Parkinson's disease patients show delayed hemodynamic changes in primary motor cortex in fine motor tasks and decreased resting-state interhemispheric functional connectivity: a functional near-infrared spectroscopy study.

Significance: People with Parkinson's disease (PD) experience changes in fine motor skills, which is viewed as one of the hallmark signs of this disease. Due to its non-invasive nature and portability, functional near-infrared spectroscopy (fNIRS) is a promising tool for assessing changes related to fine motor skills. Aim: We aim to compare activation patterns in the primary motor cortex using fNIRS, comparing volunteers with PD and sex- and age-matched control participants during a fine motor task and walking. Moreover, inter and intrahemispheric functional connectivity (FC) was investigated during the resting state. Approach: We used fNIRS to measure the hemodynamic changes in the primary motor cortex elicited by a finger-tapping task in 20 PD patients and 20 controls matched for age, sex, education, and body mass index. In addition, a two-minute walking task was carried out. Resting-state FC was also assessed. Results: Patients with PD showed delayed hypoactivation in the motor cortex during the fine motor task with the dominant hand and delayed hyperactivation with the non-dominant hand. The findings also revealed significant correlations among various measures of hemodynamic activity in the motor cortex using fNIRS and different cognitive and clinical variables. There were no significant differences between patients with PD and controls during the walking task. However, there were significant differences in interhemispheric connectivity between PD patients and control participants, with a statistically significant decrease in PD patients compared with control participants. Conclusions: Decreased interhemispheric FC and delayed activity in the primary motor cortex elicited by a fine motor task may one day serve as one of the many potential neuroimaging biomarkers for diagnosing PD.

Diagnostic reliability in teledermatology: a systematic review and a meta-analysis.

OBJECTIVES: To compare teledermatology and face-to-face (F2F) agreement in primary diagnoses of dermatological conditions. DESIGN: Systematic review and meta-analysis METHODS: MEDLINE, Embase, Cochrane Library (Wiley), CINAHL and medRxiv were searched between January 2010 and May 2022. Observational studies and randomised clinical trials that reported percentage agreement or kappa concordance for primary diagnoses between teledermatology and F2F physicians were included. Titles, abstracts and full-text articles were screened in duplicate. From 7173 citations, 44 articles were included. A random-effects meta-analysis was conducted to estimate pooled estimates. Primary outcome measures were mean percentage and kappa concordance for assessing diagnostic matches between teledermatology and F2F physicians. Secondary outcome measures included the agreement between teledermatologists, F2F dermatologists, and teledermatology and histopathology results. RESULTS: 44 studies were extracted and reviewed. The pooled agreement rate was 68.9%, and kappa concordance was 0.67. When dermatologists conducted F2F and teledermatology consults, the overall diagnostic agreement was significantly higher at 71% compared with 44% for non-specialists. Kappa concordance was 0.69 for teledermatologist versus specialist and 0.52 for non-specialists. Higher diagnostic agreements were also noted with image acquisition training and digital photography. The agreement rate was 76.4% between teledermatologists, 82.4% between F2F physicians and 55.7% between teledermatology and histopathology. CONCLUSIONS AND RELEVANCE: Teledermatology can be an attractive option particularly in resource-poor settings. Future efforts should be placed on incorporating image acquisition training and access to high-quality imaging technologies. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/FJDVG.

Factors predicting recurrence in thymic epithelial neoplasms.

OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a heterogeneous group of rare thoracic malignancies. We analysed the clinicopathological features, survival outcomes, risk factors, and patterns of recurrence in patients undergoing resection. METHODS: Records were reviewed for adult patients with TEN who underwent resection from 2006 to 2019. Survival rates were assessed using the Kaplan-Meier method. Univariable and multivariable analyses were performed using the log-rank test and Cox proportional hazards model. RESULTS: A total of 100 patients were analysed (51 females, median age 58 years). Thymoma was the most common histology (n = 92), followed by thymic carcinoma (n = 5) and thymic neuroendocrine tumour (n = 3). Stage II (Masaoka) tumours were most common (n = 51), followed by stage I (n = 27). World Health Organization B2/B3 was the most prominent histological subtype (n = 34). Complete resection (R0) was achieved in 91 patients: 86/92 thymoma, 4/5 thymic carcinoma and 1/3 neuroendocrine tumour. The most common treatment modality was surgery alone in 72 patients, followed by surgery and radiation therapy in 24, and adjuvant chemoradiotherapy in 3 patients. Only one patient with thymic carcinoma received neoadjuvant chemotherapy. The 10-year overall and disease-free survival rates were 86.6% and 83.9%, respectively. Recurrence was most common in neuroendocrine tumours (3/3). Risk factors for recurrence identified on multivariable analyses were: R1/2 resection (hazard ratio 9.30; 95% confidence interval 1.82-36.1), TEN subtype (hazard ratio 8.08; 95% confidence interval 1.24-34.6), and presence of lymphovascular invasion (hazard ratio 9.56; 95% confidence interval 2.56-25.8). CONCLUSIONS: Complete resection remains critical in patients with TEN. Incomplete resection, high-risk histology, and lymphovascular invasion highlight the need for effective adjuvant modalities. Given the rarity of these diseases, emphasis must be placed on collaborative research conducted on TEN.

Fully Automated Wound Tissue Segmentation Using Deep Learning on Mobile Devices: Cohort Study.

BACKGROUND: Composition of tissue types within a wound is a useful indicator of its healing progression. Tissue composition is clinically used in wound healing tools (eg, Bates-Jensen Wound Assessment Tool) to assess risk and recommend treatment. However, wound tissue identification and the estimation of their relative composition is highly subjective. Consequently, incorrect assessments could be reported, leading to downstream impacts including inappropriate dressing selection, failure to identify wounds at risk of not healing, or failure to make appropriate referrals to specialists. OBJECTIVE: This study aimed to measure inter- and intrarater variability in manual tissue segmentation and quantification among a cohort of wound care clinicians and determine if an objective assessment of tissue types (ie, size and amount) can be achieved using deep neural networks. METHODS: A data set of 58 anonymized wound images of various types of chronic wounds from Swift Medical's Wound Database was used to conduct the inter- and intrarater agreement study. The data set was split into 3 subsets with 50% overlap between subsets to measure intrarater agreement. In this study, 4 different tissue types (epithelial, granulation, slough, and eschar) within the wound bed were independently labeled by the 5 wound clinicians at 1-week intervals using a browser-based image annotation tool. In addition, 2 deep convolutional neural network architectures were developed for wound segmentation and tissue segmentation and were used in sequence in the workflow. These models were trained using 465,187 and 17,000 image-label pairs, respectively. This is the largest and most diverse reported data set used for training deep learning models for wound and wound tissue segmentation. The resulting models offer robust performance in diverse imaging conditions, are unbiased toward skin tones, and could execute in near real time on mobile devices. RESULTS: A poor to moderate interrater agreement in identifying tissue types in chronic wound images was reported. A very poor Krippendorff α value of .014 for interrater variability when identifying epithelization was observed, whereas granulation was most consistently identified by the clinicians. The intrarater intraclass correlation (3,1), however, indicates that raters were relatively consistent when labeling the same image multiple times over a period. Our deep learning models achieved a mean intersection over union of 0.8644 and 0.7192 for wound and tissue segmentation, respectively. A cohort of wound clinicians, by consensus, rated 91% (53/58) of the tissue segmentation results to be between fair and good in terms of tissue identification and segmentation quality. CONCLUSIONS: The interrater agreement study validates that clinicians exhibit considerable variability when identifying and visually estimating wound tissue proportion. The proposed deep learning technique provides objective tissue identification and measurements to assist clinicians in documenting the wound more accurately and could have a significant impact on wound care when deployed at scale.

A 57-Year-Old Man with Type 1 Diabetes Mellitus and a Chronic Foot Ulcer Successfully Managed with a Remote Patient-Facing Wound Care Smartphone Application.

