Blackcurrants shape gut microbiota profile and reduce risk of postmenopausal osteoporosis via the gut-bone axis: Evidence from a pilot randomized controlled trial.

This study aimed to investigate the effects of blackcurrant (BC) on gut microbiota abundance and composition, inflammatory and immune responses, and their relationship with bone mass changes. The effects of BC on bone mineral density (BMD), gut microbiota, and blood inflammatory and immune biomarkers were evaluated using DXA, stool and fasting blood collected from a pilot 3-arm, randomized, double-blind, placebo-controlled clinical trial. Fifty-one peri- and early postmenopausal women aged 45-60 years were randomly assigned into one of three treatment groups for 6 months: control, low BC (392 mg/day) and high BC (784 mg/day); and 40 women completed the trial. BC supplementation for six months effectively mitigated the loss of whole-body BMD (P<0.05). Six-month changes (%) in peripheral IL-1ß (P=0.056) and RANKL (P=0.052) for high BC group were marginally significantly lower than the control group. Six-month changes in whole-body BMD were inversely correlated with changes in RANKL (P<0.01). In proteome analysis, four plasma proteins showed increased expression in the high BC group: IGFBP4, tetranectin, fetuin-B, and vitamin K-dependent protein S. BC dose-dependently increased the relative abundance of Ruminococcus 2 (P<0.05), one of six bacteria correlated with BMD changes in the high BC group (P<0.05), suggesting it might be the key bacteria that drove bone protective effects. Daily BC consumption for 6 months mitigated bone loss in this population potentially through modulating the gut microbiota composition and suppressing osteoclastogenic cytokines. Larger-scale clinical trials on the potential benefits of BC and connection of Ruminococcus 2 with BMD maintenance in postmenopausal women are warranted. Trial Registration: NCT04431960, https://classic.clinicaltrials.gov/ct2/show/NCT04431960.

Blackcurrant Anthocyanins Improve Blood Lipids and Biomarkers of Inflammation and Oxidative Stress in Healthy Women in Menopause Transition without Changing Body Composition.

Recent cell and animal studies suggest the potential of blackcurrants (BCs; Ribes nigrum) as a dietary agent that may reduce the risk of cardiovascular disease (CVD) by improving dyslipidemia, oxidative stress, and inflammation. This study aimed to examine the effects of BC anthocyanin (ACN) extract supplementation on biomarkers of CVD risk in healthy adult women in menopause transition. The effects of BC ACN supplementation on body composition, fasting blood lipids and biomarkers of inflammation and oxidative stress were evaluated using anthropometric measures and blood samples collected from a pilot randomized controlled clinical trial in peri- and early postmenopausal women. Thirty-eight eligible peri- and early postmenopausal women aged 45-60 completed the entire trial, in which they were randomly assigned into one of three treatment groups: placebo (control group), 392 mg/day (low BC group), or 784 mg/day (high BC group) for six months. The significance of differences in outcomes was tested using repeated-measures ANOVA. Overall, following six-month BC consumption, significantly decreased triglyceride (TG) levels were observed between treatment groups (p < 0.05) in a dose-dependent manner. Plasma interleukin-1ß (IL-1ß) was significantly reduced in a dose and time dependent manner (p < 0.05). Significant decreases in thiobarbituric acid reactive substances (TBARS) levels were also observed between treatment groups (p < 0.05) in a dose-dependent manner. Six-month change in oxidized LDL was inversely correlated with changes in catalase (CAT) and total antioxidant capacity (TAC) (p < 0.05), while C-reactive protein (hs-CRP) change was positively correlated with changes in TG and IL-1ß (p < 0.01). Together, these findings suggest that daily BC consumption for six months effectively improved dyslipidemia, inflammation, and lipid peroxidation, thus potentially mitigating the risk of postmenopausal CVD development in study participants. Future studies with larger sample sizes and at-risk populations are warranted to confirm these findings.

Plasma Proteomics-Based Discovery of Mechanistic Biomarkers of Hyperbaric Stress and Pulmonary Oxygen Toxicity.

Our aim was to identify proteins that reflect an acute systemic response to prolonged hyperbaric stress and discover potential biomarker pathways for pulmonary O2 toxicity. The study was a double-blind, randomized, crossover design in trained male Navy diver subjects. Each subject completed two dry resting hyperbaric chamber dives separated by a minimum of one week. One dive exposed the subject to 6.5 h of 100% oxygen (O2) at 2ATA. The alternate dive exposed the subjects to an enhanced air nitrox mixture (EAN) containing 30.6% O2 at the same depth for the same duration. Venous blood samples collected before (PRE) and after (POST) each dive were prepared and submitted to LC-MS/MS analysis (2 h runs). A total of 346 total proteins were detected and analyzed. A total of 12 proteins were significantly increased at EANPOST (vs. EANPRE), including proteins in hemostasis and immune signaling and activation. Significantly increased proteins at O2PRE (vs. O2POST) included neural cell adhesion molecule 1, glycoprotein Ib, catalase, hemoglobin subunit beta, fibulin-like proteins, and complement proteins. EANPOST and O2POST differed in biomarkers related to coagulation, immune signaling and activation, and metabolism. Of particular interest is (EANPOST vs. O2POST), which is protective against oxidative stress.

Ultraviolet Photodissociation of Proteinogenic Amino Acids.

