Mental health and well-being in parents of excessively crying infants: Prospective evaluation of a support package.

BACKGROUND: During the first 4 months of age, approximately 20% of infants cry a lot without an apparent reason. Most research has targeted the crying, but the impact of the crying on parents, and subsequent outcomes, need to receive equal attention. This study reports the findings from a prospective evaluation of a package of materials designed to support the well-being and mental health of parents who judge their infant to be crying excessively. The resulting "Surviving Crying" package comprised a website, printed materials, and programme of Cognitive Behaviour Therapy-based support sessions delivered to parents by a qualified practitioner. It was designed to be suitable for United Kingdom (UK) National Health Service (NHS) use. METHODS: Parents were referred to the study by 12 NHS Health Visitor/Community Public Health Nurse teams in one UK East Midlands NHS Trust. Fifty-two of 57 parents of excessively crying babies received the support package and completed the Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 anxiety questionnaire, as well as other measures, before receiving the support package and afterwards. RESULTS: Significant reductions in depression and anxiety were found, with numbers of parents meeting clinical criteria for depression or anxiety halving between baseline and outcome. These improvements were not explained by reductions in infant crying. Reductions also occurred in the number of parents reporting the crying to be a large or severe problem (from 28 to 3 parents) or feeling very or extremely frustrated by the crying (from 31 to 1 parent). Other findings included increases in parents' confidence, knowledge of infant crying, and improvements in parents' sleep. CONCLUSIONS: The findings suggest that the Surviving Crying package may be effective in supporting the well-being and mental health of parents of excessively crying babies. Further, large-scale controlled trials of the package in NHS settings are warranted.

The incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus in New Zealand Maori and Pacific Island children: the Starship experience (2000-2010).

OBJECTIVES: To describe the incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus (jSLE) in a cohort of New Zealand Maori and Pacific Island children compared to European children. METHODS: A chart review was conducted of children with jSLE seen by the Starship paediatric rheumatology and/or renal services between January 2000 and November 2010. Diagnostic clinical data and lupus nephritis data at anytime were collated while classic British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were derived retrospectively. RESULTS: Thirty-two children were diagnosed with jSLE with an annual incidence of 0.52 per 100,000 per year. Compared with European children (0.31 per 100,000 per year) the incidence of jSLE was higher among Maori and Pacific (0.67 per 100,000 per year, p=0.06) and significantly higher among Asian children (1.17 per 100,000 per year, p=0.01). Compared with European children, Maori and Pacific children were more frequently diagnosed with lupus nephritis (80% vs 40%, p=0.09) and severe (WHO class 4 or 5) renal lesions (60% vs 40%, p=0.43) at presentation. Similarly, at any time during the study, lupus nephritis (100% vs 40%, p=0.001) and severe (WHO class 4 or 5) renal lesions (73.3% vs 40%, p=0.12) were more frequent among Maori and Pacific compared with European children. Furthermore, retrospective BILAG assessment of diagnostic disease severity demonstrated that Maori and Pacific children experienced the majority of severe "Category A" disease (56.8% vs 22.7%, p=0.17) which was predominantly renal (73.3% vs 40%, p=0.12) in nature. CONCLUSIONS: This is the first description of the incidence and clinical manifestations of jSLE in a cohort of New Zealand children. Although limited by the small numbers involved it confirmed anecdotal suspicions that the incidence of jSLE among Maori, Pacific and Asian children is higher than European children. Lupus nephritis is also more frequent and severe in Maori and Pacific children.

Relocalization of phospholipase D activity mediates membrane formation during meiosis.

