Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.     

Collaborative investigation of the accuracy and reproducibility of Sceptor Breakpoint susceptibility panels.

A combination Sceptor Breakpoint/ID panel (Johnston Laboratories, Inc., Towson, Md.), which determines interpretive susceptibility results (susceptible, moderately susceptible, and resistant) using two to three selected concentrations of antimicrobial agents, was tested in comparison with full-range Sceptor microdilution MIC panels. The inter- and intralaboratory interpretive reproducibilities for 24 control strains tested in three laboratories on three consecutive days were 97.0 and 95.7%, respectively. The equivalency of breakpoint results to category results obtained by the microdilution MIC procedure for 10,368 control organism-antimicrobial agent comparisons was 94.1%. The level of interpretive agreement between breakpoint and MIC category results using 101 fresh clinical isolates was 97.0% for 51 gram-negative and 50 gram-positive bacteria. Among the total 4,872 clinical organism-antimicrobial agent comparisons, major and very major discrepancies were seen in 0.2% of gram-negative bacteria and very major discrepancies were seen in 0.9% of gram-positive bacteria. All very major discrepancies with gram-positive organisms were associated with trailing endpoints using trimethoprim or sulfisoxazole and staphylococci. The breakpoint concept of testing selective antimicrobial agent concentrations was highly reproducible and accurate and allows for placement of more antimicrobial agents into a panel than is possible with full-dilution MIC testing.     

Serotonin-2A receptor gene is not associated with symptomatology of schizophrenia

The serotonin receptor type 2A (5-HT2A) is a primary candidate for involvement in major psychoses. Polymorphisms within the 5-HT2A gene have recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the T102C polymorphism on the psychopathology of schizophrenia. One hundred eighty-eight inpatients affected by schizophrenia (DSM-III-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HT2A variants by PCR techniques. Mania, depression, delusion and disorganization were the four symptomatologic factors previously derived from our psychotic population that were used to define phenotype in our sample. Genetic variants of the polymorphism under study were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and age of onset did not reveal any association either. Our results do not, therefore, support the hypothesis that the serotonin receptor 2A gene is a liability factor for the symptomatology of schizophrenia as defined by the OPCRIT checklist. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:84-87, 2000.     

Association study of MAO-A, COMT, 5-HT2A, DRD2, and DRD4 polymorphisms with illness time course in mood disorders

The aim of our study was to investigate a possible influence of monoamine oxydase A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on timing of recurrence in mood disorders. Gene variants were determined using PCR-based techniques in 550 inpatients affected by recurrent mood disorders (major depressives: n = 212; bipolars: n = 338), rapid cycling mood disorder (n = 81), and 663 controls. We investigated possible genetic influences by comparing illness time course of subjects subdivided according to genotype using multivariate analysis of variance (MANOVA). We could not observe a significantly different time course. No demographic and clinical variables such as sex, age or polarity of onset, presence of psychotic features, genetic loading, or education level influenced the observed results. Our results suggest that MAO-A, COMT, 5-HT2A, DRD2, and DRD4 gene variants are not involved in susceptibility toward different time courses in mood disorders.     

Andrology: Acrosome reaction inducibility predicts fertilization success at in-vitro fertilization

