In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats

This study was carried out to investigate the effect of in utero exposure to the cholinotoxicants, nicotine and chlorpyrifos, alone or in combination on neurobehavioral alterations and neuronal morphology latter in adult age. In the present study, 90 days old (corresponding to a human adult age) male and female offspring rats were evaluated for neurobehavioral, and neuropathological alterations following maternal, gestational exposure to nicotine and chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate), alone and in combination. Female Sprague-Dawley rats (300–350 g) with timed-pregnancy were treated with nicotine (3.3 mg/kg/day, in bacteriostatic water via s.c. implantation of mini osmotic pump), chlorpyrifos (1.0 mg/kg, daily, dermal, in 75% ethanol, 1.0 ml/kg) or a combination of both chemicals, on gestational days (GD) 4–20. Control animals received bacteriostatic water via s.c. implantation of mini osmotic pump and dermal application of 70% ethanol. The offspring at postnatal day (PND) 90 were evaluated for neurobehavioral performance, changes in the activity of plasma butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), and neuropathological alterations in the brain. Neurobehavioral evaluations included beam-walk score, beam-walk time, incline plane performance and forepaw grip time. Male and female offspring from mothers treated with nicotine and CPF, alone or in combination showed impairments in the performance of neurobehavioral tests, indicating sensorimotor deficits. Female offspring from mothers treated with a combination of nicotine and chlorpyrifos showed significant increase in plasma BChE activity. Brain regional AChE activity showed differential increases in male and female offspring. Brainstem and cerebellum of female offspring from mothers treated with nicotine or chlorpyrifos, alone or in combination showed increased AChE activity, whereas brainstem of male offspring from mothers treated with nicotine alone or a combination of nicotine and chlorpyrifos showed increase in AChE activity. Also, male offspring exposed in utero to nicotine exhibited increased AChE activity. Histopathological evaluations using cresyl violet staining showed a decrease in surviving Purkinje neurons in the cerebellum in offspring of all treatments groups. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer (GCL) of cerebellum following all exposures. These results indicate that in utero exposure to nicotine and chlorpyrifos, alone and in combination produced significant sensorimotor deficits in male and female offspring, differential increase in brain AChE activity, a decrease in the surviving neurons and an increased expression of GFAP in cerebellum in adult offspring rats at a corresponding human adult age. Collectively, this study demonstrates that maternal exposure to environmental neurotoxic chemicals, i.e., nicotine and chlorpyrifos leads to developmental abnormalities in the offspring that persist latter into adulthood.     

Fluid dynamics and noise in bacterial cell-cell and cell-surface scattering

Bacterial processes ranging from gene expression to motility and biofilm formation are constantly challenged by internal and external noise. While the importance of stochastic fluctuations has been appreciated for chemotaxis, it is currently believed that deterministic long-range fluid dynamical effects govern cell-cell and cell-surface scattering-the elementary events that lead to swarming and collective swimming in active suspensions and to the formation of biofilms. Here, we report direct measurements of the bacterial flow field generated by individual swimming Escherichia coli both far from and near to a solid surface. These experiments allowed us to examine the relative importance of fluid dynamics and rotational diffusion for bacteria. For cell-cell interactions it is shown that thermal and intrinsic stochasticity drown the effects of long-range fluid dynamics, implying that physical interactions between bacteria are determined by steric collisions and near-field lubrication forces. This dominance of short-range forces closely links collective motion in bacterial suspensions to self-organization in driven granular systems, assemblages of biofilaments, and animal flocks. For the scattering of bacteria with surfaces, long-range fluid dynamical interactions are also shown to be negligible before collisions; however, once the bacterium swims along the surface within a few microns after an aligning collision, hydrodynamic effects can contribute to the experimentally observed, long residence times. Because these results are based on purely mechanical properties, they apply to a wide range of microorganisms.     

Antisocial behavioral syndromes and DSM-IV alcohol use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: Antisocial personality disorder (ASPD), syndromal adult antisocial behavior (AABS) without conduct disorder (CD) before age 15, and CD without progression to ASPD ("CD only") are highly prevalent among adults with alcohol use disorders (AUDs). Among patients in AUD treatment, antisocial behavioral syndromes are associated with more severe AUDs and poorer treatment outcomes. Comparative data concerning associations of antisocial syndromes with clinical characteristics of AUDs and the sociodemographic and clinical correlates of these syndromes among general population adults with AUDs have not previously been available. This study examines prevalences and correlates of antisocial syndromes among adults with lifetime Diagnostic and Statistical Manual--Version IV (DSM-IV) AUDs, and describes associations of these syndromes with clinical characteristics of AUDs, in the general U.S. population. METHODS: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n=43,093, response rate=81%). Respondents (n=11,843) with lifetime AUDs were classified according to whether they met criteria for ASPD, AABS, "CD only," or no antisocial syndrome. Correlates of antisocial syndromes were examined using contingency table approaches and normal theory analyses of variance. Associations of antisocial syndromes with clinical characteristics of AUDs, including number of lifetime episodes, duration of longest or only episode, and alcohol consumption during period of heaviest drinking were examined using normal theory and logistic regression. RESULTS: Sociodemographic and clinical correlates of antisocial syndromes among respondents with AUDs were consistent with results from prior studies. Antisocial syndromes were significantly associated with phenomenology of AUDs, particularly ASPD with the most severe clinical presentations. Associations with AABS were similar to but more modest than those with ASPD; those with "CD only" were weaker and less consistent. Patterns of associations between antisocial syndromes and clinical characteristics of AUDs were generally similar between men and women. CONCLUSIONS: Antisocial syndromes, particularly ASPD, appear to identify a more pernicious clinical profile of AUDs among adults in the general U.S. population.     

