Psychosocial Factors Associated with Self-Management in Patients with Diabetes.

Despite the significant advances in research on diabetes, relatively few researchers have examined the theoretical and empirical usefulness of explanatory models that contribute to self-management of the disease. In response to the theoretical and empirical approaches related to this topic, the objective of this research was to assess a hypothetical model to explain self-management behavior in patients with type II diabetes through structural equation modeling in a population of users of the services of the State Health Department of Tamaulipas, Mexico. The study used a cross-sectional and explanatory design. The sample was intentional. A total of 183 patients with a diabetes diagnosis completed a sociodemographic data questionnaire, the Partners in Health Scale, the Duke-UNC-11, the Family Apgar, the Self-Efficacy Scale, the Personal Health Questionnaire and the Physical Activity Scale. The results indicated that the hypothetical model was improved by excluding the exercise variable. The appropriate model was used to determine the effects of depression, social support, self-efficacy, family functioning, years of formal education and years with a diagnosis on self-management. The goodness-of-fit indices (GFIs) were good, i.e., χ2/gl = 0.89 (p = 0.529), root mean square error of approximation (RMSEA) = 0.000, and comparative fit index (CFI) = 1.000, with an acceptable degree of parsimony (PNFI = 0.409 and PGFI = 317). The model explained 33.6% of the variance. Therefore, this model represents an important advance in knowledge concerning self-management and provides empirical and theoretical evidence, particularly for the Mexican or Latino population.

eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production.

Active hypusine-modified initiation elongation factor 5A is critical for cell proliferation and differentiation, embryonic development, and innate immune response of macrophages to bacterial infection. Here, we demonstrate that both virus infection and double-stranded RNA viral mimic stimulation induce the hypusination of eIF5A. Furthermore, we show that activation of eIF5A is essential for the replication of several RNA viruses including influenza A virus, vesicular stomatitis virus, chikungunya virus, mayaro virus, una virus, zika virus, and punta toro virus. Finally, our data reveal that inhibition of eIF5A hypusination using the spermidine analog GC7 or siRNA-mediated downmodulation of eIF5A1 induce upregulation of endoplasmic reticulum stress marker proteins and trigger the transcriptional induction of interferon and interferon-stimulated genes, mechanisms that may explain the broad-spectrum antiviral activity of eIF5A inhibition.

Favipiravir and/or nitazoxanide: a randomized, double-blind, 2×2 design, placebo-controlled trial of early therapy in COVID-19 in health workers, their household members, and patients treated at IMSS (FANTAZE).

BACKGROUND: The 2020 pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with the first presentation of symptoms, followed by a later 'inflammatory' phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with a better outcome. The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease. METHODS: Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial. RANDOMISATION: Participants will be randomised 1:1 by stratification, with the following factors: gender, obesity, symptomatic or asymptomatic, current smoking status presence or absence of comorbidity, and if the participant has or has not been vaccinated. BLINDING: Participants and investigators will both be blinded to treatment allocation (double-blind). DISCUSSION: We propose to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and patients treated at the Mexican Social Security Institute (IMSS) facilities. Participants with or without symptomatic COVID-19 or who tested positive will be assigned to receive favipiravir plus nitazoxanide or favipiravir plus nitazoxanide placebo. The primary outcome will be the difference in the amount of virus ('viral load') in the upper respiratory tract after 5 days of therapy. Secondary outcomes will include hospitalization, major morbidity and mortality, pharmacokinetics, and impact of antiviral therapy on viral genetic mutation rate. If favipiravir with nitazoxanide demonstrates important antiviral effects without significant toxicity, there will be a strong case for a larger trial in people at high risk of hospitalization or intensive care admission, for example older patients and/or those with comorbidities and with early disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04918927 . Registered on June 9, 2021.

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells.

