Therapeutic Exercise Intervention Using Vibration Platforms for Glycemic Control in Type 2 Diabetes: A Pilot Study.

Diabetes generates a great impact on society, as well as a concern for health professionals due to its high and increasing prevalence; there are several studies that demonstrate the effectiveness of vibration platforms and their benefits at a physiological level. The aim of this study will be to analyze the decrease in glycosylated hemoglobin and glycemia levels after the use of whole-body vibration platforms and the possible inclusion of this therapeutic option within the usual treatments. This is a double-blind, randomized controlled trial with parallel group design in a 1:1 ratio. The sample will be composed of people diagnosed with type 2 diabetes mellitus in in the Plasencia area (Cáceres, Extremadura). Participants will be randomly assigned to the intervention or control group using a randomization list and will follow the inclusion criteria: type 2 diabetics between 50 and 60 years of age and not taking diabetes medication. All participants will undergo a determination of glycosylated hemoglobin, blood pressure, lipid profile, weight and height, and different functional tests such as Time Up and Go, 10 Meters Walk Test, and 5 Sit To Stand. The experimental group will perform a whole-body vibration intervention on an oscillating platform for 12 weeks with a weekly frequency of three nonconsecutive days and a duration of 12 min. The exercises will consist of 60 s of work and 60 s with rest. The control group will carry out their normal life insisting on the importance of glycemic controls before and after their daily physical exercise. This study has been registered at clinical.trial.org, ID: NCT05968222. Whole-body vibration platforms have demonstrated their effectiveness in different pathologies such as stroke, fibromyalgia, sclerosis multiple, or Parkinson's. For that reason, an improvement in glycemic and lipid values and body composition are expected in people with diabetes after a whole-body vibration intervention for 12 weeks' duration. In addition, whole-body vibration platforms could be postulated as an alternative to usual treatments.

Deficiency of the Arabidopsis mismatch repair MSH6 attenuates Pseudomonas syringae invasion.

The MutS homolog 6 (MSH6) is a nuclear DNA mismatch repair (MMR) gene that encodes the MSH6 protein. MSH6 interacts with MSH2 to form the MutSα heterodimer. MutSα corrects DNA mismatches and unpaired nucleotides arising during DNA replication, deamination of 5-methylcytosine, and recombination between non-identical DNA sequences. In addition to correcting DNA biosynthetic errors, MutSα also recognizes chemically damaged DNA bases. Here, we show that inactivation of MSH6 affects the basal susceptibility of Arabidopsis thaliana to Pseudomonas syringae pv tomato DC3000. The msh6 T-DNA insertional mutant exhibited a reduced susceptibility to the bacterial invasion. This heightened basal resistance of msh6 mutants appears to be dependent on an increased stomatal closure, an accumulation of H2O2 and double-strand breaks (DSBs) and a constitutive expression of pathogenesis-related (NPR1 and PR1) and DNA damage response (RAD51D and SOG1) genes. Complementation of this mutant with the MSH6 wild type allele under the control of its own promoter resulted in reversal of the basal bacterial resistance phenotype and the stomatal closure back to wild type levels. Taken together, these results demonstrate that inactivation of MSH6 increases Arabidopsis basal susceptibility to the bacterial pathogen and suggests a link between DNA repair and stress signaling in plants.

Quality of Life and Side Effects Management in Cancer Treatment-A Cross Sectional Study.

Cancer disease is a world problem which is increasing in its prevalence. Oncology patients have a multitude of symptoms derived from the treatments and from the disease itself that affect their quality of life to a greater or lesser extent. The aim of this study has been to discover the physical and psychological symptoms related to chemotherapy treatment in Spanish cancer patients in order to improve their quality of life. Symptoms from the previous week were taken into account and the Memorial Symptom Assessment Scale was used to measure the frequency, severity and associated distress of 32 symptoms. A total of 246 chemotherapy patients at the University Day Hospital in Salamanca completed the scale once while receiving chemotherapy treatment. A 95% confidence interval was considered. The most prevalent symptoms were a lack of energy (76.4%), anxiety (66.7%) and a dry mouth (60.6%). Lung cancer was the most prevalent cancer in men (26%) and breast cancer was the most prevalent cancer in women (72%). There is no consensus on which is the most prevalent symptom in this population and more studies will need to be carried out to determine the best treatment protocols. Symptom's prevalence knowledge could improve the patients' care to prevent or avoid complications and to improve the cancer patients' quality of life.

