Concomitant Treatment with Doxycycline and Rifampicin in Balb/c Mice Infected with Brucella abortus 2308 Fails to Reduce Inflammation and Motor Disability.

Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.

Malaria prevalence and use of control measures in an area with persistent transmission in Senegal.

INTRODUCTION: In Senegal, the widespread use of vector control measures has resulted in a significant reduction in the malaria burden and led the country to consider the possibility of elimination. Given this shift and changing context, it is important to characterize the malaria burden across all age groups to guide decision-making on programmatic interventions to interrupt transmission and ultimately eradicate the disease. In Senegal, there is a lack of information on malaria prevalence among certain populations, particularly among adolescents and adults. This study sought to assess the magnitude of malaria infections in all age groups, as well as malaria associated factors in an area of persistent transmission in Senegal. METHODS: A cross-sectional household survey was conducted in four health posts (Khossanto, Mamakhona, Diakhaling and Sambrambougou), of the health district of Saraya, in November 2021, among individuals over 6 months of age. Households were selected using multistage sampling. Consented participants were screened for malaria parasites by microscopic examination of blood smears, and hemoglobin levels were measured using the Hemocue HB 301TM analyzer. Socio-demographic information of the participants, household heads, household assets, and information on ownership and use of preventive measures were collected using a structured questionnaire. Weighted generalized mixed effects logistic regression model was used to identify factors associated with microscopically confirmed malaria infection. RESULTS: A total of 1759 participants were enrolled in the study. Overall, about 21% of participants were classified as having Plasmodium infection; children aged 5-10 years old (26.6%), adolescents aged 10-19 years old (24.7%), and children under five years of age (20.5%) had higher rates of infection compared to adults (13.5%). Plasmodium falciparum accounted for 99.2% of the malaria infections, and most infections (69%) were asymptomatic. Around one-third of study participants had anemia (hemoglobin level <11.0 g/dl), with under five children bearing the highest burden (67.3%). Multivariate analysis showed that the odds of having a malaria infection were around 2 times higher among participants in Khossanto compared to Diakhaling (aOR = 1.84, 95% CI:1.06-3.20). Participants aged 5-9 years were more likely to have malaria infection compared to under five children (aOR = 1.40, 95% CI:1.02-1.91). Factors associated with anemia were P. falciparum infection (aOR = 1.36, p = 0.027), females (aOR = 2.16, p = 0.000), under-five age group (aOR = 13.01, p = 0.000). CONCLUSION: Malaria burden was considerable among adolescents and under ten children living in an area of persistent transmission, with adolescents more commonly presenting as asymptomatic. Interventions tailored to this specific group of the population are needed to better control the disease and reduce its burden.

Risperidone Decreases Expression of Serotonin Receptor-2A (5-HT2A) and Serotonin Transporter (SERT) but Not Dopamine Receptors and Dopamine Transporter (DAT) in PBMCs from Patients with Schizophrenia.

Dopamine and serotonin receptors and transporters play an essential role in the pathophysiology of schizophrenia; changes in their expression have been reported in neurons and leukocytes. Each antipsychotic induces a unique pattern in leukocyte function and phenotype. However, the use of polytherapy to treat schizophrenia makes it challenging to determine the specific effects of risperidone on peripheral blood mononuclear cells (PBMCs). The aim of this study was to evaluate the changes in the expression of D3, D5, DAT, 5-HT2A, and SERT in PBMCs from healthy volunteers (HV), drug-naive patients with schizophrenia (PWS), drug-free PWS, and PWS treated with risperidone for up to 40 weeks using quantitative PCR. Our study revealed elevated mRNA levels of D3, DAT, 5-HT2A, and SERT in unmedicated PWS. Treatment with risperidone led to a reduction only in the expression of 5-HT2A and SERT. Furthermore, we observed a moderate correlation between 5-HT2A expression and the positive and negative syndrome scale (PANSS), as well as SERT expression and PANSS scale. We also found a moderate correlation between 5-HT2A and SERT expression and the positive subscale. The duration of risperidone consumption had a significant negative correlation with the expression of 5-HT2A and SERT. Our study introduces the measurement of 5-HT2A and SERT expression in PBMCs as a useful parameter for assessing the response to risperidone in PWS.

