APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Risk of radial head arthroplasty revision is correlated with radial head diameter: a multicenter analysis of 405 cases.

BACKGROUND: Radial head arthroplasty (RHA) is commonly used for the treatment of comminuted radial head fractures. Indications as well as implant types continue to evolve. RHA has had good outcomes with midterm longevity. The literature is limited to small case series with varying implant types, and larger studies are needed to determine the optimal implant type and radial head diameter. METHODS: A retrospective analysis of RHA cases performed by 75 surgeons at 14 medical centers in an integrated health care system between 2006 and 2017 was completed. Patient demographics, comorbidities, implant type and head diameter, and indications for revision were recorded. Patients' in-person clinical visit data were recorded. Patients were also contacted via telephone at a minimum of 2 years to obtain abbreviated Disabilities of the Arm, Shoulder, and Hand questionnaire and Oxford scores. Implant survivorship was also captured within our integrated system. RESULTS: 405 cases met our inclusion criteria. Mean age was 51.5 ± 15.5 years (range 16-88 years) and more common in females (62%). Chart review and telephone follow-up was performed at a mean of 68.9 ± 31.5 months (range 24-146 months). Our study found that revision rate was positively correlated with increasing radial head diameter. A 26-mm head had 7.7 odds of revision compared to a size 18-mm head (95% confidence interval 1.2-150.1). More than 95% of revision cases were performed within the first 36 months of the index procedure. Obese patients had a significantly lower mean postoperative Oxford score (35.5) compared to controls (38.3) (P = .02). There was a significantly higher overall reoperation rate for terrible triad (18.4%) vs. isolated injuries (10.4%) (P = .04). There was no difference between Acumed Anatomic and Evolve radial head implants in overall reoperation, implant revision, postoperative range of motion, or patient-reported outcomes. CONCLUSIONS: Risk of revision is directly correlated with implanted radial head diameter. There were no differences in outcomes and complications between the 2 main implants used. Individuals who did not undergo a revision by 3 years' time tend to retain the implant. Terrible triad injuries had a higher all-cause reoperation rate than isolated radial head fractures, but no difference in the rate of RHA revision. These data reinforce the practice of downsizing radial head implant diameter.

Predictive Factors of Hospital-Acquired Bacterial Infections in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: We aimed to identify the predictive factors of hospital-acquired bacterial infections in patients with systemic lupus erythematosus (SLE). METHODS: This chart review study included patients with SLE who were hospitalized between 2009 and 2020 for reasons other than infection. The outcome was defined as any infection confirmed using any bacterial isolation method or diagnosed by treating physicians and required treatment with intravenous antibiotics. For statistical analysis, logistic regression analyses were performed. RESULTS: In total, 1678 patients (87.6% women) were included. The median age was 33 years (interquartile range, 24-47 years). The incidence of hospital-acquired infections was 13.9% (233 infections). Age, Systemic Lupus Erythematosus Disease Activity Index score, Systemic Lupus International Collaborating Clinics damage score, blood urea nitrogen and C-reactive protein levels, dosage of steroid in the previous month, recent use of 1 or more immunosuppressants, admission with a central venous catheter (or dialysis catheter), and use of central venous catheter or bladder catheter in the first 5 days were the predictive factors of nosocomial infections. CONCLUSION: The patients' infection risk profile should be assessed to accurately determine the risk-benefit balance of any therapeutic intervention, minimize exposure to steroids and immunosuppressants, and maintain a low threshold for the early diagnosis of infections. Further studies should assess whether the modification of some identified factors could reduce the incidence of nosocomial infections.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer's Disease.

OBJECTIVE: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance. METHODS: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. RESULTS: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. CONCLUSIONS: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

Efficacy of high-intensity interval- or continuous aerobic-training on insulin resistance and muscle function in adults with metabolic syndrome: a clinical trial.

