Main-Group Metal Complexes of Benzene: Predicted Features of Stabilization and Isomerization.
Complexes of metal atoms with organic molecules represent a broad variety of systems with many important applications, e.g., in metal-organic interfaces and organometallic chemistry. One class involves aromatic species like benzene (Bz). Here, such complexes with second-group metals are investigated systematically in terms of structure and shape, stability and isomerization, charge distribution and aromaticity, and polarity and IR spectra. Three groups of isomers are identified, varying from metastable to stable ones, in effect featuring "physisorption" or "chemisorption". In particular, the high polarity of binary complexes and nonadditive stabilization of ternary systems for some isomers are found. Also, the Bz component's shape alteration for different isomers and system sizes and related aromaticity variations are predicted to be considerable. Property evolution for the series of metal components is analyzed.


Drug Tolerance: A Known Unknown in Translational Neuroscience.
In neuropsychiatric drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss of efficacy with repeated drug exposure, is rarely addressed as a potential source of clinical failures. In this review, we argue that preclinical methods of tolerance development may have predictive validity and, therefore, inclusion of studies using repeated drug exposure early during the drug discovery and development process should serve to mitigate a proportion of clinical failures. Our analysis indicates that many published preclinical efficacy studies in the neuropsychiatry arena are conducted with acute drug administration only. Furthermore, specifically in the field of schizophrenia, there are several examples where tolerance development may be suspected as a factor contributing to translational failures. These and other examples highlight the need for built-for-purpose tolerance studies to be conducted, regardless of the target interaction mode of the drugs (i.e., agonist or antagonist, allosteric or orthosteric). We suggest that, for compounds that have failed in clinical studies, preclinical efficacy data sets need to be revisited to estimate the potential impact of tolerance development, one of the most significant known unknowns in the preclinical-to-clinical translation.


Analysis of wave patterns in MR elastography of skeletal muscle using coupled harmonic oscillator simulations.
The ability to study muscle elasticity in vivo would be of great clinical interest. Magnetic resonance elastography (MRE) has the potential to quantify noninvasively the distribution of the shear modulus in muscle tissue. Elasticity information may be derived by extracting frequencies from the wave patterns of phase-contrast MRE images. In a new approach, MRE wave patterns were reconstructed using 3D coupled harmonic oscillator calculations (CHO). To analyze in vivo MRE measurements of the biceps brachii of healthy volunteers, different anisotropic fibrous structures for the couplings between the muscle elements have to be assumed. V-shaped wave patterns as observed when excitation was applied on the tendon were reproduced by a model, where in a central band of stiff fascicles wave propagation was about twice as fast as that in surrounding tissue. Planar waves were observed for excitation near the muscle surface. They could be reconstructed by assuming a simultaneous wave excitation of all muscle fibers, where fibers along the main muscle axis were coupled more strongly than those perpendicular to the axis. The results show that CHO calculations provide a fast and reliable method for incorporating anatomical information of the investigated tissue in the reconstruction of complex wave patterns.


Validation Prognostic of the Baylor Profound Mental Status Examination.
There are no validated prognostic instruments to evaluate severe Alzheimer's disease (AD) patients. To validate the prognostic value of the Baylor Profound Mental Status Examination (BPMSE). We selected 200 patients with severe AD. The following prognostic variables were collected: hospitalization, use of the emergency room, death, and prescription of drugs. ROC curve analysis was performed to see the overall behavior of the test when predicting the adverse event. We analyzed the AUC ROC and the best cut point was determined, and by using contingency tables, the risk was calculated. For a BPMSE ≥16 points, there was a risk of 1.8 (95% CI 0.9-3.4) of prescription of psychotropic drugs in 12 months. For memantine in 12 months, for a BPMSE ≥16 points, there was a risk of 2.9 (95% CI 1.1-7.2). Emergency room visits, for a BMPSE ≤15 points, showed a risk of 1.7 (95% CI 1-3.2). The risk of hospitalization at 12 months, for a BPMSE ≤15, was 1.4 (95% CI 0.8-2.6). When comparing medians, patients with a higher BPMSE were prescribed more drugs at 12 months. BPMSE has a limited predictive value for the variables studied.


Selective pressure modulation of synaptic voltage-dependent calcium channels-involvement in HPNS mechanism.
Exposure to hyperbaric pressure (HP) exceeding 100 msw (1.1 MPa) is known to cause a constellation of motor and cognitive impairments named high-pressure neurological syndrome (HPNS), considered to be the result of synaptic transmission alteration. Long periods of repetitive HP exposure could be an occupational risk for professional deep-sea divers. Previous studies have indicated the modulation of presynaptic Ca(2+) currents based on synaptic activity modified by HP. We have recently demonstrated that currents in genetically identified cellular voltage-dependent Ca(2+) channels (VDCCs), CaV 1.2 and CaV 3.2 are selectively affected by HP. This work further elucidates the HPNS mechanism by examining HP effect on Ca(2+) currents in neuronal VDCCs, CaV 2.2 and CaV 2.1, which are prevalent in presynaptic terminals, expressed in Xenopus oocytes. HP augmented the CaV 2.2 current amplitude, much less so in a channel variation containing an additional modulatory subunit, and had almost no effect on the CaV 2.1 currents. HP differentially affected the channels' kinetics. It is, therefore, suggested that HPNS signs and symptoms arise, at least in part, from pressure modulation of various VDCCs.


Immobilization in supination versus neutral following surgical treatment of Galeazzi fracture-dislocations in adults: case series.
The goal of this study was to investigate whether immobilization in supination is necessary to prevent recurrent distal radioulnar joint (DRUJ) instability in patients older than 18 years with a Galeazzi fracture-dislocation and a stable DRUJ following open reduction and internal fixation of the radius. We performed a retrospective chart review of 10 consecutive patients who were immobilized in either supination or a neutral position following surgical treatment of a Galeazzi fracture-dislocation in which the DRUJ was noted to be stable immediately after fixation of the radius. Group 1 consisted of 5 patients who were immobilized in supination for a period of 4 weeks, and group 2 consisted of 5 patients who were immobilized in neutral for 2 weeks, followed by functional bracing. Patients were followed up for an average of 68 months (range, 26-124 mo) after surgery. No significant difference was noted between the 2 groups with respect to age, medical comorbidities (no noteworthy medical comorbidities in either group), or hand dominance. None of the patients in either group demonstrated DRUJ instability during the follow-up period or required any additional surgery. At the latest follow-up, patients in the 2 groups had comparable forearm motion. The results of the current study suggest that following open reduction and internal fixation of the radius in patients with Galeazzi fracture-dislocations and with stable DRUJs, immobilization in supination for 4 weeks does not have an advantage over immobilization in neutral for a shorter period.


Physical dimensions, torsional performance, bending properties, and metallurgical characteristics of rotary endodontic instruments. VI. Canal Master drills.
A laboratory study was performed on machine-driven Canal Master drills to determine their physical dimensions, torsional performance, bending properties, and metallurgical characteristics in fracture. Physical dimensions were determined for each of the available sizes (#50 to #100) of Canal Master drills from the manufacturer that distributes these instruments in the United States. Samples were also tested in clockwise torsion using a Maillefer memocouple. Bending properties of cantilever specimens were measured with a Tinius Olsen stiffness tester. Bending fatigue testing was performed on a unique laboratory apparatus. Scanning electron microscope examination confirmed visual observations that the stainless steel Canal Master drills exhibited ductile torsional fracture. This study is part of a continuing investigation to establish standards for all machine-driven rotary endodontic instruments.


Therapy-resistant ventricular tachycardia caused by amiodarone-induced thyrotoxicosis: a case report of electrical storm.
Electrical storm is a challenging diagnosis for the clinician and requires detailed evaluation of the patient. Amiodarone is frequently used for the cessation of ventricular tachycardia attacks. Within antiarrhythmic effects of amiodarone, there are some harmful effects of the recent drug. Thyroid gland toxicity is one of the most important adverse effects of amiodarone and is called amiodarone-induced thyrotoxicosis. Thyrotoxicosis may alter arrhythmia and lead to frequent ventricular tachycardia attacks. Herein, we report a case of electrical storm caused by amiodarone-induced thyrotoxicosis.


Pneumothorax manifesting primary lung cancer.
Pneumothorax is a rare lung cancer manifestation. We report 2 patients in which pneumothorax occurred as a first manifestation of lung cancer. Postoperative lung tissue examination after pneumothorax showed lung cancer by chance. One patient had dissemination suspected due to ruptured bulla with adenocarcinoma. Both immediately underwent additional lobectomy with mediastinal lymphadenectomy after lung cancer was diagnosed, but we detected lung cancer recurrence in the bottom of the pleural cavity on the same side some 11 months after radical surgery in the patient suspected of dissemination. We could resect it completely, followed by adjuvant radiotherapy. The possibility of lung cancer should thus be considered in pneumothorax patients, even if middle-aged.


Latest technologic and surgical developments in using InterStim Therapy for sacral neuromodulation: impact on treatment success and safety.
This article accompanies a "surgery in motion" DVD on sacral neuromodulation (SNM) with InterStim Therapy, which visualizes the implantation of the InterStim II system. The article describes the technical and surgical developments of SNM and their impact on treatment success, safety, and patient's quality of life (QoL). Relevant literature on SNM with regard to technical changes and related clinical outcomes has been reviewed. Since its introduction in the early 1990s, SNM has proven useful in the treatment of several types of chronic urinary (and bowel) dysfunction. Recent technical improvements in devices and, in particular, the introduction of the tined lead 5 yr ago made SNM progress from an elaborate, open-surgery, general anesthesia, one-stage implant procedure to a minimally invasive, local anesthesia, percutaneous technique in two stages. The permanent tined lead implant enables a longer patient testing period (minimum of 14 d recommended) and less lead migration. This has considerably reduced technical failures and improved the success rate of the test phase; the response rate was almost doubled to approximately 80%. These improvements also affected tolerability, resulting in increased QoL for the patient. The use of the recently introduced smaller implantable neurostimulator InterStim II seems to further improve patient comfort and makes the implant procedure for the physician easier and shorter. However, this must be further addressed in clinical studies. SNM with InterStim Therapy using the tined lead offers an efficient treatment modality for patients in whom conservative treatment has failed.


