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Abstract Background The Attune TKR was introduced in 2011 as a successor to its predicate design The PFC Sigma. However, following reports of early failures, there are ongoing concerns related to increased loosening rates. Given the concerns, this study aimed to compare revision rates of the Attune implant to an established predicate, and other implant designs used in a high-volume arthroplasty center. Methods We identified 10,202 patients who underwent primary cemented TKR at our institution with a minimum of 1 year follow-up, involving 2406 Attune TKR (557 S +), 4642 PFC TKR, 3154 other designs. Primary outcomes were revision for all-causes, aseptic loosening of any component, and aseptic tibial loosening. Kaplan–Meier survival and Cox regression models were used to compare groups. Matched cohorts were selected for radiographic analysis. Results 308 knees were revised. The Attune cohort had the lowest risk of revision, with a rate of 2.98 per 1000 implant-years while the PFC and All Other Implant groups had a rate of 3.15 and 4.4 respectively. Aseptic loosing was the most common cause for revision, with 76% (65/88) involving the tibia. Survival analysis showed no significant differences between the Attune and other cohorts. Radiolucent lines were detected in 7.1% of the Attune S + group, 6.8% of the standard Attune group, and 6.3% of the PFC group, with no significant differences found between them. Conclusion This study represents the largest non-registry review of the Attune TKR in comparison to a predicate and other designs. There was no significant increased revision rate for all-cause revision or aseptic loosening, or peri-implant radiolucencies. It appears that increased loosening may not be as concerning as originally thought. Level of Evidence Level III.

Background: Stiffness is a common complication following total knee arthroplasty. Manipulation under anesthesia (MUA) is an intervention that can potentially improve range of motion (ROM). Continuous passive motion (CPM) therapy has been utilized to enhance post-MUA ROM, but its effectiveness remains debated. This study assesses whether CPM therapy after MUA results in superior ROM outcomes compared to MUA alone. Methods: A retrospective analysis included patients undergoing MUA for stiff primary total knee arthroplasty between 2017 and 2022. Demographics and ROM data were collected. Patients were in 2 groups: those who received inpatient CPM post-MUA and those who received day-case MUA alone. Complications and further interventions were noted. Results: Of 126 patients, 39 underwent MUA only (day-case group), and 87 received CPM and MUA (inpatient group). Mean preoperative ROM was 69.4° (standard deviation [SD]:18.0°) and 73.9° (SD: 18.1°) for inpatient and day-case groups, respectively. Mean post-MUA ROM improved by 39.4° (SD: 17.7°) and 25.5° (SD: 11.1°) inpatient groups and day-case, respectively. The mean percentage of ROM gained at MUA maintained at final follow-up was 63.7% (40.8%) and 67.0% (47.5%) inpatient and day-case groups, respectively. Conclusions: This study found no advantage in the routine use of CPM post-MUA for stiff total knee replacement patients, suggesting it may not provide sustained ROM improvements compared to MUA alone. Cost-effectiveness and patient selection merit further investigation.

Abstract Secondary minerals in lava tubes on Earth provide valuable insight into subsurface processes and the preservation of biosignatures on Mars. Inside lava tubes near the Hawaii-Space Exploration and Analog Simulation (HI-SEAS) habitat on the northeast flank of Mauna Loa, Hawaii, a variety of secondary deposits with distinct morphologies were observed consisting of mainly sodium sulphate powders, gypsum crystalline crusts, and small coralloid speleothems that comprise opal and calcite layers. These secondary deposits formed as a result of hydrological processes shortly after the formation and cooling of the lava tubes and are preserved over long periods of time in relatively dry conditions. The coralloid speleothem layers are likely related to wet and dry periods in which opal and calcite precipitates in cycles. Potential biosignatures seem to have been preserved in the form of porous stromatolite-like layers within the coralloid speleothems. Similar secondary deposits and lava tubes have been observed abundantly on the Martian surface suggesting similar formation mechanisms compared to this study. The origin of secondary minerals from tholeiitic basalts together with potential evidence for microbial processes make the lava tubes near HI-SEAS a relevant analog for Martian surface and subsurface environments.

