Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops.

Hypoxia is a common feature of solid tumors and is associated with poor patient prognosis, therapy resistance and metastasis. Radiobiological hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response and the unfolded protein response. Recently, we found that hypoxia also leads to the robust accumulation of R-loops, which led us to question here both the mechanism and consequence of hypoxia-induced R-loops. Interestingly, we found that the mechanism of R-loop accumulation in hypoxia is dependent on non-DNA damaging levels of reactive oxygen species. We show that hypoxia-induced R-loops play a critical role in the transcriptional stress response, evidenced by the repression of ribosomal RNA synthesis and the translocation of nucleolin from the nucleolus into the nucleoplasm. Upon depletion of R-loops, we observed a rescue of both rRNA transcription and nucleolin translocation in hypoxia. Mechanistically, R-loops accumulate on the rDNA in hypoxia and promote the deposition of heterochromatic H3K9me2 which leads to the inhibition of Pol I-mediated transcription of rRNA. These data highlight a novel mechanistic insight into the hypoxia-induced transcriptional stress response through the ROS-R-loop-H3K9me2 axis. Overall, this study highlights the contribution of transcriptional stress to hypoxia-mediated tumorigenesis.

Scoliosis Causing Cervical Dystonia in a Chiropractic Office.

Cervical dystonia is a movement disorder characterized by continuous and involuntary muscular contractions that result in aberrant head and neck motions or postures. A recent study indicates that persons with a history of scoliosis may be at a higher risk of acquiring cervical dystonia later in life. Although muscular tension and contraction abnormalities are linked in both illnesses, the pathophysiological pathways linking these two ailments are not entirely understood. A 13-year-old boy previously diagnosed with adolescent idiopathic scoliosis developed symptoms of cervical dystonia, including moderate neck pain, left-sided migraines, and tingling in the neck and shoulders. During the course of three months, the patient attended 16 chiropractic therapy sessions. He reported slow but considerable improvements in his symptoms, such as the recovery of normal cervical range of motion, decreases in neck discomfort and accompanying headaches as well as paresthesia, and enhancements in sleep quality, daily functioning, and learning capacities. The patient's clinical and radiographic improvements show that chiropractic spinal manipulation may assist in reducing pain and improving spine alignment and mobility in these circumstances. To further investigate the efficacy and safety of chiropractic therapy for the treatment of cervical dystonia, particularly in the setting of associated scoliosis, more study with bigger patient populations is required.

The cross-sectional and longitudinal relationship of diabetic retinopathy to cognitive impairment: a systematic review and meta-analysis.

OBJECTIVES: To establish a potential relationship between diabetic retinopathy (DR) and different stages of cognitive impairment METHODS: Literature searches were conducted on PubMed and EMBASE, with keywords "diabetic retinopathy" and "cognitive impairment". Inclusion criteria were original human studies, and English language. Quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The register number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42021236747. The main outcome measures were odds ratios (OR) and risk ratios (RR) for cross-sectional and longitudinal studies, respectively. Meta-regression was performed to evaluate the effects of potential moderator variables, including, age, onset age of diabetes mellitus (DM), duration of DM, and HbA1c. RESULTS: Twenty-five studies (17 cross-sectional and 8 longitudinal studies) with a total of 1,963,914 subjects, were included. Among the cross-sectional studies, the pooled ORs of any cognitive impairment, early stage of cognitive impairment and dementia in subjects with DR (95% confidence interval) were 1.48 (1.08-2.02), 1.59 (1.01-2.51), and 1.13 (0.86-1.50), respectively. Among the longitudinal studies, the pooled RRs of any cognitive impairment, early stage of cognitive impairment, and dementia in subjects with DR (95% confidence interval) were 1.35 (1.12-1.65), 1.50 (1.06-2.12), and 1.31 (1.03-1.66), respectively. Meta-regression showed age, onset age of DM, duration of DM, and glycated hemoglobin (HbA1c) were not statistically associated with the outcomes. CONCLUSIONS: The presence of DR in DM patients indicates both higher odds of prevalent cognitive impairment and escalated risks of developing cognitive impairment in the future.

Organ-on-a-chip model of vascularized human bone marrow niches.