Phospholipase D (PLD) enzymes catalyze the hydrolysis of phosphatidylcholine and are involved in membrane trafficking and cytoskeletal reorganization. The Saccharomyces cerevisiae SPO14 gene encodes a PLD that is essential for meiosis. We have analyzed the role of PLD in meiosis by examining two mutant proteins, one with a point mutation in a conserved residue (Spo14pK--> H) and one with an amino-terminal deletion (Spo14pDeltaN), neither of which can restore meiosis in a spo14 deletion strain. Spo14pK--> H is enzymatically inactive, indicating that PLD activity is required, whereas Spo14pDeltaN retains PLD catalytic activity in vitro, indicating that PLD activity is not sufficient for meiosis. To explore other aspects of Spo14 function, we followed the localization of the enzyme during meiosis. Spo14p is initially distributed throughout the cell, becomes concentrated at the spindle pole bodies after the meiosis I division, and at meiosis II localizes to the new spore membrane as it surrounds the nuclei and then expands to encapsulate the associated cytoplasm during the formation of spores. The catalytically inactive protein also undergoes relocalization during meiosis; however, in the absence of PLD activity, no membrane is formed. In contrast, Spo14pDeltaN does not relocalize properly, indicating that the failure of this protein to complement a spo14 mutant is due to its inability to localize its PLD activity. Furthermore, we find that Spo14p movement is correlated with phosphorylation of the protein. These experiments indicate that PLD participates in regulated membrane formation during meiosis, and that both its catalytic activity and subcellular redistribution are essential for this function.

Disease Activity Score 28-ESR bears a similar relationship to treatment decisions across different rheumatologists, but misclassification is too frequent to replace physician judgement.

OBJECTIVES: To determine whether physician factors are associated with disease activity status in RA, independently of 28-joint disease activity score (DAS28)-ESR and to re-evaluate DAS28-ESR misclassification rates for identifying active disease in usual practice. METHODS: A prospective observational study of outpatients with RA seen by 17 rheumatologists across New Zealand. Active disease was defined by an increase in therapy together with a reason of 'active disease'; very low disease activity was defined by a decrease in therapy together with a reason of 'patient well'. The independent physician effect was assessed using logistic regression. Sensitivity and specificity of current DAS28-ESR thresholds were calculated. RESULTS: In 511 patients, 178 had active disease, 220 had low disease activity, 37 had very low disease activity and 76 had uncertain disease activity status. There was no independent effect of physician upon active disease status (P = 0.16) with DAS28-ESR [(OR) 3.7] explaining around 50% of the variability in active disease status. There was a trend towards an independent effect of physician upon very low disease activity status (P = 0.06) and greater variability in the distribution of DAS28-ESR for patients in very low disease activity. DAS28-ESR thresholds showed a significant risk of misclassification for active disease. CONCLUSIONS: DAS28-ESR discriminates satisfactorily between groups of patients with active and non-active disease, with no evidence of additional physician-specific factors to explain disease activity status. However, DAS28-ESR is not as good for discriminating remission from non-remission status. There are appreciable probabilities of misclassification error, which make DAS28-ESR inappropriate as a sole guide for treatment decisions.

Incidence of clinically suspected venous thromboembolism in British Indian patients.

Introduction Venous thromboembolism (VTE) remains a major public health issue around the world. Ethnicity is known to alter the incidence of VTE. To our knowledge, there are no reports in the literature investigating the incidence of VTE in British Indians. The aim of this study was to investigate the rates of symptomatic VTE in British Indian patients in the UK. Methods Patients referred to our institution between January 2011 and August 2013 with clinically suspected VTE were eligible for inclusion in the study. Those not of British Indian or Caucasian ethnicity were excluded. A retrospective review of these two cohorts was conducted. Results Overall, 15,529 cases were referred to our institution for suspected VTE. This included 1,498 individuals of British Indian ethnicity. Of these, 182 (12%) had confirmed VTE episodes. A further 13,159 of the patients with suspected VTE were coded as Caucasian, including 2,412 (16%) who had confirmed VTE events. VTE rates were a third lower in British Indians with clinically suspected VTE than in the equivalent Caucasian group. The British Indian cohort presented with VTE at a much earlier age than Caucasians (mean 57.0 vs 68.0 years). Conclusions This study suggests that British Indian patients have a lower incidence of VTE and are more likely to present at an earlier age than Caucasians. There was no significant difference in VTE type (deep vein thrombosis vs pulmonary embolism) among the ethnic groups. Clinicians should be aware of variations within ethnicities but should continue to adhere to existing VTE prevention guidance.

ADP-Ribosylation factors do not activate yeast phospholipase Ds but are required for sporulation.

