Morphological Hallmarks of Classical Fabry Disease: An Ultrastructural Study in a Large Spanish Family.

Fabry disease (FD) is a rare lysosomal disorder caused by α-galactosidase A deficiency, and it leads to the systemic deposition of globotriasylceramide. Demonstrations of the storage material in biopsies support this diagnosis. We report a histological and ultrastructural study of biopsies that were performed on 11 individuals from a family with the variant p.Gln279Arg in GLA, which is associated with the classical phenotype of Fabry disease. Intralysosomal deposits were found in all biopsies, corresponding to the skin, kidney, and endomyocardium in both sexes and at different ages. In nine of the skin biopsies, deposits were analysed by immunofluorescence and quantified at the ultrastructural level. Then, the findings were compared according to sex, genotype, and treatment. The quantification of the deposits in the skin biopsies revealed a broader involvement in men than in women. A significant clearance of the deposits was observed in one case after treatment. Tissue involvement was remarkable at diagnosis in all individuals. The findings from the skin biopsies were demonstrative of classic FD, thus supporting the diagnosis; repeated biopsy analyses suggested the benefit of early treatment.

Reverse total shoulder arthroplasty for complex proximal humerus fracture in the elderly: clinical and radiological results.

Background: The use of reverse total shoulder arthroplasty (RSA) for the treatment of proximal humeral fractures (PHFs) is steadily increasing. Better clinical outcomes of RSA have been correlated with tuberosity reattachment and healing. The purpose of this study was to evaluate both the clinical and radiological results of reverse shoulder arthroplasty in the management of a proximal humerus fracture in the elderly. Methods: Retrospective study including 400 consecutive 3-4 part proximal humerus fractures treated with reverse shoulder arthroplasty with a minimum of 12-month follow-up. In all the cases, the greater tuberosity was reattached with a standardized suture technique and a local bone graft. All the patients were assessed at the 12-month follow-up with Constant-Murley Score (CMS). Radiographic healing of the greater tuberosity was noted. Complications and revision rates were reported. Results: Mean final CMS for this cohort was 82 points. The greater tuberosity healed in anatomic position in 85% of the cases (N = 340), obtaining an average CMS of 85 in these patients. Healing of the greater tuberosity did not occur in 13% of the cases (N = 52) and displacement more than 5 mm occurred in 2% (N = 8) of the patients for an average CMS of 60. All patients scored above 120° in forward elevation with a mean of 150°. Mean active external rotation was 35°. The lateralization shoulder angle had a mean of 91° and the distalization shoulder angle had a mean of 54°. Low-grade scapular notching was reported in <1% of the cases. A total of 60 patients presented failure of healing or displacement of the greater tuberosity. Major complications were reported in nine patients. Of these nine patients, two acquired superficial wound infections, while two had deep shoulder prosthetic infection. Two other patients developed hematomas, one sustained an acromial stress fracture, and two had a stem loosening. There were 4 reoperations. Conclusion: Reverse shoulder arthroplasty, with the use of a fracture-specific stem, allows an improved rate of greater tuberosity healing and short-term clinical outcomes in the elderly population.

Screening for late-onset Pompe disease in Internal Medicine departments in Spain.

BACKGROUND: The screening of high-risk populations using dried blood spots (DBS) has allowed the rapid identification of patients with Pompe disease, mostly in Neurology departments. The aim of the study was to determine the prevalence of late-onset Pompe disease (LOPD) among patients not previously diagnosed or tested for this entity despite presenting possible signs or symptoms of the disease in Internal Medicine departments in Spain. METHODS: This epidemiological, observational, cross-sectional, multicenter study included a single cohort of individuals with clinical suspicion of LOPD seen at Internal Medicine departments in Spain. The diagnosis of LOPD was initially established on the basis of the result of DBS. If decreased enzyme acid-alpha-1,4-glucosidase (GAA) activity was detected in DBS, additional confirmatory diagnostic measurements were conducted, including GAA activity in lymphocytes, fibroblasts, or muscle and/or genetic testing. RESULTS: The diagnosis of LOPD was confirmed in 2 out of 322 patients (0.6%). Reasons for suspecting LOPD diagnosis were polymyositis or any type of myopathy of unknown etiology (in one patient), and asymptomatic or pauci-symptomatic hyperCKemia (in the other). The time between symptom onset and LOPD diagnosis was 2.0 and 0.0 years. Both patients were asymptomatic, with no muscle weakness. Additionally, 19.7% of the non-LOPD cases received an alternative diagnosis. CONCLUSIONS: Our study highlights the existence of a hidden population of LOPD patients in Internal Medicine departments who might benefit from early diagnosis and early initiation of potential treatments.

