Moving From 'Best Interests' to 'Will and Preference': A Study of Doctors' Level of Knowledge Relating to the Assisted Decision-Making (Capacity) Act 2015.

Aims Irish decision-making capacity legislation is due to fundamentally change from 2022, with the commencement of the Assisted Decision-Making (Capacity) Act 2015, removing 'best interests' decision-making and replacing it with a 'will and preference' basis. This study aimed to investigate awareness amongst doctors regarding this Act, and specific knowledge relating to capacity assessment and advanced healthcare directives. Methods The study utilised a cross-sectional anonymised self-report questionnaire within a second tier hospital located in a rural part of Ireland. Results Only 2% of doctors had received any formal training on the Act, 25% were unsure of their role and 45% were unsure of a patient's role in decision-making. 37% believed that best interests was retained in decision-making. 50% were unaware of their obligations in assessing capacity, 23% were unable to assess capacity correctly and 47% were unsure of any consultative obligations in decision-making. 90% were unaware of what constituted a valid Advanced Healthcare Directive. Conclusion Further training is urgently required if the Act is to be successfully implemented in 2022.

Clozaril Withdrawal Induced Catatonia

Aim To describe an uncommon side effect of sudden withdrawal of Clozapine. Method This case describes the occurrence of catatonia following the sudden discontinuation of long term Clozapine therapy. Results Symptoms resolved with treatment with benzodiazepines and IV fluids. Discussion In conclusion, catatonia can occur on sudden discontinuation of Clozapine therapy. Caution should be exercised when reducing or discontinuing this medication.

Pregnancy and breastfeeding in mental health policy: a narrative review.

OBJECTIVES: Mental health difficulties are often exacerbated during the perinatal period. Policy and guidelines are increasingly being used to enhance the quality of healthcare. We conducted a literature review of published research relating to pregnancy and breastfeeding in mental health policy. METHODS: Relevant terms were searched in Medline, CINAHL, APA PsycINFO and EMBASE for articles published in English from 1970 until 2020. Only papers that referenced policy, guidance, legislation or standards were included. While a systematic approach was used, the nature of the results necessitated a narrative review. RESULTS: Initially, 262 papers were identified, 44 met the inclusion criteria. Reproductive health is given sparse consideration in research relating to mental health policy. Despite this, some key areas emerged. These included: the need for proactive preconception psychoeducation, proactive screening of mothers of infants and young children for perinatal mental health issues, enhanced prescribing practice for women of child-bearing age, enhanced monitoring during pregnancy, development of safe modification of coercive practices should they need to be employed in emergency circumstances and targeted measures to reduce substance misuse. Themes that arose relating to breastfeeding and bonding are also described. CONCLUSIONS: Female reproductive health is often ignored in research relating to mental health policy, guidelines and standards. These tools need to be harnessed to promote good healthcare. Reproductive health should be included in the care plan of all mental health patients. These topics need to be integrated into existing relevant policies and not isolated to a separate policy.

Support for community mental health teams post-suicide.

Suicide is a relatively common event in those seeking psychiatric care. However, its impact is nonetheless traumatic and devastating for those involved in the care of the patient. Community mental health teams (CMHTs) address every aspect of a patient's life, which creates a unique relationship between the team and the patient. Patient suicide can have serious, detrimental effects on individual team members, on the functioning of the team itself and on the care of other patients in the aftermath of such an event. In spite of this, there are limited protocols to guide CMHTs in this situation. This article seeks to emphasise the impact of patient suicide on CMHTs as a specific entity. It highlights the need for more research in this area, in order to direct the formation of more coherent local and national guidelines.

Fertile ground: reproductive health consideration in mental health ward policy.

OBJECTIVES: Women of childbearing age often experience mental health problems, receive psychotropic medication and are admitted to mental health units. Approximately 40% of pregnancies are unplanned and many women experience perinatal mental health problems. It is therefore vital that consideration is given to reproductive health in mental health policy. We aimed to evaluate the consideration of pregnancy and breastfeeding in the policies of an inpatient mental health service. METHODS: The policies of a regional inpatient psychiatric unit were independently reviewed by two researchers. Policies that had implications for pregnancy and breastfeeding for patients were identified. Whether or not these policies considered pregnancy and breastfeeding and the detail of this consideration was evaluated. RESULTS: One hundred and thirteen policies were evaluated. Forty had implications for pregnancy but only 10 of these mentioned pregnancy and only 3 in detail. Only 3 of the 28 policies that had relevance to breastfeeding mothers mentioned it and none discussed it in detail. Key areas of omission included prescribing, seclusion and restraint and cultural and religious considerations. CONCLUSION: Pregnancy and breastfeeding were almost entirely absent in the ward policies of our inpatient unit. Their consideration in the acute setting is vital. An individual or group of individuals should be responsible for ensuring that reproductive health is considered in all policies as well as in a larger specific policy suitable for referencing. The rights of the reproductive woman should be comprehensively considered in inpatient mental health care policy.