Bone marrow niches (endosteal and perivascular) play important roles in both normal bone marrow function and pathological processes such as cancer cell dormancy. Unraveling the mechanisms underlying these events in humans has been severely limited by models that cannot dissect dynamic events at the niche level. Utilizing microfluidic and stem cell technologies, we present a 3D in vitro model of human bone marrow that contains both the perivascular and endosteal niches, complete with dynamic, perfusable vascular networks. We demonstrate that our model can replicate in vivo bone marrow function, including maintenance and differentiation of CD34+ hematopoietic stem/progenitor cells, egress of neutrophils (CD66b+), and niche-specific responses to doxorubicin and granulocyte-colony stimulating factor. Our platform provides opportunities to accelerate current understanding of human bone marrow function and drug response with high spatial and temporal resolution.

Hypoxia-induced SETX links replication stress with the unfolded protein response.

Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.

Understanding diagnostic settings and carer experiences for dementia diagnosis in Australia.

BACKGROUND: Australian guidelines advocate referral to comprehensive memory services for dementia diagnosis, but many patients may be diagnosed elsewhere. AIMS: To determine common settings for dementia diagnosis in Australia and to compare patient and carer experience between settings. METHODS: Exploratory cross-sectional study of patients with dementia admitted to a Melbourne sub-acute hospital. Patients who had capacity to participate were included; carers were recruited for patients without capacity. Participants completed an interviewer-administered survey which asked them to recall the diagnostic setting, discussions about diagnosis and management (clinical care) and overall experience of diagnosis. Descriptive statistics were applied and open-ended questions were analysed using inductive and deductive coding approaches. RESULTS: From 81 eligible participants, 74 consented to participate (one patient, 74 carers). Participants reported dementia diagnosis occurred a median of 24 months before interview, in the following settings: hospitals (31.3%), private specialist clinics (29.7%), memory clinics (14.9%), general practice (13.5%), community health services (9.5%) and residential care (1.4%). Recall of discussions about dementia-modulating medications was higher in participants diagnosed in memory clinics and private specialist clinics (70%) compared to other settings (15%) (P < 0.001). Discussion about living circumstances was highest in hospitals (87% vs 40%) (P < 0.001). One third of participants reported dissatisfaction with their experience. Reported satisfaction was highest for memory clinics. CONCLUSION: Results suggest majority of people with dementia are diagnosed outside memory services. Significant variability exists in experiences between services, with a high proportion of participants expressing dissatisfaction with their experience with dementia diagnosis. Strategies to standardise diagnosis of dementia, measure and improve quality of care across all settings are required.

Quantitative design strategies for fine control of oxygen in microfluidic systems.

Hypoxia, or low oxygen (O2) tension, is a central feature of important disease processes including wound healing and cancer. Subtle temporal and spatial variations (≤1% change) in the concentration of O2 can profoundly impact gene expression and cellular functions. Sodium sulfite reacts rapidly with O2 and can be used to lower the O2 concentrations in PDMS-based tissue culture systems without exposing the cell culture to the chemical reaction. By carefully considering the mass transfer and reaction kinetics of sodium sulfite and O2, we developed a flexible theoretical framework to design an experimental microfluidic system that provides fine spatial and temporal control of O2 tension. The framework packages the dimensions, fluid flow, reaction rates, concentrations, and material properties of the fluidic lines and device into dimensionless groups that facilitate scaling and design. We validated the theoretical results by experimentally measuring O2 tension throughout the experimental system using phosphorescence lifetime imaging. We then tested the system by examining the impact of hypoxia inducible factor-1α (HIF-1α) on the proliferation and migration of MDA-MB-231 breast cancer cells. Using this system, we demonstrate that mild constant hypoxia (≤4%) induces HIF-1α mediated functional changes in the tumor cells. Furthermore, slow (>12 hours), but not rapid (<1 hour), fluctuations in O2 tension impact HIF-1α mediated proliferation and migration. Our results provide a generalized framework for fine temporal and spatial control of O2 and emphasize the need to consider mild spatial and temporal changes in O2 tension as potentially important factors in disease processes such as cancer.

Feasibility of a Mobile Health Tool for Mothers to Identify Neonatal Illness in Rural Uganda: Acceptability Study.

