Prostatic urethra dilatation with the Gianturco self-expanding metallic stent: a feasibility study in cadaver specimens and dogs.
In an effort to develop a transcatheter technique for dilatation of the prostatic urethra without the use of balloons, the feasibility of using Gianturco self-expanding stents was evaluated. Initially, eight human cadaveric prostatic urethras were stented to evaluate the ability of the stent to dilate the lumen. In all cases, the device attained its unconstrained diameter immediately on placement. Subsequently, stents were placed in the prostatic urethra of 12 dogs and followed up for 1 month (four dogs), 3 months (one dog), and 6 months (seven dogs). Five bare straight-end prostheses, one nylon-covered straight-end device, and six flared-end stents were used. Three of the bare straight-end stents migrated during the follow-up, whereas the nylon-covered and flared-end stents did not. Stent diameters greater than 1.3 times the urethral diameter caused moderate to marked edema and inflammation. After 6 months, white deposits were found on the solder points, presumably from electrolysis. Our experience suggests that placement of Gianturco self-expanding stents may be a useful method of dilating and maintaining the luminal diameter of the prostatic urethra, although care must be taken to select the proper stent size.


Abatacept plus methotrexate provides incremental clinical benefits versus methotrexate alone in methotrexate-naive patients with early rheumatoid arthritis who achieve radiographic nonprogression.
This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase. Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit. Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups. More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.


The beneficial effects of pentoxifylline on caerulein-induced acute pancreatitis in rats.
In this study we aimed to investigate the effect of pentoxifylline on caerulein-induced acute pancreatitis (AP) by detecting oxidative stress markers and performing histopathological examination. Twenty-one adult female Sprague-Dawley rats were divided into three groups as follows: control, caerulein, and caerulein + pentoxifylline groups. Pancreatic tissues of rats from all groups were removed for light and electron microscopic examination and determination of oxidative stress markers. Pancreatic oxidative stress markers were evaluated by the measurements of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total glutathione (GSH). Serum amylase and lipase levels were determined spectrophotometrically. The pancreatic damage score was significantly increased (P < 0.005) in the caerulein group, whereas it was decreased (P < 0.05) in the caerulein+ with pentoxifylline group. MDA levels, CAT, SOD, GPx, and GSH activities were significantly altered (P < 0.05, P < 0.005) in the caerulein group and indicated increased oxidative stress. Oxidative stress markers were normalized with pentoxifylline administration. Caerulein administration resulted in significant increase (P < 0.05) in amylase and lipase levels; pentoxifylline reduced the levels of these enzymes. Pentoxifylline is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue antioxidant enzyme activities. We concluded that pentoxifylline may have beneficial effects in the treatment of caerulein-induced AP.


[Aneurysmal bone cyst of the left 5th rib].
A case of aneurysmal bone cyst of the left 5th rib is reported. A 57-year-old male complained of palpable lump and pain on his back. Chest X ray and CT showed expansive tumor arid pathological fracture of the left 5th rib. The tumor and the adjacent segments of the 4th and 5th ribs were resected en bloc. The pathological examination showed multiple blood filled spaces and fibrous trabeculae, confirming the diagnosis of aneurysmal bone cyst. He has been followed up for 3 years and 6 months with no signs of recurrence.


Intralesional biologics for inflammatory dermatoses: A systematic review.
Biologic medications are systemic therapeutic options for inflammatory dermatoses. Local forms of administration are less well-studied. To provide a summary of intralesional (IL) administration of biologics for various non-malignant inflammatory dermatologic conditions reported in the literature. A systematic review was performed in the PubMed and Embase databases from 2000 to 2020. Inclusion criteria included the local use of biologic medications for non-malignant cutaneous conditions. Quality was assessed with the modified Oxford Centre for Evidence-Based Medicine ratings. A total of 19 articles describing the use of 5 biologic medications in 9 dermatologic conditions were identified, comprising 172 patients. Conditions successfully treated with intralesional biologics included pemphigus vulgaris (rituximab), granuloma faciale (rituximab), perianal Crohn's disease (infliximab), lichen sclerosus (adalimumab), and necrobiosis lipoidica (etanercept and infliximab). Intralesional etanercept reduced pruritus associated with keloids. A case report of the use of infliximab for pyoderma gangrenosum did not demonstrate any efficacy. There was no consistent effect noted with treatments for sarcoidosis (infliximab) or cutaneous lymphoid hyperplasia (rituximab). Local administration of biologic medications may offer an additional method of treating refractory inflammatory dermatoses, but further study is needed to develop standardized dosing protocols, clarify efficacy rates, and identify optimal treatment candidates.


Involvement of reactive oxygen species produced via NADPH oxidase in tyrosine phosphorylation in human B- and T-lineage lymphoid cells.
In several human B- and T-lymphoid cell lines, reactive oxygen species (ROS) were produced in a time- and dose-dependent manner in response to menadione (vitamin K3) and anti-Fas (CD95/APO-1) mAb when ROS formation was determined by a chemiluminescence-based method. The ROS evoked by menadione and anti-Fas could be first observed as rapidly as within 20 seconds after the stimulation, reaching a maximum within 5-10 min, and declining slowly thereafter. Both menadione and anti-Fas also induced increased tyrosine phosphorylation of multiple cellular proteins whose pattern was similar to that observed upon hydrogen peroxide treatment. For each agent, the kinetics of the increased tyrosine phosphorylation was similar to that of ROS production, and an NADPH oxidase inhibitor, diphenyleneiodonium, prevented both of these two events. Our results suggest a close link between ROS production and tyrosine phosphorylation induced by divergent extracellular stimuli and the possible role of NADPH oxidase or its related enzyme.


Nanotechnology: A Promising Approach for Cancer Diagnosis, Therapeutics and Theragnosis.
Cancer remains the most devastating disease and the major cause of mortality worldwide. Although early diagnosis and treatment are the key approach in fighting against cancer, the available conventional diagnostic and therapeutic methods are not efficient. Besides, ineffective cancer cell selectivity and toxicity of traditional chemotherapy remain the most significant challenge. These limitations entail the need for the development of both safe and effective cancer diagnosis and treatment options. Due to its robust application, nanotechnology could be a promising method for in-vivo imaging and detection of cancer cells and cancer biomarkers. Nanotechnology could provide a quick, safe, cost-effective, and efficient method for cancer management. It also provides simultaneous diagnosis and treatment of cancer using nano-theragnostic particles that facilitate early detection and selective destruction of cancer cells. Updated and recent discussions are important for selecting the best cancer diagnosis, treatment, and management options, and new insights on designing effective protocols are utmost important. This review discusses the application of nanotechnology in cancer diagnosis, therapeutics, and theragnosis and provides future perspectives in the field.


Enhanced Permanganate Oxidation of Sulfamethoxazole and Removal of Dissolved Organics with Biochar: Formation of Highly Oxidative Manganese Intermediate Species and in Situ Activation of Biochar.
Sulfamethoxazole (SMX) is a broad-spectrum antibiotic and was largely used in breeding industry. The reaction rate of SMX with KMnO4 is slow, and the adsorption efficiency of biochar for SMX was inferior (less than 11% in 30 min). By adding biochar powder into SMX solution with the addition of permanganate, the oxidation ratio of SMX surged to 97% in 30 min, and over 58% of the total organic carbon (TOC) was simultaneously removed. KMnO4 interacted with biochar and resulted in the formation of highly oxidative intermediate manganese species, which transformed SMX into hydrolysis products, oxygen-transfer products, and self-coupling products. Brunauer-Emmett-Teller (BET) analysis showed that surface area, total pore volume, and micropore volume of biochar increased by 32.1%, 36.4%, and 80.6%, respectively, after reaction process. This in situ activation of biochar with KMnO4 enhanced its adsorption capacity and led to great improvement of TOC removal. Besides KMnO4 oxidation, biochar also enhanced TOC removal in Mn(III) oxidation (KMnO4+ bisulfite) and ozonization of SMX. Considering that KMnO4 could react with biochar and result in the formation of intermediate manganese species, while biochar can be simultaneously activated and exhibit high capacity for organic adsorption, the combination of biochar with the chemical/advanced oxidation could be a promising process for the removal of environmental pollutants.


Activatable Zymography Probes Enable In Situ Localization of Protease Dysregulation in Cancer.
Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due to a lack of methods to measure and localize protease activity directly within the tissue microenvironment, the design of protease-activated agents has been necessarily empirical, yielding suboptimal results when translated to patients. To address the need for spatially resolved protease activity profiling in cancer, we developed a new class of in situ probes that can be applied to fresh-frozen tissue sections in a manner analogous to immunofluorescence staining. These activatable zymography probes (AZP) detected dysregulated protease activity in human prostate cancer biopsy samples, enabling disease classification. AZPs were leveraged within a generalizable framework to design conditional cancer diagnostics and therapeutics and showcased in the Hi-Myc mouse model of prostate cancer, which models features of early pathogenesis. Multiplexed screening against barcoded substrates yielded a peptide, S16, that was robustly and specifically cleaved by tumor-associated metalloproteinases in the Hi-Myc model. In situ labeling with an AZP incorporating S16 revealed a potential role of metalloproteinase dysregulation in proliferative, premalignant Hi-Myc prostatic glands. Systemic administration of an in vivo imaging probe incorporating S16 perfectly classified diseased and healthy prostates, supporting the relevance of ex vivo activity assays to in vivo translation. We envision AZPs will enable new insights into the biology of protease dysregulation in cancer and accelerate the development of conditional diagnostics and therapeutics for multiple cancer types. SIGNIFICANCE: Visualization of protease activity within the native tissue context using AZPs provides new biological insights into protease dysregulation in cancer and guides the design of conditional diagnostics and therapeutics.


Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study.
The aim of our study was to provide population-based data on incidence and prognosis of synchronous peritoneal carcinomatosis and to evaluate predictors for its development. Diagnosed in 1995-2008, 18,738 cases of primary colorectal cancer were included. Predictors of peritoneal carcinomatosis were analysed by multivariable logistic regression analysis. Median survival in months was calculated by site of metastasis. In the study period, 904 patients were diagnosed with synchronous peritoneal carcinomatosis (4.8% of total, constituting 24% of patients presenting with M1 disease). The risk of peritoneal carcinomatosis was increased in case of advanced T stage [T4 vs. T1,2: odds ratio (OR) 4.7, confidence limits 4.0-5.6), advanced N stage [N0 vs. N1,2: OR 0.2 (0.1-0.2)], poor differentiation grade [OR 2.1 (1.8-2.5)], younger age [<60 years vs. 70-79 years: OR 1.4 (1.1-1.7)], mucinous adenocarcinoma [OR 2.0 (1.6-2.4)] and right-sided localisation of primary tumour [left vs. right: OR 0.6 (0.5-0.7)]. Median survival of patients with peritoneum as single site of metastasis remained dismal [1995-2001: 7 (6-9) months; 2002-2008: 8 (6-11) months], contrasting the improvement among patients with liver metastases [1995-2001: 8 (7-9) months; 2002-2008: 12 (11-14) months]. To conclude, synchronous peritoneal metastases from colorectal cancer are more frequent among younger patients and among patients with advanced T stage, mucinous adenocarcinoma, right-sided tumours and tumours that are poorly differentiated. The prognosis of synchronous peritoneal carcinomatosis remains poor with a median survival of 8 months and even worse if concomitant metastases in other organs are present.


A longitudinal follow-up of pulmonary function and respiratory symptoms in workers exposed to manganese.
The purpose of the investigation was to study the effects on the respiratory system in mine workers with long-term exposure to manganese (Mn) in the workplace. The study included a follow-up of pulmonary function and respiratory symptoms among 145 workers employed in a large Mn mine and 65 matched controls, and the assessment of Mn concentrations in environment and biological samples. Lung function was measured by recording spirometric parameters. The Mn-exposed workers reported more respiratory symptoms and a significantly higher prevalence of all grades of pulmonary function impairment. All predicted symptoms except for asthma increased significantly in the current smoking group compared with the non-smoking group. There was a significant decrease in FEV1, FVC, and FEV1% values in exposed workers compared with controls at stages 2 and 3, with an additive effect of the smoking habit. The Mn concentrations in blood, urine, and hair were significantly higher in the exposed workers than in the controls. The level of cumulative exposure index of workplace Mn was notable and did not change significantly over this study. The respiratory effects found in Mn-exposed workers were probably caused by the Mn in the workplace and the synergistic effect of smoking. These effects indicate a need for respiratory protection and improvements in the work environment.


[Development of a linear stage compatible for magnetic resonance imaging systems].
A magnetic resonance imaging (MRI) system compatible linear stage was developed. The stage was made of acrylic plastic and moving power was applied by an ultrasonic motor. Moving distance of the stage was detected by counting the number of motor rotations using a optic fiber sensor. Accuracy and precision of the stage control were measured inside and outside the magnet using a micrometer and a laser distance meter. As a result, a value of more than 95% was achieved in both of them in the 1.5 T magnetic field when it was applied for more than a 0.3 mm movement. Measurement of the slice sensitivity profile (SSP) by the delta method was performed. Slice selection by this linear stage and by radio frequency (RF) offset were compared. The result by linear stage was in good agreement with the result by RF offset. With this linear stage, a performance evaluation test of MRI equipments that need micromotion can be performed.


Lazarine leprosy: A unique phenomenon of leprosy.
Leprosy, a chronic granulomatous disease, has been known since ages but even today continues to baffle the clinicians with a wide spectrum of clinical, histopathological, and immunological characteristics. Leprosy reactions are mainly of two types, namely, Type 1 and Type 2. In Type 1 leprosy reaction, the preexisting lesions become erythematous, edematous, and rarely ulcerate. Ulcerating Type 1 reaction is called lazarine leprosy. Ulcerations may occur in borderline tuberculoid (BT) pole or borderline lepromatous pole but more common in BT pole. In this postelimination era of leprosy, we report an interesting case report of BT Hansen's disease with Type 1 lepra reaction with ulceration, namely, lazarine leprosy.


[Synchronous multiple primary cancers of the colon].
The authors report three cases with double synchronous primary cancers of the large bowel, representing 1,57% of the total 224 cases with colon and rectal cancers they have operated. In all the cases it was possible to perform surgical removal of the tumours by right hemicolectomy and segmental sigmoidectomy in two of the patients and rectosigmoidectomy in the third one. The clinical and prognostic characteristics confirmed the opinion, that has been advanced in the specialized literature, that these tumours are relatively benign.


Adenovirally delivered brain-derived neurotrophic factor to rat retina.
To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus. Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining,and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA). The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point (P < 0.01), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01). Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.


Interaction of urokinase with specific receptors stimulates mobilization of bovine adrenal capillary endothelial cells.
On the basis of 125I-labeled plasminogen activator binding analysis we have found that bovine adrenal capillary endothelial cells have specific receptors for human urinary-type plasminogen activator on the cell membrane. Each cell exposes about 37,000 free receptors with a Kd of 0.8958 x 10(-9) M [corrected]. A monoclonal antibody against the 17,500 proteolytic fragment of the A chain of the plasminogen activator, not containing the catalytic site of the enzyme, impaired the specific binding, thus suggesting the involvement of a sequence present on the A chain in the interaction with the receptor, as previously shown in other cell model systems. Both the native molecule and the A chain are able to stimulate endothelial cell motility in the Boyden chamber, when used at nanomolar concentrations. The use of the same monoclonal antibody that can inhibit ligand-receptor interaction can impair the plasminogen activator and A-chain-induced endothelial cell motility, suggesting that under the conditions used in this in vitro model system, the motility of bovine adrenal capillary endothelial cells depends on the specific interaction of the ligand with free receptors on the surface of endothelial cells.


Flow cytometry-based quantification of cytokine levels in AML patients plasma and cell culture supernatants.
Bone marrow stromal cells (BMSCs) have been found to support leukemic cell survival; however, the mechanisms responsible are far from being elucidated yet. The main aim of the current study is to identify particular cytokine/chemokine patterns of acute myeloid leukemia (AML) cells, and, on a longer term, to correlate them with the patient outcome and response to therapy. Therefore, the influence of BMSCs on in vitro modulation of cytokine secretion (IL-1beta, TNF-alpha, IL-10, IFN-gamma, IL-4, IL-5, and IL-2) by AML cells as well as the AML cells supportive capacity of BMSCs-derived soluble factors was investigated. With this purpose, we used an in vitro experimental model consisting in the evaluation of the effect of BMSC confluent layers-conditioning medium (BMSC-CM) on M4/5 AML cell cultures. Our results show that BMSC-CM from both AML patients and healthy subjects conferred a substantial beneficial effect on AML cells throughout the culture (p=0.0002 and 0.0020 respectively at 24 hours and p=0,0013 and 0,0030 respectively at 72 hours), with a temporary increase in AML cell viability conferred by BM plasma from AML patients. Significant differences were observed with respect to IL1 b secretion which was upregulated in AML cell cultures both after 24 and 72 hours following the addition of AML-BMSC-CM, in contrast to control-BMSC-CM. Our results suggest the contribution of BMSCs from AML patients to the generation of particular factors which may be key players involved in the in vivo maintenance of the malignant clone.


Usefulness of laparoscopy guided renal biopsy in dogs.
Renal biopsies were carried out in 25 mixed-breed dogs of both sexes, aged 6 to 11 years, using an automatic, laparoscopy-guided method. The aim of the study was to apply and evaluate the usefulness of this technique in the diagnosis of renal pathologies in dogs. Twenty biopsy specimens were obtained from the right kidney and five--from the left kidney. As many as 24 of the 25 effectively collected biopsy specimens were classified as excellent (96%). Significant histopathological changes were found in 23 of the 25 biopsies performed. The results of histopathological analyses show a predominance of glomerular lesions over interstitial lesions, mostly mesangial glomerulonephritis, membranous and membrane-proliferative glomerulonephritis. The study confirmed that laparoscopy-guided biopsy of the kidney in dogs is a safe and a highly useful diagnostic technique. The results of histopathological analyses of biopsy specimens correlated with clinical history, clinical examination results, blood and urine tests and ultrasound examination results have a great diagnostic value and they significantly affect treatment and prognosis. Laparoscopy-guided biopsy supports the diagnosis and differentiation of glomerular and interstitial lesions and renal neoplasia in dogs.


Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects.
The D2 /D3 antagonist amisulpride has shown promising efficacy against postoperative nausea and vomiting (PONV) at low doses. We investigated whether intravenous amisulpride has an effect on the QTc interval in a formal Thorough QT study (TQT). This was a randomized, double-blind, placebo and positive-controlled, four-way crossover study. Forty healthy Caucasian and Japanese subjects were included to receive a single administration of 5 mg and 40 mg of i.v. amisulpride or a single oral dose of moxifloxacin or placebo per period. The therapeutic dose of 5 mg amisulpride was associated with a slight, transient increase in mean ΔΔQTcF, from 2.0 ms prior to dosing to a peak of 5 ms (90% CI: 2.8, 7.1 ms) at 8 min, decreasing to 2.1 ms at 30 min after dosing. The supra-therapeutic dose of 40 mg given at twice the infusion rate was associated with prolongation in ΔΔQTcF peaking at 23.4 ms (90% CI: 21.3, 25.5 ms) at the end of infusion (8 min), returning below 10 ms within 1.5 h. Assay sensitivity was confirmed; ΔΔQTcF had increased by 12.3 ms (90% CI 10.1, 14.6 ms) at 4 h post-dose. The PK-PD relationship revealed no differences between Caucasian and Japanese subjects (p-value > 0.5). Amisulpride has a plasma concentration-dependent effect on the QTc interval. The proposed therapeutic dose for management of PONV does not lead to a prolongation of QTcF above the threshold of regulatory concern, while such effect could not be excluded for the supratherapeutic dose.