Intercellular adhesive selectivity. II. Properties of embryonic chick liver cell-cell adhesion.

Studies directed at understanding the molecular basis of liver cell homotypic adhesion are presented. An assay which measures the rate of adhesion of isotopically labeled (32PO4) embryonic chick liver cells to liver cell aggregates, described in a companion paper, has been used to investigate the problem of intercellular adhesive selectivity. Cation requirements, the effects of various inhibitors of metabolism and protein synthesis, of chelators (EDTA and EGTA), and the effects of temperature on liver cell adhesion are reported. Two mechanisms of inhibition of liver intercellular adhesion are suggested. One involves destruction of cell-surface adhesion receptors (sensitivity to proteases); the other is an energy-dependent step which may involve alterations in plasma membrane conformation and/or membrane fluidity. Finally, a model is suggested for liver cell-cell adhesion that incorporates the early tissue selectivity of intercellular adhesion previously reported, followed by a multistep process which leads to histogenic aggregation.

Intercellular adhesive selectivity. III. Species selectivity of embryonic liver intercellular adhesion.

A species difference in the intercellular adhesive selectivity of mixtures of embryonic liver cells is reported. This is first quantitative assessment of species differences in the intercellular adhesive properties of embryonic cells. A collecting aggregate assay, a new double-label assay procedure, and histological and autoradiographic procedures were used to elucidate the intercellular adhesive selectivity of developing mammalian and avian liver cells. Evidence is presented that the reported adhesive differences are not due to the different cell types composing the respective embryonic mammalian and avian livers. Finally, such heterolgous-homotypic selectivity of adhesion is not a property of all tissues, since it is shown that developing brain cells (mesencephalon) do not exhibit the avove intercellular adhesive selectivity (mammalian vs. avian). These findings provide further support for the hypothesis that generic identity as well as cell type may play an important part in determining the intercellular adhesive behavior of heterologous-homotypic mixtures of embryonic cells. A possible evolutionary divergence of morphogenetic mechanisms is discussed.

Intercellular adhesive selectivity. I. An improved assay for the measurement of embryonic chick intercellular adhesion (liver and other tissues).

An improved assay for measuring intercellular adhesive selectivity of embryonic chick liver cells is described. Three major improvements over earlier procedures are noted: (a) enhanced reproducibility of liver cell-liver cell aggregate adhesion (homotypic adhesion) was achieved; (b) 25-70% of the input cells adhered to the collecting aggregates during the course of routine experiments as compared to the 0.25% in earlier assays. This increase in cellular adhesion suggests that the observed cell pick-up is a characteristic of the majority of the dissociated liver cell population; (c) the rate of intercellular adhesion was increased 1,000-fold. The main feature of the assay is that it measures the tissue adhesive selectivities of the dissociated cell population. Studies were undertaken on three embryonic chick tissues (liver, neural retina, and mesencephalon) to determine the tissue selectivity of intercellular adhesion of these dissociated cell types. Some general properties of liver cell homotypic adhesion have been studied and are reported.

An assay for intercellular adhesive specificity.

A modification of an assay for intercellular adhesive specificity is described. The method involves the collection of radioactively labeled cells by aggregates of the same (isotypic aggregates) or different (heterotypic aggregates) types of tissue and determination of the number of cells collected by liquid scintillation counting. The use of (32)P to label the tissues permitted a much more rapid estimation of cell collection than was obtained previously. With the use of chick embryo neural retina, liver, forebrain, pectoral muscle, and heart ventricle tissue, it was shown that isotypic was always greater than heterotypic collection. Labeled neural retina cell collection by neural retina aggregates was studied as a function of time, cell suspension density, aggregate diameter, temperature, and aggregate number. Neural retina aggregates were treated with certain enzymes in an attempt to determine whether specific changes on the surface of the aggregates would interfere with labeled neural retina cell collection. Of the various proteases and glycosidases tested, only beta-galactosidase rendered the surface more nonspecific.

