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In low-to-middle-income countries, acute lower respiratory infection (ALRI) remains the leading infectious cause of death among infants and children under 5 years old. Case-control studies based on upper respiratory sampling have informed current understandings of ALRI etiologies; in contrast, minimally invasive tissue sampling (MITS) offers a method of directly interrogating lower respiratory tract pathogens to establish etiologic distributions. This study performed in the postmortem setting used MITS and a Determination of Cause of Death (DeCoDe) panel to elucidate the causes of fatal pneumonia in the community in Lusaka, Zambia. For deceased infants and children under age 5 years whose next-of-kin provided consent, a verbal autopsy was obtained and 6 lung tissue biopsies from each case were sent for histopathology and multiplex polymerase chain reaction testing. Subsequently, a multi-disciplinary DeCoDe panel met to review each case, determine if the child died of respiratory causes, construct a causal chain of diagnoses directly leading to the death, and determine if the death was preventable (i.e., if an identifiable intervention would have averted the death). Among 106 deaths, 49 were adjudicated as respiratory deaths, with etiologic causes including Klebsiella pneumoniae (13), Streptococcus pneumoniae (5), and Pneumocystis jirovecii (4), among others. Of note, for 21 respiratory deaths, a causative pathogen could not be identified despite clinical and histopathologic evidence of ALRI. A large majority of all deaths were considered preventable (90/106 or 85%). This study demonstrates the impact of certain respiratory pathogens through direct in situ tissue sampling with supportive pathologic data and presents a useful method of studying the etiologic distribution of fatal ALRIs in settings where many deaths occur in the community., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia., Design: A systematic, postmortem prevalence study., Setting: A busy, inner-city morgue in Lusaka., Participants: We sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies., Interventions: Not applicable-this was an observational study., Primary Outcomes: Prevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time., Secondary Outcomes: Shifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates., Results: From 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed 'probably due to COVID-19', and weakest among children, with an age-dependent increase in PCR signal intensity., Conclusions: COVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: A country's immunization system's effectiveness depends on its supply chain's efficacy. To assess the challenges of maintaining an efficient vaccine supply chain, Malawi conducted its assessment using The EVM2.0 tool (Effective Vaccine Management)., Methods: It is a cross-sectional study in which all EVM requirements were assessed between September and October 2021. Data were collected from eighty-two randomly selected sites using the site selection tool of the EVM. Data were entered into the EVM assessment tool 2.0 version 1.12 for analysis. This tool generates performance indicators and criteria scores for assessed sites, compared with a WHO minimum score of 80%., Results: Overall criteria scores across all levels of the immunization supply chain showed a statistically significant mean difference of 5.92 (t = 2.58, P = 0.02). Comparative overall mean criteria scores across different levels of the immunization supply chain showed no statistically significant difference for primary (p = 0.76), sub-national (p = 0.69), and lowest distribution stores (p = 0.12). However, a substantial gap was found in the overall mean scores of the health facility's service point (SP) (t = 4.12, P = 0.001). The overall category scores across all immunization supply chain levels did not show a statistically significant difference. However, among individual category scores, Infrastructure (76 %), Equipment (67 %), Policies and procedures (62 %), Financial (47 %), and Resources (64 %) were found to be below the WHO minimum score., Conclusion: Though the 2021 Malawi EVM assessment findings are promising, they still identified the gaps to be improved to ensure the vaccine availability in the right amount, at the right time, and at the right cost., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: Thermal ablation (TA) was implemented in public sector cervical cancer prevention services in Zambia in 2012. Initially introduced as a treatment modality in primary healthcare clinics, it was later included in mobile outreach campaigns and clinical research trials. We report the feasibility, acceptability, safety, and provider uptake of TA in diverse clinical contexts., Methods: Screening services based on visual inspection with acetic acid were offered by trained nurses to non-pregnant women aged 25-59 years. Women with a type 1 transformation zone (TZ) were treated with same-visit TA. Those with a type 2 or 3 TZ, or suspicious for cancer, were managed with same-visit electrosurgical excision or punch biopsy, respectively. A provider survey was conducted., Results: Between 2012 and 2020, 2123 women were treated with TA: primary healthcare clinics, n = 746; mobile outreach clinics, n = 1127; research clinics, n = 250. Of the 996 women treated in primary healthcare and research clinics, 359 (48%) were HIV positive. Mild cramping during treatment was the most common adverse effect. No treatment interruptions occurred. No major complications were reported in the early (6 weeks) follow-up period. Providers expressed an overwhelming preference for TA over cryotherapy., Conclusion: TA was feasible, safe, and acceptable in diverse clinical contexts. It was the preferred ablation method of providers when compared with cryotherapy., (© 2021 International Federation of Gynecology and Obstetrics.)

