TURN-IT: a novel turning intervention program to improve quality of turning in daily life in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility. METHODS: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires. DISCUSSION: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls. TRIALS REGISTRATION: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 .

Inflection points in longitudinal models: Tracking recovery and return to play following concussion.

The return to play (RTP) process may occur during longitudinal studies tracking recovery after concussion. This factor, which is often omitted within statistical designs, could affect the fit and overall interpretation of the statistical model. This article demonstrates the difference in results and interpretation between 2 linear mixed-model designs: (1) a between-group longitudinal (GROUP) analysis and (2) a between-group longitudinal model that used an inflection point to account for changes around the time of RTP (RTP analysis). These analyses were conducted on instrumented balance data collected on 23 concussed athletes and 25 controls over 8 weeks following concussion. Total sway area and the range of mediolateral acceleration were used as outcome measures. No significant findings were found in the GROUP design for either outcome measure. In contrast, the RTP analysis revealed significant effects of time (P = .007) and RTP change (P = .007), and group*time (P = .028) and group*RTP change (P = .022) interactions for total sway area, and effects of group (P = .011), time (P = .010), and RTP change (P = .014), and group*time (P = .013) and group*RTP change interactions (P = .013) for range of mediolateral acceleration. For both outcomes, the RTP model fit the data significantly better on comparison of likelihood ratios (P ≤ .027). These results suggest that allowing for an inflection point in the statistical design may assist understanding of what happens around clinically meaningful time points. The choice of statistical model had a considerable effect on the interpretation of findings, and provokes discussion around the best method for analyzing longitudinal datasets when important clinical time points like RTP exist.

Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi.

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.

Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

BACKGROUND: There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. METHODS/DESIGN: This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. DISCUSSION: The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. TRIAL REGISTRATION: This trial is registered at clinical trials.gov (NCT02231073).

Outbreak of haemolytic uraemic syndrome due to Shiga toxin-producing Escherichia coli O104:H4 among French tourists returning from Turkey, September 2011.

Eight cases of diarrhoea, including two cases of haemolytic uraemic syndrome (HUS), were identified among 22 French tourists who travelled to Turkey in September 2011. A strain of Escherichia coli O104:H4 stx2-positive, eae-negative, hlyA-negative, aggR-positive, ESBL-negative was isolated from one HUS case. Molecular analyses show this strain to be genetically similar but not indistinguishable from the E. coli O104:H4 2011 outbreak strain of France and Germany. Although the source of infection was not identified, we conclude that the HUS cases had probably been infected in Turkey.

Two outbreaks of botulism associated with consumption of green olive paste, France, September 2011.

Two family outbreaks of botulism (a total of nine cases) were identified in south-east and northern France in early September 2011. The source of infection was considered to be a ground green olive paste. Botulinum type A toxin was identified in seven cases and in the incriminated olive paste. Incorrect sterilisation techniques were observed at the artisanal producer's workshop. These episodes highlight the potential public health threat of Clostridium botulinum linked to inadequate sterilisation of food products.

Clustered cases of infections due to an uncommon methicillin-resistant Staphylococcus aureus originating in a maternity ward.

OBJECTIVE: We aimed to report a community outbreak of an uncommon methicillin-resistant Staphylococcus aureus (MRSA) originating in a maternity ward. PATIENTS AND METHODS: Cases were defined by epidemiological, clinical, and microbiological investigations. Microbiological investigations included phenotypic analysis, molecular typing, and whole-genome sequencing. To control the outbreak, we applied both national recommendations to prevent in-hospital transmission and the French High Council for Public Health guidelines on the management of community-acquired MRSA infections. RESULTS: Between March and July 2016, seven patients with MRSA infections were identified: six skin and soft tissue infections and one pulmonary infection, including six microbiologically confirmed infections. Infections occurred in community settings, but a link with the same maternity ward was found for all patients. All MRSA strains had a t690 spa type, were tetracycline-resistant, and produced Panton-Valentine leukocidin. All isolates belonged to the sequence type 88 (ST88). CONCLUSION: This outbreak highlights the largely underestimated risk of healthcare-associated infections in maternity wards. Healthcare workers should be aware of the importance of standard hygiene precautions and use of alcohol-based hand sanitizers for neonates and mothers.

Botulism and hot-smoked whitefish: a family cluster of type E botulism in France, September 2009.

A family cluster of three cases of type E botulism were identified in south-east France in September 2009. The suspected food source of infection was a vacuum packed hot-smoked whitefish of Canadian origin purchased by the family during a visit to Finland and consumed several weeks later in France on the day prior to symptom onset. No leftover fish was available to confirm this hypothesis. Vacuum packed hot-smoked whitefish has previously been associated with cases of type E botulism in multiple countries, including Finland, Germany, the United States and Israel.

Two severe cases of botulism associated with industrially produced chicken enchiladas, France, August 2008.