Evidence for cell-surface glycosyltransferases. Their potential role in cellular recognition.

Intact chicken embryo neural retina cells have been shown to catalyze the transfer of galactose-(14)C from uridine diphosphate galactose (UDP-galactose) to endogenous acceptors of high molecular weight as well as to exogenous acceptors. Four lines of evidence indicate that the galactosyltransferases catalyzing these reactions are at least partly located on the outside surface of the plasma membrane: (a) there is no evidence for appreciable uptake of sugar-nucleotides by vertebrate cells nor did unlabeled galactose, galactose 1-phosphate, or UDP-glucose interfere with the radioactivity incorporated during the reaction; (b) the cells remained essentially intact during the course of the reaction; (c) there was insufficient galactosyltransferase activity in the cell supernatants to account for the incorporation of galactose-(14)C into cell pellets; and (d) the intact cells could transfer galactose to acceptors of 10(6) daltons, and the product of this reaction was in the extracellular fluid. Appropriate galactosyl acceptors interfered with the adhesive specificity of neural retina cells; other compounds, which were not acceptors, had no effect. These results suggested that the transferase-acceptor complex may play a role in cellular recognition.

Use of aggregate fitness indicators to predict transition into the National Hockey League.

Athletes (n = 345) invited to the annual combine conducted by the National Hockey League (NHL) prior to the entry draft were administered tests to measure upper body strength, lower body power, aerobic and anaerobic energy systems, and body composition. Their common variance was extracted using factor analysis from which an overall composite index was derived. A score on this index in the 90th percentile is associated with 72% and 60% probability of playing in the NHL within 4 years after the draft for defensemen and forwards, respectively. These findings demonstrate that by taking into account the shared variance on standard tests of fitness, it is possible to use the athlete's results to gauge his potential for playing in the NHL.

Urethral diverticulum: a new complication associated with tension-free vaginal tape.

A case of a urethral diverticulum following the insertion of a tension-free vaginal tape (TVT) is presented. The patient was a woman with stress urinary incontinence who underwent surgery to correct intrinsic sphincter deficiency. Three cases of urethral diverticula have been published thus far as complications of TVT insertions, but this is the first complication associated with intrinsic sphincter deficiency. The high pressures in the proximal urethra that result from positioning the TVT in the middle urethra, especially when obstruction co-exists with an open bladder neck, can be a predisposing factor for this complication. The possibility of a urethral diverticulum when postvoid incontinence occurs after the insertion of a TVT should be carefully evaluated.

Relationship of physical fitness test results and hockey playing potential in elite-level ice hockey players.

The primary purpose of this study was to determine the fitness variables with the highest capability for predicting hockey playing potential at the elite level as determined by entry draft selection order. We also examined the differences associated with the predictive abilities of the test components among playing positions. The secondary purpose of this study was to update the physiological profile of contemporary hockey players including positional differences. Fitness test results conducted by our laboratory at the National Hockey League Entry Draft combine were compared with draft selection order on a total of 853 players. Regression models revealed peak anaerobic power output to be important for higher draft round selection in all positions; however, the degree of importance of this measurement varied with playing position. The body index, which is a composite score of height, lean mass, and muscular development, was similarly important in all models, with differing influence by position. Removal of the goalies' data increased predictive capacity, suggesting that talent identification using physical fitness testing of this sort may be more appropriate for skating players. Standing long jump was identified as a significant predictor variable for forwards and defense and could be a useful surrogate for assessing overall hockey potential. Significant differences exist between the physiological profiles of current players based on playing position. There are also positional differences in the relative importance of anthropometric and fitness measures of off-ice hockey tests in relation to draft order. Physical fitness measures and anthropometric data are valuable in helping predict hockey playing potential. Emphasis on anthropometry should be used when comparing elite-level forwards, whereas peak anaerobic power and fatigue rate are more useful for differentiating between defense.

Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma.

