Collaborative working in health and social care: Lessons learned from post-hoc preliminary findings of a young families’ pregnancy to age 2 project in South Wales,United Kingdom

Children of young and socially disadvantaged parents are more likely to experience adverse outcomes. In response to this, a unique young families’ project in Swansea, UK, was created, which drew together a team of multi-agency professionals, to support people aged 16–24 from 17 weeks of pregnancy throughout 1,001 days of the child's life. The aim of the JIGSO (the Welsh word for Jigsaw) project is for young people to reach their potential as parents and to break the cycle of health and social inequality. This evaluation analysed routinely collected data held by the project from January 2017 to December 2018 exploring health and social outcomes, including smoking and alcohol use in pregnancy, breastfeeding, maternal diet and social services outcomes. Outcomes were compared to local and national averages, where available. Data relating to parenting knowledge and skills were available via records of 10-point Likert scales, one collected at the start of the JIGSO involvement and one around 4–6 months later. Findings showed higher than average levels of breastfeeding initiation and lower smoking and alcohol use in pregnancy. Parents also reported enhanced knowledge and confidence in their child care skills, as well as improved family relationships. Parents with high levels of engagement with JIGSO also appeared to have positive outcomes with Social Services (their child's name was removed from child protection register or their case was closed to social services). This was a post-hoc evaluation, not an intervention study or trial, and thus findings must be interpreted with caution. Despite this, the findings are promising and more prospective research exploring similar services is required.     

Fragile X-related protein and VIG associate with the RNA interference machinery

RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease.     

Cisplatin-induced reductions in renal functional reserve uncovered by unilateral nephrectomy: an experimental study in the pig

Summary Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to90, 120 and 150 mg/m²) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [^{99 m}Tc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically,and GRF and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with 2mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S₁ portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GRF and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was <50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically silent until exposure to an additional nephrotoxic insult.This study was supported by the Cancer Research Campaign     

Community absorption of the mentally ill: The new challenge

In 1975, twelve years after enactment of the Community Mental Health Centers Act, we find one of the greatest obstacles to fulfillment of our hopes to be pervasive hostility to acceptance of the mentally ill in many communities. The River Region Program has hurdled this obstacle by breaking the artificially large mental health catchment areas into manageable segments of 16 smaller service areas close to the people it serves in seven counties of Kentucky. In each of these service areas it has involved a broad spectrum of citizens in the planning of every service. All of this is of particular relevance today in light of the Supreme Court's D,onaldson decision, that mentally ill persons cannot be confined involuntarily if they are not dangerous and can live safely in the outside world. The outside world must be prepared to receive these people, and we in the mental health field must do our job in this vital preparation.Mr. Gorman originally presented this paper as a speech at the Annual Dinner, of the River Region Mental Health — Mental Retardation Board in Louisville, Kentucky, on June 20, 1975.     

Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies.

PURPOSE: Recently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study. PATIENTS AND METHODS: Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting level of approximately 130 micromol/L to below the level of detection (< 2 micromol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose. RESULTS: This therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present (> 680 days). CONCLUSION: Elimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted.     

A longitudinal,functional study of peripheral nerve recovery in the mouse

Objectives: To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. Study Design: Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. Results: Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). Conclusions: The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.