Validation of the Spanish Versions of FACIT-PAL and FACIT-PAL-14 in Palliative Patients.

Palliative patients require several types of care to improve their quality of life as much as possible, and valid and reliable assessment instruments are essential. The objective of this study is the Spanish validation of the Functional Assessment Chronic Illness Therapy-Palliative Care (FACIT-PAL) and its abbreviated version, FACIT-PAL-14, in palliative care patients. FACIT-PAL and FACIT-PAL-14 were translated into Spanish and administered to 131 terminal oncology patients in home palliative care units, hospital palliative care units, health center teams, and social health centers. The European Organization for Research and Treatment of Cancer questionnaire, EORTC-QLQ-C15-PAL version, was used to evaluate the criterion validity. The EORTC-QLQ-C15-PAL was employed as a "gold standard", and it obtained significant results with FACIT scales. FACIT-PAL-14, FACIT-PAL, and its subscales reported high internal consistency, from 0.640 to 0.816. The exploratory factor analysis for FACIT-PAL-14 found a structure in three factors that explained the 70.10% variance, and the FACIT-PAL scale found a structure of five factors. Physical wellbeing from FACIT-PAL highly correlated to the EORTC-QLQ-C15-PAL (r = 0.700), but social and family wellbeing was correlated to a lesser extent (r = -0.323). FACIT-PAL and the TOI (Toi Outcome Index) were also highly correlated with the EORTC-QLQ-C15-PAL, with values of r = -0.708 and r = -0.709, respectively. The Spanish versions of FACIT-PAL and FACIT-PAL-14 were demonstrated to be valid and reliable scales in palliative care patients.

Robotic Systems for the Physiotherapy Treatment of Children with Cerebral Palsy: A Systematic Review.

Cerebral palsy is a neurological condition that is associated with multiple motor alterations and dysfunctions in children. Robotic systems are new devices that are becoming increasingly popular as a part of the treatment for cerebral palsy. A systematic review of the Pubmed, Web of Science, MEDLINE, Cochrane, Dialnet, CINAHL, Scopus, Lilacs and PEDro databases from November 2021 to February 2022 was conducted to prove the effectiveness of these devices for the treatment of motor dysfunctions in children who were diagnosed with cerebral palsy. Randomized clinical trials in Spanish and English were included. In total, 653 potential manuscripts were selected but only 7 of them met the inclusion criteria. Motor dysfunctions in the lower limbs and those that are specifically related to gait are the main parameters that are affected by cerebral palsy and the robotic systems Lokomat, Innowalk, Robogait and Waltbox-K are the most commonly used. There is no consensus about the effectiveness of these devices. However, it seems clear that they have presented a good complement to conventional physical therapies, although not a therapy as themselves. Unfortunately, the low quality of some of the randomized clinical trials that were reviewed made it difficult to establish conclusive results. More studies are needed to prove and test the extent to which these devices aid in the treatment of children with cerebral palsy.

Symptom Prevalence in Spanish and Colombian Oncology Patients Measured with the MSAS.

Cancer patients experience several symptoms throughout their illness and the treatments they receive. While this pathology represents a worldwide health problem, knowing the symptom prevalence in oncology patients remains a challenge; validated tools to obtain this information are essential. Furthermore, this prevalence information would help health professionals to establish appropriate treatments. The objective of this study was to ascertain the symptom prevalence in cancer patients from Spain and Colombia to improve future approaches. The frequency, severity, and distress of 32 symptoms from a validated scale experienced by cancer patients from Spain and Colombia were measured. Two hundred and forty-six patients (49.7%) who attended the Day University Hospital of Salamanca (Spain) and two hundred and forty-nine outpatients (50.3%) of the San Diego Cancer Center (Colombia) between 2016 and 2019 participated in the study. All patients filled in the Assessment Scale only once. Four hundred and ninety-five patients (333 women (67.3%) and 162 men (32.7%)) completed the Memorial Symptom Assessment Scale (Spanish version). The most frequent symptom for both samples (Spanish and Colombian) was "lack of energy" (38.4% and 13.7%, respectively). The most severe symptoms for the Spanish and Colombian samples were "problems with sexual interest or activity" (38.4%) and "dry mouth" (13.7%), respectively, and both samples agreed on the most distressing symptom: "hair loss" (Spanish, 38%; Colombian, 10.1%). The Spanish version of the MSAS has proven to be a valid and reliable tool in Spanish-speaking countries to obtain the most prevalent, severe, and distressing symptoms in Spanish and Colombian oncology patients. The prevalence of symptoms was demonstrated to be similar across both countries, and the results will help to design and adapt treatments for cancer patients, targeting these symptoms to reduce or avoid them and thus improving their quality of life.

