Displaying publications 1 - 20 of 23 in total

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  1. Yusof KM, Groen K, Rosli R, Avery-Kiejda KA
    Front Cell Dev Biol, 2021;9:732415.
    PMID: 34733847 DOI: 10.3389/fcell.2021.732415
    Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers. MicroRNAs demonstrate pivotal roles in regulating gene expression in biological processes such as lymphangiogenesis, angiogenesis, modulation of the immune system, and oxidative stress. MicroRNA profiling has led to the discovery of the molecular mechanisms involved in the pathophysiology of auto-immune, inflammation-related, and metabolic diseases. Although the role of microRNAs in regulating secondary lymphedema is yet to be elucidated, the crosstalk between microRNAs and molecular factors involved in the pathological features of lymphedema, such as skin fibrosis, inflammation, immune dysregulation, and aberrant lipid metabolism have been demonstrated in several studies. MicroRNAs have the potential to serve as biomarkers for diseases and elucidation of their roles in lymphedema can provide a better understanding or new insights of the mechanisms underlying this debilitating condition.
  2. Sharif Nia H, Rezapour M, Allen KA, Pahlevan Sharif S, Jafari A, Torkmandi H, et al.
    Asian Pac J Cancer Prev, 2019 09 01;20(9):2803-2809.
    PMID: 31554380 DOI: 10.31557/APJCP.2019.20.9.2803
    Objectives: The Center for Epidemiologic Studies Depression Scale (CES-D) was specifically created to assess
    depression in cancer patients. However, to date, the CES-D has not been validated in Farsi. Therefore, this study aimed to
    assess the psychometric properties of the CES-D in Iranian cancer patients. Methods: During a three-month period
    (October to December, 2015), a total of 380 cancer patients completed a Farsi version of the CES-D. The construct
    validity of the scale was evaluated by exploratory factor analysis. Reliability was assessed using Cronbach’s alpha
    and McDonald Omega. All of the statistical procedure were run by SPSS 22 (SPSS Inc., Chicago, IL, USA). Results:
    The construct validity of the CES-D determined three factors (somatic affect, negative affect, and positive affect),
    which explained 65.60% of the total variance. The internal consistency was greater than 0.70. Conclusion: Findings
    revealed that the Farsi version of the CES-D has acceptable validity and reliability, which can be used to measure
    depression in Iranian cancer patients.
  3. Sharif Nia H, Mohammadinezhad M, Allen KA, Boyle C, Pahlevan Sharif S, Rahmatpour P
    Palliat Support Care, 2021 May 07.
    PMID: 33958021 DOI: 10.1017/S1478951521000407
    OBJECTIVE: The spiritual well-being scale (SWBS) is a widely used clinical scale which should be evaluated for Iranian patients with cancer. The aim of this study is to evaluate the psychometric properties of the Persian version of the SWBS in Iranian patients with cancer.

    METHOD: This cross-sectional, methodological study was conducted among Iranian patients with cancer (n = 400). The participants were recruited using convenience sampling. The content, construct, convergent and discriminant validity, and reliability of the Persian version of the SWBS were evaluated.

    RESULTS: A two-factor structure for the scale was indicated with the factors being: connecting with God and meaningless life that explained 54.18% of the total variance of the concept of spiritual well-being. The results demonstrated the model had a good fit. Cronbach's alpha, McDonald's omega, and the inter-item correlation values of the factors indicated good internal consistency of the scale.

    SIGNIFICANCE OF RESULTS: These results suggest that the Persian version of the SWBS is a reliable and valid measure to assess the spiritual well-being of patients with cancer through 16 items related to connecting with God and meaningless life.