Risk for recurrence of symptomatic upper-extremity deep vein thrombosis in patients without cancer: Analysis of three RIETE cohorts.

BACKGROUND: The natural history of patients with a pacemaker-related upper-extremity deep vein thrombosis (UEDVT) has not been consistently studied. METHODS: We used the RIETE registry data to compare the outcomes during anticoagulation and after its discontinuation in noncancer patients with symptomatic UEDVT associated with a pacemaker, other catheters, or no catheter. The major outcome was the composite of symptomatic pulmonary embolism or recurrent DVT. RESULTS: As of February 2022, 2578 patients with UEDVT were included: 156 had a pacemaker-related UEDVT, 557 had other catheters, and 1865 had no catheter. During anticoagulation, 61 patients (2.3%) developed recurrent VTE, 38 had major bleeding (1.4%), and 90 died (3.4%). After its discontinuation, 52 patients (4.4%) had recurrent acute venous thromboembolism (VTE) and six had major bleeding (0.5%). On multivariable analysis, there were no differences among subgroups in the rates of VTE recurrences or major bleeding during anticoagulation. After its discontinuation, patients with a pacemaker-related UEDVT had a higher risk for VTE recurrences than those with no catheter (adjusted OR: 4.59; 95% CI: 1.98-10.6). CONCLUSIONS: Patients with pacemaker-related UEDVT are at increased risk for VTE recurrences after discontinuing anticoagulation. If our findings are validated in adequately designed trials, this may justify changes in the current recommendations on the duration of anticoagulation.

Body mass index does not decline during winter for the sedentary marine gastropod Crepidula fornicata.

Seasonal extremes in environmental conditions can substantially limit the growth and reproduction of animals. Sedentary marine animals are particularly susceptible to winter food limitation since they cannot relocate to more favourable conditions. In several temperate-zone bivalve species, substantial winter tissue mass declines have been documented; however, no comparable studies have been conducted on intertidal gastropods. Here, we investigate whether the suspension-feeding intertidal gastropod Crepidula fornicata also loses substantial tissue mass during the winter. We calculated body mass index (BMI) for individuals collected in New England at different times of year for 7 years to determine whether BMI declines through winter or varies seasonally. Remarkably, C. fornicata body mass did not decline significantly during winter months; indeed, a relatively poorer body condition was associated with higher seawater temperature, higher air temperature and higher chlorophyll concentration. In a laboratory experiment, we found that C. fornicata adults that were not fed for three weeks at 6°C (local winter seawater temperature) showed no detectable declines in BMI compared to field-collected individuals. Future studies should document energy budgets of C. fornicata and other sedentary marine animals at low winter seawater temperatures, and the impact of short-term elevated temperatures on those energy budgets.

Reflexive pedagogy at the heart of educational digital transformation in Latin American higher education institutions.

This paper makes a critical review of educational and operational issues related with pandemic and postpandemic lessons in Latin American higher education institutions (LATAM HEI), as background for uncovering key elements to innovate educational practices in technology-mediated higher education. The authors adapted the reflexive pedagogy framework to conduct in depth analysis of innovation experiences mediated with educational technologies and draw conclusions for curricular and digital transformation of LATAM HEI.

Domain Expansion and Functional Diversification in Vertebrate Reproductive Proteins.

The rapid evolution of fertilization proteins has generated remarkable diversity in molecular structure and function. Glycoproteins of vertebrate egg coats contain multiple zona pellucida (ZP)-N domains (1-6 copies) that facilitate multiple reproductive functions, including species-specific sperm recognition. In this report, we integrate phylogenetics and machine learning to investigate how ZP-N domains diversify in structure and function. The most C-terminal ZP-N domain of each paralog is associated with another domain type (ZP-C), which together form a "ZP module." All modular ZP-N domains are phylogenetically distinct from nonmodular or free ZP-N domains. Machine learning-based classification identifies eight residues that form a stabilizing network in modular ZP-N domains that is absent in free domains. Positive selection is identified in some free ZP-N domains. Our findings support that strong purifying selection has conserved an essential structural core in modular ZP-N domains, with the relaxation of this structural constraint allowing free N-terminal domains to functionally diversify.

The Importance of Gene Duplication and Domain Repeat Expansion for the Function and Evolution of Fertilization Proteins.