Upregulation of S100A8 in peripheral blood mononuclear cells from patients with depression treated with SSRIs: a pilot study.

BACKGROUND: Major depressive disorder (MDD) affects more than 350 million people worldwide, and there is currently no laboratory test to diagnose it. This pilot study aimed to identify potential biomarkers in peripheral blood mononuclear cells (PBMCs) from MDD patients. METHODS: We used tandem mass tagging coupled to synchronous precursor selection (mass spectrometry) to obtain the differential proteomic profile from a pool of PBMCs from MDD patients and healthy subjects, and quantitative PCR to assess gene expression of differentially expressed proteins (DEPs) of our interest. RESULTS: We identified 247 proteins, of which 133 had a fold change ≥ 2.0 compared to healthy volunteers. Using pathway enrichment analysis, we found that some processes, such as platelet degranulation, coagulation, and the inflammatory response, are perturbed in MDD patients. The gene-disease association analysis showed that molecular alterations in PBMCs from MDD patients are associated with cerebral ischemia, vascular disease, thrombosis, acute coronary syndrome, and myocardial ischemia, in addition to other conditions such as inflammation and diabetic retinopathy. CONCLUSIONS: We confirmed by qRT-PCR that S100A8 is upregulated in PBMCs from MDD patients and thus could be an emerging biomarker of this disorder. This report lays the groundwork for future studies in a broader and more diverse population and contributes to a deeper characterization of MDD.

Imipramine Administration in Brucella abortus 2308-Infected Mice Restores Hippocampal Serotonin Levels, Muscle Strength, and Mood, and Decreases Spleen CFU Count.

Brucellosis infection causes non-specific symptoms such as fever, chills, sweating, headaches, myalgia, arthralgia, anorexia, fatigue, and mood disorders. In mouse models, it has been associated with increased levels of IL-6, TNF-α, and IFN-γ, a decrease in serotonin and dopamine levels within the hippocampus, induced loss of muscle strength and equilibrium, and increased anxiety and hopelessness. Imipramine (ImiP), a tricyclic antidepressant, is used to alleviate neuropathic pain. This study evaluated the effects of ImiP on Balb/c mice infected with Brucella abortus 2308 (Ba) at 14- and 28-days post-infection. Serum levels of six cytokines (IFN-γ, IL-6, TNF-α, IL-12, MCP-1. and IL-10) were assessed by FACS, while the number of bacteria in the spleen was measured via CFU. Serotonin levels in the hippocampus were analyzed via HPLC, and behavioral tests were conducted to assess strength, equilibrium, and mood. Our results showed that mice infected with Brucella abortus 2308 and treated with ImiP for six days (Im6Ba14) had significantly different outcomes compared to infected mice (Ba14) at day 14 post-infection. The mood was enhanced in the forced swimming test (FST) (p < 0.01), tail suspension test (TST) (p < 0.0001), and open-field test (p < 0.0001). Additionally, there was an increase in serotonin levels in the hippocampus (p < 0.001). Furthermore, there was an improvement in equilibrium (p < 0.0001) and muscle strength (p < 0.01). Lastly, there was a decrease in IL-6 levels (p < 0.05) and CFU count in the spleen (p < 0.0001). At 28 days, infected mice that received ImiP for 20 days (Im20Ba28) showed preservation of positive effects compared to infected mice (Ba28). These effects include the following: (1) improved FST (p < 0.0001) and TST (p < 0.0001); (2) better equilibrium (p < 0.0001) and muscle strength (p < 0.0001); (3) decreased IL-6 levels (p < 0.05); and (4) reduced CFU count in the spleen (p < 0.0001). These findings suggest the potential for ImiP to be used as an adjuvant treatment for the symptoms of brucellosis, which requires future studies.

Defining operational research priorities to improve malaria control and elimination in sub-Saharan Africa: results from a country-driven research prioritization setting process.

