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Stougaard Kay opublikował 1 rok, 8 miesięcy temu
Overall, this ultrasound-responsive polymersome provides us with a fresh insight into designing next-generation stimuli-responsive drug carriers with better maneuverability and higher chemotherapeutic efficiency. OBJECTIVE Expand an existing validated measure of basic mobility (AM-PAC) for patients at the lowest levels of function. DESIGN Item replenishment for existing item response theory (IRT) derived measure, via 1) idea generation and creation of potential new items, 2) item calibration and field-testing, and 3) longitudinal pilot test. SETTING Two tertiary acute care hospitals PARTICIPANTS Consecutive inpatients (n=502) >18 years old, with AM-PAC Inpatient Mobility Short Form (IMSF) raw score ≤15; for the longitudinal pilot test, eight inpatients were evaluated. RESULTS Fifteen new AM-PAC items were developed, two of which improved mobility measurement at the lower levels of functioning. Specifically, with the 2 new items, the floor effect of the AM-PAC IMSF was reduced by 19%, statistical power and measurement breadth were greater, and in longitudinal pilot testing there was greater measurement sensitivity. CONCLUSIONS Adding 2 new items to the AM-PAC IMSF lowered the floor, increased statistical power, measurement breadth, and sensitivity. In this edition of Mythbusters, we evaluate the common claim that topical corticosteroids (TCS) can be used for treatment of postcircumcision penile adhesions (PCPA). Although many textbooks and websites of respected pediatric institutions include topical steroids as one of the options for treatment of PCPA, the scientific basis of this claim is unclear and none of the references we found cited any specific sources. In review of the literature, we could find no peer-reviewed studies that support (or even assess) the utility of TCS for PCPA. It appears that the claims regarding TCS may be extrapolations from the demonstrated effectiveness of TCS for phimosis and related problems, although these are different conditions with different etiologies. We conclude that there is no scientific evidence supporting the use of TCS for PCPA. The verdict for this urolegend 'Debunked.’ INTRODUCTION/BACKGROUND Owing to restrictions in operative experiences, urology residents can no longer solely rely on 'hands-on’ operative time to master their surgical skills by the end of residency. Simulation training could help residents master basic surgical skills and steps of a procedure to maximize time in the operative room. However, simulators can be expensive or tedious to set up, limiting the availability to residents and training programs. OBJECTIVE The authors sought to develop and validate an inexpensive, high-fidelity training model for robotic pyeloplasty. STUDY DESIGN Pyeloplasty models were created using Dragon Skin® FX-Pro tissue-mimicking silicone cast over 3-dimensional molds. Urology faculty and trainees completed a demographic questionnaire. The participants viewed a brief instructional video and then independently performed robotic dismembered pyeloplasty on the model. Acceptability and content validity were evaluated via post-task evaluation of the model. Construct validity was eval and the median score among residents was 6 (IQR = 2-6) (P less then 0.001). The material cost was $1.32/model, and the average production time was 0.12 person-hours/model. DISCUSSION AND CONCLUSION This low-cost pyeloplasty model exhibits acceptability and content validity. Construct validity is supported by significant correlation between participant expertise and simulator performance across multiple assessment domains. The model has excellent potential to be used as a training tool in urology and allows for repetitive practice of pyeloplasty skills before live cases. Published by Elsevier Ltd.We present atomic scale models of differently shaped silica surfaces loaded by gemcitabine and ibuprofene molecules, respectively. Despite the dissimilar nature of the drug molecules, their association to silica carriers show quite similar characteristics. We identify a well-defined contact layer that is stabilized by silica-molecule salt-bridges/hydrogen bonding in parallel to interactions among the drug molecules. Additional loading of the carriers leads to rough films with dynamically evolving asperities rather than layer-by-layer ordering. To elucidate the role of differently shaped silica surfaces, we compared planar slab models and spherical nanoparticles as two limiting cases. Despite the strong difference in the curvature of the silica surfaces, our molecular dynamics simulations show only small changes of the unloading characteristics. This suggests that the design of different pore shapes in mesoporous silica based drug carriers mainly affects the migration kinetics rather than the energetics of drug loading and release. Epithelial-mesenchymal transition (EMT) plays a role in not only cancer metastasis, but also drug resistance, which is associated with increased levels of efflux transporters such as P-glycoprotein (P-gp). Here, we examined whether P-gp activation during Snail-induced EMT of lung cancer cells is mediated by ezrin, radixin and moesin (ERM), which regulate transporter localization. HCC827 lung cancer cells overexpressing the transcription factor Snail showed increased Rhodamine123 efflux and increased paclitaxel resistance, reflecting increased P-gp activity. Concomitantly, the expression level of moesin, but not ezrin or radixin, was significantly increased. The increase of P-gp activity was suppressed by knockdown of moesin. Thus, the increase of P-gp activity associated with Snail-induced EMT may be mediated mainly by moesin in HCC827 cells. On the other hand, the Snail mRNA expression level was correlated with the expression level of each ERM in four non-small-cell lung cancer cell lines (HCC827, A549, H441, H1975) and in tumor tissues, but not normal tissues, of lung cancer patients. These results suggest that P-gp activation during EMT is at least partially due to increased expression of moesin. Co-administration of moesin inhibitors with anticancer drugs might block P-gp-mediated drug efflux organ-specifically, improving treatment efficacy and minimizing side effects on other organs. This work evaluates permeation of