The process of gene duplication followed by gene loss or evolution of new functions has been studied extensively, yet the role gene duplication plays in the function and evolution of fertilization proteins is underappreciated. Gene duplication is observed in many fertilization protein families including Izumo, DCST, ZP, and the TFP superfamily. Molecules mediating fertilization are part of larger gene families expressed in a variety of tissues, but gene duplication followed by structural modifications has often facilitated their cooption into a fertilization function. Repeat expansions of functional domains within a gene also provide opportunities for the evolution of novel fertilization protein. ZP proteins with domain repeat expansions are linked to species-specificity in fertilization and TFP proteins that experienced domain duplications were coopted into a novel sperm function. This review outlines the importance of gene duplications and repeat domain expansions in the evolution of fertilization proteins.

Current State of Diabetes Mellitus Prevalence, Awareness, Treatment, and Control in Latin America: Challenges and Innovative Solutions to Improve Health Outcomes Across the Continent.

PURPOSE OF REVIEW: Latin America is the scenario of great inequalities where about 32 million human beings live with diabetes. Through this review, we aimed at describing the current state of the prevalence, awareness, treatment, and control of diabetes mellitus and completion of selected guidelines of care across Latin America and identify opportunities to advance research that promotes better health outcomes. RECENT FINDINGS: The prevalence of diabetes mellitus has been consistently increasing across the region, with some variation: higher prevalence in Mexico, Haiti, and Puerto Rico and lower in Colombia, Ecuador, Dominican Republic, Peru, and Uruguay. Prevalence assessment methods vary, and potentially underestimating the real number of persons with diabetes. Diabetes unawareness varies widely, with up to 50% of persons with diabetes who do not know they may have the disease. Glycemic, blood pressure, and LDL-C control and completion of guidelines to prevent microvascular complications are not consistently assessed across studies, and the achievement of control goals is suboptimal. On the other hand, multiple interventions, point-of-care/rapid assessment tools, and alternative models of health care delivery have been proposed and tested throughout Latin America. The prevalence of diabetes mellitus continues to rise across Latin America, and the number of those with the disease may be underestimated. However, some local governments are embedding more comprehensive diabetes assessments in their local national surveys. Clinicians and public health advocates in the region have proposed and initiated various multi-level interventions to address this enormous challenge in the region.

Stigma, participation restriction and mental distress in patients affected by leprosy, cutaneous leishmaniasis and Chagas disease: a pilot study in two co-endemic regions of eastern Colombia.

BACKGROUND: Leprosy, cutaneous leishmaniasis (CL) and Chagas disease (CD) are neglected tropical diseases with a high psychosocial burden (PSB). These conditions are endemic in Norte de Santander and Arauca in Colombia, but data on the related PSB are scarce. Therefore, we assessed mental distress, participation restriction and stigma among CD, CL and leprosy patients. METHODS: In 2018, 305 leprosy, CD or CL patients were interviewed using a self-report questionnaire to assess mental distress, participation scale for participation restriction and explanatory model interview catalogue (EMIC) for stigma. Descriptive statistics and the significance of median score differences were compared. RESULTS: Fifty percent of CD patients and 49% of leprosy patients exhibited mental distress, percentages which were significantly higher than that of CL (26%). Twenty-seven percent of leprosy patients experienced participation restriction, which was lower for CL (6%) and CD (12%). Median EMIC scores were significantly higher for leprosy patients than for CD (27%) and CL (17%) patients. CONCLUSIONS: We found high levels of PSB among leprosy, CD and CL patients. Mental distress was highest among CD patients. Participation restriction and stigma were more prevalent in leprosy patients. Rural residence or lower educational status may impact PSB. Further investigation is needed to formulate evidence-based, holistic interventions.

Validation of a cross-NTD toolkit for assessment of NTD-related morbidity and disability. A cross-cultural qualitative validation of study instruments in Colombia.