ROR2 increases the chemoresistance of melanoma by regulating p53 and Bcl2-family proteins via ERK hyperactivation.

BACKGROUND: ROR2 is a tyrosine-kinase receptor whose expression is dysregulated in many human diseases. In cancer, ROR2 stimulates proliferation, survival, migration, and metastasis, and is associated with more aggressive tumor stages. The purpose of this work is to study the role of ROR2 in the chemoresistance of melanoma. METHODS: Gain- and loss-of-function experiments were used to study the biological function of ROR2 in melanoma. Cell death induced by chemotherapeutic drugs and BH-3 mimetics was evaluated using crystal violet cytotoxicity assays and annexin V/propidium iodide staining. Western blots were used to evaluate the expression of proteins implicated in cell death. The differences observed between cells with manipulation of ROR2 levels and control cells were evaluated using both Student's t-test and ANOVA. RESULTS: We describe that ROR2 contributes to tumor progression by enhancing the resistance of melanoma cells to both chemotherapeutic drugs and BH-3 mimetics. We demonstrate that ROR2 reduced cell death upon treatment with cisplatin, dacarbazine, lomustine, camptothecin, paclitaxel, ABT-737, TW-37, and venetoclax. This effect was mediated by the inhibition of apoptosis. In addition, we investigated the molecular mechanisms implicated in this role of ROR2. We identified the MDM2/p53 pathway as a novel target of ROR2 since ROR2 positively regulates MDM2 levels, thus leading to p53 downregulation. We also showed that ROR2 also upregulates Mcl-1 and Bcl2-xL while it negatively regulates Bax and Bid expression. The effect of ROR2 on the expression of these proteins is mediated by the hyperactivation of ERK. CONCLUSIONS: These results demonstrate that ROR2 contributes to melanoma progression by inhibiting apoptosis and increasing chemoresistance. These results not only position ROR2 as a marker of chemoresistance but also support its use as a novel therapeutic target in cancer.

Construct Validity of the Spanish Versions of the Memorial Symptom Assessment Scale Short Form and Condensed Form: Rasch Analysis of Responses in Oncology Outpatients.

CONTEXT: The Memorial Symptom Assessment Scale (MSAS) is a self-rating instrument for the assessment of symptom distress in cancer patients. The Spanish version of the MSAS has recently been validated. However, we lack evidence of the internal construct validity of the shorter versions (short form [MSAS-SF] and condensed form [CMSAS]). In addition, rigorous testing of these scales with modern psychometric methods is needed. OBJECTIVES: The aim of this study was to evaluate the internal construct validity and reliability of the Spanish versions of the MSAS-SF and CMSAS in oncology outpatients using Rasch analysis. METHODS: Data from a convenience sample of oncology outpatients receiving chemotherapy (n = 306; mean age 60 years; 63% women) at a university hospital were analyzed. The Rasch unidimensional measurement model was used to examine response category functioning, item hierarchy, targeting, unidimensionality, reliability, and differential item functioning by age, gender, and marital status. RESULTS: The response category structure of the symptom distress items was improved by collapsing two categories. The scales were adequately targeted to the study patients, showed overall Rasch model fit (mean Infit MnSq ranged from 0.98 to 1.05), met criteria for unidimensionality, and the reliability of scores was good (person reliability > 0.80), except for the CMSAS prevalence scale. Only four items showed differential item functioning. CONCLUSION: The present study demonstrated that the Spanish versions of the MSAS-SF and CMSAS have adequate psychometric properties to evaluate symptom distress in oncology outpatients. Additional studies of the CMSAS are recommended.