Mayaro virus (MAYV) hijacks the host's cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38ß isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38ß isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

Resultados de la reparación de Bankart/plicatura y remplissage en el tratamiento de la luxación anteroinferior recurrente del hombro. Correlación con la escala de ISIS / Bankart repair and remplissage in recurrent anteroinferior shoulder dislocation, Correlation with ISIS scale

Introducción: La luxación recurrente anteroinferior del hombro es consecuencia de una luxación aguda traumática que, en pacientes jóvenes, menores de veinte años, se ha estimado puede llegar al 97% de recurrencia, pero que disminuye a medida que aumenta la edad, excepto en pacientes mayores con rupturas asociadas del manguito rotador. Al ser una patología incapacitante que afecta la calidad de vida de las personas, hay una mayor tendencia a tratarla por métodos quirúrgicos que con rehabilitación. La lesión fundamental es el desprendimiento del labrum anterior de la glenoides conocida como la lesión de Bankart-Perthes, estructura que tiene limitaciones para cicatrizar de manera anatómica con tratamientos incruentos, perpetuando la inestabilidad. A medida que recurre la luxación se presentan lesiones óseas asociadas tanto en la glenoides denominada Bankart ósea, así como en la cabeza humeral en su región posterosuperior o lesión de Hill-Sachs, que aumentan la posibilidad de recurrencia. Se han descripto diferentes técnicas abiertas y artroscópicas para corregir la luxación, pero por la heterogeneidad de la lesión no hay un tratamiento para corregirla que sea patrón de oro. Nuestro objetivo es describir los resultados clínicos en pacientes con luxación recurrente anteroinferior de hombro que fueron sometidos a cirugía artroscópica de reparación de Bankart/plicatura y remplissage y correlacionar los resultados con la escala preoperatoria de ISIS. Materiales y métodos: se revisaron las historias clínicas de pacientes con diagnóstico de luxación de la articulación del hombro (S430) (M253), que fueron llevados a cirugía entre junio de 2015 y enero de 2019, analizando características de la(s) lesión(es), clasificación preoperatoria de acuerdo con la escala de ISIS, tipo de procedimiento(s) quirúrgico realizado y número de implantes. Resultados: de veinticinco pacientes operados por el autor senior (MMA) de luxación recurrente de hombro, veintitrés completaron el seguimiento con los procedimientos de reparación de Bankart/plicatura y la adición de un remplissage en casos de lesiones Hill-Sachs enganchantes. Todos tenían una escala de ISIS preoperatoria igual o inferior a 6. Al final del seguimiento ningún paciente reportó recurrencia de su luxación. Conclusión: en nuestra casuística, la reparación de Bankart/plicatura en pacientes con lesiones Hill-Sachs no enganchantes en asocio del remplissage produce excelentes resultados a corto y mediano plazo cuando la escala de ISIS es igual o inferior a 6. Nivel de evidencia: IV

Introduction: Recurrent anteroinferior shoulder dislocation is the consequence of an acute traumatic dislocation which, in young patients, under twenty years old, has been estimated to reach 97% of recurrence, but which decreases with increasing age, except in older patients with associated rotator cuff tears. Being a disabling pathology that affects people's quality of life, there is a greater tendency to treat it by surgical methods than with rehabilitation. The fundamental lesion is the detachment of the anterior labrum of the glenoid known as the Bankart-Perthes lesion, a structure that has limitations to heal anatomically with bloodless treatments, perpetuating instability. As the dislocation recurs, there are associated bone lesions both in the glenoid called Bony Bankart, as well as in the humeral head in its posterior superior region or Hill-Sachs lesion, which increase the possibility of recurrence. Different open and arthroscopic techniques have been described to correct dislocation, but due to the heterogeneity of the lesion, there is no gold standard treatment to correct it. Our objective is to describe the clinical results in patients with recurrent anteroinferior shoulder dislocation who underwent arthroscopic Bankart/plication repair and fill surgery and correlate the results with the preoperative ISIS scale. Materials and methods: the medical records of patients with a diagnosis of shoulder joint dislocation (S430) (M253), who were taken to surgery between June 2015 and January 2019, were reviewed, analyzing characteristics of the injury(s), classification preoperative according to the ISIS scale, type of surgical procedure(s) performed and number of implants. Results: of twenty-five patients operated by the senior author (MMA) for recurrent shoulder dislocation, twenty-three completed follow-up with Bankart/plication repair procedures and the addition of a fill in Hill-Sachs engaging lesions. All had a preoperative ISIS scale equal to or less than 6. At the end of follow-up, no patient reported recurrence of their dislocation.Conclusion: in our casuistry, Bankart/plication repair in patients with non-engaging Hill-Sachs lesions in association with filling produces excellent results in the short and medium term when the ISIS scale is equal to or less than 6. Level of Evidence: IV

Controversies in acute multiligamentary knee injuries (MLKI).