BACKGROUND: Many neglected tropical diseases (NTDs) are not fatal, but they are disabling, disfiguring and stigmatizing. More accurate data on these aspects would benefit planning, monitoring and evaluation of interventions, as well as provision of appropriate services for the often life-long consequences. In 2015, a cross-NTD toolkit was developed, consisting of a variety of existing questionnaires to measure morbidity, disability and health-related quality of life. The toolkit covers the domains of the International Classification of Functioning, Disability and Health (ICF) framework. These tools have been developed in a source country, however, it was intended for the cross-NTD toolkit to be applicable across NTDs in many countries with different cultures and languages in order to generate universally comparative data. Therefore; the present study aimed to validate several tools of the toolkit among people affected by leprosy or leishmaniasis in the cultural settings of Cartagena and Cúcuta, Colombia. METHODOLOGY: This study aimed to validate the following tools among 55 participants between 18-85 years old, affected by leprosy and leishmaniasis: (I) Clinical Profile, (II) Self-Reporting Questionnaire (SRQ), (III) WHO Quality of Life assessment-abbreviated version (WHOQOL-BREF), and (IV) WHO Quality of Life assessment-Disability (WHOQOL-DIS). The tools were administered during face-to-face interviews and were followed by open questions about the respondents' thoughts on format of the tool and the understanding, relevance and acceptability of the items. The tools were validated using a qualitative method approach based on the framework for cultural equivalence, measured by the cultural, item, semantic and operational equivalences. RESULTS: The Clinical Profile was seen as acceptable and relevant, only the semantic equivalence was not as satisfying and needs a few adaptations. The SRQ was very well understood and shows to reach the equivalences for the population of Colombia without any additional changes. Several items of the WHOQOL-BREF and the WHOQOL-DIS were not well understood and changes are recommended due to semantic difficulties. Operational equivalence of both questionnaires was not as desired in relation to the used response scales. The participants shared that the tools are relevant and important for their particular situation. CONCLUSIONS/SIGNIFICANCE: The SRQ is found to be a valid tool for Colombia and can be included in the cross-NTD toolkit. The Clinical Profile, WHOQOL-BREF & WHOQOL-DIS need changes and retesting among Colombian people affected by an NTD. The toolkit as a whole is seen as useful to show the effects leprosy and leishmaniasis have on the participants. This cultural validation will contribute to a universally applicable cross-NTD toolkit.

Tuberculosis miliar con diseminación renal y genitourinaria, Hospital Escuela Universitario, Honduras, 2017 / Tuberculosis Miliar with Renal and Genitourinary Dissemination, University School Hospital. Honduras, 2017

La tuberculosis continúa siendo un reto diagnóstico al presentarse con características clínicas poco usuales. Objetivo: exponer las características clínicas en un caso inusual de tuberculosis miliar, con diseminación genitourinaria. Presentación del caso clínico: p aciente masculino de 48 años, agricultor, de escasos recursos económicos, sin comorbilidades previas; presentó sintomatología constitucional, pérdida de peso, fiebre y dolor lumbar irradiado a ambos flancos de la región abdominal, de características específicas, de un mes de evolución, acompañado de disuria y oliguria, negó síntomas respiratorios. Al examen físico, luce crónicamente enfermo, en mal estado nutricional, sin deterioro de la conciencia, no evidenció adenopatías cervicales ni inguinales, sin presencia de signos pulmonares y con leve dolor renal bilateral a la puño percusión;en área genital se identifica una masa de borde regular, móvil, sobre el polo superior del testículo derecho. Examen hematológico, presencia de Bicitopenia (anemia microcitica hipocromica y trombocitopenia leve). Además con hiperazoemia e hiperkalemia en la bioquímica sanguínea refractaria al tratamiento; en gases arteriales acidosis metabólica con anión gap elevado, por lo que fue sometido a hemodiálisis aguda. A través de los estudios imagenológicos, por medio de la bacteria alcohol acido resistente de sedimento urinario seriado y la tinción Ziehl Neelsen en orina, se determinó el diagnóstico yse inició terapia antifimica. Conclusión: Es necesario considerar a la tuberculosis como diagnóstico diferencial, especialmente en presentaciones poco usuales, dado que es endémica en Honduras...(AU)

Melatonin receptor type 1A gene linked to Alzheimer's disease in old age.

Disruption of the circadian rhythms is a frequent preclinical and clinical manifestation of Alzheimer's disease. Furthermore, it has been suggested that shift work is a risk factor for Alzheimer's disease. Previously, we have reported association of intolerance to shift work (job-related exhaustion in shift workers) with a variant rs12506228A, which is situated close to melatonin receptor type 1A gene (MTNR1A) and linked to MTNR1A brain expression levels. Here, we studied association of that variant with clinical and neuropathological Alzheimer's disease in a Finnish whole-population cohort Vantaa 85+ (n = 512, participants over 85 years) and two follow-up cohorts. Rs12506228A was associated with clinical Alzheimer's disease (p = 0.000073). Analysis of post-mortem brain tissues showed association with higher amount of neurofibrillary tangles (p = 0.0039) and amyloid beta plaques (p = 0.0041). We then followed up the associations in two independent replication samples. Replication for the association with clinical Alzheimer's disease was detected in Kuopio 75+ (p = 0.012, n = 574), but not in the younger case-control sample (n = 651 + 669). While melatonin has been established in regulation of circadian rhythms, an independent role has been also shown for neuroprotection and specifically for anti-amyloidogenic effects. Indeed, in vitro, RNAi mediated silencing of MTNR1A increased the amyloidogenic processing of amyloid precursor protein (APP) in neurons, whereas overexpression decreased it. Our findings suggest variation close to MTNR1A as a shared genetic risk factor for intolerance to shift work and Alzheimer's disease in old age. The genetic associations are likely to be mediated by differences in MTNR1A expression, which, in turn, modulate APP metabolism.