We prospectively studied the ability of acrosome reaction (AR)inducibility to predict fertilization success in a group of232 infertile patients presenting sequentially for in-vitrofertilization (IVF). The median percentage of eggs fertilizedfor the overall patient population was 25% (interquartile range5–58%), with one to 29 oocytes available for insemination(median, five oocytes). The median percentage of eggs fertilizedat IVF increased as the percentage of spermatozoa able to undergoAR became greater: spermatozoa with a failed AR (5%) fertilizedonly 12% of eggs, while spermatozoa with AR values>9% fertilized50% of eggs. The assay had a specificity of 0.75, a sensitivityof 0.55 and an odds ratio of 2.9; thus, AR-positive patientsare 2.9 times more likely to achieve fertilization than patientswith a failed AR. Receiver operator characteristic (ROC) curveswere constructed for AR, sperm concentration and percentageof normal forms in semen. All three parameters proved to bepotentially useful in predicting the occurrence of fertilization,although AR and morphology appeared to be better than spermconcentration by ROC analysis. Patients were divided into fourclearly defined subgroups according to their traditional semencharacteristics, including morphology. The median percentageof eggs fertilized decreased as traditional semen characteristicsdeteriorated, from a median of 46% for patients with excellentsperm concentration, motility and morphology, to a median of29% for patients with suboptimal semen quality and a medianof 0% for patients with severely impaired semen. Within eachpatient subgroup, the median percentage of eggs fertilized was3-to 4-fold higher for individuals with a positive AR than forthose with a failed AR, indicating that AR has a greater effecton fertilization rate than traditional semen parameters includingmorphology. We now recognize that some men with good semen characteristicshave an unexpectedly poor AR and a markedly reduced fertilizationrate, while other men with poor traditional semen characteristicsunexpectedly retain AR and perform relatively well at IVF. Bycontrast to AR, morphology seemed to have little effect on fertilizationsuccess (two-way analysis of variance not significant). Thewife's age and oocyte quality were evenly distributed amongthe different patient subgroups, indicating that differencesin fertilization rate could not be attributed to either parameter.Our data indicate that AR has a much higher predictive valuefor IVF success than traditional semen parameters includingmorphology. We propose that AR assessment is a clinically usefuldiagnostic tool in determining a patient's likelihood of achievingfertilization at IVF.     

Raw versus cooked vegetables and cancer risk.

This review of the medical literature from 1994 to 2003 summarizes the relationship between raw and cooked vegetables and cancer risk and examines whether they may affect cancer risk differently. Twenty-eight studies examined the relationship between raw and cooked vegetables and risk for various cancers. Twenty-one studies assessed raw, but not cooked, vegetables and cancer risk. The majority of these assessed risk of oral, pharyngeal, laryngeal, esophageal, lung, gastric, and colorectal cancers. Most showed that vegetables, raw or cooked, were inversely related to these cancers. However, more consistent results were found for oral, pharyngeal, laryngeal, esophageal, and gastric cancers. Nine of the 11 studies of raw and cooked vegetables showed statistically significant inverse relationships of these cancers with raw vegetables, but only 4 with cooked vegetables. The few studies of breast, lung, and colorectal cancers also suggested an inverse relationship with both raw and cooked vegetables, but these results were less consistent. In the two studies of prostate cancer, there was no association with either raw or cooked vegetables. One of two bladder cancer studies found an inverse relationship with cooked, but not raw, vegetables. Possible mechanisms by which cooking affects the relationship between vegetables and cancer risk include changes in availability of some nutrients, destruction of digestive enzymes, and alteration of the structure and digestibility of food. Both raw and cooked vegetable consumption are inversely related to epithelial cancers, particularly those of the upper gastrointestinal tract, and possibly breast cancer; however, these relationships may be stronger for raw vegetables than cooked vegetables.     

The Impact of Local Immigration Enforcement Policies on the Health of Immigrant Hispanics/Latinos in the United States

