Performance evaluations and applications of a δ13C-DIC analyzer in seawater and estuarine waters.
Dissolved inorganic carbon (DIC) and its stable isotope (δ13C-DIC) are important parameters for studying carbon cycling in aquatic environments. Traditional methods based on isotope-ratio mass spectrometers are labor-intensive and not easily deployable at field sites. Here we report the performance of a method that simultaneously measures DIC concentration and its stable isotope by using a CO2 extraction device and a Cavity Ring-Down Spectroscopy (CRDS) detector. A multi-port valve is used to increase sample throughput and improve precision. The instrument achieves average precisions of better than ±1.95 μmol kg-1 and ±0.06‰, respectively, for DIC and δ13C-DIC in seawater based on three injections for each sample. We also provide recommendations on how to precisely determine δ13C-DIC samples with a wide range of DIC content in different types of waters by examining injection volume and concentration effects. This technique was applied to study carbon cycling in the Delaware Estuary. It demonstrates that a simultaneous and precise determination of both DIC and δ13C-DIC is a powerful and effective approach for constraining the processes controlling aquatic carbon cycling and CO2 fluxes. Both laboratory tests and field applications confirmed that this system can be used with high precision to study carbon cycling in various aquatic environments.


Editorial for "Qualitative and Quantitative Reporting of a Unique Biparametric MRI: Towards Biparametric MRI-Based Nomograms for Prediction of Prostate Biopsy Outcome in Men With a Clinical Suspicion of Prostate Cancer (IMPROD and MULTI-IMPROD Trials)".
5 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:1568-1569.


When brucellosis met the Assessment of SpondyloArthritis international Society classification criteria for spondyloarthritis: a comparative study.
To distinguish brucellosis patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) from SpA patients. Brucellosis patients diagnosed from September 2012 to December 2017 who met the ASAS classification criteria for SpA were analyzed with clinical characteristics and laboratory and imaging examinations. Axial or peripheral SpA patients were respectively included into the comparative analysis with a 4:1 ratio. Twenty-two brucellosis (10 axial and 12 peripheral) patients (male, 16 cases; 72.72%; mean (S.D.) age, 40.23 (16.49) years) and 88 SpA patients were included. All brucellosis patients had been misdiagnosed or considered as SpA before admission to our center. The brucellosis patients had shorter disease duration (axial, P = 0.001; peripheral, P = 0.108). More than half (59.09%) of the patients had contact history with livestock. The low back pain (LBP) of brucellosis patients was generally less improved with exercise (axial, P = 0.001; peripheral, P = 0.008). More brucellosis patients had myalgia (axial, P < 0.001; peripheral, P = 0.071) or fever (axial, P < 0.001; peripheral, P = 0.107). None of them had positive HLA-B27. Blood culture tests were performed in all brucellosis patients and only 4 (18.18%) were positive. Twenty (90.91%) brucellosis patients were gold-immunochromatographic assay (GICA) positive. Bone marrow edema and bone erosion in sacroiliac joints were respectively detected in 100% (10/10) and 90% (9/10) axial brucellosis patients by MRI. Adjacent muscle involvement was found in 80% (8/10) of the patients. Indicators including disease duration, contact history of livestock, features of LBP, myalgia, fever, and HLA-B27 can help the differential diagnosis of brucellosis and SpA. GICA test and sacroiliac joints MRI can furtherly confirm the diagnosis of brucellosis.


Public knowledge and attitudes regarding public health inspections of restaurants.
Foodborne diseases cause 76 million illnesses in the U.S. each year, and almost half of all money spent on food is spent in restaurants. Restaurant inspections are a critical public health intervention for the prevention of foodborne disease. A telephone survey of randomly selected Tennessee residents aged > or =18 was performed. Data were collected on respondents' demographics, knowledge, attitudes, and expectations regarding restaurant inspections. Of 2000 respondents, 97% were aware that restaurants are inspected regularly by the health department. More than half of the respondents believed that inspections should be performed at least 12 times per year; only one third were aware that inspections currently occur only twice per year in Tennessee. More than one third of the respondents considered an inspection score of > or =90 acceptable for a restaurant at which they would eat; the mean score in Tennessee is 82. When presented with a variety of scenarios, an overwhelming number of respondents felt that public health responses to safety violations should be far more draconian than they actually are. Survey answers did not differ consistently based on respondents' race, gender, or history of having worked in a restaurant. This study identified a number of public misconceptions and unrealistically high expectations of the public health restaurant-inspection system. It is important to improve consumers' understanding of inspection scores and the limitations of regulatory inspections, as well as the role of such inspections in disease prevention.