[Effects of a phytohemagglutinin extract on growth, nitrogen digestibility and the activity of invertase and (Na+-K+)-ATPase in the intestinal mucosa of the rat].
A phytohemagglutinin extract is prepared from raw kidney beans (Phaseolus vulgaris) and incorporated at a level of 1% (dry matter) in the diet of young growing rats. Beside a decrease of feed intakes, the main effects of the experimental diet are the following : growth depression, decrease of dry matter and protein digestibility and hypoglycemia. Biological value, organs weight (liver, kidneys, spleen) did not change significantly. The hemagglutinin extract induces an inhibition of saccharase activity whereas (Na+-K+)-ATPase remains unchanged. Growth depressing effect may be due to an alteration of hydrolysis and absorption mechanisms at the level of brush border of enterocytes.


Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial.
Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications. Registered on 5 June 2014 with identification no. NCT02158923 .


Multifaceted roles of plant derived small molecule inhibitors on replication cycle of SARS-CoV-2.
Coronavirus disease 2019 (COVID-19) is an illness caused by the new coronavirus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). It has affected public health and the economy globally. Currently approved vaccines and other drug candidates could be associated with several drawbacks which urges developing alternative therapeutic approaches. To provide a comprehensive review of anti-SARS-CoV-2 activities of plants and their bioactive compounds. Information was gathered from diverse bibliographic platforms such as PubMed, Google Scholar, and ClinicalTrials.gov registry. The present review highlights the potential roles of crude extracts of plants as well as plant-derived small molecules in inhibiting SARS-CoV-2 infection by targeting viral or host factors essential for viral entry, polyprotein processing, replication, assembly and release. Their anti-inflammatory and antioxidant properties as well as plant-based therapies that are under development in the clinical trial phases-1 to 3 are also covered. This knowledge could further help understanding SARS-CoV-2 infection and anti-viral mechanisms of plant-based therapeutics.


Complete differentiation of adipocyte precursors. A culture system for studying the cellular nature of adipose tissue.
Evidence for the complete morphological maturation of precursor cells into adipocytes in vitro is presented. Cells were isolated from the stromal fraction of adipose tissue from adult humans and from rats and were grown in culture. Abdominal skin fibroblasts were used as controls. All cell strains were initially fusiform and replicated. On reaching monolayer confluency, they were transferred to an enriched growth medium in which the human and rat adipocyte precursors differentiated into a homogeneous population of cells, morphologically indistinguishable from mature adipocytes. In contrast, skin fibroblasts from the same person or animal, and grown under identical culture conditions, did not accumulate lipid and retained their fusiform contour. The same results were obtained in the first six subcultures that were studied. Thus, there is firm evidence that fat tissue of adult humans and rats contains adipocyte precursors that differentiate into mature fat cells. The culture system that has been described will facilitate the elucidation of the factors involved in replication and differentiation of adipocyte precursors.


Metastatic colorectal carcinoma and kidney tumors: a report of four cases.
The prognosis of patients with metastatic colorectal carcinoma (CRC) has improved substantially over the last two decades. Longer patient survival comes at a price of more complications, including second primary neoplasms and metastases at unusual sites. Retrospective chart review. We present 4 patients with metastatic CRC who developed kidney tumors. In 2 cases, partial nephrectomy or nephrectomy was performed for second primary renal cell carcinoma. The patients survived 2.5 and more than 6 years after kidney surgery. In the other 2 patients the kidney tumors were diagnosed as CRC metastases, histologically verified in one case; these two patients died within two years of diagnosis of kidney involvement. The diagnostic approach to kidney tumors in CRC patients should include a biopsy because only patients with primary renal cell carcinoma and selected patients with metastatic CRC benefit from nephrectomy.


Role of ASA in the primary and secondary prevention of cardiovascular events.
Cardiovascular disease, which includes coronary heart disease, cerebrovascular disease and peripheral artery disease, is the leading cause of death in developed countries. Evidence from basic research, clinical investigations, observational epidemiologic studies and randomized clinical trials has provided strong support for the benefits of aspirin in decreasing the risk of cardiovascular events in a wide range of pathologies in secondary prevention. Data in primary prevention have far more uncertainties. An overview for the evidence supporting the efficacy of aspirin in primary and secondary prevention of cardiovascular disease is discussed, including the relative and absolute benefit and the risks of side effects. Finally, future developments in the field directed towards individualized treatment strategies and novel antiplatelet agents are examined.


Hydraulic fracturing water use variability in the United States and potential environmental implications.
A U.S. map of water volumes used to hydraulically fracture oil and gas wells, 2011-2014Hydraulic fracturing water volumes differ regionally across the U.S.Discussion of variation in water use and potential environmental implications.


An analysis of the diagnostic contribution of double-radiocompound renography.
The diagnostic contribution of double-radiocompound renography was tested by applying discriminant analysis to the data obtained in one group of normal subjects and in some groups of selected pathological cases which included glomerulonephritis, pyelonephritis, and hypertension. The results obtained confirm the reliability of the test and give evidence of its usefulness in diagnostic clinical work.


Atomic-scale mechanistic features of oxide ion conduction in apatite-type germanates.
Atomistic modelling studies of the apatite-type oxide ion conductor La9.33(GeO4)6O2 show that a key role of the O4 channel oxygen atoms appears to be as a reservoir for the creation of interstitial oxide ion defects, while the migration of these defects proceeds via the GeO4 tetrahedra.


Unusual Radiologic Finding of Intracranial Inflammatory Myofibroblastic Tumor Presenting a Cyst with Mural Nodule.
An intracranial cyst tumor with a mural nodule can be representative of some types of brain tumors, but is a rare presentation of intracranial inflammatory myofibroblastic tumor (IMT). Herein, we report the case of an intracranial IMT in a 48-year-old woman presenting with the extremely unusual radiologic findings of a cyst with a mural nodule.


Advantages and limitations of microtiter biofilm assays in the model of antibiofilm activity of Klebsiella phage KP34 and its depolymerase.
One of the potential antibiofilm strategies is to use lytic phages and phage-derived polysaccharide depolymerases. The idea is to uncover bacteria embedded in the biofilm matrix making them accessible and vulnerable to antibacterials and the immune system. Here we present the antibiofilm efficiency of lytic phage KP34 equipped with virion-associated capsule degrading enzyme (depolymerase) and its recombinant depolymerase KP34p57, depolymerase-non-bearing phage KP15, and ciprofloxacin, separately and in combination, using a multidrug-resistant K. pneumoniae biofilm model. The most effective antibiofilm agents were (1) phage KP34 alone or in combination with ciprofloxacin/phage KP15, and (2) depolymerase KP34p57 with phage KP15 and ciprofloxacin. Secondly, applying the commonly used biofilm microtiter assays: (1) colony count, (2) LIVE/DEAD BacLight Bacterial Viability Kit, and (3) crystal violet (CV) biofilm staining, we unravelled the main advantages and limitations of the above methods in antibiofilm testing. The diverse mode of action of selected antimicrobials strongly influenced obtained results, including a false positive enlargement of biofilm mass (CV staining) while applying polysaccharide degrading agents. We suggest that to get a proper picture of antimicrobials' effectiveness, multiple examination methods should be used and the results must be read considering the principle of each technique and the antibacterial mechanism.


Biomimetic and Self-Assembled Nanoclusters Targeting β-Catenin for Potent Anticancer Therapy and Enhanced Immunotherapy.
Immune checkpoint blockade therapies fail to induce immune response in the vast majority of cancer patients, so developing robust adjuvants for increasing tumor immune response is central for effective tumor immunotherapy. The Wnt/β-catenin pathway is a crucial oncogenic signal in relation to tumor immune evasion; however, none of the Wnt inhibitor under clinical or preclinical phases has demonstrated satisfactory specificity. Thus, new compounds or modalities that tumor specifically modulate the Wnt signal will be of great significance and value in clinical tumor immunotherapy. Herein, inspired by a natural phenomenon in cancer cells that the Achilles' Heel of oncoprotein β-catenin, H1 helix, predisposes β-catenin to oligomerization for proteasomal degradation and can be exacerbated by carnosic acid (CA, a Wnt inhibitor), we developed a size-tuned nanocluster (CAcluster) with well-defined supramolecular nanostructure by coassembling CA and H1 peptide. With the inherent enhanced permeability and retention (EPR) effect and the designed tumor microenvironment (TME) responsiveness, the CAcluster tumor specifically suppress the Wnt/β-catenin cascade in vivo, while maintaining a highly favorable biosafety profile. More importantly, the CAclusterin vivo improved the tumor response to the PD1/PD-L1 immune checkpoint blockade in melanoma and colon cancer. This study provides new insights into the biomimetic coassembly strategy to design supramolecular nanostructured adjuvants for hazard-free Wnt suppression and synergy with tumor immunotherapy.


Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.
This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed. Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus. The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD.


