Compression for preventing recurrence of venous ulcers.

BACKGROUND: Up to 1% of adults will have a leg ulcer at some time. Most leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or damaged valves. Venous ulcer prevention and treatment typically involves the application of compression bandages/stockings to improve venous return and thus reduce pressure in the legs. Other treatment options involve removing or repairing veins. Most venous ulcers heal with compression therapy, but ulcer recurrence is common. For this reason, clinical guidelines recommend that people continue with compression treatment after their ulcer has healed. This is an update of a Cochrane review first published in 2000 and last updated in 2014. OBJECTIVES: To assess the effects of compression (socks, stockings, tights, bandages) for preventing recurrence of venous leg ulcers. SEARCH METHODS: In August 2023, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, three other databases, and two ongoing trials registries. We also scanned the reference lists of included studies and relevant reviews and health technology reports. There were no restrictions on language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated compression bandages or hosiery for preventing the recurrence of venous ulcers. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies, assessed risk of bias, and extracted data. Our primary outcome was reulceration (ulcer recurrence anywhere on the treated leg). Our secondary outcomes included duration of reulceration episodes, proportion of follow-up without ulcers, ulceration on the contralateral leg, noncompliance with compression therapy, comfort, and adverse effects. We assessed the certainty of evidence using GRADE methodology. MAIN RESULTS: We included eight studies (1995 participants), which were published between 1995 and 2019. The median study sample size was 249 participants. The studies evaluated different classes of compression (UK class 2 or 3 and European (EU) class 1, 2, or 3). Duration of follow-up ranged from six months to 10 years. We downgraded the certainty of the evidence for risk of bias (lack of blinding), imprecision, and indirectness. EU class 3 compression stockings may reduce reulceration compared with no compression over six months (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.27 to 0.76; 1 study, 153 participants; low-certainty evidence). EU class 1 compression stockings compared with EU class 2 compression stockings may have little or no effect on reulceration over 12 months (RR 1.70, 95% CI 0.67 to 4.32; 1 study, 99 participants; low-certainty evidence). There may be little or no difference in rates of noncompliance over 12 months between people using EU class 1 stockings and people using EU class 2 stockings (RR 1.22, 95% CI 0.40 to 3.75; 1 study, 99 participants; low-certainty evidence). UK class 2 hosiery compared with UK class 3 hosiery may be associated with a higher risk of reulceration over 18 months to 10 years (RR 1.55, 95% CI 1.26 to 1.91; 5 studies, 1314 participants; low-certainty evidence). People who use UK class 2 hosiery may be more compliant with compression treatment than people who use UK class 3 hosiery over 18 months to 10 years (RR for noncompliance 0.69, 95% CI 0.49 to 0.99; 5 studies, 1372 participants; low-certainty evidence). There may be little or no difference between Scholl UK class 2 compression stockings and Medi UK class 2 compression stockings in terms of reulceration (RR 0.77, 95% CI 0.47 to 1.28; 1 study, 166 participants; low-certainty evidence) and noncompliance (RR 0.97, 95% CI 0.84.1 to 12; 1 study, 166 participants; low-certainty evidence) over 18 months. No studies compared different lengths of compression (e.g. below-knee versus above-knee), and no studies measured duration of reulceration episodes, ulceration on the contralateral leg, proportion of follow-up without ulcers, comfort, or adverse effects. AUTHORS' CONCLUSIONS: Compression with EU class 3 compression stockings may reduce reulceration compared with no compression over six months. Use of EU class 1 compression stockings compared with EU class 2 compression stockings may result in little or no difference in reulceration and noncompliance over 12 months. UK class 3 compression hosiery may reduce reulceration compared with UK class 2 compression hosiery; however, higher compression may lead to lower compliance. There may be little to no difference between Scholl and Medi UK class 2 compression stockings in terms of reulceration and noncompliance. There was no information on duration of reulceration episodes, ulceration on the contralateral leg, proportion of follow-up without ulcers, comfort, or adverse effects. More research is needed to investigate acceptable modes of long-term compression therapy for people at risk of recurrent venous ulceration. Future trials should consider interventions to improve compliance with compression treatment, as higher compression may result in lower rates of reulceration.