To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi ("all of us together"), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT., Competing Interests: LMH reports grant support from Gilead Sciences. KRA reports consulting for Gilead Sciences in two expert advisory meetings (December 2020 and June 2021). This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors otherwise have declared that no competing interests exist.

The HIV type-1 nonnucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV type-1 infection. Efavirenz is predominantly metabolized into inactive metabolites by cytochrome P450 (CYP)2B6, and patients with certain CYP2B6 genetic variants may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. We summarize the evidence from the literature and provide therapeutic recommendations for efavirenz prescribing based on CYP2B6 genotypes., (© 2019 The Authors Clinical Pharmacology & Therapeutics  © 2019 American Society for Clinical Pharmacology and Therapeutics.)

We hypothesized that poor sleep quality exacerbates glucose intolerance manifested as elevated glycosylated hemoglobin (HbA1c), which increases the risk for gestational diabetes. To test this, 38 pregnant and 22 non-pregnant (age, 18⁻35 years; body-mass index, 20⁻35 kg/m²) otherwise healthy women were enrolled in the study. Sleep quality was assessed during gestational week 24 (pregnant), or outside of the menstrual period (non-pregnant), using qualitative (Pittsburgh Sleep Quality Index) and objective (actigraphic wrist-watch) measures. Blood glucose, total cortisol, and depression status were evaluated. Eight pregnant and one non-pregnant women were lost to follow-up, or withdrew from the study. There was a higher incidence of poor sleep quality in pregnant (73%) relative to non-pregnant women (43%). Although actigraphic data revealed no differences in actual sleep hours between pregnant and non-pregnant women, the number of wake episodes and sleep fragmentation were higher in pregnant women. Poor sleep quality was positively correlated with higher HbA1c in both pregnant ( r = 0.46, n = 26, p = 0.0151) and non-pregnant women ( r = 0.50, n = 19, p = 0.0217), reflecting higher average blood glucose concentrations. In contrast, poor sleep was negatively correlated with cortisol responses in pregnant women ( r = -0.46, n = 25, p = 0.0167). Three pregnant women had elevated one-hour oral glucose tolerance test results (>153 mg/dL glucose). These same pregnant women exhibited poor sleep quality. These results support the suggestion that poor sleep quality is an important risk factor that is associated with glucose intolerance and attendant health complications in pregnancy.

Background: During the last 15 years, Malawi has made remarkable progress in reducing child mortality. However, maternal and newborn mortality remains persistently high. To help address these entrenched challenges, the Reproductive, Maternal, Newborn and Child Health (RMNCH) Trust Fund provided short-term catalytic financing of $11.5 million (2013-2016) to support country plans to advance the RMNCH and commodity agenda., Objectives: (1) To document how Malawi (ministries, partners, working groups) used evidence to inform decision-making and RMNCH investments, (2) To identify barriers to utilizing information and evidence in the planning and prioritization process at national and sub-national levels, and (3) To assess the utility of the RMNCH Landscape Synthesis, which uses existing information to review life-saving RMNCH commodities and services., Methods: This was a qualitative case study utilizing a Rapid Appraisal (RA) approach, where semi-structured interviews were conducted with staff members from UN agencies, development partners and the Ministry of Health (MoH) at national and district level. The analysis enlists a framework approach for manual qualitative content analysis., Results: Led by the MoH, the RMNCH Trust Fund grant proposal utilized an evidence-based and equity-focused process for prioritization of investments. Data-informed decision-making permeates similar commodity-focused working groups. However, common health information system (HIS) weaknesses, such as data quality and collection burden, persist and are more prevalent at district-level. The collation of evidence in the RMNCH Landscape Synthesis was a useful and sustainable tool to support planning., Conclusions: The evidence-based, equity-focused decision-making process for the RMNCH Trust Fund proposal provides an effective model for inter-agency investment prioritization. Strengthening data-informed decision-making will require financial and political commitments to HIS and capacity building for data use, particularly at the district-level. New initiatives (e.g. Health Data Collaborative and QED Network to Improve Quality of Care) provide opportunities to further improve evidence-informed decision-making.

