A Pilot Study of the Clinical Effectiveness of a Single Intra-Articular Injection of Stanozolol in Canines with Knee Degenerative Joint Disease and Its Correlation with Serum Interleukin-1ß Levels.

Stanozolol shows promise as an anabolic and anti-catabolic agent for treating degenerative joint disease (DJD). This study assessed the clinical efficacy of a single intra-articular stanozolol injection in canine knees with DJD and its correlation with serum IL-1ß levels. Thirty dogs (n = 30) were divided into a control group (CG, n = 10) and a study group (SG, n = 20) with DJD. Pain levels were assessed using the Brown query, and radiographs were taken at T0 and T3. IL-1ß levels were quantified via ELISA. Apart from 2 patients, all showed reduced pain intensity, with 15 patients showing improvement at T1 and 3 patients at T2. A positive correlation (r = 0.84; p < 0.01) was found between pain level and IL-1ß in 15 patients. No systemic effects were observed. Most patients (18/20) experienced reduced pain. This pilot study suggests stanozolol's potential in managing DJD in dogs. Further research is warranted to validate these findings and understand stanozolol's mechanism in DJD treatment.

The Use of Fast-Acting Insulin Topical Solution on Skin to Promote Surgical Wound Healing in Cats.

Wound healing is a complex biological process involving a coordinated sequence of events aimed at restoring tissue integrity and function. Recent advancements in wound care have introduced novel therapies, with topical insulin application emerging as a promising strategy for promoting tissue healing. This study, involving 60 female cats (n = 60) undergoing elective spaying, aimed to evaluate the effects of topical fast-acting insulin on the healing process of surgical wounds. Each surgical suture was divided into two regions: the control zone (Zcr) without insulin application and the study zone (Zst), where insulin was applied topically for 10 min every 24 h over eight consecutive days. Assessment of suture healing was conducted using an adapted scale at two time points post-surgery: T1 (day 2) and T2 (day 8). Statistically significant differences were registered in the final healing scale scores between Zcr and Zst (p < 0.022), as well as for the parameter of regional fluid (p-value = 0.017). Additionally, at T2, all Zst regions exhibited wound closure, whereas Zcr did not, although not in a statistically significant manner. The observed discrepancy at T2 between the Zcr and Zst regions may suggest a potential benefit of utilizing insulin. No side effects resulting from the insulin topical application performed by the tutors were recorded in the Zst suture group. This study represents the first exploration of the benefits of topical insulin application for surgical wound healing in cats.

Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV­2 Mpro).

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.

The Influence of Noise Level on the Stress Response of Hospitalized Cats.

The study aimed to investigate the impact of noise levels in the hospital environment on the stress experienced by hospitalized cats undergoing elective ovariohysterectomy surgery. A total of 33 domestic female cats were included in the study, divided into four groups: a control group (CG) and three experimental groups based on ward noise levels: G1 (Quiet, <60 dB), G2 (Medium, between 60 and 85 dB), and G3 (Noisy, >85 dB). Behavioral assessments, respiratory rate (RR), and plasma cortisol levels ([Cort]p) were measured as indicators of stress. A composite measure of stress, termed the final stress value (FSV), was calculated by summing scores across various behavioral categories. Data collection occurred at three time points: immediately following surgery (T1), and at 2 h (T2) and 3 h (T3) post-surgery. FSV and RR were assessed at all three time points (T1, T2, and T3), while [Cort]p levels were measured at T1 and T3. The study observed that the median values of FSV, RR, and [Cort]p tended to increase with both higher noise levels and longer exposure durations to noise. Significant differences in RR were found between group pairs G1G2 at T1 (|D| = 0.63 < cut-off = 0.98), and G2G3 at T2 (|D| = 0.69 < cut-off = 0.97). Regarding [Cort]p, significant differences were noted between the CGG1 group pair at T0 (p < 0.01), and T3 (p = 0.03). Furthermore, an excellent Spearman correlation coefficient (rho = 0.91) was found between FSV and RR, indicating that RR can serve as an effective tool for assessing stress levels in cats. The findings of this study provide valuable insights into the welfare of cats in a hospital environment and support the scientific validity of existing recommendations aimed at improving their well-being. Specifically, the study underscores the importance of minimizing noise levels in hospitals as a means to reduce stress in cats. This conclusion aligns with existing guidelines and recommendations for enhancing the welfare of hospitalized cats.

