A role for vessel-associated extracellular matrix proteins in multiple sclerosis pathology.

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA-DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA-DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA-DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA-DRB*15-positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation. These findings informed a neuropathological characterisation of these proteins in a large autopsy cohort of 41 MS cases (18 HLA-DRB1*15-positive and 23 HLA-DRB1*15-negative), and seven non-neurological controls on motor cortical, cervical and lumbar spinal cord tissue. Biglycan and decorin demonstrate a striking perivascular expression pattern in controls that is reduced in MS (-36.5%, p = 0.036 and - 24.7%, p = 0.039; respectively) in lesional and non-lesional areas. A concomitant increase in diffuse parenchymal accumulation of biglycan and decorin is seen in MS (p = 0.015 and p = 0.001, respectively), particularly in HLA-DRB1*15-positive cases (p = 0.007 and p = 0.046, respectively). Prolargin shows a faint parenchymal pattern in controls that is markedly increased in MS cases where a perivascular deposition pattern is observed (motor cortex +97.5%, p = 0.001; cervical cord +49.1%, p = 0.016). Our findings point to ECM proteins and the vascular interface playing a central role in MS pathology within and outside the plaque area. As ECM proteins are known potent pro-inflammatory molecules, their parenchymal accumulation may contribute to disease severity. This study brings to light novel factors that may contribute to the heterogeneity of the topographical variation of MS pathology.

Perceived health- related quality of life in persons with multiple sclerosis with and without a vascular comorbidity.

PURPOSE: Vascular comorbidities are prevalent and can contribute to adverse health outcomes in persons with multiple sclerosis (PwMS). Understanding the association between vascular comorbidities and health-related quality of life (HRQOL) among PwMS may be beneficial in improving outcomes and disease management. This cross-sectional study aimed to examine the relationship between vascular comorbidities and the different dimensions of HRQOL in PwMS. METHODS: Participants (n = 185) were PwMS recruited from a community-based comprehensive MS care center. Demographics, comorbid conditions, and disability level were collected via a self-report REDCap survey, with the 29-item Multiple Sclerosis Quality of Life (MSQOL-29) as the outcome measure. Regression models were used to examine the association between vascular comorbidities and the MSQOL-29, controlling for age, gender, ethnicity, level of education, marital status, MS subtype, disease duration, and disability. RESULTS: Approximately 35% reported at least one vascular comorbidity, with the most common being hypertension (27.0%), followed by hyperlipidemia (24.9%) and diabetes (8.1%). After factoring in for demographics and disability, having a vascular comorbidity was associated with lower physical HRQOL (ß = - 10.05, 95% CI: - 28.24, 23.50), but not mental HRQOL (ß = - 2.61, 95% CI: - 10.54, 5.32). Hypertension was negatively associated with several dimensions of HRQOL, including Physical Function, Change in Health, Health Perceptions, Energy, and Health Distress. CONCLUSIONS:  Having at least one vascular comorbidity is associated with lower physical HRQOL, independent of demographics and level of physical disability. Focus should be directed to the physical burden and challenges vascular comorbidities may cause on the lives of PwMS.

Establishment of regression-based normative isometric strength values for major lower limb muscle groups in persons with multiple sclerosis.

BACKGROUND: Limb weakness is a major impairment that affects mobility in persons with multiple sclerosis (PwMS). Specifically, lower limb (LL) weakness can greatly affect gait and balance, while increasing fall risk and decreasing quality of life. Numerous studies have compared LL strength of PwMS to healthy controls, however none have objectively measured strength in all major LL joints (hip, knee, and ankle) in a large number of PwMS. Additionally, while discrete normative values exist for knee extensors in PwMS, there has yet to be regression-based normative isometric strength values for all major LL muscle groups. Therefore, this study aimed to develop gender-specific regression-based normative prediction equations, with 95% confidence intervals, for maximal isometric peak torque of major LL muscles in PwMS. A secondary aim was to characterize the prevalence of LL weakness in PwMS, defined as ≥ 2 SD below values reported for healthy individuals. METHODS: A convenience sample of 175 (women: n = 135) PwMS participated in a prospective, cross-sectional study where isometric peak torque of hip flexors, extensors, and abductors, knee flexors and extensors, and ankle plantarflexors and dorsiflexors were measured using the Biodex System 4 Pro-Dynamometer®. Demographics (age, height, and weight) and disease characteristics (disease duration and disability) were collected. Performances were separated for each muscle group into strongest limb and weakest limb. For each gender, regression-based equations were generated for the LL muscle groups by limb with age, height, weight, disability, and disease duration as the covariates. Descriptive statistics were used to examine the frequency of LL weakness by gender and disability level. For comparison purposes, age-stratified (<30, 30-39, 40-49, 50-59, 60-69, >70 years) and disability-stratified (mild, moderate, and severe ambulant) discrete peak torque values were also generated for each gender. RESULTS: Regression-based normative data are presented for men and women, accounting for age, height, weight, disability, and disease duration. Men were significantly stronger (P < 0.001) than women for all LL, with the men's models accounting for a greater percent of muscle strength variation than women's models for all muscle groups, except for hip extension. Disability was inversely related to strength in all of the models. LL weakness was prevalent in hip flexion (m: 47.5%; w: 63.0%) and extension (m: 92.5%; w: 88.1%), knee extension (m: 30.0%; w: 33.3%) and flexion (m: 25.0%; w: 34.8%), and ankle plantarflexion (m: 15.0%; w: 10.4%) and dorsiflexion (m: 100.0%; w: 96.3%). PwMS with mild disability had a high prevalence of ankle dorsiflexion (94.9-100.0%) and hip extension (81.4-90.0%) weakness. CONCLUSIONS: This study is the first to provide regression-based normative data of bilateral strength in all major LL muscle groups and clinically useful prevalence data on the occurrence of weakness in these muscles. Of note, PwMS had a high prevalence of ankle dorsiflexion and hip extension weakness even when they were only mildly disabled. These findings can help guide the direction of future interventions and treatments to improve muscle function in PwMS.

Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors.

Introduction: Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. Methods: We aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. Results: We found that SNAI1, SNAI2, Vimentin, KLK10, PEBP1, Ki-67 and SSTR2 were associated with invasive NF-PitNET. Furthermore, we found that the EMT phenomenon was more common in NF-PitNET than in GH-secreting pituitary tumors. Interestingly, PEBP1 was overexpressed in recurrent NF-PitNET, and could predict growth recurrence with 100% sensitivity but only 43% specificity. In parallel with previously reported studies, SSTR3 is highly expressed in our NF-PitNET cohort. However, SSTR3 expression is highly heterogeneous among the different histological variants of NF-PitNET with very low levels in silent corticotroph adenomas. Conclusion: NF-PitNET showed an enhanced EMT phenomenon. SSTR3 targeting could be a good therapeutic candidate in NF-PitNET except for silent corticotroph adenomas, which express very low levels of this receptor. In addition, PEBP1 could be an informative biomarker of tumor regrowth, useful for predictive medicine in NF-PitNET.

Effect of Backward and Forward Walking on Lower Limb Strength, Balance, and Gait in Multiple Sclerosis: A Randomized Feasibility Trial.

BACKGROUND: Backward walking (BW) interventions have improved gait and balance in persons with stroke, cerebral palsy, and Parkinson disease but have not been studied in persons with multiple sclerosis (MS). We examined the feasibility of a BW intervention and how it affected strength, balance, and gait vs forward walking (FW) in persons with MS. METHODS: Sixteen persons with MS with a Patient-Determined Disease Steps (PDDS) scale score of 3 to 5 (gait impairment-late cane) were randomized to the FW (n = 8) or BW (n = 8) group. Participants did 30 minutes of FW or BW on a treadmill 3 times per week for 8 weeks (24 visits). Enrollment, adherence rate, and safety were tracked. The Timed Up and Go test, Six-Spot Step Test, single-leg stance, and abbreviated Activities-specific Balance Confidence scale were used to measure balance. Hip and knee flexion and extension strength (isometric peak torque), gait speed, and spatiotemporal gait parameters were measured. A 2×2 factorial multivariate analysis of covariance was used to examine changes in strength, balance, and gait, with the PDDS scale score as the covariate. RESULTS: Treatment adherence rate was 99.7%, with no safety concerns. After controlling for baseline differences in disability (PDDS scale score; P = .041), the BW group improved dominant hip flexion strength preintervention to postintervention compared with the FW group (F 1,13 = 9.03; P = .010). No other significant differences were seen between groups. CONCLUSIONS: This was the first study to look at BW as an intervention in persons with MS. Based on its feasibility, safety, and significant finding, BW should be studied in a larger, definitive trial in the future.

Establishing the Test-Retest Reliability and Minimal Detectable Change of the Multiple Sclerosis Resiliency Scale.

BACKGROUND: The Multiple Sclerosis Resiliency Scale (MSRS) was designed to assess factors connected to resilience when facing MS-related challenges. Although the MSRS has demonstrated good internal consistency and construct validity, its test-retest reliability has yet to be established. Identifying the minimal detectable change (MDC) of the scale will also improve its utility as an outcome measure for resilience-based interventions. This study aimed to determine the test-retest reliability and MDC of the MSRS. METHODS: Participants were 62 persons with MS who completed the MSRS twice, with a mean ± SD of 16.60 ± 3.97 days (range, 14-30 days) between assessments. Test-retest reliability was evaluated using a 2-way, random-effects, single-measurement intraclass correlation coefficient (ICC), with agreement between time 1 and time 2 visualized with a Bland-Altman plot. The MDC was calculated using the standard error of measurement with a 95% CI. RESULTS: At time 1, the mean ± SD MSRS score was 77.19 ± 11.97 (range, 45.83-97.00); at time 2, the mean ± SD score was 76.38 ± 12.75 (range, 46-98). The MSRS total score had good test-retest reliability (ICC = 0.88), with the subscale ICCs ranging from 0.77 (MS Peer Support) to 0.93 (Spirituality). The MDC for the total score was 11.95. CONCLUSIONS: These findings suggest that the MSRS has good test-retest reliability and that persons with MS with a difference of 12 points or more between assessments have experienced a reliable change. The results support the utility of the MSRS as a potential outcome measure for MS-related resilience.