Background: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity., Patients and Methods: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses., Results: Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of Black, 21.4% of Hispanic, and 8.6% of White patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 [95% confidence interval (CI): 1.7-31.5; P=0.007]. Among 152 White patients the HR was 14.4 (95% CI: 2.6-78.7; P=0.002), but among 153 Black patients the HR was 0.8 (95% CI: 0.05-12.7; P=0.87)., Conclusion: Among patients who initiated atazanavir/ritonavir-containing regimens, UGT1A1 slow metabolizer genotype rs887829 T/T was associated with increased bilirubin-related discontinuation of atazanavir in White but not in Black patients, this despite T/T genotype being more frequent in Black patients.

Background: Engaging community, government and non-governmental organisation (NGO) stakeholders in the design of family planning (FP) programmes is best practice. Stakeholders can provide local insights on barriers to FP. However, it can be difficult to know whether there may be limited programme perceptions if only one method of enquiry is used., Aim: This study aimed to validate the perceptions of stakeholders on barriers to FP in Malawi., Methods: The study was conducted in a rural area in Lilongwe District, Malawi and employed a mixed-methods exploratory design. Five focus groups were run with community, government and NGO stakeholders to identify barriers to using modern FP. The results of the qualitative phase were then compared using a quantitative survey of 960 women who had at least one child aged under 5 years., Results: The qualitative phase identified a range of barriers to FP, including lack of awareness, lack of access, religious beliefs, myths, and opposition by husbands. However, the quantitative survey found that these issues are not a concern for the majority of women. The main reasons given by women for not using FP were that were not currently having sex or had a child recently, and so they felt they did not need to use it., Conclusions: Perceptions of stakeholders from a qualitative approach do not necessarily reflect the perspectives of the population as documented in a quantitative survey. When involving stakeholders it is important to recognise that different approaches may elicit different responses, particularly with regard to sensitive issues or issues that apply to particular subgroups. Consequently, a deeper understanding is likely to be obtained by using a multimethod approach., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation., Methods: Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification., Results: Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks., Conclusion: Slow metabolizer genotypes were associated significantly with efavirenz discontinuation for reported CNS symptoms. This association was considerably stronger in Whites than in Blacks.