ADP-ribosylation factor (ARF) proteins in Saccharomyces cerevisiae are encoded by two genes, ARF1 and ARF2. The addition of the c-myc epitope at the C terminus of Arf1 resulted in a mutant (arf1-myc arf2) that supported vegetative growth and rescued cells from supersensitivity to fluoride, but homozygous diploids failed to sporulate. arf1-myc arf2 mutants completed both meiotic divisions but were unable to form spores. The SPO14 gene encodes a phospholipase D (PLD), whose activity is essential for mediating the formation of the prospore membrane, a prerequisite event for spore formation. Spo14 localized normally to the developing prospore membrane in arf1-myc arf2 mutants; however, the synthesis of the membrane was attenuated. This was not a consequence of reduced PLD catalytic activity, because the enzymatic activity of Spo14 was unaffected in meiotic arf1-myc arf2 mutants. Although potent activators of mammalian PLD1, Arf1 proteins did not influence the catalytic activities of either Spo14 or ScPld2, a second yeast PLD. These results demonstrate that ARF1 is required for sporulation, and the mitotic and meiotic functions of Arf proteins are not mediated by the activation of any known yeast PLD activities. The implications of these results are discussed with respect to current models of Arf signaling.

Regulation and function of PLDs in yeast.

While yeast contain multiple phospholipase D activities, only one, encoded by SPO14, appears to be a member of the phosphatidylcholine-specific phospholipase D gene family. Genetic analyses have revealed a role for this enzyme in regulated membrane trafficking events.

SPO14 separation-of-function mutations define unique roles for phospholipase D in secretion and cellular differentiation in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, phospholipase D (PLD), encoded by the SPO14 gene, catalyzes the hydrolysis of phosphatidylcholine, producing choline and phosphatidic acid. SPO14 is essential for cellular differentiation during meiosis and is required for Golgi function when the normal secretory apparatus is perturbed (Sec14-independent secretion). We isolated specific alleles of SPO14 that support Sec14-independent secretion but not sporulation. Identification of these separation-of-function alleles indicates that the role of PLD in these two physiological processes is distinct. Analyses of the mutants reveal that the corresponding proteins are stable, phosphorylated, catalytically active in vitro, and can localize properly within the cell during meiosis. Surprisingly, the separation-of-function mutations map to the conserved catalytic region of the PLD protein. Choline and phosphatidic acid molecular species profiles during Sec14-independent secretion and meiosis reveal that while strains harboring one of these alleles, spo14S-11, hydrolyze phosphatidylcholine in Sec14-independent secretion, they fail to do so during sporulation or normal vegetative growth. These results demonstrate that Spo14 PLD catalytic activity and cellular function can be differentially regulated at the level of phosphatidylcholine hydrolysis.

Rat testicular myoid cells express vasopressin receptors: receptor structure, signal transduction, and developmental regulation.

Detection of the neurohypophysial hormones vasopressin (AVP) and oxytocin (OT) in the testis of several species has led to the proposal that these peptides may have a physiological role in the regulation of testicular function. Therefore, we investigated whether the contractile myoid cells of rat seminiferous tubules express functional receptors for AVP or OT and, thus, constitute a target for these hormones. This study used primary cultures of purified peritubular myoid cells derived from rats both before and after puberty. By several criteria, myoid cells prepared from adult rats expressed vasopressin receptors (VPRs). We detected specific and saturable [3H]AVP binding to a single population of sites with a Kd of 7.5 nM and a binding capacity of 145 fmol/mg protein. AVP stimulated the accumulation of inositol phosphates in a dose-dependent manner with an EC50 of 1.7 nM. Cloning and sequencing of the myoid cell VPR confirmed it to be the V1a subtype of VPR. VPR expression by myoid cells is under developmental control, as the receptors are present in the adult rat, but absent before puberty. In contrast, OT receptors were not expressed at any stage of development. Peritubular myoid cells are also responsive to endothelin-1 (ET-1), which potently stimulated phosphoinositidase-C. However, unlike AVP, the ET-1 responses were observed both before and after sexual maturity, suggesting different roles for AVP and ET-1 in the control of myoid cell function. Our data establish that the myoid cells of the adult rat seminiferous tubule are a target for AVP. This indicates an additional role for AVP in the regulation of testicular function and male fertility in the adult rat.