BACKGROUND Wounds affect millions of people world-wide, with care being costly and difficult to deliver remotely. The ongoing COVID-19 pandemic highlights the urgent need for telehealth solutions to play a larger role as part of remote care strategies for patient monitoring and care. We describe our findings on the use of a patient-facing wound care app (Swift Patient Connect App, Swift Medical, Canada) as an innovative solution in remote wound assessment and management of a diabetic patient's wound. CASE REPORT In February 2020, a 57-year-old man with type I diabetes and peripheral arterial disease presented with osteomyelitis in the left foot at the fifth metatarsal, arising from a chronic ulcer. The wound was deep, with purulent discharge and polymicrobial growth. A 6-week course of intravenous antibiotics was administered, with slow improvement of the wound. At a follow-up appointment in June 2020, The Patient Connect app was recommended to the patient to securely share calibrated images of his wound as well to communicate with his doctor. Between June 2020 and January 2021, wound closure was accurately monitored as part of the management of this diabetic foot infection. The app was also used in the management of 2 subsequent wounds and infection episodes. CONCLUSIONS Use of the Swift Patient Connect App designed to monitor and manage wounds by a patient with diabetes and foot ulcer as part of a remote care strategy resulted in numerous benefits expressed by the patient. After initial adoption, 3 successive wounds were managed with a combination of in-person and telehealth visits complemented by the app. Incorporation of this technology as part of a novel telemedicine strategy promises to have an extensive impact on remote care delivery during the current COVID-19 pandemic and beyond.

Differences in platelet-rich plasma composition influence bone healing.

AIM: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. MATERIALS AND METHODS: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. RESULTS: Double-spin L-PRP contained higher concentrations of platelets than single-spin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3 ) compared to single-spin L-PRP (1.42 ± 0.27 mm3 ) or filtered L-PRP (1.38 ± 0.28 mm3 ). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. CONCLUSION: The preparation method of L-PRP affects their composition and potential to regenerate bone.

A Composite Lactide-Mineral 3D-Printed Scaffold for Bone Repair and Regeneration.

Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes. However, these may have drawbacks as well, including stress shielding, pseudarthrosis, disease-transmission, and infection. There is therefore a need for alternative bone substitutes, such as the use of mechanically compliant three-dimensional (3D)-printed scaffolds. Several off-the-shelf materials are available for low-cost fused deposition 3D printing such as polylactic acid (PLA) and polycaprolactone (PCL). We have previously described the feasibility of 3D-printed PLA scaffolds to support cell activity and extracellular matrix deposition. In this study, we investigate two medical-grade filaments consistent with specifications found in American Society for Testing and Materials (ASTM) standard for semi-crystalline polylactide polymers for surgical implants, a pure polymer (100M) and a copolymeric material (7415) for their cytocompatibility and suitability in bone tissue engineering. Moreover, we assessed the impact on osteo-inductive properties with the addition of beta-tricalcium phosphate (ß-TCP) minerals and assessed their mechanical properties. 100M and 7415 scaffolds with the additive ß-TCP demonstrated superior mesenchymal stem cells (MSCs) differentiation detected via increased alkaline phosphatase activity (6-fold and 1.5-fold, respectively) and mineralized matrix deposition (14-fold and 5-fold, respectively) in vitro. Furthermore, we evaluated in vivo compatibility, biosafety and bone repair potential in a rat femur window defect model. 100M+ß -TCP implants displayed a positive biosafety profile and showed significantly enhanced new bone formation compared to 100M implants evidenced by µCT (39 versus 25% bone volume/tissue volume ratio) and histological analysis 6 weeks post-implantation. These scaffolds are encouraging composite biomaterials for repairing bone applications with a great potential for clinical translation. Further analyses are required with appropriate evaluation in a larger critical-sized defect animal model with long-term follow-up.

The effect of aging on the bone healing properties of blood plasma.