Optimization of a medium composition for the heterologous production of Alcaligenes faecalis penicillin G acylase in Bacillus megaterium.

Penicillin G acylase (PGA) is a strategic enzyme in the production processes of beta-lactam antibiotics. High demand for ß-lactam semisynthetic antibiotics explain the genetic and biochemical engineering strategies devoted towards novel ways for PGA production and application. This work presents a fermentation process for the heterologous production of PGA from Alcaligenes faecalis in Bacillus megaterium with optimization. The thermal stability from A. faecalis PGA is considerably higher than other described PGA and the recombinant enzyme is secreted to the culture medium by B. megaterium, which facilitates the separation and purification steps. Media optimization using fractional factorial design experiments was used to identify factors related to PGA activity detection in supernatant and cell lysates. The optimized medium resulted in almost 6-fold increased activity in the supernatant samples when compared with the basal medium. Maximum enzyme activity in optimized medium composition achieves values between 135 and 140 IU/ml. The results suggest a promising model for recombinant production of PGA in B. megaterium with possible extracellular expression of the active enzyme.

Balneotherapy for chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by valvular incompetence, reflux, venous obstruction or a combination of these symptoms, with consequent distal venous hypertension. Clinical manifestations of CVI include oedema, pain, skin changes, ulcerations and dilated skin veins in the lower limbs. It places a large financial burden on health systems. There is a wide variety of treatment options for CVI, ranging from surgery and medication to compression and physiotherapy. Balneotherapy (treatments involving water) may be a relatively cheap and efficient way to deliver physiotherapy to people with CVI. This is an update of a review first published in 2019. OBJECTIVES: To assess the effectiveness and safety of balneotherapy for the treatment of people with chronic venous insufficiency. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials comparing balneotherapy to no treatment or other types of treatment for CVI. We also included studies that used a combination of treatments. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. disease severity, 2. health-related quality of life (HRQoL) and 3. ADVERSE EFFECTS: Our secondary outcomes were 1. pain, 2. oedema, 3. leg ulcer incidence and 4. skin pigmentation changes. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included nine randomised controlled trials involving 1126 participants with CVI. Seven studies evaluated balneotherapy versus no treatment, one study evaluated balneotherapy versus a phlebotonic drug (melilotus officinalis), and one study evaluated balneotherapy versus dryland exercises. We downgraded our certainty in the evidence due to a lack of blinding of participants and investigators, participant-reported outcomes and imprecision. Balneotherapy versus no treatment Balneotherapy compared to no treatment probably results in slightly improved disease severity signs and symptoms scores as assessed by the Venous Clinical Severity Score (VCSS; mean difference (MD) -1.75, 95% confidence interval (CI) -3.02 to -0.49; 3 studies, 671 participants; moderate-certainty evidence). Balneotherapy compared to no treatment may improve HRQoL as assessed by the Chronic Venous Insufficiency Quality of Life Questionnaire 2 (CIVIQ2) at three months, but we are very uncertain about the results (MD -10.46, 95% CI -19.21 to -1.71; 2 studies, 153 participants; very low-certainty evidence). The intervention may improve HRQoL at 12 months (MD -4.48, 95% CI -8.61 to -0.36; 2 studies, 417 participants; low-certainty evidence). It is unclear if the intervention has an effect at six months (MD -2.99, 95% CI -6.53 to 0.56; 2 studies, 436 participants; low-certainty evidence) or nine months (MD -6.40, 95% CI -13.84 to 1.04; 1 study, 59 participants; very low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on the occurrence of adverse effects. The main adverse effects were thromboembolic events (odds radio (OR) 0.35, 95% CI 0.09 to 1.42; 3 studies, 584 participants; low-certainty evidence), erysipelas (OR 2.58, 95% CI 0.65 to 10.22; 2 studies, 519 participants; low-certainty evidence) and palpitations (OR 0.33, 95% CI 0.01 to 8.52; 1 study, 59 participants; low-certainty evidence). No studies reported any serious adverse effects. Balneotherapy compared with no treatment may improve pain scores slightly at three months (MD -1.12, 95% CI -1.35 to -0.88; 2 studies, 354 participants; low-certainty evidence); and six months (MD -1.02, 95% CI -1.25 to -0.78; 2 studies, 352 participants; low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on oedema (measured by leg circumference) at 24 days to three months, but we are very uncertain about the results (standardised mean difference (SMD) 0.32 cm, 95% CI -0.70 to 1.34; 3 studies, 369 participants; very low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on the incidence of leg ulcers at 12 months, but we are very uncertain about the results (OR 1.06, 95% CI 0.27 to 4.14; 2 studies, 449 participants; very low-certainty evidence). Balneotherapy compared with no treatment may slightly reduce skin pigmentation changes as measured by the pigmentation index at 12 months (MD -3.60, 95% CI -5.95 to -1.25; 1 study, 59 participants; low-certainty evidence). Balneotherapy versus melilotus officinalis For the comparison balneotherapy versus a phlebotonic drug (melilotus officinalis), there was little or no difference in pain symptoms (OR 0.29, 95% CI 0.03 to 2.87; 1 study, 35 participants; very low-certainty evidence) or oedema (OR 0.21, 95% CI 0.02 to 2.27; 1 study, 35 participants; very low-certainty evidence), but we are very uncertain about the results. The study reported no other outcomes of interest. Balneotherapy versus dryland exercise For the comparison balneotherapy versus dryland exercise, evidence from one study showed that balneotherapy may improve HRQoL as assessed by the Varicose Vein Symptom Questionnaire (VVSymQ), but we are very uncertain about the results (MD -3.00, 95% CI -3.80 to -2.20; 34 participants, very low-certainty evidence). Balneotherapy compared with dryland exercises may reduce oedema (leg volume) after five sessions of treatment (right leg: MD -840.70, 95% CI -1053.26 to -628.14; left leg: MD -767.50, 95% CI -910.07 to -624.93; 1 study, 34 participants, low-certainty evidence). The study reported no other outcomes of interest. AUTHORS' CONCLUSIONS: For the comparison balneotherapy versus no treatment, we identified moderate-certainty evidence that the intervention improves disease severity signs and symptoms scores slightly, low-certainty evidence that it improves pain and skin pigmentation changes, and very low-certainty evidence that it improves HRQoL. Balneotherapy compared with no treatment made little or no difference to adverse effects, oedema or incidence of leg ulcers. Evidence comparing balneotherapy with other interventions was very limited. To ensure adequate comparison between trials, future trials should standardise measurements of outcomes (e.g. disease severity signs and symptoms score, HRQoL, pain and oedema) and follow-up time points.

