Design and validation of a preliminary instrument to contextualize interactions through information technologies of health professionals.

The communication of e-Health has been transformed with the advancement of information technologies, therefore it is feasible to carry out studies in the context of health professionals' interactions. Objective: This study aimed to design and validate a preliminary questionnaire to investigate the context of the communications of health professionals through information technologies considering three significant dimensions. Method: The stages provided by Hernández Sampieri guided the building, validation through Cronbach's alpha and factorial analysis. The questionnaire was applied to 43 participants who simulated health professionals. Results: We obtained an instrument that includes a demographic data section and 20 items distributed into three factors. Internal consistency reliability with Cronbach's alpha values generally of 0.848 and higher than 0.811 was obtained in each dimension. Kaiser-Meyer-Olkin's measure of sampling adequacy was regular, with 0.781, and Bartlett's test of sphericity was significant (p < 0.001). Conclusion: It is necessary to apply in real-world environments to reaffirm the results obtained.

A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. METHODS: A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. RESULTS: Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P = .7), social eating (P = .8), xerostomia (P = .9)]. CONCLUSION: In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.

Feasibility of complex exercise therapy with Standing Ovation and peripheral neuromodulation for gait rehabilitation after incomplete spinal cord injury-a case report.

BACKGROUND: Spinal cord injuries (SCIs) are a global concern, annually affecting hundreds of thousands of individuals. Among these cases, incomplete SCIs, allowing some muscle activity below the injury, pose unique challenges. This case study focuses on a 55-year-old male with a moderate incomplete SCI (AIS-D). CASE PRESENTATION: After initial treatments and pharmaceutical antispastic therapy, a novel intervention was introduced featuring the Standing Ovation gait exercise system (Standing Ovation GmbH, Hallwang, Austria). This individually tailored system, equipped with a rail system and seat-lifting unit, provided a secure environment for balance training. Over 14 training sessions spanning from October 13, 2021, to March 23, 2022, improvements in functional walking were observed. DISCUSSION AND CONCLUSION: Locomotor improvement in SCI rehabilitation is important; the potential of task-specific gait exercises with the Standing Ovation system in incomplete spinal cord injury seems to be a promising approach. Although promising, these findings call for further systematic studies with larger patient cohorts to strengthen their reliability. Ongoing research endeavors are essential to fully understand the benefits and limitations of this intervention in spinal cord injury rehabilitation.

The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through the activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by the binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here, we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analyzed the levels of the EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express the EGFR and found that EGFR-expressing cells responded to the EGF ligand by increasing ODZ1 at the mRNA and protein levels. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway, or Additionally, the siRNA-mediated knockdown of MAPK11 (p38ß MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signaling pathway through p38ß MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Evidence of the protective role of Carvacrol in a retinal degeneration animal model.

Neurodegenerative pathologies affecting the posterior segment of the eye, are characterized by being devastating and responsible for the majority of visual dysfunctions worldwide. These diseases are primarily degenerative, progressing chronically, and can inflict gradual harm to the optic nerve, retinal ganglion cells (RGC), photoreceptors, and other retinal cells. This retinal damage leads to a progressive loss of vision, marking these conditions as a significant health concern worldwide. The intravitreal administration of the phytochemical Carvacrol (CAR) is expected to demonstrate a neuroprotective and antiapoptotic effect on retinal cells, with a specific focus on RGC. This effect will be observed in a retinal degeneration model (RDM) in rabbits induced by cytotoxic and oxidative agents, namely glutamate (GLUT) and L-buthionine-S, R-sulfoximine (BSO). An in vivo study was conducted using New Zealand rabbits in which retinal damage was created to evaluate the effectiveness of CAR. The effectiveness of CAR on the functionality of retinal neuronal cells in RDM was evaluated using pupillary light reflection (PLR). Furthermore, the phytotherapeutic's influence on cell viability was determined through flow cytometry analysis. Finally, the neuroprotective and antiapoptotic capabilities of CAR were specifically scrutinized in RGC through histological studies, quantifying cell survival, and employing immunohistochemical assays to detect the apoptotic index (%) using the TUNEL technique. Our results demonstrated that CAR promoted the recovery of the pupillary contraction profile over time, maintaining the functionality of retinal cells as healthy controls. Additionally, it showed increased cell viability under oxidative and cytotoxic conditions given by GLUT-BSO agents. Finally, we found that CAR protects the survival of RGC and decreases the percentage of apoptotic cells when compared to RDM. CAR demonstrated to have positive effects on the functionality of photoreceptive nerve cells by restoring pupillary contraction. Likewise, it was shown to have neuroprotective and antiapoptotic effects when evaluated in a general and specific way on retinal nerve cells.