OBJECTIVES: Age-related changes in blood composition have been found to affect overall health. Thus, this study aimed to understand the effect of these changes on bone healing by assessing how plasma derived from young and old rats affect bone healing using a rat model. METHODS: . Blood plasma was collected from 6-month and 24-month old rats. Differences in elemental composition and metabolome were assessed using optical emission spectrometry and liquid mass spectrometry, respectively. Bilateral tibial bone defects were created in eight rats. Young plasma was randomly applied to one defect, while aged plasma was applied to the contralateral one. Rats were euthanized after two weeks, and their tibiae were analyzed using micro-CT and histology. The proteome of bone marrow was analyzed in an additional group of three rats. RESULTS: Bone-defects treated with aged-plasma were significantly bigger in size and presented lower bone volume/tissue volume compared to defects treated with young-plasma. Histomorphometric analysis showed fewer mast cells, macrophages, and lymphocytes in defects treated with old versus young plasma. The proteome analysis showed that young plasma upregulated pathways required for bone healing (e.g. RUNX2, platelet signaling, and crosslinking of collagen fibrils) whereas old plasma upregulated pathways, involved in disease and inflammation (e.g. IL-7, IL-15, IL-20, and GM-CSF signaling). Plasma derived from old rats presented higher concentrations of iron, phosphorous, and nucleotide metabolites as well as lower concentrations of platelets, citric acid cycle, and pentose phosphate pathway metabolites compared to plasma derived from young rats. CONCLUSION: bone defects treated with plasma-derived from young rats showed better healing compared to defects treated with plasma-derived from old rats. The application of young and old plasmas has different effects on the proteome of bone defects.

A Compassionate Communities Approach in a Grief and Bereavement Support Program: Bridging the Gap in Palliative Care.

Grief and bereavement support is a fundamental component of palliative care, yet there is a gap in practice as not all palliative care services offer it. The compassionate communities (CC) approach aims to build community capacity to address grief as grief support is considered everyone's responsibility. This study describes the characteristics, development, growth and attendees of a grief support program that uses a CC approach to bridge the gap of grief support in palliative care.

Bone extracts immunomodulate and enhance the regenerative performance of dicalcium phosphates bioceramics.

Immunomodulation strategies are believed to improve the integration and clinical performance of synthetic bone substitutes. One potential approach is the modification of biomaterial surface chemistry to mimic bone extracellular matrix (ECM). In this sense, we hypothesized that coating synthetic dicalcium phosphate (DCP) bioceramics with bone ECM proteins would modulate the host immune reactions and improve their regenerative performance. To test this, we evaluated the in vitro proteomic surface interactions and the in vivo performance of ECM-coated bioceramic scaffolds. Our results demonstrated that coating DCP scaffolds with bone extracts, specifically those containing calcium-binding proteins, dramatically modulated their interaction with plasma proteins in vitro, especially those relating to the innate immune response. In vivo, we observed an attenuated inflammatory response against the bioceramic scaffolds and enhanced peri-scaffold new bone formation supported by the increased osteoblastogenesis and reduced osteoclastogenesis. Furthermore, the bone extract rich in calcium-binding proteins can be 3D-printed to produce customized hydrogels with improved regeneration capabilities. In summary, bone extracts containing calcium-binding proteins can enhance the integration of synthetic biomaterials and improve their ability to regenerate bone probably by modulating the host immune reaction. This finding helps understand how bone allografts regenerate bone and opens the door for new advances in tissue engineering and bone regeneration. STATEMENT OF SIGNIFICANCE: Foreign-body reaction is an important determinant of in vivo biomaterial integration, as an undesired host immune response can compromise the performance of an implanted biomaterial. For this reason, applying immunomodulation strategies to enhance biomaterial engraftment is of great interest in the field of regenerative medicine. In this article, we illustrated that coating dicalcium phosphate bioceramic scaffolds with bone-ECM extracts, especially those rich in calcium-binding proteins, is a promising approach to improve their surface proteomic interactions and modulate the immune responses towards such biomaterials in a way that improves their bone regeneration performance. Collectively, the results of this study may provide a conceivable explanation for the mechanisms involved in presenting the excellent regenerative efficacy of natural bone grafts.

An educational intervention to implement skin-to-skin contact and early breastfeeding in a rural hospital in Mexico.