Giant aneurysm of the left atrial appendage: A case report of a rare cause of dyspnea in a 55-year old woman.
Congenital aneurysm of the left atrial appendage (LAAA) is a very rare heart with potentially serious and life-threatening complications. Diagnosis is difficult because of the asymptomatic forms, until complications arise. Early surgery is the treatment of choice, but the recommendation today remains unclear. We present a case of congenital giant left atrial appendage aneurysm (LAAA), in a 55-year-old, woman, without any medical or surgical history, who presented with dyspnea, in whom transthoracic echocardiograhpy demonstrated the presence of a giant left atrial aneurysm with thickening of the small mitral valve, a chest scan confirmed the diagnosis of LAAA and a myocardial magnetic resonance imaging revealed the presence of thickened mitral valve with bi-valvular balloonization and annular disjunction, thickening of the basal segments of the inferior and lateral wall, left atrial aneurysm with a dilated right coronary artery. Coronary angiography showed a tortuous coronary artery with a loop in the second segment without any significant stenosis. The patient is currently awaiting surgery. Left atrial appendage aneurysm is a serious illness will likely require years of medical care and follow up in the absence of surgical treatment. The choice and timing of surgical, conservative or catheter treatment always remains a challenge. Our case report shows that medical treatment is a safe approach that will delay or avoid surgery.


Reduced platelet survival following chemotherapy with vinblastine, bleomycin and cis-platinum for testicular teratoma.
Patients receiving combination chemotherapy with vinblastine, bleomycin and cis-platinum for testicular teratoma frequently demonstrated early-onset transient thrombocytopenia. We have shown that this effect is due to reduced platelet survival. The relevant literature is reviewed and it is concluded that this phenomenon may be attributable to drug synergism.


Cerebral, renal and mesenteric regional oxygen saturation of term infants during transition.
To measure cerebral regional oxygen saturation (CrSO2), renal regional oxygenation saturation (RrSO2) and mesenteric tissue regional oxygen saturation (MrSO2) during immediate transition and continuously for the first 9 hours of age. Fractional tissue oxygen extraction of the brain (CtFOE), kidneys (RtFOE), splanchnic tissue (MtFOE) were also assessed. Prospective, observational study of 61 term infants, delivered by elective caesarean section. Using near-infrared spectroscopy, changes in CrSO2, RrSO2, MrSO2 and changes in CtFOE, RtFOE and MtFOE were measured all through the first 9 hours of life. All the episodes of feeding during this period were recorded. Mean CrSO2 increased quickly to 7 minutes, with no further changes. On the other hand, mean RrSO2 and mean MrSO2 increased for 10 minutes and thereafter they remained on their newly reached level. RrSO2 and MrSO2 were significantly lower at 3-4-5-6-7 minutes of life compared to the CrSO2 (p<0.05). RtFOE and MtFOE were significantly higher at 3-4-5-6-7 minutes of life compared to the CtFOE (p<0.05). During feeding, CrSO2, RrSO2 and MrSO2 did not significantly change. During early adaptive period, oxygen delivery is preserved to 'vital' organs, like brain, at the expense of kidneys and splanchnic tissue. Term infants can provide for the increasing metabolic activity of the intestinal tract during feeding periods without compromising oxygenation.


Structure and internal consistency of a shoulder model.
A three-dimensional biomechanical model of the shoulder is developed for force predictions in 46 shoulder structures. The model is directed towards the analysis of static working situations where the load is low or moderate. Arbitrary static arm postures in the natural shoulder range may be considered, as well as different kinds of external loads including different force and moment directions. The model can predict internal forces for the shoulder muscles, for the glenohumeral, the acromioclavicular and the sternoclavicular joint as well as for the coracohumeral ligament. A solution to the statistically indeterminate force system is obtained by minimising an objective function. The default function chosen for this is the sum of the squared muscle stresses, but other objective functions may be used as well. The structure of the model is described and its ingredients discussed. The internal consistency of the model, its structural stability and the compatibility of the elements that go into it, is investigated.


Bioaccessibility of total bound fumonisin from corn flakes.
Fumonisin B1 (FB1) is often found as a natural contaminant of corn and corn-based food. Several publications have demonstrated the presence of fumonisin bound to proteins and to other compounds of the matrix. In spite of the low oral bioavailability of FB1 in rats, pigs, chickens, cows, and monkeys, FB1 can cause agriculturally significant disease and possibly human cancer. The aim of this work was to determine the bioaccessibility of total bound FB1 (TB FB1) (percentage of TB FB1, released from corn flakes to the chyme) after in vitro digestion. Two samples of corn flakes washed with solvents were incubated with gastrointestinal tract solutions simulating saliva plus stomach and duodenal juices. After hydrolysis of the chyme with KOH, TB FB1 was determined as hydrolyzed FB1 (HFB1). The bioaccessibility of TB FB1 in chyme from corn flakes was 37-64%, indicating that these derivatives should be considered in evaluation of exposure to fumonisin.


Biosynthesis of rumbrins and inspiration for discovery of HIV inhibitors.
Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets. The polyketide rumbrin (1) is a lipid peroxide production and calcium accumulation inhibitor, which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products. Here, we identify the biosynthetic gene cluster (BGC) rum of 1 and its isomer 12E-rumbrin (2) from Auxarthron umbrinum DSM3193, and elucidate their biosynthetic pathway based on heterologous expression, chemical complementation, and isotopic labeling. We show that rumbrins are assembled by a highly reducing polyketide synthase (HRPKS) that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit, and followed by methylation and chlorination. Sequent precursor-directed biosynthesis was able to yield a group of rumbrin analogues. Remarkably, inspired by the presence of a human immunodeficiency virus (HIV)-Nef-associated gene in the rum cluster, we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level. This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.