twelve model pharmaceutical compounds through a chemically modified form of poly(dimethylsiloxane) (PDMS), whereby the polymer surface had undergone silanisation. Standard polymer membrane has been widely used as a simplified skin model to investigate transdermal permeation yet does not fully mimic human skin. The surface chemistry of modified polymer was investigated such as the ability to bind to drugs, hydrophobicity and pore size using optical microscopy, the Brunauer-Emmett-Teller (BET) technique and Fourier-transform Infrared Spectroscopy (FTIR), followed by permeation analysis with UV spectroscopy. For eleven of the twelve compounds an appreciable increase in the extent of permeation was observed after six hours when using the silanised polymer compared with the standard PDMS. Furthermore, a correlation was found between the degree of permeation increase and hydrophobicity (logP) of the drug (R2 = 0.90). These findings indicate that permeation can be controlled by modifying the membrane surface, although the hydrophobicity of the permeant also plays a vital role in the extent of permeation observed. This concept study presents a potential alternative membrane for pharmaceutical transdermal analysis, providing many benefits over existing options. Bepotastine (BPT) is a H1-receptor antagonist. It is used as a besilate salt in ophthalmic solution for allergic conjunctivitis, and orally for the treatment of allergic rhinitis and utricaria/pruritus. Its systematic forced degradation study is unreported. The same was carried out in different conditions prescribed by International Conference on Harmonisation. The stressed solutions were subjected to reversed phase liquid chromatographic analysis, and BPT was observed to be labile under photobasic condition only, yielding five photodegradation products. The structures of the latter were elucidated from data generated using liquid chromatography-high resolution mass spectrometry and multi-stage mass spectrometry. Of the five, four products were further isolated and subjected to nuclear magnetic resonance spectroscopy to justify the proposed structures. Two of them, with similar accurate mass, were additionally and unambiguously characterized from their heteronuclear multiple bond correlation data, hydrogen deuterium exchange mass data, and quantum chemical analysis using density function theory calculations. One degradation product had a structure that could only be explained by unusual rearrangement involving conversions of N-oxide into hydroxylamine, similar to Meisenheimer rearrangement. The physicochemical, as well as absorption, distribution, metabolism, excretion and toxicity properties of BPT and its characterized photodegradation products were evaluated in silico by ADMET Predictor™ software. Previously, 1 mL of purified water (hyposmotic) or saline (isosmotic) which dissolved 200 μM of FITC-dextran (FD-4), a non-absorbable marker, was orally administered to rats, and luminal concentration-time profile of FD-4 was directly measured. In this study, at first, luminal FD-4 concentration was measured after oral administration of 0.5 mL of FD-4 purified water solution (200 μM). Then, kinetic analysis was conducted to calculate the fluid volume that passed through each segment of the gastrointestinal tract (Vfluid), based on the luminal FD-4 concentration-time profiles obtained from three different administration groups. In the group of 1 mL purified water administration, most of administered water was absorbed quickly from the duodenum and upper jejunum, whereas group of saline administration (1 mL) showed only a little amount of absorbed in the upper small intestine. In 0.5 mL purified water group, Vfluid in the stomach was approximately half compared to that in 1 mL purified water group. However, for small intestine, almost the same values of Vfluid were obtained regardless of the dose-volume. Our findings are valuable to improve the quality of in vitro predictive dissolution tools and/or in silico simulation for predicting oral drug absorption. Cantharidin (CTD), a natural Chinese medicine constituent extracted from mylabris, is a potent drug against hepatocellular carcinoma (HCC). However, the clinical application of CTD was limited due to its toxicity and low-solubility. In this work, a novel CTD-loaded liposome modified with 3-succinyl-30-stearyl glycyrrhetinic acid (18-GA-Suc-CTD-Lip) was prepared in order to enhance liver-targeting efficiency and anti-tumor activity. 18-GA-Suc-CTD-Lip and CTD-Lip were successfully prepared by film dispersion method and totally characterized. The anti-tumor effects in vitro were evaluated by cell proliferation inhibition assay, transwell assay, cell cycle analysis and an apoptosis test. Pharmacokinetic and biodistribution were all investigated to precisely reveal liver-targeting efficiency of 18-GA-Suc-CTD-Lip in vivo. The IC50 values of 18-GA-Suc-CTD-Lip in HepG2 (3.417 ± 0.165 nmol/L) and Huh-7 (4.478 ± 0.409 nmol/L) cells were much lower than that of CTD-Lip, indicating that anti-tumor effects of 18-GA-Suc-CTD-Lip were remarkable due to the modification of 18-GA-Suc. The maximum concentration in the liver of 18-GA-Suc-CTD-Lip (1.72 ± 0.14 μg/g) was more than twice CTD-Lip (0.75 ± 0.08 μg/g) at 30 min, illustrating that 18-GA-Suc-CTD-Lip possesses excellent liver-targeting efficiency. Conclusively, 18-GA-Suc-CTD-Lip could be a potential liver-targeting anti-tumor drug for HCC. The notochord is an embryonic tissue that acts as a hydrostatic skeleton until ossification begins in vertebrates. It is composed of outer sheath cells and inner vacuolated cells, which are generated from a common pool of disc-shaped precursors. Notochord extension during early embryogenesis is driven by the growth of vacuolated cells, reflecting in turn the expansion of their inner vacuole. Here we use desmogon, a novel desmosomal cadherin, to follow notochord development and regeneration in medaka (Oryzias latipes). We trace desmogon+ disc-shaped precursors at the single cell level to demonstrate that they operate as unipotent progenitors, giving rise to either sheath or vacuolated cells. We reveal that once specified, vacuolated cells grow asynchronously and drive notochord expansion bi-directionally. Additionally, we uncover distinct regenerative responses in the notochord, which depend