Effects of weaning American glass eels (Anguilla rostrata) with the formula diet on intestinal microbiota and inflammatory cytokines genes expression.
This study aimed to investigate the effects of weaning American glass eels (Anguilla rostrata) with the formula diet on intestinal microbiota and the expression of inflammatory cytokines genes. During the feeding trial, the control group (termed IF group) was fed with initial feed for 34 days, and the experimental group (termed FF group) was fed with initial feed for 30 days, and then weaned with the formula diet for 4 days. After feeding trial, intestines were subjected to microbiota analysis using 16S rDNA high-throughput sequencing, and expression of three inflammatory cytokines genes in gut were examined by qPCR. The results indicated that the species richness and diversity of intestinal microbiota exhibited significantly higher in FF group than that in IF group (P < 0.05). At the phylum level, the core intestinal microflora was the same for two groups. The most abundant phylum was Firmicutes in IF group, while it was Proteobacteria in FF group. Five genera were significantly higher in the IF group compared with the FF group, and Bacillus was the most major enriched biomarker at genus level. Nine genera were significantly higher in the FF group compared with the IF group, and Acidovorax was the most major enriched biomarker. Weaning from initial feeding diet to formula feeding diet enhanced the expression levels of TNF-α and IL-8, and there was no significant change in IL-1β expression between the two groups. These findings would be very useful to improve the diet formulation for weaning stage of American glass eels.


Assessment of the general public's knowledge about rheumatic diseases: evidence from a Portuguese population-based survey.
To identify incorrect beliefs and common knowledge about rheumatic diseases in the general population. Participants were selected during the follow-up of a representative cohort of adult population of Porto, Portugal; 1626 participants completed a questionnaire that included general knowledge items about rheumatic diseases.Discrete and continuous latent variable models were used to identify knowledge flaws and the target groups. Odds ratios (OR) estimated by multinomial logistic regression, and 95% confidence intervals (95%CI) were computed to evaluate magnitude of associations. A continuous latent variable model identified two dimensions: one related to general beliefs (latent 1) and another concerning characteristics, treatment and impact of rheumatic diseases (latent 2). A 3-class latent variable model refined these results: the first class presented the lowest probabilities of correct answer for items associated with the first latent (mean of 39%), and the second class presented the lowest probabilities of correct answer for items with the second latent (mean of 62%). The third class showed the highest probability of a correct answer for almost all the items (mean of 79%). The age and sex standardized prevalence of the classes was 25.7%, 30.8% and 43.5%.Taking class 2 as reference, class 1 was positively associated with the presence of rheumatic diseases (OR = 2.79; CI95% = (2.10-3.70)), with females (OR = 1.28 CI95% = (0.99-1.67)) and older individuals (OR = 1.04; CI95% = (1.03-1.05)), and was negatively associated with education (OR = 0.84; CI95% = (0.81-0.86)); class 3 was positively associated with education (OR = 1.03; CI95% = (1.00-1.05)) and the presence of rheumatic diseases (OR = 1.29; CI95% = (0.97-1.70)). There are several knowledge flaws about rheumatic diseases in the general public. One out of four participants considered false general beliefs as true and approximately 30% did not have detailed knowledge on rheumatic disease. Higher education and the presence of disease contributed positively to the overall knowledge. These results suggest some degree of effectiveness of patient education, either conducted by health professionals or self-driven.


Research on denoising method of chinese ancient character image based on chinese character writing standard model.
Ancient documents are historical evidence of cultural inheritance, and the damage brought by natural and human factors to ancient documents is inevitable, resulting in the collected images of ancient Chinese characters containing a large amount of noise, which seriously affects the accuracy of subsequent image recognition and thus creates a great obstacle to the digitization of ancient documents. To address the complexity of ancient text structure, this paper proposes a Chinese ancient text image denoising method based on the Chinese character writing standard model. The method firstly adds four additional local branches based on the global branching, and uses the supplementary character detail information to weaken the phenomenon of strokes adhering to noise due to the lack of local details; secondly, it introduces the simulation noise of ancient documents to simulate the real ancient character image morphology, which can be used for the adversarial training of this method. In the training process, the minimum absolute value deviation, smoothing loss, structural consistency loss and the refined loss function formed by the adversarial loss are used to iteratively optimize the parameters. Finally, experiments prove that the model in this paper can increase the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) of the image by at least 23.8% and 11.4%, and the user evaluation index (UV) has also reached more than 80%.


Air quality and health-related impacts of traditional and alternate jet fuels from airport aircraft operations in the U.S.
Aviation emissions from landing and takeoff operations (LTO) can degrade local and regional air quality leading to adverse health outcomes in populations near airports and downwind. In this study we aim to quantify the air quality and health-related impacts from commercial LTO emissions in the continental U.S. for two recent years' inventories, 2011 and 2016. We quantify the LTO-attributable PM2.5, O3, and NO2 concentrations and health outcomes for mortality and multiple morbidity health endpoints. We also quantify the impacts from two scenarios representing a nation-wide implementation of 5% or 50% blends of sustainable alternative jet fuels. We estimate 80 (68-93) and 88 (75-100) PM2.5-attributable and 610 (310-920) and 1,100 (570-1,700) NO2-attributable premature mortalities in 2011 and 2016, respectively. We estimate a net decrease of 28 (14-56) and 54 (27-110) in O3-attributable premature mortalities across the U.S. in 2011 and 2016, respectively due to the large O3 titration effects near the airports. We also find that the asthma exacerbations due to NO2 exposures from LTO emissions increase from 100,000 (2,500-200,000) in 2011 to 170,000 (4,400-340,000) in 2016. Implementing a 5% or 50% blend of sustainable alternative jet fuel in 2016 results in a 1% or 18% reduction, respectively in PM2.5-attributable premature mortalities. Monetizing the value of avoided total premature mortalities, we find that a 50%-blended sustainable alternative jet fuel results in a 19% decrease in PM2.5 damages per ton of fuel burned and a 2% decrease in total damages per ton of fuel burned as compared to damages from traditional jet fuel. We also quantify health impacts by state and find California to be the most impacted by LTO emissions. We find that LTO-attributable PM2.5 and NO2 premature mortalities increase by 10% and 80%, respectively from 2011 to 2016 and that NO2-attributable premature mortalities are responsible for 91% of total LTO-attributable premature mortalities in both 2011 and 2016. And since we find LTO-attributable NO2 to be unaffected by the implementation of sustainable alternative jet fuels, additional approaches focused on NOX reductions in the combustor are needed to mitigate the air quality-related health impacts from LTO emissions.


Low indoleamine 2,3-dioxygenase activity in persistent food allergy in children.
Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated. Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA. Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and β-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively). Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.


Distance measurements and origin levels of the coeliac trunk, superior mesenteric artery, and inferior mesenteric artery by multiple-detector computed tomography angiography.
The aim of this study is to determine vertebral levels of the coeliac trunk, the superior mesenteric artery, and the inferior mesenteric artery originated from the abdominal aorta and to calculate the distance measurements between these arteries and between these arteries and the aortic bifurcation by multidetector computed tomography angiography technique. It was determined that the nine different vertebral levels of the coeliac trunk, the nine different vertebral levels of the superior mesenteric artery, and the eleven different vertebral levels of the inferior mesenteric artery. The distance measurements between the coeliac trunk and the superior mesenteric artery, the inferior mesenteric artery, the aortic bifurcation were found significant between female and male. In this study, it was determined more different levels than the levels described in classical anatomy. The preoperative information of these morphological variations can contribute to the reduction of surgical time and perioperative vascular complications especially for anterior lumbar interbody fusion and defining the location of the primary lymphatic drainage site for gastrointestinal malignancies.


Toxic effects of tetracycline and its degradation products on freshwater green algae.
Tetracycline antibiotics are the most widely used antibiotics in the world and the most common veterinary drugs and feed additives used in livestock, poultry and aquaculture operations. Because antibiotics cannot be completely removed by currently existing sewage treatment facilities, these materials enter the environment directly via sewage treatment plant discharge, where they degrade. Accordingly, the metabolism and the ecological toxicity of tetracycline degradation products are worthy of attention. Herein, we investigated the effects of tetracycline and its degradation products (anhydrotetracycline and epitetracycline hydrochloride) on the growth, cell structure and algal cell oxidative stress of common Chlorella vulgaris. The results showed that the 96h-EC50 values of tetracycline (TC), anhydrotetracycline (ATC) and epitetracycline (ETC) on algal cells were 7.73, 5.96 and 8.42 mg/L, respectively. Moreover, the permeability of algal cells exposed to high concentrations of these three drugs was significantly enhanced. In addition, there were structural changes in the cells such as plasmolysis and starch granule deposition appeared, the thylakoid lamellae in the chloroplasts became blurred and deformed, and the vacuoles became larger. Exposure to higher concentrations (>5 mg/L) of TC and its degradation products ATC and ETC significantly upregulated the activity of ROS, as well as the antioxidants SOD and CAT. The levels of the lipid peroxidation product MDA also showed the same trend. Finally, ATC had the strongest toxicity toward algal cells, followed by TC and then ETC.


Emergence of a new disease as a result of interspecific virulence gene transfer.
New diseases of humans, animals and plants emerge regularly. Enhanced virulence on a new host can be facilitated by the acquisition of novel virulence factors. Interspecific gene transfer is known to be a source of such virulence factors in bacterial pathogens (often manifested as pathogenicity islands in the recipient organism) and it has been speculated that interspecific transfer of virulence factors may occur in fungal pathogens. Until now, no direct support has been available for this hypothesis. Here we present evidence that a gene encoding a critical virulence factor was transferred from one species of fungal pathogen to another. This gene transfer probably occurred just before 1941, creating a pathogen population with significantly enhanced virulence and leading to the emergence of a new damaging disease of wheat.