Sesamol loaded solid lipid nanoparticles: a promising intervention for control of carbon tetrachloride induced hepatotoxicity.
Sesamol, a component of sesame seed oil, exhibited significant antioxidant activity in a battery of in vitro and ex vivo tests including lipid peroxidation induced in rat liver homogenates. Latter established its potential for hepatoprotection. However, limited oral bioavailability, fast elimination (as conjugates) and tendency towards gastric irritation/toxicity (especially forestomach of rodents) may limit its usefulness. Presently, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its biopharmaceutical performance and compared the efficacy with that of free sesamol and silymarin, a well established hepatoprotectant, against carbon tetrachloride induced hepatic injury in rats, post induction. A self recovery group in which no treatment was given was used to observe the self-healing capacity of liver. S-SLNs prepared by microemulsification method were administered to rats post-treatment with CCl4 (1 ml/kg body weight (BW) twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). Liver damage and recovery on treatment was assessed in terms of histopathology, serum injury markers (alanine aminotransferase, aspartate aminotransferase), oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker (tumor necrosis factor alpha). S-SLNs (120.30 nm) at a dose of 8 mg/kg BW showed significantly better hepatoprotection than corresponding dose of free sesamol (FS; p < 0.001). Effects achieved with S-SLNs were comparable with silymarin (SILY), administered at a dose of 25 mg/kg BW. Self recovery group confirmed absence of regenerative capacity of hepatic tissue, post injury. Use of lipidic nanocarrier system for sesamol improved its efficiency to control hepatic injury. Enhanced effect is probably due to: a) improved oral bioavailability, b) controlled and prolonged effect of entrapped sesamol and iii) reduction in irritation and toxicity, if any, upon oral administration. S-SLNs may be considered as a therapeutic option for hepatic ailments as effectiveness post induction of liver injury, is demonstrated presently.


Intermembrane docking reactions are regulated by membrane curvature.
The polymorphism of eukaryotic cellular membranes is a tightly regulated and well-conserved phenotype. Recent data have revealed important regulatory roles of membrane curvature on the spatio-temporal localization of proteins and in membrane fusion. Here we quantified the influence of membrane curvature on the efficiency of intermembrane docking reactions. Using fluorescence microscopy, we monitored the docking of single vesicle-vesicle pairs of different diameter (30-200 nm) and therefore curvature, as mediated by neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and streptavidin-biotin. Surprisingly, the intermembrane docking efficiency exhibited an ∼30-60 fold enhancement as a function of curvature. In comparison, synaptotagmin and calcium accelerate SNARE-mediated fusion in vitro by a factor of 2-10. To explain this finding, we formulated a biophysical model. On the basis of our findings, we propose that membrane curvature can regulate intermembrane tethering reactions and consequently any downstream process, including the fusion of vesicles and possibly viruses with their target membranes.


The Economics of Patient Surgical Safety.
Adverse surgical events are a major cause of morbidity, mortality, and disability worldwide. Serious reportable events, such as wrong site surgery, retained foreign bodies, and surgical fires, are preventable adverse events that have significant consequences. These "never events" are costly to the patient, health care systems, and society and have led to many efforts to reduce their occurrence. However, these costly events still occur, and more research is needed to obtain a better understanding of their causes and how to prevent them.


Self-reported sleep and mood disturbance in chronic pain patients.
To evaluate the prevalence of self-reported sleep disturbance and its relationship to mood disturbance in chronic pain patients. Survey of patients referred to a multidisciplinary outpatient pain clinic. The sample consisted of 105 consecutive patients (59 men and 46 women), with an average age of 41.5 (SD +/-13.4) years. Self-report measures of sleep disturbance and visual analog scales of mood disturbance (anxiety and depression) and pain experience (intensity and unpleasantness). Patients were grouped according to whether they considered themselves "poor" (n = 68) or "good" (n = 37) sleepers. Poor sleepers reported more difficulties initiating and maintaining sleep and greater pain intensity and pain unpleasantness than did good sleepers. The two groups did not differ on measures of depressive or anxious mood. The results suggest that sleep disturbance is a prevalent complaint in chronic pain patients, but it is not always associated with an underlying mood disturbance.


Ventricular tachycardia or supraventricular tachycardia?
It shows a pseudo -A-V-V-A response after stopping overdrive atrial pacing of a broad complex tachycardia.