BACKGROUND: In order to reignite gains and accelerate progress toward improved malaria control and elimination, policy, strategy, and operational decisions should be derived from high-quality evidence. The U.S. President's Malaria Initiative (PMI) Insights project together with the Université Cheikh Anta Diop of Dakar, Senegal, conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps. METHODS: Five key stakeholder groups were engaged in the process: national malaria programmes (NMPs), research institutions in SSA, World Health Organization (WHO) representatives in SSA, international funding agencies, and global technical partners who support malaria programme implementation and research. Stakeholders were engaged through individual or small group interviews and an online survey, and asked about key operational challenges faced by NMPs, pressing evidence gaps in current strategy and implementation guidance, and priority OR and PE questions to address the challenges and gaps. RESULTS: Altogether, 47 interviews were conducted with 82 individuals, and through the online survey, input was provided by 46 global technical partners. A total of 33 emergent OR and PE topics were identified through the consultation process and were subsequently evaluated and prioritized by an external evaluation committee of experts from NMPs, research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools. CONCLUSION: The prioritized research list is intended to serve as a key resource for informing OR and PE investments, thereby ensuring future investments focus on generating the evidence needed to strengthen national strategies and programme implementation and facilitating a more coordinated and impactful approach to malaria operational research.

Malaria prevention knowledge, attitudes, and practices (KAP) among adolescents living in an area of persistent transmission in Senegal: Results from a cross-sectional study.

INTRODUCTION: While malaria morbidity has sharply declined in several areas in Senegal, it remains an important problem in the southern part of the country, particularly among adolescents. Understanding adolescents' knowledge, attitudes, prevention and care-seeking practices is important to inform more targeted interventions aimed at optimizing adolescents' uptake of malaria prevention and control measures. This study assessed malaria-related knowledge, attitudes, and practices (KAP) among adolescents living in a highly persistent transmission area in Senegal. METHODS: A community-based cross-sectional survey was conducted among 391 adolescents living in the Saraya health district. A multistage random sampling technique was used to select households. An electronic questionnaire developed on Open Data Kit (ODK), was used to collect data on socio-demographic characteristics, household assets, adolescents' knowledge of malaria, as well as their attitudes with regards to malaria prevention, and care-seeking behaviors. Bivariate and multivariate analyses were performed to assess factors associated with adolescents' KAP towards malaria. RESULTS: Nearly, one-third of the participants had good knowledge of malaria (34.4%) and good practice in regards to malaria preventive measures (32.8%) while 59.0% had a positive attitude and 73.8% had good care-seeking behavior regarding malaria. Multivariate analysis revealed that a primary (aOR = 5.43, p = 0.002) or secondary level of education (aOR = 10.41, p = 0.000) was associated with good knowledge of malaria transmission, signs, and prevention measures. Male individuals had lower knowledge compared to female ones (aOR = 0.40, p = 0.001). Individuals belonging to households from the highest wealth quintile were more likely to have a positive attitude towards malaria compared to those from households in the lowest wealth quintile (aOR = 3.49, p = 0.004). The odds of positive attitude towards malaria decreased among participants with koranic and primary education level, respectively (aOR = 0.14, p = 0.005) and (aOR = 0.24, p = 0.019). A positive attitude was 1.89 more likely to be (aOR = 1.89, p = 0.026) associated with good practice of prevention measures compared to adolescents who demonstrated negative attitudes. Individuals from households in the fourth (aOR = 0.42, p = 0.024), middle (aOR = 0.34, P = 0.005), and second (aOR = 0.42, p = 0.027) wealth quintiles were less likely to use malaria prevention measures compared to those from households in the highest wealth quintile. CONCLUSION: The study revealed that adolescents, generally have poor levels of malaria knowledge and low uptake of malaria prevention and control interventions. Targeted interventions for high-risk adolescents are needed, that focus on improving their knowledge of the disease and effective preventive measures, and on increasing their access to health care services and LLINs.

Screening of SERT and p11 mRNA Levels in Airline Pilots: A Translational Approach.

