Immunogenicity of a new allergoid from Felis domesticus.

BACKGROUND: The chemical modification of allergens with glutaraldehyde improves safety while maintaining clinical efficacy, which permits the administration of higher doses of immunotherapy, reducing the risk of adverse reactions. The aim of this study is to evaluate the immunogenic capacity of a new cat dander polymer by immunizing mice and quantifying immunoglobulins in serum, in comparison with the non-modified allergen. METHODS: The study consists of the immunization of three mice groups with the polymerized and the native extract, together with a negative control group. The immunoglobulin levels in serum have been measured by indirect ELISA. By means of the non-parametric Mann-Whitney U test, it was determined if there were significant differences in the values of specific antibodies between groups. RESULTS: The group immunized with the allergoid showed significantly higher specific IgG and IgG1 values to dander allergens and specific IgG to the major allergen Fel d 1, while there were no significant changes in IgG2a and IgE values. These results could be due to a higher immunization dose. The vaccine formulation was based on the optimal defined dose for clinical efficacy of allergen immunotherapy. CONCLUSIONS: This preclinical study carried out with the present assay has established that the allergoid of cat dander extract, as designed for its optimal use in allergen immunotherapy, produces a higher specific IgG than the native extract, in addition to showing significantly higher specific IgG1 levels, evidencing a greater effectiveness in immunization.

[Inflammation, malnutrition, and SARS-CoV-2 infection: a disastrous combination]. / La inflamación, la desnutrición y la infección por SARS-CoV-2: una combinación nefasta.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge.

Ocular involvement secondary to Monkeypox virus infection.

We present the case of a 37-year-old male patient with symptoms compatible with adenoviral conjunctivitis of 5 days' evolution. Topical corticosteroids, lubricants and removal of pseudomembranes were prescribed. PCR analysis of conjunctival exudate was positive for Monkeypox virus. During follow-up, the patient developed corneal ulcers with a torpid course, requiring admission for treatment with Tecovirimat. Ocular involvement by Monkeypox virus is usually mild and self-limiting. Cases with severe visual involvement have been described when there is corneal damage, as exemplified in this case. After admission to hospital for systemic treatment, the patient progressed favourably.

Biomechanical Gait Effects of a Single Intervention with Wearable Closed Loop Control FES System in Chronic Stroke Patients. A Proof-of-Concept Pilot Study.

Foot drop is a gait disturbance characterized by difficulty in performing ankle dorsiflexion during the swing phase of the gait cycle. Current available evidence shows that functional electrical stimulation (FES) on the musculature responsible for dorsal ankle flexion during gait can have positive effects on walking ability. This study aims to present a proof of concept for a novel easy-to-use FES system and evaluates the biomechanical effects during gait in stroke patients, compared to unassisted walking. Gait was quantitatively evaluated in a movement analysis laboratory for five subjects with chronic stroke, in basal condition without assistance and in gait assisted with FES. Improvements were found in all temporospatial parameters during FES-assisted gait, evidenced by statistically significant differences only in gait speed (p=0.02). Joint kinematics showed positive changes in hip abduction and ankle dorsiflexion variables during the swing phase of the gait cycle. No significant differences were found in the Gait Deviation Index. In conclusion, the present pilot study demonstrates that the use of this FES system in the tibialis anterior muscle can cause gait functional improvements in subjects with foot drop due to chronic stroke.

Prolonged voluntary wheel running reveals unique adaptations in mdx mice treated with microdystrophin constructs ± the nNOS-binding site.