Incidence of acute respiratory symptoms and COVID-19 infection in children in public schools in Bogotá, Colombia, from July to November, 2020 / Incidencia de síntomas respiratorios agudos y COVID-19 en niños de escuelas públicas de Bogotá, Colombia, entre julio y noviembre de 2020

Introduction: More than 90% of children infected with COVID-19 worldwide developed mild to moderate disease. In Colombia, during 2020, COVID-19 infections in children stayed below 9.2% of the total cases, with no trends for age group or sex. Objective: To estimate the incidence of acute respiratory symptoms and COVID-19 in children from public schools in Bogotá, Colombia during the second semester of 2020. Material and methods: A telephone survey was conducted in over 5,000 scholar children. Antecedents and use of health services were informed. Descriptive statistics were used. Results: A total of 151.470 persons per day accounting for an IR of 157,8 per 100,000 people; almost three times the rate reported by the official surveillance system in the city. Conclusion: A lack of diagnosis and consultation in children was found compared to the general population. Further research is needed to elucidate the true burden of the disease in children.

Introducción. Más del 90% de los niños infectados con COVID-19 en el mundo, desarrollaron enfermedad leve a moderada. En Colombia, durante el 2020, la infección del COVID-19 en niños se mantuvo por debajo de 9,2 % del total de los casos sin tendencias por grupo de edad o sexo. Objetivo. Estimar la incidencia de síntomas respiratorios agudos y COVID19 en niños de escuelas públicas en Bogotá (Colombia) durante el segundo semestre de 2020. Materiales y métodos. Se hizo una encuesta telefónica en más de 5.000 escolares. Se recolectó información de antecedentes médicos y uso de servicios de salud. La información obtenida se describió mediante estadística descriptiva. Resultados. Se contabilizó un total de 151.470 personas al día para una tasa de incidencia de 157,8 en 100.000 personas, casi tres veces la tasa reportada por el sistema de vigilancia oficial de la ciudad. Conclusión. Se encontraron deficiencias en el diagnóstico y consulta de los niños, al compararlos con la población general. Se necesita más investigación para dilucidar la verdadera carga de la enfermedad en la población infantil.

Quantification of upper limb dysfunction in the activities of the daily living in persons with multiple sclerosis.

BACKGROUND: Dysfunction in upper limb (UL) function has been reported as an important indicator for disease progression in persons with multiple sclerosis (PwMS), thus a relevant outcome in clinical trials. However, standard assessment of UL function is limited to Nine-Hole Peg Test (NHPT) which assesses fine dexterity. This study aimed to deeply endophenotype UL involvement in PwMS and identify the most accurate set of measures needed to capture the complexity of UL dysfunction in the activities of daily living (ADL). METHODS: 257 PwMS underwent an extensive UL assessment using standardized measures of grip strength and endurance, coordination, vibratory and tactile sensation, dexterity, capacity and functionality. Limitation in ADL was defined from an objective perspective using a timed test (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Âgées: TEMPA) and from a subjective perspective using a questionnaire (Disabilities of the Arm, Shoulder and Hand: DASH). Disease severity subgroups were compared utilizing the Kruskal-Wallis test and frequencies determined the prevalence of abnormal UL for each measure. The Jonckheere-Terpstra test compared tested variables with disease severity. Then Receiver operating characteristic (ROC) curve analysis was used to test the accuracy of each tested variable in defining abnormality in the TEMPA and DASH. Cut-off scores were calculated using the Youden index. The predictive value of various tests over TEMPA and DASH were tested using a linear regression analysis. RESULTS: UL dysfunction was highly prevalent in all the modalities tested, even in participants with no/mild disability. Box and Block Test (BBT), finger-nose test (FNT), and NHPT were independently selected with ROC analyses as the most accurate measures in detecting abnormalities in TEMPA and DASH. In multivariate regression models, BBT and FNT, and NHPT all contributed to predicting TEMPA (adj. R2 0.795, P < 0.001), while only BBT and FNT predicted DASH. CONCLUSIONS: UL dysfunction is highly prevalent in PwMS, even when global disability is mild. BBT and FNT are time-efficient and cost-effective measures that complement the NHPT for more precise monitoring of PwMS at all disease stages.

