Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in ...social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.
Display omitted
•Fiber photometry enables recording of neural projection activity in behaving mice•VTA-NAc projection activity encodes and predicts social interaction•Optogenetic control of VTA DA neurons bidirectionally modulates social behavior•Elevating VTA-NAc activity and NAc D1R signaling increases social behavior
A new method called fiber photometry allows recording of the natural neuronal activity of neuronal projections in behaving mice. Such recordings in mice partaking in social interactions reveal that the dynamics of a neural projection between the ventral tegmental area (VTA) and nucleus accumbens (NAc) encode and predict key features of social behavior.
This study, designed to determine the relative degree of testosterone deficiency, estradiol deficiency, or both at which undesirable bodily changes occur, showed that some features of male ...hypogonadism are due to both androgen deficiency and estrogen deficiency.
Testosterone therapy is prescribed for millions of men each year, and the number is increasing rapidly. Prescription sales of testosterone increased by 500% in the United States between 1993 and 2000.
1
Most testosterone prescriptions are written to treat nonspecific symptoms, such as fatigue or sexual dysfunction, when accompanied by testosterone levels below the laboratory reference range. Currently, testosterone levels that are at least 2 SD below the mean value for healthy young adults are classified as low.
1
,
2
Although convenient, this classification fails to consider the physiological consequences of specific testosterone levels.
More than 80% of circulating estradiol in men . . .
There is increased appreciation that dopamine neurons in the midbrain respond not only to reward
and reward-predicting cues
, but also to other variables such as the distance to reward
, movements
...and behavioural choices
. An important question is how the responses to these diverse variables are organized across the population of dopamine neurons. Whether individual dopamine neurons multiplex several variables, or whether there are subsets of neurons that are specialized in encoding specific behavioural variables remains unclear. This fundamental question has been difficult to resolve because recordings from large populations of individual dopamine neurons have not been performed in a behavioural task with sufficient complexity to examine these diverse variables simultaneously. Here, to address this gap, we used two-photon calcium imaging through an implanted lens to record the activity of more than 300 dopamine neurons from the ventral tegmental area of the mouse midbrain during a complex decision-making task. As mice navigated in a virtual-reality environment, dopamine neurons encoded an array of sensory, motor and cognitive variables. These responses were functionally clustered, such that subpopulations of neurons transmitted information about a subset of behavioural variables, in addition to encoding reward. These functional clusters were spatially organized, with neighbouring neurons more likely to be part of the same cluster. Together with the topography between dopamine neurons and their projections, this specialization and anatomical organization may aid downstream circuits in correctly interpreting the wide range of signals transmitted by dopamine neurons.
Purpose
Conduct a systematic review to quantify the effect of primary sacroiliac joint fusion (SIJF) for the treatment of sacroiliac (SI) joint pathology on patient reported outcomes.
Methods
...Medline, Embase, Cochrane, PubMed, and Scopus databases were searched prior to August 18th, 2020 for all English-Language studies involving the treatment of SIJ pathology through SIJF and/or conservative management (CM). The quality of included studies was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Primary outcome measure was the Visual Analogue Scale (VAS) for low back pain. Secondary outcome measure was the Oswestry Disability Index (ODI) and the incidence of adverse reactions.
Results
A total of 564 patients and six studies were included. The overall quality of evidence analyzed by this review was low (GRADE = 0). Five out of the six studies were industry funded. The VAS standardized mean difference (SMD) between SIJF and CM at three months and six months follow-up was − 1.4 95% confidence interval − 2.3, − 0.6 and − 1.5 95% CI − 1.8, − 1.1. The ODI SMD between SIJF and CM scores at three months and 6 months follow-up was − 0.9 95% CI − 1.1, − 0.7 and − 1.1 95% CI − 1.6, − 0.5. The odds ratio of adverse reactions due to SIJF compared to CM was 1.9 95% CI 0.1, 42.8.
Conclusion
Based on the limited number of independent trials with long-term follow-up, SIJF shows potential as a surgical treatment option for SIJ pathology.
PROSPERO registration
CRD42020206149 (25th September 2020).
To analyze relations among injury, demographic, and environmental factors on function, health-related quality of life (HRQoL), and life satisfaction in individuals with traumatic spinal cord injury ...(SCI).
Prospective observational registry cohort study.
Specialized acute and rehabilitation SCI centers.
Participants (N=340) from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) who were prospectively recruited from 2004 to 2014 were included. The model cohort participants were 79.1% men, with a mean age of 41.6±17.3 years. Of the participants, 34.7% were motor/sensory complete (ASIA Impairment Scale AIS grade A).
None.
Path analysis was used to determine relations among SCI severity (AIS grade and anatomic level cervical/thoracolumbar), age at injury, education, number of health conditions, functional independence (FIM motor score), HRQoL (Medical Outcomes Study 36-Item Short-Form Health Survey Version 2 Physical Component Score PCS and Mental Component Score MCS), and life satisfaction (Life Satisfaction-11 LiSat-11). Model fit was assessed using recommended published indices.
Goodness of fit of the model was supported by all indices, indicating the model results closely matched the RHSCIR data. Higher age, higher severity injuries, cervical injuries, and more health conditions negatively affected FIM motor score, whereas employment had a positive effect. Higher age, less education, more severe injuries (AIS grades A–C), and more health conditions negatively correlated with PCS (worse physical health). More health conditions were negatively correlated with a lower MCS (worse mental health), however were positively associated with reduced function. Being married and having higher function positively affected Lisat-11, but more health conditions had a negative effect.