Airline pilots are frequently exposed to numerous flights per week, changes in their circadian rhythms, and extended periods away from home. All these stressors make pilots susceptible to developing psychiatric disorders. Recently, emphasis has been placed on the need for molecular tests that help in the diagnosis of depression. The genes SLC6A4 and S100A10 encode serotonin transporter (SERT) and p11 protein, respectively. Their expression has been frequently associated with stress and depression. In this work, we quantified, by quantitative PCR, the expression of SERT and p11 in peripheral mononuclear cells of airline pilots compared to patients with depression and healthy volunteers. Moreover, by mass spectrometry, we quantified the serum serotonin levels in the same three groups. We found that SERT and p11 were overexpressed in the mononuclear cells of airline pilots and depressed patients compared to healthy volunteers. Although serum serotonin was not different between healthy volunteers and airline pilots, a decreasing trend was observed in the latter. As expected, serum serotonin in the patients was significantly lower. Alterations in SERT and p11 in airline pilots could be related to professional stress, a condition that could potentially affect their long-term mental health.

Mother's care-seeking behavior for neonatal danger signs from qualified providers in rural Bangladesh: A generalized structural equation modeling and mediation analysis.

Background: Neonatal deaths contribute to nearly half (47%) of under-five mortality globally and 67% in Bangladesh. Despite high neonatal mortality, care-seeking from qualified providers for newborn danger signs remains low. Identification of direct and indirect factors and their pathways affecting care-seeking will help to design a well-targeted intervention. This study assessed the direct, indirect, and total effect of the predictive factors on neonatal care-seeking in Bangladesh. Materials and methods: This was a cross-sectional baseline household survey conducted in 14 districts of Bangladesh in 2019 with 17,251 recently delivered women (RDW) with a live birth outcome in the preceding 15 months. We used a two-stage stratified cluster sampling process to select the samples from 14 districts. We investigated the inter-relationship of maternal background characteristics, maternal health utilizations, child/neonate factors, health service delivery-related factors and newborn danger sign knowledge with newborn care-seeking practices and estimated the direct, indirect, and total effects using Generalized Structural Equation Modeling (GSEM) and mediation analysis. p-value = 0.05 was considered statistically significant. The result of the mediation analysis was reported in Log Odds (LOD). The positive LOD (LOD > 0) implies a positive association. Results: Half of the mothers (50.8%) reported a neonatal illness and among them, only 36.5% mothers of sick neonates sought care from qualified providers. Our mediation analysis showed that maternal health utilization factors, i.e., 4 + antenatal care visits (ANC) from a qualified provider (LOD: 0.63, 95% CI: 0.49, 0.78), facility delivery (LOD: 0.74, 95% CI: 0.30, 1.17) and postnatal care (PNC) from a qualified provider (LOD: 0.50, 95% CI: 0.21, 0.78) showed the highest total effect over other factors domains, and therefore, were the most important modifiable predictors for qualified neonatal care-seeking. Other important factors that directly and/or indirectly increased the chance of newborn care-seeking from qualified providers were household wealth (LOD: 0.86, 95% CI: 0.70, 1.02), maternal education (LOD: 0.48, 95% CI: 0.32, 0.63), distance to nearest health facility (LOD: 0.20, 95% CI: 0.10, 0.30), community health worker's (CHWs) home visits during ANC (LOD: 0.24, 95% CI: 0.13, 0.36), neonatal danger sign counseling after delivery (LOD: 0.20, 95% CI: 0.06, 0.34) and women's knowledge of neonatal danger signs (LOD: 0.37, 95% CI: 0.09, 0.64). Conclusion: The inter-relationship and highest summative effect of ANC, facility delivery, and PNC on newborn care-seeking suggested the maternal care continuum altogether from ANC to facility delivery and PNC to improve care-seeking for the sick newborn. Additionally, referral training for unqualified providers, targeted intervention for poorer households, increasing CHWs home visits and neonatal danger sign counseling at the facility and community should also be considered.

Prevalence and factors associated with skin-to-skin contact (SSC) practice: findings from a population-based cross-sectional survey in 10 selected districts of Bangladesh.