Development of a Management App for Postviral Fibromyalgia-Like Symptoms: Patient Preference-Guided Approach.

BACKGROUND: Persistent fibromyalgia-like symptoms have been increasingly reported following viral infections, including SARS-CoV-2. About 30% of patients with post-COVID-19 syndrome fulfill the fibromyalgia criteria. This complex condition presents significant challenges in terms of self-management. Digital health interventions offer a viable means to assist patients in managing their health conditions. However, the challenge of ensuring their widespread adoption and adherence persists. This study responds to this need by developing a patient-centered digital health management app, incorporating patient preferences to enhance usability and effectiveness, ultimately aiming to improve patient outcomes and quality of life. OBJECTIVE: This research aims to develop a digital health self-management app specifically for patients experiencing postviral fibromyalgia-like symptoms. By prioritizing patient preferences and engagement through the app's design and functionality, the study intends to facilitate better self-management practices and improve adherence. METHODS: Using an exploratory study design, the research used patient preference surveys and usability testing as primary tools to inform the development process of the digital health solution. We gathered and analyzed patients' expectations regarding design features, content, and usability to steer the iterative app development. RESULTS: The study uncovered crucial insights from patient surveys and usability testing, which influenced the app's design and functionality. Key findings included a preference for a symptom list over an automated chatbot, a desire to report on a moderate range of symptoms and activities, and the importance of an intuitive onboarding process. While usability testing identified some challenges in the onboarding process, it also confirmed the importance of aligning the app with patient needs to enhance engagement and satisfaction. CONCLUSIONS: Incorporating patient feedback has been a significant factor in the development of the digital health app. Challenges encountered with user onboarding during usability testing have highlighted the importance of this process for user adoption. The study acknowledges the role of patient input in developing digital health technologies and suggests further research to improve onboarding procedures, aiming to enhance patient engagement and their ability to manage digital health resources effectively. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32193.

In silico drug repurposing by combining machine learning classification model and molecular dynamics to identify a potential OGT inhibitor.

O-linked N-acetylglucosamine (O-GlcNAc) is a unique intracellular post-translational glycosylation at the hydroxyl group of serine or threonine residues in nuclear, cytoplasmic and mitochondrial proteins. The enzyme O-GlcNAc transferase (OGT) is responsible for adding GlcNAc, and anomalies in this process can lead to the development of diseases associated with metabolic imbalance, such as diabetes and cancer. Repurposing approved drugs can be an attractive tool to discover new targets reducing time and costs in the drug design. This work focuses on drug repurposing to OGT targets by virtual screening of FDA-approved drugs through consensus machine learning (ML) models from an imbalanced dataset. We developed a classification model using docking scores and ligand descriptors. The SMOTE approach to resampling the dataset showed excellent statistical values in five of the seven ML algorithms to create models from the training set, with sensitivity, specificity and accuracy over 90% and Matthew's correlation coefficient greater than 0.8. The pose analysis obtained by molecular docking showed only H-bond interaction with the OGT C-Cat domain. The molecular dynamics simulation showed the lack of H-bond interactions with the C- and N-catalytic domains allowed the drug to exit the binding site. Our results showed that the non-steroidal anti-inflammatory celecoxib could be a potentially OGT inhibitor.

Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes in contemporaneous clinical practice.

