Early Intervention with a Compression Sleeve in Mild Breast Cancer-Related Arm Lymphedema: A 12-Month Prospective Observational Study.

BACKGROUND: In our previous randomized controlled trial (RCT), the progression/no progression of mild breast cancer-related arm lymphedema (BCRL) was examined among women randomized to a compression group (CG) with a compression sleeve (compression class (ccl) 1) or not (NCG) for 6 months. In the present prospective study, BCRL in the CG and NCG was followed for 12 months. METHODS: At the end of the RCT, 33 women with mild BCRL were eligible in the CG and 37 in the NCG. The proportional differences in no progression/progression of BCRL were defined as a >2% increase from start of RCT or exceeding 10% in the lymphedema relative volume as measured by the water displacement method. In addition, changes in the lymphedema relative volume and tissue dielectric constant ratio, which measures local tissue water, were examined. At the end of the RCT (i.e., after 6 months), a one-month break of the compression treatment was made in the CG. If the lymphedema relative volume progressed by definition, the compression treatment was resumed and continued, with follow-up of all women at 9 and 12 months. RESULTS: A larger proportion of women in the NCG showed progression (57%, 61%, 67%) compared to the CG (16%, 22%, 31%) at 6, 9, and 12 months (p < 0.001, 0.005, 0.012), respectively. Twelve (33%) women in the NCG did not progress at all. No changes of the lymphedema relative volume and local tissue water were found over time at any follow-ups, but were stable on a low level. CONCLUSIONS: To avoid the progression of mild BCRL into a chronic issue in the long-term, compression sleeve ccl 1 may be applied immediately after early diagnosis of mild BCRL.

Risk factors for seroma formation after axillary lymph node dissection with special focus on the impact of early shoulder exercise.

BACKGROUND: Shoulder and arm dysfunction such as reduced range of motion (ROM) and seroma formation, are common complications following axillary lymph node dissection (ALND). There are conflicting results on the effect of early postoperative exercise on the risk of seroma. This study aims to present incidence of symptomatic seroma formation in a large, population-based cohort, and assesses whether early shoulder mobilization, and other common patient and treatment-related factors are predictors of seroma. METHODS: This observational cohort study at the Surgical clinic at Lund University Hospital in Sweden, included 217 consecutive patients who underwent ALND due to breast cancer, cutaneous malignant melanoma (CMM), or carcinoma of unknown primary. A shoulder exercise program was introduced on the first postoperative day and data were collected at routine follow-up 4-6 weeks postsurgery. Main outcome was the strength of the associations between postsurgery exercise and seroma incidence based on logistic regression analyses, supported by data on seroma volume and number of aspirations. RESULTS: Two hundred patients completed the study. The overall seroma incidence was 67.5% and the odds of seroma were lower for patients practicing ROM exercise two times/day versus 0-1 time/day (OR 0.42, 95% CI 0.18-0.96, p = .038). ROM exercise greater than two times/day did not increase the volume, neither did the arm cycling exercise. ALND combined with mastectomy and CMM surgery were associated with larger seroma volumes (1116 ± 1068ml, p = .006) and (1318 ± 920 ml, p < .001), respectively, compared to the breast conserving surgery (537 ± 478ml) while neoadjuvant chemotherapy showed no influence. The effect of age, patients ≥60 years compared to younger, or BMI ≥ 30.0 were weaker (p = .08). CONCLUSIONS: Extensive surgical treatments for breast cancer and malignant melanoma produces more seroma, and higher age and obesity may also influence the risk. ROM exercises twice daily predict a lower incidence of seroma following ALND, and more frequent shoulder exercise do not increase the volumes.

Impact on Health-Related quality of life after wearing compression garment or not for six months in women with mild breast cancer-related arm lymphedema. A cross-sectional study.