PURPOSE: We carried out a randomized, clinical trial in adults of both sexes with metabolic syndrome (MS) to assess the efficacy of high-intensity, low-volume interval training (HIIT) compared to moderate-intensity continuous training (MICT) on insulin resistance (IR), muscle mass, muscle activation, and serum musclin. METHODS: Fasting glycemia, insulinemia, and glycated haemoglobin were determined by conventional methods, IR by Homeostatic model assessment (HOMA), lean mass by Dual-Energy X-ray Absorptiometry, muscle activation through carnosine by Proton Magnetic Resonance Spectroscopy, and musclin by Enzyme-Linked ImmunoSorbent Assay before and after a supervised, three-times/week, 12-week treadmill programme. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). MICT (n = 31) trained at 60% of VO2peak for 30 min. RESULTS: Patients had a mean age of 50.8 ± 6.0 years, body mass index of 30.6 ± 4.0 kg/m2, and VO2peak of 29.0 ± 6.3 mL.kg-1.min-1. Compared to MICT, HIIT was not superior at reducing Ln HOMA-IR (adjusted mean difference: 0.083 [95%CI - 0.092 to 0.257]), carnosine or musclin or at increasing thigh lean mass. HIIT increased carnosine by 0.66 mmol/kg.ww (95% CI 0.08-1.24) after intervention. Both interventions reduced IR, body fat percentage and increased total lean mass/height2 and VO2peak. Musclin showed a non-significant reduction with a small effect size after both interventions. CONCLUSION: Compared to MICT, HIIT is not superior at reducing IR, carnosine or musclin or at increasing skeletal muscle mass in adults with MS. Both training types improved IR, muscle mass and body composition. NCT03087721, March 22nd, 2017. TRIAL REGISTRATION NUMBER: NCT03087721. Registered March 22nd, 2017.

Prevalence, Incidence, and Clinical-Epidemiological Characterization of Amyotrophic Lateral Sclerosis in Antioquia: Colombia.

INTRODUCTION: The prevalence and incidence of amyotrophic lateral sclerosis (ALS) is not fully established, and this varies depending on the studied population. OBJECTIVE: To estimate the prevalence/incidence of ALS patients in Antioquia-Colombia. METHODOLOGY: Observational/descriptive study by reviewing clinical records from 2010 to 2014. Cases with possible, probable and definite ALS were included. To estimate the prevalence/incidence, capture-recapture method was used. RESULTS: Point prevalence in December 2014 was 4.9/100,000 (95% CI 2.0-7.8), and the incidence was 1.4/100,000/year (95% CI 0.5-2.2). The median survival was 4 years. Spinal-onset was observed in 62.4% of the included patients. CONCLUSION: Prevalence, incidence and clinical presentation of ALS in Antioquia are similar to most studies reported worldwide. However, prevalence in Antioquia seems to be slightly higher than in other studies from Latin -American countries. This may derive from the inclusion criteria and case detection methodology adopted, but sociodemographic and genetic factors should be considered.

Complications of Elbow Arthroscopy in a Community-Based Practice.

PURPOSE: The purpose of this study was to report the complications of elbow arthroscopy in a large community practice with multiple surgeons and to analyze potential risk factors for these complications. METHODS: Patient demographic information, surgical variables, surgeon variables, and complications were retrospectively reviewed for all elbow arthroscopies performed within the health network from 2006 to 2014. Inclusion criteria included patients of any age undergoing a primary and revision elbow arthroscopy, which may have been performed in conjunction with other procedures. Exclusion criteria included incorrectly coded procedures where arthroscopy was not performed and no postoperative follow-up. Statistical calculations were performed using a binary logistic regression analysis to fit a logistic regression model. RESULTS: 560 consecutive elbow arthroscopies in 528 patients performed between 2006 and 2014, by 42 surgeons at 14 facilities, were reviewed. 113 procedures were performed in pediatric patients under the age of 18. The average age was 38.6 years (range: 5-88). There were 444 males. The average length of follow-up was 375.8 days (2 to 2,739 days). Overall, heterotopic ossification occurred in 14 of 560 cases (2.5%) (all males), and 20 of 560 (3.5%) cases developed transient nerve palsies (8 ulnar, 8 radial, 1 median, 3 medial antebrachial cutaneous). There were 3 (0.5%) deep and 11 (2%) superficial infections. There were no vascular injuries, compartment syndrome, deep vein thrombosis, or pulmonary embolism. Elevated blood sugar was a significantly higher risk for infection (odds ratio [OR] 4.11, 95% confidence interval [CI] 1.337 to 12.645; P = .0136). Previous elbow surgery (OR 3.57, 95% CI 1.440 to 8.938; P = .006) and female sex (OR 4.05; 95% CI 1.642 to 9.970; P = .002) had a significantly higher risk for nerve injury. Relative to pediatric patients, there were higher odds in adults for nerve injury, infection, and heterotopic ossification, but none reached significance. CONCLUSIONS: Elbow arthroscopy is a safe procedure with low complication rates. Diabetes is a risk factor for infection. Prior surgery and female sex are risk factors for nerve injury. LEVEL OF EVIDENCE: Case series, level 4.