Conformational properties of the aggregation precursor state of HypF-N.
The conversion of specific proteins or protein fragments into insoluble, ordered fibrillar aggregates is a fundamental process in protein chemistry, biology, medicine and biotechnology. As this structural conversion seems to be a property shared by many proteins, understanding the mechanism of this process will be of extreme importance. Here we present a structural characterisation of a conformational state populated at low pH by the N-terminal domain of Escherichia coli HypF. Combining different biophysical and biochemical techniques, including near- and far-UV circular dichroism, intrinsic and 8-anilinonaphthalene-1-sulfonate-derived fluorescence, dynamic light scattering and limited proteolysis, we will show that this state is largely unfolded but contains significant secondary structure and hydrophobic clusters. It also appears to be more compact than a random coil-like state but less organised than a molten globule state. Increase of the total ionic strength of the solution induces aggregation of such a pre-molten globule state into amyloid-like protofibrils, as revealed by thioflavin T fluorescence and atomic force microscopy. These results show that a pre-molten globule state can be, among other possible conformational states, one of the precursor states of amyloid formation. In addition, the possibility of triggering aggregation by modulating the ionic strength of the solution provides one a unique opportunity to study both the initial precursor state and the aggregation process.


Impact of a same day admission project in reducing the preoperative bed occupancy demand in a pediatric inpatient hospital.
A same day admission approach was established for pediatric patients undergoing elective surgery owing to an increase in demand for bed availability and the need for medical, logistical, psychological, and fiscal improvements. This study aimed to assess the effectiveness of the same day admission approach for reducing demand for preoperative bed occupancy in pediatric inpatient units. Data on elective surgery patients considered for same day admission were prospectively collected in an Excel spreadsheet. Same day admission patients numbered 269 (25.87%; n = 1040), 461 (41.7%; n = 1104), 382 (38.67%; n = 998), and 560 (44.20%; n = 1267) in 2018, 2019, 2020, and 2021, respectively. Over the 4-year period between 2018 and 2021, pediatric orthopedic surgeries accounted for the majority of same day admissions (29.72%; n = 497), followed by ear, nose, and throat (21.30%; n = 356), general (16.99%; n = 284), plastic (14.53%; n = 243); urology (9.87%; n = 165); optometry and ophthalmology (3.77%; n = 63); neuro (2.51%; n = 42), and dental (1.31%; n = 22) surgeries. The total number of days of saved preoperative beds over the 4-year period was 1672 days (an average of 418 hospital days per year). This study showed that same day admission approach should be implemented in pediatrics institutions to reduce hospital bed demand. The implementation of this initiative is widely variable between specialties due to interlinked medical, operational, and logistical factors. III.


Arming alpha 2-macroglobulin with ricin A chain forms a cytotoxic conjugate that inhibits protein synthesis and kills human fibroblasts.
A conjugate containing alpha 2-macroglobulin and highly purified ricin A chain was made using N-succinimidyl-3-(2-pyridyldithio)propionate. Radioimmunoassay indicated that it contained 1.2 mol A chain per mol alpha 2-macroglobulin. The conjugate inhibited polyuridylic-acid directed translation by rat liver ribosomes and protein synthesis in human fibroblasts. There was a 90 min lag period before the beginning of inhibition in fibroblasts, but complete inhibition could be achieved. By measuring protein synthesis as a function of protein concentration, it was demonstrated that 8.25 X 10(-9) M conjugate was required to inhibit 50% of protein synthesis in 6 h. To achieve the same level of inhibition, 165-times more (1.3 X 10(-6) M) unconjugated A chain was required, and 180-times less ricin (4.6 X 10(-11) M). Ricin was more than 28 000 times more inhibitory than A chain alone. The presence of alpha 2-macroglobulin did not increase the cytotoxicity of unconjugated A chain, and it even protected the cells to a slight extent. The inhibitory action of the conjugate was blocked by antibodies specific for alpha 2-macroglobulin or ricin, and it was not prevented by galactose or antibodies specific for ricin B chain. Electron microscopy of the conjugate indirectly labelled with ferritin demonstrated that it was internalized by receptor mediated endocytosis through coated pits. These data indicate that the A chain portion of the conjugate survives the conditions in the lysosomes to the extent that it retains its ability to inactivate cytoplasmic ribosomes.


Variability in repeat serum etonogestrel concentrations among contraceptive implant users during the steady-release pharmacokinetic period.
To assess the variability of repeated measurements of serum etonogestrel concentration among contraceptive implant users. We measured 3 consecutive serum etonogestrel concentrations, drawn weekly, in women using etonogestrel implants for 12 to 36 months. We used a repeated measures test to evaluate differences. Among 20 participants, repeat serum etonogestrel concentrations did not differ from initial measurements (Friedman's test, p = 0.95). Mean serum etonogestrel concentrations had similar 95% confidence intervals at each time point: (134.09, 201.46), (135.08, 237.46), and (132.66, 192.45). We confirm that single-time measurements of serum etonogestrel concentration are acceptable pharmacokinetic outcomes for etonogestrel implant studies. Pharmacokinetic studies of the etonogestrel contraceptive implant assume single-time measurements are stable steady-state estimates based on small studies using older analysis methods. Our repeated measures study using modern liquid-chromatography mass-spectrometry analysis methods provides updated support for single-time pharmacokinetic measurements among etonogestrel implant users.


Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia.
The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1-5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). The median age was 55 years (range, 21-65). CR + CRi was 83% (54/65) and 27% in the untreated and ts-AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.


Export of metabolites from pancreatic islet mitochondria as a means to study anaplerosis in insulin secretion.
Recent evidence suggests that the mitochondrial synthesis (anaplerosis) of alpha-ketoglutarate or intermediates that can be converted to alpha-ketoglutarate, such as citrate or glutamate, are important for insulin secretion stimulated by metabolizable secretagogues. In order to focus on the productive role of mitochondria (anaplerosis) separate from the consumptive role of the cytosol (cataplerosis) in insulin secretion, pyruvate and other metabolites of insulin secretagogues were added to microgram amounts of mitochondria obtainable from rat or mouse pancreatic islets and the export of metabolites was surveyed. Cellular levels of metabolites in rat islets were also measured. The export of malate from mitochondria was the most responsive to various substrates. The export of citrate did not increase in the presence of pyruvate alone or pyruvate plus glutamate, but malate plus pyruvate caused citrate to be exported. Citrate levels in intact cells did not change with glucose. Glutamate levels did not increase in intact islets in the presence of glucose, thus not providing evidence for glutamate acting as a messenger in glucose-induced insulin secretion. The citrate level may not need to increase in order to provide increased malonyl-coenzyme A for signaling insulin secretion. Unlike many cells, insulin cells probably obtain cytosolic NADPH equivalents by exporting them from mitochondria to the cytosol via a pyruvate malate shuttle or an isocitrate shuttle. The current results suggest that the reason for anaplerosis in insulin secretion is quite complex and not fully explained by current knowledge.


[Utilization of reinforced acetabular cages with caudal flange in reconstructing pelvic defect after acetabular tumor resection].
To evaluate the surgical procedure of reinforced acetabular cage with caudal flange in reconstruction of pelvic defect after acetabular tumor resection. Between June 2003 and December 2009, 25 patients with Harrington class III pelvic defect underwent reconstruction with a reinforced acetabular cage with caudal flange and total hip arthroplasty (THA). There were 13 males and 12 females with an average age of 51.2 years (range, 13-73 years). The main clinical manifestations included hip pain and buttock pain, with a median disease duration of 6 months (range, 1-96 months). Pathological findings showed 18 cases of metastasis, 3 cases of multiple myeloma, 1 case of non-Hodgkin's lymphoma, 1 case of grade I chondrosarcoma, 1 case of giant cell tumor, and 1 case of chondroblastoma. For the patient with chondroblastoma, THA with LINK RIBBED system was used. An artificial total hip system made in China was used in 6 patients and LINK SP II system was used in the other 18 patients. No patients died perioperatively. Deep infection and hip dislocations occurred in 1 and 2 patients, respectively. At last follow-up, 8 of 18 patients with metastasis died of cancer and the average survival time was 11 months. The other 10 who were alive were followed up 15 months on average. One patient with multiple myeloma died of pulmonary infection at 21 months after operation and the other 2 with multiple myeloma and 1 with lymphoma were alive with an average follow-up of 17 months. The patient with grade I chondrosarcoma and patient with chondroblastoma were followed up 58 and 12 months, respectively, without recurrence. Recurrence occurred in the patient with giant cell tumor at 19 months after operation. Loosening of implant occurred in 3 patients because of local tumor recurrence. For the 23 patients at 6 months after operation, the mean Musculoskeletal Tumor Society (MSTS) 93 score was 81% (range, 57%-93%). Reinforced acetabular cage with caudal flange could be used together with THA for reconstruction of Harrington class III pelvic defects after acetabular tumor resection, and low incidence of postoperative complication and good functional outcome could be expected.


