Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.

The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates. The presence of the mRNA of spliced XBP1 and a high expression of cytokine mRNAs were observed during active infection. TLR8 mRNA showed an overwhelming expression in comparison with TLR7 mRNA in bronchioloalveolar aspirates of COVID-19 patients, thus suggesting the presence of monocytes and monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a synthetic mimic of SARS-CoV-2 RNA, showed induction of XBP1 splicing and the expression of proinflammatory cytokines. These responses were blunted by the IRE1α inhibitor MKC8866, the TLR8 antagonist CU-CPT9a, and knockdown of TLR8 receptor. In contrast, the IRE1α-XBP1 activator IXA4 enhanced these responses. Based on these findings, the TLR8/IRE1α system seems to play a significant role in the induction of the proinflammatory cytokines associated with severe COVID-19 disease and might be a druggable target to control cytokine storm.

Fungal Patterns Induce Cytokine Expression through Fluxes of Metabolic Intermediates That Support Glycolysis and Oxidative Phosphorylation.

Cytokine expression is fine-tuned by metabolic intermediates, which makes research on immunometabolism suitable to yield drugs with a wider prospect of application than the biological therapies that block proinflammatory cytokines. Switch from oxidative phosphorylation (OXPHOS) to glycolysis has been considered a characteristic feature of activated immune cells. However, some stimuli might enhance both routes concomitantly. The connection between the tricarboxylic acid cycle and cytokine expression was scrutinized in human monocyte-derived dendritic cells stimulated with the fungal surrogate zymosan. Results showed that nucleocytosolic citrate and ATP-citrate lyase activity drove IL1B, IL10, and IL23A expression by yielding acetyl-CoA and oxaloacetate, with the latter one supporting glycolysis and OXPHOS by maintaining cytosolic NAD+ and mitochondrial NADH levels through mitochondrial shuttles. Succinate dehydrogenase showed a subunit-specific ability to modulate IL23A and IL10 expression. Succinate dehydrogenase A subunit activity supported cytokine expression through the control of the 2-oxoglutarate/succinate ratio, whereas C and D subunits underpinned cytokine expression by conveying electron flux from complex II to complex III of the electron transport chain. Fatty acids may also fuel the tricarboxylic acid cycle and influence cytokine expression. Overall, these results show that fungal patterns support cytokine expression through a strong boost of glycolysis and OXPHOS supported by the use of pyruvate, citrate, and succinate, along with the compartmentalized NAD(H) redox state maintained by mitochondrial shuttles.

Rotator Interval vs Posterior Approach Ultrasound-guided Corticosteroid Injections in Primary Frozen Shoulder: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the efficacy of rotator interval (RI) vs posterior approach (PA) ultrasound (US) guided corticosteroid injections into the glenohumeral (GH) joint in primary frozen shoulder (PFS). DATA SOURCES: A systematic literature search for all relevant studies on Medline, Scopus, Embase, Web of Science, and Cochrane Central, up to January 2023 was conducted. STUDY SELECTION: Randomized controlled trials that directly compared the US-guided corticosteroid injection into the RI and GH joint using PA in patients clinically and radiographically diagnosed with PFS. DATA EXTRACTION: The primary outcome was pain, and the secondary outcomes were function, and range of motion (ROM). Two authors independently assessed the risk of bias using the Cochrane risk-of-bias tool version 2. A random-effects model and generic inverse variance method were performed. Effect sizes were estimated using mean difference (MD) and standardized mean difference (SMD). DATA SYNTHESIS: A total of 5 clinical trials involving 323 subjects were included for the meta-analysis. US-guided corticosteroid injections into the RI revealed significant pain relief (MD 1.33 [95% confidence interval (CI) 0.20 to 2.46]; P=.02) and significant functional improvement (SMD 1.31 [95% CI 0.11 to 2.51]; P=.03) compared with the PA after 12 weeks. CONCLUSION: The results suggest the injection of corticosteroid into RI space is more effective than PA after 12 weeks in improving both pain and functional scores in patients with PFS.

Cryotherapy versus topical nitric-zinc complex solution for the treatment of plantar warts: A randomized controlled trial.