T-cell translocation gene 1 (Ttg-1), also called rhombotin, is deregulated upon translocation into the alpha/delta T-cell receptor loci in acute lymphoblastic leukemias bearing the t(11;14)(p15;q11). Ttg-1 encodes a nuclear protein, expressed predominantly in neuronal cells, which belongs to a novel family of transcription factors possessing LIM domains. We utilized the lck proximal promoter to overexpress this candidate oncogene in immature thymocytes of transgenic mice. lckPr Ttg-1 mice develop immature, aggressive T-cell leukemia/lymphomas. Tumor incidence is proportional to the level of Ttg-1 expression. Most tumors contain CD4+8+ cells as well as CD4-8+ cells, which have an immature rather than a mature peripheral phenotype. Ttg-1-induced tumorigenesis preferentially affects a minority population of thymocytes representing an immature CD4-8+ intermediate stage between double-negative CD4-8- cells and double-positive CD4+8+ cells. This model indicates that the aberrant expression of putative transcription factors plays a primary role in the genesis of T-cell acute lymphoblastic leukemias.

The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein.

Interchromosomal translocations within lymphoid neoplasms frequently involve the antigen receptor genes. We cloned the breakpoints of the t(11;14)(p15;q11) in a CD3-negative T-cell acute lymphoblastic leukemia cell line (RPMI 8402) in order to identify new genes potentially involved in T-cell neoplasia. An extensive comparison of both breakpoints and their germ line counterparts indicated that an inadvertant recombinase-mediated break at chromosome segment 11p15 recombined with the delta T-cell receptor at 14q11. The derivative 11 breakpoint resembles a coding joint in which 11p15 rather than a variable region was introduced 5' to a D delta 1 D delta 2 J delta 1 intermediate rearrangement. Conversely, the derivative 14 breakpoint corresponds to a signal joint between the 5' heptamer-spacer-nonamer recombinational signal of D delta 1 and an isolated heptamer at 11p15. Multiple, apparently distinct transcripts were found flanking both breakpoints of 8402. RNAs of 3.5, 4.4, 1.4, and 8.0 kilobases originating from either side of the derivative 14 breakpoint were highly expressed in 8402 compared with other cells. This suggests that this translocation deregulated multiple genes and provides the opportunity to assess any multifactorial contribution they may have to malignancy. We cloned and sequenced several cDNAs representing the 1.4-kilobase transcript (termed Ttg-1 [T-cell translocation gene 1]) from an 8402 library. The predicted protein of 156 amino acids contained two internal repeats which could potentially form zinc fingers.

Botulinum toxin: a potential alternative to current treatment of neurogenic and idiopathic urinary incontinence due to detrusor overactivity.

OBJECTIVE: To analyze and report the current data on the treatment of both neurogenic and idiopathic detrusor overactivity with Botulinum toxin. METHODS: Literature review using Pub-Med and Medline from 1990 until June 30, 2006. RESULTS: Case series of patients with neurogenic detrusor dysfunction (NDD) and idiopathic detrusor overactivity (IDO) range from 15 to 200 patients with follow up from 12 to 36 weeks post-treatment. Significant improvements in cystometric bladder capacity, reflex volume at first urge to void, and bladder compliance are seen in nearly all patients. Approximately 50% of NDD patients achieved urinary continence and almost all had improvement in bladder control up to 36 weeks following treatment. Patients with IDO with urgency alone or with incontinence also had urodynamic as well as symptom improvement. Approximately 75% of patients with IDO and incontinence are dry at 12 weeks post-treatment. Urgency disappears on average in two thirds of patients. Quality of life scores also shows significant improvement for all groups. CONCLUSION: Botulinum toxin-A has emerged as a promising option for the treatment of neurogenic and refractory idiopathic detrusor overactivity. Studies to date have shown that not only is this treatment effective at decreasing urinary symptoms and incontinence, as well as improving potentially dangerous urodynamic measures, but it is also minimally invasive, reversible and safe. Questions over proper dosing and dilution, number of injection sites, and re-injection rates remain to be answered.

Carcinogen bioassay and mutagenicity studies with the hypolipidemic agent gemfibrozil.