Human serum albumin nanoparticles for ocular delivery of bevacizumab.

Bevacizumab-loaded nanoparticles (B-NP) were prepared by a desolvation process followed by freeze-drying, without any chemical, physical or enzymatic cross-linkage. Compared with typical HSA nanoparticles cross-linked with glutaraldehyde (B-NP-GLU), B-NP displayed a significantly higher mean size (310 nm vs. 180 nm) and a lower negative zeta potential (-15 mV vs. -36 mV). On the contrary, B-NP displayed a high payload of approximately 13% when measured by a specific ELISA, whereas B-NP-GLU presented a very low bevacizumab loading (0.1 µg/mg). These results could be related to the inactivation of bevacizumab after reacting with glutaraldehyde. From B-NP, bevacizumab was released following an initial burst effect, proceeded by a continuous release of bevacizumab at a rate of 6 µg/h. Cytotoxicity studies in ARPE cells were carried out at a single dose up to 72 h and with repeated doses over a 5-day period. Neither bevacizumab nor B-NP altered cell viability even when repeated doses were used. Finally, B-NP were labeled with 99mTc and administered as eye drops in rats. 99mTc-B-NP remained in the eye for at least 4 h while 99mTc-HSA was rapidly drained from the administration point. In summary, HSA nanoparticles may be an appropriate candidate for ocular delivery of bevacizumab.

Reliability and Validity of the Spanish Version of the Memorial Symptom Assessment Scale in Oncology Patients.

CONTEXT: Memorial Symptom Assessment Scale (MSAS) is a multidimensional tool developed to evaluate frequency, severity, and distress of common symptoms present in cancer patients. OBJECTIVE: To translate the original English version of MSAS and prove the reliability and validity of the Spanish version. METHODS: MSAS scale was translated into Spanish and administered to 246 cancer patients aged between 18 and 85 years. They attended the Day Hospital to receive chemotherapy. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Rotterdam Symptom Checklist were used to test criterion validity. RESULTS: TOTAL MSAS, Physical Symptom Subscale (PHYS), Psychological Symptom Subscale (PSYCH), and Global Distress Index (GDI) reported high internal consistency: 0.891, 0.801, 0.825, 0.813, respectively. Exploratory factor analysis identified two-factors structure and confirmatory factor analysis showed good adjustment rates. The emotional functioning subscale of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 highly correlated with PSYCH (r = -0.868; P < 0.001) and GDI (r = -0.810; P < 0.001), whereas social functioning subscale correlated with PSYCH (r = -0.704; P < 0.001) and GDI (r = -0.624; P < 0.001). The PHYS of Rotterdam Symptom Checklist correlated with PHYS (r = 0.876; P < 0.001) and the PSYCH with PSYCH (r = 0.872; P < 0.001). CONCLUSION: The Spanish version of MSAS was determined to be a valid and reliable scale in cancer patients.

Linear and cyclic dipeptides with antimalarial activity.

Several natural and synthetic polypeptides possess important antimalarial activity. Shorter peptides with potent antimalarial activity have also been described, among them linear di-, tri-, tetra- and pentapeptides and their cyclic analogs. In an attempt to find dipeptides with antimalarial activities we show that linear and cyclic dipeptides, the latter known as diketopiperazines, still retain the fundamental core to preserve antimalarial activity. Thirteen linear dipeptides and ten diketopiperazines were investigated. Eight linear dipeptides showed IC(50) values between 2.78 and 7.07 µM, while eight diketopiperazines were also active with IC(50) values between 2.26 and 4.26 µM on Plasmodium berghei schizont cultures.

Antimalarial activity of ultra-short peptides.

Ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. On the basis of the IC(50) data for these compounds, the effects of nature, polarity, and amino acid sequence on Plasmodium berghei schizont cultures were analyzed too. Tetrapeptides Phe-Orn-Phe-Orn (4) and Lys-Phe-Phe-Orn (5) showed a very important activity with IC(50) values of 3.31 and 2.57 microM, respectively. These two tetrapeptides are candidates for subsequent in vivo assays and SARS investigations.