on the nature of the injury sustained. By generating a desmogon CRISPR mutant we demonstrate that this cadherin is essential for proper vacuolated cell shape and therefore correct notochord and spine morphology. Our work expands the repertoire of model systems to study dynamic aspects of the notochord in vivo, and provides new insights in its development and regeneration properties. New drugs for the treatment of human leishmaniasis are urgently needed, considering the limitations of current available options. However, pre-clinical evaluation of drug candidates for leishmaniasis is challenging. The use of luciferase-expressing parasites for parasite load detection is a potentially powerful tool to accelerate the drug discovery process. We have previously described the use of Leishmania amazonensis mutants expressing firefly luciferase (Luc2) for drug testing. Here, we describe three new mutant L. amazonensis lines that express different variants of luciferases NanoLuc, NanoLuc-PEST and RedLuc. These mutants were evaluated in drug screening protocols. NanoLuc-parasites, in spite of high bioluminescence intensity in vitro, were shown to be inadequate in discriminating between live and dead parasites. Bioluminescence detection from intracellular amastigotes expressing NanoLuc-PEST, RedLuc or Luc2 proved more reliable than microscopy to determine parasite killing. Increased sensitivity was observed in vivo with RedLuc-expressing parasites as compared to NanoLuc-expressing L. amazonensis. Our data indicates that NanoLuc is not suitable for in vivo parasite burden determination. Additionally, RedLuc and the conventional luciferase Luc2 demonstrated equivalent sensitivity in an in vivo model of cutaneous leishmaniasis. Mosquito-borne Zika virus (ZIKV) was recently introduced into the Americas and now has the potential to spill back into a sylvatic cycle in the region, likely involving non-human primates and Aedes, Haemagogus, and Sabethes species mosquitoes. We investigated potential routes of mosquito-borne virus exchange between urban and sylvatic transmission cycles by characterizing mosquito communities in three urban forest parks that receive heavy traffic from both humans and monkeys in Manaus, Brazil. Parks were stratified by both distance from the urban-forest edge (0, 50, 100, and 500 m) and relative Normalized Difference Vegetation Index (NDVI) (low, medium, or high), and mosquitoes were sampled at randomly selected sites within each stratum using BG-Sentinel traps. Additionally, temperature, relative humidity, and other environmental data were collected at each site. A total of 1,172 mosquitoes were collected from 184 sites sampled in 2018, of which 98 sites were resampled in 2019. Using park as the unit of replia multiple bridge vectors in Brazilian urban forest parks. These parks may also provide refugia for both Ae. albopictus and Ae. aegypti from mosquito control programs. V.Q fever is a widespread zoonotic disease caused by Coxiella burnetii that most commonly infects not only a variety of mammals but also arthropods and in particularly ticks. The aim of this study was to detect C. burnetii infection in camels including ixodid ticks using serological and molecular assays. Between July 2018 to June 2019, blood samples from 184 male and female camels (Camelus dromedarius) were collected from 3 regions of South-East Algeria and serum samples were tested for antibodies against Coxiella burnetii using indirect enzyme-linked immunosorbent assay (ELISA) kit. The positive sera and a total of 60 ticks were tested by quantitative PCR (qPCR) for detection of C. burnetii with primers and probes specific to the transposon-like repetitive region (IS1111 gene). Positive samples were genotyped by amplification and sequencing of partial sequences based on the IS1111 gene. The seroprevalence of antibodies against C. burnetii was 75.5%. Statistical analysis pointed out three potential risk factors associated with Q fever infection geographic location, age class and season. No positive DNA of camel blood sample was observed. However, five Hyalomma dromedarii, one H. impeltatum and one H. excavatum tick species were detected positive for Coxiella burnetii DNA by qPCR, with an overall prevalence rate of 11.66% (7/60). The revealed Algerian strains by phylogenetic and comparative analysis of the IS1111 nucleotide sequences were clustered with several pathogenic C. burnetii strains isolated from ticks, human, and cattle located in Tunisia, Greece and in some Mediterranean countries, respectively. The study results clearly indicate that camels and their ticks in Algeria may play an important role as a reservoir for C. burnetii and can be considered as a significant source of Q fever transmission to other animal species and humans. INTRODUCTION The work has been reported in line with the SCARE criteria. Thoracoabdominal impalement injuries are uncommon and very few cases have been reported. Impalement injuries result when a rigid object penetrates and remains lodged within the body. It has complex anesthetic and surgical management. We describe the successful surgical and anesthetic management of a major impalement injury of the torso. CASE REPORT A 21-year old male construction worker brought to emergency with two iron construction rods impaled in torso due to fall from 2nd floor while working. Both were 1 m long and 12 mm in diameter. One had penetrated from right anterior axillary fold, deep to pectoralis major, exiting from left sternal border. Second entered below the tip of right scapula and exiting from left of xiphoid process. ATLS protocols were followed and patient resuscitated, immediately shifted to operating room, intubated in semi left lateral position. Rod impacted in right pectoral area was superficial with no injury to ribs or pleural space. Other was removed through laparotomy, thoracotomy and Hepatotomy, as it had pierced diaphragm and liver. Post-operative recovery was uneventful. DISCUSSION Resuscitation and close monitoring prior to and during surgery are vital with anticipation of major organ and vascular injuries. Hypovolemia should be corrected in the OR. Progressive dyspneacan be the most important symptom in patients with penetrating chest injury. CONCLUSION Penetrating abdominothoracic injuries demand immediate life-saving measures, appropriate