Study of kidney dysfunction in non-silicotic Egyptian workers.
Occupational exposure to silica dust could lead to renal alterations in the glomeruli and proximal tubules. In the present study, occupational exposure to silica dust has been examined as a possible risk factor with respect to subclinical signs of kidney dysfunction. One-hundred forty eight exposed workers from a ceramic factory versus 121 controls of matched age, socioeconomic status and smoking habits were included. Data was collected through a questionnaire and clinical examination. There was a high prevalence of renal complaints in the ceramic workers specially the loin pain, dysuria. Crystalluria was significantly higher in the exposed group (12.2%) than the controls (5%). Renal urinary biomarkers including the high-molecular-weight protein albumin (U.Malb); the low-molecular-weight protein α1-microglobulin (α(1)M); the lysosomal enzyme N-acetyl-β-D-glucosaminidase (NAG) urinary excretion of copper (U.Cu) and zinc (U.Zn) have been investigated. Urinary levels of silica and creatinine (U.cr) were estimated. Data from the present study showed a high significant increase in the urinary excretion of all measured urinary parameters in the group of ceramic workers compared with control subjects. There were no significant differences in the means of U.Zn/U.cr, U.Malb/U.cr, and α(1)M/U.cr among the four investigated departments of ceramic factory. The significant difference was present mainly between the individual departments and the controls, while, there was significant differences in the means of U.Cu/U.cr, U.NAG/U.cr, and U.silica/U.cr among the four departments and the controls. Among the exposed workers, significant correlation was apparent between work duration and only U.Zn/U.cr (r=0.17, p<0.05), and U.Cu/U.cr (r=0.19, p<0.05), while all measured urinary parameters were significantly correlated with each other. On conclusion silica exposure leads to renal alterations which parallel the change in proteinuria and enzymuria, as well as the increased loss in urine of each of Zn and Cu. Measurement of the levels of urinary zinc and copper may serve as a sensitive indicator of the impaired renal function caused by silica exposure. The corresponding analytes could have potential value as indicators of renal function before the kidney is irreversibly injured and, thus could be suitable as monitoring tools for at-risk persons exposed to silica. Researches should assess whether the current occupational standards for silica adequately protect workers from renal disease or this established standard needs to be revised.


Optimization of collimators for imaging positron emitters by a gamma camera.
The imaging of positron-emitting isotopes using a gamma camera requires special collimators. A ray-tracing method for simulating the point-spread function of collimators and, therefore, the total gamma camera system is presented. Simulated data obtained by this method showed good agreement with experimental data. Using this method, optimal lead and tungsten collimators for positron emitters were devised; at an object distance of B = 100 mm, these yielded a point-spread function with an FWHMtot = 9.1 mm using an intrinsic resolution of FWHMintr = 8.0 mm.


Squamous cell carcinoma arising in Warthin's tumor of the parotid gland. A light, electron microscopic, and immunohistochemical study.
The fourth recorded squamous cell carcinoma arising in a pre-existing Warthin's tumor is reported. A gradual transition was noted from the mitochondria-rich epithelium of benign portions of the tumor to organelle-poor cells forming the areas of squamous metaplasia and carcinoma. Bundles of intermediate filaments corresponding to immunoreactive keratin were demonstrated in all epithelial parts of the tumor and also in the epithelium of a benign Warthin's tumor that was studied in parallel.


The illicit preparation of morphine and heroin from pharmaceutical products containing codeine: 'homebake' laboratories in New Zealand.
Since 1983 a large number of small-scale illicit laboratories producing morphine and heroin from commercially available, codeine-based pharmaceutical products have been encountered in New Zealand. The codeine demethylation procedure is based on the use of pyridine hydrochloride. Very simple laboratory equipment and reagents are required and these can be utilised by people with little or no chemical background, following a recipe-like procedure. The process yields a characteristic product known as 'homebake'. This process is fully described.


Solid-State Isolation of Cyclic Alkyl(Amino) Carbene (cAAC)-Supported Structurally Diverse Alkali Metal-Phosphinidenides.
Cyclic alkyl(amino) carbene (cAAC)-supported, structurally diverse alkali metal-phosphinidenides 2-5 of general formula ((cAAC)P-M)n (THF)x [2: M=K, n=2, x=4; 3: M=K, n=6, x=2; 4: M=K, n=4, x=4; 5: M=Na, n=3, x=1] have been synthesized by the reduction of cAAC-stabilized chloro-phosphinidene cAAC=P-Cl (1) utilizing metallic K or KC8 and Na-naphthalenide as reducing agents. Complexes 2-5 have been structurally characterized in solid state by NMR studies and single crystal X-ray diffraction. The proposed mechanism for the electron transfer process has been well-supported by cyclic voltammetry (CV) studies and Density Functional Theory (DFT) calculations. The solid state oligomerization process has been observed to be largely dependent on the ionic radii of alkali metal ions, steric bulk of cAAC ligands and solvation/de-solvation/recombination of the dimeric unit [(cAAC)P-M(THF)x ]2 .


Serum Anti-Mullerian Hormone and Estradiol Concentrations in Gilts and Their Age at Puberty.
For experiment one, blood samples were obtained from 200 gilts at 90, 120, 150, 180, and 200 days of age. Serum samples from the 30 youngest (166.1 ± 0.7 days) and 30 oldest (198.8 ± 0.6 days) gilts exhibiting estrus by 200 days, and a further 18 gilts that remained anestrus at 200 days, were assayed for serum concentrations of anti-Mullerian hormone (AMH) and estradiol (E2). Gilts younger at puberty had higher (p < 0.05) AMH levels than those older at puberty, and both groups had higher AMH levels than anestrus gilts (p < 0.05). Regardless of age, serum E2 was higher (p < 0.05) in gilts that achieved puberty than in gilts remaining anestrus. At spontaneous pubertal estrus detection, there was no effect of pubertal age on the number of preovulatory ovarian follicles. For experiment two, 152 prepubertal gilts received an intramuscular (IM) injection of 400 IU eCG plus 200 IU hCG and then received fence-line boar contact to detect estrus onset. Serum AMH concentrations were higher (p < 0.05) in the first 25 gilts to exhibit puberty than the last 28 gilts, with the first gilts also having more preovulatory follicles (p < 0.0001). Taken together, these data support an association between serum AMH concentrations and degree of physiological maturity and ovarian follicular development in gilts.


A rare variant of erythema nodosum leprosum: a case report.
We report a patient with lepromatous leprosy who developed a rare variant of type-2 lepra reaction, characterized by pustular lesions, on switching from WHO multi drug therapy (MDT) to ofloxacin-aided MDT.


Palmaris Longus Muscle Variations: Clinical Significance and Proposal of New Classifications.
The palmaris longus muscle is one of the most variable muscles in the human body and there have been numerous variations reported. The different palmaris longus variations are interesting not only from an anatomical point of view, but they could also have definite clinical significance. The aim of this study was to examine the different types of variations of palmaris longus muscle in the Bulgarian population. Over a period of 15 years, 56 formol-carbol fixed human cadavers were studied to investigate the different variations of palmaris longus muscle (PLM). Various anatomical variations of PLM have been reported: absence (2.68%); reversed palmaris longus coexisting with an additional abductor digiti minimi muscle (0.89%); digastric (0.89%); palmaris longus with intermediate muscle belly (1.79%) and duplication (1.79%). To reveal the wide variety of the types of palmaris longus muscle and their importance for clinical practice, we make a brief literature review concerning the different types of variations, their role in the median and ulnar neuropathy in the wrist or as structures simulating a soft tissue tumour and the application of palmaris longus tendon in plastic and reconstructive surgery as grafting material. We also present new systematic anatomical and clinical classifications of palmaris longus variations by dividing them into two simple groups.


Applicability of endoscopic submucosal dissection for undifferentiated early gastric cancer: Mixed histology of poorly differentiated adenocarcinoma and signet ring cell carcinoma is a worse predictive factor of nodal metastasis.
Endoscopic submucosal dissection (ESD) is not considered an appropriate treatment for undifferentiated early gastric cancer (UEGC) due to the higher risk of nodal metastases. We aimed to investigate predictive factors for nodal metastases in UEGCs, determine whether the tumor histology is an independent factor for it, and explore whether ESD is applicable for UEGC. We reviewed the medical records of 1837 patients who underwent curative gastrectomy for poorly differentiated adenocarcinoma, signet ring cell carcinoma, and a mixed type of both tumors between 2008 and 2012. Nodal metastases were found in 208 (11.3%) patients. Multivariate analysis revealed that lymphovascular invasion and tumor histology were significantly associated with nodal metastases in mucosal cancers, the rates of which were higher in mixed type tumors (6.3%) than in the other two types (2.0-2.5%; p = 0.005). No nodal metastases were observed in poorly differentiated adenocarcinomas <2 cm and signet ring cell carcinomas <1 cm without lymphovascular invasion and confined to the mucosa. Mixed type tumors should not be considered for endoscopic resection. ESD might be applicable for mucosal tumors with poorly differentiated adenocarcinoma <2 cm and signet ring cell carcinoma <1 cm without lymphovascular invasion.


Frequency of Parkinson disease following COVID-19 infection: A two-year retrospective cohort study.
COVID-19 infection is known to cause various neurological symptoms, and potentially increases the risk of developing subsequent neurodegenerative conditions including parkinsonism. To our knowledge, no study to date has used a large data set in the United States to ascertain the risk of developing incident Parkinson disease in patients with history of COVID-19 infection compared to the risk amongst those without prior COVID-19 infection. We utilized data from TriNetX electronic health records network which includes 73 healthcare organizations and over 107 million patients. We compared adult patients with and without COVID-19 infection, with health records from January 1, 2020 through July 26, 2022, to determine the relative risk of developing Parkinson disease stratified by 3-month intervals. We used propensity score matching to control for patients' age, sex, and smoking history. We collected data on 27,614,510 patients meeting our study criteria: 2,036,930 patients with a positive COVID-19 infection (COVID-19) and 25,577,580 without a positive COVID-19 infection (non-COVID-19). After propensity score matching, age, sex, and smoking history differences became non-significant, with 2,036,930 patients in each cohort. After propensity score matching, we found significantly increased odds of new onset Parkinson disease in the COVID-19 cohort at three, six, nine, and twelve months from the index event, with peak odds ratio at six months. After twelve months there is no significant difference between the COVID-19 group and non-COVID-19 group. There may be a transiently increased risk of developing Parkinson disease in the first year following COVID-19 infection.