The ultraviolet photochemistry of the amino acids glycine, leucine, proline, and serine in their neutral forms was investigated using parahydrogen matrix-isolation spectroscopy. Irradiation by 213 nm light destroys the chirality of all three chiral amino acids as a result of the α-carbonyl C-C bond cleavage and hydrocarboxyl (HOCO) radical production. The temporal behavior of the Fourier-transform infrared spectra revealed that HOCO radicals rapidly reach a steady state, which occurs predominantly due to photodissociation of HOCO into CO + OH or CO2 + H. In glycine and leucine, the amine radicals generated by the α-carbonyl C-C bond cleavage rapidly undergo hydrogen elimination to yield methanimine and 3-methylbutane-1-imine, respectively. Breaking of the α-carbonyl C-C bond in proline appeared to yield 1-pyrroline, although due to its weak absorption it remains unconfirmed. In serine, additional products were formaldehyde and E/Z ethanimine. The present study shows that the direct production of HOCO previously observed in α-alanine generalizes to other amino acids of varying structure. It also revealed a tendency for amino acid photolysis to form imines rather than amine radicals. HOCO should be useful in the search for amino acids in interstellar space, particularly in combination with simple imine molecules.

Outcomes After Definitive Surgery for Nonagenarians with Isolated Hip Fractures within 24 hours of Admission.

BACKGROUND: Isolated hip fractures are a common orthopedic injury in the elderly population. Estimates are that there will be over 21 million hip fractures globally by 2050. Current recommendations are early operative fixation within 48 hours. Despite evidence showing that fixation of hip fractures within 24 hours is beneficial in the elderly population, the effect this has on the nonagenarian population has yet to be examined. METHODS: This is a single institution retrospective cohort study examining isolated hip fractures from 2014 to 2020 from an American College of Surgeons verified trauma center. Patients ≥65 years old with IHF were included. A total number of 1150 isolated hip fracture patients 65 years or older were included in this study. Three cohorts were examined: (1) patients ≥90 years old; (2) patients 65-89 years old; and (3) patients stratified by ≥90 vs 65-75 years old and ≥90 vs 75-89 years old. Patients were then sub stratified by timing of surgery whether it was performed ≤24 hours or >24 hours. The primary outcome was inpatient mortality. RESULTS: Nonagenarians who had delayed surgery had higher mortality rates compared to nonagenarians with early surgery (15.2% vs 4.2%; P = .02). Patients aged 65-75 had higher complication rates with delayed surgery (12.9% vs 4.1%; P = .01) as did those aged 76-89 (9.0% vs 3.2%, P = .004). DISCUSSION: Early surgical intervention of isolated hip fractures in the nonagenarian population within 24 hours is associated with good clinical outcomes as well as a lower inpatient mortality that approaches significance.

Blackcurrants Reduce the Risk of Postmenopausal Osteoporosis: A Pilot Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Beneficial effects of blackcurrant supplementation on bone metabolism in mice has recently been demonstrated, but no studies are available in humans. The current study aimed to examine the dose-dependent effects of blackcurrant in preventing bone loss and the underlying mechanisms of action in adult women. Forty peri- and early postmenopausal women were randomly assigned into one of three treatment groups for 6 months: (1) a placebo (control group, n = 13); (2) 392 mg/day of blackcurrant powder (low blackcurrant, BC, group, n = 16); and (3) 784 mg/day of blackcurrant powder (high BC group, n = 11). The significance of differences in outcome variables was tested by repeated-measures ANOVA with treatment and time as between- and within-subject factors, respectively. Overall, blackcurrant supplementation decreased the loss of whole-body bone mineral density (BMD) compared to the control group (p < 0.05), though the improvement of whole-body BMD remained significant only in the high BC group (p < 0.05). Blackcurrant supplementation also led to a significant increase in serum amino-terminal propeptide of type 1 procollagen (P1NP), a marker of bone formation (p < 0.05). These findings suggest that daily consumption of 784 mg of blackcurrant powder for six months mitigates the risk of postmenopausal bone loss, potentially through enhancing bone formation. Further studies of larger samples with various skeletal conditions are warranted to confirm these findings.

From Lateral Ankle Sprain to Above-Knee Amputation: A Unique Case Report of Group A Streptococcus Necrotizing Soft-tissue Infection.

INTRODUCTION: Necrotizing fasciitis, also referred to necrotizing soft-tissue infection (NSTI), is an infrequent entity that results in orthopedic consultation. It is a rapidly spreading typically associated with a contaminated wound that spreads rapidly along fascial planes resulting in significant morbidity and mortality. However, it is a rare occurrence that such pathology occurs in an atraumatic fashion, which is without a wound through the skin. CASE REPORT: A 33-year-old female with no significant medical history presented to a walk-in orthopedic clinic with increasing ankle pain after a lateral ankle sprain 2 days prior. Patient denies any fevers, chills, shortness of breath, numbness, tingling, paresthesia, or any additional trauma since the initial ankle sprain. The patient was afebrile, maintaining oxygenation, normotensive, but tachycardic to just over 100. Physical examination was only significant for moderate swelling and ecchymosis about the lateral malleolus. X-rays and venous ultrasound were negative for any associated pathology. After a period of observation, the patient acutely decompensated with a significant increase in pain in the lower leg on passive stretch, an increase in compartment firmness and a worsening tachycardia up to the 120's. The patient was taken emergently for fasciotomies for presumed compartment syndrome. The patient was hemodynamically unstable during the case and transferred to the intensive care unit where she continued to decompensate, requiring multiple vasopressors. The affected extremity became necrotic at the level of the foot and her hemodynamic instability continued, causing a return to the operating room for an emergent guillotine above-knee amputation. The patient progressively stabilized and underwent a formal above-knee amputation 2 days later. Cultures obtained during the second case were positive for Group A Streptococcus. CONCLUSION: This case highlights the variable presentation of NSTIs as well as has having a high index of suspicion to ensure this highly morbid and fatal disease process is diagnosed expeditiously. This case is also unique in that it developed without any obvious wounds and that monomicrobial Group A Streptococcus was the culprit, while most NSTIs are polymicrobial.

Acute progressive paraplegia in heroin-associated myelopathy.

As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component.