Cryotherapy is commonly regarded as the primary treatment method for plantar warts. A new medical device called nitric-zinc complex solution (NZCS) has also emerged as a potential alternative for wart treatment. The main aim of this study was to analyze and compare the effectiveness of cryotherapy using liquid nitrogen and NZCS in treating plantar warts. We conducted a randomized and controlled clinical trial involving patients with plantar warts. A total of 62 patients were enrolled in the study and monitored for 12 weeks or until their warts were completely resolved. The patients received either cryotherapy or NZCS, with a maximum of six treatment applications. The cure rate was 65.5% in the group treated with cryotherapy and 56.6% in the group treated with NZCS. The average number of treatment applications required for curing warts was significantly lower in the cured group (3.28 ± 1.63) than in the group with unresolved warts (5.5 ± 1.27) (p < 0.01). Moreover, the average number of applications was lower in the cryotherapy group (3.6 ± 1.8) than in the NZCS group (4.8 ± 1.8) (p < 0.01). Based on the findings, NZCS could be considered a favorable first-line treatment option for plantar warts.

A deeper look at low-frequency contact ultrasonic debridement in the clinical management of patients with diabetic foot ulcers.

The current study aimed to evaluate the dispersal of solution and microbes (aerosol) in the clinical environment during treatment with Low-frequency contact ultrasonic debridement (LFCUD) with or without suction attachment in patients with diabetic foot ulcers (DFUs). We performed 20 treatments in 10 patients divided into two groups to receive the proposed LFCUD modalities. We measured the microbial load of the environment pre-treatment (sample M1), during treatment with each LFCUD modality (sample M2) and post-treatment (sample M3). The use of LFCUD debridement without a suction attachment results in significantly higher immediate contamination of the clinic environment than the suction attachment, particularly during the procedure (1.70 ± 0.98 log 10 CFU/mL versus 0.77 ± 0.85 log 10 CFU/mL, p = 0.035). When suction is not applied, there are statistically significant differences depending on whether the DFUs are neuropathic or neuroischemic, finding a greater number of microorganisms with high loads in neuropathic DFUs. We found a statistically significant positive correlation between wound area (r = 0.450, p = 0.047) and TBI (r = 0.651, p = 0.006) with the bacterial load during the LFCUD. Based on our results, we recommend using the personal protective equipment required to protect staff members and patients during treatment with LFCUD and using a suction attachment where clinically possible to reduce clinic environmental pollution, especially in neuropathic DFUs and those with larger areas.

In Vivo Models for the Study of Hyaluronic Acid Fillers: A Review.

BACKGROUND: Hyaluronic acid (HA) filler application is one of the most frequent minimally invasive aesthetic procedures used worldwide. Its properties and characterization, performance, effects in other tissues, and response to complication treatments have been studied in several animal models. This review aims to categorize animal models considering the advantages and disadvantages regarding the purpose of the study. METHODS: Literature research was made using MEDLINE via PubMed by two reviewers using keywords "hyaluronic acid" "filler" and "animal model". Full-text articles published in English and with an in vivo animal model were included for data extraction. RESULTS: The rat model was the most common animal used to evaluate properties or characteristics and degradation of HA fillers. Rabbits were preferred for evaluating HA embolism treatments; however, anatomical names of the arteries differ in some studies. Mice and rats used as vascular occlusion model are challenging due to the size of the vessels and viscosity of the filler. CONCLUSION: There is a wide variability of options of in vivo animal models to evaluate HA fillers. The animal characteristics, laboratory resources, and HA properties should be considered in accordance with the objective of the study, when choosing the ideal model. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE.

Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In both, MS and its preclinical model, the experimental autoimmune encephalomyelitis (EAE) gastrointestinal symptoms including "leaky gut" have been reported. Oleacein (OLE), a phenolic compound from extra virgin olive oil or olive leaves, harbors a wide range of therapeutic properties. Previously, we showed OLE effectiveness preventing motor defects and inflammatory damage of CNS tissues on EAE mice. The current studies examine its potential protective effects on intestinal barrier dysfunction using MOG35-55-induced EAE in C57BL/6 mice. OLE decreased EAE-induced inflammation and oxidative stress in the intestine, preventing tissue injury and permeability alterations. OLE protected from EAE-induced superoxide anion and accumulation of protein and lipid oxidation products in colon, also enhancing its antioxidant capacity. These effects were accompanied by reduced colonic IL-1ß and TNFα levels in OLE-treated EAE mice, whereas the immunoregulatory cytokines IL-25 and IL-33 remained unchanged. Moreover, OLE protected the mucin-containing goblet cells in colon and the serum levels of iFABP and sCD14, markers that reflect loss of intestinal epithelial barrier integrity and low-grade systemic inflammation, were significantly reduced. These effects on intestinal permeability did not draw significant differences on the abundance and diversity of gut microbiota. However, OLE induced an EAE-independent raise in the abundance of Akkermansiaceae family. Consistently, using Caco-2 cells as an in vitro model, we confirmed that OLE protected against intestinal barrier dysfunction induced by harmful mediators present in both EAE and MS. This study proves that the protective effect of OLE in EAE also involves normalizing the gut alterations associated to the disease.