  4. Soleimani MA, Pahlevan Sharif S, Allen KA, Yaghoobzadeh A, Sharif Nia H, Gorgulu O
    J Relig Health, 2017 Dec;56(6):1981-1997.
    PMID: 27629419 DOI: 10.1007/s10943-016-0305-9
    The purpose of this study was to assess the psychometric properties of the Persian version of Spiritual Well-Being Scale (SWBS) in patients with acute myocardial infarction. A multisite, cross-sectional survey was employed to determine the instrument's reliability (Cronbach's α and construct reliability) and validity (face, content, and construct). Using systematic sampling of adult outpatients at primary care clinic sites in the Qazvin City, Iran (N = 300), it was found that the Cronbach's alpha and construct reliability of both factors associated with the SWBS were above 0.7. The construct validity of the scale was determined using exploratory factor analysis. The findings supported two factors: relation with God and relation with life. Further investigation through confirmatory factor analysis (eigenvalues of greater than one) confirmed a third factor construct associated with the SWBS. A total of 50.65 % of the variance were explained by these three factors. The overall findings of the study demonstrated that the SWBS is a valid and reliable instrument that has potential utility in future research and clinical practice settings.
  5. Sharif Nia H, Pahlevan Sharif S, Goudarzian AH, Allen KA, Jamali S, Heydari Gorji MA
    J Relig Health, 2017 Dec;56(6):2109-2117.
    PMID: 28229351 DOI: 10.1007/s10943-017-0376-2
    In recent years, researchers have identified that coping strategies are an important contributor to an individual's life satisfaction and ability to manage stress. The positive relationship between religious copings, specifically, with physical and mental health has also been identified in some studies. Spirituality and religion have been discussed rigorously in research, but very few studies exist on religious coping. The aim of this study was to determine the relationship between religious coping methods (i.e., positive and negative religious coping) and self-care behaviors in Iranian medical students. This study used a cross-sectional design of 335 randomly selected students from Mazandaran University of Medical Sciences, Iran. A data collection tool comprised of the standard questionnaire of religious coping methods and questionnaire of self-care behaviors assessment was utilized. Data were analyzed using a two-sample t test assuming equal variances. Adjusted linear regression was used to evaluate the independent association of religious copings with self-care. Adjusted linear regression model indicated an independent significant association between positive (b = 4.616, 95% CI 4.234-4.999) and negative (b = -3.726, 95% CI -4.311 to -3.141) religious coping with self-care behaviors. Findings showed a linear relationship between religious coping and self-care behaviors. Further research with larger sample sizes in diverse populations is recommended.
  6. Md Yusof K, Mahmud R, Abdullah M, Avery-Kiejda KA, Rosli R
    Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1055-1061.
    PMID: 33906296 DOI: 10.31557/APJCP.2021.22.4.1055
    INTRODUCTION: The survival rate of female breast cancer survivors has been reported to be higher than other types of cancer in Malaysia. Nonetheless, breast cancer survivors face new challenges from unwanted side effects of treatment or management such as fatigue, psychological disturbance, or arm swelling, which can lead to the decline of quality of life (QOL). This study aims to adapt the Malay version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) to evaluate the QOL and to test its reliability and validity in Malaysian breast cancer survivors.

    METHODS: The Malay version of the FACT-B, with Disabilities of Arms, Shoulders and Hands (DASH), and Patient Health Questionnaire Anxiety-Depression Scale (PHQ-ADS) were distributed to female breast cancer survivors which were recruited on a voluntary basis, from cancer support groups based in selected states in Malaysia. Reliability was assessed based on internal consistency (Cronbach's α), whereas concurrent validity was examined by comparing domains in FACT-B with DASH and PHQ-ADS. Finally, total scores of each domain were analysed between lymphedema and without lymphedema groups for known-group validity.

    RESULTS: A total of 113 breast cancer survivors agreed to participate (response rate = 100%) in the study. Our results showed that the Cronbach's α value for Malay FACT-B is 0.88, and each domain ranged from 0.62 to 0.88. A strong correlation was found between the physical well-being domain of FACT-B with DASH. Meanwhile, the breast cancer scale (BCS) displayed significant correlation with the instrument, Patient Health Questionnaire- Anxiety Depression Scale (PHQ-ADS), indicating that multiple factors including psychological distress were measured in the BCS domain. Furthermore, the instrument was able to detect differences in physical, functional and QOL between participants from lymphedema and without lymphedema groups.

    CONCLUSION: The Malay version of the FACT-B demonstrated reliable properties and is effective in assessing QOL and can be applied in Malaysian breast cancer survivors.