Multiligament injuries of the knee (MLKI), remain an infrequent pathology especially in developed countries compared to mono-ligament lesions. In Colombia, MLKI is frequent due to the high accident rate on motorcycles. In the city of Bogota alone, about 160 motorcycle accidents have been estimated daily, being one of the cities that proportionately use this means of transport less compared to small cities. The term MLKI, include all ruptures of two or more major ligaments and therefore it has a broad spectrum of clinical presentation which creates a great challenge for the orthopedists and the surgeons envolved in this topic. The literature is rich in studies level IV but very poor in level I and level II, which generates controversies and little consensus in the diagnosis and treatment of this pathology. However there has been a gradual and better understanding of all factors involved in the treatment of MLKI that has improved the functional results of these knees in our patients, in fact we currently are more precise to achieve accurate diagnosis, evolved from not surgical approach to operate most, applying new anatomical and biomechanical concepts, with specialized and skill surgical techniques with more stable and biocompatible fixation implants, which allow in most cases to initiate an early integral rehabilitation program. Nevertheless due to the complexity and severity of the lesions, in some patients the functional results are poor. The goal of this revision is to identify the most frequent controversies in the diagnosis and treatment of MLKI, defining which of them are agreed according to what is reported in the literature and share some concepts based from the experience of more than 25 years of the senior author (MM) in the management of these injuries. LEVEL OF EVIDENCE: V - Expert Opinion.

Broad Antiviral Activity of Ginkgolic Acid against Chikungunya, Mayaro, Una, and Zika Viruses.

The alphaviruses Chikungunya (CHIKV), Mayaro (MAYV), Una (UNAV), and the flavivirus Zika (ZIKV) are emerging or re-emerging arboviruses which are responsible for frequent epidemic outbreaks. Despite the large impact of these arboviruses on health systems, there are no approved vaccines or treatments to fight these infections. As a consequence, there is an urgent need to discover new antiviral drugs. Natural products are a rich source of compounds with distinct biological activities, including antiviral properties. Thus, we aimed to explore the potential antiviral activity of Ginkgolic acid against the arboviruses CHIKV, MAYV, UNAV, and ZIKV. Viral progeny production in supernatants from cells treated or not treated with Ginkgolic acid was quantified by plaque-forming assay. Ginkgolic acid's direct virucidal activity against these arboviruses was also determined. Additionally, viral protein expression was assessed using Western blot and immunofluorescence. Our results reveal that Ginkgolic acid promotes a dose-dependent decrease in viral titers in all tested viruses. Moreover, the compound demonstrated strong virucidal activity. Finally, we found that viral protein expression was affected by treatment with this drug. Collectively, these findings suggest that Ginkgolic acid could have broader antiviral activity.

A Functional Ubiquitin-Proteasome System is Required for Efficient Replication of New World Mayaro and Una Alphaviruses.

Mayaro (MAYV) and Una (UNAV) are emerging arboviruses belonging to the Alphavirus genus of the Togaviridae family. These viruses can produce febrile disease with symptoms such as fever, headache, myalgia, skin rash and incapacitating poly-arthralgia. Serological studies indicate that both viruses are circulating in different countries in Latin America. Viruses need the host cell machinery and resources to replicate effectively. One strategy to find new antivirals consists of identifying key cellular pathways or factors that are essential for virus replication. In this study, we analyzed the role of the ubiquitin-proteasome system (UPS) in MAYV and UNAV replication. Vero-E6 or HeLa cells were treated with the proteasome inhibitors MG132 or Lactacystin, and viral progeny production was quantified using a plaque assay method. In addition, the synthesis of viral proteins was analyzed by Western blot and confocal microscopy. Our results indicate that treatment with proteasome inhibitors decreases MAYV and UNAV protein synthesis, and also causes a significant dose-dependent decrease in MAYV and UNAV replication. Proteasome activity seems to be important at the early stages of MAYV replication. These findings suggest that the ubiquitin-proteasome system is a possible pharmacological target to inhibit these neglected alphaviruses.