BACKGROUND: Skin-to-skin contact (SSC) practice improves newborn survival and child development through preventing hypothermia in newborns, improving early initiation of breastfeeding practice, and strengthening mother-child bonding. Despite having numerous benefits, it is one of the least practiced interventions in low and middle-income countries (1 to 74%). In Bangladesh, the prevalence of SSC was 26% in 2014. In this study, we aimed to estimate the prevalence of SSC in the study districts and identify factors that facilitate or inhibit SSC practice so that context-specific recommendations can be made to advance the use of this intervention. METHODS: We used baseline household survey data of USAID's MaMoni MNCSP project conducted in 10 districts of Bangladesh in 2019. Our analysis included 13,695 recently delivered women (RDW) with a live birth outcome. Our primary outcome was the mother's reported practice of SSC. We examined various antepartum, intrapartum, newborn, and sociodemographic factors associated with SSC using a multivariable generalized linear model. Our findings were reported using adjusted Prevalence Risk Ratios (aPRRs) and 95% Confidence Intervals (CIs). RESULTS: Overall, 28% of RDW reported practicing SSC across the 10 surveyed districts. Our multivariable analysis showed that public facility delivery (aPRR 2.01; 95%CI: 1.80, 2.26), private facility delivery (aPRR 1.23; 95%CI: 1.06, 1.42) and ≥ 4 antenatal care (ANC) visits at least one from a medically trained provider (MTP) (aPRR 1.17; 95%CI: 1.03, 1.26) had a significant positive association with SSC practice. Caesarean section (aPRR 0.64; 95%CI: 0.56, 0.73) had a significant negative association with SSC practice compared to vaginal births. We also found a significant positive association of SSC practice with mothers' who perceived the birth size of their baby to be small, mothers with a higher education level (≥10 years), and mothers from households in the highest wealth quintile. CONCLUSIONS: The prevalence of SSC is very low in the surveyed districts of Bangladesh. Considering the factors associated with SSC, relevant stakeholders need to increase their efforts on improving ANC and facility delivery coverages as well as improving SSC practice in the facilities especially after caesarean deliveries. Countries with a high burden of home deliveries, also need to emphasize community-based interventions and increasing coverage of skilled birth attendance for improving this life-saving intervention.

Behavioral and Neurochemical Shifts at the Hippocampus and Frontal Cortex Are Associated to Peripheral Inflammation in Balb/c Mice Infected with Brucella abortus 2308.

Brucellosis is a zoonosis affecting 50,000,000 people annually. Most patients progress to a chronic phase of the disease in which neuropsychiatric symptoms upsurge. The biological processes underlying the progression of these symptoms are yet unclear. Peripheral inflammation mounted against Brucella may condition neurochemical shifts and hence unchained neuropsychiatric disorders. Our work aimed at establishing whether neurological, behavioral, and neurochemical disarrays are circumstantially linked to peripheral inflammation uprise secondary to Brucella abortus 2308 infections. We then evaluated, in control and Brucella-infected mice, skeletal muscle strength, movement coordination, and balance and motivation, as well as dopamine, epinephrine, norepinephrine, and serotonin availability in the cerebellum, frontal cortex, and hippocampus. Serum levels of proinflammatory cytokines and corticosterone in vehicle-injected and -infected mice were also estimated. All estimates were gathered at the infection acute and chronic phases. Our results showed that infected mice displayed motor disabilities, muscular weakness, and reduced motivation correlated with neurochemical and peripheral immunological disturbances that tended to decrease after 21 days of infection. The present observations support that disturbed peripheral inflammation and the related neurochemical disruption might lead to mood disorders in infected mice. Future experiments must be aimed at establishing causal links and to explore whether similar concepts might explain neurological and mood disorders in humans affected by brucellosis.

A Novel Approach to Depression Care: Efficacy of an Adapted Interpersonal Therapy in a Large, Urban Primary Care Setting.

The Collaborative Care Model (CoCM), in which social workers, primary care physicians, and a consulting psychiatrist work as a team, is an established approach to the treatment of common mental health conditions in primary care settings. Following implementation of a CoCM depression care program at our hospital-based academic primary care practice, we observed a low rate of retention with the use of problem solving therapy/behavioral activation (PST/BA). Our aim in this study was to evaluate the effectiveness of interpersonal psychotherapy (IPT), an evidence-based, flexible strategy that focuses on the relationship between depression and interpersonal challenges, compared to PST/BA. In 2015, most patients enrolled in our CoCM received PST/BA. In 2016, most patients received IPT. Patients who were enrolled and discharged from our CoCM depression care program in the years 2015 and 2016 and received either PST/BA or IPT, were included. Our primary measure was the difference in change in PHQ-9 score between the PST/BA and the IPT groups. Secondary outcomes included the difference in the change in GAD-7 score and measures of glycemic and blood pressure control between the two groups. Two hundred thirty four patients were included in our analysis. One hundred sixty five received PST/BA and 69 received IPT. There was no difference between groups in baseline demographics or measures of depression, anxiety, presence of hypertension, or presence of prediabetes/diabetes. Our primary analysis demonstrated a greater decrease in PHQ-9 score in patients receiving IPT (9.93) compared to those receiving PST/BA (5.41) (p < 0.0001). The proportion of patients achieving a clinical response (PHQ-9 < 10) was also greater in the IPT group (71%) compared to the PST/BA group (44%). In a CoCM depression care program, IPT was a more effective strategy in improving depression symptoms as measured by PHQ-9 scores than PST/BA.