BACKGROUND: Women with mild breast cancer-related arm lymphedema (BCRAL) mostly receive treatment with compression garments and instructions in self-care to prevent the progression of lymphedema. However, wearing a compression garment may be experienced as negative and may affect health-related quality of life (HRQOL) more than the lymphedema itself. The aim of this study was to investigate if there is a difference in lymphedema-specific HRQOL, between women with mild BCRAL wearing compression garments or not for 6 months. MATERIAL AND METHODS: Participants with mild BCRAL (Lymphedema relative volume <10%) rated their HRQOL by the Lymphedema Quality of Life Inventory (LyQLI), 6 months after diagnosis and being randomized to compression group (CG) or non-compression group (NCG). Both groups received self-care instructions, and the CG was treated with a standard compression garment, compression class 1. Data from 51 women (30 in the CG and 21 in the NCG), were analyzed. RESULTS: Both the CG and the NCG experienced a low negative impact on HRQOL in physical, psychosocial, and practical domains (score <1). However, the CG experienced a higher negative impact on median HRQOL in the practical domain compared to the NCG, 0.23/0.08 respectively, (p = 0.026). In the specific items, more participants in the CG reported a negative impact on HRQOL compared to the NCG in employment activities 23%/0%, (p = 0.032), embarrassment by lymphedema/compression garments 33%/5%, (p = 0.017), feeling discomfort/embarrassment while doing sports and hobbies 30%/5%, (p = 0.034) and having to answer questions about the lymphedema 27%/0% (p = 0.015). CONCLUSION: Overall, the lymphedema-specific HRQOL was high after 6 months in women with mild lymphedema, with only a minor difference between the groups. Some women may however perceive practical and emotional issues with the compression garment. These aspects should be considered in patient education and when planning/evaluating treatment. Trial registration: ISRCTN51918431.

Test-Retest Reliability of Local Tissue Water and Circumference Measurements in the Head and Neck Area of Healthy Women and Men.

Background: Measurements of local tissue water and circumferences are methods to evaluate lymphedema. Knowledge about reference values and reproducibility needs, however, to be determined for the head and neck (HN) area of healthy persons before it can be used in persons with HN lymphedema. The objective of this study was to evaluate the test-retest reliability including measurement errors of local tissue water and neck circumference measurements (CM) in the HN area in a healthy cohort. Methods and Results: Thirty-one women and 29 men were measured on 2 occasions, 14 days apart. The percentage of tissue water content (PWC) were calculated in four facial points and neck CM at three levels. Intraclass correlation coefficient (ICC), changes in mean, standard error of measurement (SEM%), and smallest real difference (SRD%) were calculated. Reliability for PWC was fair to excellent for both women (ICC 0.67-0.89) and men (ICC 0.71-0.87). Measurement errors were acceptable in all points in both women (SEM% 3.6%-6.4%, SRD% 9.9%-17.7%) and men (SEM% 5.1%-10.9%, SRD% 14.2%-30.3%). For the CM, ICCs were excellent both for women (ICC 0.85-0.90) and men (ICC 0.92-0.94), and measurement errors were low (SEM% for women 1.9%-2.1%, SRD% 5.1%-5.9%; SEM% for men 1.6%-2.0%, SRD% 4.6%-5.6%). Most of the lowest values were found close to bone and vessels. Conclusion: Measurements for PWC and CM in the HN area are reliable in healthy women and men, with acceptable to low measurement errors. PWC points close to bony structures and vessels should, however, be used with caution.

Family members' reasoning in relation to pleasant environments in nursing homes.

The physical environment plays an important role in how everyday life is shaped and experienced for persons living in nursing homes as well as for the residents' family and friends. Still, there is a scarcity of research exploring the perspectives of family members of residents regarding everyday life in common areas in nursing homes. In this study, we chose the term, 'a pleasant place', with the ambition of remaining open to various ideas and aspects that family members perceive as relevant when reasoning about the nursing home environment. The study aimed to explore how family members of nursing home residents reason in relation to pleasant places in nursing homes. Four focus group sessions were conducted with a total of 14 family members. Data were analysed using qualitative content analysis. The analysis resulted in four themes. 'A door ajar', highlighted the importance of a nursing home environment that provides potential opportunities for pleasurable everyday moments. 'Why does it have to be so ugly?', revealed how family members perceived institutional logics as guiding the design of the nursing homes, which were misaligned with the logics of a pleasant place. 'A place to care for?', emphasised the physical environment as an integrated aspect of care, in terms of being carefully arranged and used with sensitivity. Finally, 'allegiance to the place' showed that despite the family members' recognitions of shortcomings in the nursing home physical environments, their allegiance to the place provided a sense of the nursing home as a pleasant place. The study contributes knowledge regarding the perceived value of the design of the physical environment in nursing homes, particularly in common areas, as an integral aspect of care, and moves beyond the ideas of homelike and non-institutional nursing home environments.

Circumferential Measurements to Calculate Lower Limb Volume in Persons with Lymphedema: What Segment Length Is to Be Recommended?