The immunohistochemical expression of von Willebrand factor, T-cadherin, and Caveolin-1 is increased in kidney allograft biopsies with antibody-mediated injury.

BACKGROUND: There are only a few reports evaluating the applicability of endothelial-damage markers analysis by immunohistochemistry (IHC) in kidney allograft samples. This study analyzed the expression of Caveolin-1 (Cav), von Willebrand factor (Vwf), and T-cadherin (Cad) in kidney biopsies and their association with antibody-mediated injury. METHODS: In this retrospective study, 114 cases with antibody-mediated changes (Banff, 2020) and 72 with interstitial fibrosis/tubular atrophy were selected. IHC for Cav, Vwf and Cad was performed and evaluated according to their qualitative expression in peritubular capillaries. The cases were grouped according to the presence of microvascular inflammation (MVI), donor-specific antibodies (DSA), C4d positivity and antibody-mediated rejection (AMR). A level of significance < 0.05 was adopted. RESULTS: Vwf expression was associated with MVI (p < 0.001), DSA (p = 0.016), C4d (p < 0.001) and AMR (p < 0.001), and was higher in DSA+/C4d+ cases despite MVI (p < 0.001). The expression of Cad correlated with MVI (p = 0.015), C4d (p = 0.005) and AMR (p = < 0.001). Cad was more expressed in chronic AMR compared with acute/active cases (p = 0.001). Cav expression was associated with MVI (p = 0.029) and AMR (p = 0.016) and was also higher in chronic AMR (p = 0.049). A combined score of Vwf and Cad was higher in AMR when compared with C4d without rejection and IF/TA cases (p < 0.001). CONCLUSION: Vwf, Cad and Cav expression shows association with antibody-mediated injury and may be helpful to support AMR diagnosis.

Heparin Attenuates Visceral Apoptosis in a Swine Model of Hemorrhagic Shock and Reperfusion Injury.