Ethnopharmacological Relevance: Khat (Catha edulis) contains cathinone, an active principal that is customarily used as a psychostimulant that wards off fatigue and to some extent used as an aphrodisiac., Aim of Study: To investigate effects of escalating doses of cathinone on hormone expression by different anterior pituitary cell types using specific antibodies., Material and Methods: Eleven vervet monkeys (6 males and 5 females) divided into tests (n=9) and controls (n=2) were used. Animals were allocated as group I (saline controls), group II (0.8 mg/kg), group III (3.2 mg/kg) and group IV (6.4 mg/kg) of cathinone. All treatments were via oral route at alternate days of each week. At the end of 4-month treatment phase, GnRH agonist (ZOLADEX) was administered to group II (low dose) and group IV (high dose) alongside cathinone for 2 additional weeks., Results: High cathinone dose at long-term exposure caused proliferation of gonadotrophs but decrease in lactotrophs and corticotrophs in anterior pituitary sections of animals while effect of low dose on these cells was insignificant. Subsequent GnRH agonist co-treatment with low and high cathinone doses enhanced gonadotroph proliferation but no change on decline of lactotrophs and corticotrophs., Conclusion: We believe that there was a possible potentiation of cathinone on pituitary hormone synthesis thereby influencing reproductive function. Suppression of corticotrophic and lactotrophic functions suggest lowering of stress levels and modulation of reproductive function based on dose level and chronicity of exposure. The findings are consistent with the hypothesis that cathinone interferes with pituitary cell integrity and consequently target organs, but further studies are required to address the precise mechanism underlying this phenomenon., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Formation of episodic memories (i.e. remembered experiences) requires a process called consolidation which involves communication between the neocortex and hippocampus. However, the neuromodulatory mechanisms underlying this neocortico-hippocampal communication are poorly understood. Here, we examined the involvement of dopamine D1 receptors (D1R) and D2 receptors (D2R) mediated signaling on memory consolidation using the Novel Object Recognition (NOR) test. We conducted the tests in male Hartley guinea pigs and cognitive behaviors were assessed in customized Phenotyper home cages utilizing Ethovision XT software from Noldus enabled for the 3-point detection system (nose, center of the body, and rear). We found that acute intraperitoneal injections of either 0.25 mg/kg SCH23390 to block D1Rs or 1.0 mg/kg sulpiride to block D2Rs soon after acquisition (which involved familiarization to two similar objects) attenuated subsequent discrimination for novel objects when tested after 5-hours in the NOR test. By contrast guinea pigs treated with saline showed robust discrimination for novel objects indicating normal operational processes undergirding memory consolidation. The data suggests that involvement of dopaminergic signaling is a key post-acquisition factor in modulating memory consolidation in guinea pigs.

Although not commonly used in behavior tests guinea pigs may offer subtle behavior repertoires that better mimic human activity and warrant study. To test this, 31 Hartley guinea pigs (male, 200-250 g) were evaluated in PhenoTyper cages using the video-tracking EthoVision XT 7.0 software. Results showed that guinea pigs spent more time in the hidden zone (small box in corner of cage) than the food/water zone, or arena zone. Guinea pigs exhibited thigmotaxis (a wall following strategy) and were active throughout the light and dark phases. Eating and drinking occurred throughout the light and dark phases. An injection of 0.25 mg/kg SCH23390, the dopamine D1 receptors (D1R) antagonist, produced significant decreases in time spent in the hidden zone. There were insignificant changes in time spent in the hidden zone for guinea pigs treated with 7.5 mg SKF38393 (D1R agonist), 1.0 mg/kg sulpiride (D2R antagonist), and 1.0 or 10.0 mg/kg methamphetamine. Locomotor activity profiles were unchanged after injections of saline, SKF38393, SCH23390, and sulpiride. By contrast, a single injection or repeated administration for 7 days of low-dose methamphetamine induced transient hyperactivity but this declined to baseline levels over the 22-h observation period. Guinea pigs treated with high-dose methamphetamine displayed sustained hyperactivity and travelled significantly greater distances over the circadian cycle. Subsequent 7-day treatment with high-dose methamphetamine induced motor sensitization and significant increases in total distances moved relative to single drug injections or saline controls. These results highlight the versatility and unique features of the guinea pig for studying brain-behavior interactions., (Copyright © 2014 Wiley Periodicals, Inc.)