Exchange Bias Effect of Ni@(NiO,Ni(OH)2) Core/Shell Nanowires Synthesized by Electrochemical Deposition in Nanoporous Alumina Membranes.

Tuning and controlling the magnetic properties of nanomaterials is crucial to implement new and reliable technologies based on magnetic hyperthermia, spintronics, or sensors, among others. Despite variations in the alloy composition as well as the realization of several post material fabrication treatments, magnetic heterostructures as ferromagnetic/antiferromagnetic coupled layers have been widely used to modify or generate unidirectional magnetic anisotropies. In this work, a pure electrochemical approach has been used to fabricate core (FM)/shell (AFM) Ni@(NiO,Ni(OH)2) nanowire arrays, avoiding thermal oxidation procedures incompatible with integrative semiconductor technologies. Besides the morphology and compositional characterization of these core/shell nanowires, their peculiar magnetic properties have been studied by temperature dependent (isothermal) hysteresis loops, thermomagnetic curves and FORC analysis, revealing the existence of two different effects derived from Ni nanowires' surface oxidation over the magnetic performance of the array. First of all, a magnetic hardening of the nanowires along the parallel direction of the applied magnetic field with respect their long axis (easy magnetization axis) has been found. The increase in coercivity, as an effect of surface oxidation, has been observed to be around 17% (43%) at 300 K (50 K). On the other hand, an increasing exchange bias effect on decreasing temperature has been encountered when field cooling (3T) the oxidized Ni@(NiO,Ni(OH)2) nanowires below 100 K along their parallel lengths.

Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival.

BACKGROUND: Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance. RESULTS: Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival. CONCLUSIONS: These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.

Analyses of transcutaneous oxygen pressure values stratified for foot angiosomes to predict diabetic foot ulcer healing.

AIMS: Previous research suggested that diabetic foot ulcer (DFU) location could affect transcutaneous oxygen pressure (TcPO2) values following the angiosome concept. Up to our knowledge no studies have yet analyzed if the location of a diabetic foot ulcer can be a confounding factor that modifies TcPO2 values. The primary aim of this study was to compare the potential healing prognosis of TcPO2 differentiated for diabetic foot ulcers in different angiosome locations. METHODS: a 2-years observational cohort prospective study was performed in 81 patients with diabetic foot ulcers. Transcutaneous oxygen pressure measurements were performed at baseline by placing the electrode on two different angiosomes: dorsal zone of the foot (dorsalis pedis angiosome) and between the navicular bone and the tibial malleolus (posterior tibial angiosome). The main outcome was establishing the effectiveness of TcPO2 measurements (dorsalis pedis angiosome and posterior tibial angiosome) for predicting DFU healing. RESULTS: Transcutaneous oxygen pressure probe placed in the dorsum of the foot (dorsalis pedis angiosome) yielded a sensitivity (S) of 95 % and specificity (SP) of 73 %, and an area under the curve (AUC) of 0.902 (p < 0.001 [0.84-0.96]) for ulcers located in the forefoot and toes; while TcPO2 placed in the posterior tibial angiosome yielded an S of 100 % and SP of 85 % and an AUC of 0.894 (p < 0.001 [0-822-0.966]) for DFU located in the midfoot and heel. CONCLUSION: This study suggests that angiosome-guided TcPO2 contributes to a prognosis of successful foot ulcer healing.

A comparison of hyperspectral imaging with routine vascular noninvasive techniques to assess the healing prognosis in patients with diabetic foot ulcers.