  7. Yaghoobzadeh A, Sharif Nia H, Pahlevan Sharif S, Hosseinigolafshani SZ, Mohammadi F, Oveisi S, et al.
    Int J Aging Hum Dev, 2018 Jul;87(1):77-89.
    PMID: 28859489 DOI: 10.1177/0091415017727211
    Self-perception is found to be a central predictive factor in experiencing successful aging. The aim of this study was to explore the role of sex, socioeconomic status, and emotional support in elders' aging perception. A cross-sectional design was used with 300 older aged participants recruited from 23 clinics and health centers in Qazvin, Iran. Data were collected included questions to elicit demographic information and Barker's aging perception questionnaire. Exploratory multiple linear regression showed that the level of emotional support (β: -12.10; 95% CI: [-20.72, -3.48]), socioeconomic status (β: 2.84; 95% CI: [0.25, 5.43]), and women (β: -4.34; 95% CI: [-6.91, -1.77]) were associated with aging perception among elders. Educational level and marital status did not significantly contribute to the variance of AP. Findings revealed that aging perception was related to individual differences as well as social and emotional factors. Researchers, health-care professionals, and elders may benefit from thinking about old age as an inevitable life stage.
  8. Yaghoobzadeh A, Gorgulu O, Yee BL, Wibisono AH, Pahlevan Sharif S, Sharif Nia H, et al.
    J Am Psychiatr Nurses Assoc, 2018 01 22;24(6):522-530.
    PMID: 29357723 DOI: 10.1177/1078390317753676
    BACKGROUND: Aging perception plays a central role in the experience of healthy aging by older people. Research identified that factors such as hope, life satisfaction, and socioeconomic status influence the perception of aging in older populations.

    OBJECTIVE: This study sought to test a hypothetical model to quantitatively evaluate the relationship between hope, life satisfaction, and socioeconomic status with aging perception.

    DESIGN: A cross-sectional design was used with 504 older aged participants who live in Qazvin, Iran. Data were collected using the Barker's Aging Perception Questionnaire, Life Satisfaction Index-Z, and Herth Hope Index.

    RESULTS: The results of path analysis showed that hope was the most important factor affecting aging perception. Results drawn from correlation analysis indicated that there was a positive significant correlation ( r = .383, p < .001) between hope and aging perception. Further analysis found that hope had the strongest impact on aging perception compared with the other variables analyzed (e.g., life satisfaction and socioeconomic status).

    CONCLUSIONS: A model of aging perception in Iranian elders is presented. The findings suggested that hope had a significant and positive impact on aging perception. Implications for clinical practice and research are discussed.

  9. Yusof KM, Groen K, Rosli R, Abdullah M, Mahmud R, Avery-Kiejda KA
    Int J Mol Sci, 2022 Sep 26;23(19).
    PMID: 36232660 DOI: 10.3390/ijms231911359
    Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.
  10. Nazari R, Pahlevan Sharif S, Allen KA, Sharif Nia H, Yee BL, Yaghoobzadeh A
    J Caring Sci, 2018 Dec;7(4):197-203.
    PMID: 30607360 DOI: 10.15171/jcs.2018.030
    Introduction: A consistent approach to pain assessment for patients admitted to intensive care unit (ICU) is a major difficulty for health practitioners due to some patients' inability, to express their pain verbally. This study aimed to assess pain behaviors (PBs) in traumatic brain injury (TBI) patients at different levels of consciousness. Methods: This study used a repeated-measure, within-subject design with 35 patients admitted to an ICU. The data were collected through observations of nociceptive and non-nociceptive procedures, which were recorded through a 47-item behavior-rating checklist. The analyses were performed by SPSS ver.13 software. Results: The most frequently observed PBs during nociceptive procedures were facial expression levator contractions (65.7%), sudden eye openings (34.3%), frowning (31.4%), lip changes (31.4%), clear movement of extremities (57.1%), neck stiffness (42.9%), sighing (31.4%), and moaning (31.4%). The number of PBs exhibited by participants during nociceptive procedures was significantly higher than those observed before and 15 minutes after the procedures. Also, the number of exhibited PBs in patients during nociceptive procedures was significantly greater than that of exhibited PBs during the non-nociceptive procedure. The results showed a significant difference between different levels of consciousness and also between the numbers of exhibited PBs in participants with different levels of traumatic brain injury severity. Conclusion: The present study showed that most of the behaviors that have been observed during painful stimulation in patients with traumatic brain injury included facial expressions, sudden eye opening, frowning, lip changes, clear movements of extremities, neck stiffness, and sighing or moaning.
  11. Yusof KM, Mohd Sidik S, Mahmud R, Abdullah M, Avery-Kiejda KA, Rosli R
    Breast Cancer, 2023 Sep;30(5):810-819.
    PMID: 37306933 DOI: 10.1007/s12282-023-01475-0
    BACKGROUND: Although higher survival rates of breast cancer are achieved these days, breast cancer survivors are challenged with unwanted side effects from treatment or management that affect physical, functional, and psychological well-being of an individual. This study aimed to assess psychological distress status in Malaysian breast cancer survivors and factors that affected the condition.

