An evening of alcohol consumption negatively impacts next-day immune fitness in both hangover-sensitive drinkers and hangover-resistant drinkers.

Background: Survey research found poorer baseline immune fitness for self-reported hangover-sensitive drinkers compared to hangover-resistant drinkers. However, up to now a limited number of clinical studies revealed mixed results regarding the relationship between the concentrations of biomarkers of systemic inflammation in blood or saliva with hangover severity, and could not differentiate between hangover-sensitive drinkers and hangover-resistant drinkers. The aim of this study was to assess immune fitness and saliva biomarkers of systemic inflammation at multiple timepoints following an alcohol day and alcohol-free control day.

Differences in Next-Day Adverse Effects and Impact on Mood of an Evening of Heavy Alcohol Consumption between Hangover-Sensitive Drinkers and Hangover-Resistant Drinkers.

The combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero, are collectively referred to as the alcohol hangover. Previous research revealed that 10 to 20% of drinkers claim not to experience next-day hangovers. Past studies were usually limited to single timepoint assessments.

Serum-Stable and Selective Backbone-N-Methylated Cyclic Peptides That Inhibit Prokaryotic Glycolytic Mutases.

-Methylated amino acids (-MeAAs) are privileged residues of naturally occurring peptides critical to bioactivity. However, discovery from ribosome display is limited by poor incorporation of -methylated amino acids into the nascent peptide chain attributed to a poor EF-Tu affinity for the -methyl-aminoacyl-tRNA. By reconfiguring the tRNA's T-stem region to compensate and tune the EF-Tu affinity, we conducted Random nonstandard Peptides Integrated Discovery (RaPID) display of a macrocyclic peptide (MCP) library containing six different -MeAAs.

Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies.

Backbone macrocyclic structures are often found in diverse bioactive peptides and contribute to greater conformational rigidity, peptidase resistance, and potential membrane permeability compared to their linear counterparts. Therefore, such peptide scaffolds are an attractive platform for drug-discovery endeavors. Recent advances in synthetic methods for backbone macrocyclic peptides have enabled the discovery of novel peptide drug candidates against diverse targets.

Antimullerian Hormone and Impending Menopause in Late Reproductive Age: The Study of Women's Health Across the Nation.

Background: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years.

Objective: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP.

Design: Prospective longitudinal cohort study.

Biomarkers of the alcohol hangover state: Ethyl glucuronide (EtG) and ethyl sulfate (EtS).

Introduction: The aim of this study was to investigate the usefulness of ethyl glucuronide (EtG) and ethyl sulfate (EtS) as biomarkers of the hangover state.

Methods: Thirty-sixhealthy social drinkers participated in this study, being of naturalistic design. Eighteen participants experience regular hangovers (the hangover group), whereas the other 18 claim to not experience a hangover (the hangover-immune group).

Urine methanol concentration and alcohol hangover severity.

Background: Congeners are substances, other than ethanol, that are produced during fermentation. Previous research found that the consumption of congener-rich drinks contributes to the severity of alcohol hangover. Methanol is such a congener that has been related to alcohol hangover.

Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study).

Context: In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy.

Objective: The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength.

Design: This was an open-label, randomized controlled trial.

Response to Therapy With Teriparatide, Denosumab, or Both in Postmenopausal Women in the DATA (Denosumab and Teriparatide Administration) Study Randomized Controlled Trial.

Both antiresorptive and anabolic osteoporosis medications increase bone mineral density (BMD), but no single agent can restore normal bone strength in most osteoporotic patients. Moreover, the magnitude and consistency of the patient response to each individual agent vary depending on the anatomic site. In the DATA study, we reported that in postmenopausal osteoporotic women, 2 years of combined denosumab and teriparatide increase mean BMD at the hip and spine more than either drug alone.

Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.

Background: Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies.

Comparative Resistance to Teriparatide-Induced Bone Resorption With Denosumab or Alendronate.