Breaking the carbon dimer: the challenges of multiple bond dissociation with full configuration interaction quantum Monte Carlo methods.
The full configuration interaction quantum Monte Carlo (FCIQMC) method, as well as its "initiator" extension (i-FCIQMC), is used to tackle the complex electronic structure of the carbon dimer across the entire dissociation reaction coordinate, as a prototypical example of a strongly correlated molecular system. Various basis sets of increasing size up to the large cc-pVQZ are used, spanning a fully accessible N-electron basis of over 10(12) Slater determinants, and the accuracy of the method is demonstrated in each basis set. Convergence to the FCI limit is achieved in the largest basis with only O[10(7)] walkers within random errorbars of a few tenths of a millihartree across the binding curve, and extensive comparisons to FCI, CCSD(T), MRCI, and CEEIS results are made where possible. A detailed exposition of the convergence properties of the FCIQMC methods is provided, considering convergence with elapsed imaginary time, number of walkers and size of the basis. Various symmetries which can be incorporated into the stochastic dynamic, beyond the standard abelian point group symmetry and spin polarisation are also described. These can have significant benefit to the computational effort of the calculations, as well as the ability to converge to various excited states. The results presented demonstrate a new benchmark accuracy in basis-set energies for systems of this size, significantly improving on previous state of the art estimates.


tRNA Synthetases Are Recruited to Yeast Ribosomes by rRNA Expansion Segment 7L but Do Not Require Association for Functionality.
Protein biosynthesis is essential for any organism, yet how this process is regulated is not fully understood at the molecular level. During evolution, ribosomal RNA expanded in specific regions, referred to as rRNA expansion segments (ES). First functional roles of these expansions have only recently been discovered. Here we address the role of ES7La located in the large ribosomal subunit for factor recruitment to the yeast ribosome and the potential consequences for translation. Truncation of ES7La has only minor effects on ribosome biogenesis, translation efficiency and cell doubling. Using yeast rRNA deletion strains coupled with ribosome-specific mass spectrometry we analyzed the interactome of ribosomes lacking ES7La. Three aminoacyl-tRNA synthetases showed reduced ribosome association. Synthetase activities however remained unaltered suggesting that the pool of aminoacylated tRNAs is unaffected by the ES deletion. These results demonstrated that aminoacylation activities of tRNA synthetases per se do not rely on ribosome association. These findings suggest a role of ribosome-associated aminoacyl-tRNA synthetase beyond their core enzymatic functions.


Understanding LiOH Chemistry in a Ruthenium-Catalyzed Li-O2 Battery.
Non-aqueous Li-O2 batteries are promising for next-generation energy storage. New battery chemistries based on LiOH, rather than Li2 O2 , have been recently reported in systems with added water, one using a soluble additive LiI and the other using solid Ru catalysts. Here, the focus is on the mechanism of Ru-catalyzed LiOH chemistry. Using nuclear magnetic resonance, operando electrochemical pressure measurements, and mass spectrometry, it is shown that on discharging LiOH forms via a 4 e- oxygen reduction reaction, the H in LiOH coming solely from added H2 O and the O from both O2 and H2 O. On charging, quantitative LiOH oxidation occurs at 3.1 V, with O being trapped in a form of dimethyl sulfone in the electrolyte. Compared to Li2 O2 , LiOH formation over Ru incurs few side reactions, a critical advantage for developing a long-lived battery. An optimized metal-catalyst-electrolyte couple needs to be sought that aids LiOH oxidation and is stable towards attack by hydroxyl radicals.


Observer agreement for diagnosis of colorectal lesions with analysis of the vascular pattern by image-enhanced endoscopy.
Image-enhanced endoscopy (IEE) can differentiate neoplastic from non-neoplastic colorectal lesions through indirect analysis of pit patterns and microvascular architecture. We evaluated the accuracy of Flexible Spectral Imaging Color Enhancement (FICE) in differentiating neoplastic from non-neoplastic lesions and observer agreement in the analysis of capillary pattern of colorectal lesions. A prospective double-blind trial was conducted in two referral endoscopy centers. Vascular pattern was analyzed by IEE with magnification. Lesions were divided into two groups and examined separately by two experts. Examiners, blinded to each other's interpretations, switched groups and the lesions were reviewed. After 60 days, lesions were reevaluated. In total, 76 patients were referred to colonoscopy for colon cancer screening. Of 100 colorectal lesions, 88 were neoplastic (73 tubular adenomas, 10 tubulovillous adenomas, 1 villous adenoma, 2 serrated adenomas, 2 adenocarcinomas) and 12 were non-neoplastic (hyperplastic polyps). Mean diameter of the lesions was 6.7 mm. Examiners 1 and 2 had 95 % accuracy. The interobserver kappa coefficient was 0.80 and the intraobserver kappa coefficient was 0.88 for examiner 1 and 0.73 for examiner 2. IEE with magnification is effective for real-time predictive histological diagnosis of colorectal lesions, with inter- and intraobserver agreement ranging from good to excellent.


Results of atrial fibrillation ablation during mitral surgery in patients with poor electro-anatomical substrate.
Enlarged (> 50 mm) atria, longstanding (> 5 years) persistent atrial fibrillation (AF) and age > 70 years are considered predictive of recurrent AF following surgical ablation. The electrophysiological and clinical outcome after AF-ablation was evaluated in high-risk patients undergoing concomitant procedures. Between January 2005 and January 2009, a total of 45 patients who complied with the three major predictors of failure, but who had undergone AF ablation ('left + right bipolar radiofrequency Maze') during concomitant mitral surgery were followed up. Freedom from AF, atrial flutter (AFL) and atrial tachycardia (AT), without anti-arrhythmic therapy (discontinued at the sixth month) was the primary endpoint. Survival, freedom from AF/AFL/AT with anti-arrhythmic therapy, early events during post-ablation blanking period, freedom from congestive heart failure (CHF) and from re-hospitalization, and changes in NYHA functional class were registered. Postoperatively, 18 patients (40%) showed sinus rhythm (SR) at admission to the intensive care unit, while 16 (26%) showed junctional rhythm and five (11%) required definitive pacemaker. Eleven of the 40 patients (28%) were discharged without a pacemaker, and experienced early events during the post-ablation blanking period. After a mean of 21 +/- 14 months' follow up, the actuarial survival was 88 +/- 7%. The prevalence of SR at six, 12, and 18 months was 74%, 64%, and 64% respectively. Freedom from AF/AFL/AT was 54 +/- 10% without anti-arrhythmic medications, and 51 +/- 9% with such drugs. Freedom from CHF was 85 +/- 6%, and significantly better in SR patients (94 +/- 6%) than in AF patients (69 +/- 13%; p = 0.018). Freedom from rehospitalization was 75 +/- 8%, and better in SR patients (94 +/- 6%) than in AF patients (37 +/- 14%; p = 0.0001). Accordingly, when compared to AF patients, the NYHA class was significantly ameliorated in SR patients at both six months (1.4 +/- 0.6 versus 2.7 +/- 0.9) and at the final follow up control (1.2 +/- 0.5 versus 1.9 +/- 0.7; p < 0.0001). The E/A wave recovered in 22 (85%) of the SR patients. AF ablation during mitral valve surgery achieves good electrophysiological results, even in patients traditionally considered as poor candidates. SR recovery allows a higher freedom from CHF and rehospitalization, with a better functional recovery when compared to AF.


[Clinical exploration of nociception with the use of reflexologic techniques].
In the first part of this report a methodology is described which allows an objective and specific exploration of experimental pain in man by using some electrophysiological features of cutaneous reflexes. This method can be summarized as follows: in normal and trained volunteers, we studied simultaneously the recruitment curves of the nociceptive flexion reflex of a knee-flexor muscle (biceps femoris muscle) and that of pain sensation elicited by electrical stimulation of the ipsilateral sural nerve at the ankle. In this procedure, we found that the reflex threshold (Tr) was closely related to that of pain threshold (Tp) around a similar value (10 mA). In the same way, both the threshold of the maximal recruitment of the reflex (Tmr) and that of tolerance to pain (Tpt) were found to be close to 33 mA. These values are reliably reproducible in one subject from one session to the other, and in all subjects with minimal inter-individual variations and without any significant inter-sex difference. These close relationships between Tr and Tp and between Tmr and Tpt respectively constituted the basic ground for the elaboration of the methodology for investigating objectively the human nociceptive reactions. In the second part of the paper, this methodology is applied for studying the spinal mechanisms of morphine analgesia when the drug is given either by intravenous route in normal subjects and in paraplegic patients or administered epidurally in patients with acute postoperative pain. On the one hand, the resulting data strongly validate the model since they show that pain and nociceptive reflex are similarly depressed by morphine in a dose-response fashion. On the other hand, data also show that the spinal level is one of the main important sites of the mechanisms of morphine-induced analgesia since this drug is found to strongly depress selectively the nociceptive transmission directly at the spinal level. Finally, this method is applied for investigating the nociceptive reactions in patients affected either with a pathological lack of pain sensation or, by contrast, in patients complaining of acute or chronic pain from various origins. Since the nociceptive flexion reflex can be considered as a specific and objective physiological correlate of a pain sensation, it can be successfully employed as a useful tool for investigating some aspects of the human nociceptive reactions in both experimental and pathological situations.


Striatal dopamine and glutamate release: effects of intranigral injections of substance P.
The levels of extracellular striatal dopamine and glutamate were measured simultaneously in halothane-anaesthetized rats using microdialysis. Unilateral injections of substance P (0.07 nmol) into the substantia nigra, pars reticulata enhanced the levels of dopamine and glutamate in the ipsilateral striatum. Intranigral injections of neurokinin A (0.09 nmol) enhanced the levels of striatal dopamine, and intranigral injections of gamma-aminobutyric acid (300 nmol) or dynorphin A (0.5 nmol) decreased the levels of striatal dopamine, but none of these had any effect on the levels of striatal glutamate. Local perfusion with the dopamine agonists apomorphine (D1/D2), SKF 38393 (D1) or pergolide (D2) (each at 10(5) M) decreased the levels of striatal dopamine and enhanced the levels of striatal glutamate. In unilateral 6-hydroxydopamine-lesioned rats, basal striatal glutamate levels were decreased bilaterally. Furthermore, on the denervated side intranigral substance P stimulation of striatal glutamate levels was enhanced, while on the intact side intranigral substance P stimulation of striatal dopamine and glutamate levels was similar to that seen in normal rats. These findings suggest that striatonigral substance P provides a stimulatory regulation of ipsilateral striatal glutamate release. Furthermore, it is indicated that striatal glutamate release can also be regulated by dopamine terminals.