Operationalising health systems thinking: a pathway to high effective coverage.

BACKGROUND: The global health community has recognised the importance of defining and measuring the effective coverage of health interventions and their implementation strength to monitor progress towards global mortality and morbidity targets. Existing health system models and frameworks guide thinking around these measurement areas; however, they fall short of adequately capturing the dynamic and multi-level relationships between different components of the health system. These relationships must be articulated for measurement and managed to effectively deliver health interventions of sufficient quality to achieve health impacts. Save the Children's Saving Newborn Lives programme and EnCompass LLC, its evaluation partner, developed and applied the Pathway to High Effective Coverage as a health systems thinking framework (hereafter referred to as the Pathway) in its strategic planning, monitoring and evaluation. METHODS: We used an iterative approach to develop, test and refine thinking around the Pathway. The initial framework was developed based on existing literature, then shared and vetted during consultations with global health thought leaders in maternal and newborn health. RESULTS: The Pathway is a robust health systems thinking framework that unpacks system, policy and point of intervention delivery factors, thus encouraging specific actions to address gaps in implementation and facilitate the achievement of high effective coverage. The Pathway includes six main components - (1) national readiness; (2) system structures; (3) management capacity; (4) implementation strength; (5) effective coverage; and (6) impact. Each component is comprised of specific elements reflecting the range of facility-, community- and home-based interventions. We describe applications of the Pathway and results for in-country strategic planning, monitoring of progress and implementation strength, and evaluation. CONCLUSIONS: The Pathway provides a cohesive health systems thinking framework that facilitates assessment and coordinated action to achieve high coverage and impact. Experiences of its application show its utility in guiding strategic planning and in more comprehensive and effective monitoring and evaluation as well as its potential adaptability for use in other health areas and sectors.

Serum levels of chemokines in adolescents with major depression treated with fluoxetine.

BACKGROUND: Major depressive disorder (MDD) is a global health issue that affects 350 million people of all ages. Although between 2% and 5.6% of affected individuals are adolescents, research on young patients is limited. The inflammatory response contributes to the onset of depression, and in adult MDD patients, symptom severity has been linked to chemokine levels. AIM: To determine the differences in circulatory levels of chemokines in healthy volunteers (HVs) and adolescents with MDD, and assess the changes induced by fluoxetine consume. METHODS: The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale (HDRS). The serum levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1ß, interleukin (IL)-8, interferon gamma-induced protein (IP)-10, and eotaxin were measured in patients and HVs. RESULTS: In all cases, significant differences were detected in circulating chemokine levels between patients before treatment and HVs (P < 0.0001). All chemokines decreased at 4 wk, but only MCP-1 and IL-8 significantly differed (P < 0.05) between 0 wk and 4 wk. In the patients, all chemokines rose to their initial concentrations by 8 wk vs 0 wk, but only IP-10 did so significantly (P < 0.05). All patients experienced a significant decrease in HDRS scores at 4 wk (P < 0.0001) and 8 wk (P < 0.0001) compared with 0 wk. CONCLUSION: Despite the consumption of fluoxetine, patients had significantly higher chemokine levels, even after considering the improvement in HDRS score. The high levels of eotaxin, IP-10, and IL-8 partially explain certain aspects that are affected in MDD such as cognition, memory, and learning.

Managing possible serious bacterial infection of young infants where referral is not possible: Lessons from the early implementation experience in Kushtia District learning laboratory, Bangladesh.

