Drug repositioning identifies histone deacetylase inhibitors that promote innate immunity in non-tuberculous mycobacterial infection.

Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.

Leadership and physiotherapy: A scoping review.

Questions: The challenges faced by healthcare organizations require effective leaders. Leadership has been extensively studied in medicine and nursing, but it is limited in physiotherapy. The objective of this study is to know and analyze the published research on the characteristics of leadership in physiotherapy. Design: A scoping review was conducted following the PRISMA extension guidelines. MEDLINE, The Cochrane Library, PEDro, Embase, CINAHL, Web Of Science and Scopus databases were reviewed between 01/01/2000 and 30/06/2022.All quantitative studies addressing the characteristics of leadership in physiotherapy were selected. Data extraction was performed using a table including author, year of publication, country of origin, title, objective, measurement instrument, sample and main findings. Data synthesis: The results obtained were framed within the framework for the study of leadership designed by Bolman and Deal. Results: Eight studies were selected. The characteristics most valued or used by physiotherapists are communication, desire for continuous learning and improvement, credibility and professionalism. Conclusion: Leadership is very important for physiotherapists, and for physiotherapy, as profession they consider it very important to have vision and to lead change. Communication skills are the most highly regarded characteristic.

Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis.

Deficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial. Here, we observe that the BRCA1/BARD1 ubiquitin E3 activity is not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identify substrates for BRCA1/BARD1. We find that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results provide additional insight about the importance of BRCA1/BARD1 E3 activity in Homologous Recombination.

Leadership and gender perspective in hospital physiotherapy units.

Analyze the gender stereotypes present in the leaders of the Hospital Physiotherapy Units, determine the level of acceptance of female leadership and identify which factors influence these perceptions. Observational, descriptive, exploratory and cross-sectional study. The study subjects are the census of leaders of the Physiotherapy Units of public hospitals. The measurement instruments used are the Acceptance of Female Leadership Questionnaire (ACT-LM), and the sociodemographic and job-related variables. Most of the leaders of the hospital physiotherapy units were women (69.4%) physiotherapists. Gender stereotypes emerge in the dimension of Instrumental Characteristics, with respondents not fully agreeing that women were sufficiently competitive (18.7%) or ambitious (20.8%) to be successful in the world of work. These data were influenced by gender, showing that men have a higher regard for female leadership abilities than women themselves. In the dimension of Acceptance of Female Leadership, 17.4% of those surveyed did not fully agree that women can rise to the same extent as men. Most of the leaders of the physiotherapy units in public hospitals in Spain are women, this is reversed in favor of men in highly complex hospitals. The stereotype persists, especially among women, that they do not have enough ambition and competitiveness to succeed in the world of work.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses.

Protein ubiquitylation regulates key biological processes including transcription. This is exemplified by the E3 ubiquitin ligase RNF12/RLIM, which controls developmental gene expression by ubiquitylating the REX1 transcription factor and is mutated in an X-linked intellectual disability disorder. However, the precise mechanisms by which ubiquitylation drives specific transcriptional responses are not known. Here, we show that RNF12 is recruited to specific genomic locations via a consensus sequence motif, which enables co-localisation with REX1 substrate at gene promoters. Surprisingly, RNF12 chromatin recruitment is achieved via a non-catalytic basic region and comprises a previously unappreciated N-terminal autoinhibitory mechanism. Furthermore, RNF12 chromatin targeting is critical for REX1 ubiquitylation and downstream RNF12-dependent gene regulation. Our results demonstrate a key role for chromatin in regulation of the RNF12-REX1 axis and provide insight into mechanisms by which protein ubiquitylation enables programming of gene expression.

Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice.

In female mice, the gene dosage from X chromosomes is adjusted by a process called X chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) that silences the paternally inherited X chromosome (Xp) is initiated at the 2- to 4-cell stages. As extraembryonic cells including trophoblasts keep the Xp silenced, epiblast cells that give rise to the embryo proper reactivate the Xp and undergo a random form of XCI (rXCI) around implantation. Both iXCI and rXCI require the lncRNA Xist, which is expressed from the X to be inactivated. The X-linked E3 ubiquitin ligase Rlim (Rnf12) in conjunction with its target protein Rex1 (Zfp42), a critical repressor of Xist, have emerged as major regulators of iXCI. However, their roles in rXCI remain controversial. Investigating early mouse development, we show that the Rlim-Rex1 axis is active in pre-implantation embryos. Upon implantation Rex1 levels are downregulated independently of Rlim specifically in epiblast cells. These results provide a conceptual framework of how the functional dynamics between Rlim and Rex1 ensures regulation of iXCI but not rXCI in female mice.