Patients undergoing planned or unplanned orthopaedic procedures involving their upper or lower extremity can prevent them from safe and timely return to driving, where they commonly ask, ‘Doctor, when can I drive?’ Driving recommendations after such procedures are varied. The current evidence available is based on a heterogenous data set with varying degrees of sample size and markedly differing study designs. This instructional review article provides a scoping overview of studies looking at return to driving after upper or lower extremity surgery in both trauma and elective settings and, where possible, to provide clinical recommendations for return to driving. Medline, EMBASE, SCOPUS, and Web of Science databases were searched according to a defined search protocol to elicit eligible studies. Articles were included if they reviewed adult drivers who underwent upper or lower extremity orthopaedic procedures, were written in English, and offered recommendations about driving. A total of 68 articles were included in the analysis, with 36 assessing the lower extremity and 37 reviewing the upper extremity. The evidence available from the studies reviewed was of poor methodological quality. There was a lack of adequately powered, high quality, randomised controlled trials (RCTs) with large sample sizes to assess safe return to driving for differing subset of injuries. Many articles provide generic guidelines on return to driving when patients feel safe to perform an emergency stop procedure with adequate steering wheel control. In future, RCTs should be performed to develop definitive return to driving protocols in patients undergoing upper and lower extremity procedures.

There is a need to develop user-friendly imaging tools estimating robust quantitative biomarkers (QIBs) from multiparametric (mp)MRI for clinical applications in oncology. Quantitative metrics derived from (mp)MRI can monitor and predict early responses to treatment, often prior to anatomical changes. We have developed a vendor-agnostic, flexible, and user-friendly MATLAB-based toolkit, MRI-Quantitative Analysis and Multiparametric Evaluation Routines (“MRI-QAMPER”, current release v3.0), for the estimation of quantitative metrics from dynamic contrast-enhanced (DCE) and multi-b value diffusion-weighted (DW) MR and MR relaxometry. MRI-QAMPER’s functionality includes generating numerical parametric maps from these methods reflecting tumor permeability, cellularity, and tissue morphology. MRI-QAMPER routines were validated using digital reference objects (DROs) for DCE and DW MRI, serving as initial approval stages in the National Cancer Institute Quantitative Imaging Network (NCI/QIN) software benchmark. MRI-QAMPER has participated in DCE and DW MRI Collaborative Challenge Projects (CCPs), which are key technical stages in the NCI/QIN benchmark. In a DCE CCP, QAMPER presented the best repeatability coefficient (RC = 0.56) across test–retest brain metastasis data, out of ten participating DCE software packages. In a DW CCP, QAMPER ranked among the top five (out of fourteen) tools with the highest area under the curve (AUC) for prostate cancer detection. This platform can seamlessly process mpMRI data from brain, head and neck, thyroid, prostate, pancreas, and bladder cancer. MRI-QAMPER prospectively analyzes dose de-escalation trial data for oropharyngeal cancer, which has earned it advanced NCI/QIN approval for expanded usage and applications in wider clinical trials.

Introduction Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. Objectives This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. Methods Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. Results Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3–62.3) and 48.4% (95% CI, 39.7–57.1) among WLHIV screened in the rural vs urban settings ( p -value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1–11.9) of the WLHIV, with no significant difference in detection rates between the two settings ( p -value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). Conclusions There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

Abstract Social trust—between governments and people and between individuals—and trust in science were proposed as prerequisites for tackling covid. Others suggested less democratic societies were more able to impose strict rules stopping the virus. These propositions were tested for a group of mainly advanced countries. The dependent variable is cumulated deaths from covid. Findings are broken down between (a) OECD member countries, (b) these and countries having cooperation agreements with it, and (c) all these plus China. They are also broken down by time—between (a) the period before the appearance of “new variants” in late 2020 and (b) the period from then until end September 2021. The best, most parsimonious, models explain nearly half of the changes in the level of deaths. Trust in government improves outcomes, as does interpersonal trust. Vaccine antipathy does not play a role. Also, there is little indication that authoritarian regimes performed better than higher trust societies. In the first period, increasing wealth inequality—indicating a more divided society—is related to higher death rates. Hospital bed availability is important then, but not thereafter. Furthermore, as the pandemic persisted, the importance of pre-existing levels of social trust declined. The paper warns that institutions and cultures cannot easily be transferred from one country to another. Nor would all transfers be desired. It also suggests that some other lessons of what contributed to better outcomes under covid might be relevant for the monkeypox virus—its successor public health emergency.