Context: In postmenopausal osteoporotic women, denosumab fully inhibits teriparatide-induced bone resorption at approved doses. This property of denosumab is distinct from that of alendronate and likely contributes to the efficacy of combination denosumab and teriparatide therapy. Whether denosumab fully inhibits bone resorption when challenged by a higher dose of teriparatide is unknown.

Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT Study.

Combined teriparatide and denosumab increases spine and hip bone mineral density more than either drug alone. The effect of this combination on skeletal microstructure and microarchitecture, however, is unknown. Because skeletal microstructure and microarchitecture are important components of skeletal integrity, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) assessments at the distal tibia and radius in postmenopausal osteoporotic women randomized to receive teriparatide 20 µg daily (n = 31), denosumab 60 mg every 6 months (n = 33), or both (n = 30) for 12 months.

Two years of Denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial.

Context: Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone.

Bone loss after bariatric surgery: discordant results between DXA and QCT bone density.

Several studies, using dual-energy X-ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts.

Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial.

Background: Osteoporosis medications increase bone-mineral density (BMD) and lower but do not eliminate fracture risk. The combining of anabolic agents with bisphosphonates has not improved efficacy. We compared combined teriparatide and denosumab with both agents alone.

Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity.

Objective: Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity.

Methods: Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women.

Results: Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.

Differences in skeletal microarchitecture and strength in African-American and white women.

African-American women have a lower risk of fracture than white women, and this difference is only partially explained by differences in dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD). Little is known about racial differences in skeletal microarchitecture and the consequences for bone strength. To evaluate potential factors underlying this racial difference in fracture rates, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess cortical and trabecular bone microarchitecture and estimate bone strength using micro-finite element analysis (µFEA) in African-American (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation (SWAN).

Bone resorption and fracture across the menopausal transition: the Study of Women's Health Across the Nation.

Objective: Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women.

Methods: Women attended up to nine clinic visits for an average of 7.

Benefits and risks of bisphosphonate therapy for osteoporosis.

Context: There has been considerable concern recently in the scientific and lay media regarding the benefits vs. the risks of bisphosphonates for the treatment of osteoporosis. Risks include possible associations with osteonecrosis of the jaw (ONJ) and atypical femur fractures.

First-in-human testing of a wirelessly controlled drug delivery microchip.

The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment.

Time-dependent changes in skeletal response to teriparatide: escalating vs. constant dose teriparatide (PTH 1-34) in osteoporotic women.

Once-daily injections of teriparatide initially increase biochemical markers of bone formation and resorption, but markers peak after 6-12 months and then decline despite continued treatment. We sought to determine whether increasing teriparatide doses in a stepwise fashion could prolong skeletal responsiveness. We randomized 52 postmenopausal women with low spine and/or hip bone mineral density (BMD) to either a constant or an escalating subcutaneous teriparatide dose (30 μg daily for 18months or 20 μg daily for 6 months, then 30 μg daily for 6 months, and then 40 μg daily for 6 months).

Bone loss across the menopausal transition.

The Study of Women's Health Across the Nation (SWAN) is an NIH-funded, multidisciplinary, longitudinal observational study of middle-aged U.S. women of multiple ethnicities in or near Boston, Newark, Pittsburgh, Detroit, Chicago, Oakland, and Los Angeles.

Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis.

Context: Teriparatide increases both bone formation and bone resorption.

Objective: We sought to determine whether combining teriparatide with an antiresorptive agent would alter its anabolic action.

Design And Setting: This was a randomized controlled trial conducted in a single university hospital.

Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis.

Context: In postmenopausal women, bone mineral density (BMD) declines after teriparatide therapy is stopped. The pattern of BMD loss after teriparatide therapy is stopped in men is less clear.

Objective: The aim of the study was to determine whether the pattern of teriparatide-induced bone accrual and post-teriparatide bone loss differs between postmenopausal women and eugonadal men.