ABSTRACT
Septins play key roles in mammalian cell division and cytokinesis but have not previously been implicated in a germline human disorder. A male infant with severe neutropenia and progressive dysmyelopoiesis with tetraploid myeloid precursors was identified. No known genetic etiologies for neutropenia or bone marrow failure were found. However, next-generation sequencing of germline samples from the patient revealed a novel, de novo germline stop-loss mutation in the X-linked gene SEPT6 that resulted in reduced SEPT6 staining in bone marrow granulocyte precursors and megakaryocytes. Patient skin fibroblast-derived induced pluripotent stem cells (iPSCs) produced reduced myeloid colonies, particularly of the granulocyte lineage. CRISPR/Cas9 knock-in of the patient's mutation or complete knock-out of SEPT6 was not tolerated in non-patient-derived iPSCs or human myeloid cell lines, but SEPT6 knock-out was successful in an erythroid cell line and resulting clones revealed a propensity to multinucleation. In silico analysis predicts that the mutated protein hinders the dimerization of SEPT6 coiled-coils in both parallel and antiparallel arrangements, which could in turn impair filament formation. These data demonstrate a critical role for SEPT6 in chromosomal segregation in myeloid progenitors that can account for the unusual predisposition to aneuploidy and dysmyelopoiesis.
Subject(s)
Genetic Diseases, X-Linked/genetics , Germ-Line Mutation , Myelodysplastic Syndromes/genetics , Neutropenia/congenital , Septins/genetics , Cell Line , Cells, Cultured , Genetic Diseases, X-Linked/complications , Humans , Infant, Newborn , Male , Myelodysplastic Syndromes/complications , Neutropenia/complications , Neutropenia/genetics , TetraploidyABSTRACT
AIMS: The objectives of this research protocol are as follows: to examine the influence of the COVID-19 pandemic on health and social care for migrant women in the Son Gotleu district of Palma de Mallorca, Spain, and to develop outreach tools to target this specific group. DESIGN: This is a qualitative study that uses content analysis to obtain in-depth knowledge of personal experience (manifest content) and contextual experience (latent content) in a specific social setting. METHODS: The study population are migrant women living in Son Gotleu district, who are segmented by their age and experience of COVID-19, defined as positive or negative according to whether or not they have been infected with the disease. RESULTS: The shortcomings and needs relating to communication and health care that affect this group's current and future quality of life will be identified. CONCLUSION: The study of migrant women offers a gateway allowing vulnerability in health care to be detected. An awareness of their needs will allow prototype tools to be developed to facilitate communication and care for general and acute health needs between the scientific community and the vulnerable population.
Subject(s)
COVID-19 , Transients and Migrants , COVID-19/epidemiology , Female , Humans , Nuclear Family , Pandemics , Quality of Life , Social SupportABSTRACT
According to the theory of reasoned action (TRA), collaboration is only possible when it is perceived as useful by the participants involved. This paper describes a qualitative study using semi-structured interviews to explore the preceived usefulness of general practitioner (GPs)-community pharmacists (CPs)' collaboration from these professionals' perspectives based in two Spanish regions. Thirty-seven interviews were conducted with GPs and CPs with and without previous experience of collaborating with the other groups of professionals. Analysis of the data indicated that the GPs and CPs considered that collaboration between practitioners and pharmacists to have different forms of usefulness, ranging from positive to negative perceptions of usefulness. Negative and neutral opinions (collaboration generates conflict and/or is not benefitial) could prevent practitioners from initiating collaboration with the other group of professionals, which is explained by the TRA. These perceptions were only found among those participants without experience in collaboration. When collaboration was perceived as advantageous, it could be beneficial on three levels: health system (i.e. provision of integrated care, increased efficiency of the system), GPs and CPs (i.e. increased job satisfaction and patient loyalty) and patients (i.e. improved patient safety). Although GPs and CPs with experience identified benefits using a range of examples, GPs and CPs who had never collaborated also believed that if collaboration was undertaken there would be benefits for the health system, patients and health professionals. These results should be considered when developing strategies to encourage and improve the implementation of collaborative working relationships between GPs and pharmacists in primary care.