resuscitative care, urgent shifting of patient to tertiary care center, prompt diagnosis and immediate surgical intervention. Regulation of safety rules at construction site and early intervention in case of accidents can improve the patient outcome and minimize mortality. AIMS Chronic stress leads to the development of male sexual problems such as ejaculatory dysfunctions. The rhythmic contractions of vas deferens (VD) play an important role on the ejaculatory process. In the current study, we investigated whether infliximab (IFX) treatment has any beneficial effects on possible alterations in contractility of VD obtained from rats exposed to unpredictable chronic mild stress (UCMS). MATERIALS AND METHODS The rats were randomly divided into four groups control, control+IFX, UCMS and UCMS+IFX. IFX (5 mg/kg/week, i.p.) was administrated for 5 weeks during UCMS period. Depressive like-behaviors were evaluated using locomotor activity, forced swimming and sucrose consumption and preference tests. The blood was collected for serum biochemical determinations. VD tissues were harvested for functional studies and, measurements of oxidative stress, inflammatory and apoptotic biomarkers. KEY FINDINGS We observed increased serum concentration of corticosterone and depressive-like behaviors in rats exposed to UCMS. In VD tissues of UCMS-exposed rats, noradrenaline- and adenosine triphosphate (ATP)-induced contractile responses significantly enhanced and electrical field stimulation (EFS)-induced contractile responses markedly decreased. UCMS exposure induced inflammation, oxidative stress and apoptosis in VD. However, IFX treatment significantly improved all the aforementioned parameters. SIGNIFICANCE The results of the present study revealed that chronic stress-induced depression caused VD dysfunction by promoting inflammation and oxidative stress in VD. IFX protected against VD dysfunction through its anti-inflammatory and antioxidant effects. BACKGROUND Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Prohibitin 1 (PHB1) is known for its significant anti-proliferative activity. However, the role of PHB1 in PASMCs and PAH have not been elucidated. METHODS Monocrotaline (MCT 60 mg/kg) was used to build a PAH model in SD rats. Right ventricular systolic pressure (RVSP) and right ventricle (RV) hypertrophy were measured. Morphology of pulmonary vessels was observed by Hematoxylin-Eosin (HE) staining. Expression of PHB1 in pulmonary arteries and PASMCs was determinated by immunoblot and immunofluorescence. Cell proliferation was detected by CCK8 and EDU when PASMCs were stimulated by PDGF-BB (20 ng/mL). Furthermore, siRNA for PHB1 and Akt inhibitor were conducted to investigate the mechanism behind the role of PHB1 and AKT signaling pathway in PASMCs proliferation and apoptosis. RESULTS The protein expression of PHB1 in PAH rats lung tissue was significantly up-regulated accompanied by elevated RVSP and enhanced RV hypertrophy. Immunohistochemistry showed that PHB1 was mainly localized in the pulmonary vascular smooth muscle layer. PDGF-BB significantly up-regulated the expression of PHB1 in rat primary PASMCs in a time- and dose-dependent manner. After PHB1 knock down, PASMCs proliferation was significantly suppressed while apoptosis was significantly recovered. Meanwhile the level of proliferating cell nuclear antigen (PCNA) and P-Akt were significantly down-regulated. Perifosine (Akt inhibitor) also significantly inhibit proliferation of PASMCs. CONCLUSION PHB1 contributes to pulmonary vascular remodeling by accelerating proliferation of PASMCs which involves AKT phosphorylation. Gastric cancer (GC) is responsible for high morbidity and mortality worldwide. This cancer claims fifth place among other cancers. There are a number of factors associated with GC development such as alcohol consumption and tobacco smoking. It seems that genetic factors play significant role in GC malignancy and progression. MicroRNAs (miRs) are short non-coding RNA molecules with negative impact on the expression of target genes. A variety of studies have elucidated the potential role of miRs in GC growth. Investigation of molecular pathways has revealed that miRs function as upstream modulators of Wnt signaling pathway. This signaling pathway involves in important biological processes such as cell proliferation and differentiation, and its dysregulation is associated with GC invasion. At the present review, we demonstrate that how miRs regulate Wnt signaling pathway in GC malignancy. OBJECTIVES Advance care planning in young-onset dementia largely remains a blind spot within current literature. This study aimed to explore the engagement in and the conceptualization of advance care planning from the perspective of family caregivers of persons with young-onset dementia and to identify potential similarities and differences in this area between American and Belgian persons with young-onset dementia and their family caregivers. DESIGN An exploratory qualitative study. SETTING AND PARTICIPANTS We purposively sampled adult family caregivers of persons with young-onset dementia; our respondents were 13 American and 15 Belgian caregivers with varying familial relationships to the patient. METHODS We conducted 28 semi-structured interviews, using the same interview guide for American and Belgian respondents. Verbatim transcripts were analysed through the method of constant comparative analysis. RESULTS Important similarities between American and Belgian respondents were restricted knowledge of advance care planning, limited communication about advance directives, and their recommendation for professionals to timely initiate advance care planning. Major differences were attention paid to those end-of-life decisions depicted in the legislature of their respective countries, American caregivers placed higher emphasis on financial planning than their Belgian peers, and, in the case of consulting professionals for advance directives, American caregivers turned to lawyers, whereas Belgian caregivers relied on physicians. CONCLUSIONS AND IMPLICATIONS Specific nuances and challenges in terms of advance care planning in young-onset dementia arise from a particular societal and legal context on the one hand, and from patients’ and caregivers’ younger age on the other. Professionals’ awareness of and