Background: Circumferential measurements (CMs) every 4th cm are commonly used to assess lower limb volume (LLV), but fewer measurements would be less time-consuming. The aim of this study was therefore to establish the agreement between LLV measurements derived from CM every 4th cm (V4), 8th cm (V8), and 12th cm (V12), and to evaluate the intrarater test-retest reliability for each of the three measurement methods in persons with lower limb lymphedema (LLL). Methods and Results: Forty-two persons with unilateral or bilateral LLL were measured twice, 2 weeks apart. Volume measurements for the V4, V8, and V12 methods were derived using CM. The agreement was evaluated using intraclass correlation coefficient (ICC3.1) and Bland-Altman graphs including 95% limits of agreement (LOA). The reliability was evaluated using ICC2.1 and standard error of measurement (SEM%) and smallest real difference (SRD%). The agreement was high for the V4 and V8 methods (ICC 0.999), and for the V4 and V12 methods (ICC 0.998). The graphs revealed slightly higher agreement between the V4 and V8 than between the V4 and V12 methods visualized by the 95% LOA (-117 to 62 and -236 to 132 mL, respectively). For all three measurement methods, the test-retest reliability was high (ICC 0.993-0.995) and the measurement error low (SEM%: 1.2%-1.4% and SRD%: 3.4%-3.8%). Conclusions: The higher agreement between the V4 and V8 methods than between V4 and V12, and the high test-retest reliability in LLV measurements support the V8 method to replace the V4 method in persons with LLL.

Depression was associated with younger age, female sex, obesity, smoking, and physical inactivity, in 1027 patients with newly diagnosed type 2 diabetes: a Swedish multicentre cross-sectional study.

BACKGROUND: Depression is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The aims were to explore the prevalence of depression, anxiety, antidepressant use, obesity, Hemoglobin A1c > 64 mmol/mol, life-style factors, pre-existing CVD, in patients with newly diagnosed T2D; to explore associations with depression; and to compare with Swedish general population data. METHODS: Multicentre, cross-sectional study. INCLUSION CRITERIA: adults with serologically verified newly diagnosed T2D. Included variables: age, sex, current depression and anxiety (Hospital Anxiety and Depression Scale), previous depression, antidepressant use, obesity (BMI ≥ 30 and ≥ 40 kg/m2), Hemoglobin A1c, pre-existing CVD. Logistic regression analyses were performed. RESULTS: In 1027 T2D patients, aged 18-94 years, depression was associated with age (per year) (inversely) (odds ratio (OR) 0.97), anxiety (OR 12.2), previous depression (OR 7.1), antidepressant use (OR 4.2), BMI ≥ 30 kg/m2 (OR 1.7), BMI ≥ 40 kg/m2 (OR 2.3), smoking (OR 1.9), physical inactivity (OR 1.8), and women (OR 1.6) (all p ≤ 0.013). Younger women (n = 113), ≤ 59 years, compared to younger men (n = 217) had higher prevalence of current depression (31% vs 12%), previous depression (43 vs 19%), anxiety (42% vs 25%), antidepressant use (37% vs 12%), BMI ≥ 30 kg/m2 (73% vs 60%) and BMI ≥ 40 kg/m2) (18% vs 9%), and smoking (26% vs 16%) (all p ≤ 0.029). Older women (n = 297), ≥ 60 years, compared to older men (n = 400) had higher prevalence of previous depression (45% vs 12%), anxiety (18% vs 10%), antidepressant use (20% vs 8%), BMI ≥ 30 kg/m2 (55% vs 47%), BMI ≥ 40 kg/m2 (7% vs 3%) (all p ≤ 0.048), but not of current depression (both 9%). Compared to the Swedish general population (depression (women 11.2%, men 12.3%) and antidepressant use (women 9.8%, men 5.3%)), the younger women had higher prevalence of current depression, and all patients had higher prevalence of antidepressant use. CONCLUSIONS: In patients with newly diagnosed T2D, the younger women had the highest prevalence of depression, anxiety, and obesity. The prevalence of depression in young women and antidepressant use in all patients were higher than in the Swedish general population. Three risk factors for CVD, obesity, smoking, and physical inactivity, were associated with depression.

Early intervention with compression garments prevents progression in mild breast cancer-related arm lymphedema: a randomized controlled trial.