We tested the effects of prolonged voluntary wheel running on the muscle function of mdx mice treated with one of two different microdystrophin constructs. At 7 weeks of age mdx mice were injected with a single dose of AAV9-CK8-microdystrophin with (gene therapy 1, GT1) or without (gene therapy 2, GT2) the nNOS-binding domain and were assigned to one of four gene therapy treated groups: mdxRGT1 (run, GT1), mdxGT1 (no run, GT1), or mdxRGT2 (run,GT2), mdxGT2 (no run, GT2). There were two mdx untreated groups injected with excipient: mdxR (run, no gene therapy) and mdx (no run, no gene therapy). A third no treatment group, Wildtype (WT) received no injection and did not run. mdxRGT1, mdxRGT2 and mdxR performed voluntary wheel running for 52 weeks; WT and remaining mdx groups were cage active. Robust expression of microdystrophin occurred in diaphragm, quadriceps, and heart muscles of all treated mice. Dystrophic muscle pathology was high in diaphragms of non-treated mdx and mdxR mice and improved in all treated groups. Endurance capacity was rescued by both voluntary wheel running and gene therapy alone, but their combination was most beneficial. All treated groups increased in vivo plantarflexor torque over both mdx and mdxR mice. mdx and mdxR mice displayed ∼3-fold lower diaphragm force and power compared to WT values. Treated groups demonstrated partial improvements in diaphragm force and power, with mdxRGT2 mice experiencing the greatest improvement at ∼60% of WT values. Evaluation of oxidative red quadriceps fibers revealed the greatest improvements in mitochondrial respiration in mdxRGT1 mice, reaching WT levels. Interestingly, mdxGT2 mice displayed diaphragm mitochondrial respiration values similar to WT but mdxRGT2 animals showed relative decreases compared to the no run group. Collectively, these data demonstrate that either microdystrophin construct combined with voluntary wheel running increased in vivo maximal muscle strength, power, and endurance. However, these data also highlighted important differences between the two microdystrophin constructs. GT1, with the nNOS-binding site, improved more markers of exercise-driven adaptations in metabolic enzyme activity of limb muscles, while GT2, without the nNOS-binding site, demonstrated greater protection of diaphragm strength after chronic voluntary endurance exercise but decreased mitochondrial respiration in the context of running.

[Ebola and Marburg hemorrhagic fever viruses: update on filoviruses]. / Les fièvres hémorragiques à virus Ebota et arburg : l'actualite des filovirus.

The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

[Realities for a Sickle Cell Disease Control Strategy in the World Health Organization African Region]. / Réalités pour une stratégie de lutte contre la drépanocytose dans la région africaine de l'Organisation Mondiale de la Santé: Compte rendu du 7e Symposium International du Réseau d'Étude de la Drépanocytose en Afrique Centrale (REDAC https://www.redacnetwork.org/) Antananarivo, Madagascar. 13 - 15 juin 2018.

The Network for the Study of Sickle Cell Disease in Central Africa or REDAC, is a network of African, European and American researchers whose aim is to combat sickle cell disease. Its congresses take place every year in the partner countries with international symposia alternating with workshops. REDAC enables host countries to obtain from local authorities a real involvement in the fight through resolutions in line with national strategies of fight. The Seventh International Symposium of REDAC was held in 2018 in Antananarivo, Madagascar under the auspices of the Malagasy Minister of Health and the Malagasy Senate Authorities. The theme chosen was that of strategies to combat sickle cell disease recommended by the WHO. The presentations focused on neonatal screening, early diagnosis, management of sickle cell disease and new therapies (marrow transplant, gene therapy and treatment with hydroxyurea).

[Trunk kinematics during walking in stroke patients: A systematic review]. / Cinemática de tronco durante la marcha en pacientes con ictus: revisión sistemática.

The trunk and pelvis are affected after stroke, predisposing individuals to falls and dependency. The aim of this review was to describe the lineal and angular kinematics of the trunk and pelvis in patients with post-stroke sequels during walking. We included studies published up to June 2018 using a 2-3 D motion capture system during walking. We searched the Cochrane, Medline, PEDRo, Lilacs, Scielo, EBSCO, ClinicalKey and Elsevier databases. Twelve articles were selected. Linear kinematics showed greater lateral displacement and acceleration in all axes. Angular kinematics in the swing phase of the paretic segment showed the pelvis in posterior rotation, with elevation and lower velocity and the trunk in anterior flexion, with lateral inclination and ipsilateral rotation. The studies showed wide variability, making it impossible to establish of a common effect. However, the results allow description of the movement of the trunk and pelvis.

Subduction zone fluids and arc magmas conducted by lithospheric deformed regions beneath the central Andes.