Functional outcomes of ulnar collateral ligament reconstruction with a novel double suspensory fixation.

BACKGROUND: Ulnar collateral ligament reconstruction (UCLR) has allowed the return of overhead athletes to throwing sports. We describe a new double suspensory (DS) technique using a single tunnel in the ulna and humerus, achieving fixation with adjustable loop buttons. METHODS: Inclusion criteria included skeletally mature baseball players with clinical and magnetic resonance imaging diagnosis of UCL insufficiency who failed a trial of structured nonoperative treatment. A total of 36 baseball players underwent DS UCLR, between 2011 and 2017, by 1 surgeon with minimum 2-year follow-up. The graft was fixated with an adjustable button loop on the humeral side and a tension slide technique with a button on the ulnar side. Pre- and postoperative Kerlan-Jobe Orthopaedic Clinic and Single Assessment Numerical Evaluation and postoperative Conway scores were obtained. RESULTS: The mean age was 19.8 ± 4.6 years (range, 14-35 years). All were male. Mean years played before surgery was 14.3 ± 4.6 years (range, 8-28 years). There were 32 (89%) pitchers and 4 (11%) position players. There were 13 (36%) high school, 20 (55%) college, 2 (6%) minor league, and 1 (3%) adult league athletes. The mean follow-up was 55.3 ± 23.7 months (range, 26-97 months). There was significant improvement in Kerlan-Jobe Orthopaedic Clinic (33.2 ± 19.9 to 89.7 ± 15.1, P < .0001) and Single Assessment Numerical Evaluation (20.7 ± 16.7 to 93.6 ± 11.9, P < .0001) scores. Using Conway scoring, 25 (69%) had excellent, 5 (14%) good, 3 (8%) fair, and 3 (8%) poor scores. Mean return to play was 9 ± 1.5 months (range, 6-16 months). Only 1 (3%) athlete required a revision surgery and ultimately returned to play and 1 (3%) hardware removal. None developed ulnar nerve symptoms. CONCLUSION: DS fixation for UCLR in baseball players can lead to excellent clinical results and early return to play.

Is there a difference in the acromiohumeral distances measured on radiographic and magnetic resonance images of the same shoulder with a massive rotator cuff tear?