    METHODS: A cross-sectional study design was conducted on 162 breast cancer survivors from various breast cancer support groups in Malaysia. Psychological distress status was assessed based on depression and anxiety scores by applying the Malay version of Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7). Both instruments were self-administered along with a set of questionnaires comprising demographic, medical history, quality of life, and upper extremity function assessment. Outcomes from the PHQ-9 and GAD-7 were analyzed for severity level of psychological distress, and its association with relevant variables, arm morbidity symptoms, as well as the duration of cancer survivorship.

    RESULTS: The univariate analysis showed that breast cancer survivors with arm morbidities after breast surgery had a higher score of depression (5.0 vs 4.0, p = 0.011) and anxiety (3.0 vs 1.0, p = 0.026) than those who did not. Besides that, receiving fewer post-rehabilitation treatments (p = 0.049) and having a family history of cancer (p = 0.022) were correlated with higher anxiety level. The level of depression and anxiety was inversely proportionate with quality of life and positively correlated with greater disability of the arm function (p 

  12. Sharif Nia H, Pahlevan Sharif S, Lehto RH, Allen KA, Goudarzian AH, Yaghoobzadeh A, et al.
    Iran J Psychiatry, 2017 Jul;12(3):172-181.
    PMID: 29062368
    Objective: Limited research has examined the psychometric properties of death depression scales in Persian populations with cardiac disease despite the need for valid assessment tools for evaluating depressive symptoms in patients with life-limiting chronic conditions. The present study aimed at evaluating the reliability and validity of the Persian Version of Death Depression Scale - Revised (DDS-R) in Iranian patients who had recent acute myocardial infarction (AMI). Method: This psychometric study was conducted with a convenience sample of 407 patients with AMI diagnosis who completed the Persian version of the DDS-R. The face, content, and construct validity of the scale were ascertained. Internal consistency, test-retest, and construct reliability (CR) were used to assess reliability of the Persian Version of DDS-R. Results: Based on maximum likelihood exploratory factor analysis and consideration of conceptual meaning, a 4-factor solution was identified, explaining 75.89% of the total variance. Goodness-of-fit indices (GFI), Comparative Fit Index (CFI), Normed Fit Index (NFI), Incremental Fit Index (IFI), and Root Mean Square Error of Approximation (RMSEA) in the final DDS-R structure demonstrated the adequacy of the 4-domain structure. The internal consistency, construct reliability, and Intra-class Correlation Coefficients (ICC) were greater than .70. Conclusion: The DDS-R was found to be a valid and reliable assessment tool for evaluating death depression symptoms in Iranian patients with AMI.
  13. Nikbakht Nasrabadi A, Pahlevan Sharif S, Allen KA, Naghavi N, Sharif Nia H, Salisu WJ, et al.
    Eur J Cancer Prev, 2022 Mar 01;31(2):198-203.
    PMID: 33899748 DOI: 10.1097/CEJ.0000000000000683
    While much research has focused on the direct impact of socioeconomic status on cancer patients, what is not clear is the impact of socioeconomic status on social support and the burden of care for caregivers. In this study, a cross-sectional method, using a convenience sampling approach, was adopted to collect the data of 191 caregivers of cancer patients who were referred to the oncology clinic and cancer institute of hospitals affiliated with Tehran University of Medical Sciences, Iran. The participants completed a questionnaire on basic demographics, the short version of the Burden Scale for Family Caregivers, and Zimet Multidimensional Perceived Social Support. A maximum likelihood exploratory factor analysis with oblique rotation to assess the factor structure of the constructs and the measurement model was conducted. The two-factor model consisting of 22 items explained 65.116% of the variance. There was a significant negative relationship between social support and burden (b = -0.771, P < 0.001) and also between economic status and burden (b = -0.308, P < 0.01). Moreover, there was a significant positive association between the interaction of social support and economic status and burden (b = 0.138, P < 0.05). More specifically, the negative relationship between social support and burden was statistically stronger for participants with weak economic status (b = -0.663, P < 0.001) than those with good economic status (b = -0.356, P < 0.01). Social support and an individual's economic status are essential determinants of caregiver burden. Further studies are recommended to better inform the precise support needed by caregivers to enhance their quality of life, and ultimately, that of the patients under their care.