Analysis of Physical-Cognitive Tasks Including Feedback-Based Technology for Alzheimer's Disorder in a Randomized Experimental Pilot Study.

INTRODUCTION: Alzheimer's disease causes great changes, with the prefrontal cortex being the most frequently damaged zone; these changes affect physical and cognitive behavior and compromise autonomy. OBJECTIVE: The objective of this study was to evaluate the effects of physical-cognitive tasks on memory, attention, balance, gait, and risk of falling in Alzheimer's by using feedback-based technology. METHODS: Forty patients with Alzheimer's were recruited from an Alzheimer's Association; of these, 15 met the inclusion criteria and were included in the pilot RCT (eight in the control group; seven in the experimental group). ASSESSMENT TOOLS: The Cognitive Mini-Examination Scale, Oddball Test and Attention Network, Berg Scale, Tinetti, Timed Up and Go, and Geriatric Deterioration Scale. The experimental group was treated with physical-cognitive tasks by using combined feedback-based technology (visual, acoustic, simultaneous, immediate, and terminal feedback, as well as knowledge of the results and performance) under the supervision of physiotherapists twice per week for 16 thirty-minute sessions. The control group underwent their usual care (pharmacological treatment, mobility exercises, and cognitive stimulation sessions). RESULT: In the experimental group, the contrast tests showed differences for the re-test (except in attention), with the significative Timed Up and Go test being significant (p = 0.020). The interaction between groups showed significant differences for the experimental group according to the MEC (p = 0.029; d = 0.14) and Tinetti (p = 0.029; d = 0.68). DISCUSSION/CONCLUSION: Memory, balance, gait, and risk of falling improved in the Alzheimer's patients through the use of physical-cognitive tasks involving combined feedback-based technology. The effects on attention were inconclusive. The outcomes should be treated with caution due to the sample. This can promote intergenerational bonds, use at home, and adherence to treatment.

Nicotine promotes Mycobacterium tuberculosis H37Rv growth and overexpression of virulence genes.

Tobacco consumption increases the susceptibility to develop infectious diseases such as tuberculosis (TB). Nicotine (Nc) is the main component of cigarette smoke with immunomodulatory properties, however, its effect on Mycobacterium tuberculosis (Mtb) has been scarcely investigated. The present study evaluated the effect of nicotine on the growth of Mtb and on the induction of virulence-related genes. Mycobacteria were exposed to different concentrations of nicotine then Mtb growth was evaluated. Subsequently, the expression of the virulence-related genes lysX, pirG, fad26, fbpa, ompa, hbhA, esxA, esxB, hspx, katG, lpqh, and caeA was evaluated by RT-qPCR. The effect of nicotine on intracellular Mtb was also evaluated. The results showed that nicotine promotes the growth of Mtb both extracellularly and intracellularly and increases the expression of genes related to virulence. In summary, nicotine promotes the growth of Mtb and the expression of virulence-related genes that could be correlated with the increased the risk of smokers developing TB.

Mycobacterium tuberculosis cell-wall and antimicrobial peptides: a mission impossible?

Mycobacterium tuberculosis (Mtb) is one of the most important infectious agents worldwide and causes more than 1.5 million deaths annually. To make matters worse, the drug resistance among Mtb strains has risen substantially in the last few decades. Nowadays, it is not uncommon to find patients infected with Mtb strains that are virtually resistant to all antibiotics, which has led to the urgent search for new molecules and therapies. Over previous decades, several studies have demonstrated the efficiency of antimicrobial peptides to eliminate even multidrug-resistant bacteria, making them outstanding candidates to counterattack this growing health problem. Nevertheless, the complexity of the Mtb cell wall makes us wonder whether antimicrobial peptides can effectively kill this persistent Mycobacterium. In the present review, we explore the complexity of the Mtb cell wall and analyze the effectiveness of antimicrobial peptides to eliminate the bacilli.

Effect of Physiotherapy Treatment with Immersive Virtual Reality in Subjects with Stroke: A Protocol for a Randomized Controlled Trial.

BACKGROUND: Many stroke survivors suffer from sensorimotor deficits, especially balance impairments. The purpose of this trial is to investigate whether the designed Immersive Virtual Reality training program is better in the short term (15 sessions) and in the medium term (30 sessions) than physiotherapy training with Bayouk, Boucher and Leroux exercises, with respect to static balance in sitting and standing, dynamic balance and quality of life in patients with balance impairment in stroke survivors. METHODS: This study is a randomized controlled trial with two treatment arms and evaluators blinded, and a functionality treatment group in combination with specific balance exercise training according to Bayouk, Boucher and Leroux (control group) or a balanced treatment using Immersive VR. The primary outcome will be static, Dynamic balance and gait measured by Bestest Assessment Score (BESTest), Berg Scale (BBS), Pass Scale (PASS) and Time Up and Go test (TUG). The secondary outcome will be the stroke-associated quality of life using the Stroke Quality of Life Scale (ECVI-38). CONCLUSIONS: The results of this study may add new insights into how to address balance using Immersive Virtual Reality after a stroke. If the new training approach proves effective, the results may provide insight into how to design more comprehensive protocols in the future for people with balance impairments after stroke.

