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Mitochondrion May 2024Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile...
OBJECTIVES
Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d.
METHODS
An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented.
RESULTS
After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea.
DISCUSSION
Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.
Topics: Humans; Male; Thymidine Kinase; Administration, Oral; Adult; Treatment Outcome; Mitochondrial Diseases; Nucleosides
PubMed: 38599303
DOI: 10.1016/j.mito.2024.101879 -
Journal of Science and Medicine in Sport Jun 2024Inter-individual developmental differences confound the capability to accurately evaluate youth athletic performance, highlighting the need for considerate methodology...
OBJECTIVES
Inter-individual developmental differences confound the capability to accurately evaluate youth athletic performance, highlighting the need for considerate methodology and analytical approaches. The present study demonstrated how Percentile Comparison Methods (PCMs) were developed, tested, and applied to identify athlete developmental profiles in Australian youth swimming.
DESIGN
Cross-sectional.
METHODS
Participants were N = 866 female 100-metre (m) Front-Crawl swimmers, aged 9-15 years, competing at 36 Australian regional-national level long course events. At respective events, swim performance time was collated alongside, age, date of birth, and anthropometric measures to identify age group, relative age, and maturity status. Quadratic relative age and maturity status with 100-m performance regression trendlines were generated. Then, individual swim performances at a given relative age or maturity status were converted into percentile rank distributions and compared with raw (unadjusted) annual age-group performance percentile ranks.
RESULTS
At a cohort level, initial testing confirmed relative age and maturity-adjusted percentile rankings were associated with general rank improvements for relatively younger and later maturing swimmers compared to raw ranks (and vice versa). When assessing individual swimmer plots, where three percentile rank scores were compared and rank change threshold criteria applied, five Percentile Comparison Method profile types were identified, namely: 'Early Developing' (19 %); 'Later Developing' (18 %); 'Consistent' (15 %); 'Mixed' (38 %) and 'Counteracting' (10 %). Percentile Comparison Method plots helped identify developmentally (dis-)advantaged swimmers; specific factors leading to (dis-)advantage, and likely onward development trajectories.
CONCLUSIONS
Overall and with practical considerations, Percentile Comparison Methods can improve the validity of youth athletic performance evaluation as well as inform athlete development programming.
Topics: Humans; Adolescent; Child; Swimming; Female; Cross-Sectional Studies; Athletic Performance; Australia; Athletes; Adolescent Development; Age Factors; Child Development; Anthropometry
PubMed: 38594115
DOI: 10.1016/j.jsams.2024.03.004 -
Journal of the American Heart... Apr 2024We aimed to describe the frequency and yield of genetic testing in supravalvar aortic stenosis (SVAS) following negative evaluation for Williams-Beuren syndrome (WS).
BACKGROUND
We aimed to describe the frequency and yield of genetic testing in supravalvar aortic stenosis (SVAS) following negative evaluation for Williams-Beuren syndrome (WS).
METHODS AND RESULTS
This retrospective cohort study included patients with SVAS at our institution who had a negative evaluation for WS from May 1991 to September 2021. SVAS was defined as (1) peak supravalvar velocity of ≥2 meters/second, (2) sinotubular junction or ascending aortic score <-2.0, or (3) sinotubular junction score <-1.5 with family history of SVAS. Patients with complex congenital heart disease, aortic valve disease as the primary condition, or only postoperative SVAS were excluded. Genetic testing and diagnoses were reported. Of 162 patients who were WS negative meeting inclusion criteria, 61 had genetic testing results available (38%). Chromosomal microarray had been performed in 44 of 61 and was nondiagnostic for non-WS causes of SVAS. Sequencing of 1 or more genes was performed in 47 of 61. Of these, 39 of 47 underwent sequencing, 20 of 39 (51%) of whom had a diagnostic variant. Other diagnoses made by gene sequencing were Noonan syndrome (3 , 1 , Alagille syndrome (3 ), neurofibromatosis (1 ), and homozygous familial hypercholesterolemia (1 ). Overall, sequencing was diagnostic in 29 of 47 (62%).