Preparation, characterization, and performance of magnetic iron-carbon composite microparticles for chemotherapy.

Magnetic microcarrier particles useful for delivering chemotherapeutic drug molecules are described. The particles are formed by joint deformation of iron and carbon in a ball mill. Physical, chemical, and functional characterization has been carried out on the particles. Physical characteristics include microscopy, particle size analysis (0.5-5 microm), surface area (250 m2/g), water vapor adsorption isotherm (hydrophobic surface), and analysis of the iron-carbon interface by Mössbauer spectroscopy, X-ray diffraction, and differential thermal analysis. Chemical analysis was used to identify elements in the particles other than carbon and iron. Functional characteristics measured included the particles' ability to adsorb and desorb doxorubicin, cytotoxicity, and their magnetic susceptibility.

Adsorption and desorption of chemotherapeutic drugs from a magnetically targeted carrier (MTC).

Magnetically targeted carriers (MTCs) are composite microparticles made from metallic iron and activated carbon. Particles, loaded with doxorubicin in the pharmacy (MTC-DOX), are infused intra-arterially through the artery feeding the tumor. With the aid of an externally positioned permanent dipole magnet, they can be localized and retained within a tumor mass. MTC-DOX is currently in use in a Phase I/II clinical study as a delivery vehicle for doxorubicin in primary hepatocellular carcinoma. The adsorption and desorption of doxorubicin, mitomycin C, camptothecin, methotrexate, verapamil and 9AC onto MTCs have been analyzed. Each of these chemotherapeutic agents has a different mechanism of action, suggesting that some benefit may be derived from combined delivery to a tumor using MTCs and magnetic targeting. Each drug displays different behavior with respect to adsorption and desorption. However, this behavior can be described for each drug with a non-linear thermodynamic model. The thermodynamic model predicts a controlled release rate by adjusting a number of parameters, including initial drug loading concentrations. This is confirmed with in vitro extraction experiments using human plasma as the extraction medium.

Electrokinetic isolation of vesicles and ribosomes derived from Serratia marcescens.

Ribosomes and vesicles derived from the bacterium Serratia marcescens were separated from each other and from solubles using density gradient electrophoresis. Transport relationships were used to determine the electrophoretic mobilities of the particles. The effects of convection, sedimentation and diffusion were found to be negligible. The electrophoretic mobility obtained for the ribosome peak is -7 x 10(-5) cm2/(V.s). Under appropriate conditions, two vesicles peaks were obtained, the first with a mobility of -4 x 10(-5) cm2/(V.s) and the second with -9 x 10(-6) cm2/(V.s). This information can be used to predict the resolution of the separands in large-scale electrophoretic separations.

Research activities and interests of dietetic educators.

Dietetic educators need to conduct research for academic promotion and tenure, and they are often called upon to provide leadership for research in the profession. A study was conducted to develop a profile of the research productivity, skill needs, and research environment of dietetic educators. Questionnaires were sent to 854 full-time faculty members in coordinated, didactic (Plan IV), technician, and graduate programs in dietetics; responses were received from 354 (41%). More than one-fourth of respondents (26.2%) reported spending no time in research, while 29.2% spent 9 or more hours per week in that activity. Those with doctoral degrees, at the rank of professor, working in major research institutions spent significantly more time in research than did other faculty members. In the previous 5 years, 67.3% had written proposals and served as principal investigator for at least one study, and 58% had received research funding. Half had written research papers, and 65% had written other publications. Only 60.2% had presented research papers, but 74.8% had given other types of presentations. Nearly 75% of educators indicated interest in collaborative studies; more than half reported a need for skills in getting funded, generating statistics, and writing research protocols. Most educators had a personal interest in research, had access to computers, and agreed that research was both rewarded and essential for academic advancement. Only 15.2% agreed that research was financially or administratively supported, and 22.8% said that they were confused about the relative importance of research in relation to teaching and service. These findings provide baseline data for setting goals and making recommendations for further research involvement.