Could Frailty be an Explanatory Factor of the Association between Depression and Other Geriatric Syndromes in Later Life?
This study aimed to investigate whether frailty could be an explanatory factor of the association between depression and the number of geriatric syndromes. Cross-sectional baseline data from a cohort study (MiMiCS-FRAIL) were analyzed in a sample of 315 older adults. Depression was measured according to DSM-5 criteria and a self-report questionnaire (PHQ-9). Frailty was assessed according to the FRAIL questionnaire and a 30-item Frailty Index (FI). We considered six geriatric syndromes. Multiple linear regression analyses were performed and adjusted for potential confounders. Multiple linear regression analyses yielded significant associations between depression and geriatric syndromes. These associations decreased substantially in strength when frailty was added to the models. Findings were consistent for different definitions of depression and frailty. Among depressed patients, frailty may be hypothesized as a causal pathway toward adverse health outcomes associated with depression. Longitudinal studies should explore the causality of this association. Frailty should be treated or prevented in order to minimize the impact of other geriatric syndromes among depressed older adults. Screening for frailty would be of utmost importance in mental health care, as frailty is neglected especially in this field. Integrated care models are crucial for clinical practice in mental illness care.


Effect of acute immunoneutralization of inhibin in ewes during the late luteal phase of the oestrous cycle on ovarian hormone secretion and follicular development during the subsequent follicular phase.
Ewes with ovarian autotransplants received either inhibin antiserum (10 ml i.v.; n = 6) or sheep serum (10 ml i.v.; n = 5) on day 10 of the luteal phase with additional daily injections (1 ml i.v.) from 48 h after the initial injection until the end of blood sampling, 9 days later. Luteal regression was induced by injection of prostaglandin F2 alpha (PGF2 alpha) 4.2 days after the initial plasma injection. Jugular and ovarian venous blood samples were taken every 4 h over the experimental period, and more frequent samples (every 10-15 min for 2-3 h) were taken to examine pulsatile secretory responses from the ovary to GnRH-induced (150 ng i.m. 1 and 4 days after initial treatment) or endogenous LH pulses (24 and 48 h after injection of PGF2 alpha). Plasma FSH concentrations, ovarian steroid secretion and ovarian follicular development were measured. Immunization against inhibin resulted in a two- to threefold increase (P < 0.001) in plasma FSH concentrations, which remained higher than controls until injection of PGF2 alpha. Within 24 h of immunization, there was an increase in the number of small ovarian follicles (P < 0.01) and by 4 days after treatment, immunized ewes had four or five (P < 0.01) large ovarian follicles and, despite little change in the basal steroid secretion, a four- to sixfold increase (P < 0.05) in the amplitude of the steroidogenic response to a GnRH-induced LH pulse.(ABSTRACT TRUNCATED AT 250 WORDS)


Antisense treatment of caliciviridae: an emerging disease agent of animals and humans.
The Earth's oceans are the primary reservoir for an emerging family of RNA viruses, the Caliciviridae, which can cause a spectrum of diseases in marine animals, wildlife, farm animals, pets and humans. Certain members of this family have unusually broad host ranges, and some are zoonotic (transmissible from animals to humans). The RNA virus replicative processes lack effective genetic repair mechanisms, and, therefore, virtually every calicivirus replicate is a mutant. Hence, traditional therapeutics dependent on specific nucleic acid sequences or protein epitopes lack the required diversity of sequence or conformational specificity that would be required to reliably detect, prevent or treat infections from these mutant clusters (quasi-species) of RNA viruses, including the Caliciviridae. Antisense technology using phosphorodiamidate morpholino oligomers shows promise in overcoming these current diagnostic and therapeutic problems inherent with newly emerging viral diseases.


[Burns by electric scalpel blade: four cases].
A burn due to the plate of a diathermy knife is a rare but serious accident owing to the depth of the lesion and its localization, especially when it occurs in a surgical context that creates difficulties for both the patient and the surgeon. Such burns are unpredictable and also serious not only because of their location but also because they occur during a surgical operation in patients who are already ill. Such burns have to be dealt with by specialists. Prevention is the only way of avoiding this kind of accident.


Predictors of same day cancellation of elective surgery.
Same day cancellations of surgery have adverse effects on both patients and health care systems. To date, the majority of research has evaluated reasons for same day cancellation, and relatively little is known about risk factors for cancellation. The aim of this study is to develop and evaluate the accuracy of a model for preoperatively predicting which patients are at risk for experiencing same day cancellation. While accurately predicting which patients are likely to experience same day cancellation remains challenging, predictive models may aid in the early identification of patients at risk for cancellation. Future studies are required to assess whether the use of predictive analytics leads to reduced cancellation rates in practice.


Differential regulation of two distinct families of glucose transporter genes in Trypanosoma brucei.
A tandemly arranged multigene family encoding putative hexose transporters in Trypanosoma brucei has been characterized. It is composed of two 80% homologous groups of genes called THT1 (six copies) and THT2 (five copies). When Xenopus oocytes are microinjected with in vitro-transcribed RNA from a THT1 gene, they express a glucose transporter with properties similar to those of the trypanosome bloodstream-form protein(s). This THT1-encoded transport system for glucose differs from the human erythrocyte-type glucose transporter by its moderate sensitivity to cytochalasin B and its capacity to transport D-fructose. These properties suggest that the trypanosomal transporter may be a good target for antitrypanosomal drugs. mRNA analysis revealed that expression of these genes was life cycle stage dependent. Bloodstream forms express 40-fold more THT1 than THT2. In contrast, procyclic trypanosomes express no detectable THT1 but demonstrate glucose-dependent expression of THT2.


Very early onset of Wernicke's encephalopathy after gastric bypass.
Postoperative complications resulting from bariatric surgery can lead to severe vitamin-deficiency states, such as Wernicke's encephalopathy (WE). We present a 29-year-old woman with BMI 41.7 with no history of alcoholism who developed acute WE after a gastric bypass for morbid obesity. After persistent vomiting for 2 weeks postoperatively, symptoms began with headache, vertigo, diplopia, nystagmus, tingling and weakness in both upper and lower extremities, urinary incontinence, and memory loss to recent events. All investigations, including upper GI endoscopy, Gastrografin meal and even MRI, were normal. A dramatic improvement occurred in 24 hrs after starting 100 mg thiamine infusion daily. We recommend that patients undergoing bariatric surgery should be started on thiamine supplementation once oral intake begins, because this case showed that postoperative acute WE can develop before 6 weeks, unlike other reports.


Application of Decomposition Analysis of Spatial Accessibility (DASA) in Health Services Research.
Withdrawal mapping is effective in showing the educational impact of residency programs and medical schools. It is often used for advocacy and education purposes, but it lacks grounding in the theoretical foundation of spatial accessibility research. This study proposes an improved technique called Decomposition Analysis of Spatial Accessibility, or DASA, to decompose spatial accessibility by applying the withdrawal mapping concept to the classical 2SFCA application. This study applies the DASA technique to three case studies with policy implications. The first case study details the contribution of Black surgeons to public access to the surgical workforce. The second case study details the contribution of international medical graduates from the original seven travel-ban countries. The third case study demonstrates the market competition between family physicians and general pediatricians. The study showcases the usefulness (particularly for workforce-planning for underserved populations) of the DASA technique in understanding subgroup contributions in spatial accessibility analyses.


'Statistical significance' in research: wider strategies to meaningfully interpret findings.
The P -value is frequently used in research to determine the probability that the results of a study are chance findings. A value less than 0.05 was once typically considered only to mean that results are 'statistically significant', as it indicates the chance they are false positives is less than one in 20 (5%). However, P<0.05 has transcended into meaning a study has had positive findings and its results are true and meaningful, increasing the likelihood it will be published. This has led to researchers over-emphasising the importance of the P-value, which may lead to a wrong conclusion and unethical research practices. To explain what the P -value means and explore its role in determining results and conclusions in quantitative research. Some researchers are calling for a move away from using statistical significance towards meaningful interpretation of findings. This would require all researchers to consider the magnitude of the effect of their findings, contemplate findings with less certainty, and place a greater emphasis on logic to support or refute findings - as well as to have the courage to consider findings from multiple perspectives. The authors argue that researchers should not abandon P -values but should move away from compartmentalising research findings into two mutually exclusive categories: 'statistically significant' and 'statistically insignificant'. They also recommend that researchers consider the magnitudes of their results and report whether findings are meaningful, rather than simply focusing on P -values. Lessening the importance of statistical significance will improve the accuracy of the reporting of results and see research disseminated based on its clinical importance rather than statistical significance. This will reduce the reporting of false positives and the overstatement of effects.


[Clinical and genetic analysis of a pedigree of Kennedy disease].
To review the clinical and genetic features of a pedigree of Kennedy disease in China. The clinical data of patients from a Kennedy disease family were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis. In the pedigree, 4 patients were identified as Kennedy disease. Clinical manifested with adult-onset, progressive proximal limb muscle weakness and atrophy, gynecomastia, oligospermia were also presented. The number of trinucleotide CAG repeats in exon 1 of the androgen receptor gene was 51 in the proband. The electrophysiological study showed sensory and motor involvement and their serum triglycerides values were elevated significantly. Androgen receptors gene testing is the most reliable diagnosing method, the patients suspected as Kennedy disease should have a gene testing of androgen receptors.


Recent Updates of Lipoprotein(a) and Cardiovascular Disease.
In recent years, epidemiological studies, genome-wide association studies, and Mendelian randomization studies have shown a strong association between increased levels of lipoproteins and increased risks of coronary heart disease and cardiovascular disease (CVD). Although lipoprotein(a) [Lp(a)] was an independent risk factor for ASCVD, the latest international clinical guidelines do not recommend direct reduction of plasma Lp(a) concentrations. The main reason was that there is no effective clinical medicine that directly lowers plasma Lp(a) concentrations. However, recent clinical trials have shown that proprotein convertase subtilisin/kexin-type 9 inhibitors (PCSK9) and second-generation antisense oligonucleotides can effectively reduce plasma Lp(a) levels. This review will present the structure, pathogenicity, prognostic evidences, and recent advances in therapeutic drugs for Lp(a).