BACKGROUND: A shortage of community health workers to triage sick neonates and poor recognition of neonatal illness by mothers contribute significantly toward neonatal deaths in low- and middle-income countries. Providing low-resource communities with the tools and knowledge to recognize signs of neonatal distress can lead to early care-seeking behavior. To empower and educate mothers to recognize signs of neonatal illness, we developed a neonatal health assessment device consisting of a smartphone app and a wearable sensor (the NeMo system). OBJECTIVE: The aim of this study was to determine if mothers in rural Uganda were willing and able to use the NeMo system during the first week of their infant's life. We also assessed mothers' responses to the device's recommendation to seek care. METHODS: A total of 20 mothers were enrolled in the study after giving birth in the Iganga District Hospital. Each mother was trained to use the NeMo system to assess her infant for signs of illness before leaving the hospital and was given the NeMo system to use at home for 1 week. Throughout the week, the smartphone tracked the mothers' usage of NeMo, and the study team visited twice to observe mothers' ability to use NeMo. Each mother was interviewed at the end of 1 week to gather qualitative feedback on her experience with the NeMo system. RESULTS: In total, 18 mothers completed the study; 2 mothers were withdrawn during the week because of extenuating health circumstances. Moreover, 1 day after enrollment and training, 75% (15/20) of mothers used NeMo properly with no mistakes. Three days after enrollment and training, only 1 mother placed the wearable sensor improperly on her infant. On the final study day, only 1 mother connected the device improperly. Mothers used NeMo an average of 11.67 (SD 5.70) times on their own at home during the 5 full study days. Although the frequency of use per day decreased from day 1 to day 5 of the study (P=.04), 72% (13/18) of mothers used NeMo at least once per day. In total, 64% (9/14) of mothers who received an alert from the NeMo system to seek care for their infants either called the health care professional working with the study team or reused the system immediately and found no danger signs. All 18 mothers agreed or strongly agreed that the NeMo system was easy to use and helped them know when to seek care for their babies. CONCLUSIONS: NeMo is a feasible and acceptable tool to aid mothers in rural Uganda to assess their infant's health.

Predicting the effects of SNPs on transcription factor binding affinity.

MOTIVATION: Genome-wide association studies have revealed that 88% of disease-associated single-nucleotide polymorphisms (SNPs) reside in noncoding regions. However, noncoding SNPs remain understudied, partly because they are challenging to prioritize for experimental validation. To address this deficiency, we developed the SNP effect matrix pipeline (SEMpl). RESULTS: SEMpl estimates transcription factor-binding affinity by observing differences in chromatin immunoprecipitation followed by deep sequencing signal intensity for SNPs within functional transcription factor-binding sites (TFBSs) genome-wide. By cataloging the effects of every possible mutation within the TFBS motif, SEMpl can predict the consequences of SNPs to transcription factor binding. This knowledge can be used to identify potential disease-causing regulatory loci. AVAILABILITY AND IMPLEMENTATION: SEMpl is available from https://github.com/Boyle-Lab/SEM_CPP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Lipid digestion of oil-in-water emulsions stabilized with low molecular weight surfactants.

Altering sn-fatty acid position of glycerol mono-oleate (GMO) from sn-1 to sn-2 decreases fatty acid bioaccessibility by 25.9% providing possible strategies to tailor lipemic responses of food emulsions. Lipid digestion kinetics and fatty acid bioaccessibility of monomodal O/W emulsions stabilized at their minimum surfactant concentration (0.5 < MSC > 0.7 (w/w)) were studied in the TNO Intestinal Model (TIM-1) gastrointestinal (GI) tract. No significant differences were observed between induction times nor rate constants when using 1-GMO and 1-GMS, Span 60, Tween 60 and Tween 80 as surfactants in O/W emulsions, as determined by fitting a three-parameter shifted logistic model to the cumulative bioaccessibility. Comparable trends were observed between area under the curve (AUC) of the absolute bioaccessibility and total overall bioaccessibility.

A Novel Mobile Health Tool for Home-Based Identification of Neonatal Illness in Uganda: Formative Usability Study.