Acute endogenous endophthalmitis due to Bartonella henselae.

A 45-year-old man presented with progressively worsening vitreitis of 1 week's duration. Treatment for cat-scratch disease 3 years prior to presentation and persistent vitreitis led to vitrectomy, and analysis of the vitrectomy specimen revealed inflammatory cells and necrotic debris; polymerase-chain-reaction analysis of the vitreous fluid sample, done by use of a novel heminested protocol, demonstrated the presence of Bartonella henselae DNA. Treatment with doxycycline led to improvement in the intraocular inflammation but resulted in a poor visual outcome.     

Hypertension Management in Minority Communities: A Clinician Survey

BACKGROUND: Rates of blood pressure (BP) control are lower in minority populations compared to whites. OBJECTIVE: As part of a project to decrease health-related disparities among ethnic groups, we sought to evaluate the knowledge, attitudes, and management practices of clinicians caring for hypertensive patients in a predominantly minority community. DESIGN/PARTICIPANTS: We developed clinical vignettes of hypertensive patients that varied by comorbidity (type II diabetes mellitus, chronic renal insufficiency, coronary artery disease, or isolated systolic hypertension alone). We randomly assigned patient characteristics, e.g., gender, age, race/ethnicity, to each vignette. We surveyed clinicians in ambulatory clinics of the 4 hospitals in East/Central Harlem, NY. MEASUREMENTS: The analysis used national guidelines to assess the appropriateness of clinicians' stated target BP levels. We also assessed clinicians' attitudes about the likelihood of each patient to achieve adequate BP control, adhere to medications, and return for follow-up. RESULTS: Clinicians' target BPs were within 2 mm Hg of the recommendations 9% of the time for renal disease patients, 86% for diabetes, 94% for isolated systolic hypertension, and 99% for coronary disease. BP targets did not vary by patient or clinician characteristics. Clinicians rated African-American patients 8.4% (p = .004) less likely and non-English speaking Hispanic patients 8.1% (p = .051) less likely than white patients to achieve/maintain BP control. CONCLUSIONS: Clinicians demonstrated adequate knowledge of recommended BP targets, except for patients with renal disease. Clinicians did not vary management by patients' sociodemographics but thought African-American, non-English-speaking Hispanic and unemployed patients were less likely to achieve BP control than their white counterparts.     

Tranexamic acid use decreases transfusion rate in children with cerebral palsy undergoing proximal femoral varus derotational osteotomy

Previous studies demonstrated the safety of tranexamic acid (TXA) use in cerebral palsy (CP) patients undergoing proximal femoral varus derotational osteotomy (VDRO), but were underpowered to determine if TXA alters transfusion rates or estimated blood loss (EBL). The purpose of this study was to investigate if intraoperative TXA administration alters transfusion rates or EBL in patients with CP undergoing VDRO surgery.We conducted a retrospective review of 390 patients with CP who underwent VDRO surgery between January 2004 and August 2019 at a single institution. Patients without sufficient clinical data and patients with preexisting bleeding or coagulation disorders were excluded. Patients were divided into 2 groups: those who received intraoperative TXA and those who did not.Out of 390 patients (mean age 9.4 ± 3.8 years), 80 received intravenous TXA (TXA group) and 310 did not (No-TXA group). There was no difference in mean weight at surgery (P = .25), Gross Motor Function Classification System level (P = .99), American Society of Anesthesiologist classification (P = .50), preoperative feeding status (P = .16), operative time (P = .91), or number of procedures performed (P = .12) between the groups. The overall transfusion rate was lower in the TXA group (13.8%; 11/80) than the No-TXA group (25.2%; 78/310) (P = .04), as was the postoperative transfusion rate (7.5%; 6/80 in the TXA group vs 18.4%; 57/310 in the No-TXA group) (P = .02). The intraoperative transfusion rate was similar for the 2 groups (TXA: 7.5%; 6/80 vs No-TXA: 10.3%; 32/310; P = .53). The EBL was slightly lower in the TXA group, although this was not significant (TXA: 142.9 ± 113.1 mL vs No-TXA: 177.4 ± 169.1 mL; P = .09). The standard deviation for EBL was greater in the No-TXA group due to more high EBL outliers. The percentage of blood loss based on weight was similar between the groups (TXA: 9.2% vs No-TXA: 10.1%; P = .40). The number needed to treat (NNT) with TXA to avoid one peri-operative blood transfusion in this series was 9.The use of intraoperative TXA in patients with CP undergoing VDRO surgery lowers overall and postoperative transfusion rates.Level of evidence: III, Retrospective Comparative Study.