A prospective registry analysis of psychosocial and metabolic health between women with and without metabolic syndrome after a complicated pregnancy.
Pregnancy complications affect over one quarter of Australian pregnancies, and this group of mothers is vulnerable and more likely to experience adverse cardiometabolic health outcomes in the postpartum period. Metabolic syndrome is common in this population and may be associated with postpartum mental health issues. However, this relationship remains poorly understood. To compare the differences in psychosocial parameters and mental health outcomes between women with metabolic syndrome and women without metabolic syndrome 6 months after a complicated pregnancy. This study is prospective registry analysis of women attending a postpartum healthy lifestyle clinic 6 months following a complicated pregnancy. Mental health measures included 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalised Anxiety Disorder questionnaire (GAD-7), self-reported diagnosed history of depression, anxiety and/or other psychiatric condition, and current psychotropic medication use. Women with metabolic syndrome reported significantly more subjective mental health concerns, were more likely to have a history of depression and other psychiatric diagnoses and were more likely prescribed psychotropic medications. However, there were no significant differences in PHQ-9 and GAD-7 scores. Amongst new mothers who experienced complications of pregnancy, those with metabolic syndrome represent a particularly vulnerable group with regards to psychosocial disadvantage and mental health outcomes. These vulnerabilities may not be apparent when using common standardised cross-sectional mental health screening tools such as PHQ-9 and GAD-7.


Interactions of renal prostaglandins, renin-angiotensin system and renal kallikrein-kinin system in human hypertension.
Dietary sodium deprivation lowered blood pressure in patients with essential hypertension, while indomethacin induced a rise in blood pressure with significant decreases in plasma angiotensin II concentration and urinary excretion of sodium and PGE. In contrast, captopril lowered blood pressure in them with significant decrease in plasma angiotensin II concentration and significant increase in urinary excretion of sodium and PGE. These data strongly indicate that the decreased PG generation in the nephron could elevate blood pressure by means of sodium retention caused by the reduced renal excretory function in spite of the decreased R-A system in human, suggesting the involvement of renal tubular PGE2 in the regulation of blood pressure.


How can we improve the acceptability of vaccination against Human Papillomavirus (HPV) in France? An original qualitative study with focus groups comprising parents and school staff, interviewed separately.
It has been proven that vaccination is effective against Human Papillomavirus (HPV) infections, genital warts, and pre-cancerous and cancerous cervical lesions. Nevertheless, the HPV vaccine coverage of 37.4 % in 2021 in France is one of the lowest in Europe. To explore and understand the reason why French population is so late compared to its neighbours, we carried out focus groups with mothers and with National Education school staff. We aimed to identify knowledge and perceptions of HPV in both study populations, as well as factors influencing HPV vaccination. Between January 2020 and March 2021, we performed a qualitative study using an inductive approach with a thematic content analysis (TCA). We conducted semi-structured focus groups with 29 people including 15 mothers of adolescents in middle schools and 14 school staff from the national education system. Different factors influenced the decision-making process of parents and school staff: knowledge and perceptions of HPV and its vaccine, sources of information about HPV and vaccination. Mothers' discourses differed from those of school staff. They mentioned the importance of gynaecological monitoring and the negative image of pharmaceutical companies, and questioned internet as a reliable source of information. For their part, school staff mentioned cultural and/or religious affiliation, municipalities' role to inform the population, and ethical dilemma or logistical challenges regarding HPV vaccination in schools. The results of these focus groups provided information on which elements may harm or help HPV vaccination. Identified perceptions, beliefs, knowledge, barriers, and facilitators will help us to build an intervention program focus on general practitioners (GP), school staff, parents, and adolescents.


Modeling, Simulation and Data Processing for Additive Manufacturing.
Additive manufacturing or, more commonly, 3D printing is one of the fundamental elements of Industry 4 [...].


Identification of isolated cavity features within molecular dynamics simulated chromatographic surfaces.
Highly ordered morphological features were characterized for molecular dynamics simulated alkyl-modified silica models that represent chromatographic materials with enhanced shape recognition capability. Deep cavities (8-10A wide) within the alkyl chains were identified for C18 polymeric models corresponding to shape-selective RPLC stationary phases. The all-trans conformational distal-end segments of these isolated cavities averaged over a 100 ps simulation time interval were observed to increase (up to 15 A) in models with an increase in both surface coverage and corresponding shape selectivity. Similar-structure cavities with significant alkyl chain ordered regions (>11A) were isolated from two independent C18 models (differing in bonding chemistry, density and temperature) that represent highly shape-selective materials. The size and depth of these ordered regions increased (up to 28 A) for the extended-length C30 alkyl phase models. These initial results offer a physical representation of alkyl-modified surfaces that may facilitate the identification of potential molecular features that may be involved in the shape-selective retentive processes, as well as illustrating the potential for such computational techniques to predict the molecular recognition capabilities of novel analyte-specific sorbents.


Outcomes of a hospital-wide plan to improve care of comatose survivors of cardiac arrest.
Therapeutic hypothermia (TH) improves outcomes in comatose survivors of cardiac arrest. Few hospitals have protocol-driven plans that include TH. We implemented a series of process interventions designed to increase TH use and improve outcomes in patients successfully resuscitated from out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA). Linked interventions including a TH order sheet, verbal and written feedback to individual providers, an educational program, TH "kit" and on-call consultants to assist with patient care and hypothermia induction were implemented between January 1, 2005 and December 31, 2007 in a large, university-affiliated, tertiary care center. We then completed a retrospective review of all patients treated for cardiac arrest during the study period. Descriptive statistics, chi-squared analyses, or Fisher's exact test were used as appropriate. A p value <0.05 was considered significant. 135 OHCA patients and 106 IHCA patients were eligible for post-arrest care. TH use increased each year in the OHCA group (from 6% to 65% to 76%; p<0.001) and IHCA group (from 0% to 36% to 53%; p=.02). A good outcome was achieved in 21% and 8% of comatose patients with OHCA and IHCA, respectively. Patients with OHCA and ventricular dysrhythmia were more likely to have a good outcome with TH treatment than without it (good outcome in 57% vs. 8%; p=.005). Implementing a series of aggressive interventions increased appropriate TH use and was associated with improved outcomes in our facility.


GABA from putrescine is bound in macromolecular form in keratinocytes.
We report for the first time that the neurotransmitter gamma-aminobutyric acid (GABA) exists in macromolecular form in keratinocytes. GABA derived from putrescine (Pu) has been identified as a component of acid-precipitable material of cultured human keratinocytes. Confluent, stratified cultures of human foreskin keratinocytes exposed to [3H]-Pu for 4 hours took up about 14% of the radioactivity from the medium and 1% of the total cell-associated radioactivity was precipitable by trichloroacetic acid (TCA). Both attached and shed cells were examined by HPLC for Pu and its radioactive metabolites in TCA-insoluble and TCA-soluble fractions. GABA accounted for the major portion (54%) of the radioactivity derived from Pu in the TCA-precipitable material of attached keratinocytes. Pu and spermidine represented lesser amounts, 35% and 9% respectively, of the total TCA-precipitable radioactivity. In addition, a large portion of acid soluble radioactivity derived from Pu (63%) was GABA, whereas Pu and spermidine represented 29% and 6% respectively of the total TCA-soluble radioactivity. The exact origin of GABA in acid-precipitable material, as well as its form of attachment, is currently under investigation.


Depressive symptoms, vascular risk factors, and Alzheimer's disease.
Depressive symptoms in the elderly are associated with an increased Alzheimer's disease (AD) risk. We sought to determine whether the association between depressive symptoms and AD is explained by a history of vascular risk factors and stroke. Five hundred and twenty-six elderly persons from New York City without dementia at baseline were followed for a mean of 5 years. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAM). Incident AD was ascertained using standard criteria. Diabetes, hypertension, heart disease, current smoking and stroke were ascertained by self-report. Proportional hazards regression was used to relate HAM scores to incident AD. HAM scores were higher in persons with hypertension, heart disease, and stroke, which in turn were related to higher AD risk. AD risk increased with increasing HAM scores as a continuous logarithmically transformed variable (HR for one point increase=1.4; 95% CI=1.1,1.8) and as a categorical variable (HR for HAM >or= 10=3.4; 95% CI=1.5,8.1; p for trend=0.004 with HAM=0 as the reference). These results were virtually unchanged after adjustment for vascular risk factors and stroke, individually (HR for HAM >or= 10=3.4; 95% CI=1.5,8.1; p for trend = 0.004), and in a composite measure (HR for HAM >or= 10=3.0; 95% CI=1.2,7.8; p for trend=0.02). The prospective relation between depressive symptoms and AD is not explained by a history of vascular risk factors and stroke, suggesting that other mechanisms may account for this association.


