The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

Has This Prepubertal Girl Been Sexually Abused?

Context The legal and social sequelae of interpreting genital findings as indicative of sexual abuse are significant. While the absence of genital trauma does not rule out sexual abuse, the physical examination can identify genital findings compatible with sexual abuse. Objectives To determine the diagnostic utility of the genital examination in prepubertal girls for identifying nonacute sexual abuse. Data Sources Published articles (1966-October 2008) that appeared in the MEDLINE database and were indexed under the search terms of child abuse, sexual or child abuse and either physical examination; genitalia; female, diagnosis; or sensitivity and specificity; and bibliographies of retrieved articles and textbooks. Study Selection Three of the authors independently reviewed titles of articles obtained from MEDLINE and selected articles for full-text review. Data Extraction Two authors independently abstracted data to calculate sensitivity, specificity, and likelihood ratios for the diagnosis of nonacute genital trauma caused by sexual abuse in prepubertal girls. Results Data were not pooled due to study heterogeneity. The presence of vaginal discharge (positive likelihood ratio, 2.7; 95% confidence interval, 1.2-6.0) indicates an increased likelihood of sexual abuse. In the posterior hymen, hymenal transections, deep notches, and perforations prompt concerns for genital trauma from sexual abuse, but the sensitivity is unknown. Without a history of genital trauma from sexual abuse, the majority of prepubertal girls will not have a hymenal transection (specificity close to 100%). Conclusions Vaginal discharge as well as posterior hymenal transections, deep notches, and perforations raise the suspicion for sexual abuse in a prepubertal girl, but the findings do not independently confirm the diagnosis. Given the broad 95% confidence intervals around the likelihood ratios for the presence of findings along with the low or unknown sensitivity of all physical examination findings evaluated, the physical examination cannot independently confirm or exclude nonacute sexual abuse as the cause of genital trauma in prepubertal girls

Has This Prepubertal Girl Been Sexually Abused?

Context The legal and social sequelae of interpreting genital findings as indicative of sexual abuse are significant. While the absence of genital trauma does not rule out sexual abuse, the physical examination can identify genital findings compatible with sexual abuse. Objectives To determine the diagnostic utility of the genital examination in prepubertal girls for identifying nonacute sexual abuse. Data Sources Published articles (1966-October 2008) that appeared in the MEDLINE database and were indexed under the search terms of child abuse, sexual or child abuse and either physical examination; genitalia; female, diagnosis; or sensitivity and specificity; and bibliographies of retrieved articles and textbooks. Study Selection Three of the authors independently reviewed titles of articles obtained from MEDLINE and selected articles for full-text review. Data Extraction Two authors independently abstracted data to calculate sensitivity, specificity, and likelihood ratios for the diagnosis of nonacute genital trauma caused by sexual abuse in prepubertal girls. Results Data were not pooled due to study heterogeneity. The presence of vaginal discharge (positive likelihood ratio, 2.7; 95% confidence interval, 1.2-6.0) indicates an increased likelihood of sexual abuse. In the posterior hymen, hymenal transections, deep notches, and perforations prompt concerns for genital trauma from sexual abuse, but the sensitivity is unknown. Without a history of genital trauma from sexual abuse, the majority of prepubertal girls will not have a hymenal transection (specificity close to 100%). Conclusions Vaginal discharge as well as posterior hymenal transections, deep notches, and perforations raise the suspicion for sexual abuse in a prepubertal girl, but the findings do not independently confirm the diagnosis. Given the broad 95% confidence intervals around the likelihood ratios for the presence of findings along with the low or unknown sensitivity of all physical examination findings evaluated, the physical examination cannot independently confirm or exclude nonacute sexual abuse as the cause of genital trauma in prepubertal girls

Utility of hepatic transaminases to recognize abuse in children

OBJECTIVE: Although experts recommend routine screening of hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in cases of potential child physical abuse, this practice is highly variable. Our objective was to determine the sensitivity and specificity of routine transaminase testing in young children who underwent consultation for physical abuse. PATIENTS AND METHODS: This was a prospective, multicenter, observational study of all children younger than 60 months referred for subspecialty evaluation of possible physical abuse. The child abuse team at each center recommended screening transaminases routinely as standard of care for all cases with a reasonable concern for physical abuse. Sensitivity and specificity for transaminases and clinical examination findings to detect identified abdominal injuries were determined, and receiver operating characteristic analysis was undertaken. RESULTS: Of 1676 consultations, 1272 (76%) patients underwent transaminase testing, and 54 (3.2% [95% confidence interval: 2.4-4.2]) had identified abdominal injuries. Area under the curve for the highest level of either transaminase was 0.85. Using a threshold level of 80 IU/L for either AST or ALT yielded a sensitivity of 77% and a specificity of 82% (positive likelihood ratio: 4.3; negative likelihood ratio: 0.3). Of injuries with elevated transaminase levels, 14 (26%) were clinically occult, lacking abdominal bruising, tenderness, and distention. Several clinical findings used to predict abdominal injury had high specificity but low sensitivity. CONCLUSIONS: In the population of children with concern for physical abuse, abdominal injury is an important cause of morbidity and mortality, but it is not so common as to warrant universal imaging. Abdominal imaging should be considered for potentially abused children when either the AST or ALT level is \u3e80 IU/L or with abdominal bruising, distention, or tenderness