BACKGROUND: The use of unfractionated heparin in hypovolemic shock, aortic clamping, and visceral reperfusion is still not established, despite evidence of inhibition of early cell damage. This study investigated the potential protective effect of unfractionated heparin on hepatic and renal apoptosis in a porcine ischemia and reperfusion model. METHODS: Twenty-one male swine (Sus scrofa) were divided into 3 groups: sham (n = 5), heparin (n = 8), and nonheparin (n = 8). The heparin and nonheparin groups underwent hypovolemic shock for 30 min, supraceliac aortic clamping for 1 h and reperfusion for 3 h. Unfractionated heparin 200 mg/kg was administered to the heparin group during aortic clamping. Hemodynamic and laboratory parameters were monitored, including aminotransferase and serum urea. Histological lesion scores were applied to hematoxylin and eosin-stained liver and kidney sections. Apoptosis quantification was performed by caspase-3 immunohistochemistry. RESULTS: The proposed model caused a severe cardiocirculatory disturbance in the heparin and nonheparin groups, observed by the carotid-femoral pressure gradient and lactic acidosis. There was no significant difference in hemodynamic and laboratory parameters between these two groups. The mean values of liver and renal histological lesion scores did not present any significant differences. Caspase-3 immunoexpression was lower in the heparin than the nonheparin group for both liver and kidney. CONCLUSIONS: Attenuation of liver and kidney cell apoptosis in pigs undergoing systemic heparinization suggests a potential use for heparin in modulating cell death under critical hemodynamic conditions.

Fucoidan Inhibition of Osteosarcoma Cells Is Species and Molecular Weight Dependent.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50 kDa), medium (MMW, 50-100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma.

Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.

Analysis of infection rates and duration of short and long-term hemodialysis catheters in a teaching hospital.

BACKGROUND: Short-term (ST) and long-term tunneled (LTT) central venous catheters for hemodialysis (CVCH) are critical for hemodialysis therapy. However, few studies have been conducted in Brazil to investigate the incidence of complications with these two types of catheters. OBJECTIVES: To analyze complications and duration of CVCH in a hemodialysis center at a teaching hospital. METHODS: Single-center, longitudinal, and retrospective study of 115 consecutive patients undergoing hemodialysis catheter placement (67 ST and 48 LTT) over a 2-year period, analyzing overall survival, patency, loss of access, and incidence of complications. RESULTS: Sixty percent of the patients were male and mean age was 62 years. The most common puncture site was the right internal jugular vein. Systemic arterial hypertension was present in 95% of cases. Median catheter in-place duration was 50 days (ST) vs. 112 days (LTT; p < 0.0001). There was no difference in overall survival. Incidence of catheter-related infection was higher in ST CVCH, with Staphylococcus sp. the microorganism most often found. The infection rate per 1000 days was higher in ST than in LTT catheters (16.7 events/1000 days vs. 7.0 events/1000 days). Low income was the only factor related to higher incidence of infection. CONCLUSIONS: The in-place duration of long-term catheters was significantly longer compared to short-term CVCH, but still below the values reported in the literature and without impact on overall survival. Low income was a factor associated with catheter infection.