Identification of an inhibitory circuit that regulates cerebellar Golgi cell activity.
Here we provide evidence that revises the inhibitory circuit diagram of the cerebellar cortex. It was previously thought that Golgi cells, interneurons that are the sole source of inhibition onto granule cells, were exclusively coupled via gap junctions. Moreover, Golgi cells were believed to receive GABAergic inhibition from molecular layer interneurons (MLIs). Here we challenge these views by optogenetically activating the cerebellar circuitry to determine the timing and pharmacology of inhibition onto Golgi cells and by performing paired recordings to directly assess synaptic connectivity. In contrast to current thought, we find that Golgi cells, not MLIs, make inhibitory GABAergic synapses onto other Golgi cells. As a result, MLI feedback does not regulate the Golgi cell network, and Golgi cells are inhibited approximately 2 ms before Purkinje cells, following a mossy fiber input. Hence, Golgi cells and Purkinje cells receive unique sources of inhibition and can differentially process shared granule cell inputs.


Transplantation Treatment of Extensive Soft-Tissue Defects in Lower Extremities with a Combination of Cross-Bridge Flap and Combined Free-Tissue Flap Covered by Vacuum Sealing Drainage: One Case Report.
This article reported the ultilization of cross-bridge flap transplantation and combined free-tissue flap transplantation to treat a 54-year-old male with Gustilo type III-C injuries. Thorough debridement, external fixation and vacuum sealing drainage were performed in the fist-stage treatment. After the removal of negative pressure on VSD devices, the joined free-tissue flaps and the cross-bridge flap were performed to repair the extensive soft-tissue defects. One month later the pedicle of cross-bridge flap was divided and the external fixator connecting both the lower legs was removed. In 3-month follow-up, the extensive defects was completely covered by a nearly normal skin and radiograph showed tibia and talus healing.


A novel set-up for the ex vivo analysis of mechanical properties of mouse aortic segments stretched at physiological pressure and frequency.
Cyclic stretch is known to alter intracellular pathways involved in vessel tone regulation. We developed a novel set-up that allows straightforward characterization of the biomechanical properties of the mouse aorta while stretched at a physiological heart rate (600 beats min-1 ). Active vessel tone was shown to have surprisingly large effects on isobaric stiffness. The effect of structural vessel wall alterations was confirmed using a genetic mouse model. This set-up will contribute to a better understanding of how active vessel wall components and mechanical stimuli such as stretch frequency and amplitude regulate aortic mechanics. Cyclic stretch is a major contributor to vascular function. However, isolated mouse aortas are frequently studied at low stretch frequency or even in isometric conditions. Pacing experiments in rodents and humans show that arterial compliance is stretch frequency dependent. The Rodent Oscillatory Tension Set-up to study Arterial Compliance is an in-house developed organ bath set-up that clamps aortic segments to imposed preloads at physiological rates up to 600 beats min-1 . The technique enables us to derive pressure-diameter loops and assess biomechanical properties of the segment. To validate the applicability of this set-up we aimed to confirm the effects of distension pressure and vascular smooth muscle tone on arterial stiffness. At physiological stretch frequency (10 Hz), the Peterson modulus (EP ; 293 (10) mmHg) for wild-type mouse aorta increased 22% upon a rise in pressure from 80-120 mmHg to 100-140 mmHg, while, at normal pressure, EP increased 80% upon maximal contraction of the vascular smooth muscle cells. We further validated the method using a mouse model with a mutation in the fibrillin-1 gene and an endothelial nitric oxide synthase knock-out model. Both models are known to have increased arterial stiffness, and this was confirmed using the set-up. To our knowledge, this is the first set-up that facilitates the study of biomechanical properties of mouse aortic segments at physiological stretch frequency and pressure. We believe that this set-up can contribute to a better understanding of how cyclic stretch frequency, amplitude and active vessel wall components influence arterial stiffening.


[Comparative study of tensile strength of enamel/resin/metal interface. Effect of bonding resins, retention mechanisms and metal alloys].
The purpose of this study was to compare the enamel/resin/metal bond tensile strength by using human canines, in which castings were bonded. These castings were obtained by Co-Cr or Ni-Cr alloys and showed four types of mechanisms of retention: 50 micrograms aluminum oxide abrasive, electrochemical etch, acrylic beads metal mesh. The castings were bonded utilizing Comspan Opaque and Panavia Ex. The specimens were subjected to tensile forces after 24 hours in an Instron machine. The castings subjected to 50 micrograms aluminum oxide abrasive and bonded utilizing Panavia EX showed the biggest bond tensile strength.


Foot-controlled robotic-enabled endoscope holder for endoscopic sinus surgery: A cadaveric feasibility study.
To evaluate the feasibility of a unique prototype foot-controlled robotic-enabled endoscope holder (FREE) in functional endoscopic sinus surgery. Cadaveric study. Using human cadavers, we investigated the feasibility, advantages, and disadvantages of the robotic endoscope holder in performing endoscopic sinus surgery with two hands in five cadaver heads, mimicking a single nostril three-handed technique. The FREE robot is relatively easy to use. Setup was quick, taking less than 3 minutes from docking the robot at the head of the bed to visualizing the middle meatus. The unit is also relatively small, takes up little space, and currently has four degrees of freedom. The learning curve for using the foot control was short. The use of both hands was not hindered by the presence of the endoscope in the nasal cavity. The tremor filtration also aided in the smooth movement of the endoscope, with minimal collisions. The FREE endoscope holder in an ex-vivo cadaver test corroborated the feasibility of the robotic prototype, which allows for a two-handed approach to surgery equal to a single nostril three-handed technique without the holder that may reduce operating time. Further studies will be needed to evaluate its safety profile and use in other areas of endoscopic surgery. NA. Laryngoscope, 126:566-569, 2016.


Peptide pool immunization and CD8+ T cell reactivity.
Mice were immunized twice with a pool of five peptides selected among twenty 8-9-mer peptides for their ability to form stable complexes at 37°C with recombinant H-2K(b) (half-lives 10-15h). Vaccine-induced immunity of splenic CD8(+) T cells was studied in a 24h IFNγ Elispot assay. Surprisingly, IFNγ spot-formation was observed without addition of peptide to the assay culture at 3 weeks and 3 months after immunization. To clarify if IFNγ spot formation in the absence of peptide exposure ex vivo is caused by the peptide-pool per se, mice were immunized with single peptides. Three of the five peptides induced normal peptide immunity i.e. the specific T cell reactivity in the Elispot culture was strictly dependent on exposure to the immunizing peptide ex vivo. However, immunization with two of the peptides, a VSV- and a Mycobacterium-derived peptide, resulted in IFNγ spot formation without peptide in the Elispot culture. Immunization with a mixture of the VSV-peptide and a "normal" peptide also resulted in IFNγ spot formation without addition of peptide to the assay culture. Peptide-tetramer staining of CD8(+) T cells from mice immunized with a mixture of VSV-peptide and "normal" peptide showed peptide specific binding by CD8(+) T cells for both of the peptides. Thus, although immunization with certain peptides alone or in a mixture of peptides may result in IFNγ spot formation without peptide in the assay culture, specific immunity against the individual immunizing peptide in the mixture remains intact. Our data suggest that certain peptides exhibit sustained immunogenicity in vivo for prolonged periods of time.


Clinical management of pyoderma gangrenosum.
Pyoderma gangrenosum is a noninfectious neutrophilic dermatosis that usually starts with sterile pustules which rapidly progress to painful ulcers of variable depth and size with undermined violaceous borders. In 17 to 74% of cases, pyoderma gangrenosum is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatological or hematological disease or malignancy. Diagnosis of pyoderma gangrenosum is based on a history of an underlying disease, typical clinical presentation and histopathology, and exclusion of other diseases that would lead to a similar appearance. Randomized, double-blinded prospective multicenter trials investigating the treatment of pyoderma gangrenosum are not available. The treatments with the best clinical evidence are systemic corticosteroids (in the initial phase usually 100 to 200 mg/day) and cyclosporine (mainly as a maintenance treatment). Combinations of corticosteroids with cytotoxic drugs such as azathioprine, cyclophosphamide or chlorambucil are used in patients with disease that is resistant to corticosteroids. The combination of corticosteroids with sulfa drugs, such as dapsone, or clofazimine, minocycline and thalidomide, has been used as a corticosteroid-sparing alternative. Limited experience has been documented with methotrexate, colchicine, nicotine, and mycophenolate mofetil, among other drugs. Alternative treatments include local application of granulocyte-macrophage colony-stimulating factor, intravenous immunoglobulins and plasmapheresis. Skin transplants (split-skin grafts or autologous keratinocyte grafts) and the application of bioengineered skin is useful in selected cases in conjunction with immunosuppression. Topical therapy with modern wound dressings is useful to minimize pain and the high risk of secondary infection. The application of topical antibacterials cannot be recommended because of their potential to sensitize and their questionable efficacy, but systemic antibacterial therapy is mandatory when infection is present. Despite recent advances in therapy, the prognosis of pyoderma gangrenosum remains unpredictable.


Mapping the differential effects of procaine on frequency and amplitude of reticularly elicited hippocampal rhythmical slow activity.
Hippocampal rhythmical slow activity (RSA, theta) was elicited in urethanized rats by high-frequency stimulation in the reticular formation. The effects of procaine infusion (0.5 microliters, 20% wt/vol) at various loci in the ascending system from pontine reticular formation to the medial septum/diagonal band area were investigated. It was found that procaine injected at points in the ascending system anterior to the supramammillary nucleus, in the region of the medial forebrain bundle or in the medial septum, reduced the amplitude of reticularly elicited RSA but had no effect on its frequency. Procaine injected at points in the ascending system from just anterior to the reticular formation stimulation site, up to, and including the supramammillary nucleus, reduced both the frequency and amplitude of reticularly elicited RSA. These results indicate that the frequency of reticularly elicited RSA is encoded in the supramammillary area, rather than in the medial septum/diagonal band as have previously been suggested.