BACKGROUND: Early diagnosis and compression treatment are important to prevent progression in breast cancer-related arm lymphedema (BCRAL). However, some mild BCRAL can be reversible, and therefore, compression treatment may not be needed. The aim of this study was to investigate the proportion of women with mild BCRAL showing progression/no progression of lymphedema after treatment with or without compression garments, differences in changes of lymphedema relative volume (LRV), local tissue water and subjective symptoms during 6 months. Also, adherence to self-care was examined. MATERIAL AND METHODS: Seventy-five women diagnosed with mild BCRAL were randomized to a compression group (CG) or noncompression group (NCG). Both groups received self-care instructions, and the CG were treated with a standard compression garment (ccl 1). Women in the NCG who progressed in LRV ≥2%, or exceeded 10% dropped out, and received appropriate treatment. The proportion showing progression/no progression of LRV, and changes in LRV was measured by Water Displacement Method. Changes in local tissue water were measured by Tissue Dielectric Constant (TDC), subjective symptoms by Visual Analogue Scale, and self-care by a questionnaire. RESULTS: A smaller proportion of LRV progression was found in the CG compared to the NCG at 1, 2 and 6 months follow-up (p ≤ 0.013). At 6 months, 16% had progression of LRV in the CG, compared to 57% in the NCG, (p = 0.001). Thus, 43% in the NCG showed no progression and could manage without compression. Also, CG had a larger reduction in LRV, at all time-points (p ≤ 0.005), and in the highest TDC ratio, when same site followed, at 6 months (p = 0.025). Subjective symptoms did not differ between the groups, except at 1 month, where the CG experienced more reduced tension (p = 0.008). There were no differences in adherence to self-care. CONCLUSION: Early treatment with compression garment can prevent progression in mild BCRAL. Trial registration: ISRCT nr ISRCTN51918431.

Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial.

INTRODUCTION: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). METHODS: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQ-C30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing. RESULTS: Overall, 976 questionnaires (501 in the SLN biopsy only group and 475 in the completion ALND group) were analysed, corresponding to a response rate of 82.6%. No significant group differences in overall HRQoL were identified. Participants receiving SLN biopsy only, reported significantly lower symptom scores on the EORTC subscales of pain, arm symptoms and breast symptoms. The Lymph-ICF domain scores of physical function, mental function and mobility activities were significantly in favour of the SLN biopsy only group. CONCLUSION: One year after surgery, arm morbidity is significantly worse affected by ALND than by SLN biopsy only. The results underline the importance of ongoing attempts to safely de-escalate axillary surgery. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov prior to initiation (https://clinicaltrials.gov/ct2/show/NCT02240472).

The Effect of Exercise for the Prevention and Treatment of Cancer-Related Lymphedema: A Systematic Review with Meta-analysis.

INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the effects of exercise on (i) the prevention of cancer-related lymphedema (CRL) and (ii) the treatment of CRL, lymphedema-associated symptoms, and other health outcomes among individuals with CRL. METHODS: An electronic search was undertaken for exercise studies measuring lymphedema and involving individuals at risk of developing or with CRL. The Effective Public Health Practice Project Quality scale was used to assess study quality, and overall quality of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed to evaluate effects of exercise on CRL incidence, existing CRL status, lymphedema-associated symptoms, and health outcomes. RESULTS: Twelve studies ( n = 1955; 75% moderate-high quality) and 36 studies ( n = 1741; 58% moderate-high quality) were included in the prevention and treatment aim, respectively. Relative risk of developing CRL for those in the exercise group compared with the nonexercise group was 0.90 (95% confidence interval (CI), 0.72 to 1.13) overall and 0.49 (95% CI, 0.28 to 0.85) for those with five or more lymph nodes removed. For those with CRL in the exercise group, the standardized mean difference (SMD) before to after exercise of CRL was -0.11 (95% CI, -0.22 to 0.01), and compared with usual care postintervention, the SMD was -0.10 (95% CI, -0.24 to 0.04). Improvements after intervention were observed for pain, upper-body function and strength, lower-body strength, fatigue, and quality of life for those in the exercise group (SMD, 0.3-0.8; P < 0.05). CONCLUSIONS: Findings support the application of exercise guidelines for the wider cancer population to those with or at risk of CRL. This includes promotion of aerobic and resistance exercise, and not just resistance exercise alone, as well as unsupervised exercise guided by symptom response.

