SLC6A4 gene variants moderate associations between childhood food insecurity and adolescent mental health.

BACKGROUND: Food insecurity is a persistent concern in the United States and has been shown to affect child mental health and behavior. The SLC6A4 gene has been indicated as a moderator of the effects of chronic stress on anxiety in adolescents aged 14-21. However, it is unclear if SLC6A4 may also play a role in the effects of childhood food insecurity, a form of chronic stress, on adolescent mental health. This study aimed to identify effects of food insecurity on adolescents' mental health and delinquent behavior when both mom and child go hungry in the child's early years, and the potential interaction with SLC6A4 variants (SS/LL). METHODS: The data and sample for this research are from the Future of Families and Child Wellbeing Study. The cohort consists of 4898 children (age 1-15 years, male = 47%, African American = 50%) and their respective caregivers sampled from large cities in the United States from 1998 to 2000. RESULTS: The SLC6A4 serotonin transporter short/short allele emerged statistically significant as a moderator of childhood food insecurity and adolescent mental health. Specifically, the presence of the short/short allele increased anxiety symptoms in adolescents with exposure to food insecurity in childhood. CONCLUSION: The SLC6A4 short/short allele amplifies risk of anxiety-related mental illness when children experience food insecurity. The gene-environment interaction provides insight into the mechanistic pathway of the effects of poverty-related adversity, such as food insecurity, on developmental trajectories of mental health.

Estudio evolutivo de metabolitos porfirínicos de un caso de porfiria cutánea tardía / Porphyrins in a case of porphyria cutanea tarda: follow-up study

Resumen Las porfirias son errores congénitos poco frecuentes del metabolismo de las porfirinas. La porfiria cutánea tardía (PCT) es la más frecuente dentro de este grupo de enfermedades. Reportamos el estudio evolutivo de metabolitos porfirínicos de una paciente de 51 años con porfiria cutánea tardía, cuatro años después de su diagnóstico. Durante este período, se le indicó un esquema terapéutico de flebotomías en el Instituto de Hematología e Inmunología. Uno de los exámenes complementarios para su seguimiento fue la determinación de porfirinas totales en la orina, plasma y heces. Los resultados del estudio bioquímico de las porfirinas mostraron mejoría en todos los parámetros, lo que contribuyó a corroborar la utilidad del estudio de estos metabolitos como seguimiento de esta enfermedad y efectividad del tratamiento.

Abstract Porphyrias are rare congenital errors in the metabolism of porphyrins. Porphyria cutanea tarda is the most frequent among different types of porphyrias. We report the follow-up study of porphyrin metabolites of a 51-year-old patient with porphyria cutanea tarda four years later of her diagnosis. During this period, it was indicated a therapeutic scheme of phlebotomies in the Institute of Hematology and Immunology. One of the complementary examinations for its follow-up was the determination of total porphyrins in the urine, plasma and feces. Porphyrins in plasma decreased from 13 500 nmol/L at onset of disease to 250 nmol/L four years later. Although, porphyrins in feces and plasma could not quantify, we observed non-presence of peaks at 405 nm and 615.1 nm, respectively. These results contributed to corroborate the usefulness of the study of these metabolites for monitoring of this disease and effectiveness of the treatment.

Hydrogen Bond Dynamics of Cellulose through Inelastic Neutron Scattering Spectroscopy.

This work explores the dynamics of hydrogen bond networks in cellulose through inelastic neutron scattering (INS) and periodic CASTEP calculations. Estimated spectra were based on the crystal structure of cellulose Iα and Iß and replicate the INS spectrum of cellulose samples with remarkable similarity, allowing a reliable assignment of INS bands to vibrational modes of cellulose. Comparison of cellulose samples from varied sources, from bacterial to kraft pulp, allows the identification of characteristic INS bands, arising from C2-OH torsional motions, which easily identify which allomorph-Iα or Iß-is prevalent. A high crystallinity index is revealed by the presence of well-defined INS bands associated with highly cooperative CH bending modes along the chain. Hydrating kraft cellulose samples clearly affects those INS bands related with the hydroxymethyl group, identified as the preferred binding site for water molecules. At high humidity content level, a significant proportion of the water molecules is aggregated in clusters within the amorphous cellulose domains. The formation of ice microcrystals leads to a partial disruption of the hydrogen-bond network, as can be concluded from the observed red-shift of the torsional OH vibrational modes. The full assignment and interpretation of cellulose's INS spectra herein provided is a sound basis for future use of INS spectroscopy in the characterization of functionalized cellulose fibers and composite materials.