The Cervical Cancer Prevention Program in Zambia (CCPPZ) has increasingly used community-level structures to increase the uptake and ensure the sustainability of the program. Traditional marriage counselors, the alangizi, who have existed in the Zambian society for many years, are one of the structures used by the program to impart cervical cancer knowledge and increase access to screening and care using an existing community structure. Several steps were followed in developing this intervention: (a) ensuring the alangizi understood the process of screening by encouraging them to go through the screening process; (b) workshops were arranged for the alangizi to meet and share experiences during which lessons were given on cervical cancer by health workers as well; and (c) eight alangizi were chosen to help document the lessons as part of ensuring that cervical cancer information is accurate and passed in a consistent manner. Over 70 alangizi, who had undergone cervical cancer screening, were trained by CCPPZ. A 'Cervical Cancer Training Manual for Marriage Counsellors' was developed to help the alangizi integrate cervical cancer lessons in their routine teachings. An evaluation was conducted during the training of the alangizi that forms the basis for this paper. The results show that although the alangizi face key challenges in their work (e.g. changing social contexts), they are still considered relevant by most communities in Zambia and are potentially an important avenue for cervical cancer and other health information. This paper shows that it is possible to integrate sexual and reproductive health messages into existing structures in the community. However, it is important to design culturally specific and sensitive healthcare strategies that embrace locally accepted good practices.

Dysregulation of dopamine (DA) homeostasis is implicated in neurodegenerative diseases, drug addiction, and neuropsychiatric disorders. The neuronal plasma membrane dopamine transporter (DAT) is essential for the maintenance of DA homeostasis in the brain. α-Synuclein is a 140-amino acid protein that forms a stable complex with DAT and is linked to the pathogenesis of neurodegenerative disease. To elucidate the potential functional consequences of DAT/α-synuclein interaction, we explored α-synuclein modulation of DAT activity in midbrain dopaminergic neurons obtained from TH::RFP mice, immortalized DA neurons, and a heterologous system expressing DAT. We used dual pipette whole cell patch clamp recording to measure the DAT-mediated current before and after dialysis of recombinant α-synuclein into immortalized DA neurons. Our data suggest that intracellular α-synuclein induces a Na+ independent but Cl--sensitive inward current in DAT-expressing cells. This current is blocked by DAT blocker GBR12935 and is absent when heat-inactivated α-synuclein is dialyzed into these cells. The functional consequence of this interaction on DAT activity was further examined with real-time monitoring of transport function using a fluorescent substrate of DAT, 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+). Overexpression of α-synuclein in DAT-positive immortalized DA neurons and CHO cells expressing DAT decreased the magnitude and rate of DAT-mediated substrate uptake without a decrease in the initial binding of the substrate at the plasma membrane. Taken together our findings are consistent with the interpretation that DAT/α-synuclein interaction at the cell surface results in a DAT-dependent, Na+-insensitive, Cl-sensitive inward current with a decrease in substrate uptake, suggesting that DAT/α-synuclein interaction can modulate dopamine transmission and thus neuronal function.

Methamphetamine (METH) is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy) in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist) did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

Objective: To make a rapid assessment of the common myths and misconceptions surrounding the causes of cervical cancer and lack of screening among unscreened low-income Zambian women., Methods: We initiated a door-to-door community-based initiative, led by peer educators, to inform unscreened women about the existence of a new see-and-treat cervical cancer prevention program. During home visits peer educators posed the following two questions to women: 1. What do you think causes cervical cancer? 2. Why haven't you been screened for cervical cancer? The most frequent types of responses gathered in this exercise were analyzed thematically., Results: Peer educators contacted over 1100 unscreened women over a period of two months. Their median age was 33 years, a large majority (58%) were not educated beyond primary school, over two-thirds (71%) did not have monthly incomes over 500,000 Zambian Kwacha (US$100) per month, and just over half (51%) were married and cohabiting with their spouses. Approximately 75% of the women engaged in discussions had heard of cervical cancer and had heard of the new cervical cancer prevention program in the local clinic. The responses of unscreened low-income Zambian women to questions posed by peer educators in urban Lusaka reflect the variety of prevalent 'folk' myths and misconceptions surrounding cervical cancer and its prevention methods., Conclusion: The information in our rapid assessment can serve as a basis for developing future educational and intervention campaigns for improving uptake of cervical cancer prevention services in Zambia. It also speaks to the necessity of ensuring that programs addressing women's reproductive health take into account societal inputs at the time they are being developed and implemented. Taking a community-based participatory approach to program development and implementation will help ensure sustainability and impact.