Subject(s)
Cooperative Behavior , General Practitioners/psychology , Health Knowledge, Attitudes, Practice , Pharmacists/psychology , Adult , Community Pharmacy Services , Female , Humans , Interviews as Topic , Male , Middle Aged , Qualitative Research , SpainABSTRACT
There is a universal shortage of nurses, with a current needs-based shortage of 5.9 million. This is not solely a recruitment issue but one of retention, triggered by high levels of work-induced stress, burnout, and reports of low job satisfaction resulting in poor care delivery. Some of the health repercussions on nurses include anxiety, insomnia, depression, migraines, irritability, absenteeism, and sometimes alcoholism and drug abuse. To tackle some of these costly issues, a qualitative exploration into how inner resources is used by nurses to cope with stress at different points of their careers is proposed. Through the lens of grounded theory, semi-structured interviews will be carried out with two distinct sets of participants: (1) Student nurses registered at the University of the Illes Baleares between 2022-2025. (2) Experienced nurses on the Balearic nursing register. Interviews will be coded and then analysed using Atlas.ti. Expected results will inform curriculum improvements that will benefit the well-being of (student) nurses, from the outset of their training, pre-empting potential psycho-social risks before they arise in the workplace. This is vital as it addresses nurses' mental health as well as chronic issues of retention and absenteeism.
ABSTRACT
BACKGROUND: Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. METHODS/DESIGN: This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. DISCUSSION: This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. TRIAL REGISTRATION: This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14.
Subject(s)
Adhesives/therapeutic use , Bandages, Hydrocolloid , Nursing Homes , Polyurethanes/therapeutic use , Pressure Ulcer/therapy , Primary Health Care/methods , Adult , Aged , Bandages , Female , Humans , Male , Middle Aged , Severity of Illness Index , Treatment Outcome , Wound Healing , Young AdultABSTRACT
BACKGROUND: Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. In some Scandinavian countries, this infection is treated with penicillin V since the resistances of pneumococci to this antibiotic are low. Four reasons justify the undertaking of this study; firstly, the cut-off points which determine whether a pneumococcus is susceptible or resistant to penicillin have changed in 2008 and according to some studies published recently the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (minimum inhibitory concentration>2 µg/ml); secondly, there is no correlation between pneumococcal infection by a strain resistant to penicillin and therapeutic failure in pneumonia; thirdly, the use of narrow-spectrum antibiotics is urgently needed because of the dearth of new antimicrobials and the link observed between consumption of broad-spectrum antibiotics and emergence and spread of antibacterial resistance; and fourthly, no clinical study comparing amoxicillin and penicillin V in pneumonia in adults has been published. Our aim is to determine whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of uncomplicated community-acquired pneumonia. METHODS: We will perform a parallel group, randomised, double-blind, trial in primary healthcare centres in Spain. Patients aged 18 to 65 without significant associated comorbidity attending the physician with signs and symptoms of lower respiratory tract infection and radiological confirmation of the diagnosis of pneumonia will be randomly assigned to either penicillin V 1.6 million units thrice-daily during 10 days or amoxicillin 1,000 mg thrice-daily during 10 days. The main outcome will be clinical cure at 14 days, defined as absence of fever, resolution or improvement of cough, improvement of general wellbeing and resolution or reduction of crackles indicating that no other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%. DISCUSSION: This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years. TRIAL REGISTRATION: EudraCT number 2012-003511-63.