Balneotherapy for chronic venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by valvular incompetence, reflux, venous obstruction, or a combination of these with consequent distal venous hypertension. Clinical manifestations of CVI include oedema, pain, skin changes, ulcerations and dilated skin veins in the lower limbs. It can result in a large financial burden on health systems. There is a wide variety of treatment options or therapies for CVI, ranging from surgery and medication to compression and physiotherapy. Balneotherapy (treatments involving water) is a relatively cheap option and potentially efficient way to deliver physical therapy for people with CVI. OBJECTIVES: To assess the efficacy and safety of balneotherapy for the treatment of people with chronic venous insufficiency (CVI). SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the Clinical Trials.gov trials register to August 2018. We searched the LILACS and IBECS databases. We also checked references, searched citations and contacted study authors to identify additional studies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials comparing balneotherapy with no treatment or other types of treatment for CVI. We also included studies that used a combination of treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed studies retrieved by the search strategies. Both review authors independently assessed selected studies for complete analysis. We resolved conflicts through discussion. We attempted to contact trial authors for missing data, obtaining additional information. For binary outcomes (leg ulcer incidence and adverse events), we presented the results using odds ratio (OR) with 95% confidence intervals (CI). For continuous outcomes (disease severity, health-related quality of life (HRQoL), pain, oedema, skin pigmentation), we presented the results as a mean difference (MD) with 95% CI. MAIN RESULTS: We included seven randomised controlled trials with 891 participants (outpatients in secondary care). We found no quasi-randomised controlled trials. Six studies (836 participants) evaluated balneotherapy versus no treatment. One study evaluated balneotherapy versus a phlebotonic drug (melilotus officinalis) (55 participants). There was a lack of blinding of participants and investigators, imprecision and inconsistency, which downgraded the certainty of the evidence.For the balneotherapy versus no treatment comparison, there probably was no improvement in favour of balneotherapy in disease severity signs and symptom score as assessed using the Venous Clinical Severity Score (VCSS) (MD -1.66, 95% CI -4.14 to 0.83; 2 studies, 484 participants; moderate-certainty evidence). Balneotherapy probably resulted in a moderate improvement in HRQoL as assessed by the Chronic Venous Insufficiency Questionnaire 2 (CVIQ2) at three months (MD -9.38, 95% CI -18.18 to -0.57; 2 studies, 149 participants; moderate-certainty evidence), nine months (MD -10.46, 95% CI -11.81 to -9.11; 1 study; 55 participants; moderate-certainty evidence), and 12 months (MD -4.99, 95% CI -9.19 to -0.78; 2 studies, 455 participants; moderate-certainty evidence). There was no clear difference in HRQoL between balneotherapy and no treatment at six months (MD -1.64, 95% CI -9.18 to 5.89; 2 studies, 445 participants; moderate-certainty evidence). Balneotherapy probably slightly improved pain compared with no treatment (MD -1.23, 95% CI -1.33 to -1.13; 1 study; 390 participants; moderate-certainty evidence). There was no clear effect related to oedema between the two groups at 24 days (MD 43.28 mL, 95% CI -102.74 to 189.30; 2 studies, 153 participants; very-low certainty evidence). There probably was no improvement in favour of balneotherapy in the incidence of leg ulcers (OR 1.69, 95% CI 0.82 to 3.48; 2 studies, 449 participants; moderate-certainty evidence). There was probably a reduction in incidence of skin pigmentation changes in favour of balneotherapy at 12 months (pigmentation index: MD -3.59, 95% CI -4.02 to -3.16; 1 study; 59 participants; low-certainty evidence). The main complications reported included erysipelas (OR 2.58, 95% CI 0.65 to 10.22; 2 studies, 519 participants; moderate-certainty evidence), thromboembolic events (OR 0.35, 95% CI 0.09 to 1.42; 3 studies, 584 participants; moderate-certainty evidence) and palpitations (OR 0.33, 95% CI 0.01 to 8.52; 1 study; 59 participants; low-certainty evidence), with no clear evidence of an increase in reported adverse effects with balneotherapy. There were no serious adverse events reported in any of the studies.For the balneotherapy versus a phlebotonic drug (melilotus officinalis) comparison, we observed no clear difference in pain symptoms (OR 0.29, 95% CI 0.03 to 2.87; 1 study; 35 participants; very low-certainty evidence) and oedema (OR 0.21, 95% CI 0.02 to 2.27; 1 study; 35 participants; very low-certainty evidence). This single study did not report on the other outcomes of interest. AUTHORS' CONCLUSIONS: We identified moderate- to low-certainty evidence that suggests that balneotherapy may result in a moderate improvement in pain, quality of life and skin pigmentation changes and has no clear effect on disease severity signs and symptoms score, adverse effects, leg ulcers and oedema when compared with no treatment. For future studies, measurements of outcomes such as disease severity sign and symptom score, quality of life, pain and oedema and choice of time points during follow-up must be standardised for adequate comparison between trials.

Immediate and Late Effects of Early Weaning on Rat Gastric Cell Differentiation.