Two severe familial cases of botulism were reported to the health authorities in Brittany, north-west France, on 11 August 2008. An investigation was undertaken to identify additional cases, the vehicle of transmission, and to put in place adapted control measures.

Introduction of human papillomavirus (HPV) vaccination into national immunisation schedules in Europe: Results of the VENICE 2007 survey.

The European Union Member States are simultaneously considering introducing HPV vaccination into their national immunisation schedules. The Vaccine European New Integrated Collaboration Effort (VENICE) project aims to develop a collaborative European vaccination network. A survey was undertaken to describe the decision status and the decision-making process regarding the potential introduction of human papillomavirus (HPV) vaccination in to their national immunisation schedules. A web-based questionnaire was developed and completed online in 2007 by 28 countries participating in VENICE. As of 31 October 2007,five countries had decided to introduce HPV vaccination into the national immunisation schedule, while another seven had started the decision-making process with a recommendation favouring introduction. Varying target populations were selected by the five countries which had introduced the vaccination. Half of the surveyed countries had undertaken at least one ad hoc study to support the decision-making process. According to an update of the decision-status from January 2008, the number of countries which had made a decision or recommendation changed to 10 and 5 respectively. This survey demonstrates the rapidly evolving nature of HPV vaccine introduction in Europe and the existence of expertise and experience among EU Member States. The VENICE network is capable of following this process and supporting countries in making vaccine introduction decisions. A VENICE collaborative web-space is being developed as a European resource for the decision-making process for vaccine introduction.

Hemolytic uremic syndrome due to Shiga toxin-producing Escherichia coli infection.

The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin-producing Escherichia coli (STEC) infection, which has a major outbreak potential. Since the early 2010s, STEC epidemiology is characterized by a decline of the historically predominant O157 serogroup and the emergence of non-O157 STEC, especially O26 and O80 in France. STEC contamination occurs through the ingestion of contaminated food or water, person-to-person transmission, or contact with ruminants or their contaminated environment. The main symptom is diarrhea, which is bloody in about 60% of patients and occurs after a median incubation period of three days. Shiga toxins released by STEC induce a cascade of thrombogenic and inflammatory changes of microvascular endothelial cells. HUS is observed in 5-15% of STEC infection cases, defined by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal injury. The diagnosis of STEC infection relies on biological screening for Shiga toxins and STEC in stools and serology. Treatment of STEC-HUS is mainly symptomatic, as no specific drug has proved effective. The effect of antibiotics in STEC infection and STEC-HUS remains debated; however, some bacteriostatic antibiotics might have a beneficial effect. Proofs of evidence of a benefit from complement blockade therapy in STEC-HUS are also lacking. Clinical and bacteriological STEC-HUS surveillance needs to be continued. Ongoing prospective studies will document the role of bacteriostatic antibiotics in STEC infection and STEC-HUS, and of complement blockade therapy in STEC-HUS.

Hospital workplace experiences of registered nurses that have contributed to their resignation in the Durban metropolitan area.

TITLE: Hospital workplace experiences of registered nurses that have contributed to their resignation in the Durban Metropolitan Area. AIM: The purpose of this research was to explore and describe the hospital workplace experiences that had contributed to the resignations of Registered Nurses in the Durban Metropolitan Area. METHODOLOGY: The broad perspective governing this research is qualitative in nature. The researcher employed a phenomenological approach specifically because the researcher was interested in identifying, describing and understanding the subjective experiences of individual nurses at the two Private and two Provincial health care institutions selected to participate in the study - in respect of their decision (s) to resign from their employment, and/or to leave the nursing profession. Two semistructured interviews were conducted with each participant by the researcher. The researcher applied the principle of theoretical saturation and a total of fifteen participants were interviewed and thirty interviews were conducted. Experiential themes and subthemes in the data were identified by a process of meaning condensation, and the data were managed by means of a qualitative software package - NVIVO (QSR - NUD*IST). FINDINGS: The resignations of registered nurses in the Durban Metropolitan Area were found to be linked to their respective hospital workplace experiences. These experiences related to their physical working conditions and environment and included the following: unsupportive management structures, autocratic and dehumanizing management styles, negative stereotypy of nurses and the nursing profession, lack of autonomy in the workplace, professional jealousies and fractures within the profession, sub-optimal physical working conditions and shortage of staff, equipment and lack of appropriate surgical supplies, concerns regarding occupational safety e.g. the increasing exposure of health care personnel to HIV and AIDS; lack of opportunities for promotion or continuing one's professional education, the experience of workplace violence--predominantly in the form of verbal and psychological abuse, inaccurate systems of performance assessment (Joint Performance Management, Reports, Personal Profile systems)--compounded by favouritism and racism; and inadequate remuneration. CONCLUSION: In terms of the findings of this study, the participants' lived experiences in terms of their respective hospital workplace experiences indicated that neither the maintenance factors nor the motivator factors were optimally represented, experienced or enjoyed in their respective workplaces. In terms of Herzberg's Motivator-Maintenance theory, the registered nurses who participated in this study may be described as being 'not satisfied' and 'dissatisfied' with their hospital workplace experiences, physical conditions and environment. A number of recommendations pertaining to strategies for the retention of registered nurses were made for the consideration of both Provincial and Private health care authorities, hospital management structures and the nursing profession respectively. Recommendations for further nursing research were also made.