Molybdenum-oxide nanoplates are grown directly from the surface of molybdenum substrates using a catalyst-free flame synthesis technique. To investigate the effects of oxidizing routes, e.g., from gas-phase O2, H2O, and CO2 as reactants, on the growth and morphology of the molybdenum-oxide nanostructures, quasi-1D counterflow diffusion flames are strategically utilized and probed at specific locations within their flame structures. Moreover, two separate flame structures are compared using different fuels (i.e., methane and hydrogen) and diluted with nitrogen to have near-identical temperature profiles. For example, the H2O oxidizing route is scrutinized by assessing growth at the same elevated temperature locations at the fuel sides of the reaction zones of a CH4 flame (comprising H2O and CO2 as synthesis reactants) and an H2 flame (comprising only H2O as synthesis reactant). The temperature effect on the resultant morphologies are examined at 1280 K, 1500 K, and 1720 K. Single-crystalline MoO2 nanoplates (of thicknesses of 60-80 nm, widths of 200-450 nm, and lengths of 1-2 µm) that are regularly distributed with high-surface-area-exposed packing are obtained at 1720 K on the air side of the CH4 flame (with O2, H2O, and CO2 as synthesis reactants) for 10 min growth durations. Based on the results and Gibbs free energy calculations, the CO2 route is deduced to seed the growth of the nanoplates at the nucleation stage heterogeneously, with subsequent condensation-based growth from volatile intermediate species, such as MoO2(OH)2, playing an important role. With such studies revealing fundamental growth mechanisms, scale-up of the process with different flame configurations is afforded.

Bladder cancer can often exhibit genomic and morphological heterogeneity. Here, the authors use genomics analysis to show lineage plasticity of bladder cancers with squamous differentiation, and identify key transcription factors related to this morphological and immune heterogeneity.

Background: Adipose-derived mesenchymal stem cells (ADMSCs) have recently been studied for the treatment of knee osteoarthritis. The goal is pain reduction and improvement of joint function leading to superior health-related quality of life. Objectives: The aim of this study was to provide a comprehensive meta-analysis assessing the evidence on the use of ADMSCs in knee osteoarthritis. Design: This is a Meta-analysis of randomised controlled trials. Data Sources and Methods: PubMed/MEDLINE, Embase, and Cochrane Databases were searched for randomized controlled trials using ADMSCs to treat patients with knee osteoarthritis. Only trials comparing ADMSCs to placebo or conservative treatment were included. The outcomes studied were improvement in functional, pain, and quality of life scores along with radiographic findings. Results: A total of four trials were included, representing 138 patients with knee osteoarthritis. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores favored ADMSCs with a statistically and clinically significant difference over controls at 6- and 12-month follow-ups ( p value

The sexually dimorphic expression of cytochromes P450 (CYP) drug metabolizing enzymes has been reported in all species examined. These sex differences are initially expressed during puberty and are solely regulated by sex differences in th e circulating growth hormone (GH) profiles. Once established, however, the different m ale- and female-dependent CYP isoforms are permanent and immutable, suggesting that adult CYP expression requires imprinting. Since the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectiv ely blocked GH secretion in some newborn male rats while others also received a concurrent physiologic replacement of rat GH. Rats were subsequently challenged, peripubertally, w ith either a masculine-like episodic GH regimen or the GH vehicle alone. The results demonstrate that episodic GH regulation of male-specific CYP2C11 and CYP3A2, as well as femal e-predominant CYP2C6, are dependent on developmental GH imprinting. Moreover, the induction and/or activation of major components in the signal transduction pathway regulati ng the expression of the principal CYP2C11 isoform is obligatorily dependent on perinata l GH imprinting without which CYP2C11 and drug metabolism would be permanently and prof oundly suppressed. Since there are additional adult metabolic functions also regulated by GH, pediatric drug therapy that is known to disrupt GH secretion could unintention ally impair adult health.