BACKGROUND: While early identification of neonatal illness can impact neonatal mortality rates and reduce the burden of treatment, identifying subtle clinical signs and symptoms of possible severe illness is especially challenging in neonates. The World Health Organization and the United Nations Children's Fund developed the Integrated Management of Neonatal Childhood Illness guidelines, an evidence-based tool highlighting seven danger signs to assess neonatal health. Currently, many mothers in low-resource settings rely on home visits from community health workers (CHWs) to determine if their baby is sick. However, CHWs visit infrequently, and illness is often detected too late to impact survival. Thus, delays in illness identification pose a significant barrier to providing expedient and effective care. Neonatal Monitoring (NeMo), a novel neonatal assessment tool, seeks to increase the frequency of neonatal screening by task-shifting identification of neonatal danger signs from CHWs to mothers. OBJECTIVE: This study aimed to explore the usability and acceptability of the NeMo system among target users and volunteer CHWs by assessing ease of use and learnability. METHODS: Simulated device use and semistructured interviews were conducted with 32 women in the Iganga-Mayuge districts in eastern Uganda to evaluate the usability of the NeMo system, which involves a smartphone app paired with a low cost, wearable band to aid in identification of neonatal illness. Two versions of the app were evaluated using a mixed methods approach, and version II of the app contained modifications based on observations of the first cohort's use of the system. During the posed scenario simulations, participants were offered limited guidance from the study team in order to probe the intuitiveness of the NeMo system. The ability to complete a set of tasks with the system was tested and recorded for each participant and closed- and open-ended questions were used to elicit user feedback. Additionally, focus groups with 12 CHWs were conducted to lend additional context and insight to the usability and feasibility assessment. RESULTS: A total of 13/22 subjects (59%) using app version I and 9/10 subjects (90%) using app version II were able to use the phone and app with no difficulty, despite varying levels of smartphone experience. Following modifications to the app's audio instructions in version II, participants' ability to accurately answer qualitative questions concerning neonatal danger signs improved by at least 200% for each qualitative danger sign. All participants agreed they would trust and use the NeMo system to assess the health of their babies. Furthermore, CHWs emphasized the importance of community sensitization towards the system to encourage its adoption and regular use, as well as the decision to seek care based on its recommendations. CONCLUSIONS: The NeMo system is an intuitive platform for neonatal assessment in a home setting and was found to be acceptable to women in rural Uganda.

Conservation of conformational dynamics across prokaryotic actins.

The actin family of cytoskeletal proteins is essential to the physiology of virtually all archaea, bacteria, and eukaryotes. While X-ray crystallography and electron microscopy have revealed structural homologies among actin-family proteins, these techniques cannot probe molecular-scale conformational dynamics. Here, we use all-atom molecular dynamic simulations to reveal conserved dynamical behaviors in four prokaryotic actin homologs: MreB, FtsA, ParM, and crenactin. We demonstrate that the majority of the conformational dynamics of prokaryotic actins can be explained by treating the four subdomains as rigid bodies. MreB, ParM, and FtsA monomers exhibited nucleotide-dependent dihedral and opening angles, while crenactin monomer dynamics were nucleotide-independent. We further show that the opening angle of ParM is sensitive to a specific interaction between subdomains. Steered molecular dynamics simulations of MreB, FtsA, and crenactin dimers revealed that changes in subunit dihedral angle lead to intersubunit bending or twist, suggesting a conserved mechanism for regulating filament structure. Taken together, our results provide molecular-scale insights into the nucleotide and polymerization dependencies of the structure of prokaryotic actins, suggesting mechanisms for how these structural features are linked to their diverse functions.

Diagnosis of dementia in Australia: a narrative review of services and models of care.