Anterior optic pathway pathology in CNS demyelinating diseases.

The anterior optic pathway is one of the preferential sites of involvement in CNS inflammatory demyelinating diseases, such as multiple sclerosis and neuromyelitis optica, with optic neuritis being a common presenting symptom. What is more, optic nerve involvement in these diseases is often subclinical, with optical coherence tomography demonstrating progressive neuroretinal thinning in the absence of optic neuritis. The pathological substrate for these findings is poorly understood and requires investigation. We had access to post-mortem tissue samples of optic nerves, chiasms and tracts from 29 multiple sclerosis (mean age 59.5, range 25-84 years; 73 samples), six neuromyelitis optica spectrum disorders (mean age 56, range 18-84 years; 22 samples), six acute disseminated encephalomyelitis (mean age 25, range 10-39 years; 12 samples) cases and five non-neurological controls (mean age 55.2, range 44-64 years; 16 samples). Formalin-fixed paraffin-embedded samples were immunolabelled for myelin, inflammation (microglial/macrophage, T- and B-cells, complement), acute axonal injury and astrocytes. We assessed the extent and distribution of these markers along the anterior optic pathway for each case in all compartments (i.e. parenchymal, perivascular and meningeal), where relevant. Demyelinated plaques were classified as active based on established criteria. In multiple sclerosis, demyelination was present in 82.8% of cases, of which 75% showed activity. Microglia/macrophage and lymphocyte inflammation were frequently found both in the parenchymal and meningeal compartments in non-demyelinated regions. Acute axonal injury affected 41.4% of cases and correlated with extent of inflammatory activity in each compartment, even in cases that died at advanced age with over 20 years of disease duration. An antero-posterior gradient of anterior optic pathway involvement was observed with optic nerves being most severely affected by inflammation and acute axonal injury compared with the optic tract, where a higher proportion of remyelinated plaques were seen. In neuromyelitis optica spectrum disorder, cases with a history of optic neuritis had extensive demyelination and lost aquaporin-4 reactivity. In contrast, those without prior optic neuritis did not have demyelination but rather diffuse microglial/macrophage, T- and B-lymphocyte inflammation in both parenchymal and meningeal compartments, and acute axonal injury was present in 75% of cases. Acute demyelinating encephalomyelitis featured intense inflammation, and perivenular demyelination in 33% of cases. Our findings suggest that chronic inflammation is frequent and leads to neurodegeneration in multiple sclerosis and neuromyelitis optica, regardless of disease stage. The chronic inflammation and subsequent neurodegeneration occurring along the optic pathway broadens the plaque-centred view of these diseases and partly explains the progressive neuroretinal changes observed in optic coherence tomography studies.

The Role of Cognitive Impairment on Physical Therapy Attendance and Outcomes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Many persons with multiple sclerosis (PwMS) experience cognitive impairments, which may affect their ability to engage in physical therapy. There is limited information on how cognitive impairments are associated with PwMS' ability to participate and improve their functional outcomes. This study aimed to assess the relationship between cognitive functioning and PwMS' attendance, total goal attainment, and functional improvement following physical therapy intervention. METHODS: Participants (n = 45) were PwMS who participated in a larger self-management study and enrolled in physical therapy within the past 2 years. Objective cognitive functioning was examined using tests of prospective memory, retrospective memory, working memory, and processing speed, along with a self-report measure. Bivariate analyses were conducted to examine the relationship between cognitive functioning and each physical therapy outcome (session attendance, attaining goals, and changes in functional outcome measures), followed by logistic regressions with age, education, gender, and disability level as covariates. RESULTS: Difficulty learning new verbal information was associated with a greater likelihood of "no showing" one or more of their physical therapy sessions. Reductions in working memory and processing speed were associated with PwMS not meeting all their rehabilitation goals. Despite deficits in new learning, memory, and processing speed, 85.2% of those with pre-/postscores showed improvements in at least one functional outcome measure following physical therapy intervention. DISCUSSION AND CONCLUSIONS: These findings demonstrate the ability for PwMS to make functional motor gains despite the presence of cognitive impairments and highlight the potential contributions of cognitive functioning on attendance and goal attainment of physical therapy intervention.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A362, which includes background, methods, results, and discussion in the authors' own voices).