CONCLUSIONS
When WS is excluded, gene sequencing for SVAS is high yield, with the highest yield for the gene. Therefore, we recommend gene sequencing using a multigene panel or exome analysis. Hypercholesterolemia can also be considered in individuals bearing the stigmata of this disease.
Topics: Humans; Williams Syndrome; Aortic Stenosis, Supravalvular; Retrospective Studies; Genetic Testing; Aorta
PubMed: 38591341
DOI: 10.1161/JAHA.123.034048 -
European Journal of Pediatrics Jul 2024Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic... (Observational Study)
Observational Study
Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of term and preterm neonates according to Neomar's neonatal skin color scale. Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color. We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74-0.83) and after (0.79-0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 h after discontinuing phototherapy (0.78). Conclusions: Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar's scale during and mainly after phototherapy may help reduce the number of blood samples required. What is Known: • Controversies exist on the reliability of jaundice meters during and after phototherapy in covered skin. Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in covered skin in a multiethnic population depending on skin color based on our own validated neonatal skin color scale during and after phototherapy.
Topics: Humans; Bilirubin; Infant, Newborn; Skin Pigmentation; Prospective Studies; Reproducibility of Results; Female; Phototherapy; Jaundice, Neonatal; Male; Neonatal Screening; Infant, Premature; Gestational Age
PubMed: 38581462
DOI: 10.1007/s00431-024-05516-4 -
Movement Disorders Clinical Practice Jun 2024Core stability exercises (CSE) have been shown to be effective in improving trunk function in several neurological diseases, but the evidence is scarce on Hereditary... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Core stability exercises (CSE) have been shown to be effective in improving trunk function in several neurological diseases, but the evidence is scarce on Hereditary Ataxias (HA).
OBJECTIVE
To evaluate the effectiveness of a 5-week home-based CSE program in terms of ataxia severity, trunk function, balance confidence, gait speed, lower limb motor function, quality of life, health status and falls rate in HA individuals at short- and long-term.
METHODS
This is an assessor-blind randomized controlled clinical trial parallel group 1:1. The individuals were divided in experimental group (EG) performed standard care in addition to CSE, and control group (CG) performed standard care alone. The CSE home-program was conducted 1-h/day, 5-day/week for 5-week. The assessment was performed at baseline, endpoint (5-week), and follow-up (10-week). The primary outcomes were ataxia severity assessed by the Scale for the Assessment and Rating of Ataxia and trunk function assessed by Spanish-version of Trunk Impairment Scale 2.0. The secondary outcomes were balance confidence assessed by Activities-specific Balance Confidence (ABC), gait speed by 4-meter walk test (4-MWT), the lower limb motor function by 30-s sit-to-stand, quality of life by EuroQol 5-dimension 5-level (EQ-5D-5L), health-status by EQ-5D and falls rate.
RESULTS
Twenty-three HA individuals were recruited (51.8 ± 11.10 years). Statistically significant group-time interaction was shown in ABC (F:5.539; P = 0.007), EQ-5D-5L Total (F:4.836; P = 0.013), EQ 5D (F:7.207; P = 0.006).
CONCLUSIONS
No statistical differences between groups for ataxia severity and trunk function were observed. However, were differences for balance confidence, gait speed, quality of life, and falls rate in HA individuals.
Topics: Humans; Male; Female; Postural Balance; Pilot Projects; Adult; Exercise Therapy; Quality of Life; Middle Aged; Treatment Outcome; Accidental Falls; Single-Blind Method; Severity of Illness Index
PubMed: 38563436
DOI: 10.1002/mdc3.14036 -
Heliyon Apr 2024This research investigates the physico-chemical, mineralogical and geochemical attributes of alluvial clayey sediments in the Nkoteng-Mbandjock regions of the Sanaga...
Mineralogical and geochemical characteristics of the Nkoteng-Mbandjock alluvial clays from Sanaga valley deposits (Cameroon, Central Africa): Implications for source weathering and provenance.