BACKGROUND: Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes (NSTE-ACS) during hospitalization is still a matter of contention within the cardiology community. Our aim was to analyze in-hospital and one-year follow-up outcomes of patients with NSTE-ACS pretreated with dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT). METHODS: A retrospective study was carried out with NSTE-ACS patients planned to undergo an invasive strategy and were included in the Portuguese Registry of ACS between 2018-2021. A composite primary outcome (in-hospital re-infarction, stroke, heart failure, hemorrhage, death) was compared regarding antiplatelet strategy (DAPT versus SAPT). Secondary outcomes were defined as one-year all-cause mortality and one-year cardiovascular rehospitalization. RESULTS: A total of 1469 patients were included, with a mean age of 66±12 years and 73.9% were male. DAPT regime was used in 38.2% and SAPT in 61.8% of patients. NSTE myocardial infarction was the most frequent presentation (88.5%). Revascularization after 24h occurred in 44.8% patients (63% of these after 48h). Enoxaparin was the anticoagulant more frequently used (45.1%). The primary outcome was more frequently observed in the SAPT group (10.4%, p=0.033), mainly driven by more ischemic events. Time until revascularization > 48h and SAPT regime were independent predictors of the primary outcome (OR 1.66, p=0.036 and OR 2.03, p=0.008, respectively). CONCLUSION: NSTE-ACS patients pretreated with SAPT had worse in-hospital outcomes. This difference can be probably explained by a delay in time until revascularization. Pretreatment DAPT strategy and crossover between heparins is still frequently used in clinical practice.

Evaluation of clinical and genetic factors in obstructive sleep apnoea.

Purpose: To evaluate the correlation between several presumed candidate genes for obstructive sleep apnoea (OSA) and clinical OSA phenotypes and propose a predictive comprehensive model for diagnosis of OSA. Methods: This case-control study compared polysomnographic patterns, clinical data, morbidities, dental factors and genetic data for polymorphisms in PER3, BDNF, NRXN3, APOE, HCRTR2, MC4R between confirmed OSA cases and ethnically matched clinically unaffected controls. A logistic regression model was developed to predict OSA using the combined data. Results: The cohort consisted of 161 OSA cases and 81 controls. Mean age of cases was 53.5 ± 14.0 years, mostly males (57%) and mean body mass index (BMI) of 27.5 ± 4.3 kg/m2. None of the genotyped markers showed a statistically significant association with OSA after adjusting for age and BMI. A predictive algorithm included the variables gender, age, snoring, hypertension, mouth breathing and number of T alleles of PER3 (rs228729) presenting 76.5% specificity and 71.6% sensitivity. Conclusions: No genetic variant tested showed a statistically significant association with OSA phenotype. Logistic regression analysis resulted in a predictive model for diagnosing OSA that, if validated by larger prospective studies, could be applied clinically to allow risk stratification for OSA.

A mandibular advancement device associated with lingual control: a new treatment option for obstructive sleep apnea?

PURPOSE: Oral appliances (OA) have become the main alternative to positive pressure airway devices (PAP) for the control of obstructive sleep apnea (OSA). Despite literature support, controversies about the mode of action and the effectiveness of these devices persist. The aim of this study was to evaluate the efficacy of modified mandibular advancement devices (MAD) in patients with OSA who failed treatment with MAD and to evaluate the role of the tongue as a factor in patients who failed treatment with MAD. MATERIALS AND METHODS: Patients unable to control the apnea-hypopnea index (AHI) using a MAD were subsequently treated with a modified version that included a tongue trimming accessory. The objective was to stabilize the tongue by preventing it from sliding with the consequent collapse of the upper airway (UA). New polysomnography (PSG) was performed with the modified MAD in place. RESULTS: A total of 20 patients who failed MAD therapy were studied including 15 men (75%) with mean age (± standard deviation) of 58.5 ± 13.1 years and BMI 29.6 ± 5.0 Kg/m2. After installing the tongue trimmer, the number of patients who achieved complete success with the new MAD (AHI < 5) went from 0 to 30% and those who achieved partial success (5 < AHI < 10) went from 0 to 20%. The number of patient responders (AHI reduced by at least 50%) went from 20 to 75%. CONCLUSION: The results suggest that the tongue, even in the presence of a MAD, may be one of the contributing factors for the collapse of the UA and consequent device ineffectiveness. By stabilizing the tongue through the insertion of a tongue trimmer, the MAD became more effective in many cases.

Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Effectiveness of Acupuncture on Health-Related Quality of Life in Patients Receiving Maintenance Hemodialysis.

Patients with kidney failure (KF) receiving maintenance hemodialysis (HD) experience numerous symptoms that impair their health-related quality of life (HRQOL) and contribute to high mortality rates. Acupuncture is often used for symptom enhancement and HRQOL. This blinded, randomized, controlled patient-assessor trial evaluated the effectiveness of acupuncture compared with sham acupuncture on patients' HRQOL receiving maintenance HD as a secondary analysis. Seventy-two participants were randomly assigned to verum acupuncture (VA), sham acupuncture (SA), or waiting-list (WL) groups. The outcome was an improvement in HRQOL, assessed using the Kidney Disease Quality of Life-Short Form, version 1.3 (KDQOL-SF™ v1.3) at baseline, after treatment, and at 12-week follow-up. Non-parametric tests were used for statistical analysis. Of the 72 randomized patients, 67 were included in the complete analysis set. As for the changes between baseline and after treatment, the VA group showed significantly increased scores on most of the KDQOL-SF™ v1.3 scales compared to SA or WL groups (p < 0.05). No statistically significant differences between groups were observed in the changes from baseline to follow-up (p > 0.05). Compared to the sham treatment, acupuncture improved the HRQOL in patients receiving maintenance HD after treatment but not at follow-up.

Integrating Acupuncture into a Dialysis Center.

A growing interest in integrating traditional Chinese medicine (TCM) and conventional medicine (CM) to create a more comprehensive approach to healthcare has been verified. Scientific evidence supports acupuncture as an integrative treatment for specific health conditions. The aim of this study was to assess the acceptance and feasibility by patients and healthcare professionals of integrating acupuncture in a dialysis center. Individuals undergoing hemodialysis (HD) who participated in a patient-assessor-blinded randomized controlled trial that evaluated the effect of acupuncture on functional capacity and quality of life were included. Acceptance was measured by adherence (percentage of patients who completed treatments and dropouts) and patients' and healthcare professionals' opinions toward acupuncture (pre- and pro-intervention questionnaires). Feasibility was measured by safety (number of reported adverse events) and effectiveness (changes in functional capacity, peripheral muscle strength, and health-related quality of life scores after treatment). Forty-eight patients were included, and forty-five (93.8%) were analyzed. No adverse events were reported. All patients completed the treatment, and only three patients (6.2%) were lost to the 12-week post-treatment follow-up. The attitudes of patients and health professionals were favorable to acupuncture, namely in relation to its use, degree of discomfort, recommendation to others, and interference with routine care and clinical setting. Integrating acupuncture into a dialysis center seems viable and well-accepted by patients with kidney failure on maintenance HD, doctors and nurses.

Whole-exome identifies germline variants in families with obstructive sleep apnea syndrome.

Background: Obstructive sleep apnea syndrome (OSAS) (OMIM #107650) is characterized by complete or partial obstruction of the upper airways, resulting in periods of sleep associated apnea. OSAS increases morbidity and mortality risk from cardiovascular and cerebrovascular diseases. While heritability of OSAS is estimated at ∼40%, the precise underlying genes remain elusive. Brazilian families with OSAS that follows as seemingly autosomal dominant inheritance pattern were recruited. Methods: The study included nine individuals from two Brazilian families displaying a seemingly autosomal dominant inheritance pattern of OSAS. Whole exome sequencing of germline DNA were analyzed using Mendel, MD software. Variants selected were analyzed using Varstation® with subsequent analyses that included validation by Sanger sequencing, pathogenic score assessment by ACMG criteria, co-segregation analyses (when possible) allele frequency, tissue expression patterns, pathway analyses, effect on protein folding modeling using Swiss-Model and RaptorX. Results: Two families (six affected patients and three unaffected controls) were analyzed. A comprehensive multistep analysis yielded variants in COX20 (rs946982087) (family A), PTPDC1 (rs61743388) and TMOD4 (rs141507115) (family B) that seemed to be strong candidate genes for being OSAS associated genes in these families. Conclusion: Sequence variants in COX20, PTPDC1 and TMOD4 seemingly are associated with OSAS phenotype in these families. Further studies in more, ethnically diverse families and non-familial OSAS cases are needed to better define the role of these variants as contributors to OSAS phenotype.