Background: There have been conflicting reports regarding the effect of smoking on complications after surgical treatment of ankle fractures. This study aimed at identifying the complications for which smokers and subgroups of smokers are at a higher risk compared to nonsmokers when undergoing surgery for fixation of rotational ankle fractures. Methods: The American College of Surgeons National Surgical Quality Improvement Program data set from 2008 to 2019 was used to compare the 30-day wound, cardiac, renal, and infectious complications, related readmissions, and return to the operating room between the 2 cohorts. Results: Of 33 741 patients included, 25 642 (76.0%) were nonsmokers and 8099 (24.0%) were smokers. Multivariate analysis showed that smokers were at a higher risk for deep wound infection (OR 2.34, 95% CI 1.48-3.69, P < .001), wound dehiscence (OR 2.43, 95% CI 1.56-3.77, P < .001), related return to the operating room (OR 1.69, 95% CI 1.36-2.11, P < .001), and related readmissions (OR 1.67, 95% CI 1.32-2.09, P < .001). Smokers at an increased risk for deep infection included patients between 50 and 59 years (OR 5.75, 95% CI 1.78-18.5, P = .003), who were Black (OR 4.24, 95% CI 1.04-17.23, P = .044), who had body mass index (BMI) 35 to 39.9 (OR 3.73, 95% CI 1.46-9.50, P = .006), or operative times between 60 and 90 minutes (OR 3.64, 95% CI 1.79-7.39, P < .001). Smoker subgroups at a higher risk for wound dehiscence included patients between 50 and 59 years (OR 9.86, 95% CI 3.29-29.53, P < .001), with operative times between 90 and 120 minutes (OR 4.88, 95% CI 1.89-12.58, P < .001), with BMI 30 to 34.9 (OR 3.06, 95% CI 1.45-6.45, P = .003) and who underwent spinal/epidural anesthesia (OR 9.31, 95% CI 2.31-37.58, P = .002). Conclusion: Smokers were at an increased risk for deep wound infection, wound dehiscence, related reoperations, and related readmissions after ankle fracture surgery. Certain subgroups were at an even higher risk for these complications. Level of Evidence: Level III, retrospective cohort study.

Introduction Although individualized target glycated hemoglobin (HbA1c) levels are recommended in older people with type 2 diabetes, studies report high levels of potential overtreatment. We aimed to investigate the proportion of older patients (aged ≥65 years) who potentially received an inappropriately intensive treatment (HbA1c level

PurposeRadiolabeled Prostate-Specific Membrane Antigen (PSMA) PET/CT is the current standard-of-care for lesion detection in patients with biochemically recurrent (BCR) prostate cancer (PCa). However, rigorous verification of detected lesions is not always performed in routine clinical practice. To aid future 18F-radiolabeled PSMA PET/CT interpretation, we aimed to identify clinical/imaging characteristics that increase the likelihood that a PSMA-avid lesion is malignant.Materials and methods262 patients with BCR, who underwent 18F-DCFPyL PSMA PET/CT, were retrospectively analyzed. The malignant nature of 18F-DCFPyL PET-detected lesions was verified through any of the following metrics: (1) positive histopathological examination; (2) additional positive imaging; (3) a ≥50% decrease in Prostate-Specific Antigen (PSA) following irradiation of the lesion(s).ResultsIn 226/262 PET scans (86.3%) at least one lesion suspicious for recurrent PCa was detected ('positive scan'). In 84/226 positive scans (37.2%), at least one independent verification metric was available. PSMA PET-detected lesions were most often confirmed to be malignant (PCa) in the presence of a CT-substrate (96.5% vs. 55.6% without CT-substrate), with SUVpeak ≥3.5 (91.4% vs. 60.0% with SUVpeak2 PET-positive lesions (94.1% vs. 64.2% in patients with 1-2 PET-positive lesions; pConclusionsIn this study, the clinical verification of 18F-DCFPyL PET-positive lesions in patients with BCR was performed. Diagnostic certainty of PET-detected lesions increases in the presence of characteristic abnormalities on CT, when SUVpeak is ≥3.5, when PSA-levels exceed 2.0 ng/mL or in patients with more than two PET-positive lesions.