BACKGROUND: Serious infections account for 25% of global newborn deaths annually, most in low-resource settings where hospital-based treatment is not accessible or feasible. In Bangladesh, one-third of neonatal deaths are attributable to serious infection; in 2014, the government adopted new policy for outpatient management of danger signs indicating possible serious bacterial infections (PSBI) when referral was not possible. We conducted implementation research to understand what it takes for a district health team to implement quality outpatient PSBI management per national guidelines. METHODS: PSBI management was introduced as part of the Comprehensive Newborn Care Package in 2015. The study piloted this package through government health systems with limited partner support to inform scale-up efforts. Data collection included facility register reviews for cases seen at primary level facilities; facility readiness and provider knowledge and skills assessments; household surveys capturing caregiver knowledge of newborn danger signs and care-seeking for newborn illness; and follow-up case tracking, capturing treatment adherence and outcomes. Analysis consisted of descriptive statistics. RESULTS: Over the 15-month implementation period, 1432 young infants received care, of which 649 (45%) were classified as PSBI. Estimated coverage of care-seeking increased from 22% to 42% during the implementation period. Although facility readiness and providers' skills increased, providers' adherence to guidelines was not optimal. Among locally managed PSBI cases, 75% completed the oral antibiotic course and 15% received the fourth day follow-up. Care-seeking remained high among private providers (95%), predominantly village health doctors (over 80%). CONCLUSIONS: Facility readiness, including health care provider knowledge and skills were strengthened; future efforts should focus on improving provider adherence to guidelines. Social and behavior change strategies targeting families and communities should explore shifting care-seeking from private, possibly less-qualified providers. Strategies to improve private sector management of PSBI cases and improved linkages between private and public sector providers could be explored.

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics.

Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

Evaluating malaria programmes in moderate- and low-transmission settings: practical ways to generate robust evidence.

BACKGROUND: Many countries have made substantial progress in scaling-up and sustaining malaria intervention coverage, leading to more focalized and heterogeneous transmission in many settings. Evaluation provides valuable information for programmes to understand if interventions have been implemented as planned and with quality, if the programme had the intended impact on malaria burden, and to guide programmatic decision-making. Low-, moderate-, and heterogeneous-transmission settings present unique evaluation challenges because of dynamic and targeted intervention strategies. This paper provides illustration of evaluation approaches and methodologies for these transmission settings, and suggests how to answer evaluation questions specific to the local context. METHODS: The Roll Back Malaria Monitoring and Evaluation Reference Group formed a task force in October 2017 to lead development of this framework. The task force includes representatives from National Malaria Programmes, funding agencies, and malaria research and implementing partners. The framework builds on existing guidance for process and outcome evaluations and impact evaluations specifically in high transmission settings. RESULTS: The theory of change describes how evaluation questions asked by national malaria programmes in different contexts influence evaluation design. The transmission setting, existing stratification, and data quality and availability are also key considerations. The framework is intended for adaption by countries to their local context, and use for evaluation at sub-national level. Confirmed malaria incidence is recommended as the primary impact indicator due to its sensitivity to detect changes in low-transmission settings. It is expected that process evaluations provide sufficient evidence for programme monitoring and improvement, while impact evaluations are needed following adoption of new mixes of interventions, operational strategies, tools or policies, particularly in contexts of changing malaria epidemiology. Impact evaluations in low-, moderate-, or heterogeneous-transmission settings will likely use plausibility designs, and methods highlighted by the framework include interrupted time series, district-level dose-response analyses, and constructed control methods. Triangulating multiple data sources and analyses is important to strengthen the plausibility argument. CONCLUSIONS: This framework provides a structure to assist national malaria programmes and partners to design evaluations in low-, moderate- or heterogeneous-transmission settings. Emphasizing a continuous cycle along the causal pathway linking process evaluation to impact evaluation and then programmatic decision-making, the framework provides practical guidance in evaluation design, analysis, and interpretation to ensure that the evaluation meets national malaria programme priority questions and guides decision-making at national and sub-national levels.

Alterations in the Levels of Growth Factors in Adolescents with Major Depressive Disorder: A Longitudinal Study during the Treatment with Fluoxetine.