Dehydration of the oceanic subducting slab promotes the formation of magmatic arcs, intra-slab intermediate-depth seismicity, and hydration of the overlying mantle wedge. However, the complex permeability structure of the overriding plate controls the magma and fluid migration and their accumulation at shallower depths. In this regard, mapping the inner structure of the overriding crust and mantle is crucial to understand the magmatic and hydrological processes in subduction zones. We integrate 3-D P-wave, [Formula: see text], and electrical resistivity tomographic models of the northern Chilean subduction zone to map the magmatic and fluids derived from the subducting oceanic Nazca plate. Results show a continental crust relatively thick (50-65 km) characterized by a lower zone of high [Formula: see text] values (7.2-7.6 km/s), which is interpreted as the presence of plutonic rocks. The mantle lithospheric wedge is weakly hydrated ([Formula: see text] = 1.75-1.8) while the forearc continental crust is traversed by regions of reduced electrical resistivity values ([Formula: see text] [Formula: see text]) interpreted as zones of relatively high permeability/fracturing and fluid content. These regions spatially correlate with upper plate trans-lithospheric deformation zones. Ascending melts accumulate preferentially in the back-arc, whereas hydrothermal systems form trenchward of the volcanic arc. The results highlight the complex permeability structure of the upper South American plate.

Modelling the effect of temperature on transmission of dengue.

The main entomological parameters involved in the rate of dengue virus transmission include the longevity of female mosquitoes, the time interval between bites and the extrinsic incubation period of the virus. Field and laboratory data provide estimates for these parameters, but their interactions with other factors (e.g. host population density and environmental parameters) make their integration into a transmission model quite complex. To estimate the impact of these parameters on transmission, we developed a model of virus transmission by a vector population which predicts the number of potentially infective bites under a range of temperatures and entomological parameters, including the daily survival rate of females, the interval between bites and the extrinsic incubation period. Results show that in a stable population, an increase in mosquito longevity disproportionately enhances the number of potential transmissions (e.g. by as much as five times when the survival rate rises from 0.80 to 0.95). Halving the length of the biting interval with a 10- degrees C rise in temperature increases the transmission rate by at least 2.4 times. Accordingly, the model can predict changes in dengue transmission associated with short-term variation in seasonal temperature and also with potentially long-lasting increases in global temperatures.

Type 1 wild poliovirus and putative enterovirus 109 in an outbreak of acute flaccid paralysis in Congo, October-November 2010.

An outbreak of flaccid paralysis syndrome in adults is ongoing in Congo. Molecular analysis of faecal, throat and cerebrospinal samples identified wildtype 1 poliovirus and an additional enterovirus C strain related to enterovirus 109 as the cause. As of 22 November, the cumulative number of cases was 409, of which 169 (41.3%) were fatal. This is one of the largest wild type 1 poliovirus outbreaks ever described associated with an unusually high case fatality rate.

[Inflammation, malnutrition, and SARS-CoV-2 infection: a disastrous combination]. / La inflamación, la desnutrición y la infección por SARS-CoV-2: una combinación nefasta.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge.

Destiny ot the Gabonese international center of medical research.

In 2009, the Franceville International Medical Research Center (CIRMF) celebrated its 30th anniversary, at the same time as the Republic of Gabon celebrated the 50th anniversary of its independence. The CIRMF went into operation in 1979 when the president of the Republic, M. Omar Bongo Ondimba, decided to establish it in partnership with the Elf-Aquitaine corporation. Three decades later, it was time to assess its work. The day of this 30th anniversary, more than 300 people were working at the Center. To convince the authorities to make a major investment, the Directorate-General of the CIRMF presented the successful results obtained for science, the projects underway and planned, and its international outreach. Mission accomplished: in 2009 a renovation of the CIRMF began. It has worked successfully in the following fields of research: antiretroviral agents, hepatitis viruses, the diversity of plasmodium, emerging viral diseases, and still topics such as neonatal diagnosis of sickle-cell anemia and an exhaustive inventory of the fauna and flora of the tropical forest. The CIRMF has achieved success and can be proud of its 30th anniversary of international biomedical research in the natural environment of Gabon.

Efectividad de la entrevista motivacional en la atención fisioterápica de los trastornos musculoesqueléticos de la espalda / Effectiveness of the motivational interview in the physiotherapy care of musculoskeletal disorders of the back: A quasi-experimental study