Introduction and Objective: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) has become an increasingly utilized approach to treating various bladder pathologies requiring extirpation. As surgeons have become more experienced with ICUD, especially with lesser-used diversions such as continent cutaneous reservoirs, the technique has evolved. Methods: We describe our technique and recent advances in the practical creation of robotic ICUD with a continent catheterizable pouch (CCP) built upon the open principles of the previously described “Indiana Pouch,” which uses the distal ileum and right colon. Modifications in anatomic mobilization and exposure, bowel segmentation using novel robotic bowel staplers, catheterizable channel creation, and addition of ileal chimney for uretero-enteric anastomoses are highlighted. The addition of the ileal chimney allows for ease of reconstruction in a fashion familiar to surgeons accustomed to performing intracorporeal ileal conduit and, therefore, may result in lower ureteroenteric stricture rates. Table 1 demonstrates the supplies used intraoperatively. Use of indocyanine green to assess vascularity in bowel and ureter intraoperatively is demonstrated. The port configurations are demonstrated using the DaVinci ® Xi platform. Also described are short-term outcomes of our initial experience. Results: Eleven consecutive patients (5 female) who have undergone ICUD with CCP were included. Of the eleven, seven had malignant indications (bladder or urethral cancer) while 4 were for benign causes (2 radiation cystitis, 2 interstitial cystitis). Mean blood loss was 235cc (range 100–500cc) and mean operative time was 8.5 h (range 7–13). There were no conversions to an open procedure and no patient required a blood transfusion. Hospital stay was 7.2 days on average (range 4–18) with no 30-day post-discharge readmissions. One patient had a Clavien grade 3 or greater complication at 30 days (Table 2). No urine leaks or bowel leaks were observed and no patient experienced stomal stenosis or uretero-enteric stenosis. At three months follow up, all patients were continent and satisfied with their diversion. Conclusions: RARC with CCP ICUD is a safe and effective approach to bladder removal and reconstruction. As more surgeons utilize RARC, growing attention to techniques of intracorporeal reconstruction will allow further implementation of this technique to cystectomy patients. Patients with adequate renal function (glomerular filtration rate of 40 mL/min or greater) and hepatic function, who understand the requirement for regular clean-intermittent-catheterization and who possess mental acuity and manual dexterity to empty their pouch 4–6 times daily should be offered CCP ICUD as a reconstructive option following RARC.

Background and purpose — Simulation is an adjunct to surgical education. However, nothing can accurately simulate fluoroscopic procedures in orthopedic trauma. Current options for training with fluoroscopy are either intraoperative, which risks radiation, or use of expensive and unrealistic virtual reality simulators. We introduce FluoroSim, an inexpensive digital fluoroscopy simulator without the need for radiation. Patients and methods — This was a multicenter study with 26 surgeons in which everyone completed 1 attempt at inserting a guide-wire into a femoral dry bone using surgical equipment and FluoroSim. 5 objective performance metrics were recorded in real-time to assess construct validity. The surgeons were categorized based on the number of dynamic hip screws (DHS) performed: novices (< 10), intermediates (10–39) and experts (≥ 40). A 7-point Likert scale questionnaire assessed the face and content validity of FluoroSim. Results — Construct validity was present for 2 clinically validated metrics in DHS surgery. Experts and intermediates statistically significantly outperformed novices for tip–apex distance and for cut-out rate. Novices took the least number of radiographs. Face and content validity were also observed. Interpretation — FluoroSim discriminated between novice and intermediate or expert surgeons based on tip–apex distance and cut-out rate while demonstrating face and content validity. FluoroSim provides a useful adjunct to orthopedic training. Our findings concur with results from studies using other simulation modalities. FluoroSim can be implemented for education easily and cheaply away from theater in a safe and controlled environment.

Introduction: The vascular pathology of patients with type 1 neurofibromatosis (NF-1) is known. Aneurysms of the brachial artery in NF-1 patients are rare and surgical treatment remains a challenge. Report: A patient known to have NF-1 presented with swelling of the left arm. Computed tomography angiography showed a ruptured aneurysm of the brachial artery. Operative reconstruction was performed using reversed saphenous vein. Discussion: Up to now four cases had been published describing brachial aneurysms in NF-1 patients. This case describes the successful reconstruction of a ruptured brachial aneurysm, using a saphenous vein. Keywords: Aneurysm, von Recklinghausen, Neurofibromatosis, Vasculopathy

Typical Martsolf syndrome is characterized by congenital cataracts, postnatal microcephaly, developmental delay, hypotonia, short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2. Genetic analysis of 85 unrelated "mutation negative" probands with Martsolf or Martsolf-like syndromes identified two individuals with different homozygous null mutations in ITPA, the gene encoding inosine triphosphate pyrophosphatase (ITPase). Both probands were from multiplex families with a consistent, lethal and highly distinctive disorder; a Martsolf-like syndrome with infantile-onset dilated cardiomyopathy. Severe ITPase-deficiency has been previously reported with infantile epileptic encephalopathy (MIM 616647). ITPase acts to prevent incorporation of inosine bases (rI/dI) into RNA and DNA. In Itpa-null cells dI was undetectable in genomic DNA. dI could be identified at a low level in mtDNA without detectable mitochondrial genome instability, mtDNA depletion or biochemical dysfunction of the mitochondria. rI accumulation was detectable in proband-derived lymphoblastoid RNA. In Itpa-null mouse embryos rI was detectable in the brain and kidney with the highest level seen in the embryonic heart (rI at 1 in 385 bases). Transcriptome and proteome analysis in mutant cells revealed no major differences with controls. The rate of transcription and the total amount of cellular RNA also appeared normal. rI accumulation in RNA-and by implication rI production-correlates with the severity of organ dysfunction in ITPase deficiency but the basis of the cellulopathy remains cryptic. While we cannot exclude cumulative minor effects, there are no major anomalies in the production, processing, stability and/or translation of mRNA.