Solitary extramedullary plasmacytoma of the parotid gland imaged with 18F-FDG PET/CT.
A 75-year-old woman presented with a 1-year history of an enlarging mass in the left parotid gland. Biopsy revealed a parotid plasmacytoma, and the patient was referred for a staging F-FDG PET/CT to evaluate the presence of multiple myeloma bone involvement. The PET/CT scan showed intense FDG uptake in the neck mass but no FDG-avid lymphadenopathy or distant metastases. Plasmacytoma involving the parotid gland is extremely rare. We present the F-FDG PET/CT imaging of solitary parotid plasmacytoma.


Epidural lumbar block or lumbar plexus block combined with general anesthesia: efficacy and hemodynamic effects on total hip arthroplasty.
Anesthesia for total hip arthroplasty (THA) is a challenge due to the advanced age and associated diseases of patients. The objective of this study was to evaluate whether the efficacy of the nociceptive blockade, secondary hemodynamic effects, difficulty to execute the technique, and influence in intraoperative bleeding of lumbar plexus block combined with general anesthesia is equivalent to epidural lumbar block in patients undergoing THA. Patients with physical status ASA I to III were randomly separated into two groups, Epidural and Lumbar. In the Epidural group, continuous epidural lumbar block with 10 to 15 mL of 0.5% ropivacaine was performed. Patients in the Lumbar group underwent posterior lumbar plexus block with 0.4 mL.kg(-1) of 0.5% ropivacaine. All patients underwent general anesthesia. The difficulty to perform the technique, its efficacy, and secondary hemodynamic effects were evaluated. Forty-one patients were included in this study. The length of time to execute the epidural block was shorter, but the number of attempts to position the needle was similar in both groups. Epidural block was more effective. In the Lumbar group, an increase in diastolic blood pressure and mean arterial pressure (MAP) and in the double product was observed after the incision, and anesthetic consumption was greater. After the blockade, MAP was lower 50, 60, and 70 minutes after the epidural block. Bleeding was similar in both groups. Nociceptive blockade, which was not associated with hemodynamic instability when combined with general anesthesia, was more effective in epidural block. Lumbar plexus block proved to be a useful technique when combined with general anesthesia when epidural block is contraindicated.


Comparative study of dirithromycin and azithromycin in the treatment of acute bacterial exacerbations of chronic bronchitis.
We compared the clinical and microbiological efficacy of dirithromycin with that of azithromycin in outpatients with acute bacterial exacerbations of chronic bronchitis who could be graded into stage III according to Ball's system of stratification. A total of 80 patients was studied. Of these, 40 were treated with dirithromycin as a once-daily dose of 500 mg for 5 days, and 40 with azithromycin as a once-daily dose of 500 mg for 3 days. At post-therapy, treatment success (cure or improvement) was achieved in 36 out of 40 (90%) patients receiving dirithromycin compared with 37 out of 40 (92.5%) in the azithromycin group. At the late post-therapy visit, 34 out of 36 (94.4%) dirithromycin-treated patients were cured as were 33 of 37 (89.2%) azithromycin-treated patients. A small proportion of patients treated with dirithromycin (10%) or with azithromycin (12.5%) suffered mild side effects. Gastrointestinal disorders, including abdominal cramps, nausea, or diarrhea, were common adverse effects. The main pathogens isolated before treatment were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Eradication rates at the end of treatment were 90% (36 out of 40) for the dirithromycin group and 92.5% (37 out of 40) for the azithromycin group. Persistence of H. influenzae isolates was found in 3 out of 11 (27.3%) patients treated with dirithromycin and in 2 out of 9 (22.2%) who had received azithromycin. At the late post-therapy visit, eradication occurred in 34 out of 36 (94.4%) strains in the dirithromycin group and in 33 out of 37 (89.2%) in the azithromycin group. We conclude that dirithromycin and azithromycin appear to be equally effective in the treatment of acute bacterial exacerbations of chronic bronchitis.


[Infection pathogen analysis of 2388 patients in an open hematology ward from 1993 to 2004].
To investigate the incidence of infection and pathogens in hematology ward. The data of incidence, pathogen, and outcome of infection of 2388 hospitalized patients in an open hematology ward of Peking Union Medical College Hospital from 1993 to 2004 were analyzed retrospectively. The overall incidence of infection was 34.3% according to the person-times of hospitalization, 24.4% for nosocomial infection and 9.9% for community-acquired infection. Most of the pathogenic bacteria of the nosocomial infection were Gram negative. The most common bacteria in the sputum samples included Enterobacter (27%), Pseudomonas aeruginosa (16%) and coagulase negative Staphylococcus (MRSCoN, 12%), the most common bacteria in the blood samples included Escherichia coli (43%), Enterobacter cloacae (11%), and Klebsiella (11%). Whereas in the community-acquired infection the most common bacteria in the sputum samples were Haemophilus parainfluenzae (15%), MRSCoN (28%), and Staphylococcus epidermidis (10%), and the most common bacteria in the blood samples were MRSCoN (28%), E. coli (28%), and Klebsiella (9.4%). Fungi were more often found in nosocomial infection, especially in the sputum samples. 12-year follow up showed that in nosocomial infection Pseudomonas aeruginosa remained the most common bacteria in the sputum samples, whereas E. coli and Enterobacter cloacae became the major bacteria in the blood samples. In community-acquired infection, the proportion of Staphylococcus aureus, that of Klebsiella in blood samples, and that of E. coli in throat swab samples increased in recent years. The incidence of fungi infection had increased in both nosocomial infection and community acquired infection. The mortality of nosocomial infection was 6.1%, higher than that of the community-acquired infection, however, not statistically significant (P = 0.17). There was a trend of decrease in the mortality of community-acquired infection but did not in the nosocomial infection. The patients in hematology ward are susceptible to infection, especially nosocomial infection that has a higher mortality rate in comparison with the community-acquired infection, however, not statistically significant. The pathogens of nosocomial infection are most likely G- bacteria, fungi and other bacteria resistant to most antibiotics. The mortality rate of nosocomial infection remains almost unchanged in the 12-year follow up.


Levels and Determinants of Place-Of-Death Congruence in Palliative Patients: A Systematic Review.
Introduction: Congruence, understood as the agreement between the patient's preferred place of death and their actual place of death, is emerging as one of the main variables indicating the quality of end-of-life care. The aim of this research was to conduct a systematic literature review on levels and determinants of congruence in palliative patients over the period 2010-2021. Method: A systematic review of the literature in the databases of PubMed, Scopus, Web of Science, PsycINFO, CINAHL, Cuiden, the Cochrane Library, CSIC Indexes, and IBECS. Information was extracted on research characteristics, congruence, and associated factors. Results: A total of 30 studies were identified, mainly of retrospective observational design. The congruence values varied substantially between the various studies, ranging from 21 to 100%. The main predictors of congruence include illness-related factors (functional status, treatments and diagnosis), individual factors (age, gender, marital status, and end of life preferences), and environmental factors (place of residence, availability of health, and palliative care services). Conclusion: This review, in comparison with previous studies, shows that treatment-related factors such as physical pain control, marital status, having a non-working relative, age, discussing preferred place of death with a healthcare professional, and caregiver's preference have been associated with higher levels of congruence. Depending on the study, other factors have been associated with either higher or lower congruence, such as the patient's diagnosis, gender, or place of residence. This information is useful for designing interventions aimed towards greater congruence at the end of life.


Congenital Syphilis Misdiagnosed as Suspected Nonaccidental Trauma.
Congenital syphilis (CS) is a preventable infection, yet the incidence has surged to the highest rates in 20 years. Because 50% of live-born infants with CS are asymptomatic at birth, there is an increasing likelihood that pediatric providers will encounter older infants whose diagnoses were missed at birth, emphasizing the importance of timely prenatal screening and treatment. We present one such case of an infant admitted twice at 3 and 4 months of age with long bone fractures and suspected nonaccidental trauma. On her second presentation, several additional symptoms prompted evaluation for and eventual diagnosis of CS. In this case, it is demonstrated that an isolated long bone fracture can be a first presentation of CS, with other classic findings possibly appearing later. Pediatric providers should be familiar with the varied presentations of CS in older children, including the radiographic findings that we describe. The rising rates of CS reveal deficiencies in our current strategy to prevent CS and, thus, we recommend reconsideration of universal syphilis screening in the third trimester and at delivery, with timely treatment to prevent CS during pregnancy.


Reconstitution of normal and hyperactivated forms of casein kinase-2 by variably mutated beta-subunits.
Twenty-one mutants of the noncatalytic beta-subunit of human casein kinase-2 have been created, expressed in Escherichia coli, and purified to homogeneity. They are either modified at the autophosphorylation site (mutants beta delta 1-4 and beta A 5,6) or bear variable deletions in their C-terminal part (mutants beta delta 209-215, beta delta 194-215, beta delta 181-215, beta delta 171-215, beta delta 150-215) or have undergone Ala substitutions for the acidic and basic residues which are concentrated in the sequences 55-70 and 171-180, respectively. All these mutants have been examined for their ability to functionally replace the wild type beta-subunit. All substitutions and the deletions delta 1-4, delta 194-215, and delta 209-215 are compatible with effective binding of the catalytic alpha-subunit, as judged by sucrose density gradient analysis, stimulation of catalytic activity, and protection against thermal denaturation. Deletions delta 171-215 and delta 150-215, however, give rise to truncated molecules which are unable to associate with the alpha-subunit. The intermediate deletion delta 181-215 is still compatible with association, albeit the reconstituted holoenzyme exhibits an altered sedimentation coefficient. The holoenzymes reconstituted with substituted mutants beta A 55,57, beta A55-57, and, to a lesser extent, beta A 59-61, beta A63,64, and beta A5,6 display a basal activity which is higher (up to 4-fold) than that of the wild type holoenzyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Laser microirradiation as a versatile system for probing protein recruitment and protein-protein interactions at DNA lesions in plants.
Plant protoplasts are generated by treatment with digestion enzymes, producing plant cells devoid of the cell wall and competent for efficient polyethylene glycol mediated transformation. This way fluorescently tagged proteins can be introduced to the protoplasts creating an excellent system to probe the localization and function of uncharacterized plant proteins in vivo. We implement the method of laser microirradiation to generate DNA lesions in Arabidopsis thaliana, which enables monitoring the recruitment and dynamics of the DNA repair factors as well as bimolecular fluorescence complementation assay to test transient, conditional interactions of proteins directly at sites of DNA damage. We demonstrate that laser microirradiation in protoplasts yields a physiological cellular response to DNA lesions, based on proliferating cell nuclear antigen (PCNA) redistribution in the nucleus and show that factors involved in DNA repair, such as MRE11 or PCNA are recruited to induced DNA lesions. This technique is relatively easy to adopt by other laboratories and extends the current toolkit of methods aimed to understand the details of DNA damage response in plants. The presented method is fast, flexible and facilitates work with different mutant backgrounds or even different species, extending the utility of the system.