Objetivo: Evaluar la efectividad de la entrevista motivacional (EM) junto al tratamiento fisioterapéutico habitual en pacientes con trastornos musculoesqueléticos (TME) de la espalda en atención primaria (AP). Métodos: Estudio cuasiexperimental en pacientes que iniciaron su tratamiento en el año 2020 en una unidad de fisioterapia tras diagnóstico médico de TME en la espalda, con seguimiento prospectivo de 2grupos con actuación terapéutica: grupo experimental (GE) y grupo de control (GC). Se empleó la EM solo en el GE. A ambos grupos se les entrevistó telefónicamente a los 3y 6meses de finalizar el tratamiento fisioterápico, preguntando por el cumplimiento de pautas domiciliarias y por la percepción subjetiva del estado de salud (escala de Barthel). Se ajustaron modelos de regresión lineales (coeficiente de regresión, IC del 95%) y logísticos (OR, IC del 95%). Resultados: La población de estudio fue de 154 personas (76,6% mujeres). La salud percibida fue significativamente mejor (p<0,001) en el GE que en el GC, tanto a los 3meses de seguimiento (7,4 versus 5,0, respectivamente) como a los 6(7,1 versus 4,6, respectivamente). Hubo una fuerte asociación entre percepción de salud y cumplimiento (coeficiente de regresión 3,0 [IC del 95%=2,5-3,4]). La asociación entre la EM y el cumplimiento terapéutico se mantuvo tras ajustes multivariados (OR a 6meses=383,6 [IC del 95% = 31,0-4.742,4]). Conclusiones: la incorporación de la EM como complemento de los tratamientos de fisioterapia es una herramienta factible y efectiva para mejorar el cumplimiento de las pautas domiciliarias y la percepción subjetiva de salud. (AU)

Objective: To evaluate the effectiveness of motivational interviewing (MI) combined with the usual physiotherapy treatment in patients with back musculoskeletal disorders (MSD) in primary care (PC). Methods: Quasi-experimental study with 2groups with therapeutic action (control group and experimental group) and prospective follow-up, in a physiotherapy unit in PC, in patients who began their treatment in 2020, with a medical diagnosis of MSD in the back. MI was used only in the face-to-face visits of the experimental group. Both groups were interviewed by telephone about 3and 6months after finishing the physiotherapy treatment. For this purpose, the Barthel scale was used for the subjective perception of the state of health, and the scale of compliance with home guidelines. Linear (regression coefficient, 95% CI) and logistic (OR, 95% CI) regression models were fitted. Results: The study population was 154 people (76.6% women). Perceived health was significantly better (P<.001) in the experimental group than in the control group, both at 3(7.4 versus 5.0, respectively) and at 6months of follow-up (7.1 versus 4.6, respectively). There was a strong association between perceived health and compliance (regression coefficient 3.0 [95% CI=2.5–3.4]). The strong association between MI and treatment adherence was maintained after multivariate adjustments (6-month OR=383.6 [95% CI 31.0–4742.4]). Conclusions: MI is a feasible and effective complement to physiotherapy treatments to improve compliance with home recommendations and subjective perception of health. (AU)

Immunophenotypic Pattern of De Novo Malignancy After Liver Transplantation.

Long-term survival after liver transplantation is affected by de novo neoplasia. The incidence of this type of malignancy is increased in the setting of immunosuppressive therapy. The aim of this study was to characterize the immunologic pattern of liver transplant recipients with de novo malignancies. Fifty-one liver recipients were studied, 19 of whom had a history of de novo neoplasia. Immunophenotypic patterns among patients with/without tumors were compared. The subpopulations of CD4+ T lymphocytes and CD8+ T lymphocytes differed between the 2 types of patients studied. In patients with tumor, activation membrane markers in CD4+ T lymphocytes and CD8+ T-lymphocytes, such as CD56 or CD25, were expressed in a greater proportion, whereas activation markers CD314 and CD16 were reduced in CD56bright natural killer (NK) cells. We concluded that cytotoxic response seems to be more activated in de novo neoplasia patients, which highlights the still unknown malignancy risk effect on these immune cells.

Individual-based network model for Rift Valley fever in Kabale District, Uganda.

Rift Valley fever (RVF) is a zoonotic disease, that causes significant morbidity and mortality among ungulate livestock and humans in endemic regions. In East Africa, the causative agent of the disease is Rift Valley fever virus (RVFV) which is primarily transmitted by multiple mosquito species in Aedes and Mansonia genera during both epizootic and enzootic periods in a complex transmission cycle largely driven by environmental and climatic factors. However, recent RVFV activity in Uganda demonstrated the capability of the virus to spread into new regions through livestock movements, and underscored the need to develop effective mitigation strategies to reduce transmission and prevent spread among cattle populations. We simulated RVFV transmission among cows in 22 different locations of the Kabale District in Uganda using real world livestock data in a network-based model. This model considered livestock as a spatially explicit factor in different locations subjected to specific vector and environmental factors, and was configured to investigate and quantitatively evaluate the relative impacts of mosquito control, livestock movement, and diversity in cattle populations on the spread of the RVF epizootic. We concluded that cattle movement should be restricted for periods of high mosquito abundance to control epizootic spreading among locations during an RVF outbreak. Importantly, simulation results also showed that cattle populations with heterogeneous genetic diversity as crossbreeds were less susceptible to infection compared to homogenous cattle populations.

