Meningococcal Vaccination:: An Update on Meningococcal Vaccine Recommendations for the Primary Care Physician.

Neisseria meningitidis is an aerobic, gram-negative, diplococcus bacterium that is a leading cause of meningitis and sepsis in the United States. Particularly at-risk groups include those with complement deficiencies, people using complement inhibitors, individuals with anatomic or functional asplenia, patients with HIV infection and travelers to endemic countries. There are currently three quadrivalent meningococcal vaccines (Serogroups A, C, W, Y) and two recombinant serogroup B vaccines available for use in the United States, and recommendations for vaccine use have changed rapidly in the past 10-15 years. This article summarizes updated ACIP recommendations for meningococcal vaccination for the primary care provider.

Disseminated Tuberculosis Involving Lung, Peritoneum, and Endometrium in an Immunocompetent 17-Year-Old Patient.

A 17-year-old Guatemalan female with a recent history of spontaneous abortion requiring dilation and curettage at 16 weeks' gestation presented two weeks post-procedure to a pediatric hospital for three days of worsening generalized abdominal pain, diarrhea, fevers, and cough. The patient's vital signs showed hypoxia, tachypnea, tachycardia, and hypotension; she was alert and oriented with a thin body habitus and suprapubic abdominal tenderness without rebound, guarding, or hepatosplenomegaly. She had no crackles, rales, or wheezing on lung examination. Labs revealed neutrophilic leukocytosis, acute kidney injury, transaminitis, and coagulopathy. Pelvic ultrasound demonstrated a septated pelvic fluid collection with an endometrial thickening. CT abdomen and pelvis showed significant nodular omental thickening and ascites. CT angiogram of the chest demonstrated an apical lung cavity and bilateral micro-nodularity without lymphadenopathy. Due to concern for septic shock secondary to endometritis, the patient was started on broad-spectrum antibiotics and intubated for acute hypoxic respiratory failure. Repeat dilation and evacuation revealed degenerative first trimester products of conception and necrotizing granulomatous endometritis with Mycobacterium tuberculosis (M. tuberculosis) bacteria. Paracentesis indicated tuberculosis (TB) in ascites fluid, and bronchoalveolar lavage (BAL) showed pulmonary TB. Human immunodeficiency virus (HIV) screen and serum QuantiFERON®-TB Gold testing were negative. Rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy was initiated alongside piperacillin-tazobactam for the treatment of both disseminated TB and septic abortion. She was extubated with hemodynamic stability, but fevers persisted. Repeat fallopian tube fluid sampling after five weeks of RIPE indicated numerous acid-fast bacilli. The patient's septic clinical picture clouded her TB diagnosis as it appeared unusual that a healthy 17-year-old would concurrently have a septic abortion and disseminated TB; the lack of lymphadenopathy on CT scan also contributed to diagnostic uncertainty. Among patients from endemic regions, TB is a cause of spontaneous abortion. Conversely, during pregnancy, progesterone suppresses the T-helper 1 (Th1) proinflammatory response and increases susceptibility to TB. Peripartum women are at higher risk for disseminated TB, and postpartum women are twice as likely to experience reactivation of latent TB than nonpregnant women. Disseminated TB must be considered in pregnant adolescents presenting with appropriate clinical characteristics and imaging findings.

Water quality impacts of urban and non-urban arid-land runoff on the Rio Grande.

