Alternatively activated myeloid (M2) cells enhance cognitive function in immune compromised mice

It was recently shown that adaptive immunity plays a key role in cognitive function. T cells appear to be major players in learning and memory; thus, mice devoid of functional T cells are impaired in performance of cognitive tasks such as Morris water maze (MWM), Barnes maze and others. This is a reversible phenomenon; injection of immune deficient mice with T cells from wild type counterparts improves their cognitive function. Recently we described a critical role for T cell-derived IL-4 as having beneficial effects on learning and memory through regulation of meningeal myeloid cell phenotype. In the absence of IL-4, meningeal myeloid cells acquire a pro-inflammatory skew. Thus, the presence of IL-4 in the meningeal spaces maintains a delicate balance of pro- and anti-inflammatory myeloid cell phenotype. Here we show that macrophages alternatively activated in vitro (M2 cells) can circumvent the need for ‘pro-cognitive’ T cells when injected intravenously into immune deficient mice. These results show for the first time that M2 myeloid cells are new and unexpected players in cognitive function, conferring beneficial effects on learning and memory without adaptive immune influence. These results might lead to development of new therapeutic approaches for cognitive pathologies associated with malfunction of adaptive immunity, such as chemo-brain, age-related dementia, HIV-dementia, and others.     

Role of Social Support in the Relationship between Sexually Transmitted Infection and Depression among Young Women in Canada

Background

Individuals with a self-reported history of sexually transmitted infection (STI) are at high risk for depression. However, little is known about how social support affects the association between STI and depression among young women in Canada.

Methods

Data were drawn from the Canadian Community Health Survey (CCHS), conducted in 2005. A total of 2636 women aged 15–24 years who provided information on STI history were included in the analysis. Depression was measured by a depression scale based on the Composite International Diagnostic Interview Short-Form (CIDI-SF). The 19-item Medical Outcomes Study (MOS) Social Support Survey assessed functional social support. A log-binomial model was used to estimate the prevalence ratio (PR) for self-reported STI history associated with depression and to assess the impact of social support on the association.

Results

The adjusted PR for self-reported STI history associated with depression was 1.61 (95% CI, 1.03 to 2.37), before social support was included in the model. The association between STI history and depression was no longer significant when social support was included in the model (adjusted PR, 1.28; 95% CI, 0.83 to 1.84). The adjusted PRs for depression among those with low and intermediate levels of social support versus those with a high level of social support were 5.62 (95% CI, 3.50 to 9.56) and 2.19 (1.38 to 3.68), respectively.

Conclusions

Social support is an important determinant of depression and reduces the impact of self-reported STI on depression among young women in Canada.Key words: depression, sexually transmitted infection, social support, young women     

Mannheimia haemolytica chimeric protein vaccine composed of the major surface-exposed epitope of outer membrane lipoprotein PlpE and the neutralizing epitope of leukotoxin

Mannheimia haemolytica is commonly identified in cattle with shipping fever pneumonia. Vaccines currently available do not provide complete protection against the disease. In an effort to develop a vaccine that delivers the immunogenic regions of leukotoxin (LKT) A and the outer membrane protein (OMP) PlpE, a total of four chimeric proteins were constructed. Mice were subcutaneously immunized with 25, 50 and 75mug quantities of each chimeric protein. The specificity of the immune response was confirmed by Western blot analysis and enzyme-linked immunosorbent assays (ELISA). Moreover, the hyperimmune sera were bactericidal to M. haemolytica in the presence of complement and neutralized LKT. While all of the chimeric proteins induced some level of immune response two, SAC87 and SAC89, were most promising. These results demonstrate that a functional immune response against M. haemolytica can be induced by vaccination with recombinant chimeric proteins created from specific immunogenic regions of the LKT and PlpE proteins.     

Phenotype delineation of ZNF462 related syndrome

Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features.     

Effectiveness of external cues to facilitate task performance in people with neurological disorders: a systematic review and meta-analysis

Purpose: To examine in people with neurological disorders, which method/s of providing external cues to improve task performance are most effective.

Methods: Medline, EMBASE, and PsycINFO were systematically searched. Two reviewers independently screened, extracted data, and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results: Twenty six studies were included. Studies examined a wide-range of cues including visual, tactile, auditory, verbal, and multi-component cues. Cueing (any type) improved walking speed when comparing cues to no cues (mean difference (95% confidence interval): 0.08?m/s (0.06–0.10), I²?=?68%, low quality of evidence). Remaining evidence was analysed narratively; evidence that cueing improves activity-related outcomes was inconsistent and rated as very low quality. It was not possible to determine which form of cueing may be more effective than others.

Conclusion: Providing cues to encourage successful task performance is a core component of rehabilitation, however there is limited evidence on the type of cueing or which tasks benefit most from external cueing. Low-quality evidence suggests there may be a beneficial effect of cueing (any type) on walking speed. Sufficiently powered randomised controlled trials are needed to inform therapists of the most effective cueing strategies to improve activity performance in populations with a neurological disorder.

• Implications for rehabilitation

• Providing cues is a core component of rehabilitation and may improve successful task performance and activities in people with neurological conditions including stroke, Parkinson’s disease, Alzheimer’s disease, traumatic brain injury, and multiple sclerosis, but evidence is limited for most neurological conditions with much research focusing on stroke and Parkinson’s disease.

• Therapists should consider using a range of different types of cues depending on the aims of treatment and the neurological condition. There is currently insufficient evidence to suggest one form of cueing is superior to other forms.

• Therapists should appreciate that responding optimally to cues may take many sessions to have an effect on activities such as walking.

• Further studies should be conducted over a longer timeframe to examine the effects of different types of cues towards task performance and activities in people with neurological conditions.

     

Task Sharing of Injectable Contraception Services in Pakistan: A Randomized Controlled Trial

Provision of injectable contraceptive services by lay health workers is endorsed by normative bodies, but support for this practice is not universal. We assessed whether lay providers (lady health workers, LHWs) could perform as well as clinically trained providers (family welfare workers, FWWs) on appropriate screening, counseling, and injection of intramuscular and subcutaneous depot medroxyprogesterone acetate (DMPA) using a randomized controlled trial. In the urban sample (n = 355), 88 percent of FWW DMPA clients were appropriately screened versus 77 percent of LHW clients (noninferiority test p = 0.88). In rural facilities (n = 105), over 90 percent of both providers’ clients were screened appropriately. Appropriate counseling was low overall, but LHWs were significantly noninferior to FWWs (p = 0.003). Notably, LHWs demonstrated better injection technique than FWWs. We could not conclude that LHWs screened new DMPA users as well as FWWs from an urban sample of providers but results from the rural sample suggests that service delivery context played an important role.