  14. Yusof KM, Avery-Kiejda KA, Ahmad Suhaimi S, Ahmad Zamri N, Rusli MEF, Mahmud R, et al.
    Diagnostics (Basel), 2021 Jul 21;11(8).
    PMID: 34441238 DOI: 10.3390/diagnostics11081303
    Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk factors of BCRL in long term breast cancer survivors. A total of 160 female breast cancer subjects were recruited on a voluntary basis and arm lymphedema was assessed through self-reporting of diagnosis, arm circumference measurement, and ultrasound examination. A total of 33/160 or 20.5% of the women developed BCRL with significantly higher scores for upper extremity disability (37.14 ± 18.90 vs. 20.08 ± 15.29, p < 0.001) and a lower score for quality of life (103.91 ± 21.80 vs. 115.49 ± 16.80, p = 0.009) as compared to non-lymphedema cases. Univariate analysis revealed that multiple surgeries (OR = 5.70, 95% CI: 1.21-26.8, p < 0.001), axillary lymph nodes excision (>10) (OR = 2.83, 95% CI: 0.94-8.11, p = 0.047), being overweight (≥25 kg/m2) (OR = 2.57, 95% CI: 1.04 - 6.38, p = 0.036), received fewer post-surgery rehabilitation treatment (OR = 2.37, 95% CI: 1.05-5.39, p = 0.036) and hypertension (OR = 2.38, 95% CI: 1.01-5.62, p = 0.043) were associated with an increased risk of BCRL. Meanwhile, multivariate analysis showed that multiple surgeries remained significant and elevated the likelihood of BCRL (OR = 5.83, 95% CI: 1.14-29.78, p = 0.034). Arm swelling was more prominent in the forearm area demonstrated by the highest difference of arm circumference measurement when compared to the upper arm (2.07 ± 2.48 vs. 1.34 ± 1.91 cm, p < 0.001). The total of skinfold thickness of the affected forearm was also significantly higher than the unaffected arms (p < 0.05) as evidenced by the ultrasound examination. The continuous search for risk factors in specific populations may facilitate the development of a standardized method to reduce the occurrence of BCRL and provide better management for breast cancer patients.
  15. Scazzuso F, Ptaszyński P, Kaczmarek K, Chun KRJ, Khelae SK, Földesi C, et al.
    J Interv Card Electrophysiol, 2024 Apr;67(3):493-501.
    PMID: 37505337 DOI: 10.1007/s10840-023-01582-0
    BACKGROUND: Cryoballoon ablation is a well-established anatomical approach for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Although widely adopted, regional variations in standards of care have not been well characterized.

    METHODS: Patients with AF were enrolled in the Cryo Global Registry (NCT02752737) from May 2016 to Sept 2021 at 128 sites in 37 countries and treated with cryoballoon ablation according to local clinical practice. Baseline patient and procedural characteristics were summarized for 8 regions (Central Asia & Russia, East Asia, Europe, Middle East, North America, South Africa, South America, and Southeast Asia). Serious procedure-related adverse events (SAEs) were evaluated in a subset of patients with ≥ 7 days of follow-up.

    RESULTS: A total of 3,680 patients undergoing initial PVI for AF were included. Cryoballoon ablation was commonly performed in patients with paroxysmal AF. Mean age ranged from 47 ± 12 years in the Middle East to 64 ± 11 years in East Asia. Mean procedure time was ≤ 95 min in all regions. Average freeze duration ranged from 153 ± 41 s in Southeast Asia to 230 ± 29 s in Central Asia & Russia. Acute procedural success was ≥ 94.7% in all geographies. In 3,126 subjects with ≥ 7 days of follow-up, 122 procedure-related SAEs were reported in 111 patients (3.6%) and remained low in all regions. One procedure-related death was reported during data collection.

    CONCLUSIONS: Despite regional variations in patient selection and procedural characteristics, PVI using cryoballoon ablation was performed with high acute success and short procedural times around the world.

    CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.