Expression pattern of XBP1(S) in human B-cell lymphomas.

The transcription factor XBP1 (X-box-binding protein 1) is essential for plasma cell (PC) differentiation and immunoglobulin secretion. XBP1 is widely expressed, but its activity is precisely controlled by mRNA splicing in response to endoplasmic reticulum (ER) stress. It is the active form of XBP1, XBP1(S), which is required for PC differentiation. The relationship between XBP1(S) expression and PC differentiation in human tissue and its expression in hematologic malignancies has eluded assessment. With a novel antibody, we now define XBP1(S) expression in a large series of normal and neoplastic lymphoid tissues. We establish that XBP1(S) provides a specific marker of advanced plasma differentiation and in lymphoid malignancies is restricted to PC-derived neoplasms and plasmablastic diffuse large B-cell lymphomas. XBP1(S) expression delineates heterogeneity amongst plasmablastic diffuse large B-cell lymphomas, identifying a distinct tumor sub-group. Furthermore, our results establish a direct and practical means of assessing ER stress in human tumors.

Perfil clínico de las infecciones de piel y tejido celular subcutáneo en el Hospital Nacional Cayetano Heredia 1994-1999 / Clinic profile of skin and soft tissue infections in the National Hospital Cayetano Heredia 1994-1999

Las infecciones de piel y tejido celular subcutáneo (IPSC) son entidades observadas frecuentemente en los servicios de atención médica, cuyo diagnóstico y tratamiento se basa en las caratcterísticas de las lesiones y el grado de compromiso de los tejidos. Estas infecciones incluyen una amplia variedad de presentaciones clínicas importantes de reconocer para su adecuado manejo. OBJETIVOS: Describir las características clínicas y epidemiológicas de las IPSC en un grupo de pacientes en el Hospital Nacional Cayetano Heredia (HNCH) entre 1994 y 1999. PACIENTES Y METODOS: Se condujo un estudio descriptivo de tipo transversal y retrospectivo por revisión de los registros de 82 pacientes adultos con IPSC reclutados en cuatro ensayos clínicos en el HNCH entre 1994 y 1999. RESULTADOS: Se incluyeron 82 pacientes evaluados por IPSC. La edad y el tiempo de enfermedad promedio fueron treinta y siete años y cuatro días respectivamente. 43,9 por ciento refirió un antecedente contributorio, específicamente un traumatismo en 41,6 por ciento de ellos. El 100 por ciento de los pacientes presentó dolor a la palpación y eritema. El diagnóstico de celulitis fue el más frecuente (63 por ciento), localizándose mayormente en miembros inferiores (p<0,01), el tiempo de enfermedad más corto correspondió a erisipela (p=0,03). La piodermitis se presentó más frecuentemente en varones (p=0,01). CONCLUSIONES: En menos del 50 por ciento de pacientes con IPSC se asociaron antecedentes contributorios, en todos se evidenció dolor y eritema. La celulitis fue la IPSC, encontrada con mayor frecuencia.

Síndrome de secresión inapropiada de hormona a antidiurética: implicancias clínicas / Syndrome of secresion inappropiate of antidiuretic hormone: clinical implicate

El síndrome de secresión inapropiada de hormona antidiurética (SIADH) fue descubierto en 1957 y se le describió como un síndrome clínico caracterizado por hiponatremia, hiposmolaridad plasmática, pérdida renal de sodio y orina hiperosmolar con relación al plasma; asociado a diversas neoplasias, enfermedades infecciosas pulmonares y lesiones neurológicas. Por alta prevalencia del SIADH en pacientes de riesgo y el mal estado general la sintomatología de este síndrome podría ser atribuida a la enfermedad de fondo, no administrando el tratamiento adecuado y aumentando así la morbilidad de los pacientes. Se realiza una revisión de los criterios diagnósticos, los factores etiológicos, las manifestaciones clínicas, las diversas teorías que explican la fisiopatología del síndrome, el diagnóstico diferencial con otros tipos de hiponatremia y finalmente, el tratamiento sugerido.