Parastomal hernia, defined as an “incisional hernia related to an abdominal wall stoma”, is a frequent complication after conduit urinary diversion that can negatively impact quality of life and present a clinically significant problem for many patients. Parastomal hernia (PH) rates may be as high as 65% and while many patients are asymptomatic, in some series up to 30% of patients require surgical intervention due to pain, leakage, ostomy appliance problems, urinary obstruction, and rarely bowel obstruction or strangulation. Local tissue repair, stoma relocation, and mesh repairs have been performed to correct PH, however, long-term results have been disappointing with recurrence rates of 30%–76% reported after these techniques. Due to high recurrence rates and the potential morbidity of PH repair, efforts have been made to prevent PH development at the time of the initial surgery. Randomized trials of circumstomal prophylactic mesh placement at the time of colostomy and ileostomy stoma formation have shown significant reductions in PH rates with acceptably low complication profiles. We have placed prophylactic mesh at the time of ileal conduit creation in patients at high risk for PH development and found it to be safe and effective in reducing the PH rates over the short-term. In this review, we describe the clinical and radiographic definitions of PH, the clinical impact and risk factors associated with its development, and the use of prophylactic mesh placement for patients undergoing ileal conduit urinary diversion with the intent of reducing PH rates.

Vegetables are a substantial part of our lives and possess great commercial and nutritional value. Weeds not only decrease vegetable yield but also reduce their quality. Non-chemical weed control is important both for the organic production of vegetables and achieving ecologically sustainable weed management. Estimates have shown that the yield of vegetables may be decreased by 45%−95% in the case of weed−vegetable competition. Non-chemical weed control in vegetables is desired for several reasons. For example, there are greater chances of contamination of vegetables by herbicide residue compared to cereals or pulse crops. Non-chemical weed control in vegetables is also needed due to environmental pollution, the evolution of herbicide resistance in weeds and a strong desire for organic vegetable cultivation. Although there are several ways to control weeds without the use of herbicides, cover crops are an attractive choice because these have a number of additional benefits (such as soil and water conservation) along with the provision of satisfactory and sustainable weed control. Several cover crops are available that may provide excellent weed control in vegetable production systems. Cover crops such as rye, vetch, or Brassicaceae plants can suppress weeds in rotations, including vegetables crops such as tomato, cabbage, or pumpkin. Growers should also consider the negative effects of using cover crops for weed control, such as the negative allelopathic effects of some cover crop residues on the main vegetable crop.

Arc-wire or laser-wire additive manufacturing seems promising because it allows large parts to be produced with significant deposition rates (ten times higher than powder bed additive manufacturing), for a lower investment cost. These additive manufacturing techniques are also very interesting for the construction or the repair of parts. A versatile 3D printing device using a Wire Arc Additive Manufacturing (WAAM) station or laser device Wire Laser Additive Manufacturing (WLAM) for melting a filler wire is developed to repair and build large titanium parts. The final objectives of the study are to optimize the process parameters to control the dimensional stability, the metallurgical and mechanical properties of the produced parts. In this paper, an experimental study is carried out to determine the first order process parameter ranges (synergic law, laser power, wire feed speed, travel speed) appropriate for these two techniques, for repair or construction parts on Ti-6 Al-4V.

Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG) is the classical MeCP2 DNA recognition sequence, but additional methylated sequence targets have been reported. Here we show by in vitro and in vivo analyses that MeCP2 binding to non-CG methylated sites in brain is largely confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in mouse brain is proportional to mCAC + mCG density and unexpectedly defines large genomic domains within which transcription is sensitive to MeCP2 occupancy. Our results suggest that MeCP2 integrates patterns of mCAC and mCG in the brain to restrain transcription of genes critical for neuronal function.

