Effectiveness of Balance Rehabilitation Unit (BRU) Posturography Versus Conventional Rehabilitation in Patients With Unilateral Peripheral Vestibular Dysfunction.

BACKGROUND: Patients with unilateral peripheral vestibular deficit (UPVD) experience vertigo, dizziness, disability, negative influences on their quality of life, anxiety, and depression. In vestibular rehabilitation, virtual reality (VR) has proven to be effective. This investigation sought to evaluate the efficacy of the Balance Rehabilitation Unit (BRUTM) (MedicaaTM Montevideo, Uruguay, Balance Suite, version BRU 415) in patients with UPVD. METHODS: A prospective, randomized, controlled study involved 38 patients from the Otoneurologic Service at the National Institute of Rehabilitation "Luis Guillermo Ibarra Ibarra" in Mexico. A physician specialist diagnosed the patients with UPVD and assigned them randomly to one of two groups. Group 1 (n = 19) received traditional vestibular rehabilitation, whereas Group 2 (n = 19) received BRUTM-supported vestibular rehabilitation. Both groups were monitored by medical professionals. Patients were evaluated with the Dizziness Handicap Inventory, static and dynamic balance assessments, the dynamic gait index, and the sensory organization test. The statistical analysis was conducted using the Student's t-test, with p 0.05 considered statistically significant. RESULTS: The difference in mean age between the conventional therapy and BRUTM groups was not statistically significant. Both conventional vestibular rehabilitation and the BRUTM led to statistically significant improvements in all assessed parameters, with no statistically significant differences between the two groups. CONCLUSION: Balance, mobility, and quality of life were enhanced similarly in UPVD patients by BRUTM-supported vestibular rehabilitation and conventional vestibular rehabilitation. In addition, BRUTM facilitated patient motivation, exercise feedback, and confidence enhancement.

Combined Nutrition in Very-Low-Birth-Weight Preterm Infants in the Neonatal Intensive Care Unit.

Background Adequate nutritional support is crucial for achieving optimal growth and development in very-low-birth-weight (VLBW) preterm infants. This study evaluated the efficacy of combined nutrition (CN) (parenteral plus enteral nutrition (EN)) as an alternative nutrition protocol for VLBW infants in the neonatal intensive care unit (NICU). Methods This retrospective cohort study collected clinical and growth data from the medical records of VLBW infants weighing between 1,000 and 1,500 grams in the NICU of the Hospital of Obstetrics and Gynecology "Dr. Víctor Manuel Espinosa de los Reyes Sánchez" of the Centro Médico Nacional "La Raza" Instituto Mexicano del Seguro Social, Mexico. Parenteral nutrition (PN) alone or CN (PN plus EN) was used for nutritional management. Statistical tests, such as Student's t-test, Mann-Whitney U test, and chi-square test as appropriate, were used to compare the clinical characteristics and growth data of the two groups, and relative risk was calculated to determine the probability of comorbidities according to feeding type. Statistical significance was set at p<0.05. Results The study included 90 VLBW infants, with 27 receiving PN alone and 63 receiving CN. No statistically significant differences were found concerning sex, age, or Apgar score. The CN group showed better weight gain with statistically significant differences at 28 days (p=0.002), with no increase in the relative risk of necrotizing enterocolitis (NEC) or other complications. Conclusions The CN protocol met the caloric and nutritional needs, without increasing morbidity and mortality. The protocol had a positive impact on weight gain and a shorter NICU stay and should be considered as a nutritional alternative for VLBW infants.

Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator.

Cancer is a global public health problem that is related to different environmental and lifestyle factors. Although the combination of screening, prevention, and treatment of cancer has resulted in increased patient survival, conventional treatments sometimes have therapeutic limitations such as resistance to drugs or severe side effects. Oriental culture includes herbal medicine as a complementary therapy in combination with chemotherapy or radiotherapy. This study aimed to identify the bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach. The herb contains gallic acid, caffeic acid, coumaric acid, quercetin, quercitrin, isorhamnetin, kaempferol, bersaldegenin, bryophyllin a, bryophyllin c, bryophynol, bryophyllol and bryophollone, stigmasterol, campesterol, and other elements. Its phytochemicals participate in the regulation of proliferation, apoptosis, cell migration, angiogenesis, metastasis, oxidative stress, and autophagy. They have the potential to act as epigenetic drugs by reverting the acquired epigenetic changes associated with tumor resistance to therapy-such as the promoter methylation of suppressor genes, inhibition of DNMT1 and DNMT3b activity, and HDAC regulation-through methylation, thereby regulating the expression of genes involved in the PI3K/Akt/mTOR, Nrf2/Keap1, MEK/ERK, and Wnt/ß-catenin pathways. All of the data support the use of K. pinnata as an adjuvant in cancer treatment.

Linearolactone Induces Necrotic-like Death in Giardia intestinalis Trophozoites: Prediction of a Likely Target.