Improved motif-scaffolding with SE(3) flow matching.

Protein design often begins with knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds for a diverse range of motifs. However, the generated scaffolds tend to lack structural diversity, which can hinder success in wet-lab validation. In this work, we extend FrameFlow, an SE(3) flow matching model for protein backbone generation, to perform motif-scaffolding with two complementary approaches. The first is motif amortization, in which FrameFlow is trained with the motif as input using a data augmentation strategy. The second is motif guidance, which performs scaffolding using an estimate of the conditional score from FrameFlow, and requires no additional training. Both approaches achieve an equivalent or higher success rate than previous state-of-the-art methods, with 2.5 times more structurally diverse scaffolds. Code: https://github.com/microsoft/frame-flow.

Dermoscopic Evaluation of Actinic Changes in the Lips of Indigenous Children Living at High Altitude in Ecuador: A Descriptive Study.

BACKGROUND High altitude increases sunlight exposure, resulting in actinic keratosis, which predisposes people to skin cancer. The dermoscopy procedure evaluates keratotic and pigmented skin changes. This study aimed to describe the clinical and dermoscopic actinic changes in the lips of 25 indigenous children living at high altitude in Ecuador. MATERIAL AND METHODS An observational study was conducted in a public school in the Andes region of Ecuador (August-November 2019). Twenty-five children, males and females, age 5-15 years were assessed by complete physical examination, digital dermoscopic photographs, and punch biopsies. Descriptive statistics and Fisher's exact test were used to summarize and analyze the data. RESULTS We included 17 (68%) boys and 8 (32%) girls with a mean age of 9.8±2.0 years. Clinical lips findings reported desquamation [52% Upper Lip (UL); 40% Lower Lip (LL)], fissuring (8% UL; 8% LL), scabs (8% UL; 8% LL), and discoloration (40% UL; 20% LL). Dermoscopic features included a white-yellow lip color (24% UL; p=0.02). The main morphologic pattern of blood vessels was monomorphic (88% UL; p<0.001), polymorphous (60% LL; p<0.001), dotted pattern (64% UL; 28% LL; p=0.02), and linear-irregular (32% UL; 72% LL; p=0.01). Girls had radiating white structures on UL (p=0.025), while boys presented white structureless areas (UL 63.6%; LL 77.8%; p=0.032). No differences in dermoscopic findings were observed according to Fitzpatrick scale score (FSS). Punch biopsies showed no indications of actinic cheilitis. CONCLUSIONS Dermoscopic features in indigenous children living in high altitudes were related to actinic damage, but histopathological findings were negative.

Comparison of wound surface area measurements obtained using clinically validated artificial intelligence-based technology versus manual methods and the effect of measurement method on debridement code reimbursement cost.

BACKGROUND: Evidence shows that ongoing accurate wound assessments using valid and reliable measurement methods is essential to effective wound monitoring and better wound care management. Relying on subjective interpretation in measuring wound dimensions and assuming a rectilinear shape of all wounds renders an inconsistent and inaccurate wound area measurement. OBJECTIVE: The authors investigated the discrepancy in wound area measurements using a DWMS versus TPR methods and compared debridement codes submitted for reimbursement by assessment method. METHODS: The width and length of 177 wounds in 56 patients were measured at an outpatient clinic in the United States using the TPR method (width × length formula) and a DWMS (traced wound dimensions). The maximal allowable payment for debridement was calculated for both methods using the reported CPT codes based on each 20-cm2 estimated surface area. RESULTS: The average wound surface area was significantly higher with the TPR method than with the DWMS (20.20 and 12.81, respectively; P = .025). For patients with dark skin tones, ill-defined wound edges, irregular wound shapes, unhealthy tissues, and the presence of necrotic tissues, the use of the DWMS resulted in significantly lower mean differences in wound area measurements of 14.4 cm2 (P < .008), 8.2 cm2 (P = .040), 6.8 cm2 (P = .045), 13.1 cm2 (P = .036), and 7.6 cm2 (P = .043), respectively, compared with the TPR method. Use of the DWMS for wound surface area measurement resulted in a 10.6% lower reimbursement amount for debridement, with 82 fewer submitted codes, compared with the TPR method. CONCLUSIONS: Compared with the DWMS, TPR measurements overestimated wound area more than 36.6%. This overestimation was associated with dark skin tones and wounds with irregular edges, irregular shapes, and necrotic tissue.

Extracting medicinal chemistry intuition via preference machine learning.