Dry blood spot testing for hepatitis C in people who injected drugs: reaching the populations other tests cannot reach.
The aim of the study was to evaluate the effectiveness of Dry Blood Spot testing (DBST) for hepatitis C within a geographical area. This is a prospective cohort study of all individuals living in Tayside who had received a hepatitis C virus (HCV) DBST between 2009 and 2011. During the study, 1123 DBSTs were carried out. 946 individuals had one test. 295 (31.2%) of these individuals were HCV antibody positive on their first test. Overall, 94.3% (902/956) individuals returned for the results of their test. During the course of the study 177 individuals were retested and 29 new cases of hepatitis C were detected. 249 individuals attended for further follow-up, and 164 (65.5%) were PCR positive. All 164 PCR-positive individuals were offered referral into specialist HCV services for further assessment. Data showed 62.5% were genotype 3, 65.1% had a low viral load (<600 000 iu/ml) and 77.5% had a Fibroscan score below 7 KPa. To date, 40 have commenced treatment and a further 16 are currently in the assessment period. Overall, we have retained in services or treated 63.6% (105/164) of patients who were initially referred and with effective support mechanisms in place we have achieved sustained viral response rates of 90%. The study has shown that DBST is a complementary technique to conventional venepuncture for the diagnosis of HCV. The majority of patients have low viral loads and low fibrosis scores, so that while this group of patients may be difficult to reach and may be challenging to maintain in therapy, they are easier to cure.


A community hospital develops an integrated, comprehensive toxicology laboratory.
A model system was developed at the author's institution for providing toxicology and therapeutic drugs monitoring services. These services were expanded with chromatography instrumentation and the Syva EMIT-st Drug Detection System. An emergency screen for various drugs in urine takes about one hour. The drugs or drug families detected are opiates, barbiturates, benzodiazepines, amphetamines, phenothiazines, cocaine metabolite, acetaminophen, and ethyl alcohol. Confirmation and quantitation of drugs in serum can be done by either higher performance liquid chromatography, gas chromatography, or radioimmunoassay. Sample preparation takes from five to 15 minutes and chromatography requires about 15 minutes in most cases. While more than 60 drugs can be quantitated using these procedures, rarely are more than one or two drugs present in patient samples.


Cholinesterase inhibition activity of Marsilea quadrifolia Linn. an edible leafy vegetable from West Bengal, India.
Maesilea quadrifolia Linn. (Marsileaceae) is a leafy vegetable well known in India. The current study aims to explore the phytochemical profile of M. quadrifolia and investigate its anti-cholinesterase potential. The methanol extract of the plant was subjected to qualitative and quantitative phytochemical screening (total alkaloidal content, saponin content and phenol content) and its anti-cholinesterase potential was tested by TLC bioautography and other screening methods using acytylcholinesterase (AChE) and butyrylcholinesterase (BChE). The study revealed that the extract contains various classes of phytoconstituents including steroids, saponins, alkaloids and other polyphenols. Total alkaloid, phenolic and saponin contents were found to be 19.3 mg g⁻¹ and 158.5 ± 1.02 mg g⁻¹ as gallic acid equivalents and 2.63 mg g⁻¹ of the extract, respectively. The TLC bioautography method exhibited the inhibition of both enzymes. In a microtiter plate assay, the IC₅₀ values of the extract for AChE and BChE were found to be 51.89 ± 0.24 µg mL⁻¹ and 109.43 ± 2.82 µg mL⁻¹, respectively. These findings suggest that M. quadrifolia is a potential lead as an AChE and BChE inhibitor, which may be useful in the management of Alzheimer's disease.


Effects of fasting, elevated plasma glucose and plasma insulin concentrations on milk secretion in women.
In order to determine whether short term variations in plasma glucose and/or insulin influence milk lactose secretion in women, the effects of fasting and increased blood insulin and glucose on milk volume and composition were studied with glucose clamp methodology in exclusively and partially breast-feeding women. Twenty hours of fasting had no discernable effect on the output of milk or its macronutrient composition. Four hours of increased plasma insulin, studied under conditions where plasma glucose was maintained at the fasting level, had no effect on milk volume, milk glucose concentration, total fat content or lactose secretion rate. Increased plasma glucose, maintained at twice fasting levels for 4 to 6 h, produced a threefold increase in milk glucose concentration but had no significant effect on the rate of lactose synthesis. In partially breast-feeding women producing no more than 200 ml milk per day, a similar degree of hyperglycaemia increased milk glucose more than fourfold but did not significantly increase the milk secretion rate. It is concluded that human milk production is isolated from the homeostatic mechanisms that regulate glucose metabolism in the rest of the body, in part because the lactose synthetase system has a Km for glucose lower than the concentration available in the Golgi compartment.


The impact of lymph node ratio on disease recurrence in papillary thyroid microcarcinoma.
Lymph node (LN) metastases in papillary thyroid microcarcinomas (microPTCs) are common. The lymph node ratio (LNR) has been proposed as a risk factor for recurrence in papillary thyroid cancer. However, its relevance in microPTC is undetermined. Patients who underwent resection of their microPTC with concomitant LN clearance between 2005 and 2018 were identified. The LNR was calculated as the ratio of positive LNs to the total number of LNs. Data on 50 patients (36 female [72%]; median age 47 years [range: 19-84]) who underwent LN clearance (28 central [56%] vs 22 central + lateral [44%]) were analysed. Positive LNs were found in over two-thirds of the patients (n = 34; 68%). After a median follow-up of 61 months, 14 patients (28%) had developed recurrence. Positive LNs were not found to impact recurrence-free survival; extranodal extension and an LNR ≥ 0.26 were found to significantly increase the risk of recurrence on unadjusted analyses (p < 0.05). LN metastases are frequent among patients with microPTC. A higher LNR seems to be associated with recurrence. Additional studies are needed to further clarify these findings and to assess the possible role of LNR in treatment and surveillance.


[Dynamics of the pupillary light reflex in unilateral Horner's syndrome].
The aim of this study was to characterise the changes of the dynamic pupillary light reflex in patients with unilateral Horner's syndrome by appropriate pupillographic parameters. The dynamic changes of pupillary diameter in response to light flashes of 100 ms were recorded in darkness with two infrared video cameras in 15 patients. Significant changes in the pupillary light reflex of the affected side were observed only during the phase of redilatation. The decelerated redilatation was defined by the following parameters: (1) time parameters (percentage of redilatation after 4 s and after 5 s, time to reach 67% and 75% of redilatation) and (2) amplitude-adjusted velocity parameters (relative velocity at 67% and at 75% of redilatation). A slowed pupil redilatation in patients with Horner's syndrome can be detected also after short light flashes and is characterised by prolonged redilatation time parameters and reduced amplitude-adjusted redilatation velocity parameters.


Cost-effectiveness analysis of an orphan drug tebentafusp in patients with metastatic uveal melanoma and a call for value-based pricing.
The normative regimens recommendations for treating metastatic uveal melanoma (mUM) are absent in the US. Recently, a phase III randomized clinical trial revealed that tebentafusp yielded a conspicuously longer overall survival than the control group. Based on the prominent efficacy, this study aimed to assess whether tebentafusp is cost-effective compared to the control group in patients with untreated mUM. A three-state partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) from the perspective of US payers. Scenario analyses and sensitivity analyses were conducted to explore the conclusion uncertainty. Compared with control group, tebentafusp therapy yielded an additional 0.47 QALYs (1.19 vs. 0.72 QALYs) and an incremental cost of $444 280 ($633 822 vs. $189 542). The resultant ICER of $953 230/QALY far outweighed the willingness-to-pay threshold of $200 000/QALY. The ICER was always more than $750 000/QALY in all the univariable and probabilistic sensitivity analyses. Scenario analyses indicated that reducing the unit price of tebentafusp to $33.768/µg was associated with a favorable result of tebentafusp being cost-effective. For treatment-naive patients with mUM, the cost of tebentafusp therapy was not worth the improvement in survival benefits at the current price compared to the investigator's choice of therapy. The cost-effectiveness of tebentafusp could be promoted using value-based pricing.


Falls and SGLT-2 inhibitors in geriatric patients-A case report.
With this case report, we want to assess the synergistic effect of both a diuretic and an SGLT-2 inhibitor on the fall event of a patient who is 65 years old and has a history of repeated falls before. After we modified the medications appropriately, she has never experienced a fall event again. So as we know, older adults do not take fall events as a pathological condition instead of a normal physiological aging process. So primary-care physicians should question the fall history of an older patient before starting a drug such as SGLT-2 inhibitors, which is known as an agent that has side effects including falls, dehydration, etc.