Antenatal prediction of graduated risk of hyaline membrane disease by amniotic fluid foam test for surfactant.
We measured amniotic fluid surfactant by the semiquantitative foam stability test within 24 hours before delivery of 410 infants, 64 of whom developed HMD diagnosed by standard criteria. When surfactant titers were ranked in eight categories, they predicted graded risks of HMD. On this basis we defined five "risk groups" with significantly different incidences of HMD (I = 0.5%; II = 10%; III = 25%; IV = 41%; V = 79%). Infants in Groups I and II were heavier and more mature than those in Groups III to V. However, among infants of equivalent GA or birth weight, the incidence of HMD still correlated significantly with the foam test results. Within each risk group the incidence of HMD was equal among infants delivered by vagina and by cesarean section, slightly greater among males than females, and inversely proportional to GA. In Group V the incidence of HMD was 100% among infants at less than 33 weeks' GA. We used this relationship to devise a system that improved prediction of HMD by combining the foam test results with GA.


Evidence of uterine inadequacy to egg implantation in stimulated in vitro fertilization cycles.
From 104 IVF cycles 166 embryos were immediately transferred (63 embryo transfers, ET), whereas 151 embryos were frozen until later transfer (77 embryo transfers). There were 8 (12.7%) or 19 (24.7%) pregnancies after fresh or frozen-thawed ET, respectively. Sixteen pregnancies (29.1%) originated from 55 ETs of frozen-thawed embryos coming from IVF cycles in which pregnancy was not induced by fresh ET. The pregnancy rate after fresh ET (10.5%) was lower than that obtained when the same patients received frozen-thawed embryos (27.1%, P less than 0.02). It is concluded that a normal pregnancy rate may result if the embryos originating from an unsuccessful IVF-ET cycle are transferred in a favorable uterus.


Structural effects of spike protein D614G mutation in SARS-CoV-2.
A single mutation from aspartate to glycine at position 614 has dominated all circulating variants of the severe acute respiratory syndrome coronavirus 2. D614G mutation induces structural changes in the spike (S) protein that strengthen the virus infectivity. Here, we use molecular dynamics simulations to dissect the effects of mutation and 630-loop rigidification on S-protein structure. The introduction of the mutation orders the 630-loop structure and thereby induces global structural changes toward the cryoelectron microscopy structure of the D614G S-protein. The ordered 630-loop weakens local interactions between the 614th residue and others in contrast to disordered structures in the wild-type protein. The mutation allosterically alters global interactions between receptor-binding domains, forming an asymmetric and mobile down conformation and facilitating transitions toward up conformation. The loss of salt bridge between D614 and K854 upon the mutation generally stabilizes S-protein protomer, including the fusion peptide proximal region that mediates membrane fusion. Understanding the molecular basis of D614G mutation is crucial as it dominates in all variants of concern, including Delta and Omicron.


A novel method to predict regulatory regions based on histone mark landscapes in macrophages.
Macrophages as phagocytes and professional antigen presenting cells play critical roles in both innate and adaptive immunity. Main transcription factors acting during their differentiation and function are known, but the behavior and co-operation of these factors still remained unexplored. We introduce a new approach to map nucleosome-free regions using exclusively active enhancer and core promoter marking histone modification ChIP-seq data. We could detect approximately 56,000 potential active enhancers/promoters showing different lengths and histone modification shapes. Beside the highly enriched PU.1 and C/EBP sites, we could also detect binding sites for RUNX and AP-1, as well as for the MiT (MITF-TFE) family and MEF2 proteins. The PU.1 and C/EBP transcription factors are known for transforming cells into macrophages. The other transcription factors found in this study can play a role in macrophages as well, since it is known that the MiT family proteins are responsible for phagocytic activity and the MEF2 proteins specify monocytic differentiation over the granulocyte direction. Our results imply that this method can provide novel information about transcription factor organization at enhancers and core promoters as well as about the histone modifications surrounding regulatory regions in any immune or other cell types.


Fasciculation frequency at the biceps brachii and brachialis muscles is associated with amyotrophic lateral sclerosis disease burden and activity.
Fasciculations are most commonly seen in the biceps brachii muscle in amyotrophic lateral sclerosis (ALS). In this study we have explored the association between fasciculation frequency in a single location-biceps brachii and brachialis muscles (BB), and disease burden and activity. Sonographic muscle studies were performed in 90 ALS patients, 47 of whom were seen in subsequent follow-up. The association between fasciculations frequency at the BB and ALS Functional Rating Scale-Revised (ALSFRS-R) and manual muscle testing (MMT) scores was determined. High fasciculation frequency at the BB, where detection rate was the highest, was associated with shorter disease duration, greater muscle thickness, higher MMT scores, and faster rate of decline in ALSFRS-R initially, and MMT subsequently. High fasciculation frequency at the BB as determined by sonography, is associated with less impairment at time of examination, and a more active disease with a more rapid progression.


Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight.
Cosmic radiation is known to induce DNA and lipid damage associated with increased oxidative stress and remains a major concern in space travel. Hydrogen, recently discovered as a novel therapeutic medical gas in a variety of biomedical fields, has potent antioxidant and anti-inflammatory activities. It is expected that space mission activities will increase in coming years both in numbers and duration. It is therefore important to estimate and prevent the risks encountered by astronauts due to oxidative stress prior to developing clinical symptoms of disease. We hypothesize that hydrogen administration to the astronauts by either inhalation or drinking hydrogen-rich water may potentially yield a novel and feasible preventative/therapeutic strategy to prevent radiation-induced adverse events.