Complex interactions and enduring effects of health conditions after SCI have a negative effect on function, HRQoL, and life satisfaction. Modeling relations among these types of concepts will inform clinicians how to positively effect outcomes after SCI (eg, development of screening tools and protocols for managing individuals with traumatic SCI who have multiple health conditions).
Objective:
The aim was to formulate practice guidelines for management of osteoporosis in men.
Evidence:
We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system ...to describe the strength of recommendations and evidence quality.
Consensus Process:
Consensus was guided by systematic evidence reviews, one in-person meeting, and multiple conference calls and e-mails. Task Force drafts were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee; representatives of ASBMR, ECTS, ESE, ISCD; and members at large. At each stage, the Task Force received written comments and incorporated needed changes. The reviewed document was approved by The Endocrine Society Council before submission for peer review.
Conclusions:
Osteoporosis in men causes significant morbidity and mortality. We recommend testing higher risk men aged ≥70 and men aged 50–69 who have risk factors (e.g. low body weight, prior fracture as an adult, smoking, etc.) using central dual-energy x-ray absorptiometry. Laboratory testing should be done to detect contributing causes. Adequate calcium and vitamin D and weight-bearing exercise should be encouraged; smoking and excessive alcohol should be avoided. Pharmacological treatment is recommended for men aged 50 or older who have had spine or hip fractures, those with T-scores of −2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors. Treatment should be monitored with serial dual-energy x-ray absorptiometry testing.
Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus ...teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy.
This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of −2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301.
Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and −0·6% (−1·0 to −0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 13% of 218 in the romosozumab group vs 22 10% of 214 in the teriparatide group), hypercalcaemia (two <1% vs 22 10%), and arthralgia (22 10% vs 13 6%). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal.
Transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture.
Amgen, Astellas, and UCB Pharma.
Abstract Background With the increased use of patient-reported outcomes measures (PROMs) to assess spine surgery outcomes, it is important to understand how patients interpret their health changes ...over time. The measurement of cognitive-appraisal processes enables the quantification of how individuals think about quality of life (QOL). This study examined how appraisal processes were associated with patients’ views of their role in managing their health—patient activation. Methods This longitudinal cohort study from August 2019 to January 2022 included 222 adults undergoing spine surgery for cervical ( n = 107) and/or lumbar ( n = 148) pathology at an academic medical center. PROMs assessed disability (Neck Disability Index for cervical or Oswestry Disability Index for lumbar) and mental health (PROMIS-29 v2.0), cognitive-appraisal processes (QOLAP v2 -SF), and patient activation (Patient Activation Measure). ANOVA models were used to examine the relationships between QOL and cognitive appraisal processes before and after surgery, overall and stratified by patient-activation stage. Effect sizes facilitated interpretation. Results There were significant improvements in pain-related disability and mental health following surgery. Cognitive appraisal processes explained substantial amounts of variance, particularly with changes in mental health (45% before surgery, 75% at three months, and 63%, at 12-months after surgery). With respect to physical disability, less disability was associated with a lesser focus on negative aspects of QOL. Appraisal explained the most variance before surgery for high-activation patients. At 12-months post-surgery, however, appraisal explained the most variance for the low-activation patients. Appraisal explained similar amounts of variance in mental health at baseline and three-months post-surgery for all activation groups, but substantially more variance in the low-activation group at 12-months post-surgery. There were differences in the direction of appraisal-outcome associations by activation group in selected appraisal items/domains. Conclusions Cognitive-appraisal processes demonstrate a significant relationship with QOL among spine surgery patients. These processes explain substantial variance in pain-related disability and mental health, especially among those high in activation before surgery and those low in activation at 12-months post-surgery. Our findings suggest that patients’ ways of thinking about their health may be effective targets of motivational coaching, to help them become more engaged over the recovery trajectory.
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.
Patients and Intervention: We randomized 93 postmenopausal women with low bone mineral density (BMD) to alendronate 10 mg daily (group 1), teriparatide 40 μg sc daily (group 2), or both (group 3) for 30 months. Teriparatide was begun at month 6.
Main Outcome Measures: BMD of the lumbar spine, proximal femur, proximal radius, and total body was measured by dual-energy x-ray absorptiometry (DXA) every 6 months. Lumbar spine trabecular BMD was measured at baseline and month 30 by quantitative computed tomography. Serum osteocalcin, N-terminal propeptide of type 1 collagen, and N-telopeptide levels were assessed frequently. Women who had at least one repeat DXA scan on therapy were included in the analyses (n = 69).
Results: DXA spine BMD increased more in women treated with teriparatide alone than with alendronate alone (18 ± 11 vs. 7 ± 4%; P < 0.001) or both (18±11 vs. 12 ± 9%; P = 0.045). Similarly, femoral neck BMD increased more in women treated with teriparatide alone than with alendronate alone (11 ± 5 vs. 4 ± 4%; P < 0.001) or both (11 ± 5 vs. 3 ± 5%; P < 0.001). Quantitative computed tomography spine BMD increased 1 ± 7, 61 ± 31, and 24 ± 24% in groups 1, 2, and 3 (P < 0.001 for all comparisons). Serum osteocalcin, N-terminal propeptide of type 1 collagen, and cross-linked N-telopeptides of type I collagen increased more with teriparatide alone than with both (P < 0.001 for each marker).
Conclusion: Alendronate reduces the ability of teriparatide to increase BMD and bone turnover in women.
Administration of alendronate reduces the ability of a 2-year course of teriparatide to increase bone mineral density of the lumbar spine and proximal femur as measured by various tests in women with postmenopausal osteoporosis.
PDF