Experiences of caregivers of boys with Duchenne Muscular Dystrophy: "When I look at him, my world falls apart" / Experiencias de cuidadoras de niños con Distrofia Muscular de Duchenne: "Cuando lo volteo a mirar, se me une el cielo con la tierra"

Resumen La Distrofia Muscular de Duchenne (DMD) es una enfermedad neuromuscular, clasificada como una enfermedad huérfana o rara, transmitida por la madre, y que conlleva al deterioro físico progresivo y fatal de quienes la desarrollan, que en su mayoría son hombres. Aun con los tratamientos farmacológicos disponibles, el pronóstico de vida de los pacientes sigue siendo desalentador. Los niños van perdiendo progresivamente la movilidad y funcionalidad hasta que fallecen. En consecuencia, el progreso de esta enfermedad requiere de cuidados frecuentes o permanentes que implican altos niveles de exigencia para las cuidadoras de niños y de jóvenes que han desarrollado la DMD. El apoyo proveniente del sistema de salud es escaso para ambos, lo que se traduce en una intensa sobrecarga para las madres y mujeres de la familia que son quienes, habitualmente, cuidan a la persona diagnosticada con DMD durante su vida. Este estudio cualitativo de tipo fenomenológico tuvo como objetivos analizar el significado de la experiencia de ser cuidadora de niños y jóvenes que viven con DMD en Colombia, develando el sentido que tiene para las mujeres familiares asumir el rol de cuidadora. Se entrevistaron siete mujeres entre los 25 y los 64 años encargadas de cuidar, por lo menos, a un niño o joven con diagnóstico de DMD, previo consentimiento informado. Adicionalmente, los cuidadores desarrollaron un ejercicio de asociaciones libres. Para el análisis de datos se realizó un análisis temático de las narrativas, encontrando tres temas fundamentales alrededor de los cuales se le da sentido a esta experiencia: (1) descubrir la enfermedad, (2) vivir en función del paciente y (3) reconstruir el sentido de vida. Así, en un momento inicial las cuidadoras se enfrentan al diagnóstico de la enfermedad brindado por los médicos, quienes les explican su curso y su naturaleza. La cuidadora inicia un proceso de duelo, en el que la tristeza, la negación y la resignación tienen lugar, y emociones como la frustración y la impotencia se presentan en su máxima expresión. La manera en la que es comunicado el diagnóstico es evaluada por las cuidadoras como poco sensible. De hecho, ninguna de las participantes en el estudio recibió apoyo psicológico durante el proceso. En segundo lugar, ser la figura de cuidado implicó cambios a nivel personal, familiar y social, para lograr responder a las necesidades de los niños con DMD. En este sentido, algunas debieron renunciar a sus empleos, alejarse de amistades e incluso algunas manifestaron que se han separado de su pareja o han vivido experiencias de deterioro en las relaciones con su pareja y familia extensa. Además, junto con sus hijos han vivenciado experiencias de discriminación, vulneración de derechos y escaso apoyo social, experiencias que son factores de riesgo para la salud mental. Finalmente, la enfermedad termina por constituirse en el elemento vinculante entre ellas y sus niños. Los hallazgos de la presente investigación permiten identificar que, en el proceso de enfermedad, se produce una reconstrucción del sentido de vida. Así, las estrategias de afrontamiento se dirigen a lograr una transformación espiritual. La presencia de la enfermedad es interpretada como una manera de ser probadas y desarrollar sus cualidades como mujer y como madre. Entonces, el cuidado y la relación madre-hijo, son componentes motivacionales que transforman y dan sentido a la vida. En conclusión, los resultados muestran que el significado de la DMD está fuertemente vinculado a un proceso de intenso sufrimiento y estrés psicológico, con alta carga negativa. En particular, durante los primeros años después del diagnóstico, que debe ser asimilado y elaborado para aprender a convivir con la DMD y la certeza de la muerte prematura de un hijo.

Abstract Duchenne muscular dystrophy (DMD) is a neuromuscular disease that leads to progressive and fatal physical deterioration. The progression of this disease requires frequent or permanent care that implies high levels of demand for the caregivers of children who have developed DMD. Certainly, this disease affects diagnosed children and their caregivers as well. The support from the health system is scarce for both, which translates into an intense burden for the mothers and women of the family who care the person diagnosed with DMD during their lifetime. This qualitative study with phenomenological approach aimed to analyze the meaning of the experience of being a caregiver for boys and young men living with DMD in Colombia. After obtaining their informed consent, caregivers were interviewed and a thematic analysis of their narratives was performed to determine three key topics that endow their experiences with meaning: (1) finding out about the disease, (2) living according to the needs of boys and young men, and (3) providing a new meaning to life. The results show that the meaning of DMD is strongly associated with intense suffering and psychological stress, with a high negative burden, especially during the initial years after diagnosis. The study suggests that it is important to assimilate and process these experiences and findings to learn how to live with DMD and identify the certainty of a child's premature death.

Risk factors for infusion-related reactions following Ocrelizumab infusion in a community setting: Development of an electronic medical record-based explanatory model.