Asymmetric synthesis of corsifuran A by an enantioselective oxazaborolidine reduction.
Corsifuran A has been prepared in an enantiomerically pure form for the first time by an asymmetric reduction procedure, allowing confirmation of the absolute stereochemistry of the natural product as (R).


Radiation and chemotherapy variable response induced by tumor cell hypoxia: impact of radiation dose, anticancer drug, and type of cancer.
Hypoxia is a condition in which proliferating tumor cells are deprived of oxygen due to limited blood supply from abnormal tumor microvasculature. This study aimed to investigate the molecular changes that occur in tumor cell hypoxia with special emphasis placed on the efficacy of chemotherapeutic and radiation-related effects. Four commercially available chemotherapeutic agents: cisplatin, cyclophosphamide, doxorubicin, and 5-fluorouracil, were tested for their cytotoxic activity on the cancer cell lines PC3 (prostate), HepG2 (liver), and MCF-7 (breast). Tumor cell lines under hypoxia were treated with both IC50 concentrations of the different chemotherapeutic agents and irradiated with 5 and 10 Gy using a 137Cs gamma source. Hypoxia-inducible factor-1α (HIF-1α) protein levels were examined using an ELISA assay. Hypoxic cells showed a significant change in cell viability to all chemotherapeutic agents in comparison to normoxic controls. HepG2 cells were more resistant to the cytotoxic drug doxorubicin compared to other cancer cell lines. The flow cytometric analysis showed that hypoxic cells have lower levels of total apoptotic cell populations (early and late apoptosis) compared to normoxic cells suggesting decreased hypoxia-induced apoptosis in cancer cells. The highest reduction in HIF-1α level was observed in the MCF-7 cell line (95.5%) in response to the doxorubicin treatment combined with 10 Gy irradiation of cells. Chemoradiotherapy could result in minimal as well as a high reduction of HIF-1α based on cell type, type of chemotherapy, and amount of ionizing radiation. This study highlights future research work to optimize a combined chemoradiotherapeutic regime in individual cancer cell hypoxia.


[The content of the carcinoembryonic antigen in the blood serum of patients with bladder tumors at various stages of combined treatment in relation to the disease stage].
Serum level of a tumor marker, carcinoembryonic antigen (CEA), was examined in patients at different stages of vesical cancer before and during combined treatment, including preoperative large-fraction radiotherapy and surgery. Sixty patients with histologically documented vesical cancer, stages T1N0M0, T2N0M0, T3N0-1M0 and T4N0M0 were investigated. All patients underwent large-fraction radiotherapy prior to surgery. Transvesical resection of the bladder wall with the tumor or cystectomy was performed within 24-72 hrs after radiation exposure. Serum CEA was measured repeatedly (on admission, after preoperative radiotherapy, postoperatively, at discharge) by enzyme immunoassays. It is demonstrated that CEA variation in the course of combined treatment depends on the stage of cancer. CEA level decreased after preoperative large-fraction radiotherapy in patients with T1, T3 and T4 stages of cancer, and increased in patients at the T2 stage. Following combined treatment, serum CEA was reduced two-fourfold as compared to pretreatment values in patients with first, third and fourth stages of vesical cancer, an evidence of the adequacy and radical quality of treatment and a favorable predictive sign.


Associations Between Stroke Localization and Delirium: A Systematic Review and Meta-Analysis.
Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium. We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status. We included papers in any language, through a combined search from January 2010 to June 2021. Case studies with less than 20 patients, case-control studies, and randomized controlled trials were excluded. MEDLINE, EMBASE, PsycINFO, CINAHL, and Alois databases were searched. Pooled relative risks were calculated using bivariate random effects models or network meta-analysis. Methodological quality was assessed across 8 factors. 31 patient samples representing 8329 patients were included. Delirium was more common in patients with supratentorial lesions than infratentorial (RR [Relative Risk] 2.01, CI [Confidence Interval] 1.49-2.72); anterior circulation lesions than posterior (RR 1.41, CI 1.13-1.78); and cortical lesions than subcortical (RR 1.54, CI 1.25-1.89). Stroke side was not associated with delirium (right vs. left: RR 0.99, CI 0.77-1.28). Delirium was more common in patients with hemorrhagic strokes than ischemic (RR 1.74, CI 1.42-2.11) and patients with preexisting qualitative atrophy (RR 1.66, CI 1.21-2.27). Several brain localizations and types of strokes were associated with delirium. Conclusions were in part limited by the heterogeneity of studies and broad or qualitative lesion descriptions. These results may assist in anticipating the risk of delirium in acute stroke and highlight brain networks and pathologies that may be involved in the pathophysiology of delirium.