Diuretic treatment of the patient with diabetes and heart failure. Role of SGLT2 inhibitors and similarities with carbonic anhydrase inhibitors. / Tratamiento diurético del paciente con diabetes e insuficiencia cardiaca. El papel de los inhibidores de la SGLT2 y semejanzas con los inhibidores de la anhidrasa carbónica.

Sodium-glucose cotransporter-2 inhibitors have changed the concept of the effects that hypoglycemic drugs have on hearth failure (HF). For the first time, a therapeutic group has modified the evolution of HF. Its effect goes beyond glycemic control, and different theories have been postulated to justify this benefit. In the article we sent, we analyze the influence of the different pharmacological groups used in type 2 diabetes mellitus on HF, and we present the theory of the mechanism of action associated with the benefit of these drugs. In our opinion, this benefit in HF is secondary to its diuretic effect, specifically an effect very similar to carbon dioxide inhibitors. We think that our theory is novel, explains the mechanism of action and we have not found in the literature any article that explains the mechanism of action in such a precise way.

Ebolavirus and other filoviruses.

Since Ebola fever emerged in Central Africa in 1976, a number of studies have been undertaken to investigate its natural history and to characterize its transmission from a hypothetical reservoir host(s) to humans. This research has comprised investigations on a variety of animals and their characterization as intermediate, incidental, amplifying, reservoir, or vector hosts. A viral transmission chain was recently unveiled after a long absence of epidemic Ebola fever. Animal trapping missions were carried out in the Central African rain forest in an area where several epidemics and epizootics had occurred between 2001 and 2005. Among the various animals captured and analyzed, three species of fruit bats (suborder Megachiroptera) were found asymptomatically and naturally infected with Ebola virus: Hypsignathus monstrosus (hammer-headed fruit beats), Epomops franqueti (singing fruit bats), and Myonycteris torquata (little collared fruit bats). From experimental data, serological studies and virus genetic analysis, these findings confirm the importance of these bat species as potential reservoir species of Ebola virus in Central Africa. While feeding bats drop partially eaten fruit and masticated fruit pulp (spats) to the ground, possibly promoting indirect transmission of Ebola virus to certain ground dwelling mammals, if virus is being shed in saliva by chronically and asymptomatically infected bats. Great apes and forest duikers are particularly sensitive to lethal Ebola virus infection. These terrestrial mammals feed on fallen fruits and possibly spats, suggesting a chain of events leading to Ebola virus spillover to these incidental hosts. This chain of events may occur sporadically at different sites and times depending on a combination of the phenology of fruit production by different trees, animal behavior, and various, but as yet still unknown environmental factors, which could include drought. During the reproductive period, infected body fluid can also be shed in the environment and present a potential risk for indirect transmission to other vertebrates.

Arenaviruses.

The Arenaviridae family contains 22 recognized virus species, each of them strongly associated with a rodent species (except Tacaribe virus which is associated with a species of bat), suggesting an ancient co-evolutionary process. Although the concept of co-evolution between rodents and arenaviruses is now largely accepted, little has been uncovered in terms of dating the phenomenon and the mechanisms of evolution, including speciation and pathogenicity. These questions are targeted in the present chapter. Old World arenaviruses are associated with the Eurasian rodents in the family Muridae. New World arenaviruses are associated with American rodents in the subfamily Sigmodontinae. The correlation between the rodent host phylogeny and the viruses suggests a long association and a co-evolutionary process. Furthermore, three distinct New World arenaviruses share a common ancestor, demonstrating a unique recombination event that probably occurred in that ancestor. This shows that recombination among arenaviruses of different lineages might occur in nature. Recombination and co-evolutionary adaptation appear as the main mechanisms of arenavirus evolution, generating a high degree of diversity. The diversity among rodent host reservoir and virus species and the potential to exchange genomic material provide a basis for the emergence of new viruses and the risk of these becoming pathogenic for humans.