responsiveness to these specificities could facilitate the advance care planning process. Based on our interpretation of results, several recommendations for practice and policy are made. OBJECTIVES To identify clinical and/or functional variables predictive of successful oxygen-weaning among older patients affected by respiratory insufficiency undergoing pulmonary rehabilitation. DESIGN Retrospective study. SETTING AND PARTICIPANTS Data are from 154 patients aged 65 years and older (mean age = 78.1 years; female 50.6%) admitted to a pulmonary rehabilitation unit to follow an in-patient program. Patients must require oxygen therapy at admission. METHODS All patients performed the 6-Minute Walking Test at admission and before discharge as well as a spirometry at a steady state. Multivariate logistic regressions were performed to identify positive and negative predictors of successful oxygen weaning. RESULTS Successful oxygen weaning was obtained in 47 participants (30.5%). The restrictive pattern was associated with a 4-fold likelihood of successful oxygen weaning at the end of the rehabilitation program compared with the obstructive one. A positive association was also found for arterial oxygenation index (PaO2/FiO2 ratio) at baseline. A decreased likelihood of successful oxygen weaning was reported for the subjective dyspnea perception score at exertion evaluated with a modified Borg scale. CONCLUSIONS AND IMPLICATIONS The restrictive pattern, PaO2/FiO2 ratio, and modified Borg dyspnea scale score under exertion were significantly associated with successful oxygen-weaning. The identified predictors may support clinicians at precociously identifying patients who may not require oxygen therapy after discharge. Therefore, these findings would make it possible for clinicians to better tailor the rehabilitation program. Having a hepatitis B virus (HBV) or hepatitis C virus (HCV) infection places a child at higher risk for subsequent chronic hepatitis B (CHB) or chronic hepatitis C (CHC) infection. The risk of mother-to-child transmission is higher for HBV (20% to 90%) than for HCV ( less then 5%). Perinatal HBV infection generally causes CHB infection while perinatal HCV infection has a certain rate of spontaneous viral clearance (around 20% to 30%). Of the two, only HBV infection can benefit from passive/active perinatal immunoprophylaxis. The risk of CHB in children with HBV horizontal transmission decreases with age, whereas HCV transmission among teenagers commonly results into a long-life infection and CHC infection. Children with CHB or CHC should be carefully assessed for the need for antiviral treatment. When treatment cannot be deferred, pediatric CHB infection has different first-line treatment options standard interferon (for children aged≥1 year), pegylated interferon (for children aged≥3 years), and the oral nucleotide analogues entecavir (for children aged≥2 years) and tenofovir (for children aged≥12 years). The choice of treatment depends on the child’s age, virus genotypes, previous treatment failure and presence of contraindications. Expected responsiveness rate is 25% of hepatitis B e-antigen clearance, with both standard interferon and nucleotide analogues. Direct antiviral agents are first-line treatment for CHC infection in children aged 3 years or older. Hepatitis C virus sustained virus response is as high as 97%. Therefore, if direct antiviral agents can be proven to be safe and well tolerated in very young children, HCV eradication could be planned after the first screening. OBJECTIVES Patient-reported cognitive complaint (CI) is poorly described in older adults with cancer. The purpose of this study was to quantify the prevalence and examine the associations of patient-reported CI in older adults with gastrointestinal (GI) malignancies at diagnosis. MATERIALS AND METHODS Using participants ≥60 years with GI malignancies from the Cancer & Aging Resilience Evaluation (CARE) Registry that underwent a Geriatric Assessment (GA), we examined CI using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form 4a Cognitive Function. Cognition scores were dichotomized into normal (scores of 15-20) and impaired (4-14), and bivariate and multivariate analyses were used to examine associations. RESULTS A total of 264 participants with GI malignancy were included, mean age of 70.0 ± 7.1, 55.7% male, pancreatic cancer was the most common cancer (24.2%) and majority were stage III/IV (68.2%). 29.3% of participants endorsed CI. CI was not associated with demographic and clinical domains, but was associated with many GA impairments including instrumental Activities of Daily Living (iADL) impairment (adjusted odds ratio [aOR] 6.0, 95% confidence interval 3.0-11.8), falls (aOR 2.7, 1.4-5.4), anxiety (aOR 10.3, 5.2-20.4), and depression (aOR 10.2, 5.2-20.4). CI was also associated with reduced global mental (aOR 18.7, 8.1-42.2) and physical (aOR 4.7, 2.4-8.9) quality of life, and prior hospitalizations (aOR 2.4, 1.2-4.8). CONCLUSION We found a high prevalence of patient-reported CI in older adults with GI malignancies that was associated with increased GA impairments, reduced health-related quality of life, and increased healthcare utilization. Published by Elsevier Ltd.In this paper, we have proposed a two-phase procedure (combining discrete graphs and wavelets) for constructing true epidemic growth. In the first phase, a graph-theory-based approach was developed to update partial data available and in the second phase, we used this partial data to generate plausible complete data through wavelets. We have provided two numerical examples. This procedure is novel and implementable and adaptable to machine learning modeling framework. INTRODUCTION The role of bipolar radial head prostheses (RHP) in elbow fracture-dislocation is controversial, with some reports of poorer stabilization than with monopolar designs. The aim of the present study was to compare mono- versus bi-polar RHPs in elbow fracture-dislocation. The study hypothesis was that mono- and bi-polar RHPs do not differ in clinical and radiological results, complications or revision rates. MATERIAL AND METHODS A single-center retrospective study included 58 patients, with a mean age of 55 years (range, 21-84 years). All received RHP for elbow dislocation with association terrible triad, Monteggia