Major depressive disorder (MDD) has a prevalence of 5% in adolescents. Several studies have described the association between the inflammatory response and MDD, but little is known about the relationship between MDD and growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF. It must be appointed that there are scarce reports on growth factors in adolescents with MDD and even fewer with a clinical follow-up. In this work, we evaluated the levels of growth factors (IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF) in MDD adolescents and the clinical follow-up during eight weeks of treatment with fluoxetine. Methods. All patients were diagnosed according to the DSM-IV-TR, and the severity of the symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS). Growth factors IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were quantified by cytometric bead array using serum samples from 22 adolescents with MDD and 18 healthy volunteers. Results. All patients showed clinical improvement since the fourth week of pharmacological treatment according to the HDRS. Considerably higher levels of IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were detected in MDD adolescents as compared to healthy volunteers. A significant but temporal decrease was detected in basic FGF, G-CSF, and GM-CSF at week four of fluoxetine administration. Conclusions. To the best of our knowledge, this is the first report to show alterations in the levels of growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF in MDD adolescents during eight weeks of clinical follow-up. These disturbances might be involved in the physiopathology of MDD since such growth factors have been proven to participate in the neural development and correct functioning of the CNS; therefore, subtle alterations in it may contribute to MDD.

The impact of tooth brushing versus tooth brushing and chlorhexidine application to avoid postoperative pneumonia in children.

BACKGROUND: The pathogenesis of postsurgical pneumonia is a complicated and multifactorial process, in which elements like oral bacteria, orotracheal intubation, and dental hygiene play an important role. The objective of this study was to evaluate the efficacy of 2 types of oral hygiene interventions in decreasing cases of postsurgical pneumonia. METHODS: In pediatric patients scheduled for surgery, a quasi-experimental study was carried out over a 2-year period to evaluate the efficacy of 2 types of oral hygiene interventions. There were 2 groups of intervention with 1 group for comparison. Intervention groups were tooth brushing by a dentist (intervention group 1) and dental brushing by parents + chlorhexidine gluconate (intervention group 2). Data from the year with no oral hygiene interventions were used as the baseline group. RESULTS: A total of 2,535 surgical procedures were followed. Baseline group incidence of postoperative pneumonia was 10 per 1,000 surgeries, 0.2 per 1,000 surgeries in the intervention group 1 (P = .04), and 0.8 per 1,000 surgeries in the intervention group 2. Intervention group 1 was protective against postoperative pneumonia (odds ratio, 0.06; P = .02; 95% confidence interval, 0.033-0.079), but there was no benefit with intervention group 2 (odds ratio, 0.87; P = .599; 95% confidence interval, 0.52-1.46). CONCLUSIONS: Dental brushing performed before surgery by a pediatric dentist was effective in reducing the incidence of postoperative pneumonia in pediatric patients.

Are new national malaria strategic plans informed by the previous ones? A comprehensive assessment of sub-Saharan African countries from 2001 to present.

BACKGROUND: New national malaria strategic plans (NMSPs) should build upon the achievements and challenges identified during the implementation of previous plans, but there is limited research on the transition process between NMSPs. This study aims to fill this gap through an assessment of NMSPs across sub-Saharan Africa. METHODS: The study reviewed the two most recent NMSPs for selected sub-Saharan African countries. Targets for six core malaria indicators were extracted from each NMSP and compared to the coverage achieved according to corresponding population-based surveys completed near the end of the NMSP term. Implementation challenges and proposed solutions identified through the NMSP analysis were documented. The current NMSP was reviewed to determine whether proposed solutions had been integrated into the strategy. RESULTS: Twenty-two countries in sub-Saharan Africa were included in the assessment. Of the 135 verified targets, only 4 were achieved. No country reached more than one of the six targets assessed in each NMSP. Despite this low success rate, only four of the 22 countries lowered a subsequent target, with most setting the next target at an equal or greater level. Most NMSPs identified solutions to address implementation challenges faced, but the solutions were not always fully incorporated in the new strategy. CONCLUSIONS: The results show a disconnect between NMSPs. Most targets were set according to global goals rather than the individual country's previous achievements and limitations. This indicates a need to revise the NMSP development process to guide programmes in defining targets based on their country context and incorporate strategies to address challenges identified in the previous NMSP. This will allow countries to set and meet achievable targets as they work toward global goals.