Safety of Biologics for Atopic Diseases During Pregnancy.
The high prevalence of atopic diseases in women of childbearing age reveals the need to determine the safety of biologics during pregnancy. This review summarizes the effects of 7 Food and Drug Administration-approved biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and tralokinumab) on maternal and fetal outcomes. For this purpose, we reviewed English-language publications to investigate whether the use of biologics for atopic diseases during pregnancy increased the risk of preterm delivery, stillbirth, low birth weight, or congenital malformations. Most publications found were case reports, case series, or observational studies reporting outcomes in a total of 313 pregnancies. No randomized controlled studies were identified. We found that biologics do not seem to influence maternal or fetal outcomes. Indeed, worsening of the underlying atopic disease during pregnancy appears to be more detrimental to the viability of the pregnancy. Given the small sample size and scarcity of studies, future research should include prospective studies with comparable control groups without exposure to biologics and multicenter registries for long-term follow-up.


Fire as a control agent of demographic structure and plant performance of a rare Mediterranean endemic geophyte.
We examine the effects of fire and/or surrounding vegetation cover on demographic stage densities and plant performance for a rare endemic geophyte, Acis nicaeensis (Alliaceae), in Mediterranean xerophytic grasslands of the 'Alpes-Maritimes' French 'département', through sampling plots in unburned and burned treatments. Fire increases density of flowering individuals and seedling emergence, as well as clump densities and number of individuals per clump, per limiting vegetation height and cover, and increasing bare soil cover. In contrast, fire has no effect on reproductive success. Nevertheless, two growing seasons after fire, all parameters of demographic stages and plant performance do not significantly differ between the two treatments. Small-scale fire is beneficial for the regeneration of this threatened geophyte at a short-time scale. In this context, a conservation planning with small and controlled fires could maintain the regeneration window for populations of rare Mediterranean geophytes.


Effect of exercise training on glucose tolerance, in vivo insulin sensitivity, lipid and lipoprotein concentrations in middle-aged men with mild hypertriglyceridemia.
The effects of 9 weeks of aerobic exercise training with maintenance of stable body weight upon insulin sensitivity and upon glucose, lipid, and lipoprotein concentrations were studied in 10 middle-aged men with mild hypertriglyceridemia. Following training, mean maximum oxygen consumption improved from 33.5 +/- 1.9 to 39.3 +/- 1.9 mL/kg/min (means +/- SEM), (P less than 0.01). Glucose concentrations, both fasting and during oral glucose tolerance testing, remained stable but both fasting insulin concentrations and insulin responses to oral glucose decreased (P less than 0.1 and less than 0.01, respectively). In vivo insulin sensitivity improved 25 +/- 6.1% (P less than 0.01) following training. Exercise training resulted in decreases in fasting serum triglyceride concentrations from 203 +/- 12.6 to 126 +/- 9.0 mg/dL (P less than 0.01), primarily as a result of the reduction in VLDL-triglycerides (P less than 0.01). The magnitude in percentage decrease of VLDL-triglycerides was found to be significantly correlated (r = 0.71, P less than 0.05) with the magnitude in percent increase in max VO2. Serum cholesterol levels declined from 211 +/- 8.9 to 193 +/- 11.9 mg/dL (P less than 0.01), and the ratio of HDL-cholesterol to total cholesterol was improved. This study demonstrates that exercise training at a level of intensity feasible for many middle-aged men has beneficial effects on several factors that have been associated with an increased risk of cardiovascular disease.


Access to inclusive and culturally sensitive mental healthcare in Black, Indigenous, and People of Color pharmacy students and residents.
Disparities in accessing culturally sensitive mental healthcare exist and may be exacerbated in pharmacy trainees. The purpose of this study was to identify barriers to culturally sensitive mental healthcare and how to improve access for racially and ethnically minoritized pharmacy students and residents. This institutional review board-exempt study included in-person and virtual focus groups. Eligible participants were first-, second-, third-, and fourth-year doctor of pharmacy (PharmD) students and pharmacy residents completing a postgraduate year 1 or 2 program who identified as Black, Indigenous, and People of Color (BIPOC). Barriers to care, identity's influence on seeking care, and areas in which the training programs are doing well or areas for improvement were assessed. Responses were transcribed and analyzed using an open coding system by 2 reviewers, followed by discussion as a team to reach consensus. This study enrolled 8 first-year, 5 second-year, 7 third-year, and 2 fourth-year PharmD students and 4 residents (N = 26). Barriers to care included time, access to resources, and internal and external stigma. Identity barriers included cultural and family stigma and lack of representation in therapists with regard to race, ethnicity, and gender. Areas going well included supportive faculty and paid time off, while areas for improvement included wellness days, reduced workload, and increased diversity within the workforce. This study is the first to identify barriers to culturally sensitive mental healthcare in pharmacy trainees who identify as BIPOC while providing insight on how to increase culturally sensitive mental healthcare resources.


