G2019S LRRK2 mutation in familial and sporadic Parkinson's disease in Russia.

Among mutations associated with autosomal dominant and sporadic Parkinson's disease (PD) the G2019S substitution in the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequently identified. To estimate its frequency in Russia, we analyzed 208 patients with PD from the Northwestern region of Russia. Of these, 51 patients were probands from families with PD compatible with autosomal dominant inheritance. The control group represented 161 subjects without neurological disorders settled in the same region. The frequency of the G2019S mutation was greater in familial PD (2 [3.9%] of 51) than in sporadic PD (1 [0.6%] of 157). In addition, this mutation was found in the proband's father, who also had PD, in 1 PD family, and in 1 carrier without signs of PD at age 40 in another PD family. All carriers were heterozygous for the G2019S mutation and reported the Ashkenazi Jewish origin. The mutation was not found in the control group.     

Molecular Modeling Evidence for His438 Flip in the Mechanism of Butyrylcholinesterase Hysteretic Behavior

Cholinesterases display a hysteretic behavior with certain substrates and irreversible inhibitors. For years, this behavior has remained puzzling. However, several lines of evidence indicated that it is caused by perturbation of the catalytic triad and its water environment. In the present study, using molecular dynamics simulations of Ala328Cys BuChE mutant and wild-type BuChE in the absence and presence of a co-solvent (sucrose, glycerol), we provide evidence that hysteresis originates in a flip of the catalytic triad histidine (His438). This event is controlled by water molecules that interact with active site residues. The physiological significance of this phenomenon is still an issue.     

Apoptosis-based evaluation of chemosensitivity in ovarian cancer patients

OBJECTIVE: Induction of apoptosis in target cells is a key mechanism by which chemotherapy induces cell killing. We have established an in vitro system for determining the chemosensitivity of epithelial ovarian cancer cells to carboplatin and paclitaxel (Taxol). Practical assays to predict the likelihood of individual tumor sensitivity are needed to facilitate the choice of adequate treatment. We sought to determine whether epithelial ovarian cancer cells (EOC) collected from the ascites fluid of patients known to be clinically chemosensitive or chemoresistant to carboplatin and paclitaxel would show a similar response to chemotherapeutic drugs after in vitro treatment. METHODS: Thirteen patients with stage III and IV ovarian cancer treated with carboplatin and paclitaxel were studied. Caspase-3 activation was used as a surrogate marker for activation of chemotherapy-induced programmed cell death. We compared the in vitro apoptotic response to the clinical response of the patients from whom the tumor cells were isolated. Clinical sensitivity was defined as no evidence of disease recurrence for 6 months after optimal debulking surgery and completion of chemotherapy. RESULTS: Of seven chemosensitive patients, five cell samples treated in vitro had increased caspase-3 activity in response to both carboplatin and paclitaxel. Five of six chemoresistant cases did not show caspase-3 activity in response to only one or to neither agent. CONCLUSION: Quantifiable markers of apoptosis such as caspase-3 activation have the potential to predict the clinical response to chemotherapy. Application of this assay in clinical laboratories could optimize the potential for efficient treatment and avoid the toxicities of ineffective drugs.     

The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke Prevention in Patients with Atrial Fibrillation

Anticoagulation is important in stroke prevention in patients with atrial fibrillation. Until recently, heparins and vitamin K antagonists were the only available therapy for stroke reduction in atrial fibrillation (AF) patients. Non-vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are now available and offer new options for stroke prevention. This article reviews the available data on the use of NOACs for primary and secondary stroke prevention in AF patients and describes specific patient populations to guide clinician in making the informed decision regarding appropriate use of those agents. It also addresses the use of NOACs early after acute stroke and use of thrombolysis while on NOAC.     

Sexting and Young Adolescents: Associations with Sexual Abuse and Intimate Partner Violence

Study ObjectiveTo explore whether sexting by young adolescent girls and boys is associated with adverse life experiences including exploitative or violent sexual relationships.Design and SettingCross-sectional, anonymous survey of a convenience sample of minor adolescents younger than age 18 years recruited while waiting for care in clinics affiliated with a children's hospital in a low-resource, high-poverty, urban community.ParticipantsFive hundred fifty-five adolescents aged 14-17 years, 63% girls and 37% boys.Main Outcome MeasuresWe measured sexting by asking, “Have you ever sent a sexually suggestive or naked picture of yourself to another person through text or e-mail?” The survey also measured risk behaviors, sexual abuse, intimate partner violence (IPV), and arrest and included a validated depression scale.ResultsMean age was 15.6 ± 1.1 years; 59% were Hispanic, 28% were black; 44% of girls and 46% of boys ever had sex; 24% of girls and 20% of boys ever sent a sext. More girls than boys reported sexual abuse (16% vs 3%; P < .01), IPV victimization (15% vs 7%; P < .01), and depression (33% vs 17%; P < .01). More boys than girls reported arrest (15% vs 7%; P < .01). Independent associations with sexting for girls were: ever had sex (odds ratio [OR], 4.59; 95% confidence interval [CI], 2.29-9.19; P < .001); sexual abuse (OR, 3.81; 95% CI, 1.80-8.05; P < .001); IPV victim (OR, 2.72; 95% CI, 1.11-6.62; P < .05), and for boys: ever had sex (OR, 4.26; 95% CI, 1.47-12.32; P < .01); sexual abuse (OR, 38.48; 95% CI, 1.48-999.46; P < .05); IPV perpetration (OR, 16.73; 95% CI, 1.64-170.75; 95% CI, P < .05), as well as cannabis use, older age, other race, and arrest.ConclusionFor young adolescents, sexting is independently associated with exploitative and abusive sexual relationships including sexual abuse and IPV with similarities and differences in predictors of sexting for girls and boys.