Characterization of wastewater effluents in the Danube River Basin with chemical screening, in vitro bioassays and antibiotic resistant genes analysis.
Averaged 7-day composite effluent wastewater samples from twelve wastewater treatment plants (WWTPs) in nine countries (Romania, Serbia, Hungary, Slovenia, Croatia, Slovakia, Czechia, Austria, Germany) in the Danube River Basin were collected. WWTPs' selection was based on countries' dominant technology and a number of served population with the aim to get a representative holistic view of the pollution status. Samples were analyzed for 2248 chemicals of emerging concern (CECs) by wide-scope target screening employing LC-ESI-QTOF-MS. 280 compounds were detected at least in one sample and quantified. Spatial differences in the concentrations and distribution of the compounds classes were discussed. Additionally, samples were analyzed for the possible agonistic/antagonistic potencies using a panel of in vitro transactivation reporter gene CALUX® bioassays including ERα (estrogenics), anti-AR (anti-androgens), GR (glucocorticoids), anti-PR (anti-progestins), PPARα and PPARγ (peroxisome proliferators) and PAH assays. The potency of the wastewater samples to cause oxidative stress and induce xenobiotic metabolism was determined using the Nrf2 and PXR CALUX® bioassays, respectively. The signals from each of the bioassays were compared with the recently developed effect-based trigger values (EBTs) and thus allowed for allocating the wastewater effluents into four categories based on their measured toxicity, proposing a putative action plan for wastewater operators. Moreover, samples were analyzed for antibiotics and 13 antibiotic-resistant genes (ARGs) and one mobile genetic element (intl1) with the aim to assess the potential for antibiotic resistance. All data collected from these various types of analysis were stored in an on-line database and can be viewed via interactive map at https://norman-data.eu/EWW_DANUBE.


Association of endothelial nitric oxide synthase gene T-786C promoter polymorphism with gastric cancer.
To investigate the role of endothelial nitric oxide synthase -786T > C promoter polymorphism in the etiology of gastric cancer (GC). A total of 150 GC patients and 150 control subjects were included in the study. The information on demographic features was elicited with an informed consent from all the patients and control subjects using a structured questionnaire. Helicobacter pylori (H. pylori) infectivity status was tested in antral biopsies from all the subjects by rapid urease test following the method of Vaira et al. Genomic DNA was isolated from whole blood samples following the salting out method of Lahiri et al. Genotype analysis of the rs2070744 polymorphism was carried out by allele-specific polymerase chain reaction method. The genotypes were determined based on the appearance of bands on an agarose gel stained with ethidium bromide under ultraviolet gel documentation with the help of 100 bp ladder. Odds ratios and corresponding 95%CIs were determined using java stat online software. There was a significant difference in the distribution of C allele (C vs T; P = 0.000, OR = 5.038) in patient group compared to the control subjects exhibiting a fivefold increased risk for GC. When the T/T and C/C genotypes were compared, there was an enhanced GC risk for individuals with C/C genotype (T/T vs C/C; P = 0.000). Among the demographic factors, smoking and alcoholism were the common risk factors in patients compared to the control subjects (P < 0.05). Patients with smoking and alcoholism developed cancer even in heterozygous T/C condition (smoking: P = 0.020 and alcoholism: P = 0.005). Individuals with H. pylori infection showed seven fold increased risk for cancer. All the patients with C/C genotype revealed a significant association between H. pylori infection and GC. Among the patients 2.4% of them revealed familial incidence of GC. No significant difference was noticed between cases and controls with regard to consanguinity (P = 0.473). The Present data suggest that eNOS-786 C/C genotype and C allele may be considered as potential risk factors in patients with GC.


Nitrogen deposition in and near an urban ecosystem.
Excess nitrogen (N) is a serious water-quality problem in most of the estuaries in the United States, especially those downstream of developed coastal basins. Understanding sources of N is a key first step in managing and mitigating N pollution. While the major sources of this N, atmospheric deposition, wastewater, fertilizer, and other agricultural sources are well-known, their relative importance as N sources to particular estuaries is not. Much of this uncertainty is due to difficulties associated with estimating the amount of atmospheric N deposition. Here, we show that deposition is 47% higher in urban and 22% higher in suburban areas compared to nonurban areas and that this deposition is primarily due to dry deposition. Moreover, this deposition is not being measured by the current deposition monitoring networks that were designed to measure broader regional patterns causing an underestimation of N inputs in urban areas.


Drug Resistance in Hematological Malignancies.
Hematological malignancies define a highly heterogeneous set of blood-, bone marrow-, and organ-associated diseases with highly variable prognoses that constantly relapse upon treatment [...].


Analysis of the catalytic and binding residues of the diadenosine tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans by site-directed mutagenesis.
The contributions to substrate binding and catalysis of 13 amino acid residues of the Caenorhabditis elegans diadenosine tetraphosphate pyrophosphohydrolase (Ap(4)A hydrolase) predicted from the crystal structure of an enzyme-inhibitor complex have been investigated by site-directed mutagenesis. Sixteen glutathione S-transferase-Ap(4)A hydrolase fusion proteins were expressed and their k(cat) and K(m) values determined after removal of the glutathione S-transferase domain. As expected for a Nudix hydrolase, the wild type k(cat) of 23 s(-1) was reduced by 10(5)-, 10(3)-, and 30-fold, respectively, by replacement of the conserved P(4)-phosphate-binding catalytic residues Glu(56), Glu(52), and Glu(103) by Gln. K(m) values were not affected, indicating a lack of importance for substrate binding. In contrast, mutating His(31) to Val or Ala and Lys(83) to Met produced 10- and 16-fold increases in K(m) compared with the wild type value of 8.8 microm. These residues stabilize the P(1)-phosphate. H31V and H31A had a normal k(cat) but K83M showed a 37-fold reduction in k(cat). Lys(36) also stabilizes the P(1)-phosphate and a K36M mutant had a 10-fold reduced k(cat) but a relatively normal K(m). Thus both Lys(36) and Lys(83) may play a role in catalysis. The previously suggested roles of Tyr(27), His(38), Lys(79), and Lys(81) in stabilizing the P(2) and P(3)-phosphates were not confirmed by mutagenesis, indicating the absence of phosphate-specific binding contacts in this region. Also, mutating both Tyr(76) and Tyr(121), which clamp one substrate adenosine moiety between them in the crystal structure, to Ala only increased K(m) 4-fold. It is concluded that interactions with the P(1)- and P(4)-phosphates are minimum and sufficient requirements for substrate binding by this class of enzyme, indicating that it may have a much wider substrate range then previously believed.


Feasibility of a preventive mass vaccination campaign with two doses of oral cholera vaccine during a humanitarian emergency in South Sudan.
As an adjunct to cholera prevention measures, WHO advises the use of oral cholera vaccine through mass vaccination campaigns in high-risk areas and for vulnerable population groups. We assessed the feasibility and acceptability of a mass vaccination campaign using 1) a predominantly fixed and 2) a mobile door-to-door strategy. Vaccination included administration of two doses (given 2 weeks apart) of oral cholera vaccine to individuals older than 1 year of age, in four refugee camps: Jamam, Doro, Batil and Gendrassa, and the host population in Maban County, South Sudan, from December 2012 to February 2013. A total of 258 832 doses were administered to a population of 166 000 (126 000 refugees and 40 000 host population). The first round coverage for the refugees was above 84% for Doro, Jamam and Batil and 104% for Gendrassa. The second dose reached the same coverage as the first dose. For the host population, the coverage for the first dose was above 90% in Doro and Jamam and 53% in Gendrassa and Batil. For the second round, the coverage was above 79% in Doro and Jamam and above 70% in Batil and Gendrassa. The vaccination of a large population in an emergency context proved to be feasible and acceptable and achieved high coverage. This is encouraging and is a way forward for reducing cholera related morbidity and mortality among vulnerable populations.


Demyelination and axonal loss in multifocal motor neuropathy: distribution and relation to weakness.
Multifocal motor neuropathy (MMN) is characterized by a slowly progressive, asymmetric weakness of the limbs without sensory loss. The arms are usually affected to a greater extent than the legs, and distal muscles more than proximal muscles. The distribution of electrophysiological abnormalities and its correlation with weak muscle groups in MMN have not been investigated systematically. The aim of the present study was to assess whether electrophysiological abnormalities have a preferential or random distribution, whether electrophysiological abnormalities in a nerve correlate with weakness in the innervated muscles, and whether these results are relevant for the development of optimal electrodiagnostic protocols. We compared the pattern of weakness and electrophysiological abnormalities in 39 patients with a lower motoneuron syndrome and a positive response to intravenous immunoglobulins. All patients underwent an extensive standardized electrophysiological examination. Electrophysiological evidence of demyelination was found more often in the nerves of the arms and was distributed randomly over lower arm, upper arm and shoulder segments. Electrophysiological evidence of axonal loss presented more frequently in longer nerves, occurring most often in the leg nerves. For the arm nerves, it is possible that the length dependence of axonal loss is due to the random distribution of demyelinating lesions that lead to axonal degeneration. Weakness was associated with features of demyelination and axonal loss in the nerves of the arm, and with features of axonal loss in leg nerves. However, a substantial number (approximately one-third) of electrophysiological abnormalities were found in nerves innervating non-weakened muscles. These results imply that in MMN, conduction block is most likely to be found in long arm nerves innervating weakened muscles, but if conduction block cannot be detected in these nerves, the electrophysiological examination should be extended to other arm nerves including those innervating non-weakened muscles.


Reflections on facilitated discharge from a mental health service.
The aim of this paper is to review research evidence and describe our experience of facilitated discharge from mental health services to primary care. A literature review of facilitated discharge was conducted. In addition, the clinical characteristics of 21 discharged and 21 non-discharged patients from one shared care service were compared in a retrospective file review. Thirty-one patients in another facilitated discharge program were surveyed. Discharged patients had a higher level of function. There was a trend towards discharged patients being female and employed with less chronic illness, involuntary treatment, behavioural symptoms, depot medication, triage contact, service contact with family, and more mood disorder. Of the 10 survey respondents, 60% reported feeling better compared with their last service contact, 70% felt not having contact was a good thing and most saw their doctors regularly and reported a good relationship. There was a trend towards more stable patients being discharged and it appeared that they responded positively to this, without a clear indication of which factors best determine suitability for discharge. Consequently, we elected to incorporate discharge planning processes as a core function of case management and increase shared care with the primary care sector.


Superconducting accelerometer using niobium-on-sapphire rf resonator.
An accelerometer is described which uses a rf niobium-on-sapphire resonator as its sensor element. The accelerometer uses a magnetically levitated spool as a test mass and the spool modulates the inductance of the resonator; its position is servo controlled to maintain the resonator at the external rf excitation frequency. The accelerometer has high sensitivity over the full audio frequency range, but is optimized for frequencies between 100 Hz and 1 kHz, where the calculated displacement sensitivity approaches 10(-15) cm for a 1 Hz measurement bandwidth. The system noise sources are analyzed and possible improvements are discussed.