Trends of inpatient palliative care use among hospitalized patients with Parkinson's disease.
Palliative care in Parkinson's Disease (PD) is an effective intervention to improve quality of life, although historically, access and availability have been very restricted. We performed a retrospective cohort study using the National Inpatient Sample (NIS) data from 2007 to 2014. Diagnostic codes were used to identify patients with PD and palliative care referral. Trends were calculated and logistic analysis performed to identify predictors of palliative care use. We identified 397,963 hospitalizations from 2007 to 2014 for patients with PD. Of these, 10,639 (2.67%) were referred to palliative care. The rate of consultation increased from 0.85% in 2007 to 4.49% in 2014. For 1 unit in year increase, there was 1.23 time the odds of receiving palliative consultation (OR 1.23, CI 1.21-1.25, p < 0.0001). Hispanics (OR 0.90, CI 0.81-1.01, p = 0.0550), Black (OR 0.90, CI 0.81-1.01, p = 0.0747) and White patients had similar rates of referral after adjustment. Women were less likely to be referred to palliative care (OR 0.90, CI 0.87-0.94, p < 0.0001). Other factors strongly associated with a higher rate of referrals included private insurance when compared to Medicare (OR 2.14, CI 1.89-2.41, p < 0.0001) and higher income (OR 1.41, CI 1.30-1.53, p < 0.0001). There has been a significant increase in palliative care referrals among hospitalized patients with PD in the US, although the overall rate remains low. After controlling for confounders, racial and ethnic disparities were not found. Women, patients with Medicare/Medicaid, and those with lower income were less likely to be referred to palliative care.


Maternal diabetes causes abnormal dynamic changes of endoplasmic reticulum during mouse oocyte maturation and early embryo development.
The adverse effects of maternal diabetes on oocyte maturation and embryo development have been reported. In this study, we used time-lapse live cell imaging confocal microscopy to investigate the dynamic changes of ER and the effects of diabetes on the ER's structural dynamics during oocyte maturation, fertilization and early embryo development. We report that the ER first became remodeled into a dense ring around the developing MI spindle, and then surrounded the spindle during migration to the cortex. ER reorganization during mouse early embryo development was characterized by striking localization around the pronuclei in the equatorial section, in addition to larger areas of fluorescence deeper within the cytoplasm. In contrast, in diabetic mice, the ER displayed a significantly higher percentage of homogeneous distribution patterns throughout the entire ooplasm during oocyte maturation and early embryo development. In addition, a higher frequency of large ER aggregations was detected in GV oocytes and two cell embryos from diabetic mice. These results suggest that the diabetic condition adversely affects the ER distribution pattern during mouse oocyte maturation and early embryo development.


Postoperative locoregional recurrence pattern and treatment management of stage pT4 sigmoid colon cancer: a retrospective cohort study.
This study aimed to explore the pattern of locoregional recurrence after surgery in patients with non-metastatic stage pT4 sigmoid colon cancer and the role of adjuvant radiotherapy on survival. We retrospectively analyzed data from 208 patients who underwent surgery in our hospital. The patients were randomly divided into training and validation groups at a 1:1 ratio. Patients at high risk for locoregional recurrence were screened using Cox regression analysis. Based on the data of 2,886 patients in the Surveillance, Epidemiology, and End Results (SEER) database, the effect of adjuvant radiotherapy on overall survival (OS) and cancer-specific survival (CSS) was evaluated by Kaplan-Meier curves. Of the 208 patients, 57 (27.4%) presented with locoregional recurrences (14 anastomotic and 43 abdominal or pelvic lymph node recurrences). Multivariate analysis showed that serum CEA, differentiation, lymph node dissection number, and N stage were independent predictors of locoregional recurrence-free survival (all p < 0.05). A risk-stratification model was constructed, and a total score of ≥ 6.5 points was considered the high-risk group for locoregional recurrence. Both the training and validation sets presented that the model had a good predictive ability (area under the curve = 0.828 and 0.724, respectively). Analysis of SEER data revealed that adjuvant radiotherapy significantly prolonged OS and CSS in the high-risk population (all p < 0.05, vs. no radiotherapy). Patients with a total risk score of 6.5 or more had a high likelihood of locoregional recurrence, and perhaps adjuvant radiotherapy could improve their survival.


Polysaccharide Sequence Influences the Specificity and Catalytic Activity of Glucuronyl C5-Epimerase.
Heparin is a widely used biotherapeutic produced from animal tissues. However, it might be possible to produce a bioengineered version using a multienzyme process, relying on the isolation of the E. coli K5 capsule heparosan and its chemical conversion to N-sulfoheparosan, NSH. Glucuronyl C5-epimerase, the first enzyme that acts on NSH, catalyzes the reversible conversion of glucuronic acid (GlcA) to iduronic acid (IdoA). Using full-length NSH, containing different amounts of N-acetylglucosamine (GlcNAc) residues, we demonstrate that C5-epimerase specificity relates to polysaccharide sequence, particularly the location of GlcNAc residues within the chain. We leveraged the deuterium exchange and the novel β-glucuronidase heparanase BP, which cleaves at the GlcA residue. Liquid chromatography-mass spectrometry and gel permeation chromatography of partial/complete heparanase BP digestion products from various NSH substrates treated with C5-epimerase provide information on C5-epimerase activity and action pattern. This study provides insight into optimizing the large-scale production of bioengineered heparin.