Objective There is an impetus for the timely diagnosis of dementia to enable optimal management of patients, carers and government resources. This is of growing importance in the setting of a rising prevalence of dementia in an aging population. The Australian Clinical Practice Guidelines and Principles of Care for People with Dementia advocate referral to comprehensive memory services for dementia diagnosis, but in practice many patients may be diagnosed in other settings. The aim of the present study was to obtain evidence of the roles, effectiveness, limitations and accessibility of current settings and services available for dementia diagnosis in Australia. Methods A literature review was performed by searching Ovid MEDLINE using the terms 'dementia' AND 'diagnosis OR detection'. In addition, articles from pertinent sources, such as Australian government reports and relevant websites (e.g. Dementia Australia) were included in the review. Results Literature was found for dementia diagnosis across general practice, hospitals, memory clinics, specialists, community, care institutions and new models. General practitioners are patients' preferred health professionals when dealing with dementia, but gaps in symptom recognition and initiation of cognitive testing lead to underdiagnosis. Hospitals are opportunistic places for dementia screening, but time constraints and acute medical issues hinder efficient dementia diagnosis. Memory clinics offer access to multidisciplinary skills, demonstrate earlier dementia diagnosis and potential cost-effectiveness, but are disadvantaged by organisational complexities. Specialists have increased confidence in diagnosing dementia than generalists, but drawbacks include long wait lists. Aged care assessment teams (ACAT) are a potential service for dementia diagnosis in the community. A multidisciplinary model for dementia diagnosis in care institutions is potentially beneficial, but is time and cost intensive. New models with technology allow dementia diagnosis in rural regions. Conclusion Memory clinics are most effective for formal dementia diagnosis, but healthcare professionals in other settings play vital roles in recognising patients with dementia and initiating investigations and referrals to appropriate services. What is known about this topic? Delays in dementia diagnosis are common, and it is unclear where majority of patients receive a diagnosis of dementia in Australia. While the Australian Clinical Practice Guidelines and Principles of Care for People with Dementia advocate referrals to services such as memory clinics for comprehensive assessment and diagnosis of dementia, such services may have limited capacity and may not be readily accessible to all. What does this paper add? This paper presents an overview of the various settings and services available for dementia diagnosis in Australia including evidence of the roles, accessibility, effectiveness and limitations of each setting. What are the implications for practitioners? This concerns a disease that is highly prevalent and escalating, and highlights the roles for practitioners in various settings including general practices, acute hospitals, specialist clinics, community and nursing homes. In particular, it discusses the potential roles, advantages and challenges of dementia diagnosis in each setting.

Species-specific activity of antibacterial drug combinations.

The spread of antimicrobial resistance has become a serious public health concern, making once-treatable diseases deadly again and undermining the achievements of modern medicine1,2. Drug combinations can help to fight multi-drug-resistant bacterial infections, yet they are largely unexplored and rarely used in clinics. Here we profile almost 3,000 dose-resolved combinations of antibiotics, human-targeted drugs and food additives in six strains from three Gram-negative pathogens-Escherichia coli, Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa-to identify general principles for antibacterial drug combinations and understand their potential. Despite the phylogenetic relatedness of the three species, more than 70% of the drug-drug interactions that we detected are species-specific and 20% display strain specificity, revealing a large potential for narrow-spectrum therapies. Overall, antagonisms are more common than synergies and occur almost exclusively between drugs that target different cellular processes, whereas synergies are more conserved and are enriched in drugs that target the same process. We provide mechanistic insights into this dichotomy and further dissect the interactions of the food additive vanillin. Finally, we demonstrate that several synergies are effective against multi-drug-resistant clinical isolates in vitro and during infections of the larvae of the greater wax moth Galleria mellonella, with one reverting resistance to the last-resort antibiotic colistin.

Evaluation for occult sepsis incorporating NIRS and emergency sonography.

PURPOSE: We aim to determine whether the combination of regional tissue oxygen saturation (StO2) measurement using near-infrared spectroscopy (NIRS), inferior vena cava (IVC) collapsibility and ejection fraction (EF) is able to detect occult sepsis. METHODS: We included adult patients in the emergency department with at least one of the following: fever; any one component of the quick sepsis-related organ function assessment (SOFA) score; heart rate≥100 beats per minute; or white cell count <4.0×109/L or >12.0×109/L. StO2 parameters, IVC collapsibility and EF were assessed. Primary outcome was composite of admission to intensive care unit, hypotension requiring fluid resuscitation or vasopressor use, and antibiotic escalation. RESULTS: We included 184 patients with mean age of 55.4years and slight male predominance (51.6%). Increase in temperature (adjusted odds ratio [aOR] 3.05; 95% confidence interval [CI] 1.16 to 8.02), higher white cell counts (aOR 1.10; 95% CI 1.03 to 1.19), increase in time taken to new StO2 baseline (aOR 1.03; 95% CI 1.01 to 1.06) and reduced EF (aOR 33.9; 95% CI 2.19 to 523.64) had higher odds of achieving the primary outcome. CONCLUSION: Change in StO2 and time taken to reach new StO2 baseline, combined with EF could potentially predict sepsis among patients with infection.

Challenges to DNA replication in hypoxic conditions.