Background: Gastric glands grow and cells reach differentiation at weaning in rats. By considering that early weaning (EW) can affect the timing of development, we aimed to compare molecular and cellular markers of differentiation in pups and adults. Methods: Wistar rats were separated into suckling-control (S) and EW groups at 15 days. Stomachs were collected at 15, 18, and 60 days for RNA and protein extraction, and morphology. Results: After EW, the expression of genes involved in differentiation (Atp4b, Bhlha15 and Pgc) augmented (18 days), and Atp4b and Gif were high at 60 days. EW increased the number of zymogenic cells (ZC) in pups and adults and augmented mucous neck cells only at 18 days, whereas parietal and transition cells (TC) were unchanged. Conclusions: EW affected the gastric mucosa mostly in a transient manner as the changes in gene expression and distribution of differentiated cells that were detected in pups were not fully maintained in adults, except for the size of ZC population. We concluded that though most of EW effects were immediate, such nutritional change in the infancy might affect part of gastric digestive functions in a permanent manner, as some markers were kept unbalanced in the adulthood.

Frequency of HPV in oral cavity squamous cell carcinoma.

BACKGROUND: The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. METHODS: Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5+/GP6+ as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro-Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. RESULTS: Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. CONCLUSION: In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

Risk factors and short and medium-term survival after open and endovascular repair of abdominal aortic aneurysms.

BACKGROUND: Infrarenal abdominal aortic aneurysms (AAA) are responsible for high rates of rupture-associated morbidity and mortality and can be treated by open or endovascular surgery. OBJECTIVES: To analyze risk factors and survival associated with surgical and endovascular AAA treatment methods. METHODS: A retrospective, longitudinal study involving 41 patients who underwent endovascular or open AAA repair, whether elective or emergency, over a 48-month period, with analysis of preoperative comorbidities, 30-day and 1-year survival, in-hospital mortality, length of hospital stay, transfusion of blood products, duration of surgery, and development of acute kidney failure. Inferential statistics and survival analysis considered a 95% CI and p < 0.05 as significant. RESULTS: Twelve of the 41 patients were treated with open surgery and 29 with endovascular techniques. The majority were male (75%), with an average age of 71 (range: 56 - 90 years). There were no differences in demographic or risk factors between the groups. Overall survival rates for open and endovascular repair were different for both 30 days (37 vs. 72%, p = 0.01) and 360 days (37 vs. 67%, p = 0.01). However, survival rates in elective cases were similar at 30 days (71 vs. 76%, p = 0.44) and 360 days (both 71%, p = 0.34). Endovascular repair showed shorter length of hospital stay (3.0 vs. 4.4 days; p = 0.02) and duration of surgery (111 vs. 163 min; p < 0.01) compared to open repair. CONCLUSIONS: There was no difference in short- or medium-term survival of AAA patients treated electively with endovascular or open surgery. Hospital stays and duration of surgery were both shorter with minimally invasive treatment.

Mesenchymal stem cells from sternum: the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics.

BACKGROUND: In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cellular characteristics and therapeutic results. METHODS: To study the proliferative and differentiation potential of mesenchymal stem cells (MSC), isolated from bone marrow (BM) of sternum, we made a comparative analysis between samples of patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years and no differences in cardiovascular risk factors. BM samples were collected (16.4 ± 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5 ± 1.5 × 107 cells/mL. RESULTS: Morphology, immunophenotype and differentiation ability had proven that the cultivated sternal BM cells had MSC features. The colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p = 0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F number (r = 0.499, p = 0.049). The MSC culture was established in 29% of collected samples, achieved passage 9, without significant difference in expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins was associated with culture establishment for IHD patients (p = 0.049 and p = 0.006, respectively). CONCLUSIONS: Together, these results show that the sternum bone can be used as a source for MSC isolation, and that ischemic or valvular diseases do not influence the cellular yield, culture establishment or in vitro growth kinetics.

Clinical performance of topical sodium fluoride when supplementing carbamide peroxide at-home bleaching gel.