This research investigates the physico-chemical, mineralogical and geochemical attributes of alluvial clayey sediments in the Nkoteng-Mbandjock regions of the Sanaga valley, Cameroon. The primary objective is to elucidate the source area-weathering and provenance of these sediments. Grain size distribution analyses were conducted using the Robinson-Kӧln's pipetting method. The physico-chemical parameters were evaluated by an HACH-HQ11d brand electric pH meter, while the mineralogical compositions were determined by X-ray Diffraction. Major and trace element concentrations were measured employing X-ray Fluorescence and Inductively Coupled Plasmas-Mass Spectrometry. Textural classification identified the Sanaga valley alluvial clay deposits as predominantly silty clayey and clayey muddy. Geochemical classification diagram positioned them in the shale and Fe-shale fields. Weathering indices of alteration exhibited a consistent trend indicating a high degree of weathering in the source rock. A low NaO/KO ratio (average 0.18) and a high Index of Compositional Variability (ICV; average 2.29) suggested immature sediments. Additionally, low SiO/AlO ratio (average 3.93) implied an origin from stable settings with recycled inputs. These characteristics were further supported by elemental ratios such as Zr/Sc (average 47.12), U/Th (average 0.24) and Th/Sc (average 1.48). Furthermore, indicators like V/Cr (average 1.17), U/Th (average 0.24) and authigenic U (average -1.67) values suggested the deposition of the Sanaga valley alluvial clay under oxic conditions. The collective analysis of major and trace element distribution revealed felsic sources with minimal contributions from mafic rocks. These findings contribute to a comprehensive understanding of the geological processes and conditions influencing the composition and characteristics of the studied alluvial clay deposits in the Sanaga valley.
PubMed: 38560138
DOI: 10.1016/j.heliyon.2024.e28395 -
Diabetes Jul 2024Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older...
Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with and without diabetes, as well as determined their relative contribution to slower walking speed in older adults with diabetes. Participants with diabetes (n = 159) had lower cardiorespiratory fitness and mitochondrial respiration in permeabilized fiber bundles compared with those without diabetes (n = 717), following adjustments for covariates including BMI, chronic comorbid health conditions, and physical activity. Four-meter and 400-m walking speeds were slower in those with diabetes. Mitochondrial oxidative capacity alone or combined with cardiorespiratory fitness mediated ∼20-70% of the difference in walking speed between older adults with and without diabetes. Additional adjustments for BMI and comorbidities further explained the group differences in walking speed. Cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity contribute to slower walking speeds in older adults with diabetes.
Topics: Humans; Aged; Male; Female; Walking Speed; Cardiorespiratory Fitness; Mitochondria, Muscle; Diabetes Mellitus; Muscle, Skeletal; Middle Aged
PubMed: 38551899
DOI: 10.2337/db23-0827 -
Journal of Physiological Anthropology Mar 2024Local alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping...
Local alternating heat and cold stimulation affects hemodynamics and oxygenation in fatigued muscle tissue and autonomic nervous activity: a single-arm interventional study.
BACKGROUND
Local alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping effect and consequently promoting increased tissue blood flow and oxygenation. This study aimed to examine the effects of local alternating heat and cold stimulation, using a wearable thermal device, on the hemodynamics of fatigued muscle tissue and autonomic nervous activity.
METHODS
Twenty healthy individuals experienced fatigue in the periarticular muscles of the shoulder joint due to a typing task. Local alternating heat and cold stimulations were then applied to the upper trapezius muscle. Muscle hardness was measured using a muscle hardness meter, and muscle tissue hemodynamics and oxygenation were evaluated using near-infrared spectroscopy before and after the stimulation. Autonomic nervous activity was also evaluated using heart rate variability.
RESULTS
Alternating heat and cold stimulation decreased muscle hardness of the fatigued trapezius muscle from 1.38 ± 0.15 to 1.31 ± 0.14 N (P < 0.01). The concentration of total hemoglobin in the trapezius muscle tissue increased from - 0.21 ± 1.36 to 2.29 ± 3.42 µmol/l (P < 0.01), and the tissue hemoglobin oxygen saturation also increased from 70.1 ± 5.4 to 71.1 ± 6.0% (P < 0.05). Additionally, the heart rate variability parameter, which is an index of sympathetic nervous activity, increased from 3.82 ± 2.96 to 6.86 ± 3.49 (P < 0.01). A correlation was found between increased tissue hemoglobin oxygen saturation and increased parameters of sympathetic nervous activity (r = 0.50, P < 0.05).
