgical intervention account for one-third of the global burden of disease.^1,2 Surgery is responsible for 65% of cancer cure and control, it is key to trauma management, and access to cesarean delivery reduces neonatal deaths by up to 70%.¹ The magnitude and ubiquity of surgical conditions makes tracking their prevalence and treatment within local and national monitoring systems essential to fully capture the health and welfare of populations in Canada, including Indigenous Peoples.About 1.67 million people in Canada are Indigenous, representing 4.9% of the total population (58% First Nations, 4% Inuit, 35% Métis).³ Health inequities exist for the Indigenous population; life expectancy at birth is 5–11 years shorter than for non-Indigenous Peoples^4,5 and higher rates of communicable and noncommunicable diseases, unintentional injury and suicide are well documented.^4,6–14 These health inequities are direct impacts of the social determinants of health, which are in turn effects of colonialism and government policies, including the Indian residential school system.^8,11 People living in remote regions have less access to publicly funded health care than other people in Canada, with worse outcomes.¹⁵Given the substantial impact of surgical disease on population health and the recognized disparities in health care access for Indigenous Peoples in Canada, understanding access to surgical services and subsequent outcomes is a key step to addressing health inequities. To date, limited research has been conducted on surgical and postoperative care involving Indigenous Peoples in Canada and the available literature has not been synthesized. Our objective was to systematically review studies comparing postoperative outcomes between Indigenous and non-Indigenous Peoples in Canada.     

Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai,Uganda: A pragmatic,cluster-randomized trial

BackgroundEffective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called “Health Scouts” to promote engagement in HIV treatment and prevention services.Methods and findingsThe study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV–positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV–positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect.ConclusionsA novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02556957","term_id":"NCT02556957"}}NCT02556957.

Larry Chang and co-workers study an intervention by which community health workers aim to promote engagement in HIV treatment and prevention services in Uganda.     

Interactions between hymenopteran species associated with gall-forming wasps: the Leptocybe invasa community as a case study

1. Leptocybe invasa is native to Australia and induces galls on various species of Eucalyptus. Two genetically distinct lineages of this wasp have been detected outside its native range, namely, Leptocybe Lineage A and Leptocybe Lineage B.
2. The parasitoid Selitrichodes neseri was released in South Africa as a biological control agent against L. invasa. Another parasitoid of L. invasa, Quadrastichus mendeli, as well as Megastigmus zebrinus (parasitoid) and Megastigmus pretorianensis (role unknown), have also been recorded emerging from L. invasa galls. The objective of this study was to investigate the interactions between the different hymenopterans associated with L. invasa galls in South Africa.
3. L. invasa galls were dissected and species-specific primers and restriction enzymes were used to identify the larvae where interactions were noted.
4. S. neseri, Q. mendeli and M. zebrinus were confirmed to parasitize Leptocybe Lineage A, and S. neseri was confirmed to parasitize Leptocybe Lineage B. Furthermore, there were direct interactions between these parasitoids, where parasitoids were found parasitising each other. The gall forming experiment confirmed that M. pretorianensis is not a gall former, but other potential roles remain uncertain.