Fragile X-related protein and VIG associate with the RNA interference machinery

RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease.     

Anatomical "circuitry" in the brain mediating alcohol drinking revealed by THP-reactive sites in the limbic system

The involvement of aldehyde adducts in the etiology of alcoholism continues to be supported by a number of experimental findings. These metabolites are synthesized endogenously from a condensation reaction of a biogenic aldehyde with a catechol- or indole-amine and act in the brain to augment or suppress the drinking of ethyl alcohol. When given by the intracerebroventricular route in an animal which does not prefer alcohol, certain tetrahydro-isoquinolines and beta-carbolines can augment significantly the voluntary intake of alcohol even in aversive concentrations. This paper describes the historical background and current status of the "Multiple Metabolite" theory of alcoholism. The recent identification of anatomical structures in the limbic-midbrain, limbic-forebrain of the Sprague-Dawley rat, which mediate changes in the intake of alcohol induced by tetrahydropapaveroline (THP) is also described. When injected in a low dose of 25 ng in a specific site, over a 3-day period, THP induces persistent increases in the intake of alcohol even in aversive concentrations. These THP-reactive sites comprise the substantia nigra, reticular formation, medial lemniscus, zona incerta, medial forebrain bundle, nucleus accumbens, olfactory tubercle, lateral septal nucleus, preoptic area, stria terminalis, and rostral hippocampus. A higher dose of 250 ng THP microinjected at homologous loci tends to inhibit the rat's self-selection of alcohol or exert no effect on drinking. Morphological mapping of histologically identified sites sensitive to THP revealed a distinct "circuitry" of neuronal structures overlapping both dopaminergic and enkephalinergic pathways. This "circuit" extends from the tegmental-nigral area of the midbrain rostrally to structures within the limbic-forebrain. When a THP-reactive structure, the N. accumbens, was lesioned by either of two neurotoxins, 6-hydroxydopamine or 5.7-dihydroxytryptamine, the rats' preference for alcohol increased sharply. This suggests that impairment of transmitter release, denervation supersensitivity or other perturbation of receptor function within this and other structures play a part in the aberrant drinking of alcohol. It is envisaged that a dopamine-enkephalin link underlies the mechanism for the onset, maintenance and permanency of alcohol preference generated by an aldehyde adduct. Finally, the "Two-Channel, Brain Metabolite" theory of alcoholism proposes that the transitory presence of an endogenously formed aldehyde adduct within cells of the brain causes a permanent perturbation of normal receptor processes and transmitter activity within synapses of specific structures of the limbic system. This theory thus explains the nature of the rewarding properties of alcohol as well as its complex addictive liability which is physiologically irreversible.     

Bite wound infections of the lower extremity

Animal bite wounds of the lower extremity are considered high-risk wounds for infection, especially in the medically compromised individual. Management should be aggressive. Copious irrigation and debridement of the wound clearly proves to be of greater value in the prevention of infection than the indiscriminate use of so-called "prophylactic" antibiotic agents. Frankly infected wounds must also be managed aggressively, incorporating the use of antibiotics to eradicate the infection. Empiric use of an agent containing clavulanic acid or sulbactam is suggested until results are obtained from the bacterial culture and sensitivity. Tetanus prophylaxis should be considered for every bite wound, whereas rabies prophylaxis is warranted in selected cases.     

Environmental, medical, and family history risk factors for Parkinson's disease: a New England-based case control study

Controversy persists about the etiology of Parkinson's disease (PD). Pesticides, herbicides, well-water consumption, head injury, and a family history of PD have been reported as risk factors for PD. The purpose of this study was to (1) investigate the impact of environmental factors on PD risk (2) estimate the chronology, frequency, and duration of those exposures associated with PD; and (3) investigate the effects of family history on PD risk. One-hundred and forty PD cases were recruited from Boston University Medical Center. The control group was composed of 147 friends and in-laws of PD patients. Environmental, medical, and family history data were obtained by structured interview from each participant for events recalled prior to PD onset for cases, or corresponding censoring age for controls (mean age = 56 years of age for each group). A traditional stratified analysis, adjusting for birth cohort and sex, was employed. Four factors were associated with increased risk for PD: (1) head injury (OR=6.23, confidence interval [CI]: 2.58-15.07); (2) family history of PD (OR=6.08, CI: 2.35-15. 58); (3) family history of tremor (OR=3.97, CI: 1.17-13.50); and (4) history of depression (OR=3.01, CI: 1.32-6.88). A mean latency of 36. 5 (SE=2.81) years passed between the age of first reported head injury and PD onset. A mean latency of 22 (SE=2.66) years passed between the onset of the first reported symptoms of depression and onset of PD. Years of education, smoking, and well-water intake were inversely associated with PD risk. PD was not associated with exposure to pesticides or herbicides. These findings support the role of both environmental and genetic factors in the etiology in PD. The results are consistent with a multifactorial model. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:742-749, 1999.     