CONCLUSIONS
Local alternating heat and cold stimulation affected the hemodynamic response in fatigued muscle tissue and autonomic nervous activity. This stimulation is more efficient than conventional contrast baths in terms of mobility and temperature control and has potential as a new versatile therapeutic intervention for muscle fatigue.
TRIAL REGISTRATION
UMIN-CTR (UMIN000040087: registered on April 7, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045710 . UMIN000040620: registered on June 1, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359 ).
Topics: Humans; Hot Temperature; Hemodynamics; Cold Temperature; Muscle, Skeletal; Hemoglobins
PubMed: 38528599
DOI: 10.1186/s40101-024-00358-3 -
Methods and Protocols Feb 2024Serratiopeptidase, a bacterial metalloprotease known for its pain-relieving and anti-inflammatory properties, can be produced through fermentation with . This study...
Serratiopeptidase, a bacterial metalloprotease known for its pain-relieving and anti-inflammatory properties, can be produced through fermentation with . This study aimed to identify key factors related to nutrient composition and physicochemical conditions for production in Erlenmeyer flasks and to scale up the mixture to a bioreactor to obtain the maximum proteolytic activity. A Plackett-Burman design was used to determine whether the presence of silkworm pupae (at 1.5%) was a significant parameter for serratiopeptidase production. Along with the variables pH, temperature, and time, they were optimized using a Taguchi experimental design, resulting in values of 7, 25 °C, and 36 h, respectively. Scaling up with a ka of 25.45 ± 3.12 h showed the highest serratiopeptidase production at 24 h. A factorial design was used for ultrafiltration, resulting in an LMH (liters per square meter per hour) of 960 L/mh, a TMP (transmembrane pressure) of 15 psi, and a concentration factor of five, with a specific activity of 24,325.81 ± 1515.69 U/mg. Afterward, the retentate was purified using strong anion exchange chromatography and ultrafiltration, yielding a 19.94 ± 3.07% recovery and a purification factor of 1.59 ± 0.31. In conclusion, waste from the sericulture industry can be used for serratiopeptidase production.
PubMed: 38525777
DOI: 10.3390/mps7020019 -
Frontiers in Aging 2024Exercise has been shown to improve physical function, mitigate aspects of chronic disease and to potentially alter the trajectory of age-related onset of frailty and...
Exercise has been shown to improve physical function, mitigate aspects of chronic disease and to potentially alter the trajectory of age-related onset of frailty and sarcopenia. Reliable and valid preclinical models are necessary to elucidate the underlying mechanisms at the intersection of age, exercise, and functional decline. The purpose of this study was to compare, head to head, the effects of two common pre-clinical models of endurance exercise: high intensity interval training (HIIT) and voluntary wheel running (VWR). The hypothesis was that a prescribed and regimented exercise program, HIIT, would prove to be a superior training method to unregulated voluntary exercise, VWR. To investigate this hypothesis, we evaluated adult (n = 24, designated 10 m, aged 6 months at the beginning of the study, 10 months at its completion) and older adult (n = 18, designated 26 m, aging from 22 months to 26 months over the course of the study) C57BL/6 male mice. These mice were randomly assigned (with selection criteria) to a 13-week program of voluntary wheel running (VWR), high intensity interval training (HIIT), or sedentary control (SED). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass, body composition (with EchoMRI), plantar flexor torque (in 10 m), and measured muscle wet mass post-training. Overall, adult CFAB scores decreased while body mass and percent body fat increased as they matured; however, exercise significantly mitigated the changes ( < 0.05) compared to SED. Older adults demonstrated preservation of function (CFAB) and reduced body fat ( < 0.05) compared to SED. To conclude, both types of exercise maintained physical function equally in older mice.
PubMed: 38523671
DOI: 10.3389/fragi.2024.1356954