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Factors associated with the delay of diagnosis of leprosy in north-eastern Colombia: a quantitative analysis.

OBJECTIVES: To determine the average time in months between the beginning of symptoms and the diagnostic confirmation of leprosy by the health system and to investigate factors associated with diagnostic delay. METHODS: A total of 249 patients older than 15 years diagnosed with leprosy between 2011 and 2015, in 20 endemic municipalities of north-eastern Colombia, provided informed consent and were interviewed face-to-face. Clinical histories from health centres or hospitals where study participants were treated for leprosy were also reviewed. RESULTS: The mean delay in diagnosis of leprosy was 33.5 months. About 14.9% of patients showed a visible deformity or damage (disability grade 2, DG2) at the time of diagnosis. In multivariable regression analysis, five or more consultancies required to confirm the diagnosis and not seeking care immediately after noticing first symptoms were associated with longer diagnostic delay. CONCLUSIONS: Our study found a significant delay in diagnosis of leprosy in north-eastern Colombia, which might explain the continuously high rate of DG2 among new cases being notified in the country. Both patient- and health system-related factors were associated with longer diagnostic delay. Interventions to increase awareness of disease among the general population and timely referral to a specialised health professional are urgently needed in our study setting.

Tuberculosis miliar con diseminación renal y genitourinaria: reporte de un caso / Miliary tuberculosis, with renal and genitourinary disemination; Case Report

Antecedentes: A pesar de los grandes avances en la medicina contemporánea; la Tuberculosis continúa siendo un reto diagnóstico, en especial al presentarse con características clínicas poco usuales. Caso clínico: Paciente masculino de 48 años, agri-cultor, de escasos recursos económicos, sin comorbilidades previas, el cual presenta sintomatología constitucional, pérdida de peso, iebre y dolor lumbar irradiado a ambos lancos de la región abdominal, de características poco especíicas, de un mes de evolución; acompañado de disuria y oliguria, y niega síntomas respiratorios. Al examen físico luce crónicamente enfermo, en mal estado nutricio-nal, sin deterioro de la conciencia, no se evidencia adenopatías cervicales ni inguinales; sin presencia de signos pulmonares, con leve dolor con la puño percusión renal bilateral, en el área genital, se identiica una masa de borde regular, móvil sobre el polo superior del testículo derecho. En el examen hematológico con presencia de Bicitopenia anemia microcitica hipocromica y trombocitopenia leve, en gases arteriales acidosis metabólica con Anión Gap elevado, además con hiperazoemia e hiperkalemia en la bioquímica sanguínea refractaria al tratamiento, razón por la cual fue sometido a Hemodiálisis aguda. Al evaluar radiografía de tórax se observa patrón micro-nodular difuso, no se realiza baciloscopias por falta de expectoración ni por lavado gástrico, en el ultrasonido renal y de vías urinarias se visualizó nefromegalia y la presencia de masa heterogénea de aspecto granulomatoso en testículo derecho; por lo que se solicitó tomografía toracoabdominal, en donde se observa patrón micronodular múltiple a nivel pulmonar, con afectación renal, ganglionar y testicular, se solicita BAAR de sedimento urinario seriado con resultados positivos, y la tinción Ziehl Neelsen en orina con resultado positivo; con ello se inicia terapia antiimica. Discusión: La Tuberculosis renal no tiene un cuadro clínico clásico; generalmente se presenta con manifestaciones atípicas; como en nuestro caso con sintomatología urinaria, hiperazoemia que culmino en terapia de restitución renal de emergencia, con posterior recuperación de la función renal.

Clinical and epidemiological differences between men and women with systemic sclerosis: a study in a Spanish systemic sclerosis cohort and literature review.