BACKGROUND: The purpose of our study was to compare the acromiohumeral distance (AHD) between radiographic and magnetic resonance images (MRIs) of the same shoulder with massive rotator cuff tears (MRCTs). METHODS: Thirty-four shoulders with MRCTs that had an MRI and radiograph of the same shoulder within an average of 40.3 days (range: 8-109 days) were identified. AHD was measured digitally on radiograph and MRI by 3 examiners. Shoulders were grouped into Hamada grades <3 (group 1) and Hamada grades ≥3 (group 2). RESULTS: The mean age was 66.4 years (range: 51-89). There were 19 men (59%). The Kappa for inter-rater reliability was 0.982 (95% confidence interval [CI] 0.975, 0.988) for radiographs and 0.88 (95% CI 0.75, 0.94) for MRI. There was a significant difference in the mean AHD of group 1 on radiograph vs. MRI (7.9 mm vs. 2.5 mm, respectively; P < .0001), but no difference in group 2 (1.8 mm vs. 2.2 mm, respectively; P = .45). There was no difference in AHD in group 1 between shoulders with Goutallier stage <3 (8.1 ± 1.9 mm) and those with Goutallier stage ≥3 (7.3 ± 2.1 mm) (P = .3479). There was no difference in AHD in group 2 between shoulders with Goutallier stage <3 (3.0 ± 0.1 mm) and those with Goutallier stage ≥3 (1.5 ± 1.0 mm) (P = .079). CONCLUSION: There is a significant difference in AHD measurements between radiograph and MRI of the same shoulder with MRCT in early Hamada grades. AHDs measured on radiograph and MRI should not be used interchangeably in early Hamada grades to assess outcomes of superior capsule reconstruction and similar procedures.

Genetic origin of a large family with a novel PSEN1 mutation (Ile416Thr).

INTRODUCTION: A small percentage of Alzheimer's disease (AD) cases are caused by genetic mutations with autosomal dominant inheritance. We report a family with a novel variant in PSEN1. METHODS: We performed clinical and genetic evaluation of 93 related individuals from a Colombian admixed population. 31 individuals had whole-genome sequencing. RESULTS: Genetic analysis revealed a missense variant in PSEN1 (NM_000021.3: c.1247T>C p.Ile416Thr), which originated on an African haplotype and segregated with AD logarithm of the odds score of 6. Their clinical phenotype is similar to sporadic AD except for earlier age at onset: the mean age at onset for mild cognitive impairment was 47.6 years (standard deviation 5.83) and for dementia 51.6 years (standard deviation 5.03). DISCUSSION: Ile416Thr is a novel pathogenic variant that causes AD in the sixth decade of life. The history of the region that included slave importation and admixtures within a confined geographic locale represents a "mini-population bottleneck" and subsequent emergence of a rare dominant mutation.

Incidence of dementia in elderly Latin Americans: Results of the Maracaibo Aging Study.

INTRODUCTION: There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans. METHODS: The Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) was used to diagnose dementia, which was classified as Alzheimer's disease, vascular dementia, or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years (p-y) of follow-up. RESULTS: The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% confidence interval [CI] 7.13-11.44; 8026 total p-y), 5.18 for Alzheimer's disease (95% CI 3.72-7.03; 7916 total p-y), and 3.35 for vascular dementia (95% CI 2.19-4.91; 7757 total p-y). DISCUSSION: Among Maracaibo Aging Study participants younger than 65 years, the incidence of dementia was higher than that of US Whites. Among individuals older than 65 years, the incidence was comparable to the mean of previous incidence estimates for other populations worldwide.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Reverse total shoulder arthroplasty for the treatment of proximal humeral fractures: patterns of use among newly trained orthopedic surgeons.

BACKGROUND: This study compared the use of reverse and hemishoulder arthroplasty for the treatment of proximal humeral fractures among orthopedic surgeons taking part II of the American Board of Orthopaedic Surgery board examination. We hypothesized that the use of reverse shoulder arthroplasty for fractures in the elderly is increasing amongst newly trained orthopedic surgeons. MATERIALS AND METHODS: We queried the American Board of Orthopaedic Surgery database for the cases of proximal humeral fractures treated with arthroplasty submitted between 2005 and 2012. We evaluated the prosthesis used, patient-specific factors, complications, and the difference in use by shoulder fellowship-trained surgeons. RESULTS: From 2005 to 2012, 5395 board-eligible orthopedic surgeons submitted cases to the database. Of these, 435 (mean, 54 per year) were proximal humeral fractures treated with arthroplasty. The overall incidence of reverse shoulder arthroplasty for fracture increased from 2% to 4% during 2005 to 2007 to 38% in 2012. Shoulder surgeons treated 5 times more proximal humeral fractures with shoulder arthroplasty and were also more than 20 times more likely to use a reverse implant (P < .0001). The difference in complication rates between reverse and hemishoulder arthroplasty was not significant (P = .49). Patients who received a hemiarthroplasty tended to be younger (mean age, 70.8 vs 75.7 years; P = .0015). CONCLUSIONS: Overall, the use of a hemiarthroplasty for fracture is still more common (62% in 2012), although the relative proportion of reverse implants is rising. Among shoulder surgeons, more than 50% of the arthroplasties performed for fractures during the past 3 years (2010-2012) have been reverse arthroplasties.