We evaluated whether activating dopamine D1 receptors (D1R) with an agonist will mimic the effects of long-term potentiation (LTP)-inducing electrical stimulation and trigger the expression of the presynaptic growth-associated protein 43 (GAP-43), a putative synaptic plasticity factor. Thus, we conducted GAP-43 protein analyses together with assessments of LTP across CA3/CA1 synapses in guinea pigs administered with SKF38393 (the D1R agonist) and/or SCH23390 (the D1R antagonist). Our results showed that guinea pigs treated with SKF38393 coupled with low-frequency stimulation gradually exhibited an LTP-like potentiation in correlation with increased GAP-43 protein expression. However, when SKF38393 treatment was preceded by administration of SCH23390, this antagonized the occurrence of both synaptic potentiation and GAP-43 up-regulation. By comparison, persistent LTP was readily expressed after brief high frequency tetanic stimulation in control guinea pigs, whereas animals injected with SCH23390 and tetanized only developed early-LTP but not late-LTP. Western blot analyses showed GAP-43 up-regulation in the tetanized control guinea pigs but not those injected with SCH23390. We conclude that direct D1R activations with an agonist can mimic LTP-inducing electrical stimulation to produce GAP-43 up-regulation and synaptic plasticity.

The basic goal of the project was to determine whether dopaminergic DA1 receptor (DA1R) signaling couples growth-associated protein 43 (GAP-43; a putative "plasticity" protein) and long-term potentiation (LTP; an enduring form of synaptic plasticity). Thus, guinea pigs were prepped to stimulate the CA3 and evoke population spikes in the CA1 neurons in the hippocampus in vivo. Animals were injected with either saline or SCH23390 (a selective DA1R antagonist), 1-2 h prior to recordings. It was found that tetanic stimulation (100 Hz, 1 s, three trains at 15 s intervals) readily produced early-LTP and late-LTP in the saline group. In contrast, none of the guinea pigs pre-treated with SCH23390 developed late-LTP, though early-LTP had been present. Furthermore, both GAP-43 mRNA and protein were up-regulated after LTP induction in the saline group. However, GAP-43 protein up-regulation was blocked in animals treated with SCH23390. Anti-GAP-43 immunoreactivity was intense in CA3/CA1 synaptic regions, whereas GAP-43 mRNA hybridization was localized to somatic layers in the hippocampus. Altogether, our results suggest that dopaminergic DA1 signaling partly couples GAP-43 and LTP.

The purpose of this study is to provide a point of reference regarding the neurotoxic effects resulting from exposure to environmental contaminants. Benzo(a)pyrene is a member of the polycyclic aromatic hydrocarbon (PAH) family and it is a by-product of combustion processes. Thus, persons living near factories or hazardous waste sites face the danger of exposure through contact with contaminated air, water and soil. In an effort to understand the impact of environmental contaminants, we have investigated the effects of gestational B(a)P aerosol exposure on long-term potentiation (LTP), a cellular correlate of learning and memory in the F1 generation. Briefly, timed-pregnant rats were exposed to B(a)P via nose-only inhalation on gestation days 11-21 for 4 hr per day. Dams were maintained to term and pups were weaned on postnatal day 30. Subsequent electrophysiological studies during postnatal days 60-70 revealed a diminution in LTP across the perforant path-granular cells synapses in the hippocampus of F1 generation animals that were transplacentally exposed to B(a)P aerosol relative to unexposed controls. Additionally, NMDA receptor subunit 1 (NR1) protein was found to be downregulated in the hippocampus of B(a)P exposed F1 generation animals. Taken together, our results suggest that gestational exposure to B(a)P aerosol attenuates the capacity for LTP in the F1 generation.

The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study.