This paper presents an overview of recent research performed at Rutgers University and the University of Connecticut on the synthesis and processing of nanostructured materials. Highlights of this collaborative research program include: (1) synthesis of carbide strengthened steel and hard cermet powders from aqueous solution precursors, (2) synthesis of ceramic powders and ceramic matrix composites from metalorganic precursors, (3) densification of powder compacts by liquid phase sintering, (4) formation of high quality coatings by thermal spraying, and (5) demonstration of superior hardness and wear resistance in bulk cermet materials and coatings. Nanostructured bulk materials with designed multifunctional coatings present unprecedented opportunities for advances in materials properties and performance for a broad range of structural applications.

This paper places embodiment in an evolutionary perspective and endeavors to show that as incipient speakers began forging a linguistic system, they molded their grammatical distinctions and syntactic functions on their perception of the outside world, but that in the course of evolution, these perceptually-tinkered features were gradually replaced with mental constructs, specifically conceived to serve linguistic purposes and serve them with increased potentiality and greater efficiency. The shift from perceptual to conceptual implements is perhaps most conspicuously visible in writing, where open-ended figurative hieroglyphs were replaced with a small set of abstract letters, but the process is pervasive. In syntax, the phenomenal notion of agency, so deeply anchored in our activities, and the entire grammatical system built thereupon were replaced with a model where agency is irrelevant and syntax is structured on the purely mental constructs of subject and object. The paper continues with further cases of disembodiment.

PurposeIdentification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non-muscle-invasive bladder cancer (NMIBC), the most common form of urothelial carcinoma, is understudied.Experimental designGermline analysis was conducted on paired tumor/normal sequencing results from two distinct cohorts of patients initially diagnosed with NMIBC. Associations between clinicopathologic features and clinical outcomes with the presence of P/LP germline variants in ≥76 hereditary cancer predisposition genes were analyzed.ResultsA similar frequency of P/LP germline variants were seen in our two NMIBC cohorts [12% (12/99) vs. 8.7% (10/115), P = 0.4]. In the combined analysis, P/LP germline variants were found only in patients with high-grade NMIBC (22/163), but none of the 46 patients with low-grade NMIBC (13.5% vs. 0%, P = 0.005). Fifteen (9.2%) patients with high-grade NMIBC had P/LP variants in DNA damage response genes, most within the nucleotide excision repair (ERCC2/3) and homologous recombination repair (BRCA1, NBN, RAD50) pathways. Contrary to prior reports in patients with NMIBC not receiving Bacillus Calmette-Guerin (BCG), P/LP germline variants were not associated with worse recurrence-free or progression-free survival in patients treated with BCG or with risk of developing upper tract urothelial carcinoma.ConclusionsOur results support offering germline counseling and testing for all patients with high-grade bladder cancer, regardless of initial tumor stage. Therapeutic strategies that target impaired DNA repair may benefit patients with high-grade NMIBC.

A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p

Botulinum neurotoxin (BoNT) potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC) in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP) to link biotinylated molecules to glycophorin A (GPA) on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

Objective. HDT bed rest condition is a simulated microgravity condition in which subject lies on bed inclined −6 degree feet up. To determine the influence of a simulated microgravity (HDT bed rest) on oral cavity, 10 healthy male volunteers were studied before, during, just after, and after 6 weeks of the simulated microgravity condition of −6° head-down-tilt (HDT) bed rest. Materials and Methods. Facial nerve function, facial sensation, chemosensory system, salivary biomarkers were measured. Results. Lactate dehydrogenase, MIP 1 alpha, malonaldehyde, 8-hydroxydeoxyguanosine, and thiocyanate were found to increase significantly, while flow rate, sodium, potassium, calcium, phosphate, protein, amylase activity, vitamin E and C, and mouth opening were decreased in simulation environments in contradiction to normal. The threshold for monosodium glutamate (MSG) and capsaicin increased during microgravity as compared to normal conditions. Moderate pain of teeth, facial oedema, mild pain, loss of sensation of pain and temperature, decreased tongue, and mandibular movement in simulation microgravity environments were observed. Conclusions. These results suggest that reversible effect of microgravity is oedema of face, change in taste, abnormal expression of face, teeth pain, and xerostomia. Further study will be required on large scale on long-term effects of microgravity on oral cavity to prevent the adverse effects.