A Case of a Large Malignant Pericardial Effusion on Computed Tomography Without Electrocardiographic Gating.

A 67-year-old female was admitted due to dyspnea. A computed tomography (CT) disclosed a suspicious pulmonary mass and a pericardial effusion. A transthoracic echocardiogram confirmed a large-volume circumferential pericardial effusion. A pericardiocentesis was performed, and the cytological and histochemical studies later confirmed the diagnosis of pulmonary adenocarcinoma. This case report highlights the casualty of having found a cardiac tamponade through a CT not synchronized with an electrocardiogram.

Staphylococcus argenteus Infections, Brazil.

In 2015, two new species related to the Staphylococcus aureus were proposed. We describe five isolates of the new species Staphylococcus argenteus cultured from human cases of bacteremia and skin and soft tissue infections. This is the first report of S. argenteus, from South America, causing community-acquired and nosocomial infections.

Fibromyalgia and menopause: an open study on postmenopausal hormone therapy.

BACKGROUND: Fibromyalgia women (FM) seems to get worse at menopause suggesting some influence of estrogens on its pathophysiology. We aimed to study the influence of postmenopausal hormone therapy (HT) in FM, the relationship with sleep and FM impact. METHODS: We analyzed prospectively 69 menopausal women, divided in two groups, FM group (FMG; N.=32) and comparison group (CG; N.=28) submitted to HT for twelve weeks (1.2 mg/g transdermal estradiol, 100 mg micronized natural progesterone oral/daily). Data on Utian Quality of Life Questionnaire (UQOL) and Pittsburgh Sleep Quality Index (PSQI) were obtained in both groups, at entrance and twelve weeks after HT. FM patients also completed the Fibromyalgia Impact Questionnaire - Revised (FIQ-R) and fibromyalgia severity (FS). RESULTS: FM patients improved significantly the FIQ-R (P=0.0001, median FIQ-R score 30% lower), mainly the severity of FM, assessed by FS (P<0.0001). Both groups had improved quality of life and sleep (UQOL: P=0.0001; P=0.001, PSQI: P<0.0001; P=0.007, respectively). Differences between first and second PSQI were greater for CG than for FMG (P=0.008). CONCLUSIONS: HT improving sleep and quality of life in both groups; it was a significant clinical improvement seen by FIQ and FS in FM patients. These changes characterize improvement of functional status and symptoms severity.

Can CT-based assessment of lateral malleolus anatomy indicate when and how to perform an intramedullary fixation in distal fibula fractures? An analysis of 150 ankles.

PURPOSE: The primary aim was to analyse the lateral malleolus morphology with a focus on the shape of the distal fibula for IM fixation of the fibula in infra- and transsyndesmotic fracture patterns. The secondary aim was to propose a treatment algorithm according to the lateral malleolar anatomy. METHODS: 77 healthy, skeletally mature volunteers underwent CT scanning of the ankle. The fibula medullary canal and its cortical thickness were quantitatively analysed at 4 different levels measured from the fibular tip (1.5 cm, 3.0 cm, 4.5 cm, and 6.0 cm). A geometric classification was proposed, and a decision algorithm was developed. Statistical significance was set at a p-value < 0.05. RESULTS: The smallest diameter of the medullary canal of the fibula was at 6.0 cm from the tip of the fibula, in 98.2% of the ankles. The distal fibula can be classified into triangular and rectangular type, according to the cortical thickness index (p < 0.0001). In 16.7% ankles, the internal diameter of the fibula at 6.0 cm was equal or narrower than 3.5 mm (p < 0.05). CONCLUSION: The shape of the distal fibula as evaluated by CT-guided analysis allows for IM osteosynthesis of the lateral malleolus in 83% of individuals. In our study, the smallest diameter of the medullary canal of the fibula was located 6.0 cm from the tip of the lateral malleolus. Coronal CT evaluation is advantageous in indicating which type of IM implant should be used safely for infra- and transsyndesmotic fracture patterns, potentially reducing intraoperative risks.