The lead optimization process in drug discovery campaigns is an arduous endeavour where the input of many medicinal chemists is weighed in order to reach a desired molecular property profile. Building the expertise to successfully drive such projects collaboratively is a very time-consuming process that typically spans many years within a chemist's career. In this work we aim to replicate this process by applying artificial intelligence learning-to-rank techniques on feedback that was obtained from 35 chemists at Novartis over the course of several months. We exemplify the usefulness of the learned proxies in routine tasks such as compound prioritization, motif rationalization, and biased de novo drug design. Annotated response data is provided, and developed models and code made available through a permissive open-source license.

The Molecular Role of Polyamines in Age-Related Diseases: An Update.

Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging.

Chiranthodendron pentadactylon Larreat (Sterculiaceae), a Potential Nephroprotector against Oxidative Damage Provoked by STZ-Induced Hyperglycemia in Rats.

BACKGROUND: Chiranthodendron pentadactylon, known in Mexico as the "tree of the little hands", flower's infusion is used to treat kidney failure associated with diseases such as diabetes. The aim of this work is to evaluate the antioxidant effect of the methanolic extract of its flowers on oxidative damage in kidneys caused by streptozotocin in rats. METHODS: The extract phytochemical profile was performed with HPLC. Antioxidant potential in vitro was determined with DPPH and total phenolic tests; antioxidant evaluation in vivo was performed in diabetic rats administered daily via the intragastric route (100 and 200 mg/kg) for 6 weeks; serum glucose/creatinine, food/water consumption, and urinary volume were measured. Relative weight, protein/DNA ratios and oxidative stress were measured in renal tissue. RESULTS: The extract showed 20.53% of total phenolic content and IC50 of 18.05 µg/mL in DPPH, and this was associated with ferulic acid, phloretin and α-amyrin. Both doses showed a moderate decrease in the protein/DNA ratio in renal tissue, and the same behavior was observed for total urinary protein loss and serum creatinine, while the best antioxidant effect was exerted by a lower dose, which increased catalase activity and decreased lipid peroxidation in the kidneys. CONCLUSIONS: Results demonstrated that C. pentadactylon methanolic flower's extract improves renal function through antioxidant mechanisms during experimental diabetes.

Analysis of correlation of pre-therapeutic assessment and the final diagnosis in endometrial cancer: role of tumor volume in the magnetic resonance imaging.

Objective: To evaluate whether the introduction of tumor volume as new parameter in the MRI assessment could improve both concordance between preoperative and postoperative staging, and the identification of histological findings. Methods: A retrospective observational study with 127 patients with endometrial cancer (EC) identified between 2016 and 2021 at the Juan Ramon Jimenez University Hospital, Huelva (Spain) was carried out. Tumor volume was measured in three ways. Analyses of Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) were performed. Results: Although preoperative MRI had an 89.6% and 66.7% sensitivity for the detection of deep mucosal invasion and cervical stroma infiltration, preoperative assessment had an intraclass correlation coefficient of 0.517, underestimating tumor final stage in 12.6% of cases, with a poor agreement between preoperative MRI and postoperative staging (κ=0.082) and low sensitivity (14.3%) for serosa infiltration. The cut-off values for all three volume parameters had good/excellent AUC (0.73-0.85), with high sensitivity (70-83%) and specificity (64-84%) values for all histopathological variables. Excellent/good agreement was found all volume parameters for the identification of deep myometrial invasion (0.71), cervical stroma infiltration (0.80), serosa infiltration (0.81), and lymph node metastases (0.81). Conclusion: Tumor volume measurements have good predictive capacity to detect histopathological findings that affect final tumor staging and might play a crucial role in the preoperative assessment of patients with endometrial cancer in the future.

Developmental Toxicity Study of DL-4-Hydroxy-4-Phenylhexanamide (DL-HEPB) in Rats.

Antiepileptic drugs affect embryonic development when administered during pregnancy, generating severe alterations, such as as cleft lip, spina bifida, heart abnormalities, or neuronal alterations. The compound DL-4-hydroxy-4-phenylhexanamide (DL-HEPB), a phenyl alcohol amide structurally different from known anticonvulsants, has shown good anticonvulsant effects in previous studies. However, its effects on intrauterine development are unknown. So, the purpose of this study was to determine the potential of DL-HEPB to produce alterations in conceptus. Pregnant Wistar rats were orally exposed to 0, 50, 100, and 200 mg/kg of DL-HEPB during organogenesis, and their food consumption and weight gain were measured. On gestation day 21, pregnant females were euthanized to analyze the fetuses for external, visceral, and skeletal malformations. A significant decrease in food consumption and body weight was observed in mothers, without any other manifestation of toxicity. In fetuses, no external malformations, visceral, or skeletal abnormalities, were observed under the dose of 100 mg/kg, while the dose of 200 mg/kg caused malformations in low frequency in brain and kidneys. In view of the results obtained, DL-HEPB could be a good starting point for the design of new highly effective anticonvulsant agents, with much lower developmental toxicity than that shown by commercial anticonvulsants.