The role of serotonin in depression and anxiety.

Although many serotonin (5-hydroxytryptamine; 5-HT) receptors have been identified, our knowledge of many of the subtypes is limited. However, we do know that 5-HT1A agonists are involved in the treatment of certain anxiety disorders, that 5-HT1C and 5-HT2 receptor antagonists may be indicated for the treatment of generalized anxiety disorder, and that 5-HT1D receptor agonists are used in the treatment of migraine. Recent research has identified that various abnormalities in serotonergic function are involved in the pathogenesis of depression and anxiety, and has facilitated the development of new pharmacological agents with great therapeutic potential, for example the selective serotonin reuptake inhibitors (SSRIs). These agents appear to be effective in the treatment of many anxiety states and may have greater efficacy than other agents in the treatment of certain affective disorders. As the central serotonergic system continues to be "mapped", newer and more selective drugs are likely to be introduced, thereby possibly improving the overall successful management of depression and anxiety disorders.

The determination of thiomalate in physiological fluids by high-performance liquid chromatography and electrochemical detection.

Methods are described for the determination of free thiomalate in the plasma and urine of patients receiving the anti-rheumatic drug sodium aurothiomalate. Thiomalate is separated by reversed-phase chromatography and detected using a gold electrochemical cell. Plasma analyses require maximal sensitivity while urine estimations require selectivity rather than sensitivity: different phosphate buffer-methanol eluents and electrode potentials are used. On-column sensitivity for thiomalate is 40 fmol injected.

Effect of carbohydrate ingestion on performance of non-fasted cyclists during a simulated 80-mile time trial.

The purpose of this study was to determine the effect of carbohydrate supplementation on finishing time of a realistically simulated 80 mile bicycle time trial. Fourteen trained cyclists pedalled at self-selected pace on their own bicycles on windload simulators. Two trials were performed one week apart. Each trial was preceded by two days of prescribed diet, with a final feeding 3-4 h prior to exercise. Following each 10 mile segment, subjects ingested either a non-caloric placebo (PL) or the carbohydrate maltodextrin supplement (MD; 5% maltodextrin +2% fructose) at dosage of 0.25 g.kg-1 body weight (mean intake rate, total: 37 g.h-1, 148 g) in a double blind, counter-balanced design. Mean (+/- SEM) finishing times were faster by 5% with MD (241.0 +/- 2.1 minutes versus 253.2 +/- 2.1 minutes), p < 0.05. With MD, serum glucose levels rose sharply after 40 miles and were significantly higher than PL (p < 0.05). Final glucose values were 6.0 +/- 0.2 mmol.l-1 and 4.1 +/- 0.2 mmol.l-1 for MD and PL, respectively. With MD, free fatty acid levels were significantly lower (p < 0.05), and riders sustained higher average intensity over the entire distance. At the finish, intensities were 64.7 +/- 1.9% VO2max and 55.3 +/- 1.9% VO2max for GP and PL, respectively. Mean carbohydrate oxidation was significantly higher (p < 0.05) for MD, 2.01 +/- 0.2 g.min-1 and 1.64 +/- 0.2 g.min-1 for MD and PL, respectively. These data show that ingestion of MD, during ultraendurance exercise, in comparison to PL, decreases the time to finish a self-paced bicycle time trial.

Social factors and first onset schizophrenia among Asians and whites.

Previous studies from the Indian subcontinent had suggested that the onset and outcome of schizophrenia is linked with social factors. We set out to study the inception rates and social factors in whites and Asians who were presenting for the first time ever to various catchment facilities in Ealing catchment area. A total of 62 cases (38 white and 24 Asians) were diagnosed as having schizophrenia. Using well established and previously validated standardised instruments we collected information on various social factors and inception rates of schizophrenia. The inception rates and social factors were largely similar in these two groups. By and large the social factors in the two groups were broadly similar except that Asians were significantly more likely to show increased religious activity compared with their white counterparts. Contrary to previous findings Asians were more likely to have had longer duration of symptoms prior to seeking help. These findings are discussed in relation to Asian support systems and suggestions made for future research.