Urban surface runoff from storms impacts the water quality dynamics of downstream ecosystems. While these effects are well-documented in mesic regions, they are not well constrained for arid watersheds, which sustain longer dry periods, receive intense but short-lived storms, and where stormwater drainage networks are generally isolated from sewage systems. We used a network of high-frequency in situ water quality sensors located along the Middle Rio Grande to determine surface runoff origins during storms and track rapid changes in physical, chemical, and biological components of water quality. Specific conductivity (SpCond) patterns were a reliable indicator of source, distinguishing between runoff events originating primarily in urban (SpCond sags) or non-urban (SpCond spikes) catchments. Urban events were characterized by high fluorescent dissolved organic matter (fDOM), low dissolved oxygen (including short-lived hypoxia <2 mg/L), smaller increases in turbidity and varied pH response. In contrast, non-urban events showed large turbidity spikes, smaller dissolved oxygen sags, and consistent pH sags. Principal component analysis distinguished urban and non-urban events by dividing physical and biogeochemical water quality parameters, and modeling of DO along the same reach demonstrated consistently higher oxygen demand for an urban event compared to a non-urban event. Based on our analysis, urban runoff poses more potential ecological harm, while non-urban runoff poses a larger problem for drinking water treatment. The comparison of our results to other reports of urban stormwater quality suggest that water quality responses to storm events in urban landscapes are consistent across a range of regional climates.

Clinic-Based Pediatric Disclosure Intervention Trial Improves Pediatric HIV Status Disclosure in Ghana.

BACKGROUND: Disclosing HIV status to HIV-positive children is a major challenge facing families and health care providers. Despite recommendations for disclosure, rates remain low. We tested whether a pediatric HIV disclosure intervention delivered as an integral component of routine HIV health care in Ghana would improve disclosure to children. METHODS: Dyads of HIV-infected children aged 7-18 years and their caregivers were enrolled from 2 HIV clinics in Accra and Kumasi, Ghana. The sites were randomly assigned to one of the 2 intervention arms to avoid treatment contamination between intervention and control participants. Trained interventionist used theory-guided therapeutic communication and personalized interaction to promote disclosure. Disclosure outcomes were measured at 12-week intervals. All analyses were completed using a modified intention-to-treat approach. RESULTS: We enrolled 446 child-caregiver dyads (N = 240 intervention group; N = 206 control group); 52% of the children were boys, mean age 9.78 (±2.27) years. For disclosure at 1 year, a better overall treatment effect was observed (P < 0.001). Children in the treatment group had greater disclosure at each time point (P < 0.001) and a higher proportion of them had been disclosed to by 1 year (51.4% vs. 16.2%; P < 0.001; un-adjusted hazard ratio = 3.98: 95% confidence interval: 2.63 to 6.03) and 3 years (71.3% vs. 34.0%; unadjusted hazard ratio = 4.21: 95% confidence interval: 3.09 to 5.72). In the multivariate Cox model, factors associated with disclosure were treatment group (P < 0.001), children <11 years of age (P < 0.001), HIV-infected caregivers (P = 0.015), and caregiver's with greater education (P = 0.022). CONCLUSIONS: This practical clinic-based disclosure intervention shows excellent promise as a means of improving HIV pediatric disclosure outcomes.

High prevalence of non-adherence to antiretroviral therapy among undisclosed HIV-infected children in Ghana.

Adherence to antiretroviral therapy (ART) remains one of the greatest obstacles in pediatric HIV care. We sought to determine the prevalence of adherence to ART among undisclosed HIV-infected children and adolescents in Ghana. We analyzed baseline data from HIV-infected children and adolescents aged 7-18 years old enrolled in the SANKOFA Pediatric HIV disclosure intervention study in Ghana. Antiretroviral medication adherence was measured using caregiver 3-day recall; child 3-day recall; and pharmacy records for antiretroviral time-to-refill. Four hundred and twenty child-caregiver dyads were enrolled from January 2013 to June 2016. The median adherence (interquartile range), as measured by time-to-refill, was 93.2% (68.0%-100.0%). However, only 47.5% of children had ≥95% adherence ("good adherence") using time-to-refill data. Children of caregivers who had received secondary or higher level of education versus no school (aOR, 2.90, 95% Confidence Interval, CI 1.29-6.56), p = 0.010) or elementary education only (aOR, 2.20, CI, 1.24-3.88, p = 0.007) were more likely to have "good adherence" (≥95%). In this cohort of children unaware of their HIV positive status, median ART adherence rate was sub-optimal (by World Health Organization definition) while 38% had poor adherence (<85%).