fracture-dislocation, transolecranal dislocation or divergent dislocation. Two groups were compared Mono-RHP, with monopolar prosthesis (n=40), and Bi-RHP, with bipolar prosthesis (n=18). All patients underwent clinical and radiological examination at last follow-up. RESULTS Mean follow-up was 42.7 months (range, 12-131 months). There were no significant (p>0.05) inter-group differences in range of motion or Mayo Elbow Performance Score. Mono- versus bi-polar design did not correlate with onset of complications (p=0.89), surgical revision (p=0.71), persistent or recurrent instability (p=0.59), or ulnohumeral (p=0.62) or capitulum (p=0.159) osteoarthritis at last follow-up. DISCUSSION AND CONCLUSION No differences were found between mono- and bi-polar RHPs in the treatment of elbow fracture-dislocation. Clinical and radiographic results were similar, as were complications and revision rates. The literature is inconclusive, reporting contradictory conclusions. We see no contraindications to bipolar RHPs in elbow dislocation with association, notably terrible triad injury. LEVEL OF EVIDENCE III, Retrospective case-control study. INTRODUCTION It is common practice to obtain follow-up radiographs of non-operatively treated isolated greater tuberosity (GT) fractures 1 to 2 weeks after trauma. However, the majority of non-operatively treated GT fractures remain stable and do not require reconsideration of the initial treatment decision. Radiological follow-up therefore might be unnecessary. Our primary objective was to study whether radiological folow-up changes the initial treatment recommendation, hypothesizing no change. MATERIALS AND METHODS Radiographs of 25 patients diagnosed with an isolated GT fracture were selected from our hospital database and presented on a web-based platform. Sixty-eight trauma- and orthopedic surgeons evaluated these radiographs. First the radiographs directly post-trauma and then, in random order, the radiographs 5-14 days post-trauma alongside the first radiographs. Each observer evaluated each set of radiographs once. The observers answered which treatment they would recommend (non-operative/operative), -observer variation. Radiological follow-up of a non-operatively treated isolated GT fracture therefore seems justifiable. LEVEL OF EVIDENCE III, diagnostic study. INTRODUCTION The outcomes of the Latarjet procedure for anterior shoulder instability are highly satisfactory although recurrences are possible. Surgical revision is challenging, and often requires an iliac crest bone graft as described by Eden and Hybinette. The aims of our study were to analyze the outcomes of the Eden-Hybinette technique after failed Latarjet procedure, determine the failure and complication rates, and analyze the risk of osteoarthritis. We hypothesized that the Eden-Hybinette technique would yield good outcomes after failed Latarjet procedure. MATERIAL AND METHODS Retrospective multicenter study (9 hospitals) by the French Shoulder and Elbow Society (SoFEC) involving 46 patients who underwent revision surgery with an Eden-Hybinette procedure after failed Latarjet stabilization. The patients had a minimum follow-up of 1year and the outcomes were evaluated based on the Rowe score, Walch-Duplay score and radiographs. RESULTS The mean age at the final assessment was 32years. The mean follow-up was 38 months and 86% of patients had a stable shoulder with an overall satisfaction rate of 80%. Postoperatively, the Rowe score averaged 76/100 and the Walch-Duplay score averaged 68/100; 60% of patients had resumed their sports participation. Return to sport was statistically correlated with age (p=0.0001), osteoarthritis (p=0.05) and time elapsed between the two surgical procedures (p=0.0001). The Rowe score was statistically correlated with osteoarthritis (p=0.01). DISCUSSION/CONCLUSION Our study is one of the largest on the Eden-Hybinette procedure for recurrent anterior shoulder instability. The outcomes at 3years’ follow-up were satisfactory in 80% of patients and 86% had stable shoulders. The osteoarthritis rate was low (11%), although the follow-up period was relatively short. LEVEL OF EVIDENCE IV, non-randomized multicenter retrospective study. There is a lack of comprehensive studies on the seroprevalence of tick-borne pathogens in the Republic of Korea. Therefore, the aim of this study was to investigate the seroprevalences of Anaplasma spp. (A. phagocytophilum/A. platys), Borrelia burgdorferi sensu lato, Babesia gibsoni, Ehrlichia spp. (E. canis/E. ewingii), and Ehrlichia chaffeensis in dogs across the Republic of Korea in 2017 and 2018. A total of 2215 serum samples collected from 938 companion dogs, 969 shelter dogs, and 308 military working dogs were examined using commercial enzyme-linked immunosorbent assay (ELISA) and indirect fluorescence immunoassay (IFA) kits. Data collected for each animal, including breed, sex, age, region, season, and dog type, were used for statistical analysis. The overall seroprevalence was highest for Anaplasma spp. (15.1 %), followed by Ehrlichia spp. (10.3 %), B. burgdorferi sensu lato (6.4 %), E. chaffeensis (2.3 %), and B. gibsoni (1.7 %). One hundred and sixty-one dogs had antibodies against two or three different pathogens. The most common combinations were Anaplasma spp. – Ehrlichia spp. (2.1 %), Anaplasma spp. – E. chaffeensis (1.4 %), and Anaplasma spp. – B. burgdorferi sensu lato (1.2 %). Season was significantly associated with the seroprevalences of B. burgdorferi sensu lato and Ehrlichia spp., with dogs presenting the highest percentage of positive results during summer. Anaplasma spp. and B. gibsoni were significantly more prevalent in the northern and southern regions, respectively. The seroprevalences of Anaplasma spp., B. burgdorferi sensu lato, and Ehrlichia spp. were significantly higher in military working dogs, while the seroprevalence of E. chaffeensis was higher in companion dogs. The current findings are important for future surveillance of canine tick-borne pathogens and designing appropriate approaches for the diagnosis and control of these pathogens in the Republic of Korea. Rhipicephalus microplus is responsible for major economic losses in cattle ranching in Brazil, and the development of multiple acaricide resistance is a major concern to control this ectoparasite. To determine the resistance of