Background: Early skin-to-skin contact promotes infant physiologic stability, provides warmth and makes breast milk readily available. Despite the known benefits of early skin-to-skin contact, this practice is not included within standard care in the Mexican public healthcare system. After birth, newborns are usually taken to an incubator in the nursery where they transition to extrauterine life and receive either dextrose 5% or infant formula for their first feed. The aim of this study was to assess if a dual educational intervention in a rural hospital in Mexico could modify current practice and accomplish early skin-to-skin contact and early breastfeeding. Methods: A two-step educational intervention was designed. The first step was to educate the labor and birthing staff of the hospital, and the second step was to educate all pregnant women with uncomplicated pregnancies at 36 weeks' gestation. The educational intervention explored the benefits, implications and steps of early skin-to-skin contact and early breastfeeding. All births were registered for the three month period following the intervention. The time of onset of skin-to-skin (SSC) contact, its duration and time of initiation of breastfeeding were recorded and analyzed using ANOVA testing. Results: A total of 142 births met our inclusion criteria, from those, 77% (n = 109) received skin-to-skin contact and early breastfeeding. The average time of initiation of skin-to-skin contact in the first and last month of the study was 18.5 (± 2.2) and 9.6 (± 2.2) minutes of life, respectively (p < 0.001). The average duration of SSC in the first and last month was 22 (± 10.9) and 40.9 (± 17.4) minutes, respectively (p < 0.001). The average time of onset of breastfeeding in the first and last month was 48.9 (± 15) and 34.4 (± 16.7) minutes of life, respectively (p < 0.001). Conclusions: A simple and low-cost educational intervention achieved the inclusion of skin-to-skin contact and early breastfeeding as part of standard care in a rural hospital. Further studies could replicate our intervention in similar settings to test the generalizability of the findings.

Factors Associated With Knowledge and Comfort Providing Palliative Care: A Survey of Pediatricians in Mexico.

BACKGROUND:: Lack of education and training in palliative care has been described to be one of the most important barriers to pediatric palliative care implementation. OBJECTIVE:: To examine what factors determine the degree of knowledge and level of comfort Mexican pediatricians have providing pediatric palliative care. METHODS:: A questionnaire that assessed palliative care concepts was developed and applied online to Mexican pediatricians, both generalists and specialists. RESULTS:: A total of 242 pediatricians responded. The majority had not received palliative care education (92.6%) and felt uncomfortable discussing palliative needs with patients and families (92.1%). The mean score of the questionnaire was 6.8 (±1.4) of 10 correct answers. Knowledge in palliative care was associated with exposure to oncologic patients ( P = .01) and previous palliative care education ( P = .02) but inversely related to the pediatrician's age ( P = .01). Comfort addressing patient's palliative care needs was associated with knowledge in palliative care ( P < .01), exposure to oncologic patients ( P = .03), and previous education in palliative care ( P = .02). CONCLUSIONS:: Although Mexican pediatricians have basic knowledge of palliative care concepts, they do not feel comfortable addressing palliative care needs, suggesting that the main barrier for implementing palliative care is not the lack of knowledge but rather feeling uncomfortable when addressing these issues with patients and families. Educational programs should incorporate strategies that could help physicians develop comfort in approaching palliative care patients.

Noninvasive Localized Cold Therapy: A New Mode of Bone Repair Enhancement.

IMPACT STATEMENT: A variety of biological, mechanical, and physical therapeutic modalities of varying complexity, efficacy, cost, and safety profile have been developed to enhance bone healing. There have been sporadic reports of spontaneous bone formation after repeated cold exposure. In this study we report for the first time, the anabolic effect of cold exposure on bone healing in vivo resulting in a doubling of bone volume. Although the precise mechanism is not fully understood, cold is well known to stimulate osteoclastogenesis and modulate inflammation. The impact of this finding is considerable for tissue regeneration because cold application is noninvasive, safe, and easily implemented.

Development and validation of an algorithm to predict the treatment modality of burn wounds using thermographic scans: Prospective cohort study.

