Publications by authors named "M Kotowicz"

225 Publications

The steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction.

Nat Commun 2021 06 7;12(1):3328. Epub 2021 Jun 7.

CEDOC, Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.

Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of Drosophila larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.
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http://dx.doi.org/10.1038/s41467-021-23218-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184853PMC
June 2021

The Predictability of Frailty Associated with Musculoskeletal Deficits: A Longitudinal Study.

Calcif Tissue Int 2021 May 20. Epub 2021 May 20.

School of Medicine, Epi-Centre for Healthy Ageing, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, Deakin University, PO Box 281 Barwon Health, Geelong, VIC, 3220, Australia.

We investigated and quantified the predictability of frailty associated with musculoskeletal parameters. This longitudinal study included 287 men aged ≥ 50 yr at baseline (2001-2006) from the Geelong Osteoporosis Study. Baseline musculoskeletal measures included femoral neck bone mineral density (BMD), appendicular lean mass index (ALMI, kg/m) and whole-body fat mass index (FMI, kg/m) and lower-limb strength. Frailty at the 15 yr-follow-up (2016-2019) was defined as ≥ 3 and non-frail as < 3, of the following: unintentional weight loss, weakness, low physical activity, exhaustion, and slowness. Binary regression models and AUROC curves quantified the attributable risk of musculoskeletal factors to frailty and their predictive ability. Potential confounders included anthropometry, smoking, alcohol, FMI, socioeconomic status and comorbidities. Forty-eight (16.7%) men were frail at 15 yr-follow-up. Musculoskeletal models were better predictors of frailty compared to the referent (confounders only) model (AUROC for musculoskeletal factors 0.74 vs 0.67 for the referent model). The model with the highest AUROC (0.74; 95% CI 0.66-0.82) included BMD, ALMI and muscle strength (hip abductors) and was better than the referent model that included only lifestyle factors (p = 0.046). Musculoskeletal parameters improved the predictability model as measured by AUROC for frailty after 15 years. In general, muscle models performed better compared to bone models. Musculoskeletal parameters improved the predictability of frailty of the referent model that included lifestyle factors. Muscle deficits accounted for a greater proportion of the risk for frailty than did bone deficits. Targeting musculoskeletal health could be a possible avenue of intervention in regards to frailty.
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http://dx.doi.org/10.1007/s00223-021-00865-wDOI Listing
May 2021

Association between serum interleukin-6 and frailty in older men: cross-sectional data.

Eur Geriatr Med 2021 Mar 27. Epub 2021 Mar 27.

IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, (Barwon Health), PO Box 281, Geelong, VIC, 3220, Australia.

Purpose: To investigate the association between serum interleukin-6 (IL-6) and frailty.

Methods: Participants were 581 men aged 60-90 yr (median (IQR): 74 yr (67-83 yr)) from the Geelong Osteoporosis Study. Tallies of ≥ 3, 1-2 and 0 for weight loss/exhaustion/physical-inactivity/slowness/weakness indicated frailty, pre-frailty and robustness, respectively. Anthropometry, lower-limb muscle strength and physical performance were measured and health behaviours self-reported. Serum IL-6 was measured using an enzyme-linked immunosorbent assay and log-transformed (ln-IL-6). Total antioxidant capacity (TAC) was also measured using quantitative colorimetric determination. Multivariable ordinal logistic regression models tested associations between ln-IL-6 and frailty while considering age, anthropometry, comorbidities, TAC, medications that affect inflammatory processes, lifestyle and socioeconomic status.

Results: There were 49(8.4%) frail and 315(54.2%) pre-fail men. A relationship was evident between ln-IL-6 and frailty before and after accounting for age (adjusted OR = 1.24, 95%CI 1.01-1.53). Adjusting for medications attenuated the association (OR = 1.20, 95%CI 0.98-1.48). No other confounders were identified.

Conclusion: These data suggest that IL-6 is positively associated with frailty in men, partly explained by advancing age and medications known to affect inflammation.
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http://dx.doi.org/10.1007/s41999-021-00490-8DOI Listing
March 2021

Associations between Bone Material Strength Index, Calcaneal Quantitative Ultrasound, and Bone Mineral Density in Men.

J Endocr Soc 2021 Apr 22;5(4):bvaa179. Epub 2020 Nov 22.

Deakin University, IMPACT - Institute for Mental and Physical Health and Clinical Translation, Geelong, VIC, Australia.

Objectives: Impact micro-indentation (IMI) measures bone material strength index (BMSi) in vivo. This study investigated how IMI is associated with calcaneal quantitative ultrasound and bone densitometry parameters in men.

Methods: BMSi was measured on the tibial plateau using the OsteoProbe in 377 men (age 33-96 years) from the Geelong Osteoporosis Study. Broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) were assessed at the calcaneus using an ultrasonometer. Areal BMD was measured at several skeletal sites using dual-energy x-ray absorptiometry. Linear associations between parameters were tested using Pearson's correlation. Multivariable regression techniques were used to determine associations between BMSi and other measures of bone, independent of confounders.

Results: BMSi was negatively correlated with age (r = -0.171, = .001), weight (r = -0.100, = .052), and body mass index (r = -0.187, = .001), and positively with height (r = +0.109, = .034). There was some evidence to support a positive association between BMSi and BUA (β = 0.052, = .037), SOS (β = 0.013, = .144), and SI (β = 0.036, = .051). After age adjustment, this association was attenuated. No correlations were observed between BMSi and BMD at any skeletal site (r values ranged from -0.006 to +0.079, all ≥ .13).

Conclusion: There was a small positive association between BMSi and quantitative ultrasound (QUS) parameters, which were not independent of age. No associations were detected between BMSi and BMD. This suggests that BMSi and QUS are capturing common age-dependent properties of bone. Further research on the utility of IMI alone and complementary to conventional bone testing methods for predicting fracture risk is warranted.
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http://dx.doi.org/10.1210/jendso/bvaa179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940167PMC
April 2021

Dynapenia and Low Cognition: A Cross-Sectional Association in Postmenopausal Women.

J Clin Med 2021 Jan 6;10(2). Epub 2021 Jan 6.

IMPACT-The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC 3220, Australia.

Dynapenia is a key contributor to physical frailty. Cognitive impairment and dementia accompany frailty, yet links between skeletal muscle and neurocognition are poorly understood. We examined the cross-sectional relationship between lower limb muscle strength and global cognitive function. Participants were 127 women aged 51-87 years, from the Geelong Osteoporosis Study. Peak eccentric strength of the hip-flexors and hip abductors was determined using a hand-held dynamometer, and dynapenia identified as muscle strength -scores < -1. Cognition was assessed using the Mini-Mental State Examination (MMSE), and MMSE scores below the median were rated as low. Associations between dynapenia and low cognition were examined using logistic regression models. Hip-flexor dynapenia was detected in 38 (71.7%) women with low cognition and 36 (48.7%) with good cognition ( = 0.009); for hip abductor dynapenia, the pattern was similar (21 (39.6%) vs. 9 (12.2%); < 0.001). While the observed difference for hip-flexor strength was attenuated after adjusting for age and height (adjusted Odds Ratio (OR) 1.95, 95%CI 0.86-4.41), low cognition was nearly 4-fold more likely in association with hip abductor dynapenia (adjusted OR 3.76, 95%CI 1.44-9.83). No other confounders were identified. Our data suggest that low strength of the hip abductors and low cognition are associated and this could be a consequence of poor muscle function contributing to cognitive decline or vice versa. As muscle weakness is responsive to physical interventions, this warrants further investigation.
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http://dx.doi.org/10.3390/jcm10020173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825045PMC
January 2021