Corrigendum: Intrathecal drug delivery: Advances and applications in the management of chronic pain patient.

[This corrects the article DOI: 10.3389/fpain.2022.900566.].

Telerehabilitation as a Therapeutic Exercise Tool versus Face-to-Face Physiotherapy: A Systematic Review.

Digital physiotherapy, often referred to as "Telerehabilitation", consists of applying rehabilitation using telecommunication technologies. The objective is to evaluate the effectiveness of therapeutic exercise when it is telematically prescribed. METHODS: We searched PubMed, Embase, Scopus, SportDiscus and PEDro (30 December 2022). The results were obtained by entering a combination of MeSH or Emtree terms with keywords related to telerehabilitation and exercise therapy. RCTs on patients over 18 years and two groups were included, one working with therapeutic exercise through telerehabilitation and one working with conventional physiotherapy group. RESULTS: a total of 779 works were found. However, after applying the inclusion criteria, only 11 were selected. Telerehabilitation is most frequently used to treat musculoskeletal, cardiac and neurological pathologies. The preferred telerehabilitation tools are videoconferencing systems, telemonitoring and online platforms. Exercise programs ranged from 10 to 30 min and were similar in both intervention and control groups. In all the studies, results proved to be similar for telerehabilitation and face-to-face rehabilitation in both groups when measuring functionality, quality of life and satisfaction. CONCLUSION: this review generally concludes that intervention through telerehabilitation programs is as feasible and efficient as conventional physiotherapy in terms of functionality level and quality of life. In addition, telerehabilitation shows high levels of patients' satisfaction and adherence, being values equivalent to traditional rehabilitation.

Meaningful and experiential learning in a fascial approach in practice education in the degree of physiotherapy: A pilot study at a Spanish University.

BACKGROUND AND INTRODUCTION: A pilot experience of teaching innovation was developed in the masotherapy practice classes of the University of Seville's degree of physiotherapy using an active learning approach. OBJECTIVE: Significant experiential learning-specific teaching strategies were implemented to address learning style diversity and promote dynamic participation, active listening, and the creation of clinical simulation learning environments. METHODS: The strategies implemented included establishing an affective climate in the classroom that would encourage interaction among participants, facilitating the flow of information and the teaching-learning process, considering students' previous ideas, elaborating upon content maps and key questions to guide the teaching-learning process, establishing discussions favoring student brainstorming, using illustrations and videos ("visual thinking"), implementing experimental demonstrations and simulated clinical scenarios, and collaborative activities mediated by information and communication technology. RESULTS: The evaluation, which was developed using a questionnaire (pretest-posttest) that allowed the development of learning ladders and considered the complexity of the generated knowledge, revealed significant advances in student learning. CONCLUSION: The implementation of significant experiential learning-specific teaching strategies is useful for achieving the learning objectives of this subject. Further research is needed to conclude firmly in this regard.

Effectiveness of feedback-based technology on physical and cognitive abilities in the elderly.

Aging raises a social and health challenge because the passing of time causes changes in cognitive and physical functions that impair functionality and quality of life. In addition, advancements in technology and information technology have led to the development of new techniques for retraining based on the feedback technology provides. To solve the negative consequences of aging, a randomized clinical trial was carried out to assess the effectiveness of a protocol using feedback-based technology to improve physical and cognitive functions in older adults. For the purpose of this study, 200 patients were selected from a Social and Community Services Center in the province of Seville and only 46 of them became participants of the study (after applying the inclusion criteria). These patients were divided into two groups: control and experimental. Physical and cognitive abilities were assessed using the Miniexamen cognoscitivo Test (an adaptation of the MiniMental examination test), Yesevage's Depression Scale, Oddball Test, Attention Network Test, Berg Scale, Tinetti Scale, and Timed Up and Go Test. The intervention applied to the experimental group consisted of a supervised protocol using the Nintendo® Wii video game console and the Wii-Fit© video game during 16 sessions, 2 times a week with a duration of 30 min per session. The control group did not receive any treatment. The experimental group showed statistically significant improvements in all the physical variables (balance, gait, autonomy, and fall risk), as other authors had proven, and in memory and reaction times; there were no improvements in attention networks. The control group (placebo) even showed a decrease in their functions, with worse results on the Timed up and Go test Scale. The intervention using feedback-based technology has been proven effective in improving physical and cognitive abilities and in preventing and promoting healthy aging.