Reverse shoulder arthroplasty for proximal humeral fractures: update on indications, technique, and results.

The introduction of the reverse shoulder arthroplasty has provided shoulder surgeons with more options for the treatment of complex proximal humeral fractures in the elderly. Early reported results suggest that the average functional outcome may be better than hemiarthroplasty in certain patients and specific clinical scenarios. In addition, these results seem to be reached more quickly with less dependence on rehabilitation. The reverse prosthesis may be particularly useful in patients aged older than 70 years, especially those with severely comminuted fractures in osteopenic bone. These factors likely have a negative impact on the results of hemiarthroplasty and internal fixation. Despite the potential benefits of reverse arthroplasty for fracture, there is a significant learning curve with the use of this prosthesis, and it has its own set of complications. The surgeon must show appropriate judgment when selecting a reverse arthroplasty in the setting of a proximal humeral fracture and, furthermore, be well acquainted with the surgical technique and prosthetic options at the time of surgery. Although the longevity of this prosthesis remains unknown, midterm outcomes are promising.

An 1H-MRS framework predicts the onset of Alzheimer's disease symptoms in PSEN1 mutation carriers.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia; the main risk factors are age and several recently identified genes. A major challenge for AD research is the early detection of subjects at risk. The aim of this study is to develop a predictive model using proton magnetic resonance spectroscopy (1H-MRS), a noninvasive technique that evaluates brain chemistry in vivo, for monitoring the clinical outcome of carriers of a fully penetrant mutation that causes AD. METHODS: We studied 75 subjects from the largest multigenerational pedigree in the world (∼5000 people) that segregates a unique form of early-onset Alzheimer's disease (EOAD) caused by a fully penetrant mutation in the Presenilin-1 gene (PSEN1 p.Glu280Ala [E280 A]). Forty-four subjects were carriers of the mutation, and 31 were noncarriers. Seventeen carriers had either mild cognitive impairment (MCI) or early-stage AD (collectively MCI-AD). In right and left parietal white mater and parasagittal parietal gray matter (RPPGM and LPPGM) of the posterior cingulate gyrus and precuneus, we measured levels of the brain metabolites N-acetylaspartate (NAA), inositol (Ins), choline (Cho), and glutamate-glutamine complex (Glx) relative to creatine (Cr) levels (NAA/Cr, Ins/Cr, Cho/Cr, and Glx/Cr, respectively) with two-dimensional 1H-MRS. Using advanced recursive partition analysis and random forest analysis, we built classificatory decision trees for both mutation carrier status and the presence of MCI-AD symptoms, fitting them to 1H-MRS data while controlling for age, educational level, and sex. RESULTS: We found that (1) the combination of LPPGM Cho/Cr<0.165 and RPPGM Glx/Cr>1.54 fully excluded carriers; (2) LPPGM Cho/Cr>0.165, RPPGM Glx/Cr<1.54, and left parietal white mater NAA/Cr>1.16 identified asymptomatic carriers with sensitivity of 97.7% and specificity of 77.4%; and (3) RPPGM NAA/Cr>1.05 defined asymptomatic subjects (independent of carrier status) with sensitivity of 100% and a specificity of 96.6%. CONCLUSIONS: Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Colombian Adaptation of the Self-Compassion Scale (SCS).