Gemfibrozil, a novel hypolipidemic agent identified chemically as 2,2-dimethyl-5-(2,5-xylyoxy) valeric acid, was evaluated for mutagenic potential in in vitro assays with Salmonella typhimurium. For evaluation of tumorigenic potential, gemfibrozil was administered in the diet (0.30, and 300 mg gemfibrozil/kg) to groups of noninbred CD-1 mice (72/sex) and noninbred CD rats (50/sex) for 78 and 104 weeks, respectively. In the bacterial mutagenesis assays, between 100 and 2,500 microgram gemfibrozil/plate failed to induce a significant increase in revertant bacterial colonies. Neither was a mutagenic response in bacterial assays induced at concentrations up to 300 microgram of five in vivo metabolites of gemifibrozil isolated from rat urine/plate. In mice, gemfibrozil did not significantly increase the frequency or the mean latency period of tumors. In rats, the statistically significant increases in hepatocellular tumors and interstitial cell tumors of the testes were dose related. Adrenal medullary and pancreatic acinar tumors were increased in male rats but were inversely dose related. Under the conditions of this assay, gemfibrozil did not elicit a tumorigenic potential in mice and female rats. In male rats and related to the hepatocellular tumor response, the peroxisome proliferation seen did not occur in humans chronically administered hypolipidemics.

The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.

Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to crossreactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants.

Potentiation of lymphomagenesis by methylnitrosourea in mice transgenic for LMO1 is blocked by O6-alkylguanine DNA-alkyltransferase.

We evaluated induction of lymphomas by the methylating carcinogen, N-methylnitrosourea [MNU], in transgenic mice expressing both LMO1 and the DNA repair gene, MGMT, in the thymus. The goal was to determine whether environmental mutagens shorten the latency or increase the incidence of LMO1 + lymphomas and whether mice transgenic for both LMO1 and MGMT, and thereby able to repair O6-methylguanine DNA adducts induced by MNU, would be protected. Mice heterozygous for LMO1 or MGMT were crossed and offspring treated with MNU at 6 weeks of age. MNU induced lymphoma incidence was highest in the LMO1 mice, 91% and lowest in the hMGMT + mice, 15%. MNU induced K-ras mutations in codon 12 in non-MGMT transgenics resulted in a shorter latency of tumors and accounting for half of the early lymphomas in LMO1 mice. The effect of MNU was abrogated in the LMO1/hMGMT transgenic mice, indicating the ability of MGMT expression to block the carcinogenic effect of MNU even in cancer prone mice. Thus, methylating agents potentiate lymphomagenesis of LMO1, in part through activation of K-ras and the MAPK pathway, a process which appear to synergize with LMO1 mediated transcription activation. O6-alkylguanine DNA-alkyltransferase mediated DNA repair effectively blocks chemical carcinogenesis in mice carrying the LMO1 oncogene.

Kinetics of native insulin in diabetic, obese, and aged men.

The kinetics of unlabeled porcine insulin were studied in 69 nondiabetic male subjects aged 18-83 yr with obesity indexes of 0.93 - 1.51 and in 12 maturity-onset diabetics age 46-78 yr with obesity indexes of 0.95-1.56 by using the euglycemic clamp technique. Analysis of the insulin kinetic data by using a mathematical model permitted the determination, for each individual, of steady state distribution masses and degradation rate constants. The individuals were grouped to allow comparison of the results on the basis of age, obesity index, or diabetes. The responses over a period of 120 min to an infusion and wash out of insulin show some transient as well as steady state differences with age, obesity, or diabetes. Analysis of these data by use of compartmental models leads to the conclusion that in the steady state the ratio of insulin in extravascular spaces to that in plasma (T/P) is decreased in the moderately obese group (26%) and in the diabetic group (17%) but increased in the older group (13%) when each is compared with the appropriate control. Since extravascular insulin includes both insulin bound to receptors and insulin in the interstitial fluid, the observed changes in the extravascular to plasma mass ratio most likely reflect changes in in vivo binding to receptors, although the magnitude of the change would be modified somewhat by changes in the size of the interstitial spaces relative to plasma. In addition, the rate of entry of new insulin into plasma (BSDR) was increased in the diabetic population (45%; P less than 0.02) as well as in the moderately obese group (27%) but was decreased somewhat in the older group (11%). The following general conclusions can be drawn from the results: The pattern of parameter changes seen with obesity is similar to that seen with maturity-onset diabetes. The decrease in T/P seen with obesity and with maturity-onset diabetes cannot be accounted for solely by changes in fasting plasma insulin levels in these populations. The pattern of changes seen in the older subjects is opposite that seen in the maturity-onset diabetics, which suggests that diabetes is a perturbation distinct from the normal aging process. Finally, the changes in the metabolism of insulin are not large, making it unlikely that they are the sole cause of the major alterations in glucose tolerance seen with aging, obesity, or diabetes.