Population spikes, population excitatory postsynaptic potentials and intracellular excitatory postsynaptic potentials were recorded in the CA1 area of guinea-pig hippocampal slices in response to low frequency stimulation of the stratum radiatum. Tetanic stimulation of the same afferents during an application of saccharin (10 mM, 10 min) failed to induced a long-term potentiation of the population spike, population excitatory postsynaptic potential and intracellularly recorded excitatory postsynaptic potential. A post-tetanic application of saccharin did not prevent long-term potentiation of the population spike from developing. Saccharin did not change the input resistance, the membrane potential or the ability to induce action potentials in the CA1 neurons. The slope of the intracellular excitatory postsynaptic potentials recorded in normal medium, in normal medium containing 2-amino-5-phosphonovalerate, or in Mg(2+)-free medium containing 6-cyano-7-nitroquinoxaline-2,3-dione was not significantly altered by saccharin. The depolarizations of CAI neurons produced by superfusion of N-methyl-D-aspartate or during a brief tetanic stimulation of the stratum radiation were also not altered by the drug. It therefore appears that saccharin blocks the induction of long-term potentiation by a mechanism that does not involve a blockade of N-methyl-D-aspartate receptors. Application of fluid samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex caused neurite growth in PC-12 cells, suggesting that growth-related substances were present in the collected samples. If these samples were superfused onto hippocampal slices, long-term potentiation developed. If however, the samples were co-applied with saccharin, neither neurite growth in PC-12 cells nor long-term potentiation in hippocampal slices was observed, raising the possibility that growth-related substances are involved in long-term potentiation.

In chronic, unanesthetized, normally respiring cats, stimulation of the nucleus reticularis pontis oralis induced inhibitory postsynaptic potentials (IPSPs) in masseter motoneurons during active sleep, but not during wakefulness or quiet sleep. Strychnine, when applied juxtacellularly by microiontophoresis to masseter motoneurons, specifically suppressed the active sleep-dependent IPSPs. In contrast, bicuculline did not suppress the active sleep-dependent IPSPs. These results indicate these IPSPs are mediated by the putative neurotransmitter glycine.

In transversely sectioned rat hippocampal slices, population spikes and population "EPSPs" were recorded from CA1 neurones in response to the stimulation of Schaffer collateral and commissural inputs. High frequency tetanic stimulation (400 Hz, 200 pulses) of an input induced LLP of the homosynaptic response without significantly changing the heterosynaptic response. This LLP was not interrupted by either a 400 Hz tetanus given to the heterosynaptic input or by verapamil (0.33 microM) which blocks Ca++ channels, but not transmitter release. A low frequency tetanus (20 Hz, 200 pulses) given to an input induces co-occurring homosynaptic and heterosynaptic depressions of about 20 min duration. This tetanus could also mask an established LLP in homosynaptic or heterosynaptic pathway. Verapamil counteracts homo- and heterosynaptic depressions. The population spike as well as the population "EPSP" were depressed following iontophoretic application of Ca++ (2-100 nA) at the CA1 cell body area. These results indicate that homosynaptic and heterosynaptic depressions are at least partly due to an accumulation of Ca++ into CA1 neurones. An established LLP is not interrupted by LLP of another input. Homo- and heterosynaptic depressions mask, but not reverse, LLP.

Samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex induced neurite growth in PC-12 cells in culture and synaptic long-term potentiation (LTP) in guinea pig hippocampal slices. If these samples were preheated and cooled, or if they were collected in the absence of a tetanic stimulation of the rabbit neocrotex, they did not induce neurite growth in PC-12 cells or LTP in the guinea pig hippocampus. These results suggest that neurite-inducing factors are released during tetanic stimulations and that these substances are involved in LTP.

In guinea pig hippocampal slices incubated in Ba2+, stimulation of stratum radiatum induced an EPSP that was followed by an increased frequency of miniature EPSPs in CA1 neurons. These miniature EPSPS, which were presumably due to the asynchronous release of transmitter, were increased after the induction of long-term potentiation.

In this study, 79 patients undergoing arthroscopic meniscectomy were entered into a randomized double-blind controlled trial in which intraarticular bupivacaine (Marcaine), was compared with a saline placebo. Intraarticular bupivacaine was shown to be an effective and safe method of achieving analgesia after arthroscopic meniscectomy.