Detection of Plasmid-Mediated Resistance against Colistin in Multi-Drug-Resistant Gram-Negative Bacilli Isolated from a Tertiary Hospital.

The aim of this study was to determine the prevalence of plasmid-mediated colistin resistance mcr-1 to mcr-5 genes among colistin and multi-drug-resistant Gram-negative bacilli strains isolated from patients in a tertiary hospital in Toluca, Mexico. The presence of mcr genes among the 241 strains collected was assessed by PCR. In the case of mcr-carrying E. coli, further PCR tests were performed to determine the presence of blaCTX-M and whether the strains belonged to the O25b-ST131 clone. Conjugation experiments were also carried out to assess the horizontal transmission of colistin resistance. A total of twelve strains (5.0%), of which four were E. coli; four were P. aeruginosa; three were K. pneumoniae, and one E. cloacae, were found to be resistant to colistin. Of these strains, two E. coli isolates were found to carry mcr-1, and Southern blot hybridization demonstrated its presence on an approximately 60 kb plasmid. Both mcr-1-carrying E. coli strains were found to co-express blaCTX-M, belong to the O25b-ST131 clone, and horizontally transmit their colistin resistance. The results of this study confirm the presence of plasmid-mediated colistin resistance in hospitalized patients in Mexico and demonstrated that the multi-drug-resistant O25b-ST131 E. coli clone can acquire mcr genes and transmit such resistance traits to other bacteria.

Values of tumor volume on magnetic resonance imaging for a surgical approach to endometrial cancer.

OBJECTIVE: To analyze the relationship between tumor volume in Endometrial Cancer (EC) on Magnetic Resonance Imaging (MRI) and lymph node metastasis to establish which patients benefit from omitting the lymphadenectomy. METHODS: A retrospective observational study with 194 patients with EC identified between 2016 and 2021 at the Juan Ramón Jiménez University Hospital, Huelva (Spain) was carried out. Preoperative MRI of 127 patients was assessed. The tumor volume was analyzed on MRI by the ellipsoid formula and another alternative method with a manual ROI in different sections. Risk factors for node metastases were analyzed to understand its relationship and to identify an optimum criterion for the tailored surgery. RESULTS: Univariate analysis showed risk factors for lymph node metastases were histological grade (p = 0.001), tumor with a volume greater than >25 cm3 (p < 0.001), lymphovascular space invaded (p = 0.007), and preoperative Ca 125 serum >28 (p < 0.001). Multivariate analysis indicated that tumor volume index >25 cm3 was an independent risk factor for lymph node metastases. The patients without significant proposed risk factors (volume index >25 cm3  [OR = 0.64], Ca 125 > 28 [OR = 0.32], and high histological grade [OR = 2.6]) did not present lymph node metastases, independent of myometrial invasion. CONCLUSIONS: Lymphadenectomy can be omitted in patients with Endometrioid carcinoma that do not have any of the following risk factors: high-grade tumor, elevated Ca 125 (>28), and tumor volume on MRI greater than 25 cm3 . Tumor volume might predict the state of lymph nodes in EC and it could give information regarding surgical management.

Use of Artificial Vision during the Lye Treatment of Sevillian-Style Green Olives to Determine the Optimal Time for Terminating the Cooking Process.

This study focuses on characterizing the temporal evolution of the surface affected by industrial treatment with NaOH within the processing tanks during the lye treatment stage of Manzanilla table olives. The lye treatment process is affected by multiple variables, such as ambient temperature, the initial temperature of the olives before lye treatment, the temperature of the NaOH solution, the concentration of the solution, the variety of olives, and their size, which are determinants of the speed of the lye treatment process. Traditionally, an expert, relaying on their subjective judgement, manages the cooking process empirically, leading to variability in the termination timing of the cook. In this study, we introduce a system that, by using an artificial vision system, allows us to know in a deterministic way the percentage of lye treatment achieved at each moment along the cooking process; furthermore, with an interpolator that accumulates values during the lye treatment, it is possible to anticipate the completion of the cooking by indicating the moment when two-thirds, three-fourths, or some other value of the interior surface will be reached with an error of less than 10% relative to the optimal moment. Knowing this moment is crucial for proper processing, as it will affect subsequent stages of the manufacturing process and the quality of the final product.