Objectives. We sought to understand how local immigration enforcement policies affect the utilization of health services among immigrant Hispanics/Latinos in North Carolina.Methods. In 2012, we analyzed vital records data to determine whether local implementation of section 287(g) of the Immigration and Nationality Act and the Secure Communities program, which authorizes local law enforcement agencies to enforce federal immigration laws, affected the prenatal care utilization of Hispanics/Latinas. We also conducted 6 focus groups and 17 interviews with Hispanic/Latino persons across North Carolina to explore the impact of immigration policies on their utilization of health services.Results. We found no significant differences in utilization of prenatal care before and after implementation of section 287(g), but we did find that, in individual-level analysis, Hispanic/Latina mothers sought prenatal care later and had inadequate care when compared with non-Hispanic/Latina mothers. Participants reported profound mistrust of health services, avoiding health services, and sacrificing their health and the health of their family members.Conclusions. Fear of immigration enforcement policies is generalized across counties. Interventions are needed to increase immigrant Hispanics/Latinos’ understanding of their rights and eligibility to utilize health services. Policy-level initiatives are also needed (e.g., driver’s licenses) to help undocumented persons access and utilize these services.Federal immigration enforcement policies have been increasingly delegated to state and local jurisdictions, leading to increased enforcement activities by local police. This shift has resulted largely from the implementation of 2 federal initiatives: section 287(g) of the Immigration and Nationality Act and the Secure Communities program. Section 287(g) authorizes Immigration and Custom Enforcement to enter into agreements with state and local law enforcement agencies to enforce federal immigration law during their regular, daily law enforcement activities. The original intention was to “target and remove undocumented immigrants convicted of violent crimes, human smuggling, gang/organized crime activity, sexual-related offenses, narcotics smuggling and money laundering.”1 Added to the Immigration and Nationality Act in 1996, section 287(g) was not widely used in its first decade, but its use accelerated in the mid- to late 2000s.2,3The Secure Communities program differs from section 287(g) in that it does not authorize local enforcement bodies to arrest individuals for federal immigration violations. Instead, when individuals are arrested for nonimmigration matters, the Secure Communities program facilitates the sharing of local arrestees’ fingerprints and information with Immigration and Custom Enforcement and the Federal Bureau of Investigation, which checks them against immigration databases. If these checks reveal that an individual is unlawfully present in the United States or otherwise removable because of a criminal conviction, Immigration and Custom Enforcement takes enforcement action.4Some evidence suggests that both section 287(g) and the Secure Communities program contribute to Hispanic/Latino immigrants’ general mistrust of local law enforcement and fear of utilizing a variety of public services, such as police protection and emergency services.2,5–7 Although many immigrant Hispanics/Latinos in the United States experience barriers to care because of a lack of bilingual and bicultural services, low health literacy, insufficient public transportation, and limited knowledge of available health services,8–12 studies have suggested that individuals lacking legal status may have more difficulty obtaining health services and may experience worse health outcomes than do individuals with legal status.13–18 Among immigrant Hispanics/Latinos, the fear of deportation, a lack of required forms of documentation, interaction with law enforcement personnel, and racial profiling are factors also associated with reduced utilization of health services and worse health.6,19–22 Such fears lead to incomplete sequences of care,19,20,23,24 promote the use of nonstandard and unsafe contingencies for care,16,25–27 and contribute to public health hazards, as immigrants delay preventive care or treatment.13,22,28 These fears further affect long-term health outcomes as immigrant Hispanics/Latinos alter their physical activity, food purchasing behaviors, and food consumption because of concerns about being in public.29 They may withhold information from health care providers19 and experience high levels of stress, leading to compromised mental health.20,30,31The Patient Protection and Affordable Care Act bars undocumented or recent legal immigrants from receiving financial assistance for health insurance32; thus, many will continue to remain uninsured and dependent on public health services and free clinics for a significant portion of their care. Because these services are associated with government authority, there is the potential that increasing immigration enforcement policies will deter noncitizens from seeking needed care, not only to their detriment but also to the detriment of public health.Currently there is little research examining the impact of recent immigration enforcement policies on the access to and utilization of health care, and there has been a call to better understand the public health impact of current immigration policies and their enforcement.29 Through mixed methods, we explored the effect of local immigration enforcement policies on access to and utilization of health services among immigrant Hispanics/Latinos in North Carolina. We analyzed vital records data to determine whether there were differences in utilization of prenatal services by Hispanic/Latina mothers pre- and postimplementation of section 287(g), and we conducted focus groups and in-depth interviews with Hispanics/Latinos living in counties that had implemented section 287(g) and in “sanctuary” counties, counties in which leaders, including politicians and clergy, have spoken out against the program.     

CD4+ T cells regulate glucose homeostasis independent of adipose tissue dysfunction in mice

Obesity is frequently associated with a chronic low-grade inflammation in the adipose tissue (AT) and impaired glucose homeostasis. Adipose tissue macrophages (ATMs) have been shown to accumulate in the inflamed AT either by means of recruitment from the blood or local proliferation. ATM proliferation and activation can be stimulated by TH2 cytokines, such as IL-4 and IL-13, suggesting involvement of CD4-positive T cells in ATM proliferation and activation. Furthermore, several studies have associated T cells to alterations in glucose metabolism. Therefore, we sought to examine a direct impact of CD4-positive T cells on ATM activation, ATM proliferation and glucose homeostasis using an in vivo depletion model. Surprisingly, CD4 depletion did not affect ATM activation, ATM proliferation, or insulin sensitivity. However, CD4 depletion led to a significant improvement of glucose tolerance. In line with this, we found moderate disturbances in pancreatic endocrine function following CD4 depletion. Hence, our data suggest that the effect on glucose metabolism observed after CD4 depletion might be mediated by organs other than AT and independent of AT inflammation.