BACKGROUND: In 2017, ocrelizumab became the first FDA approved disease modifying therapy (DMT) for primary progressive multiple sclerosis (MS). Although effective, adverse infusion-related reactions (IRR), such as erythema, pruritus, hives, and throat irritation, were frequently reported. OBJECTIVE: To develop an explanatory model of factors associated with increased odds of IRR development to further enhance clinical decision-making when administering ocrelizumab in a community setting. METHODS: A retrospective chart review was performed (n = 422) by extracting patient demographic factors and co-occurring conditions and symptoms from electronic medical records. Bivariate analyses were conducted to examine which demographic and clinical characteristics were associated with IRR development, and variables with a p-value of <.10 were then entered into a logistic regression to create the explanatory model. RESULTS: Being female (odds ratio [OR]: 2.60), Hispanic/Latinx (OR: 3.98), and having a history of a co-occurring tremor (OR: 3.78) were risk factors for increased odds of having an IRR. CONCLUSIONS: These findings may be helpful in guiding clinical practice routines and improving patient expectations regarding the likelihood of IRR development based on their individual demographics and co-occurring conditions and symptoms.

Incidence of acute respiratory symptoms and COVID-19 infection in children in public schools in Bogotá, Colombia, from July to November, 2020 / Incidence of acute respiratory symptoms and COVID-19 infection in children in public schools in Bogotá, Colombia, from July to November, 2020

INTRODUCTION: More than 90% of children infected with COVID-19 worldwide developed mild to moderate disease. In Colombia, during 2020, COVID-19 infections in children stayed below 9.2% of the total cases, with no trends for age group or sex. OBJECTIVE: To estimate the incidence of acute respiratory symptoms and COVID-19 in children from public schools in Bogotá, Colombia during the second semester of 2020. MATERIAL AND METHODS: A telephone survey was conducted in over 5,000 scholar children. Antecedents and use of health services were informed. Descriptive statistics were used. RESULTS: A total of 151.470 persons per day accounting for an IR of 157,8 per 100,000 people; almost three times the rate reported by the official surveillance system in the city. CONCLUSION: A lack of diagnosis and consultation in children was found compared to the general population. Further research is needed to elucidate the true burden of the disease in children.

Introducción. Más del 90% de los niños infectados con COVID-19 en el mundo, desarrollaron enfermedad leve a moderada. En Colombia, durante el 2020, la infección del COVID-19 en niños se mantuvo por debajo de 9,2 % del total de los casos sin tendencias por grupo de edad o sexo. Objetivo. Estimar la incidencia de síntomas respiratorios agudos y COVID19 en niños de escuelas públicas en Bogotá (Colombia) durante el segundo semestre de 2020. Materiales y métodos. Se hizo una encuesta telefónica en más de 5.000 escolares. Se recolectó información de antecedentes médicos y uso de servicios de salud. La información obtenida se describió mediante estadística descriptiva. Resultados. Se contabilizó un total de 151.470 personas al día para una tasa de incidencia de 157,8 en 100.000 personas, casi tres veces la tasa reportada por el sistema de vigilancia oficial de la ciudad. Conclusión. Se encontraron deficiencias en el diagnóstico y consulta de los niños, al compararlos con la población general. Se necesita más investigación para dilucidar la verdadera carga de la enfermedad en la población infantil.

Chemoenzymatic Synthesis of the New 3-((2,3-Diacetoxypropanoyl)oxy)propane-1,2-diyl Diacetate Using Immobilized Lipase B from Candida antarctica and Pyridinium Chlorochromate as an Oxidizing Agent.

To exploit the hydrolytic activity and high selectivity of immobilized lipase B from Candida antarctica on octyl agarose (CALB-OC) in the hydrolysis of triacetin and also to produce new value-added compounds from glycerol, this work describes a chemoenzymatic methodology for the synthesis of the new dimeric glycerol ester 3-((2,3-diacetoxypropanoyl)oxy)propane-1,2-diyl diacetate. According to this approach, triacetin was regioselectively hydrolyzed to 1,2-diacetin with CALB-OC. The diglyceride product was subsequently oxidized with pyridinium chlorochromate (PCC) and a dimeric ester was isolated as the only product. It was found that the medium acidity during the PCC treatment and a high 1,2-diacetin concentration favored the formation of the ester. The synthesized compounds were characterized using IR, MS, HR-MS, and NMR techniques. The obtained dimeric ester was evaluated at 100 ppm against seven bacterial strains and two Candida species to identify its antimicrobial activity. The compound has no inhibitory activity against the bacterial strains used but decreased C. albicans and C. parapsilosis growth by 49% and 68%, respectively. Hemolytic activity was evaluated, and the results obtained support the use of the dimeric ester to control C. albicans and C. parapsilosis growth in non-intravenous applications because the compound shows hemolytic activity.

Potent and Specific Antibacterial Activity against Escherichia coli O157:H7 and Methicillin Resistant Staphylococcus aureus (MRSA) of G17 and G19 Peptides Encapsulated into Poly-Lactic-Co-Glycolic Acid (PLGA) Nanoparticles.

Antimicrobial peptides constitute an excellent alternative against conventional antibiotics because of their potent antimicrobial spectrum, unspecific action mechanism and low capacity to produce antibiotic resistance. However, a potential use of these biological molecules as therapeutic agents is threatened by their low stability and susceptibility to proteases. In order to overcome these limitations, encapsulation in biocompatible polymers as poly-lactic-glycolic-acid (PLGA) is a promising alternative for increasing their stability and bioavailability. In this work, the effect of new synthetic antimicrobial peptides GIBIM-P5S9K (G17) and GAM019 (G19) encapsulated on PLGA and acting against methicillin resistant Staphylococus aureus (MRSA) and Escherichia coli O157:H7 was studied. PLGA encapsulation allowed us to load around 7 µg AMPs/mg PLGA with an efficiency of 90.5%, capsule sizes around 290 nm and positive charges. Encapsulation improved antimicrobial activity, decreasing MIC50 from 1.5 to 0.2 (G17NP) and 0.7 (G19NP) µM against MRSA, and from 12.5 to 3.13 µM for E. coli O157:H7. Peptide loaded nanoparticles could be a bacteriostatic drug with potential application to treat these bacterial E. coli O157:H7 and MRSA infections, with a slow and gradual release.

Is the "Habsburg jaw" related to inbreeding?

Background: The "Habsburg jaw" has long been associated with inbreeding due to the high prevalence of consanguineous marriages in the Habsburg dynasty. However, it is thought that mandibular prognathism (MP) is under the influence of a dominant major gene.Aim: To investigate the relationship between the "Habsburg jaw" and the pedigree-based inbreeding coefficient (F) as a relative measure of genome homozygosity.Subjects and methods: The degree of MP and maxillary deficiency (MD) of 15 members of the Habsburg dynasty was quantified through the clinical analysis of 18 dysmorphic features diagnosed from 66 portraits.Results: A statistically significant correlation (r = 0.711, p = 0.003) between MP and MD was observed among individuals. Only MP showed a statistically significant positive regression on F as evidenced from univariate analysis (b = 6.36 ± 3.34, p = 0.040) and multivariate analysis (PCA) performed from single dysmorphic features (b = 14.10 ± 6.62, p = 0.027, for the first PC).Conclusion: Both MP and MD are generally involved in the "Habsburg jaw." The results showed a greater sensitivity to inbreeding for the lower third of the face and suggest a positive association between the "Habsburg jaw" and homozygosity and therefore a basically recessive inheritance pattern.

Quantification characteristics of digital spiral analysis for understanding the relationship among tremor and clinical measures in persons with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a degenerative neurological condition causing demyelination and neuronal loss. Tremor, a symptom of MS, is prevalent in 45.0-46.8% NARCOMS registrants. Although several tools to measure tremor exist, few outcomes are quantitative or regularly utilized clinically. NEW METHOD: Introduction of a novel adaptation of the digital spiral drawing to find a quick, sensitive, and clinically useful technique, to predict tremor in persons with MS (pwMS). Digital spiral measures included: Segment Rate (SEGRT), Standard Deviation (SD) of Radial Velocity (VSD-R), SD of Tangential Velocity (VSD-T), SD of Overall Velocity (VSD-O), Mean Drawing Velocity (MNV-O) and Mean Pen Pressure Acceleration (MNA-P). Digital spiral measures were compared with the manual Archimedes Spiral (AS) drawing and the following clinical measures: Finger-Nose Test (FNT), presence of visually observed intention tremor (VOT), Nine-Hole Peg Test (NHPT), and Box and Block Test (BBT). RESULTS: All clinical measures utilized demonstrated significant relationships with all digital variables, except VSD-R. The forward-stepwise regression revealed BBT accounted for the most variance, followed by SEGRT. Comparison with Existing Methods: SEGRT is more sensitive in detecting VOT and better for quantifying tremor than AS. BBT and SEGRT are optimal predictive measures for tremor. CONCLUSIONS: SEGRT has stronger sensitivity and negative predictive value than AS in detecting VOT. All clinical measures (NHPT, FNT, BBT, and AS) were significantly associated with the digital variables (SEGRT, VSD-T, VSD-O, MNV-O, and MNA-P) except for VSD-R. After controlling for Patient Determined Disease Steps (PDDS), BBT and SEGRT are the best predictive measures for tremor.

High Antifungal Activity against Candida Species of Monometallic and Bimetallic Nanoparticles Synthesized in Nanoreactors.

Among all novel challenges nowadays worldwide, infectious disease is probably one of the most important. It is well-known that common treatments used include high doses of antibiotics, which are very invasive therapies for patients. These treatments are more intensive when the infection is related to multidrug resistant microorganisms. In this sense, in this work we report the use of reverse micelles to form less than 5 nm gold, silver, and gold-silver nanoparticles (NPs) with biological activity against five opportunistic Candida strains responsible of several diseases in human beings. As a result, we evaluate the interface properties and droplet-droplet interactions of micelles founding high fluidity in the polar head of the surfactant, necessary to form a flexible interaction channel in the "dimmer" micelle-micelle. In this condition, we form monodispersed, highly reactive NPs with sizes less than 5 nm with high antifungal activity against C. parapsilosis, C. Krusei, C. glabrata, C. guillermondii, and C. albicans, with minimum inhibitory concentrations (MIC50) less than 0.7 ppm in all cases, the lowest reported to the best of our knowledge. These are very promising results to develop alternative therapies to treat fungal diseases in humans, animals, and plants, or to coat conventional surfaces in surgery rooms.

Association Between Religion and Suicidal Behaviors in Cancer Patients / Asociación entre religión y conductas suicidas en pacientes con cáncer

Abstract Background: Whereas most studies have focused on how the religious beliefs positively interfere with the presence or execution of suicidal behaviors, few have identified differences among religious beliefs and how these can not only be consider as a protective factor for suicide, but also as a variable that influences the expression of the suicidal related behaviors. Objective: To provide evidence about the effect of religious practices and beliefs on suicidal behavior in cancer patients in Colombia. Methods: This is a hospital-based cross-sectional study with a sample of 132 patients with cancer. Socio-demographic data were measured, in which the religious affiliation was included. The instruments used include the Scale of Suicidal Ideation (SSI), the item 9 of Beck Depression Scale (BDI-IA) and the Beck Hopelessness Inventory (BHS). Results: In our study, 93% of the patients had advanced stages of cancer, where 51.52% of them were in stage IV. Cancer patients who reported non-Catholic Christians were 3 and 4 times more likely to have some manifestation of suicidal behavior. Conclusions: It is recognized in non-Catholic Christians patients a greater chance to express suicidal ideation, which could be related to their level of suicide acceptability. It is considered that religion and their perception of death affects the expression and acceptance of suicidal ideation, reason why it is necessary more research on the effect of different religions on suicidal behavior, in order to include these aspects in the patient intervention.

Resumen Introducción: Mientras que la mayoría de los estudios se han centrado en cómo las creencias religiosas interfieren positivamente con la presencia ola ejecución de conductas suicidas, pocos han identificado diferencias entre creencias religiosas y cómo estas no solo se pueden considerar un factor protector contra el suicidio, sino también una variable que influye en la expresión de los comportamientos suicidas. Objetivo: Proporcionar evidencia sobre el efecto de las prácticas y creencias religiosas en la conducta suicida de los pacientes con cáncer en Colombia. Métodos: Es un estudio transversal con una muestra de 132 pacientes con cáncer. Se aplicó la Escala de Ideación Suicida (SSI), el ítem 9 del Inventario de Depresión de Beck (BDI-IA) y el Inventario de Desesperanza de Beck (BHS); además, en la entrevista se recogieron datos sociodemográficos entre los que se incluye la afiliación religiosa. Resultados: El 93% de los pacientes presentaban estadios de cáncer avanzados, de los que el 51,52% estaba en estadio IV. Los pacientes con cáncer que informaron ser cristianos no católicos tienen 3 y 4 veces más probabilidades de alguna conducta suicida. Conclusiones: Se distingue en los pacientes cristianos no católicos una mayor expresión de la ideación suicida, lo que podría estar relacionado con el grado de aceptabilidad del suicidio. Se considera que la religión y su percepción de la muerte afecta a la expresión y la aceptación de las ideas suicidas, por lo que se requiere más investigación sobre el efecto de las diversas religiones en las conductas suicidas, con el objetivo de incluir estos aspectos en la intervención de los pacientes.

Association Between Religion and Suicidal Behaviors in Cancer Patients.

BACKGROUND: Whereas most studies have focused on how the religious beliefs positively interfere with the presence or execution of suicidal behaviors, few have identified differences among religious beliefs and how these can not only be consider as a protective factor for suicide, but also as a variable that influences the expression of the suicidal related behaviors. OBJECTIVE: To provide evidence about the effect of religious practices and beliefs on suicidal behavior in cancer patients in Colombia. METHODS: This is a hospital-based cross-sectional study with a sample of 132 patients with cancer. Socio-demographic data were measured, in which the religious affiliation was included. The instruments used include the Scale of Suicidal Ideation (SSI), the item 9 of Beck Depression Scale (BDI-IA) and the Beck Hopelessness Inventory (BHS). RESULTS: In our study, 93% of the patients had advanced stages of cancer, where 51.52% of them were in stage IV. Cancer patients who reported non-Catholic Christians were 3 and 4 times more likely to have some manifestation of suicidal behavior. CONCLUSIONS: It is recognized in non-Catholic Christians patients a greater chance to express suicidal ideation, which could be related to their level of suicide acceptability. It is considered that religion and their perception of death affects the expression and acceptance of suicidal ideation, reason why it is necessary more research on the effect of different religions on suicidal behavior, in order to include these aspects in the patient intervention.