Prevalence and correlates of depression among caregivers of children living with HIV in Ghana: findings from the Sankofa pediatric disclosure study.

Prior studies show an association between caregiver depression and child health outcomes. There has been little examination of depression among caregivers of HIV-infected children in sub-Saharan countries where pediatric HIV is concentrated. Using baseline data collected in the pediatric HIV disclosure intervention trial, Sankofa, we examined the prevalence and factors associated with depression among caregivers (N = 446) of children infected with HIV in Ghana. Data were analyzed with descriptive and regression analyses. The mean age of the caregivers was 42.2 ± 10.4 years. Eighty percent of the caregivers were female and 59% were HIV-infected. Twenty-eight percent (n = 126) of the caregivers were found to have mild to severe depression. In the adjusted model, factors significantly associated with caregiver depression included: HIV-positive caregiver status (P = 0.04), low income (P = 0.02), lower social support, (P = 0.01), lower HIV knowledge, (P = 0.01), worse HIV illness perceptions (P≤0.001), and greater perceived HIV stigma (P≤0.001). Although we found a high prevalence of depression among our study participants, several of the risks factors identified are modifiable and amenable to interventions that are locally available and affordable.

Spectrum of disease in HIV-positive patients presenting to a tertiary care hospital: a retrospective, cross-sectional review in Kumasi, Ghana.

BACKGROUND: HIV remains a significant public health dilemma in West and Central Africa. HIV-related morbidity and mortality are unjustly high, yet little is known about the spectrum of complicating comorbidities in HIV-positive patients who are admitted to hospitals in these regions. METHODS: This study involved a retrospective chart review to determine the common comorbidities and mortality rate of HIV-infected patients admitted over a six month period to the internal medicine service at the Komfo Anokye Teaching Hospital (KATH), a tertiary care center in Ghana. Patients admitted with a known or new HIV diagnosis from January to July 2016 were included. Data were collected regarding the number of new versus known cases admitted, the most common presenting complaints, final admitting diagnoses, and causes of mortality in these patients. RESULTS: During the six-month study period, 250 HIV-positive patients were admitted to KATH, and 245 of these individuals had valid survival time recorded. Of these patients, 145/245 (59.2%) were female. Median age of patients included in the study was 42 years old (IQR 35-51). The mortality rate for HIV patients admitted to the hospital was 35.5% (87 patients). One hundred and forty-five (59.4%) patients had a known history of HIV documented in their patient charts, while the remaining patients were newly diagnosed with HIV during their inpatient stay. Pulmonary tuberculosis predominated among diagnostic findings, with 40.4% of HIV-infected patients diagnosed with the condition while admitted. Patients presenting with neurological symptoms on admission were 2.14 (95% CI: 1.27-3.61) times more likely to die than those without neurological symptoms (p = .004). CONCLUSIONS: Over 40% of HIV-positive patients admitted to KATH were newly diagnosed with HIV at admission. While pulmonary tuberculosis was the most common co-morbidity, patients presenting with neurological symptoms were at higher risk of death. This study suggests that enhanced outpatient screening is needed for early diagnosis and prompt HAART initiation, as well as increased access to diagnostic modalities and treatment for HIV-positive patients with neurological symptoms.

HIV Pre-Exposure Prophylaxis and Women: Survey of the Knowledge, Attitudes, and Beliefs in an Urban Obstetrics/Gynecology Clinic.