Impedance of Extracellular Fluid, Volume, and Local Tissue Water Can Be Reliably Measured in People With Lower Limb Lymphedema.

OBJECTIVE: Lower limb lymphedema (LLL) is a chronic condition. To be able to evaluate changes of LLL over time and effects of interventions, reliable measurement methods are important. Currently, there is limited knowledge of the reliability of commonly used measurement methods in LLL. The study objective was to evaluate the test-retest (intrarater) reliability of impedance of extracellular fluid, volume, and local tissue water measurements in people with unilateral or bilateral LLL and measurement errors both for a group of people and for a single individual. METHODS: Forty-two people with mild to moderate unilateral or bilateral, primary or secondary LLL were measured twice, 2 weeks apart. Impedance of extracellular fluid was measured by bioimpedance spectroscopy and calculated as arm-to-leg ratio, volume with circumference measurements every 4 cm, and local tissue water with tissue dielectric constant at 14 points. Test-retest reliability was evaluated using the intraclass correlation coefficient [ICC(2,1)], changes in the mean, SE of measurement in relative terms (SEM%), and the smallest real difference in relative terms (SRD%). RESULTS: For the impedance ratio, the reliability was high [ICC(2,1) = 0.79-0.90] and the measurement errors were acceptable (SEM% = 5.0%-5.2%; SRD% = 14.0%-14.4%). For volume, the reliability was high (ICC = 0.99) and the measurement errors were low (SEM% = 1.1%-1.7%; SRD% = 3.1%-4.6%). For the tissue dielectric constant, the reliability was fair to excellent [ICC(2,1) = 0.68-0.96] and the measurement errors were acceptable (SEM% = 4.2%-9.7%; SRD% = 11.7%-26.8%). CONCLUSIONS: Measurements of impedance of extracellular fluid, volume, and local tissue water are reliable in people with mild to moderate LLL. The measurement errors were acceptable in all 3 methods indicating that real, clinical changes in lymphedema can be measured both for a group of people and a single individual. IMPACT: The results from this test-retest reliability study can help clinicians and researchers to interpret if real clinical changes in lymphedema occur over time or after an intervention in people with mild to moderate LLL.

Tissue Dielectric Constant and Water Displacement Method Can Detect Changes of Mild Breast Cancer-Related Arm Lymphedema.

Background: Most commonly, volume measurements are used to evaluate the effect of lymphedema treatment, but as the accumulation of lymph fluid can be local, this method may not always be the best. Tissue dielectric constant (TDC) can be applied to identify local lymphedema changes, but has not been used before when evaluating treatment in mild arm lymphedema. Thus, the overall aim of this study was to examine if TDC and water displacement method (WDM) can measure changes in mild breast cancer-related lymphedema during the 6-month standard treatment. More specifically, we examined changes within and between three defined groups based on lymphedema thresholds of TDC and WDM at start of treatment, as well as changes of the highest TDC ratio and site. Methods and Results: Forty-six women with mild arm lymphedema, received treatment with compression sleeves, mostly ccl 1, and instructions about self-care. Local tissue water was measured by TDC at six defined sites and lymphedema relative volume (LRV) by WDM before treatment and at first, second, third, and sixth month. There was a significant decrease in the site with the highest TDC ratio, as well as LRV at all follow-up visits. At 6 months, TDC ratio had decreased mean 0.26 (p < 0.001) and LRV mean - 3.3% (p < 0.001). There was a significant difference between the groups in change of TDC ratio, but not in LRV. Sixty percent changed the overall highest TDC ratio to another site during 6 months. Conclusion: Both TDC and WDM could detect changes in mild arm lymphedema but should be interpreted separately.

Clinical Heart Failure Among Patients With and Without Severe Mental Illness and the Association With Long-Term Outcomes.