Effects of depressed mood versus clinical depression on neuropsychological test performance among African American men impacted by HIV/AIDS

The utility of self-report measures in identifying those at risk for depressive disorder and the adverse impact of depression versus depressed mood and HIV serostatus on neuropsychological (NP) test performance were examined in a large sample (N = 243) of gay and bisexual African American men. Results indicate high rates of depression relative to recent population estimates, regardless of methodology, but that the use of standard cut-scores for self-report inventories may significantly overestimate psychiatric morbidity. Limited independent effects of serostatus or depression on NP test performance were observed. More importantly, a complex set of adverse effects of depression and its interaction with serostatus which varied according to the methodology used to assess depression were observed. These findings are discussed in light of ongoing controversy regarding the relative influence of depression on neuropsychological functioning among people living with HIV/AIDS.     

Knee joint kinematics during the sidestep cutting maneuver: potential for injury in women.

PURPOSE: There is a paucity of data describing female lower limb biomechanics during "high risk" movements linked to noncontact ACL injury. This study compared, across gender, knee kinematics associated with sidestepping maneuvers to provide insight into why women display a significantly higher incidence of this injury than do men. METHODS: Thirty participants (16 men, 14 women) had bilateral knee joint kinematic data recorded while sidestepping. A custom software package (JTMOTION) quantified maximum, minimum, and range of motion during stance for each of the three clinical knee joint rotations (flexion/extension, adduction/abduction and external/internal rotation) over 20 (leg x condition x trial (5)) trials. RESULTS: Gender differences possessed limited clinical significance with all maximum values well within safe ranges of knee motion. Women did, however, display increased intertrial variability for axial rotation patterns during cutting compared with men. This variability was thought to be unaffected by gender, with experience level found statistically (P < 0.01) to be the major determinant of knee kinematic variability during sidestepping. Hence, the level of exposure to sidestep cutting may have a large impact on the subsequent risk of ACL injury when when one performs these maneuvers. CONCLUSIONS: Gender differences in knee motions during cutting did not contribute to the increased risk of noncontact ACL injury in women compared with men. The reasons for this increased incidence, therefore, remain unclear. The potential relationship between gender and other parameters linked to ACL injury such as joint geometry, ligament morphology, and physical conditioning requires further investigation.     

Comparison of Euroqol EQ-5D and SF-36 in patients with chronic fatigue syndrome

The objective of the study was to compare the Euroqol EQ-5D (Euroqol) and short-form 36 (SF-36) health questionnaires in patients with chronic fatigue syndrome (CFS). One hundred and twenty-seven out-patients referred to a hospital-based infectious disease clinic with a diagnosis of CFS were contacted by post and asked to complete both questionnaires. Additional data were determined from hospital casenotes. Eighty-five patients returned correctly completed questionnaires. Euroqol health values and visual analogue scale (VAS) scores were strongly and significantly correlated with all dimensions of the SF-36, with the exception of physical limitation of role. SF-36 dimensions were in turn strongly and significantly correlated with each other, with the same exception. Patients reported a high degree of physical disability and a moderate degree of emotional or psychological ill-health. The Euroqol elements dealing with mobility and self-care referred to inappropriately severe degrees of disability for these patients with CFS. Similarly some dimensions in the SF-36 were oversensitive and did not discriminate between patients with moderate or severe disability. It was concluded that Euroqol scores correlated strongly with SF-36 scores and provided useful information about patients with CFS and that Euroqol would be a useful tool for the rapid assessment of health status in CFS. The current Euroqol instrument refers to inappropriately severe degrees of disability for patients with CFS and would need to be modified to be maximally useful in this situation.