OBJECTIVE: To compare the potential healing prognosis of the different routine noninvasive techniques implemented in the International Working Group Diabetic Foot Guidelines with the novel use of hyperspectral imaging (HSI) in patients with diabetic foot ulcers (DFUs). METHODS: Twenty-one patients with active DFUs participated in this 1-year prospective study in a specialized diabetic foot unit between December 2018 and January 2020. HSI was performed at baseline to quantify tissue oxygenation and should be presented on an anatomical map by analyzing the following parameters: (1) oxygen saturation of the hemoglobin, (2) tissue hemoglobin index, (3) the near-infrared perfusion index, and (4) tissue water index. In addition, transcutaneous oxygen pressure (TcpO2), systolic toe and ankle pressures, ankle-brachial index, and toe-brachial index values were calculated for the ulcerated limb. The primary outcome measure was wound healing, defined as complete epithelization without any drainage confirmed for at least 10 days after closure was first documented at 24 weeks. RESULTS: During the follow-up period 14 patients (66.66 %) healed and 7 patients did not heal (33.3%) by 24 weeks. The TcpO2 optimal cut-off point as determined by a balance of sensitivity and specificity of 28.5 mm Hg that yielded a sensitivity of 91% and a specificity of 100%, and area under the curve of 0.989 (P = .005; 95% confidence interval [CI], 0.945-1.000). Followed by the oxygen saturation of the hemoglobin optimal cut-off point as determined by a balance of sensitivity and specificity of 48.5 mm Hg that yielded a sensitivity of 93% and a specificity of 0.71%, and area under the curve of 0.932 (P = .013; 95% CI, 0.787-1.000). The logistic regression analyses showed that TcpO2 was the only variable associated with wound healing at 24 weeks (P < .001; 95% CI, 0.046-0.642). CONCLUSIONS: The HSI was shown to be effective in the prognosis of DFU healing compared with other noninvasive test; only TcpO2 values resulted in better diagnosis potential in wound healing.

Trendelenburg (Head-Down tilt) and head rotation: Ultrasonographic effects on the internal jugular vein for catheterization safety.

Most guidelines fail to specify patient positioning during central venous catheterization. The objective was to determine the effects of head-down tilt (Trendelenburg position) and head rotation on the internal jugular vein (IJV). A prospective, observational, longitudinal, and descriptive study using healthy adult volunteers, of both sexes, was performed. The change in position and cross-sectional areas (CSA) of the right IJV and common carotid artery (CA) were measured by ultrasonography during Trendelenburg position (TP) (0°, 5°, 10°, and 15°) and contralateral head-rotation (HR) (0°, 45°, and 90°) for a total of 12 positions. The neutral supine position was first, randomizing the other 11 positions, with 5-min rest intervals in between. Vital signs and symptoms were recorded. A total of 54 volunteers were recruited between the ages of 21 and 32, of which 30 were men. Any degree of TP or HR significantly increased the CSA. The largest area obtained was 1.78 cm2 with a TP15HR90 which did not have a statistical difference with TP10HR45 1.59 cm2 . A HR90 tended to displace the IJV medially, overlaying the CA. Any degree of TP or HR will significantly increase CSA or the right IJV. A 5° to 10° TP is recommended when the patient's condition allows it, with a 45° HR, without significantly displacing the IJV anterior to the CCA.

Could X-ray Predict Long-term Complications in Patients with Diabetic Foot Osteomyelitis?

OBJECTIVE: To analyze the association between radiologic changes on plain X-rays in patients with diabetic foot osteomyelitis and the development of complications at the 1-year follow-up. METHODS: A prospective, observational study was conducted involving 115 patients with diabetic foot osteomyelitis. X-ray features that were evaluated during 1-year follow-up visits included affected bone marrow, active periosteal reaction, sequestrum, cortical disruption, and other types of signs. Researchers analyzed the association between the presence of X-ray changes and complication development, such as bone or soft tissue infections, ulcer recurrence, reulceration, amputation, death, and other diabetic foot disease-related events. RESULTS: During follow-up, of 115 patients included in the study, 33 patients (28.7%) showed radiologic changes, and 85 (73.9%) developed complications. The presence of radiologic changes after ulcer healing had a significant association with complication development during the 1-year follow-up in addition to those found at different follow-up visits. Patients who showed radiologic changes had higher percentages of complications during the 1-year follow-up, and patients without radiologic changes had lower percentages of complications. CONCLUSIONS: The presence of radiologic changes is related to the development of complications in patients who suffer from diabetic foot osteomyelitis.

Topical treatment for plantar warts: A systematic review.