BACKGROUND: Patients with severe mental illness (SMI) including schizophrenia, bipolar disorder, and severe depression have earlier onset of cardiovascular risk factors, predisposing to worse future heart failure (HF) compared with the general population. We investigated associations between the presence/absence of SMI and long-term HF outcomes. METHODS: We identified patients with HF with and without SMI in the Duke University Health System from 2002 to 2017. Using multivariable Cox regression, we examined the primary outcome of all-cause mortality. Secondary outcomes included rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation. RESULTS: We included 20 906 patients with HF (SMI, n=898; non-SMI, n=20 008). Patients with SMI presented clinically 7 years earlier than those without SMI. We observed an interaction between SMI and sex on all-cause mortality (P=0.002). Excess mortality was observed among men with SMI compared with men without SMI (hazard ratio, 1.36 [95% CI, 1.17-1.59]). No association was observed among women with and without SMI (hazard ratio, 0.97 [95% CI, 0.84-1.12]). Rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation were similar between patients with and without SMI (6.1% versus 7.9%, P=0.095). Patients with SMI receiving these procedures for HF experienced poorer prognosis than those without SMI (hazard ratio, 2.12 [95% CI, 1.08-4.15]). CONCLUSIONS: SMI was associated with adverse HF outcome among men and not women. Despite equal access to procedures for HF between patients with and without SMI, those with SMI experienced excess postprocedural mortality. Our data highlight concurrent sex- and mental health-related disparities in HF prognosis, suggesting that patients with SMI, especially men, merit closer follow-up.

Expression of Paracrine Effectors in Human Adipose-Derived Mesenchymal Stem Cells Treated With Plasma From Brown Bears (Ursus arctos).

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for novel cell therapeutic applications. Hibernating brown bears sustain tissue integrity and function via unknown mechanisms, which might be plasma borne. We hypothesized that plasma from hibernating bears may increase the expression of favorable factors from human ADSCs. In an experimental study, ADSCs from patients with ischemic heart disease were treated with interventional media containing plasma from hibernating and active bears, respectively, and with control medium. Extracted RNA from the ADSCs was sequenced using next generation sequencing. Statistical analyses of differentially expressed genes were performed using fold change analysis, pathway analysis, and gene ontology. As a result, we found that genes associated with inflammation, such as IGF1, PGF, IL11, and TGFA, were downregulated by > 10-fold in ADSCs treated with winter plasma compared with control. Genes important for cardiovascular development, ADM, ANGPTL4, and APOL3, were upregulated in ADSCs when treated with winter plasma compared with summer plasma. ADSCs treated with bear plasma, regardless if it was from hibernating or active bears, showed downregulation of IGF1, PGF, IL11, INHBA, IER3, and HMOX1 compared with control, suggesting reduced cell growth and differentiation. This can be summarized in the conclusion that plasma from hibernating bears suppresses inflammatory genes and activates genes associated with cardiovascular development in human ADSCs. Identifying the involved regulator(s) holds therapeutic potential.

Whole genome sequencing of Clostridioides difficile PCR ribotype 046 suggests transmission between pigs and humans.

BACKGROUND: A zoonotic association has been suggested for several PCR ribotypes (RTs) of Clostridioides difficile. In central parts of Sweden, RT046 was found dominant in neonatal pigs at the same time as a RT046 hospital C. difficile infection (CDI) outbreak occurred in the southern parts of the country. OBJECTIVE: To detect possible transmission of RT046 between pig farms and human CDI cases in Sweden and investigate the diversity of RT046 in the pig population using whole genome sequencing (WGS). METHODS: WGS was performed on 47 C. difficile isolates from pigs (n = 22), the farm environment (n = 7) and human cases of CDI (n = 18). Two different core genome multilocus sequencing typing (cgMLST) schemes were used together with a single nucleotide polymorphisms (SNP) analysis and the results were related to time and location of isolation of the isolates. RESULTS: The pig isolates were closely related (≤6 cgMLST alleles differing in both cgMLST schemes) and conserved over time and were clearly separated from isolates from the human hospital outbreak (≥76 and ≥90 cgMLST alleles differing in the two cgMLST schemes). However, two human isolates were closely related to the pig isolates, suggesting possible transmission. The SNP analysis was not more discriminate than cgMLST. CONCLUSION: No general pattern suggesting zoonotic transmission was apparent between pigs and humans, although contrasting results from two isolates still make transmission possible. Our results support the need for high resolution WGS typing when investigating hospital and environmental transmission of C. difficile.

Individual parental conversations with non-birthing parents.