Enhancement of nitric oxide synthesis by the aqueous extract of Spiraea prunifolia var. simpliciflora's root in RAW 264.7 cells.
The effects of aqueous extract of Spiraea prunifolia var. simpliciflora's root, a traditional medicine for the treatment of malaria in Chinese medicine, on the generation of nitric oxide (NO) are investigated in RAW 264.7 cells. NO generation from IFN-gamma primed RAW 264.7 cells is markedly increased by the addition of aqueous extract in a dose-dependent manner. The enhancement of NO generation by the aqueous extract is accompanied by a significantly increased expression of inducible nitric oxide synthase (iNOS). However, the aqueous extract of Spiraea prunifolia var. simpliciflora's root does not affect the viability of RAW 264.7 cells, as assessed by MTT assay. Polymyxin B does not inhibit NO generation by the aqueous extract in IFN-gamma primed RAW 264.7 cells. However, polymyxin B significantly decreases NO generation by lipopolysaccharide (LPS) in IFN-gamma primed RAW 264.7 cells. These data indicate that the signaling pathway of the aqueous extract-induced NO generation is not dependent on PKC. These results strongly support the mechanism by which the aqueous extract may exert anti-malarial effect via direct cytotoxicity of NO as well as NO-mediated modulation of immune functions.


Arthroscopic Evaluation of Syndesmotic Instability and Malreduction.
Ankle fractures are a common injury treated by orthopaedic surgeons. The distal tibiofibular syndesmosis can be injured during these fractures as well as in isolation. They pose a significant challenge with regard to the diagnosis of instability as well as evaluating reduction after fixation. Multiple studies have demonstrated that traditional radiographic analysis fails to accurately identify syndesmotic diastasis, instability, or malreduction. Ankle arthroscopy has been proposed as an alternative way to evaluate the syndesmosis. Ten transtibial amputation cadavers were utilized for this study. Two distinct analyses were undertaken. The first, analysis of instability, utilized 2 dissection groups, a superficial dissection only and a partial disruption instability model. The second analysis was of syndesmotic malreduction. For this, all 10 specimens underwent complete disruption of the syndesmosis and subsequent fixation in either anatomic alignment or malreduction. Both analyses were performed by surgeons blinded to the condition of the syndesmosis. Two groups of surgeons were able to identify syndesmotic instability a combined 75% of the time. Malreduction diagnosis was mixed with a 100% accurate diagnosis of sagittal plane displacement but only 50% accuracy for rotation and 17% for an anatomic reduction. Syndesmotic injury during ankle fracture presents a significant problem to the treating surgeon. Ankle arthroscopy has been shown in the literature to be highly sensitive for diagnosing instability but has not been evaluated in diagnosing malreduction. The current study shows moderate success in diagnosing both malreduction and instability. Therapeutic, Level V: Basic Science.


Reconstruction of the Free Energy Profile for SUMO1 from Nonequilibrium Single-Molecule Pulling Experiments.
Free energy profiles form the cornerstone in the study of protein folding and function. In this study, the free energy profile of SUMO1 protein is directly reconstructed using an extension of the Jarzynski equality from atomic force microscope (AFM) based single-molecule force spectroscopy (SMFS) experiments. SUMO1 is a ubiquitin-like posttranslational modifier protein having a β clamp motif in its structure, imparting it with mechanical stability. We use the Jarzynski equality to obtain the equilibrium free energy profile from repeated nonequilibrium single-molecule pulling experiments. Indeed, the free energy values determined by the Jarzynski equality are lesser than the normal work average at all extensions. The free energy profiles constructed for the two velocities (100 and 400 nm/s) overlap with each other. The unfolding free energy barrier is estimated to be ∼7.5 kcal/mol. We anticipate that the Jarzynski equality can be applied in a similar manner to other ubiquitin-like proteins to extract their differences in the free energy profile, and hence, the effect of sequence diversity of structurally homologous proteins on the free energy landscape can be studied.


Integration of clinicopathological and mutational data offers insight into lung cancer with tumor spread through air spaces.
Tumor spread through air spaces (STAS) was defined as a unique tumor invasion pattern in adenocarcinoma (ADC) by The World Health Organization Classification of Lung Tumors in 2015. Since then, STAS had been shown to be associated with local recurrence and poor survival results, as the typical signature and potential mechanisms of STAS remained unclear. Our objectives were to comprehensively demonstrate the clinicopathological and genetic signatures in STAS-positive lung cancer patients. The clinicopathological and gene alteration characteristics of 878 STAS-positive lung cancer patients were presented. Associations between parameters were evaluated using the Chi-square test, Fisher's exact test, and logistic regression. The capture-based targeted next generation sequencing (NGS) with a platform of 68 lung cancer-related genes was conducted in 139 cases, and the mutational spectrum was summarized. STAS was identified in 391 female and 481 male patients, of which ADC accounted for the majority of cases (92.6%). The concomitant solid or micropapillary subtype was observed in 92.12% patients with ADC. Poorly differentiated histological subtypes were more frequent and negatively correlated with tumor size in smaller tumor cases (P=0.036, Pearson's R=-0.075). Furthermore, in the subgroup of nodules within 3 cm, the distribution of the solid and micropapillary subtypes were significantly frequent in lymph node-positive patients (P<0.001). Tumor protein p53 (TP53) alterations were more frequent in smoking patients (27.6%, P=0.007), human epidermal growth factor receptor 2 (HER2) alterations were more common in female (10.8%, P=0.025), while Kirsten rat sarcoma viral oncogene (KRAS) (20.3%, P=0.024) and TP53 (45.9%, P=0.003) were more prevalent in males. Poorly differentiated histological subtypes likely played a crucial role in promoting the invasiveness of STAS, especially in small tumor-size cases. Epidermal growth factor receptor (EGFR), TP53, KARS, anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) were the five most frequent alterations in STAS-positive ADC.


Comparative analysis of zygotic developmental genes in Rhodnius prolixus genome shows conserved features on the tracheal developmental pathway.
Most of the in-depth studies on insect developmental genetic have been carried out in the fruit fly Drosophila melanogaster, an holometabolous insect, so much more still remains to be studied in hemimetabolous insects. Having Rhodnius prolixus sequenced genome available, we search for orthologue genes of zygotic signaling pathways, segmentation, and tracheogenesis in the R. prolixus genome and in three species of Triatoma genus transcriptomes, concluding that there is a high level of gene conservation. We also study the function of two genes required for tracheal system development in D. melanogaster - R. prolixus orthologues: trachealess (Rp-trh) and empty spiracles (Rp-ems). From that we see that Rp-trh is required for early tracheal development since Rp-trh RNAi shows that the primary tracheal branches fail to form. On the other hand, Rp-ems is implied in the proper formation of the posterior tracheal branches, in a similar way to D. melanogaster. These results represent the initial characterization of the genes involved in the tracheal development of an hemimetabolous insect building a bridge between the current genomic era and V. Wigglesworth's classical studies on insects' respiratory system physiology.


The impact of silver nanoparticles on the co-composting of sewage sludge and agricultural waste: Evolutions of organic matter and nitrogen.
This study evaluated the influence of silver nanoparticles (AgNPs) on evolutions of organic matter and nitrogen during co-composting of sewage sludge and agricultural waste. Two co-composting piles were conducted, one was treated without AgNPs (pile 1) and the other with AgNPs (pile 2). Results showed that the AgNPs affected the quality of final composts. Less organic matter (OM) losses were determined in pile 2 (57.96%) than pile 1 (61.66%). 27.22% and 30.1% of the initial total organic matter (TOC) was decomposed in pile 1 and pile 2, respectively. The final water soluble carbon (WSC) concentration in pile 2 was 23559.27mg/kg DW compost which was significantly lower than pile 1 (25642.75mg/kg DW compost). Changes of different forms of nitrogen in the two piles showed that AgNPs could reduce the losses of TN but increase the losses of mineral N.


Primary pericardial spindle cell sarcoma mimicking left main coronary artery disease.
Primary spindle cell sarcoma in the heart is a very uncommon disease. Although primary atrial or pulmonary vein spindle cell sarcomas have been sporadically reported, pericardial spindle cell sarcoma is rarely seen in currently available data. The commentary here is on a primary pericardial spindle cell sarcoma that was preliminarily misjudged to be left main coronary artery disease.


Influence of Copper Oxide Nanoparticles on Gene Expression of Birch Clones In Vitro under Stress Caused by Phytopathogens.
Recently, metal oxide nanoparticles (NPs) have attracted attention as promising components for the protection and stimulation of plant microclones in tissue culture in vitro. However, the effect of NPs on the genetic mechanisms underlying plant adaptive responses remains poorly understood. We studied the effect of column-shaped CuO NPs 50 nm in diameter and 70-100 nm in length at a concentration of 0.1-10 mg/L on the development of phytopathogenic fungi Alternaria alternata, Fusarium oxysporum, and Fusarium avenaceum in culture, as well as on the infection of downy birch micro-clones with phytopathogens and the level of genes expression associated with the formation of plant responses to stress induced by microorganisms. CuO NPs effectively suppressed the development of colonies of phytopathogenic fungi A. alternata and F. avenaceum (up to 68.42% inhibition at 10 mg/L CuO NPs) but not the development of a colony of F. oxysporum. Exposure to the NPs caused multidirectional responses at the level of plant genes transcription: 5 mg/L CuO NPs significantly increased the expression level of the LEA8 and MYB46 genes and decreased the expression of DREB2 and PAL. Infection with A. alternata significantly increased the level of MYB46, LEA8, PAL, PR-1, and PR-10 transcripts in birch micro-clones; however, upon exposure to a medium with NPs and simultaneous exposure to a phytopathogen, the expression of the MYB46, PR-1, and PR-10 genes decreased by 5.4 times, which is associated with a decrease in the pathogenic load caused by the effect of NPs and the simultaneous stimulation of clones in vitro. The results obtained can be used in the development of preparations based on copper oxide NPs for disinfection and stimulation of plant phytoimmunity during clonal micropropagation of tree crops.