This clinical study evaluated the use of 0.11% topical sodium fluoride (SF) desensitizing agent to treat tooth sensitivity during a nightguard tooth whitening procedure. Thirty-two subjects bleached their teeth with 10% carbamide peroxide (CP) gel using an at-home bleaching technique with custom trays. During bleaching treatment, subjects were divided into 2 groups (n = 16). The subjects in Group 1 received a topical gel containing 0.11% SF; the subjects in Group 2 received a placebo gel (PG). Each subject was instructed to place the gel in his/her bleaching tray for 30 min every day following bleaching treatment. Results showed the use of SF did not affect the whitening efficacy of the 10% CP gel. Subjects who received the PG had significantly higher tooth sensitivity when compared with subjects who received SF (P < 0.00). The use of daily 0.11% SF after 10% CP bleaching gel reduced tooth sensitivity during the bleaching treatment.

A maximum of two readily releasable vesicles per docking site at a cerebellar single active zone synapse.

Recent research suggests that in central mammalian synapses, active zones contain several docking sites acting in parallel. Before release, one or several synaptic vesicles (SVs) are thought to bind to each docking site, forming the readily releasable pool (RRP). Determining the RRP size per docking site has important implications for short-term synaptic plasticity. Here, using mouse cerebellar slices, we take advantage of recently developed methods to count the number of released SVs at single glutamatergic synapses in response to trains of action potentials (APs). In each recording, the number of docking sites was determined by fitting with a binomial model the number of released SVs in response to individual APs. After normalization with respect to the number of docking sites, the summed number of released SVs following a train of APs was used to estimate of the RRP size per docking site. To improve this estimate, various steps were taken to maximize the release probability of docked SVs, the occupancy of docking sites, as well as the extent of synaptic depression. Under these conditions, the RRP size reached a maximum value close to two SVs per docking site. The results indicate that each docking site contains two distinct SV-binding sites that can simultaneously accommodate up to one SV each. They further suggest that under special experimental conditions, as both sites are close to full occupancy, a maximal RRP size of two SVs per docking site can be reached. More generally, the results validate a sequential two-step docking model previously proposed at this preparation.

Spatiotemporal dynamics of epidemiology diseases: mobility based risk and short-term prediction modeling of COVID-19.

Nowadays, epidemiological modeling is applied to a wide range of diseases, communicable and non-communicable, namely AIDS, Ebola, influenza, Dengue, Malaria, Zika. More recently, in the context of the last pandemic declared by the World Health Organization (WHO), several studies applied these models to SARS-CoV-2. Despite the increasing number of researches using spatial analysis, some constraints persist that prevent more complex modeling such as capturing local epidemiological dynamics or capturing the real patterns and dynamics. For example, the unavailability of: (i) epidemiological information such as the frequency with which it is made available; (ii) sociodemographic and environmental factors (e.g., population density and population mobility) at a finer scale which influence the evolution patterns of infectious diseases; or (iii) the number of cases information that is also very dependent on the degree of testing performed, often with severe territorial disparities and influenced by context factors. Moreover, the delay in case reporting and the lack of quality control in epidemiological information is responsible for biases in the data that lead to many results obtained being subject to the ecological fallacy, making it difficult to identify causal relationships. Other important methodological limitations are the control of spatiotemporal dependence, management of non-linearity, ergodicy, among others, which can impute inconsistencies to the results. In addition to these issues, social contact, is still difficult to quantify in order to be incorporated into modeling processes. This study aims to explore a modeling framework that can overcome some of these modeling methodological limitations to allow more accurate modeling of epidemiological diseases. Based on Geographic Information Systems (GIS) and spatial analysis, our model is developed to identify group of municipalities where population density (vulnerability) has a stronger relationship with incidence (hazard) and commuting movements (exposure). Specifically, our framework shows how to operate a model over data with no clear trend or seasonal pattern which is suitable for a short-term predicting (i.e., forecasting) of cases based on few determinants. Our tested models provide a good alternative for when explanatory data is few and the time component is not available, once they have shown a good fit and good short-term forecast ability.

Impact of Preoperative Mapping and Intraoperative Neuromonitoring in Minimally Invasive Parafascicular Surgery for Deep-Seated Lesions.