OBJECTIVES: The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in Ssc patients, and contradictory results have often been show among those studies that have been performed. METHODS: A prospective study was conducted with the Spanish RESCLE register to analyse the influence of gender on survival of SSc patients. RESULTS: In total, 1506 SSc patients (1341 women, 165 men) were recruited from 21 centres. Older age at onset (OR 1.02), shorter time from onset to diagnosis (OR 0.96), smoking (OR 2.57), interstitial lung disease (ILD) (OR 1.58), less predisposition to sicca syndrome and to antinuclear antibody positivity (OR 0.29 and 0.43, respectively), and higher compliance with the ACR 1980 criteria (OR 1.79) were independently associated with the male sex. During follow-up, 30.4% of men versus 14.6% of women died (p<0.001). Survival at 10 years from the onset of symptoms was 75.3% for men and 92.9% for women (p<0.001), and the difference remained after selecting only SSc-related deaths (85.6% vs. 96.1%, p<0.001). The mortality predictive factors were diffuse SSc (OR 2.26), ILD (OR 1.82), digital ulcers (OR 1.38), tendon friction rubs (OR 1.74), male sex (OR 1.53), increased age at onset (OR 1.13) and isolated PH (considering only deaths from diagnosis), both in the overall (OR 3.63) and female cohorts (OR 3.97). The same risk factors were observed in the male cohort, except for isolated PH and ILD. CONCLUSIONS: The present study confirms the existence of epidemiological, clinical, laboratory and prognostic gender differences in systemic sclerosis patients.

Vertical leaping mechanics of the Lesser Egyptian Jerboa reveal specialization for maneuverability rather than elastic energy storage.

BACKGROUND: Numerous historical descriptions of the Lesser Egyptian jerboa, Jaculus jaculus, a small bipedal mammal with elongate hindlimbs, make special note of their extraordinary leaping ability. We observed jerboa locomotion in a laboratory setting and performed inverse dynamics analysis to understand how this small rodent generates such impressive leaps. We combined kinematic data from video, kinetic data from a force platform, and morphometric data from dissections to calculate the relative contributions of each hindlimb muscle and tendon to the total movement. RESULTS: Jerboas leapt in excess of 10 times their hip height. At the maximum recorded leap height (not the maximum observed leap height), peak moments for metatarso-phalangeal, ankle, knee, and hip joints were 13.1, 58.4, 65.1, and 66.9 Nmm, respectively. Muscles acting at the ankle joint contributed the most work (mean 231.6 mJ / kg Body Mass) to produce the energy of vertical leaping, while muscles acting at the metatarso-phalangeal joint produced the most stress (peak 317.1 kPa). The plantaris, digital flexors, and gastrocnemius tendons encountered peak stresses of 25.6, 19.1, and 6.0 MPa, respectively, transmitting the forces of their corresponding muscles (peak force 3.3, 2.0, and 3.8 N, respectively). Notably, we found that the mean elastic energy recovered in the primary tendons of both hindlimbs comprised on average only 4.4% of the energy of the associated leap. CONCLUSIONS: The limited use of tendon elastic energy storage in the jerboa parallels the morphologically similar heteromyid kangaroo rat, Dipodomys spectabilis. When compared to larger saltatory kangaroos and wallabies that sustain hopping over longer periods of time, these small saltatory rodents store and recover less elastic strain energy in their tendons. The large contribution of muscle work, rather than elastic strain energy, to the vertical leap suggests that the fitness benefit of rapid acceleration for predator avoidance dominated over the need to enhance locomotor economy in the evolutionary history of jerboas.

C9orf72 hexanucleotide repeat expansions are not a common cause of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a polygenic neuropsychiatric disorder characterized by repetitive thoughts and behaviors that cause distress. The pathogenic repeat expansion [GGGGCC]n found at the C9orf72 locus is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and has also been documented in patients with psychosis and schizophrenia. Furthermore, obsessions and compulsions have been identified in patients diagnosed with ALS and/or FTD and carrying the pathogenic repeat expansion. Here, we performed genetic screening for the C9orf72 repeat expansion on 573 patients diagnosed with OCD. None of the patients were found to carry the expansion. The results show that patients with OCD do not commonly carry the pathogenic repeat expansion and therefore should not be routinely screened. OCD and psychotic patients who do test positive for the C9orf72, however, should be closely observed for the later development of FTD and ALS.

Clinical association between Kikuchi׳s disease and systemic lupus erythematosus: A systematic literature review.

OBJECTIVE: To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE). METHODS: We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients. RESULTS: The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio = 5.0); mean age at diagnosis was 34 years (range: 14-56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis. CONCLUSIONS: While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE.