A portable system to measure knee extensor spasticity after spinal cord injury.

BACKGROUND: The pendulum test is a quantitative method used to assess knee extensor spasticity in humans with spinal cord injury (SCI). Yet, the clinical implementation of this method remains limited. The goal of our study was to develop an objective and portable system to assess knee extensor spasticity during the pendulum test using inertial measurement units (IMU). METHODS: Spasticity was quantified by measuring the first swing angle (FSA) using a 3-dimensional optical tracking system (with external markers over the iliotibial band, lateral knee epicondyle, and lateral malleolus) and two wireless IMUs (positioned over the iliotibial band and mid-part of the lower leg) as well as a clinical exam (Modified Ashworth Scale, MAS). RESULTS: Measurements were taken on separate days to assess test-retest reliability and device agreement in humans with and without SCI. We found no differences between FSA values obtained with the optical tracking system and the IMU-based system in control subjects and individuals with SCI. FSA values from the IMU-based system showed excellent agreement with the optical tracking system in individuals with SCI (ICC > 0.98) and good agreement in controls (ICC > 0.82), excellent test-retest reliability across days in SCI (ICC = 0.93) and good in controls (ICC = 0.87). Notably, FSA values measured by both systems showed a strong association with MAS scores ( ρ  ~ -0.8) being decreased in individuals with SCI with higher MAS scores, reflecting the presence of spasticity. CONCLUSIONS: These findings suggest that our new portable IMU-based system provides a robust and flexible alternative to a camera-based optical tracking system to quantify knee extensor spasticity following SCI.

Infection of Fetal Membranes with Mycobacterium tuberculosis and Tissue Processing to Isolate RNA for Expression Analysis.

This chapter outlines the methodology employed to infect the chorionic and amniotic membranes with Mycobacterium tuberculosis during pregnancy. Particularly, congenital tuberculosis, a rare and serious condition associated with cases in neonates and reactivation of latent tuberculosis in pregnant mothers, is interesting to study. Understanding the mechanisms of infection and the response of fetal membranes is crucial for developing effective treatments in these cases, which will promote better neonatal and maternal health in situations of tuberculosis during pregnancy. Establishing a standardized infection model in the chorioamniotic membranes is imperative, followed by a treatment protocol for isolating both cellular and mycobacterial RNA. This will enable the expression analysis during the maternal-fetal interface interaction with M. tuberculosis. The proposed methodology might be invaluable for qRT-PCR, microarrays, and sequencing research.

Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection.

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.

Plitidepsin as an Immunomodulator against Respiratory Viral Infections.

Plitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2. In resiquimod (a ligand of TLR7/8)-stimulated THP1 human monocytes, plitidepsin-mediated reductions of IL-6 mRNA and IL-6 levels were also noticed. Additionally, although resiquimod-induced binding to DNA of NF-κB family members was unaffected by plitidepsin, a decrease in the regulated transcription by NF-κB (a key transcription factor involved in the inflammatory cascade) was observed. Furthermore, the phosphorylation of p65 that is required for full transcriptional NF-κB activity was significantly reduced by plitidepsin. Moreover, decreases of IL-6 levels and other proinflammatory cytokines were also seen in either SARS-CoV-2 or H1N1 influenza virus-infected mice, which were treated at low enough plitidepsin doses to not induce antiviral effects. In summary, plitidepsin is a promising therapeutic agent for the treatment of viral infections, not only because of its host-targeted antiviral effect, but also for its immunomodulatory effect, both of which were evidenced in vitro and in vivo by the decrease of proinflammatory cytokines.

Prolonged, Atypical, and Fulminant Mpox in a HIV/HBV-Coinfected Patient: A Case Report.

Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent global outbreak in countries around the world. A 39-year-old male with human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox, presented to our hospital with disseminated skin lesions (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for monkeypox virus. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. Sixty-five days after a positive monkeypox virus PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox because it could be related to higher mortality.

A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity.

Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models.

Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22-23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant.

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.

Suicidio más allá del diagnóstico: un enfoque centrado en la persona y su circunstancia / Suicide Beyond Diagnosis: A Person and Their Circumstances-Centered Approach

Existe una pluralidad de enfoques sobre el suicidio. En la literatura científica y en el ámbito sanitario es hegemónico el modelo biomédico. En este trabajo se presen-ta un modelo alternativo, existencial-contextual, de estudio, comprensión, prevención y posvención del suicidio en el ámbito sanitario. El trabajo se divide en dos partes. La primera expone los tres elementos esenciales del modelo existencial-contextual: la no-ción de persona, el concepto de problemas de la vida y la práctica de la relación de cui-dado y acompañamiento. La segunda desarrolla algunas de las diferencias asistenciales más importantes entre el modelo biomédico y el existencial-contextual del suicidio. Se concluye en la necesidad de superar el paradigma suicidológico biomédico tradicional y construir un espacio amplio transdisciplinar de reflexión suicidológica crítica a la altura de nuestro tiempo. Este cambio de paradigma requiere pasar de una lógica que prioriza lo patológico-biológico-farmacológico a otra socio-psico-política del suicidio que integre las aportaciones del modelo biomédico sin reducirse a ellas. (AU)

There is a plurality of understanding approaches to suicide. In the scientific literature and the healthcare field, the biomedical model is hegemonic. This paper pre-sents an alternative existential-contextual model for the study, understanding, preven-tion and postvention of suicide in the healthcare field. The academic paper is divided into two parts. The first part sets out the three essential elements of the existential-contex-tual model: the notion of personhood, the concept of life problems and the practice of caring and supportive relationships. The second one develops some of the most impor-tant differences in care between the biomedical and the existential-contextual models of suicide. It concludes with the need to overcome the traditional biomedical suicidological paradigm and to build a broad transdisciplinary space for critical suicidological reflection that is up to date with our times. This paradigm shift requires moving from a logic that prioritizes the pathological-biological-pharmacological to a socio-psycho-political logic of suicide that integrates the contributions of the biomedical model without being reduced to them. (AU)

[Modified CAMBRA questionnaire as a method for population-based caries risk screening without exploratory methods: a cross-sectional observational pilot study]. / Cuestionario de autoevaluación CAMBRA como método de cribado poblacional del riesgo de caries sin métodos exploratorios: un estudio piloto observacional transversal.

OBJECTIVE: Caries Management by Risk Assessment (CAMBRA) is a questionnaire used to diagnose the patient's overall caries risk. This study aimed to present a self-assessment questionnaire based on CAMBRA which, unlike the original, is completed by parents/caregivers, without the need for a dental examination, allowing a presumptive diagnosis to be established in children under seven years of age excluded from the oral health programme of the National Health System to establish individualised recommendations for caries risk and their early inclusion in preventive programmes of the Madrid Health Service (Madrid, Spain). METHODS: A cross-sectional observational study was carried out following STROBE guidelines using for the first time a self-assessment questionnaire based on CAMBRA in a population of children aged from three to six years from a nursery school in Madrid (Spain). The results were analysed using descriptive statistics and Fisher's exact statistic was used to study the relationship between qualitative variables. RESULTS: The questionnaire was answered by the parents of 120 children (response rate=53.1%), of whom 40.8% presented a low a priori caries risk, 42.5% a moderate risk and 16.7% a high caries risk. CONCLUSIONS: The present study allow the identification of patients at risk of presenting and/or developing caries. However, future studies should evaluate its sensitivity and specificity by comparing it with a confirmatory diagnosis after a dental examination. Nevertheless, the modified CAMBRA questionnaire could be a useful tool for population screening, facilitating the access of the population at risk of caries and risk of exclusion to preventive and community plans.

OBJETIVO: Caries Management by Risk Assessment (CAMBRA) es un cuestionario de diagnóstico del riesgo global de caries dental. Este estudio tuvo como objetivo presentar un cuestionario de autoevaluación basado en CAMBRA que, a diferencia del original, es cumplimentado por padres/madres/cuidadores, sin necesidad de una exploración odontológica, permitiendo establecer un diagnóstico de presunción en menores de siete años excluidos del programa de salud oral del Sistema Nacional de Salud, con el fin de instaurar recomendaciones individualizadas al riesgo de caries y su inclusión precoz en programas preventivos del Servicio Madrileño de Salud (Madrid, España). METODOS: Se llevó a cabo un estudio observacional transversal basado en las recomendaciones STROBE, empleando por primera vez un cuestionario de autoevaluación basado en CAMBRA en niños/as de tres a seis años de una escuela infantil de Madrid (España). Los resultados se analizaron mediante una estadística descriptiva y para el estudio de la relación entre variables cualitativas se utilizó el estadístico exacto de Fisher. RESULTADOS: El cuestionario fue respondido por padres de 120 niños, de los cuales, el 40,8% presentó, a priori, un riesgo de caries bajo, el 42,5% un riesgo moderado y el 16,7% un riesgo alto de caries. CONCLUSIONES: El presente estudio permite la identificación de pacientes en riesgo de presentar y/o desarrollar caries. No obstante, futuros estudios han de evaluar su sensibilidad y especificidad mediante su comparativa frente a un diagnóstico de confirmación tras una exploración odontológica. Pese a ello, el cuestionario CAMBRA modificado podría ser una herramienta útil para el cribado poblacional, facilitando el acceso de la población en riesgo de caries y en riesgo de exclusión a planes preventivos y comunitarios.

Cuestionario de autoevaluación CAMBRA como método de cribado poblacional del riesgo de caries sin métodos exploratorios: un estudio piloto observacional transversal / Modified CAMBRA questionnaire as a method for population-based caries risk screening without exploratory methods: a cross-sectional observational pilot study

Fundamentos: Caries Management by Risk Assessment (CAMBRA) es un cuestionario de diagnóstico del riesgo global de caries dental. Este estudio tuvo como objetivo presentar un cuestionario de autoevaluación basado en CAMBRA que, a diferencia del original, es cumplimentado por padres/madres/cuidadores, sin necesidad de una exploración odontológica, permitiendo establecer un diagnóstico de presunción en menores de siete años excluidos del programa de salud oral del Sistema Nacional de Salud, con el fin de instaurar recomendaciones individualizadas al riesgo de caries y su inclusión precoz en programas preventivos del Servicio Madrileño de Salud (Madrid, España). Métodos: Se llevó a cabo un estudio observacional transversal basado en las recomendaciones STROBE, empleando por primera vez un cuestionario de autoevaluación basado en CAMBRA en niños/as de tres a seis años de una escuela infantil de Madrid (España). Los resultados se analizaron mediante una estadística descriptiva y para el estudio de la relación entre variables cualitativas se utilizó el estadístico exacto de Fisher. Resultados: El cuestionario fue respondido por padres de 120 niños, de los cuales, el 40,8% presentó, a priori, un riesgo de caries bajo, el 42,5% un riesgo moderado y el 16,7% un riesgo alto de caries. Conclusiones: El presente estudio permite la identificación de pacientes en riesgo de presentar y/o desarrollar caries. No obstante, futuros estudios han de evaluar su sensibilidad y especificidad mediante su comparativa frente a un diagnóstico de confirmación tras una exploración odontológica. Pese a ello, el cuestionarioCAMBRA modificado podría ser una herramienta útil para el cribado poblacional, facilitandoel acceso de la población en riesgo de caries y en riesgo de exclusión a planes preventivos y comunitarios.(AU)

Background:Caries Management by Risk Assessment (CAMBRA) is a questionnaire used to diagnose the patient’s overall caries risk. This study aimed to present a self-assessment questionnaire based on CAMBRA which, unlike the original, is completed by parents/caregivers, without the need for a dental examination, allowing a presumptive diagnosis to be established in children under seven years of age excluded from the oral health programme of the National Health System to establish individualised recommendations for caries risk and their early inclusion in preventive programmes of the Madrid Health Service (Madrid, Spain). Methods: A cross-sectional observational study was carried out following STROBE guidelines using for the first time a self-assessment questionnaire based on CAMBRA in a population of children aged from three to six years from a nursery school in Madrid (Spain). The results were analysed using descriptive statistics and Fisher’s exact statistic was used to study the relationship between qualitative variables. Results: The questionnaire was answered by the parents of 120 children (response rate=53.1%), of whom 40.8% presented a low a priori caries risk, 42.5% a moderate risk and 16.7% a high caries risk. Conclusion: The present study allow the identification of patients at risk of presenting and/or developing caries. However, future studies should evaluate its sensitivity and specificity by comparing it with a confirmatory diagnosis after a dental examination. Nevertheless, the modified CAMBRA questionnaire could be a useful tool for population screening, facilitating the access of the population at risk of caries and risk of exclusion to preventive and community plans.(AU)

Intravitreal methotrexate in type B lymphoblastic leukemia-Case Report.

Leukemia is a common neoplasia that, in its progress, can have ocular involvement due to direct infiltration or secondary to hematological alterations typical of the disease. These findings are consistent with an involvement of the central nervous system and are thus related to the prognosis. Despite the existing systemic therapies, there needs to be more literature that shows the treatment in the ocular involvement of this disease. A case report of a child with ocular involvement due to treatment-refractory acute lymphoblastic leukemia, successfully managed with intravitreal methotrexate, is presented.

Spasticity Predicts Motor Recovery for Patients with Subacute Motor Complete Spinal Cord Injury.

OBJECTIVE: A motor complete spinal cord injury (SCI) results in the loss of voluntary motor control below the point of injury. Some of these patients can regain partial motor function through inpatient rehabilitation; however, there is currently no biomarker to easily identify which patients have this potential. Evidence indicates that spasticity could be that marker. Patients with motor complete SCI who exhibit spasticity show preservation of descending motor pathways, the pathways necessary for motor signals to be carried from the brain to the target muscle. We hypothesized that the presence of spasticity predicts motor recovery after subacute motor complete SCI. METHODS: Spasticity (Modified Ashworth Scale and pendulum test) and descending connectivity (motor evoked potentials) were tested in the rectus femoris muscle in patients with subacute motor complete (n = 36) and motor incomplete (n = 30) SCI. Motor recovery was assessed by using the International Standards for Neurological Classification of Spinal Cord Injury and the American Spinal Injury Association Impairment Scale (AIS). All measurements were taken at admission and discharge from inpatient rehabilitation. RESULTS: We found that motor complete SCI patients with spasticity improved in motor scores and showed AIS conversion to either motor or sensory incomplete. Conversely, patients without spasticity showed no changes in motor scores and AIS conversion. In incomplete SCI patients, motor scores improved and AIS conversion occurred regardless of spasticity. INTERPRETATION: These findings suggest that spasticity represents an easy-to-use clinical outcome that might help to predict motor recovery after severe SCI. This knowledge can improve inpatient rehabilitation effectiveness for motor complete SCI patients. ANN NEUROL 2023.

Corticospinal excitability across lower limb muscles in humans.

Electrophysiological studies in nonhuman primates reported the existence of strong corticospinal output from the primary motor cortex to distal compared with proximal hindlimb muscles. The extent to which corticospinal output differs across muscles in the leg in humans remains poorly understood. Using transcranial magnetic stimulation over the leg representation of the primary motor cortex, we constructed motor evoked potential (MEP) recruitment curves to measure the resting motor threshold (RMT), maximum MEP amplitude (MEP-max), and slope in the biceps femoris, rectus femoris, tibialis anterior, soleus, and a foot muscle (i.e., abductor hallucis) in intact humans. We found that the RMT was lower and the MEP-max and slope were larger in the abductor hallucis compared with most other muscles tested. In contrast, the RMT was higher and the MEP-max and slope were lower in the biceps femoris compared to all other muscles tested. Corticospinal responses in the rectus femoris, tibialis anterior, and soleus were in between those obtained from other leg muscles, with the soleus having a higher RMT and lower MEP-max and slope than the rectus femoris and tibialis anterior. To examine the origin of increases in corticospinal excitability in the abductor hallucis, we compared short-interval intracortical inhibition (SICI) and F-waves between the abductor hallucis and tibialis anterior. SICI was similar across muscles while the F-wave amplitude was larger in the abductor hallucis compared with the tibialis anterior. These results support a nonuniform distribution of corticospinal output to leg muscles, highlighting that increases in corticospinal excitability in a foot muscle could be related to a spinal origin.NEW & NOTEWORTHY We provide evidence on how corticospinal output differs across muscles in the leg in intact humans. We found that corticospinal responses were larger in a distal intrinsic foot muscle and were smaller in the biceps femoris compared to all other muscles in the leg. Increases in corticospinal excitability to an intrinsic foot muscle could have a spinal origin.

"Long-term oncologic outcomes and risk factors for distant recurrence after pathologic complete response following neoadjuvant treatment for locally advanced rectal cancer. A nationwide, multicentre study".

BACKGROUND: Pathologic complete response (pCR) after multimodal treatment for locally advanced rectal cancer (LARC) is used as surrogate marker of success as it is assumed to correlate with improved oncologic outcome. However, long-term oncologic data are scarce. METHODS: This retrospective, multicentre study updated the oncologic follow-up of prospectively collected data from the Spanish Rectal Cancer Project database. pCR was described as no evidence of tumour cells in the specimen. Endpoints were distant metastases-free survival (DMFS) and overall survival (OS). Multivariate regression analyses were run to identify factors associated with survival. RESULTS: Overall, 32 different hospitals were involved, providing data on 815 patients with pCR. At a median follow-up of 73.4 (IQR 57.7-99.5) months, distant metastases occurred in 6.4% of patients. Abdominoperineal excision (APE) (HR 2.2, 95%CI 1.2-4.1, p = 0.008) and elevated CEA levels (HR = 1.9, 95% CI 1.0-3.7, p = 0.049) were independent risk factors for distant recurrence. Age (years) (HR 1.1; 95%-CI 1.05-41.09; p < 0.001) and ASA III-IV (HR = 2.0; 95%-CI 1.4-2.9; p < 0.001), were the only factors associated with OS. The estimated 12, 36 and 60-months DMFS rates were 96.9%, 91.3%, and 86.8%. The estimated 12, 36 and 60-months OS rates were 99.1%, 94.9% and 89.3%. CONCLUSIONS: The incidence of metachronous distant metastases is low after pCR, with high rates of both DMFS and OS. The oncologic prognosis in LARC patients that achieve pCR after neoadjuvant chemo-radiotherapy is excellent in the long term.

ß-Cyclodextrins as affordable antivirals to treat coronavirus infection.

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and ß coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-ß-cyclodextrin (HßCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HßCD and U18666A, yet only HßCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, ß-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. ß-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to ß-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of ß-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.

Microbiological and Chemical characterization of water kefir: An innovative source of potential probiotics for bee nutrition / Caracterización microbiológica y química del kéfir de agua: una fuente innovadora de potenciales probióticos para la nutrición de las abejas

Abstract We evaluated the microbial composition of water kefir grains and beverage overthe course of one year to determine whether the number and type of microorganisms changedover the time. Bacteria and yeast colonies with different morphologies were isolated fromwater kefir and their antimicrobial activity was evaluated against Paenibacillus larvae andAscosphaera apis. A chemical characterization of kefir was also carried out. Our results con-firmed that bacteria and yeasts were more numerous in kefir grains compared with those in thebeverage. The counts of microorganisms declined, although an important microbial community was still present in kefir after the long storage period. Eleven strains which inhibited bee pathogens were isolated from kefir. Genotypic results demonstrated that these isolates included Lentilactobacillus hilgardii, Lentilactobacillus buchneri and Saccharomyces cerevisiae. Thus, water kefir may be an innovative source of potential probiotic strains for bee nutrition in order to control honeybee diseases.

Resumen Evaluamos la composición microbiana del kéfir de agua durante un ano para determinar si la cantidad y el tipo de microorganismos cambiaban con el tiempo. Se aislaron colonias de bacterias y de levaduras con diferentes morfologías, y su actividad antimicrobiana se evaluó frente a Paenibacillus larvaey Ascosphaeraapis. También se realizó una caracterización química del kéfir. Nuestros resultados confirmaron que las bacterias y las levaduras eran más numerosas en los gránulos de kéfir en comparación con la parte líquida. Los recuentos de microorganismos disminuyeron, aunque una cantidad igualmente importante se encontró en el kéfir después de un año. Se aislaron del kéfir once cepas que inhibieron los mencionados patógenos de abejas. Los resultados genotípicos demostraron que estos aislamientos eran Lentilactobacillus hilgardii, Lentilactobacillus buchneri y Saccharomyces cerevisiae. Por lo tanto, el kéfir de agua podría ser una fuente innovadora de potenciales cepas probióticas para contribuir a la nutrición y sanidad de las abejas.

Development of a Remote Version of the Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP): Validity and Reliability.

BACKGROUND: The Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP V1.0) was developed in 2010 as a 3-domain assessment for upper extremity function after tetraplegia (domains: Strength, Sensibility, and Prehension). A remote version (rGRASSP) was created in response to the growing needs of the field of Telemedicine. OBJECTIVE: The purpose of this study was to assess the psychometric properties of rGRASSP, establishing concurrent validity and inter-rater reliability. METHODS: Individuals with tetraplegia (n = 61) completed 2 visits: 1 in-person and 1 remote. The first visit was completed in-person to administer the GRASSP, and the second visit was conducted remotely to administer the rGRASSP. The rGRASSP was scored both by the administrator of the rGRASSP (Examiner 1), and a second assessor (Examiner 2) to establish inter-rater reliability. Agreement between the in-person and remote GRASSP evaluations was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman agreement plots. RESULTS: The remote GRASSP demonstrated excellent concurrent validity with the GRASSP (left hand intraclass correlation coefficient (ICC) = .96, right ICC = .96). Concurrent validity for the domains was excellent for strength (left ICC = .96, right ICC = .95), prehension ability (left ICC = .94, right ICC = .95), and prehension performance (left ICC = .92, right ICC = .93), and moderate for sensibility (left ICC = .59, right ICC = .68). Inter-rater reliability for rGRASSP total score was high (ICC = .99), and remained high for all 4 domains. Bland-Altman plots and limits of agreements support these findings. CONCLUSIONS: The rGRASSP shows strong concurrent validity and inter-rater reliability, providing a psychometrically sound remote assessment for the upper extremity in individuals with tetraplegia.

Evaluación de la satisfacción con la asistencia recibida por los pacientes de diálisis peritoneal durante la pandemia / Assessing satisfaction with the care given by peritoneal dialysis patients during the pandemic

Introducción: La pandemia por COVID-19 obligó a nuestra unidad a intercalar consultas presenciales con consultas telefónicas, sin que esto supusiera un aumento de las consultas urgentes; por ello, nos parecía necesario conocer la opinión del paciente al respecto. Objetivo: Evaluar la satisfacción de los pacientes en tratamiento con diálisis peritoneal sobre la calidad de la atención recibida mediante un modelo mixto de visitas presenciales y telemáticas.Material y Método: Estudio descriptivo transversal realizado entre febrero-marzo de 2021, mediante una encuesta telefónica anónima, realizada por un entrevistador independiente.Criterios inclusión: mayores de 18 años, en diálisis peritoneal y que dieron su consentimiento.Variables recogidas: edad, sexo, cuidador principal, proveedor (Baxter®/Fresenius®), ingreso hospitalario (Si/No).Cuestionario satisfacción (9 preguntas): 2 abiertas, 1 semicerrada con respuesta dicotómica y texto libre, y 6 cerradas con respuesta tipo Likert, del 0-10.Resultados: De los 78 pacientes en diálisis peritoneal obtuvimos 71 participantes. El 59, 1% (n=42) eran hombres, edad media de 66,1 años (23,33-91,23 años). La puntuación media sobre la atención asistencial, con el modelo mixto de visitas, fue de 9,5±1,13. En relación a los aspectos a mejorar en las consultas telefónicas, un 61,2% (n=41) consideraron que no es necesario asignar un horario, un 11,2% (n=8) manifestaron que es necesario recibir los cambios por escrito, un 4,5% (n=3) solicitaron mejorar la petición de analítica en el centro de salud y ninguno consideró necesaria la videollamada.Conclusiones: La satisfacción mostrada por los pacientes con nuestro modelo mixto de visitas parece que transmite una buena calidad asistencial, subsidiaria de mejoras e individualización.(AU)

Introduction: The COVID-19 pandemic forced our unit to alternate inperson consultations with telephone consultations, without this increasing urgent visits. Therefore, it seemed necessary to know the patient’s opinion regarding this matter. Objective: To assess the satisfaction of patients receiving peritoneal dialysis with the quality of care received through a mixed model of inperson and teleconsultations. Material and Method: PA descriptive cross-sectional study was conducted between February and March 2021, using an anonymous telephone survey conducted by an independent interviewer. Inclusion criteria: aged over 18, receiving peritoneal dialysis, and giving their consent. Variables collected: age, sex, primary caregiver, provider (Baxter®/Fresenius®), hospital admission (Yes/No). Satisfaction questionnaire (9 questions): 2 openended, 1 semiclosed with a dichotomous response and free text, and 6 closed with Likert-type response from 0-10. Results: Of the 78 peritoneal dialysis patients, 71 participants were included. 59.1% (n=42) were men, with an average age of 66.1 years (23.33-91.23 years). The average score for healthcare received through the mixed model of visits was 9.5 ±1.13. Regarding aspects to improve in phone consultations, 61.2% (n=41) considered it unnecessary to assign a specific time, 11.2% (n=8) stated the need to receive changes in writing, 4.5% (n=3) requested an improvement in the request for laboratory analysis at the healthcare center, and none considered video calls necessary. Conclusions: The patient’s satisfaction with our mixed model of visits seems to reflect a good quality of care, subject to improvement and individualization.(AU)