R. microplus to acaricides in 26 ranches in the semi-arid region of Paraíba State, Brazil, larval assays were performed with cypermethrin, chlorpyriphos, amitraz, ivermectin and fipronil and resistance was observed in all locations. The frequency of populations resistant to cypermethrin, chlorpyriphos, amitraz and ivermectin was, respectively, 96 %, 72 %, 83 % and 92 % while none was resistant to fipronil. Resistance to one, two, three and four acaricides was recorded, respectively, in 4 %, 15 %, 31 % and 50 % of the farms. Errors in the control management of R. microplus determined the development of resistance to acaricides in all evaluated properties pointing towards development of new strategies for its control. In order to control multiple acaricide-resistant cattle tick populations in this area it is recommended to apply suppressive treatments with fipronil and/ or fluazuron. Tick-borne encephalitis virus (TBEV; family Flaviviridae) is the most medically important tick-borne virus in Europe and Asia. Ixodes ricinus and I. persulcatus ticks are considered to be the main vector ticks of TBEV in nature due to their specific ecological associations with the vertebrate hosts. Nevertheless, recent TBEV prevalence studies in ticks suggest that Dermacentor reticulatus ticks might play a relevant role in the maintenance of TBEV in nature. The goal of this study was to evaluate the vector competency of D. reticulatus for TBEV through experimental tick infections and comparative in vivo transmission studies involving D. reticulatus and I. ricinus ticks. We observed that after a transcoxal micro-capillary inoculation, adult female D. reticulatus ticks efficiently replicated TBEV during the observed period of 21 days. The mean virus load reached up to 2.5 × 105 gene copies and 6.4 × 104 plaque forming units per tick. The infected D. reticulatus ticks were able to transmit the virus to mice. The course of infection in mice was comparable to the infection after a tick bite by I. ricinus while the virus spread and clearance was slightly faster. Moreover, D. reticulatus ticks were capable of tick-to-tick non-viraemic transmission of TBEV to the Haemaphysalis inermis nymphs during co-feeding on the same animal. The co-feeding transmission efficiency was overall slightly lower (up to 54 %) in comparison with I. ricinus (up to 94 %) and peaked 1 day later, at day 3. In conclusion, our study demonstrated that D. reticulatus is a biologically effective vector of TBEV. In line with the recent reports of its high TBEV prevalence in nature, our data indicate that in some endemic foci, D. reticulatus might be an underrecognized TBEV vector which contributes to the expansion of the TBEV endemic areas. Surgical education requires more than time and commitment; it is a period of a professional development that relies on one’s resilience and fortitude. While training programs makes substantial efforts to onboard learners and prepare them for the experiences to come, most are likely underutilizing one of the greatest resources available to learners their personal communities. Every intern who enters residency brings with them the emotional bonds and benefits of family, friends, and/or other community members who may or may not understand the nature of surgical training and the professional journey ahead. In an effort to support our own learners and increase the awareness of resources available to them, we hosted an orientation for interns’ friends and families. The programming allowed for residents and their personal supports to better understand residency culture, meet educational leadership, and discuss the experiences of more senior residents, faculty and their families over time. Additionally, some education was provided regarding the signs and symptoms of burnout and depression; our aim was to help residents’ communities feel better able to recognize and respond to such symptoms. The preliminary feedback regarding the program is strong, encouraging its continued implementation. OBJECTIVE The daily orthopedic trauma meeting is considered to serve a dual purpose; a way of discussing management of trauma patients and as a forum for teaching trainees. This study is first to explore orthopedic trainees’ perspectives on the educational value of trauma meetings and identify factors that influence educational benefit across England. DESIGN An online questionnaire was created including free text responses questions. After initial pilot testing, orthopedic registrar trainees with a national training number within England were emailed and the questionnaire completed online. Results were analyzed using thematic analysis and online survey software. SETTING A national study conducted across England in trauma and orthopedic departments in a secondary care setting. RESULTS One hundred and thirteen responses were recorded nationally with wide spread of seniority and geographical location. About 73.5 % of trainees found the trauma meeting to be educationally valuable. However, only 30.1% of trainees ng trauma meetings. OBJECTIVE To obtain a legal understanding of the „key” or „critical” portions of an operation, pertaining to attending supervision, resident autonomy, and patient safety. DESIGN Snowball sampling, a subset of purposive sampling, was used to develop a population of 47 risk managers and legal counsel, who were given an online, qualitative questionnaire. Interpretive description was used to analyze qualitative data. Individual responses were coded with simultaneous categorization and assessment of underlying relationships. SETTING Online, qualitative questionnaire. PARTICIPANTS Hospital risk managers and legal counsel from across the United States. RESULTS Overall, 25 of 47 (53%) risk managers completed the survey. Qualitative responses could be organized into 3 major themes (1) variation in the definition of „key” or „critical” portions of an operation, (2) differing expectations of attending supervision and resident autonomy, and (3) the need for clear communication and trust among attendings, residents, and patients. CONCLUSIONS Among risk managers, the primary liaisons between surgeons and patients in malpractice litigation, there is widespread variation in understanding the „key” and „critical” portions of an operation and the dynamic between appropriate attending supervision