Uptake of HIV pre-exposure prophylaxis (PrEP) is low among women at risk for HIV acquisition. Of 468,000 women, whom the United States Centers for Disease Control and Prevention estimates to be eligible for PrEP, only 10,000 unique women have begun therapy through the third quarter of 2015. These data suggest insufficient HIV prevention efforts. This study, conducted at the site of an urban academic medical center with an emergency department HIV prevalence rate of 4%, assesses the knowledge, attitudes, and beliefs of women toward PrEP. A self-administered survey was conducted among women at a family planning obstetrics/gynecology clinic at Temple University Hospital (Philadelphia, PA). Participants assessed their HIV acquisition risk and answered eight questions regarding knowledge, attitudes, and beliefs toward PrEP. Three hundred eighty-nine surveys met inclusion criteria. Sixty-five percent of women were black, and 73% were between 18 and 33 years of age. The median self-perceived risk score was 0 (interquartile range = 2) using a Likert scale. Thirty-three percent of women believed that PrEP could work, and 27% knew that such a regimen existed. Concerns existed toward cost (44%) and side effects (39%). Fifty-seven percent of women surveyed stated that they would take a medication to prevent HIV, and 64% felt comfortable discussing the subject with her doctor. Our data demonstrate a lack of PrEP knowledge, although willingness for uptake among women at risk for HIV acquisition, and a need for directed education and outreach.

Impact of HIV-Status Disclosure on Adherence to Antiretroviral Therapy Among HIV-Infected Children in Resource-Limited Settings: A Systematic Review.

Pediatric HIV remains a significant global health dilemma, especially in resource-constrained nations. As access to ART increases around the world, areas of concern in pediatric HIV treatment include age-appropriate disclosure of HIV status to children and development of adherence habits over time. This review was conducted to synthesize quantitative associations reported between disclosure and adherence among children living with HIV in resource-limited settings. An electronic database search of PubMed, MEDLINE and Cochrane returned 1348 results after removal of duplicates, 14 of which were found to meet inclusion criteria. Review of these reports showed conflicting results regarding the impact of disclosure on adherence, with 5 showing no association, 4 showing a negative impact of disclosure on adherence, and 5 showing positive benefits of disclosure for adherence habits. Thus, there was no clear consensus on the effect, if any, that disclosure has on medication adherence. Longitudinal, prospective research needs to be conducted to evaluate further impacts that disclosure may have on adherence habits over time, and interventions must be structured to link the two processes together in order to maximize health benefit to the child or adolescent.

Alternate pleckstrin homology domain orientations regulate dynamin-catalyzed membrane fission.

The self-assembling GTPase dynamin catalyzes endocytic vesicle scission via membrane insertion of its pleckstrin homology (PH) domain. However, the molecular mechanisms underlying PH domain-dependent membrane fission remain obscure. Membrane-curvature-sensing and membrane-curvature-generating properties have been attributed, but it remains to be seen whether the PH domain is involved in either process independent of dynamin self-assembly. Here, using multiple fluorescence spectroscopic and microscopic techniques, we demonstrate that the isolated PH domain does not act to bend membranes but instead senses high membrane curvature through hydrophobic insertion into the membrane bilayer. Furthermore, we use a complementary set of short- and long-distance Förster resonance energy transfer approaches to distinguish PH-domain orientation from proximity at the membrane surface in full-length dynamin. We reveal, in addition to the GTP-sensitive "hydrophobic mode," the presence of an alternate, GTP-insensitive "electrostatic mode" of PH domain-membrane interactions that retains dynamin on the membrane surface during the GTP hydrolysis cycle. Stabilization of this alternate orientation produces dramatic variations in the morphology of membrane-bound dynamin spirals, indicating that the PH domain regulates membrane fission through the control of dynamin polymer dynamics.

α2- and ß-adrenoceptors involvement in nortriptyline modulation of auditory sustained attention and impulsivity.