Linearolactone (LL) is a neo-clerodane type diterpene that has been shown to exert giardicidal effects; however, its mechanism of action is unknown. This work analyzes the cytotoxic effect of LL on Giardia intestinalis trophozoites and identifies proteins that could be targeted by this active natural product. Increasing concentrations of LL and albendazole (ABZ) were used as test and reference drugs, respectively. Cell cycle progression, determination of reactive oxygen species (ROS) and apoptosis/necrosis events were evaluated by flow cytometry (FCM). Ultrastructural alterations were analyzed by transmission electron microscopy (TEM). Ligand-protein docking analyses were carried out using the LL structure raised from a drug library and the crystal structure of an aldose reductase homologue (GdAldRed) from G. intestinalis. LL induced partial arrest at the S phase of trophozoite cell cycle without evidence of ROS production. LL induced pronecrotic death in addition to inducing ultrastructural alterations as changes in vacuole abundances, appearance of perinuclear and periplasmic spaces, and deposition of glycogen granules. On the other hand, the in silico study predicted that GdAldRed is a likely target of LL because it showed a favored change in Gibbs free energy for this complex.

Expanding the Study of the Cytotoxicity of Incomptines A and B against Leukemia Cells.

Heliangolide-type sesquiterpene lactones (HTSLs) are phytocompounds with several pharmacological activities including cytotoxic and antitumor activity. Both bioactivities are related to an α-methylene-γ-lactone moiety and an ester group on carbon C-8 in the sesquiterpene lactone (SL) structure. Two HTSLs, incomptines A (AI) and B (IB) isolated from Decachaeta incompta, were evaluated for their cytotoxic activity on three leukemia cell lines: HL-60, K-562, and REH cells. Both compounds were subjected to a molecular docking study using target proteins associated with cancer such as topoisomerase IIα, topoisomerase IIß, dihydrofolate reductase, methylenetetrahydrofolate dehydrogenase, and Bcl-2-related protein A1. Results show that IA and IB exhibit cytotoxic activity against all cell lines used. The CC50 value of IA was 2-4-fold less than etoposide and methotrexate, two anticancer drugs used as positive controls. The cytotoxic activity of IB was close to that of etoposide and methotrexate. The molecular docking analysis showed that IA and IB have important interaction on all targets used. These findings suggest that IA and IB may serve as scaffolds for the development of new treatments for different types of leukemia.

An insight into the promoter methylation of PHF20L1 and the gene association with metastasis in breast cancer.

BACKGROUND: Plant homeodomain finger protein 20-like 1 (PHF20L1) is a protein reader involved in epigenetic regulation that binds monomethyl-lysine. An oncogenic function has been attributed to PHF20L1 but its role in breast cancer (BC) is not clear. OBJECTIVES: To explore PHF20L1 promoter methylation and comprehensive bioinformatics analysis to improve understanding of the role of PHF20L1 in BC. MATERIAL AND METHODS: Seventy-four BC samples and 16 control samples were converted using sodium bisulfite treatment and analyzed with methylation-specific polymerase chain reaction (PCR). Bioinformatic analysis was performed in the BC dataset using The Cancer Genome Atlas (TCGA) trough data visualized and interpreted in the MEXPRESS website. Methylation, gene expression and survival evaluation were performed with R v. 4.0.2 software. Using multiple bioinformatic tools, we conducted a search for genes co-expressed with PHF20L1, analyzed its ontology and predicted associated miRNAs and miRNA-PHF20L1 networks. The expression and prognostic value of PHF20L1 and co-expressed genes were analyzed. RESULTS: We found demethylation in PHF20L1 promoter in both BC samples and healthy tissues. Data mining with 241 patients demonstrated changes in methylation of promoter regions in basal-like and luminal A subtypes. Expression of the PHF20L1 gene had a negative correlation with methylation. Twelve genes were co-expressed. PHF20L1 is a target of miR96-5p, miR9-5p and miR182-5p, which are involved in proliferation and metastasis. PHF20L1 gene expression was not associated with overall survival (OS), or relapse-free survival (RFS), but was associated with distant metastasis-free survival (DMFS). CONCLUSIONS: Our findings showed differences in methylation of PHF20L1 promoter region near TSS and upstream in BC subtypes; its overexpression impacted DMFS. We found that PHF20L1 is targeted by miR96-5p, miR9-5p and miR182-5p, which are involved in proliferation and metastasis, and regulates genes engaged in processes such as alternative splicing.

Pediatric pineal germinomas: Epigenetic and genomic approach.

OBJECTIVE: We identify and correlate chromosomal alterations, methylation patterns and gene expression in pediatric pineal germinomas. METHODS: CGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with MatLab software, MapViewer, DAVID, GeneCards and Hippie. RESULTS: Amplifications were found in 1q24.2, 1q31.3, 2p11.2, 3p22.2, 7p13, 7p15.2, 8p22, 12p13.2, 14q24.3 y 22q12; and deletions were found in 1q21.2, 9p24.1, 10q11.22, 11q11, 15q11.2 and 17q21.31. In the methylation analysis, we observed 10,428 CpG Islands with a modified methylation status that may affect 11,726 genes. We identified 1260 overexpressed genes and 470 underexpressed genes. The genes RUNDC3A, CDC247, CDCA7L, ASAH1, TRA2A, LPL and NPC2 were altered among the three levels. CONCLUSIONS: We identified the 1q24.2 and 1q31.3 amplified regions and the 1q21.3 and 11q11 deleted regions as the most important aims. The genes NPC2 and ASAH1 may play an important role in the development, progression and tumor maintenance. The ASAH1 gene is an ideal candidate to identify drug responses. These genomic and epigenetic studies may help to characterize the formation of pineal germ cell tumors to determine prognostic markers and also to identify shared characteristics in gonadal and extragonadal tumors.

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview.

The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.