The low-temperature luminescence properties of bovine alpha-lactalbumin.

The luminescence of bovine alpha-lactalbumin at 77 K has been studied and compared with that of lysozyme. Alpha-Lactalbumin has several unusual properties, including a fluorescence spectrum showing vibrational fine structure, an abnormal phosphorescence spectrum, a high fluorescence: phosphorescence ratio and an abnormal phosphorescence decay. These properties are largely due to the proximity of tryptophan residues to disulphide bonds. Reduction of all these bonds causes considerable changes in alpha-lactalbumin luminescence, as does denaturation in acid solution. Reduction of a single labile disulphide bond has little effect, and the properties of alpha-lactalbumin III, a variant lacking one disulphide bond and one trypotophan residue, are similar to those of the normal protein. Several differences between alpha-lactalbumin and lysozyme are reported. The results support the suggestion that the two tryptophan residues found in the active site cleft of alpha-lactalbumin may be largely responsible for its luminescence.

Factors affecting the luminescence of tryptophan at 77 K.

The effects of solvent polarity, heavy atoms and sulphur-containing compounds on the fluorescence and phosphorescence of indole and tryptophan have been investigated. The low-temperature luminescence of a group of dipeptides containing tryptophan is also reported. The phosphorescence to fluorescence quantum yield ratio and the phosphorescence lifetime are shown to be particularly sensitive to environmental factors. The relevance of these results to the interpretation of protein luminescence spectra is briefly discussed.

Stable insect cell cultures for recombinant protein production.

Insect cells are relatively cheap to maintain and are capable of producing accurately translated and correctly processed heterologous proteins. Recent research has focused on the development of improved expression vectors for continuous, high-level production of foreign proteins, including a number of membrane-targeted receptors, in Drosophila and lepidopteran insect cells. Mosquito cells have also been employed for studies on the control of vector-borne diseases, such as malaria.

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats.

Carbon dioxide (CO2) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO2 as a euthanasia agent.

Secretion of single-chain urokinase-type plasminogen activator from insect cells.

A cDNA encoding human urokinase-type plasminogen activator was inserted downstream from the polyhedrin promoter of the baculovirus Autographa californica nuclear polyhedrosis virus. A protein of similar Mr to urokinase (UK) was synthesized and approx. 90% was secreted from recombinant virus-infected Spodoptera frugiperda cells. Zymography and Western blotting analysis of the insect-derived protein demonstrated that it was comprised solely of the high-Mr form of UK. No low-Mr UK was detected. Amidolytic activity assays showed that 96% of the insect cell-derived UK was in the single-chain proenzyme form. The yield of UK from insect cells was 1986 international units/ml/10(6) infected cells.

Synthesis of functional GABAA receptors in stable insect cell lines.

We have synthesised the beta 1-subunit of the bovine GABAA receptor in stable, continuous insect (Spodoptera frugiperda) cell lines. A cDNA was integrated randomly into the insect cell genome under control of a baculovirus immediate early (IE-1) gene promoter. Transformed cells were obtained by co-transfection of the insect cells with pIEK1.GR beta 1, encoding the beta 1 subunit cDNA, and pIEK1.neo, encoding the neomycin resistance gene. G-418-resistant clones were selected and expanded into continuous cell lines synthesising functional, GABA-gated, homo-oligomeric chloride channels. These cell lines had significant advantages over the transient baculovirus expression system for the characterisation of receptors using electrophysiological recording techniques.

Mutational analysis of the mouse 5-HT7 receptor: importance of the third intracellular loop for receptor-G-protein interaction.

The mouse serotonin (5-HT) receptor subtype, 5-HT7, belongs to the family of seven transmembrane G-protein-coupled receptors. To identify the structural basis for the coupling of 5-HT7 receptor to G alpha(s) we constructed a number of receptor mutants in which amino acid residues were either substituted or deleted from the second and third intracellular loops. Wild-type and mutant 5-HT7 receptors were expressed in insect cells using the baculovirus vectors. Two mutant receptor species, 5-HT7(E325G) and 5-HT7(K327S), demonstrated markedly impaired abilities to stimulate adenylyl cyclase. The results suggest the importance of the C-terminal region of the third intracellular loop in receptor-G-protein interaction and that specific charged residues, E325 and K327, may play a critical role in this interaction.