Inelastic neutron scattering study of reline: shedding light on the hydrogen bonding network of deep eutectic solvents.

The solids choline chloride and urea, mixed in a 1 : 2 molar proportion, form the iconic deep eutectic solvent "Reline". A combination of computational and vibrational spectroscopy tools, including inelastic neutron scattering (INS), have been used to probe intermolecular interactions in the eutectic mixture. Reline's experimental spectra were estimated using discrete and periodic ab initio calculations of a molecular aggregate with two choline chloride and four urea units. This is the minimum size required to achieve satisfactory agreement with experiment, as smaller clusters cannot represent all of reline's significant intermolecular interactions. The INS spectrum of reline, compared with that of pure choline chloride, reveals a displacement of chloride anions away from their preferred positions on top of choline's methyl groups, whose torsional movement becomes less hindered in the mixture. Urea, which adopts a planar (sp2) shape in the crystal, becomes non-planar (sp3) in reline, a feature herein discussed for the first time. In reline, urea molecules form a wide range of hydrogen bonds, from soft contacts to stronger associations, the latter being responsible for the deviation from ideality. The chloride's interactions with choline are largely conserved at the hydroxyl end while becoming weaker at the cationic headgroup. The interplay of soft and strong interactions confers flexibility to the newly formed hydrogen-bond network and allows the ensemble to remain liquid at room temperature.

Use of lysis and recycle to control excess sludge production in activated sludge treatment: bench scale study and effect of chlorinated organic compounds.

The most widely used treatment system in the pulp and paper industry--the activated sludge--produces high quantities of sludge which need proper disposal. In this paper a modified activated sludge process is presented. A synthetic wastewater, prepared to simulate the effluent of bleached and unbleached pulp and paper plant wastewater, was submitted to treatment in a bench scale aerobic reactor. The excess sludge was lysed in a mechanical mill--Kaddy mill--and totally recycled to the aeration tank. In the first phase the synthetic wastewater, without the chlorinated compounds, was fed to the reactor. In the second phase increasing dosages of the chlorinated compounds were used. Total recycle of excess sludge after disintegration did not produce adverse effects. During the first phase average COD removal efficiency was 65% for the control unit, which operated in a conventional way, and 63% for the treatment unit, which operated with total recycle. During the second phase the COD removal efficiency increased to 77% in the control unit and 75% in the treatment unit. Chlorinated organics removal was 85% in the treatment unit and 86% for the control unit. These differences are not significant.

Transcriptional complementarity in breast cancer: application to detection of circulating tumor cells.

BACKGROUND: We used a combination of genetic subtraction, silicon DNA microarray analysis, and quantitative PCR to identify tissue- and tumor-specific genes as diagnostic targets for breast cancer. METHODS AND RESULTS: From a large number of candidate antigens, several specific subsets of genes were identified that showed concordant and complementary expression profiles. Whereas transcriptional profiling of mammaglobin resulted in the detection of 70% of tumors in a panel of 46 primary and metastatic breast cancers, the inclusion of three additional markers resulted in detection of all 46 specimens. Immunomagnetic epithelial cell enrichment of circulating tumor cells from the peripheral blood of patients with metastatic breast cancer, coupled with RT-PCR-based amplification of breast tumor-specific transcripts, resulted in the detection of anchorage-independent tumor cells in the majority of patients with breast cancer with known metastatic disease. CONCLUSION: Complementation of mammaglobin with three additional genes in RT-PCR increases the detection of breast cancers in tissue and circulating tumor cells.

Identification and characterization of prostein, a novel prostate-specific protein.