The term hypoxia refers to any condition where insufficient oxygen is available and therefore encompasses a range of actual oxygen concentrations. The regions of tumours adjacent to necrotic areas are at almost anoxic levels and are known to be extremely therapy resistant (radiobiological hypoxia). The biological response to radiobiological hypoxia includes the rapid accumulation of replication stress and subsequent DNA damage response, including both ATR- and ATM-mediated signalling, despite the absence of detectable DNA damage. The causes and consequences of hypoxia-induced replication stress will be discussed.

Spontaneous healing of a tear of an anterior cruciate ligament graft: A case report.

BACKGROUND: Almost 30% of young athletic patients sustain a second anterior cruciate ligament (ACL) injury within 24months of their ACL reconstruction and returning to pivoting sports. Most patients with high athletic demand and significant anteroposterior instability often require ACL revision surgery to restore their pre-injury activity levels. CASE REPORT: A 24-year old gentleman ruptured his hamstring tendon autograft during a twisting injury seven months after his ACL reconstruction. Eight months post-injury, it was observed that spontaneous healing of his graft had occurred. This was confirmed with clinical examination and radiological imaging. CONCLUSION: Hamstring tendon autografts may demonstrate some self-reparative potential. This could be due to the higher response of extra-articular ligaments and tendons in response to growth factors observed in some studies. Limitations in diagnostic magnetic resonance imaging could also lead to over-interpretation of a partially torn graft.

FtsZ-Dependent Elongation of a Coccoid Bacterium.

UNLABELLED: A mechanistic understanding of the determination and maintenance of the simplest bacterial cell shape, a sphere, remains elusive compared with that of more complex shapes. Cocci seem to lack a dedicated elongation machinery, and a spherical shape has been considered an evolutionary dead-end morphology, as a transition from a spherical to a rod-like shape has never been observed in bacteria. Here we show that a Staphylococcus aureus mutant (M5) expressing the ftsZ(G193D) allele exhibits elongated cells. Molecular dynamics simulations and in vitro studies indicate that FtsZ(G193D) filaments are more twisted and shorter than wild-type filaments. In vivo, M5 cell wall deposition is initiated asymmetrically, only on one side of the cell, and progresses into a helical pattern rather than into a constricting ring as in wild-type cells. This helical pattern of wall insertion leads to elongation, as in rod-shaped cells. Thus, structural flexibility of FtsZ filaments can result in an FtsZ-dependent mechanism for generating elongated cells from cocci. IMPORTANCE: The mechanisms by which bacteria generate and maintain even the simplest cell shape remain an elusive but fundamental question in microbiology. In the absence of examples of coccus-to-rod transitions, the spherical shape has been suggested to be an evolutionary dead end in morphogenesis. We describe the first observation of the generation of elongated cells from truly spherical cocci, occurring in a Staphylococcus aureus mutant containing a single point mutation in its genome, in the gene encoding the bacterial tubulin homologue FtsZ. We demonstrate that FtsZ-dependent cell elongation is possible, even in the absence of dedicated elongation machinery.

Voices of Alzheimer Caregivers on Positive Aspects of Caregiving.

PURPOSE: To discover positive gains as constructed by family caregivers of relatives with Alzheimer's disease. DESIGN AND METHODS: Fifty-seven Hong Kong Chinese primary caregivers provided 669 diary recordings over an 8-week period, describing daily events and experiences in which positive gains were achieved. The diaries were analyzed independently by two researchers using thematic analysis. RESULTS: Ten themes related to positive gains were identified: (a) insights about dementia and acceptance of the condition, (b) a sense of purpose and commitment to the caregiving role, (c) feelings of gratification when the care-recipient (CR) was functioning relatively well, (d) mastering skills to handle the CR, (e) increased patience and tolerance, (f) cultivating positive meanings and humor amidst difficult circumstances, (g) letting go of things, such as when the CR's qualities had been lost or personal agenda had become unrealistic, (h) developing a closer relationship with the CR, (i) finding support, and (j) feeling useful helping other caregivers. IMPLICATIONS: In addition to treating negative outcomes such as depression, practitioners and researchers should, identify means to promote positive gains. Strategies mentioned in the caregivers' diaries, such as reframing stressful situations in a more positive light, may provide input into the design of such interventions.