RATIONALE: The catecholamine innervation of the prefrontal cortex controls attentional focus and inhibits inappropriate behavioral responses. The mechanism of action with which norepinephrine (NE) reuptake inhibitors modulate these cognitive functions has not been fully investigated. OBJECTIVE: We investigated the effect of systemic administration of the NE reuptake blocker nortriptyline (NT) on attention and impulsivity using an auditory sustained attention task. The task was designed to assess impulsive behavior and the maintenance of attentional focus to an auditory stimulus presented at interresponse time durations (IRT) between 5 and 80 s. RESULTS: NT (2.0 but not 3.0 mg/kg) improved sustained attention and decreased the percentage of premature responses without changing their latency. To better understand the adrenergic component of NT action, we tested the effect of noradrenergic receptor antagonists alone or together with NT. The α(2)-receptor antagonist yohimbine, the α(1)-receptor antagonist prazosin, or the ß-receptor antagonist propranolol alone did not significantly affect attentive performance or premature responses. However, the beneficial effects of NT on sustained attention and premature responses were attenuated by pretreatment with either yohimbine or propranolol. On the contrary, prazosin did not affect the NT-mediated improvement in sustained attention. CONCLUSIONS: We conclude that sustained attention displays an inverse U-shaped dependence on NT, mediated-at least in part-by α(2)- and ß-adrenoceptors. We speculate that low doses of NT improve performance by maximizing the phasic release of NE, while higher doses of NT would elevate tonic levels of NE, thus producing suboptimal levels of phasically released NE.

Layer-specific noradrenergic modulation of inhibition in cortical layer II/III.

Norepinephrine (NE) is released in the neocortex after activation of the locus coeruleus of the brain stem in response to novel, salient, or fight-or-flight stimuli. The role of adrenergic modulation in sensory cortices is not completely understood. We investigated the possibility that NE modifies the balance of inhibition acting on 2 different γ-aminobutyric acid (GABA)ergic pathways. Using patch-clamp recordings, we found that the application of NE induces an α(1) adrenergic receptor-mediated decrease of the amplitude of inhibitory postsynaptic currents (IPSCs) evoked by stimulation of layer I (LI-eIPSCs) and a ß and α(2) receptor-mediated increase in the amplitude of IPSCs evoked by stimulation of layer II/III (LII/III-eIPSCs). Analysis of minimal stimulation IPSCs, IPSC kinetics, and sensitivity to the GABA(A) receptor subunit-selective enhancer zolpidem corroborated the functional difference between LI- and LII/III-eIPSCs, suggestive of a distal versus somatic origin of LI- and LII/III-eIPSCs, respectively. These findings suggest that NE shifts the balance between distal and somatic inhibition to the advantage of the latter. We speculate that such shift modifies the balance of sensory-specific and emotional information in the integration of neural input to the upper layers of the auditory cortex.

Nicotinic modulation of auditory attentional shift in the rat.

Numerous studies have demonstrated cognitive improvements resulting from the application of nicotine, especially in those tasks aimed at measuring attention. While the neuro-pharmacological relationship between nicotine and acetylcholine-driven attentional processes has been examined, studies tend to focus on the duration of time in which a subject can attend to a specific stimulus or series of stimuli rather than on the subjects' adaptive attentional capabilities. The present study addresses the possibility that the cholinergic agonist nicotine could improve performance on a task testing the ability to shift attention between sensory modalities under both normal and pharmacologically impaired conditions. In a pilot set of experiments, we tested the effects of nicotine in a cross-modal experimental task designed to tax both the auditory and visual systems of male Sprague-Dawley rats. Nicotine (0.2 mg/kg) significantly improved performance on both auditory and visual trials, under repetitive trial conditions, and significantly decreased overall response latency. For the primary study, we tested the effects of decreasing cholinergic neurotransmission by systemic administration of the muscarinic antagonist atropine. Atropine (12.5 mg/kg) significantly impaired performance in auditory shift trials and perseverative trials, while significantly increasing the overall response latency. We then tested the effect of nicotine within the impaired model. Systemic administration of nicotine significantly improved performance in auditory and visual shift trials, while showing moderate improvements in response latency and perseverative trial conditions. These results indicate the potential therapeutic use of nicotine as a cognitive enhancer, as well as provide evidence for cholinergic system compensations.

Effect of the environment on the dendritic morphology of the rat auditory cortex.

The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer-specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (Layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density.