In this report, we describe the application of a systematic, genome-based approach to identify prostein, a novel prostate-specific protein expressed in normal and malignant prostate tissues. Characterization of the prostein gene shows that prostein cDNA encodes a 553-amino acid protein. The protein is predicted to be a type IIIa plasma membrane protein with a cleavable signal peptide and 11 transmembrane-spanning regions. The prostein gene is located on chromosome 1 at the WI-9641 locus between q32 and q42. Prostein mRNA is shown to be uniquely expressed in normal and cancerous prostate tissues using Northern blot, eDNA microarray, and real-time PCR analyses. Furthermore, prostein mRNA expression does not appear to be prostate tumor grade related and is restricted exclusively to prostate cell lines. Immunohistochemical staining using a mouse monoclonal antibody generated against prostein demonstrates that this protein is specifically detected in prostate tissues both at the plasma membrane and in the cytoplasm. Prostein expression is androgen responsive because treatment of LNCaP cells with androgen up-regulates prostein message and protein expression levels. These results validate prostein as a prostate-specific marker with potential utility in the diagnosis and treatment of prostate cancer.

An improved plasmid DNA expression vector for direct injection into skeletal muscle.

In previous work, the direct injection of 50 micrograms of a plasmid DNA vector encoding firefly luciferase (VR1205) into murine quadriceps muscle produced an average of 6.5 ng of luciferase per muscle at 7 days postinjection. In this report, various elements of the VR1205 vector were modified to increase gene expression levels or to eliminate undesired viral sequences. Expression of the modified vectors was then compared to VR1205 using the intramuscular injection assay. In general, modifications to promoter, enhancer, and intronic sequences either decreased luciferase expression levels or had no effect. However, modifications to the polyadenylation and transcriptional termination sequences, plasmid backbone elements, and the luciferase gene itself each increased luciferase expression levels. The best-expressing vector, designated VR1255, contained a combination of these incrementally beneficial changes. A single intramuscular injection of 50 micrograms of VR1255 produced 300 ng of luciferase at 7 days postinjection, an expression level 46-fold higher than the VR1205 vector (or 22-fold higher, excluding modifications to the luciferase gene) and 154-fold higher than a commercially available luciferase expression vector. Thus, VR1255 represents an improved plasmid DNA vector that may be useful for gene therapy applications.

A nuclear mutation in maize blocks the processing and translation of several chloroplast mRNAs and provides evidence for the differential translation of alternative mRNA forms.

A mutant designated crp1 (chloroplast RNA processing 1) was identified in a screen for transposon-induced maize mutants with defects in chloroplast gene expression. crp1 is a recessive, nuclear mutation that causes the loss of the cytochrome f/b6 complex and a reduction in photosystem I. The molecular basis for these protein losses is unique relative to previously described mutants with defects in organelle gene expression; it involves defects in the metabolism of two organellar mRNAs and in the translation of two organellar proteins. Mutants lack the monocistronic forms of the petB and petD mRNAs (encoding cytochrome f/b6 subunits), but contain normal levels of their polycistronic precursors. Pulse-labeling experiments revealed normal synthesis of the petB gene product, but a large decrease in synthesis of the petD gene product. These results suggest that petD sequences are more efficiently translated in a monocistronic than in a polycistronic context, thereby providing evidence that the elaborate RNA processing typical of chloroplast transcripts can play a role in controlling gene expression. Structural predictions suggest that the petD start codon lies in a stable hairpin in the polycistronic RNA, but remains unpaired in the monocistronic transcript. Thus, processing to a monocistronic form may increase translational efficiency by releasing the translation initiation region from inhibitory interactions with upstream RNA sequences. Synthesis of a third cytochrome f/b6 subunit, encoded by the petA gene, was undetectable in crp1, although its mRNA appeared unaltered. Two mechanisms are consistent with the simultaneous loss of both petA and petD protein synthesis: the translation of the petA and petD mRNAs might be coupled via a mechanism independent of crp1, or the crp1 gene may function to coordinate the expression of the two genes, which encode subunits of the same complex.

The effect of chronic atrial overdrive suppression pacing on the incidence of supraventricular tachyarrhythmias.