BACKGROUND: Self-Compassion is crucial for assessing how people relate to their suffering in moments of personal difficulty. The objective of this study was to check the psychometric properties of the Self-Compassion Scale (SCS) in a Colombian sample. METHOD: The Spanish version of the SCS was adapted to the Colombian context via a content validity technique. This version was administered to 751 Colombians from the general community. Psychometric analysis was performed using R studio packages. RESULTS: 7 models were tested, the best fit was found for the bifactor ESEM model (χ2/df = 0.86, CFI = 1, TLI= 1, RMSEA= 0.00, SRMR= 0.01). This model produced optimal reliability indices (ωh = 0.83, FD= 0.93, H= 0.96). CONCLUSIONS: The study produced initial psychometric evidence of the structure of the SCS in Colombia, with evidence of a general factor in the bifactor ESEM model. More research is needed to justify the complete usage of the SCS in the country.

Classification system of graft tears following superior capsule reconstruction.

OBJECTIVE: Superior capsule reconstruction (SCR) is a treatment option for irreparable massive rotator cuff tears (MRCT). The purpose of this study is to describe a classification system for graft integrity and tear location. METHODS: Patients who underwent SCR at a single institution were included. Pre-operative age, gender, prior surgery, Hamada grade, and Goutallier stage were recorded. An MRI was performed postoperatively to assess graft integrity and tear location. RESULTS: 53 patients met inclusion criteria. Mean age was 60.1 ± 7.9 years. A post-operative MRI was performed in 42 (80%) patients at a mean of 14 ± 7 months (range, 6-40 months). MRIs demonstrated an intact graft in 16 (38%) shoulders. Of the 26 graft tears, 14 (54%) were from the glenoid, 5 (19%) mid-substance, 6 (23%) from the tuberosity, and 1 (3.8%) had complete graft absence. CONCLUSION: Graft tears are common following SCR. We describe four different graft tear locations and submit a classification system that can be used in future studies to better compare outcomes based on graft integrity and tear location. Clinical correlation with graft integrity and graft tear location needs to be further investigated.

Safety of High-Intensity, Low-Volume Interval Training or Continuous Aerobic Training in Adults With Metabolic Syndrome.

OBJECTIVE: The aim of the study was to evaluate the safety of high-intensity, low-volume interval training (HIIT-low volume) compared with moderate-intensity continuous aerobic training (MICT) in adults with metabolic syndrome. METHODS: This is a controlled, randomized, clinical trial in patients without history of ischemic heart disease or diabetes, who underwent a supervised, 3 sessions/week, 12-week treadmill exercise program. The HIIT-low volume (n = 29) sessions consisted of 6 intervals with 1-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). The MICT (n = 31) trained at 60% of VO2peak for 30 minutes. A new approach to record and classify all clinical events according to possible causality based on Naranjo's algorithm was developed. RESULTS: Patients were 50.8 ± 6.0 years old, 70% women, with body mass index of 30.6 ± 4.0 kg/m2 and VO2peak of 29.0 ± 6.3 mL·kg-1·min-1. In total, 60 clinical events were recorded in the HIIT-low volume group and 48 in the MICT group, with 59.3% classified as general disease. Only 21 events were classified as adverse reactions possibly related to exercise, without any serious adverse reactions. Both interventions had a similar incidence of musculoskeletal events (incidence rate ratio, 1.1; 95% confidence interval, 0.6-1.8), but HIIT-low volume had a higher incidence of cardiovascular events (incidence rate ratio, 2.9; 95% CI, 0.4-22.8) after adjusting for age, sex, and body mass index (HIIT-low volume: chest pain [n = 1] and symptoms of venous insufficiency of lower limbs [n = 2]; MICT: chest pain [n = 1]). CONCLUSIONS: The HIIT-low volume and MICT are safe in patients with metabolic syndrome. We recommend a muscle-conditioning program prior to both and to avoid HIIT-low volume in treadmill in patients with venous insufficiency of the lower limbs.Trial registration number NCT03087721.

Substance Use-Related Cognitive Decline in Families with Autosomal Dominant Alzheimer's Disease: A Cohort Study.

BACKGROUND: Cigarette smoking is a known risk factor for Alzheimer's disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. OBJECTIVE: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. METHODS: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. RESULTS: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. CONCLUSION: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.