Effect of Acupuncture on Functional Capacity in Patients Undergoing Hemodialysis: A Patient-Assessor Blinded Randomized Controlled Trial.

Decreased functional capacity (FC) in patients undergoing hemodialysis (HD) is associated with adverse health events and poor survival. Acupuncture is recognized as a safe and effective integrative treatment. The aim of this study is to evaluate the effect of acupuncture treatment on the FC in chronic kidney disease with GFR category 5 (CKG G5) patients undergoing HD. In this patient-assessor blinded randomized controlled trial, seventy-two KF patients were randomly assigned to experimental (n = 24), placebo (n = 24) and control groups (n = 24). The primary outcome was the improvement in FC assessed by the 6-Minute Walk Test (6-MWT). Secondary outcomes included assessment of peripheral muscle strength by the Handgrip Strength Test (HGS) and the 30-Second Sit-to-Stand Test (STS-30) at baseline, after treatment and at 12-week follow up. A mixed ANOVA with interaction time*group was used. The experimental group increased walk distance (p < 0.001), lower limbs strength (p < 0.001) and handgrip strength (p = 0.012) after nine acupuncture sessions and stabilized in the follow-up (p > 0.05). In the placebo and control groups the 6-MWT and 30STS results decreased (p < 0.001) and the HGS scores did not change through time (p > 0.05). Acupuncture treatment improved FC and muscle strength in patients undergoing HD.

Effect of Acupuncture on Functional Capacity and Health-Related Quality of Life of Hemodialysis Patients: Study Protocol for a Randomized Controlled Trial.

The proposed randomized controlled trial protocol will evaluate the effect of acupuncture treatment on the functional capacity (FC) and health-related quality of life (HRQOL) in chronic kidney disease (CKD) with glomerular filtration rate (GFR) category 5 (CKG G5) patients receiving maintenance dialysis. Patients undergoing hemodialysis (HD) from a dialysis center will be randomly assigned to experimental, placebo and control groups. In order to determine the difference between the same number of treatments performed three times or one treatment a week, experimental (verum acupuncture) and placebo (sham acupuncture) groups will receive a total of nine acupuncture treatments; however, both groups will be divided into subgroups A and B. The same selection of acupuncture points will be applied to both experimental subgroups and the placebo subgroups will receive acupuncture on non-acupuncture points. The results will be assessed by the 6-min Walk Test, Handgrip Test, 30-sec Sit-to-Stand and Kidney Disease Quality of Life-Short Form and will be held at baseline, after treatment and 12 weeks post-treatment follow up. This paper describes the rationale and design for a randomized, patient-assessor blinded controlled trial, which may provide evidence for the clinical application of acupuncture in CKG G5 patients undergoing HD.

Freeze-Dried Microfluidic Monodisperse Microbubbles as a New Generation of Ultrasound Contrast Agents.

We succeeded in freeze-drying monodisperse microbubbles without degrading their performance, that is, their monodispersity in size and echogenicity. We used microfluidic technology to generate cryoprotected highly monodisperse microbubbles (coefficient of variation [CV] <5%). By using a novel retrieval technique, we were able to freeze-dry the microbubbles and resuspend them without degradation, that is, keeping their size distribution narrow (CV <6%). Acoustic characterization performed in two geometries (a centimetric cell and a millichannel) revealed that the resuspended bubbles conserved the sharpness of the backscattered resonance peak, leading to CVs ranging between 5% and 10%, depending on the geometry. As currently observed with monodisperse bubbles, the peak amplitudes are one order of magnitude higher than those of commercial ultrasound contrast agents. Our work thus solves the question of storage and transportation of highly monodisperse bubbles. This work might open pathways toward novel clinical non-invasive measurements, such as local pressure, impossible to carry out with the existing commercial ultrasound contrast agents.