BACKGROUND: The clinical evaluation of a burn wound alone may not be adequate to predict the severity of the injury nor to guide clinical decision making. Infrared thermography provides information about soft tissue viability and has previously been used to assess burn depth. The objective of this study was to determine if temperature differences in burns assessed by infrared thermography could be used predict the treatment modality of either healing by re-epithelization, requiring skin grafts, or requiring amputations, and to validate the clinical predication algorithm in an independent cohort. METHODS AND FINDINGS: Temperature difference (ΔT) between injured and healthy skin were recorded within the first three days after injury in previously healthy burn patients. After discharge, the treatment modality was categorized as re-epithelization, skin graft or amputation. Potential confounding factors were assessed through multiple linear regression models, and a prediction algorithm based on the ΔT was developed using a predictive model using a recursive partitioning Random Forest machine learning algorithm. Finally, the prediction accuracy of the algorithm was compared in the development cohort and an independent validation cohort. Significant differences were found in the ΔT between treatment modality groups. The developed algorithm correctly predicts into which treatment category the patient will fall with 85.35% accuracy. Agreement between predicted and actual treatment for both cohorts was weighted kappa 90%. CONCLUSION: Infrared thermograms obtained at first contact with a wounded patient can be used to accurately predict the definitive treatment modality for burn patients. This method can be used to rationalize treatment and streamline early wound closure.

Comparison and agreement of outcome scores through nine months after acetabular fracture fixation.

INTRODUCTION: The Modified Merle d'Aubigne-Postel Score and the Harris Hip Score are commonly used to assess the functional outcomes after acetabular fractures. A previous report showed that correlation between scores is good, that there is poor concordance among functional classes, and that the distribution of the scores is highly asymmetrical. Several issues were not addressed in this report, mainly that the data set was treated as transversal data without comparison of scores through time; therefore the objective of this article is to assess the degree of correlation and concordance between the Modified Merle d'Aubigne-Postel Score and the Harris Hip Score during the first 9 months after acetabular fracture treatment. METHODS: Both scores were recorded in a cohort of 23 previously healthy patients after 3, 6 and 9 months after fixation of acetabular fractures. Through a mixed-effects repeated measures model, we assessed differences between standardized scores. Pearson's interclass correlation coefficients for full scores and each of their domains, as well as agreement for clinical graduation classification was calculated. RESULTS: Between score correlation was 89%. We found no differences between scores at 3, 6 and 9 month follow-ups. Agreement between scores was 0.95, while agreement for clinical graduation classification was 0.67. DISCUSSION: Very short term correlation and concordance between scores is excellent, while concordance for clinical graduation classification is modest. We suggest the widespread use of the simpler score.

Effects of Local Use of Insulin on Wound Healing in Non-diabetic Patients.

BACKGROUND: Clinical trials have shown the positive effects of local insulin therapy in the formation of new vessels and fibrosis in acute and chronic diabetic wounds without major adverse effects. OBJECTIVE: The aim of this study was to investigate the effects of local insulin use on wound healing in non-diabetic patients. METHODS: A randomized, split-plot, double-blind, placebo-controlled trial was conducted. Ten non-diabetic patients with full-thickness acute wounds were recruited (5 due to trauma, 3 to burns, and 2 to pressure). All wounds received standard bedside treatment. Each wound was divided into 2 zones. One side received a standard care plus insulin, while the other received standard care plus injection of saline solution. A biopsy specimen was taken from both sites on days 0 and 14. The amount of blood vessel growth and the percentage of fibrosis were evaluated. RESULTS: A significant difference in the number of new vessels was observed on the insulin-treated site (70.6 [29.21]) compared to saline only (26.5 [34.3]; P < .04). The percentage of fibrosis (insulin 34.7 [28.02] vs saline 27.8 [29.9]) showed no significant difference. No adverse events related to the study occurred. The clinical implications of this study are considerable in terms of the formation of blood vessels but not fibrosis. CONCLUSION: We suggest that local insulin administration is a safe therapeutic option for angiogenesis in wounds of non-diabetic patients.