AIM: The aim of this study was to describe Child Health Service (CHS) nurses' experiences with conducting individual parental conversations (IPCs) with non-birthing parents. BACKGROUND: CHS nurses in Sweden mainly focus on monitoring a child's physical and mental development and the mothers' health in order to support their parenthood. The assignment of the CHS includes identifying dysfunctional social relationships in a family and strengthening responsive parenting. An imbalance arises within the family when someone in the family suffers from illness, which could have a negative effect on the whole family's health and well-being. METHODS: An inductive, descriptive qualitative study design was used to describe and to gain an understanding of the CHS nurses' experiences. Data were collected in 13 interviews, and a qualitative content analysis was performed. FINDINGS: The analysis of interviews with CHS nurses resulted in two main categories, each with three subcategories. The main categories are: working for equality and applying a family focus, and dealing with challenges in the developing assignment. The IPCs stimulate the CHS nurses to work for more equality and to apply a family focus, which can be a way of strengthening the families' health and the children's upbringing. Developing the CHS nurses' assignment can be a challenge that appears to entail positive outcomes for CHS nurses, while also generating the need for CHS nurses to receive supervision to find ways to improve their approach and practice.

Cross-border spread of blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae: a European collaborative analysis of whole genome sequencing and epidemiological data, 2014 to 2019.

Analysis of sequencing data for 143 blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae isolates from 13 European national collections and the public domain resulted in the identification of 15 previously undetected multi-country transmission clusters. For 10 clusters, cases had prior travel/hospitalisation history in countries outside of the European Union including Egypt, Iran, Morocco, Russia, Serbia, Tunisia and Turkey. These findings highlight the benefit of European whole genome sequencing-based surveillance and data sharing for control of antimicrobial resistance.

Genetic controls of short- and long-term stomatal CO2 responses in Arabidopsis thaliana.

BACKGROUND AND AIMS: The stomatal conductance (gs) of most plant species decreases in response to elevated atmospheric CO2 concentration. This response could have a significant impact on plant water use in a future climate. However, the regulation of the CO2-induced stomatal closure response is not fully understood. Moreover, the potential genetic links between short-term (within minutes to hours) and long-term (within weeks to months) responses of gs to increased atmospheric CO2 have not been explored. METHODS: We used Arabidopsis thaliana recombinant inbred lines originating from accessions Col-0 (strong CO2 response) and C24 (weak CO2 response) to study short- and long-term controls of gs. Quantitative trait locus (QTL) mapping was used to identify loci controlling short- and long-term gs responses to elevated CO2, as well as other stomata-related traits. KEY RESULTS: Short- and long-term stomatal responses to elevated CO2 were significantly correlated. Both short- and long-term responses were associated with a QTL at the end of chromosome 2. The location of this QTL was confirmed using near-isogenic lines and it was fine-mapped to a 410-kb region. The QTL did not correspond to any known gene involved in stomatal closure and had no effect on the responsiveness to abscisic acid. Additionally, we identified numerous other loci associated with stomatal regulation. CONCLUSIONS: We identified and confirmed the effect of a strong QTL corresponding to a yet unknown regulator of stomatal closure in response to elevated CO2 concentration. The correlation between short- and long-term stomatal CO2 responses and the genetic link between these traits highlight the importance of understanding guard cell CO2 signalling to predict and manipulate plant water use in a world with increasing atmospheric CO2 concentration. This study demonstrates the power of using natural variation to unravel the genetic regulation of complex traits.

Bone marrow- and adipose tissue-derived mesenchymal stem cells from donors with coronary artery disease; growth, yield, gene expression and the effect of oxygen concentration.

Mesenchymal stem cells (MSCs) for cardiovascular cell therapy are procured from different sources including bone marrow and adipose tissue. Differently located MSCs differ in growth potential, differentiation ability and gene expression when cultured in vitro, and studies show different healing abilities for different MSC subgroups. In this study, bone marrow derived MSCs (BMSCs) and adipose tissue derived MSCs (ADSCs) from six human donors with coronary artery disease were compared for growth potential and expression of target genes (Angpt1, LIF, HGF, TGF-ß1 and VEGF-A) in response to exposure to 1% and 5% O2, for up to 48 h. We found greater growth of ADSCs compared to BMSCs. ADSCs expressed higher levels of Angpt1, LIF and TGF-ß1 and equal levels of VEGF-A and HGF as BMSCs. In BMSCs, exposure to low oxygen resulted in upregulation of TGF-ß1, whereas other target genes were unaffected. Upregulation was only present at 1% O2. In ADSCs, LIF was upregulated in both oxygen concentrations, whereas Angpt1 was upregulated only at 1% O2. Different response to reduced oxygen culture conditions is of relevance when expanding cells in vitro prior to administration. These findings indicate ADSCs as better suited for cardiovascular cell therapy compared to BMSCs.