Chronic overdrive suppression pacing has been suggested as an effective adjunctive method for reducing the incidence of cardiac tachyarrhythmias. Documentation of effectiveness during prolonged monitoring is lacking, however. To assess more accurately the long-term utility of this treatment modality for medically refractory supraventricular tachyarrhythmias (SVTs), 10 patients with atrially implanted Intermedics Intertach pacemakers were randomly assigned to either a low or a high bradycardia (back-up) pacing rate. SVT counts were performed during matching follow-up periods both at the initial rate and after rate crossover. The primary antitachycardia modality of this pacemaker (P mod) provides burst pacing to terminate tachycardia episodes, and P mod counters were utilized to quantitate SVT episodes. Tachycardia termination algorithms were programmed to "no restart" and were not changed during the study. The P mod use counter, therefore, reflected the number of discrete episodes of SVTs. Pacemaker implantation diagnoses include atrial flutter, concealed bypass tract, AV nodal reentry, intraatrial reentry, and Wolff-Parkinson-White associated tachycardia. Patient age was 59 +/- 18 yrs. The average pacemaker back-up low rate was 45.7 +/- 4 versus a back-up high rate of 85.1 +/- 2 beats/min. Follow-up was for 57.4 days +/- 33 days at the low rate and 57.3 days +/- 34 days at the high rate (r = 0.99). There was no difference in SVT incidence with a P mod usage of 98.4 +/- 106 at the low rate and 100.8 +/- 94 at the high rate (p = NS). In this blinded, randomized cross-over trial, chronic atrial overdrive suppression pacing did not reduce the overall incidence of SVT episodes during prolonged monitoring.

Physical determinants of the endocardial P wave.

UNLABELLED: Reliable atrial sensing of intrinsic P wave activity is important to ensure optimal atrial or dual chamber pacemaker function. Various physical factors (e.g., posture, respiration, exercise) may influence P wave characteristics and impair adequate sensing. To investigate this phenomenon, we measured the average of three P wave amplitudes (PWA) and calculated slew rates from telemetered printouts acquired from Pacesetter pacemakers in 32 patients. These measurements were performed in various body positions, with upright exercise and in varying stages of respiration. RESULTS: the mean supine PWA increased on full inspiration (3.56 +/- 1.3 mV versus 3.25 +/- 1.2 mV during quiet respiration, P less than 0.001), and also increased significantly with full expiration. The mean PWA increased on assuming the erect position (3.25 +/- 1.2 mV increasing to 3.49 +/- 1.3 mV, P less than 0.001); in the upright position, the mean erect PWA during quiet respiration was not significantly influenced by the stage of respiration. The mean upright exercise PWA did not differ significantly from the preexercise erect PWA (3.50 +/- 1.2 with exercise, and 3.47 +/- 1.5 before exercise; P = NS). Calculated slew rates were not different lying versus standing. CONCLUSIONS: the mean supine PWA increases significantly at the extremes of respiration and on assuming the erect body position; upright exercise results in no appreciable change in the erect PWA. Atrial sensitivity adjustments based on standard supine testing should be adequate for all body positions.

Atrial automatic tachycardia-reversion pacemakers: their economic viability and impact on quality-of-life.

UNLABELLED: Refractory supraventricular tachyarrhythmias may be both difficult and costly to control medically and can interfere with the patient's lifestyle. Newer treatment modalities are available for their management, and these require comprehensive assessment. We therefore compared costs and selective indices of patient benefit in a group of 17 patients in whom an atrial antitachycardia (Intermedics Intertach 262-12) pacemaker was placed for refractory supraventricular tachyarrhythmias. Prior medical therapy was compared to subsequent automatic antitachycardia pacemaker treatment. The total medical costs (admissions, emergency room visits, office visits, and medication costs) and the number of hospitalizations and medications were compared prior to implantation (F/U 69.3 +/- 61 months) and after implantation (F/U 15.3 +/- 7.8 months). A detailed quality-of-life questionnaire was also obtained 36.6 +/- 11 months after implantation. RESULTS: There were significant per patient differences in total cost before and after implantation: monthly costs were $505 +/- $833 before pacemaker implantation and $105 +/- $117 monthly afterward (P less than 0.005). Pacemaker implantation hospitalization costs were $19,063 +/- $8,362. Monthly medication costs averaged $46 before versus $15 after implantation (P less than 0.01). The number of medication types also differed with an average 5.5 medication types per patient before versus 1.2 after implantation (P less than 0.001). There were 8.6 yearly hospital admissions in the whole group before implantation, versus 4.7 admissions in the group per year thereafter. Patients demonstrated significant improvement in 80% of the quality-of-life parameters studied. CONCLUSION: Adjunctive atrial automatic tachycardia-reversion pacemaker therapy may be cost-competitive over time when compared to medical therapy alone in patients with refractory supraventricular tachyarrhythmias and appears to improve overall quality-of-life.