and resident autonomy. Better collaboration and transparency between surgeons and legal experts are required to facilitate a shared mental model regarding attending supervision and resident autonomy. BACKGROUND The goal of this study was to determine the frequency and predictive factors of partial (PCI) and total clinical inertia (TCI) of general physicians (GPs) in Central Bosnia Canton in the care of type 2 diabetes mellitus patients. MATERIAL AND METHODS A longitudinal study was conducted with a prospective data collection. Total of 541 subjects of over 40 years of age with type 2 diabetes mellitus of both genders were included in the study. Total of 532 subjects completed the study. Questionnaires for physicians and patients and the Perceived Stress Scale were used, as well as anthropometric measurements and measurements of the glucose level in plasma, HbA1c, triglycerides, AST, ALT, creatinine and eGFR, which were examined on the day of study entry, after 6 months and after one year. RESULTS TCI was 5.8% and PCI was 25.6%. Patients with poorly regulated glycaemia and elevated triglyceride levels had the highest probability of PCI and TCI. Patients with an unaccomplished targeted level of blood pressure were more likely to experience PCI. Patients treated by both an internist and a general physician were more likely to have TCI as compared to patients treated only by an internist. CONCLUSIONS Patients with poor glycemic control experience PCI and TCI more often. In our study, referring to a diabetologist was observed as a non-inert procedure, which resulted in lower PCI and TCI, compared to studies where clinical inertia was defined only as non-intensification of medication therapy. AIMS Seventy percent of Africans living with diabetes are undiagnosed. Identifying who should be referred for testing is critical. Therefore we evaluated the ability of the Atherosclerosis Risk in Communities (ARIC) diabetes prediction equation with A1C added (ARIC + A1C) to identify diabetes in 451 African-born blacks living in America (66% male; age 38 ± 10y (mean ± SD); BMI 27.5 ± 4.4 kg/m2). METHODS All participants denied a history of diabetes. OGTTs were performed. Diabetes diagnosis required 2-h glucose ≥200 mg/dL. The five non-invasive (Age, parent history of diabetes, waist circumference, height, systolic blood pressure) and four invasive variables (Fasting glucose (FPG), A1C, triglycerides (TG), HDL) were obtained. Four models were tested Model-1 Full ARIC + A1C equation; Model-2 All five non-invasive variables with one invasive variable excluded at a time; Model-3 All five non-invasive variables with one invasive variable included at a time; Model-4 Each invasive variable singly. Area under the receiver operator characteristic curve (AROC) predicted diabetes. Youden Index identified optimal cut-points. RESULTS Diabetes occurred in 7% (30/451). Model-1, the full ARIC + A1C equation, AROC = 0.83. Model-2 With FPG excluded, AROC = 0.77 (P = 0.038), but when A1C, HDL or TG were excluded AROC remained unchanged. Model-3 with all non-invasive variables and FPG alone, AROC=0.87; but with A1C, TG or HDL included AROC declined to ≤0.76. Model-4 FPG as a single predictor, AROC = 0.87. A1C, TG, or HDL as single predictors all had AROC ≤ 0.74. Optimal cut-point for FPG was 100 mg/dL. CONCLUSIONS To detect diabetes, FPG performed as well as the nine-variable updated ARIC + A1C equation. Published by Elsevier Ltd.The search for novel compounds to combat multi-resistant bacterial infections includes exploring the potency of antimicrobial peptides and derivatives thereof. Complementary to high-throughput screening techniques, biophysical and biochemical studies of the biological activity of these compounds enable deep insight, which can be exploited in designing antimicrobial peptides with improved efficacy. This approach requires the combination of several techniques to study the effect of such peptides on both bacterial cells and simple mimics of their cell envelope, such as lipid-only vesicles. These efforts carry the challenge of bridging results across techniques and sample systems, including the proper choice of membrane mimics. This review describes some important concepts toward the development of potent antimicrobial peptides and how they translate to frequently applied experimental techniques, along with an outline of the biophysics pertaining to the killing mechanism of antimicrobial peptides. RATIONALE AND OBJECTIVES Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury. MATERIALS AND METHODS We studied supine sheep in four groups Permissive Atelectasis (n = 6)-16 hours protective tidal volume (VT) and zero positive end-expiratory pressure; Mild (n = 5) and Moderate Endotoxemia (n = 6)- 20-24 hours protective ventilation and intravenous lipopolysaccharide (Mild = 2.5 and Moderate = 10.0 ng/kg/min), and Surfactant Depletion (n = 6)-saline lung lavage and 4 hours high VT. Measurements performed immediately after anesthesia induction served as controls (n = 8). Atelectasis was defined as regions of gas fraction less then 0.1 in transmission or computed tomography scans. 18F-FDG kinetics measured with positron emission tomogr suggests an injurious remote effect of atelectasis even with protective tidal volumes. PURPOSE To compare the quantitative and qualitative lung perfusion data acquired with dual energy CT (DECT) to that acquired with a large field-of-view cadmium-zinc-telluride camera single-photon emission CT coupled to a CT system (SPECT-CT). MATERIALS AND METHODS A total of 53 patients who underwent both dual-layer DECT angiography and perfusion SPECT-CT for pulmonary hypertension or pre-operative lobar resection surgery were retrospectively included. There were 30 men and 23 women with a mean age of 65.4±17.5 (SD)years (range 18-88years). Relative lobar perfusion was calculated by dividing the amount (of radiotracer or iodinated contrast agent) per lobe by the total amount in both lungs. Linear regression, Bland-Altman analysis, and Pearson’s correlation coefficient were also calculated. Kappa test was used to test agreements in morphology and severity of perfusion defects assessed on SPECT-CT and on DECT iodine maps with a one-month interval. Wilcoxon rank sum test was used to compare the sharpness of perfusion defects and radiation dose among modalities.