Improving delivery of preventative care services using population management strategies.
Consistent and timely delivery of comprehensive preventative care services is a challenge, particularly in underserved patient populations. Previous quality improvement (QI) research has focused on the development of bundled measures of preventative services delivery, but these bundles have not been studied on a population level. We aimed to improve preventative care service delivery on a clinic population level through the use of a bundled measure that includes immunisations, lead screening and use of screening tools among underserved patients under 2 years old. A QI study was conducted at a community-based academic primary care clinic. A population-level bundled measure was adapted from an existing tool. We used plan-do-study-act cycles to optimise results and tracked bundle outcome rates using a p-type statistical process control chart. Interventions included (1) staff education on measure components, (2) introduction of exam room-based phlebotomy to address lead screening completion rates and (3) population management strategies, including development of a patient registry and use of reminders and visit tracking to increase attendance at well-child visits. The percent of bundle completion by 14 months of age increased from a baseline of 58%-77% following implementation of the QI initiatives. A mean shift was identified after the population manager began proactive targeted outreach for the 12-month visit. Targeted systems for outreach aimed at bringing patients into the clinic and patient-centred strategies for visit completion are effective at ensuring timely delivery of comprehensive preventative care to an underserved paediatric population.


3D US-CT/MRI registration for percutaneous focal liver tumor ablations.
US-guided percutaneous focal liver tumor ablations have been considered promising curative treatment techniques. To address cases with invisible or poorly visible tumors, registration of 3D US with CT or MRI is a critical step. By taking advantage of deep learning techniques to efficiently detect representative features in both modalities, we aim to develop a 3D US-CT/MRI registration approach for liver tumor ablations. Facilitated by our nnUNet-based 3D US vessel segmentation approach, we propose a coarse-to-fine 3D US-CT/MRI image registration pipeline based on the liver vessel surface and centerlines. Then, phantom, healthy volunteer and patient studies are performed to demonstrate the effectiveness of our proposed registration approach. Our nnUNet-based vessel segmentation model achieved a Dice score of 0.69. In healthy volunteer study, 11 out of 12 3D US-MRI image pairs were successfully registered with an overall centerline distance of 4.03±2.68 mm. Two patient cases achieved target registration errors (TRE) of 4.16 mm and 5.22 mm. We proposed a coarse-to-fine 3D US-CT/MRI registration pipeline based on nnUNet vessel segmentation models. Experiments based on healthy volunteers and patient trials demonstrated the effectiveness of our registration workflow. Our code and example data are publicly available in this r epository.


Efficacy and safety of intense pulsed light in treatment of melasma in Chinese patients.
Melasma is commonly seen in the Asian population. Traditional therapies are less effective and may cause adverse effects. The objective was to study the efficacy and safety of a new intense pulsed light (IPL) device in the treatment of melasma in Chinese patients. Eighty-nine women with melasma were enrolled in this open-labeled study. Subjects received a total of four IPL treatments at 3-week intervals. Changes in facial hyperpigmentation and telangiectasis were evaluated using an objective, skin colorimeter (Mexameter, Courage & Khazaka), the melasma area and severity index (MASI), and a global evaluation by the patients and blind investigators. Sixty-nine of 89 patients (77.5%) obtained 51% to 100% improvement, according to the overall evaluation by dermatologists. Self-assessment by the patients indicated that 63 of 89 patients (70.8) considered more than 50% or more improvement. Mean MASI scores decreased substantially from 15.2 to 4.5. Mexameter results demonstrated a significant decrease in the degree of pigmentation and erythema beneath the melasma lesions. Patients with the epidermal-type melasma responded better to treatment than the mixed type. Adverse actions were minimal. IPL treatment is a good option for patients with melasma. Adverse actions of IPL were minimal and acceptable.


Selective grazing of acyanogenic white clover: Variation in behaviour among populations of the slug Deroceras reticulatum.
Collections of the slug Deroceras reticulatum were made from grassland sites containing contrasting frequencies of the cyanogenic morph of white clover, Trifolium repens. In choice chamber experiments, slugs obtained from sites with a low frequency of cyanogenic clover showed a significantly greater degree of selective eating of acyanogenic morphs than slugs taken from a site containing a high frequency of cyanogenic clover. Differences in selectivity between populations were caused both by differences in the rate of initiation of feeding on cyanogenic morphs, and by differences in the extent of damage once feeding had been initiated. The implications of these results for the cyanogenic polymorphism of T. repens are discussed.


Vector control and entomological capacity for onchocerciasis elimination.
Mass drug administration (MDA) of ivermectin is currently the main strategy to achieve elimination of transmission (EoT) of onchocerciasis. Modelling suggests that EoT may not be reached in all endemic foci using annual MDA alone. Onchocerciasis and loiasis are coendemic in forest areas of Central Africa where ivermectin treatment can lead to severe adverse events in individuals with heavy loiasis load, rendering MDA inappropriate. Vector control has been proposed as a complementary intervention strategy. Here, we discuss (i) achievements and pitfalls of previous interventions; (ii) epidemiological impact, feasibility, and combination with MDA to accelerate and/or protect EoT; (iii) role of modelling; (iv) opportunities for innovative methods of vector monitoring and control; and (v) strengthening entomological capacity in endemic countries.


Identification of two mitochondrial-targeting cyclometalated iridium(III) complexes as potent anti-glioma stem cells agents.
Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4'-Bis(hydroxymethyl)-2,2'-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26-9.05 μM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes.


Aquaporin-1 plays a key role in erythropoietin-induced endothelial cell migration.
Water influx through aquaporin-1 (AQP-1) has been linked to the ability of different cell types to migrate, and therefore plays an important part in processes like metastasis and angiogenesis. Since the erythroid growth factor erythropoietin (Epo) is now recognized as an angiogenesis promoter, we investigated the participation of AQP-1 as a downstream effector of this cytokine in the migration of endothelial cells. Inhibition of AQP-1 with either mercury ions (Hg2+) or a specific siRNA led to an impaired migration of EA.hy926 endothelial cells exposed to Epo (wound-healing assays). Epo also induced the expression of AQP-1 at mRNA and protein levels, an effect which was dependent on the influx of extracellular calcium through L-type calcium channels as well as TRPC3 channels. The relationship between Epo and AQP-1 was further confirmed at shorter exposure times, as the cytokine was unable to trigger calcium influxes in cells where AQP-1 had previously been knocked down. Moreover, Epo promoted changes in the subcellular localization of AQP-1 as well as rearrangements in the actin cytoskeleton, which are consistent with a migratory phenotype. Worthy of note, carbamylated erythropoietin (cEpo), the non-erythropoietic and non-promigratory derivative of Epo, was incapable of AQP-1 modulation. The therapeutical implications of aquaporin targeting in angiogenesis-related diseases highlight the importance of the present results in the context of the relationship between AQP-1 and Epo.


The Clinical Significance of CA19-9 and Tumor Size Ratios for Predicting Prognosis After Conversion Surgery in Patients With Stage IV Gastric Cancer.
The clinical benefit of conversion surgery (CS) after chemotherapy remains unclear for stage IV gastric cancer (GC) patients. This study aimed to investigate the prognostic factors used to determine whether CS is a promising therapeutic strategy. We retrospectively analyzed data from 156 patients diagnosed with unresectable stage IV GC who underwent chemotherapy as the initial treatment, including 40 patients who had R0 resection in CS. The median survival time of the CS patients was significant longer than that of patients who underwent chemotherapy alone. A multivariate analysis identified only pN3 as an independent prognostic factor in CS patients. Among the differentiated tumor type patients, carbohydrate antigen 19-9 (CA19-9) levels were significantly higher in pN3 patients than in pN0-2 patients before chemotherapy. Among undifferentiated tumor type patients, pN3 patients had a significantly lower tumor size ratio (before chemotherapy/before surgery) than pN0-2 patients. Although it is clinically difficult to diagnose lymph node metastasis using preoperative examinations, CA19-9 levels and tumor size ratios may be preoperative indicators for predicting pN3, which is associated with a poor prognosis in CS.


Degradome sequencing reveals an integrative miRNA-mediated gene interaction network regulating rice seed vigor.
It is well known that seed vigor is essential for agricultural production and rice (Oryza sativa L.) is one of the most important crops in the world. Though we previously reported that miR164c regulates rice seed vigor, but whether and how other miRNAs cooperate with miR164c to regulate seed vigor is still unknown. Based on degradome data of six RNA samples isolated from seeds of the wild-type (WT) indica rice cultivar 'Kasalath' as well as two modified lines in 'Kasalath' background (miR164c-silenced line [MIM164c] and miR164c overexpression line [OE164c]), which were subjected to either no aging treatment or an 8-day artificial aging treatment, 1247 different target transcripts potentially cleaved by 421 miRNAs were identified. The miRNA target genes were functionally annotated via GO and KEGG enrichment analyses. By STRING database assay, a miRNA-mediated gene interaction network regulating seed vigor in rice was revealed, which comprised at least four interconnected pathways: the miR5075-mediated oxidoreductase related pathway, the plant hormone related pathway, the miR164e related pathway, and the previously reported RPS27AA related pathway. Knockout and overexpression of the target gene Os02g0817500 of miR5075 decreased and enhanced seed vigor, respectively. By Y2H assay, the proteins encoded by five seed vigor-related genes, Os08g0295100, Os07g0633100, REFA1, OsPER1 and OsGAPC3, were identified to interact with Os02g0817500. miRNAs cooperate to regulate seed vigor in rice via an integrative gene interaction network comprising miRNA target genes and other functional genes. The result provided a basis for fully understanding the molecular mechanisms of seed vigor regulation.