BACKGROUND: Transsulcal tubular retractor-assisted minimally invasive parafascicular surgery changes the surgical strategy for deep-seated lesions by promoting a deficit-sparing approach. When integrated with preoperative brain mapping and intraoperative neuromonitoring (IONM), this approach may potentially improve patient outcomes. In this study, we assessed the impact of preoperative brain mapping and IONM in tubular retractor-assisted neuro-oncological surgery. METHODS: This retrospective single-center cohort study included patients who underwent transsulcal tubular retractor-assisted minimally invasive parafascicular surgery for resection of deep-seated brain tumors from 2016 to 2022. The cohort was divided into 3 groups: group 1, no preoperative mapping or IONM (17 patients); group 2, IONM only (25 patients); group 3, both preoperative mapping and IONM (38 patients). RESULTS: We analyzed 80 patients (33 males and 47 females) with a median age of 46.5 years (range: 1-81 years). There was no significant difference in mean tumor volume (26.2 cm3 [range 1.07-97.4 cm3]; P = 0.740) and mean preoperative depth of the tumor (31 mm [range 3-65 mm], P = 0.449) between the groups. A higher proportion of high-grade gliomas and metastases was present within group 3 (P = 0.003). IONM was related to fewer motor (P = 0.041) and language (P = 0.032) deficits at hospital discharge. Preoperative mapping and IONM were also related to shorter length of stay (P = 0.008). CONCLUSIONS: Preoperative and intraoperative brain mapping and monitoring enhance transsulcal tubular retractor-assisted minimally invasive parafascicular surgery in neuro-oncology. Patients had a reduced length of stay and prolonged overall survival. IONM alone reduces postoperative neurological deficit.

Western diet consumption by host vertebrate promotes altered gene expression on Aedes aegypti reducing its lifespan and increasing fertility following blood feeding.

BACKGROUND: The high prevalence of metabolic syndrome in low- and middle-income countries is linked to an increase in Western diet consumption, characterized by a high intake of processed foods, which impacts the levels of blood sugar and lipids, hormones, and cytokines. Hematophagous insect vectors, such as the yellow fever mosquito Aedes aegypti, rely on blood meals for reproduction and development and are therefore exposed to the components of blood plasma. However, the impact of the alteration of blood composition due to malnutrition and metabolic conditions on mosquito biology remains understudied. METHODS: In this study, we investigated the impact of whole-blood alterations resulting from a Western-type diet on the biology of Ae. aegypti. We kept C57Bl6/J mice on a high-fat, high-sucrose (HFHS) diet for 20 weeks and followed biological parameters, including plasma insulin and lipid levels, insulin tolerance, and weight gain, to validate the development of metabolic syndrome. We further allowed Ae. aegypti mosquitoes to feed on mice and tracked how altered host blood composition modulated parameters of vector capacity. RESULTS: Our findings identified that HFHS-fed mice resulted in reduced mosquito longevity and increased fecundity upon mosquito feeding, which correlated with alteration in the gene expression profile of nutrient sensing and physiological and metabolic markers as studied up to several days after blood ingestion. CONCLUSIONS: Our study provides new insights into the overall effect of alterations of blood components on mosquito biology and its implications for the transmission of infectious diseases in conditions where the frequency of Western diet-induced metabolic syndromes is becoming more frequent. These findings highlight the importance of addressing metabolic health to further understand the spread of mosquito-borne illnesses in endemic areas.

Bond strength of adhesive systems with different solvents to dry and wet dentin.

AIM: This study evaluates bond strength between dentin and composite using adhesives with different solvents to dry and wet dentin. MATERIALS AND METHODS: Ninety bovine incisors were used; the vestibular surfaces were worn by the exposure of an area with a diameter of 4 mm of dentin. The specimens were divided into 6 groups, according to the type of adhesive used and hydratation stals: Group SB-wet: Single Bond 2 in wet dentin, Group SBdry: Single Bond 2 in dry dentin, Group SL-wet: Solobond M in wet dentin, Group SL-dry: Solobond M in dentin dry. Group XPwet: XP Bond in wet dentin, Group XP-dry: XP Bond in dentin dry. They were cut to obtain specimens in the shape of stick with 1 × 1 mm and subjected to microtensile test in universal testing machine with a cross speed of 1mm/min. The data were analyzed with ANOVA and Tukey's tests (5%). RESULTS: ANOVA showed significant differences for surface treatment and interaction, but no difference was found for adhesive factor. The Tukey's test showed that the samples with wet dentin shown higher values of bond strength. CONCLUSION: The adhesive did not influence in the bond strength. The groups with wet dentin showed higher values of bond strength than groups with dry dentin.