There are a wide variety of treatments for plantar warts, but none has been shown to be effective in all patients. We aimed to perform a systematic review of the efficacy of different topical treatments on plantar warts. Systematic electronic searches (Pubmed, Cochrane Library, Embase, and Web of Science) were conducted in April 2020. Meta-analyses, systematic reviews, and retrospective or prospective clinical trials of the effects of topical and nonsurgical treatments of plantar warts were included. Two authors performed the study selection and data extraction. Any discrepancies between the two reviewers were discussed with a third reviewer. Forty-four studies were included. The average cure rates of the most frequent treatments were variable across the studies: cryotherapy (45.61%), salicylic acid (13.6%), cantharidin-podophyllin-salicylic acid formulation (97.82%), laser (79.36%), topical antivirals (72.45%), intralesional bleomycin (83.37%), and intralesional immunotherapy (68.14%). Twenty-two studies (50%) had a level of evidence 1b and grade of recommendation A, five studies (11.4%) had a level of evidence 2b and grade of recommendation B, two studies (4.5%) had a level of evidence 3b and grade of recommendation B, and 15 studies (34,1%) with a level of evidence 4 and grade of recommendation C. First-choice treatments for common warts, such as cryotherapy and salicylic acid, have low-cure rates for plantar warts. Other treatments, such as CPA formulation, immunotherapy, and intralesional bleomycin, which have compassionate use, have higher cure rates. This review should stimulate future high-quality research to evaluate these specialized treatments.

Contribution of students to nursing practice settings during clinical training: Design and validation of a questionnaire.

BACKGROUND: A validated questionnaire to measure the contributions of nursing students to clinical settings could potentially assist in the improved management of students in healthcare institutions. AIM: To develop and test the psychometric properties of the questionnaire 'Nursing Student Contributions to Clinical Settings' (CEEEC, Spanish acronym for 'Contribuciones de los Estudiantes de Enfermería a los Entornos Clínicos'). DESIGN: Instrument design and psychometric testing. PARTICIPANTS/SETTINGS: A multicentre study involving 1,098 nursing professionals from three universities and five hospitals of Spain, between January 2019 and March 2020. METHODS: The study was carried out in two phases. Phase 1 involved the questionnaire design by experts (n = 28), which required a review of the available literature, cognitive interviews and Delphi rounds, and a preliminary validity study, which included a pilot test with responses from a sample of nurses (n = 143). Phase 2 involved a formal validation with a wider sample of nurses (n = 927), including factor analysis and a study of convergent validity with the Practice Environment Scale-Nursing Work Index and Health Sciences-Evidence Based Practice. RESULTS: Experts selected 42 items on student contributions. After cognitive interviews, three items were eliminated and seven failed to reach the minimum content validity index (78%). Based on the remaining 32 items, the discrimination index of each item was calculated, and those with <0.3, eight items were sequentially eliminated. The resulting questionnaire contained 24 items grouped into a single factor, which explained 41% of the variance. The internal consistency was excellent (Cronbach's alpha: 0.94), and the convergent validity was confirmed. CONCLUSIONS: A 24-item questionnaire was designed and validated to measure the contributions of nursing students to clinical practice settings. IMPACT: Most hospitals are also teaching centres where nursing students undergo clinical practice. The application of this test will provide insight into the nursing professionals' perception of the students' role.

Comparison of suturing models: the effect on perception of basic surgical skills.

BACKGROUND: Acquisition of Basic Surgical Skills (BSS) are essential for medical students. The objective was to determine it's fidelity impact. METHODS: Using four suturing models (SM) (pigskin, sponge, commercial pad, and orange), SM-quality and student-SM interaction were evaluated. After a 1-h class, participants were divided into groups and randomly assigned exercises in SM in 15-min intervals. The experiment included completing three individual simple stitches and a 3-stitch continuous suture in each SM. RESULTS: Eighty-two medical students participated. Suturing quality was better in pigskin and sponge, which were also the preferred models (p < 0.001). Significant differences in quality between the insertion and exit point, and firmness of knots (p < 0.05) in both simple and continuous sutures, as well as between length and distance in continuous ones (p < 0.001) were identified. CONCLUSIONS: Acquisition and quality of BSS are influenced by the intrinsic characteristics of SM. An adequate degree of resistance, consistency, and elasticity are necessary.

