PATIENTS AND METHODS: A total of 120 men, aged 40-70 years, with TD (serum total testosterone [TT] ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo. In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study. Participants were seen six times in the 48-week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone-binding globulin, liver function test, prostate- specific antigen (PSA) and adverse events.
RESULTS: The mean (sd) age of the participants was 53.4 (7.6) years. A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48-week period. Two men in the placebo arm and one man in the treatment arm developed myocardial infarction. Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne. Overall, TU injections were well tolerated.
CONCLUSIONS: TU significantly increases serum testosterone in men with TD. PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits. There was no significant adverse reaction that led to the cessation of treatment.
METHODS: The fructophilic characteristics of strain Sy-1 were determined, and the genome was sequenced using Illumina iSeq100 and Oxford Nanopore. The average nucleotide identity and phylogenetic analyses based on 16S rRNA, 92 core genes, and whole-genome sequence were performed to unravel the phylogenetic position of strain Sy-1. NCBI Prokaryotic Genome Annotation Pipeline annotated the genome, while the EggNOG-mapper, BLASTKoala, and GHOSTKoala were used to add functional genes and pathways information.
RESULTS: Strain Sy-1 prefers D-fructose over D-glucose and actively metabolizes D-glucose in the presence of electron acceptors. Genomic annotation of strain Sy-1 revealed few genes involved in carbohydrate transport and metabolism, and partial deletion of adhE gene, in line with the characteristic of FLAB. The 16S rRNA gene sequence of strain Sy-1 showed the highest similarity to unknown LAB species isolated from the gut of honeybees. The phylogenetic analyses discovered that strain Sy-1 belonged to the Lactobacillaceae family and formed a separate branch closer to type strain from the genera of Acetilactobacillus and Apilactobacillus. The ANI analysis showed the similarity of the closest relative, Apilactobacillus micheneri Hlig3T. The assembled genome of Sy-1 contains 3 contigs with 2.03 Mbp and a 41% GC content. A total of 1,785 genes were identified, including 1,685 protein-coding genes, 68 tRNA, and 15 rRNA. Interestingly, strain Sy-1 encoded complete genes for the biosynthesis of folate and riboflavin. High-performance liquid chromatography analysis further confirmed the high production of folic acid (1.346 mg/L) by Sy-1.
DISCUSSION: Based on phylogenetic and biochemical characteristics, strain Sy-1 should be classified as a novel genus in the family of Lactobacillaceae and a new member of FLAB. The genome information coupled with experimental studies supported the ability of strain Sy-1 to produce high folic acid. Our collective findings support the suitable application of FLAB strain Sy-1 in the functional food and pharmaceutical industries.
STUDY DESIGN: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF- α, and hs-CRP were measured.
MAIN OUTCOME MEASURE: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR).
RESULTS: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF- α (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF- α, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66).
CONCLUSIONS: Insulin resistance was independently associated with obesity, high VAT, low physical performance, and high levels of TNF- α in midlife Singaporean women. These variables entirely explained the significant differences in insulin resistance between women of Chinese, Malay and Indian ethnicity.