Thermography as a Method for Bedside Monitoring of Infantile Hemangiomas.

Infantile hemangiomas occur in 3 to 10% of infants. To predict the clinical course and counsel on treatment, it is crucial to accurately determine the hemangiomas' extension, volume, and location. However, this can represent a challenge because hemangiomas may present irregular patterns or be covered by hair, or their depth may be difficult to estimate. Diagnosis is commonly made by clinical inspection and palpation, with physicians basing their diagnoses on visual characteristics such as area, texture, and color. Doppler ultrasonography or magnetic resonance imaging are normally used to estimate depth or to confirm difficult assessments. This paper presents an alternative diagnosis tool-thermography-as a useful, immediate means of carrying out accurate hemangioma examinations. We conducted a study analyzing infantile hemangiomas with a custom thermographic system. In the first phase of the study, 55 hemangiomas of previously diagnosed patients were analyzed with a thermal camera over several sessions. An average temperature variation before and after treatment of -0.19 °C was measured. In the second phase, we selected nine patients and assessed their evolution over nine months by analyzing their thermographic images and implementing dedicated image processing algorithms. In all cases, we found that the thermal image analysis concurred with the independent diagnoses of two dermatologists. We concluded that a higher temperature inside the tumor in the follow-up was indicative of an undesirable evolution.

Use of failure-to-rescue after emergency surgery as a dynamic indicator of hospital resilience during the COVID-19 pandemic. A multicenter retrospective propensity score-matched cohort study.

BACKGROUND: Surgical failure-to-rescue (FTR, death rate following complications) is a reliable cross-sectional quality of care marker, but has not been evaluated dynamically. We aimed to study changes in FTR following emergency surgery during the COVID-19 pandemic. MATERIAL AND METHODS: Matched cohort study including all COVID-19-non-infected adult patients undergoing emergency general surgery in 25 Spanish hospitals during COVID-19 pandemic peak (March-April 2020), non-peak (May-June 2020), and 2019 control periods. A propensity score-matched comparative analysis was conducted using a logistic regression model, in which period was regressed on observed baseline characteristics. Subsequently, a mixed effects logistic regression model was constructed for each variable of interest. Main variable was FTR. Secondary variables were post-operative complications, readmissions, reinterventions, and length of stay. RESULTS: 5003 patients were included (948, 1108, and 2947 in the pandemic peak, non-peak, and control periods), with comparable clinical characteristics, prognostic scores, complications, reintervention, rehospitalization rates, and length of stay across periods. FTR was greater during the pandemic peak than during non-peak and pre-pandemic periods (22.5% vs. 17.2% and 12.7%), being this difference confirmed in adjusted analysis (odds ratio [OR] 2.13, 95% confidence interval [95% CI] 1.27-3.66). There was sensible inter-hospital variability in FTR changes during the pandemic peak (median FTR change +8.77%, IQR 0-29.17%) not observed during the pandemic non-peak period (median FTR change 0%, IQR -6.01-6.72%). Greater FTR increase was associated with higher COVID-19 incidence (OR 2.31, 95% CI 1.31-4.16) and some hospital characteristics, including tertiary level (OR 3.07, 95% CI 1.27-8.00), medium-volume (OR 2.79, 95% CI 1.14-7.34), and high basal-adjusted complication risk (OR 2.21, 95% CI 1.07-4.72). CONCLUSION: FTR following emergency surgery experienced a heterogeneous increase during different periods of the COVID-19 pandemic, suggesting it to behave as an indicator of hospital resilience. FTR monitoring could facilitate identification of centres in special needs during ongoing health care challenges.

Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient.

Advances in our understanding of the biology of spinal systems in organizing and defining the content of exteroceptive information upon which higher centers define the state of the organism and its role in the regulation of somatic and automatic output, defining the motor response of the organism, along with the unique biology and spatial organization of this space, have resulted in an increased focus on therapeutics targeted at this extracranial neuraxial space. Intrathecal (IT) drug delivery systems (IDDS) are well-established as an effective therapeutic approach to patients with chronic non-malignant or malignant pain and as a tool for management of patients with severe spasticity and to deliver therapeutics that address a myriad of spinal pathologies. The risk to benefit ratio of IDD makes it a useful interventional approach. While not without risks, this approach has a significant therapeutic safety margin when employed using drugs with a validated safety profile and by skilled practioners. The present review addresses current advances in our understanding of the biology and dynamics of the intrathecal space, therapeutic platforms, novel therapeutics, delivery technology, issues of safety and rational implementation of its therapy, with a particular emphasis upon the management of pain.