Evolution of the TcPO2 values following hyperoxygenated fatty acids emulsion application in patients with diabetic foot disease: results of a clinical trial.

OBJECTIVE: The use of emollients to lubricate dry skin to prevent diabetic foot ulcers (DFUs), especially in neuroischaemic feet, has been recommended. This study analyses the effect of daily topical application of hyperoxygenated fatty acids emulsion on transcutaneous oxygen pressure (TcPO2) in the feet of neuropathic and neuroischaemic patients with diabetes. METHOD: Patients with diabetes and no active foot ulcer were included in this longitudinal, prospective, non-comparative clinical trial. The evolution of TcPO2 (mmHg) values after the application of the tested emulsion (Corpitol Emulsion, Laboratoires Urgo Medical, France) was evaluated for a three-month period. Modifications of skin features (skin dryness, skin shedding and skin colour) were also analysed. TcPO2 was performed using a TCM400 device (Radiometer, Denmark). RESULTS: A total of 50 patients were included in the study. Patients with neuroischaemia showed a significant increase in TcPO2 values (35.69±13.88mmHg) after two months' application of the tested emulsion that remained at month three (day 60: 42.34±10.98mmHg; p=0.006; day 90: 41.62±10.88mmHg; p=0.011). Skin dryness and shedding showed an improvement from baseline to the end of the study in both groups, secondary to the use of the tested emulsion (p<0.001 and p<0.001, respectively). Skin colour also showed differences from baseline to the final visit in the neuroischaemic patients (p=0.029). Patients with neuropathy did not show any change in skin colour from baseline to the final visit. CONCLUSIONS: Analysis of the use of the tested emulsion showed an increase in TcPO2 and an improvement in skin trophism in patients with neuroischaemic foot.

Diagnostic Accuracy of Bone Culture Versus Biopsy in Diabetic Foot Osteomyelitis.

OBJECTIVE: To compare the diagnostic accuracy of bone culture (microbiology) and biopsy (histology) in patients with acute or chronic diabetic foot osteomyelitis (DFO). METHODS: This cross-sectional study involved patients for whom providers had a clinical suspicion of DFO. Two bone samples were taken: one for microbiologic testing and another for histologic testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated for bone culture results in relation to the probability of DFO diagnosis. RESULTS: Fifty-two patients were included; 69% had positive bone culture results, and 90.4% had positive histology results (P = .013), and of those 90.4%, 25.5% had acute and 74.5% had chronic DFO. The sensitivity of the microbiologic bone culture result was 0.70, the specificity was 0.40, the positive predictive value was 0.92, and the negative predictive value was 0.13. CONCLUSIONS: Histology provides more accurate diagnosis of DFO than microbiology, especially for patients with chronic DFO. These patients could be underdiagnosed because of false-negative results provided by bone culture. Providers should perform both tests to confirm the presence of DFO.

Localized gallbladder perforation: a systematic review of treatment and prognosis.

BACKGROUND: The optimal management of localized gallbladder perforation (Neimeier type II) has yet to be defined. The aim of this systematic review was to identify factors associated with improved patient outcomes. METHODS: Systematic review of studies that described the management of Neimeier type II perforation, reported complications of the first intervention, necessity of added interventions, resolution of the pathology, and days of hospital stay were included. The search strategy was conducted in EMBASE, Mayo Journals, MEDLINE, SCOPUS, and Web of Science (December 2020) RESULTS: A total of 122 patients (53% male) from case reports, series, and cohorts were included for analysis. In total 56 (46%) and 44 (36%)patients were treated with open and laparoscopic cholecystectomy respectively. Overall risk of bias was moderate. The need for another intervention was higher in the laparoscopic group (5 vs 17, p=<0.001) as well as prevalence of complications (4 vs 16, p=<0.001), but lower for days of hospital stay (median days 5. vs 15, p = 0.008) against open cholecystectomy. Preoperative percutaneous catheter drainage did not influence outcome. CONCLUSION: Open cholecystectomy has a lower need for further surgical procedures and postoperative complications, but a longer hospital stay. These outcomes did not vary with preoperative percutaneous drainage. The effect of timing of cholecystectomy did not influence the outcomes.

Oleanolic acid ameliorates intestinal alterations associated with EAE.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment. METHODS: Mice with MOG35-55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects. RESULTS: We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS. CONCLUSION: These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.