A checklist of the helminth parasites of sympatric rodents from two Mayan villages in Yucatán, México.

In this survey, 19 species of helminths including Cestoda (Davaineidae, Hymenolepididae, and Taeniidae), Acanthocephala (Oligacanthorhynchidae), and Nematoda (Trichuridae, Ornithostrongylidae, Heligmonellidae, Oxyuridae, and Gongylonematidae) from Rattus rattus, Mus musculus, Sigmodon toltecus, Heteromys gaumeri, and Peromyscus yucatanicus in two Mayan villages in Yucatán, México, were recorded. Ten species of helminths were collected in both localities. The highest species richness was recorded in R. rattus from Xkalakdzonot (6 taxa). Twelve species are new records for Yucatán and two are registered for the first time in México. This survey constitutes the first checklist of helminth parasites in small rodents in the south-southeast of México.

[Extensively drug-resistant tuberculosis (XDR-TB): successful therapies used in the clinic to the disease]. / Tuberculosis extensamente resistente a antibióticos (TB-XDR): terapias utilizadas con éxito en la clínica para curar la enfermedad.

Mycobacterial species have practically evolved along humankind, sometimes provoking serious diseases. Among them, tuberculosis (TB), produced by M. tuberculosiscomplex bacteria, is historically the single most devastating infectious agent. Like many other microorganisms, M. tuberculosis resistant to antibiotics have risen as a consequence of selective pressure for mutants able to persist despite being attacked with drugs that would otherwise erradicate them from the infected person. Given the current long-term (6-9 months) therapy with multiple antibiotics, many people abandon their treatments, therefore promoting that bacteria that were not eliminated during therapy get exposed to suboptimal antibiotic concentrations, probably leading to mutations and drug resistance. In this scenario, extremely-drug resistant (XDR) TB was recognized not more than a decade ago, prompting concerns for a more complicated drug regimen with few available molecules. In recent years, either old antibiotics have been rediscovered as good measures to control XDR-TB, or new ones have emerged as alternatives to cure patients of this type of infection. In this work we aim to provide the medical community in Mexico with information of such drug regimens that have succesfully worked, in order to get their consideration for use in our country.

The synthetic cathelicidin HHC-10 inhibits Mycobacterium bovis BCG in vitro and in C57BL/6 mice.

Tuberculosis causes close to 1.5 million deaths in the world, with new cases exceeding 9 million in recent years. Coinfection with HIV further worsens the global situation. New molecules that overcome the limitations of currently used drugs are needed. We aimed to determine whether HHC-10 is active against the Mycobacterium tuberculosis complex bacteria Mycobacterium bovis bacille calmette guerin (BCG) in vitro and in vivo. For this, HHC-10 was tested in vitro using different peptide concentrations, and in vivo, in C57BL/6 mice infected intratracheally, at two doses (1.25 and 2.5 mg kg(-1), once a week, 4 weeks). Interferon (IFN)-γ, TNF-α, interleukin (IL)-4, and IL-10 mRNA transcript levels were compared between treated and nontreated mice. In vitro, HHC-10 decreased 69% and 88% the number of colony-forming units (CFU) per millileter recovered after 24-hr treatment at 50 and 100 µg/ml, respectively. In vivo, BCG CFUs in mouse lungs were reduced 77.8% and 95.8% at 1.25 and 2.5 mg kg(-1), respectively. IFN-γ expression was lower in the HHC-10-treated group than that of nontreated animals. Considering genomic conservation between BCG and M. tuberculosis, the in vitro and in vivo activities of HHC-10 observed in this study suggest that the use of this peptide may be useful as therapeutic agent against tuberculosis.