  16. Zucchelli G, Chun KRJ, Khelae SK, Földesi C, Kueffer FJ, van Bragt KA, et al.
    J Interv Card Electrophysiol, 2023 Apr;66(3):711-722.
    PMID: 36331681 DOI: 10.1007/s10840-022-01388-6
    BACKGROUND: Cryoballoon ablation (CBA) is an effective first-line treatment for symptomatic atrial fibrillation (AF), as recently demonstrated by three randomized trials. This sub-analysis of the Cryo Global Registry aims to examine current clinical practices of first-line CBA.

    METHODS: AF patients treated with first-line CBA were compared to CBA in antiarrhythmic drug (AAD)-refractory patients at 12 months. Efficacy was examined using time-to-first atrial arrhythmia recurrence following a 90-day blanking period. Healthcare utilization was evaluated by repeat ablations and hospitalizations. Disease burden was examined by assessing quality of life (QOL) and patients' reporting of symptoms.

    RESULTS: Of 1394 patients, 433 (31.1%) were treated with first-line CBA, which was more frequent in high-volume centers. Serious procedure-related adverse event rates were similar. Efficacy at 12 months was higher in the first-line group (87.8 vs. 81.6%, HRunadj 0.64 (95% CI 0.47-0.88); p 

  17. Pinkham K, Park DJ, Hashemiaghdam A, Kirov AB, Adam I, Rosiak K, et al.
    Stem Cell Reports, 2019 04 09;12(4):712-727.
    PMID: 30930246 DOI: 10.1016/j.stemcr.2019.02.012
    Inherent plasticity and various survival cues allow glioblastoma stem-like cells (GSCs) to survive and proliferate under intrinsic and extrinsic stress conditions. Here, we report that GSCs depend on the adaptive activation of ER stress and subsequent activation of lipogenesis and particularly stearoyl CoA desaturase (SCD1), which promotes ER homeostasis, cytoprotection, and tumor initiation. Pharmacological targeting of SCD1 is particularly toxic due to the accumulation of saturated fatty acids, which exacerbates ER stress, triggers apoptosis, impairs RAD51-mediated DNA repair, and achieves a remarkable therapeutic outcome with 25%-100% cure rate in xenograft mouse models. Mechanistically, divergent cell fates under varying levels of ER stress are primarily controlled by the ER sensor IRE1, which either promotes SCD1 transcriptional activation or converts to apoptotic signaling when SCD1 activity is impaired. Taken together, the dependence of GSCs on fatty acid desaturation presents an exploitable vulnerability to target glioblastoma.
  18. Twining JP, Sutherland C, Zalewski A, Cove MV, Birks J, Wearn OR, et al.
    Proc Natl Acad Sci U S A, 2024 Mar 19;121(12):e2312252121.
    PMID: 38466845 DOI: 10.1073/pnas.2312252121
    The social system of animals involves a complex interplay between physiology, natural history, and the environment. Long relied upon discrete categorizations of "social" and "solitary" inhibit our capacity to understand species and their interactions with the world around them. Here, we use a globally distributed camera trapping dataset to test the drivers of aggregating into groups in a species complex (martens and relatives, family Mustelidae, Order Carnivora) assumed to be obligately solitary. We use a simple quantification, the probability of being detected in a group, that was applied across our globally derived camera trap dataset. Using a series of binomial generalized mixed-effects models applied to a dataset of 16,483 independent detections across 17 countries on four continents we test explicit hypotheses about potential drivers of group formation. We observe a wide range of probabilities of being detected in groups within the solitary model system, with the probability of aggregating in groups varying by more than an order of magnitude. We demonstrate that a species' context-dependent proclivity toward aggregating in groups is underpinned by a range of resource-related factors, primarily the distribution of resources, with increasing patchiness of resources facilitating group formation, as well as interactions between environmental conditions (resource constancy/winter severity) and physiology (energy storage capabilities). The wide variation in propensities to aggregate with conspecifics observed here highlights how continued failure to recognize complexities in the social behaviors of apparently solitary species limits our understanding not only of the individual species but also the causes and consequences of group formation.
  19. Sartelli M, Weber DG, Ruppé E, Bassetti M, Wright BJ, Ansaloni L, et al.
    World J Emerg Surg, 2016;11:33.
    PMID: 27429642 DOI: 10.1186/s13017-016-0089-y
    Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.
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