HISTORIQUE: Les essais cliniques démontrent les effets positifs de l'insulinothérapie localisée pour former de nouveaux vaisseaux ou une fibrose en cas de plaies aiguës ou chroniques causées par le diabète, sans entraîner de réactions indésirables majeures. OBJECTIF: La présente étude visait à évaluer les effets de l'utilisation localisée d'insuline chez des patients non diabétiques. MÉTHODOLOGIE: Les chercheurs ont réalisé un essai aléatoire et contrôlé contre placebo, en parcelles divisées et à double insu. Ils ont recruté dix patients non diabétiques ayant des plaies aiguës de pleine épaisseur (cinq à cause d'un traumatisme, trois à cause de brûlures et deux à cause de pression). Toutes les plaies ont fait l'objet de soins standards au chevet du patient et chacune a été divisée en deux zones. Une zone faisait l'objet de soins standards avec l'ajout d'insuline et l'autre zone, de soins standards avec l'injection de soluté physiologique. Les chercheurs ont prélevé une biopsie dans chaque zone les jours 0 et 14. Ils ont évalué la croissance des vaisseaux sanguins et le pourcentage de fibrose. RÉSULTATS: Les chercheurs ont observé une différence significative dans le nombre de nouveaux vaisseaux de la zone traitée à l'insuline (70,6 ± 29,21) par rapport à celle traitée à l'aide de soluté physiologique (26,5 ± 34,3; P <0,04). Ils n'ont pas constaté de différence significative dans le pourcentage de fibrose (insuline 34,7 ± 28,02 et soluté physiologique 27,8 ± 29,9) ni de réactions indésirables liées à l'étude. Les conséquences cliniques de la présente étude sont considérables à l'égard de la formation de vaisseaux sanguins, mais pas de la fibrose. CONCLUSION: Selon les chercheurs, l'administration localisée d'insuline serait sécuritaire pour l'angiogenèse des plaies des patients non diabétiques.

Prevalence of Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase Genes of North Central Mexico HIV Isolates.

This study set out to determine the frequency of antiretroviral drug resistance mutations in treatment-naive subjects of the north central Mexican state of San Luis Potosí. Mexican studies of antiretroviral drug resistance mutations have focused mainly on large metropolitan areas and border towns subjected to intense international migrations. This study set forth to describe the frequency of these mutations in a Mexican region less subjected to such migratory influences and more representative of smaller Mexican cities. Thirty-eight full-length pol sequences spanning the protease, reverse-transcriptase, and integrase-encoding regions were obtained from 42 treatment-naive human immunodeficiency virus (HIV)-infected subjects. Most exhibited subtype B homology, but CRF02_AG was also detected. Evidence of APOBEC3 hypermutation was seen in two samples. Calibrated population analysis revealed a surveillance drug resistance mutation prevalence of 4.9% for protease inhibitors, of 2.7% for nucleoside reverse transcriptase inhibitors, of 8.1% for non-nucleoside reverse transcriptase inhibitors, and an overall prevalence of 9.5%. This corresponds to an intermediate level of transmitted drug resistance according to the World Health Organization. The identification of integrase mutations suggests that transmitted drug mutations are being imported, as inhibitors targeting integrase have not been widely used in Mexico. Our results provide a greater understanding of HIV diversity in Mexico and highlight the way internal migrations allow HIV mutations and genetic features to permeate regions less subjected to international migrations. The implications of these findings will become more evident as Mexico hosts increased repatriations of migrants in the coming years.

* Hypoxia Biomimicry to Enhance Monetite Bone Defect Repair.

Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors. This pilot study investigates the effect of local delivery of DFO on bone formation and osseointegration of an anatomically matched bone graft substitute, in the treatment of segmental bone defects. Three-dimensional printing was used to create monetite grafts, which were implanted into 10 mm midshaft ulnar defects in eight rabbits. Starting postoperative day 4, one graft site in each animal was injected with 600 µL (200 µM) of DFO every 48 h for six doses. Saline was injected in the contralateral limb as a control. At 8 weeks, micro-CT and histology were used to determine new bone growth, vascularity, and assess osseointegration. Six animals completed the protocol. Bone metric analysis using micro-CT showed a significantly greater amount of new bone formed (19.5% vs. 13.65% p = 0.042) and an increase in bone-implant contact area (63.1 mm2 vs. 33.2 mm2 p = 0.03) in the DFO group compared with control. Vascular channel volume was significantly greater in the DFO group (20.9% vs. 16.2% p = 0.004). Histology showed increased bone formation within the osteotomy gap, more bone integrated with the graft surface as well as more matured soft tissue callus in the DFO group. This study demonstrates a significant increase in new bone formation after delivery of DFO in a rabbit long bone defect bridged by a 3D-printed bioresorbable bone graft substitute. Given the safety, ease of handling, and low expense of this medication, the results of this study support further investigation into the use of iron chelators in creating a biomimetic environment for bone healing in segmental bone loss.

Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

Validación al español del Self-Harm Questionnaire para detección de autolesionismo en adolescentes / Validation into Spanish language of the Self-Harm Questionnaire for detection of self-harming in adolescents

ANTECEDENTES: El autolesionismo comprende las conductas encaminadas al daño físico de la propia persona. Estas conductas son un fenómeno en aumento entre los adolescentes y pueden ser consideradas como predictores de muerte por suicidio, por lo que su identificación oportuna es una necesidad. El Cuestionario de autolesionismo permite identificar la presencia de pensamientos y conductas autolesivas.OBJETIVO: Validar el cuestionario de autolesionismo al español y determinar su valor diagnóstico para detectar autolesionismo en adolescentes mexicanos que reciben atención psiquiátrica.MÉTODO: Se realizó el procedimiento de traducción-retrotraducción para la adaptación de la escala al idioma español. Se seleccionó una muestra de 106 adolescentes de entre 11 y 17 años de edad en seguimiento por trastornos afectivos o ansiedad para la aplicación de la escala. Se evaluó la consistencia interna mediante el coeficiente de fiabilidad a de Cronbach y se determinó el coeficiente de correlación de Spearman por medio de una prueba test-retest tres meses después de la primera administración. Posteriormente, se realizó una revisión del expediente clínico para determinar la presencia de autolesionismo y realizar un análisis de la sensibilidad y especificidad del cuestionario para detectar el fenómeno.RESULTADOS: El cuestionario traducido presentó un a de Cronbach de 0.960 y una estabilidad temporal a tres meses de 0.9787. La sensibilidad para detectar autolesionismo fue de 97.96%, y la especificidad de 54.39%, comparadas con el expediente clínico.DISCUSIÓN Y CONCLUSIÓN: Los resultados de este estudio sugieren que la escala traducida es una herramienta válida y confiable para detectar autolesionismo en adolescentes mexicanos. La identificación rápida y oportuna de esta población es crucial para evitar suicidios. El uso de la escala puede ayudar a identificar a estos pacientes.

BACKGROUND: Self-injurious behaviour englobes conducts in which persons hurt or harm themselves. These conducts are an increasing phenomena among adolescents, and can be considered as predictors of death by suicide, making their opportune identification a necessity. The Self Harm Questionnaireallows the identification of thoughts and self-injurious conducts.OBJECTIVE: The objective of this study was to validate it into the Spanish language and to determine its diagnostic value for detecting self- injurious behaviour in Mexican adolescents under psychiatric follow up.METHOD: The translation-retrotranslation procedure was used for the adaptation of the questionnaire into Spanish. A sample of 106, 11 to 17 year-old adolescents under follow up because of affective disorders or anxiety was selected for the application of the questionnaire. Internal consistence was evaluated through the Cronbach a reliability coefficient, and the Spearman correlation coefficient was determined through a test-retest after 3 months of the first administration of the probe. Afterwards, an evaluation of the clinical records was performed to assess the sensitivity and specificity of the test to detect self-injurious behaviour.RESULTS: The translated questionnaire possess a Cronbach a of 0.960, and a 3 month temporal stability of 0.9787. The sensitivity to detect self-injurious behaviour was 97.96%, and its specificity was 54.39%, compared to the clinical records.DISCUSSION AND CONCLUSION: This study results suggest that the translated questionnaire is a valid and reliable tool to detect self-injurious behaviour in Mexican adolescents. Rapid and opportune identification of this population of patients is crucial to avoid suicides. The use of this questionnaire can help identify these patients.