Subject(s)
Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Community Health Services , Penicillin V/administration & dosage , Pneumonia, Pneumococcal/drug therapy , Research Design , Administration, Oral , Adolescent , Adult , Aged , Double-Blind Method , Humans , Middle Aged , Pneumonia, Pneumococcal/microbiology , Spain , Streptococcus pneumoniae , Young AdultABSTRACT
The tarnished plant bug, Lygus lineolaris, is a major strawberry pest. Only marginally effective control methods exist to manage this pest. Various predators attack L. lineolaris, but their potential is overlooked. In this study, we explore the potential of two omnivorous predators of the tarnished plant bug: the damsel bug, Nabis americoferus, and the minute pirate bug, Orius insidiosus. Firstly, the predation rate of these predators was measured in laboratory tests. Secondly, their potential release rates and release periods were determined in the field using strawberry plants. The results show that N. americoferus feeds on all nymphal stages and adults of the tarnished plant bug, while O. insidiosus attacks only smaller nymphs (up to the N2 stage). In the field, all tested densities of N. americoferus (0.25, 0.5, and 0.75 individual/plant) reduced the population of the tarnished plant bug for several weeks compared with the control treatment, but the effect of O. insidiosus alone was marginal. Additionally, for all the release periods tested, Nabis americoferus was efficient in reducing the pest population. These results demonstrate the potential of N. americoferus to control the tarnished plant bug in strawberry fields. We discuss the possible application of these results for establishing an effective and economically viable biological control strategy.
ABSTRACT
BACKGROUND: Although general practitioners (GPs) and community pharmacists (CPs) are encouraged to collaborate, a true collaborative relationship does not exist between them. Our objective was to identify and analyze factors affecting GP-CP collaboration. METHODS: This was a descriptive-exploratory qualitative study carried out in two Spanish regions: Catalonia (Barcelona) and Balearic Islands (Mallorca). Face-to-face semi-structured interviews were conducted with GPs and CPs from Barcelona and Mallorca (January 2010-February 2011). Analysis was conducted using Colaizzi's method. RESULTS: Thirty-seven interviews were conducted. The factors affecting the relationship were different depending on timing: 1) Before collaboration had started (prior to collaboration) and 2) Once the collaboration had been initiated (during collaboration). Prior to collaboration, four key factors were found to affect it: the perception of usefulness; the Primary Care Health Center (PCHC) manager's interest; the professionals' attitude; and geography and legislation. These factors were affected by economic and organizational aspects (i.e. resources or PCHC management styles) and by professionals' opinions and beliefs (i.e. perception of the existence of a public-private conflict). During collaboration, the achievement of objectives and the changes in the PCHC management were the key factors influencing continued collaboration. The most relevant differences between regions were due to the existence of privately-managed PCHCs in Barcelona that facilitated the implementation of collaboration. In comparison with the group with experience in collaboration, some professionals without experience reported a skeptical attitude towards it, reporting that it might not be necessary. CONCLUSIONS: Factors related to economic issues, management and practitioners' attitudes and perceptions might be crucial for triggering collaboration. Interventions and strategies derived from these identified factors could be applied to achieve multidisciplinary collaboration.
Subject(s)
Community Pharmacy Services , General Practitioners , Interprofessional Relations , Pharmacists , Adult , Female , Humans , Male , Middle Aged , Qualitative Research , Quality Assurance, Health Care , SpainABSTRACT
Spiders and scorpions are notorious for their fearful dispositions and their ability to inject venom into prey and predators, causing symptoms such as necrosis, paralysis, and excruciating pain. Information on venom composition and the toxins present in these species is growing due to an interest in using bioactive toxins from spiders and scorpions for drug discovery purposes and for solving crystal structures of membrane-embedded receptors. Additionally, the identification and isolation of a myriad of spider and scorpion toxins has allowed research within next generation antivenoms to progress at an increasingly faster pace. In this review, the current knowledge of spider and scorpion venoms is presented, followed by a discussion of all published biotechnological efforts within development of spider and scorpion antitoxins based on small molecules, antibodies and fragments thereof, and next generation immunization strategies. The increasing number of discovery and development efforts within this field may point towards an upcoming transition from serum-based antivenoms towards therapeutic solutions based on modern biotechnology.