The influence of the response-stimulus interval on implicit and explicit learning of stimulus sequence.
Three experiments investigated the influence of the response-stimulus interval (RSI) on implicit and explicit learning of stimulus sequences. Participants responded to numerals presented in predetermined positions with alternating long and short RSIs. Half of the participants were instructed explicitly to learn the position sequence. In the transfer phase of Experiments 1 and 2, changing RSI patterns reduced the expression of incidental and intentional learning of position sequence. In Experiment 3 the position sequence was transformed, except that sub-sequences demarcated by long RSIs remained unchanged; this greatly reduced the expression of intentional learning, and slightly reduced that of incidental learning. These results indicate that in implicit learning, stimulus sequences are learned under the constraints of RSIs, whereas in explicit learning, learning independent of RSIs, as well as learning constrained by RSIs, occurs.


Bilateral obstruction of the vertebral arteries in a three-year-old child.
A three-year-old boy developed gait instability, nausea, vomiting, cranial nerve disturbances, hypotonus and dysarthria. Angiography of the four main cranial arteries showed complete obstruction of both vertebral arteries at the level of C1 to C2. Abundant collateral circulation was observed, which by-passed the obstruction to the vertebral arteries before their enterance into the posterior cranial fossa. The left vertebral artery was hypoplastic and both internal carotid arteries showed coiling in their extracranial portions. A high erythrocyte sedimentation rate at the beginning of the disease suggests an inflammatory alteration of both dysplastic vertebral arteries. The child recovered completely one month after the onset of symptoms. All other reported cases of childhood vertebro-basilar obstruction are reviewed and it is emphasized that the site of arterial obstruction has an important bearing on the clinical outcome.


Laparoscopic treatment of polycystic ovaries: is it time to relinquish the procedure?
To evaluate the role of laparoscopic ovarian drilling and treatment with metformin in the management of the polycystic ovary syndrome (PCOS). A literature search was conducted using the keywords laparoscopy, laparoscopic ovarian drilling, laparoscopic ovarian diathermy, PCOS, metformin, and ovulation. The MEDLINE and EMBASE databases and the Cochrane Database of Systematic Reviews were searched. No randomized comparisons have been done between laparoscopic ovarian drilling and metformin therapy. However, the ovulation and pregnancy rates appear to be similar for both techniques. Both treatments decrease the incidence of ovarian hyperstimulation and the cancellation rate of IVF cycles. However, unlike laparoscopic ovarian drilling, metformin may decrease the incidence of type 2 diabetes and coronary heart disease. Given the similar magnitude of the results without the potential risks and complication of surgery, we propose that laparoscopic ovarian drilling should be used sparingly in favor of less invasive treatment with metformin.


Incidence and clinical significance of accelerated junctional rhythm following open heart surgery.
Accelerated junctional rhythm following open heart surgery may lead to hemodynamic impairment due to loss of synchronized atrial contraction. Therefore, in this study we evaluated the frequency, duration, and hemodynamic effects of accelerated junctional rhythm in 30 patients undergoing coronary artery bypass (CAB) and in 30 undergoing valve replacement (VR). Accelerated junctional rhythm was defined as a rate greater than 55 bpm. Patients were continuously monitored postoperatively and rhythm strips obtained at least every 4 hours. Ten VR patients (33%) and four CAB patients (13%) exhibited accelerated junctional rhythm, the difference between these groups being significant (p less than 0.02). Nine of the 14 were hemodynamically compromised requiring inotropic support (9) and/or pacemaker insertion (2). The time of appearance of accelerated junctional rhythm ranged from immediate to 6 days (mean 26 +/- 52 hours, SD) and it lasted a mean of 16 +/- 22 hours. The rate ranged from 62 to 150 bpm. The sinus rate prior to the onset of accelerated junctional rhythm was significantly lower than the sinus rate in those not developing accelerated junctional rhythm. In conclusion, accelerated junctional rhythm is seen frequently following open heart surgery and may lead to hemodynamic deterioration. It is seen more frequently following VR, in approximately 33% of patients. Its manifestation appears to result from a combination of acceleration of junctional focus and slowing of sinus node discharge.


The effects of coital lubricants on sperm motility in vitro.
Infertility affects approximately 15% of couples, and in about one-third the primary cause is a male factor. Patients undergoing infertility investigations frequently experience sexual dysfunction, which often is due to inadequate vaginal lubrication. This can lead to increased use of coital lubricants. The effects of such lubricants on sperm motility have not been widely studied, although sperm motility is one of the best prognostic indicators of fertilization. Using a prospective longitudinal control-based study, we analysed the effect of adding four lubricants: KY jelly, baby oil, olive oil and saliva on sperm motion in 16 samples from patients undergoing infertility investigations. Sperm samples were prepared by density gradient centrifugation prior to mixing with lubricants. Motility parameters were determined using computer-assisted semen analysis after 5, 15 and 30 min. All lubricants except baby oil significantly decreased percentage progressive motility, progressive velocity, curvilinear velocity and lateral head displacement at 12.5% concentration. At a lower concentration of 6.25%, both olive oil and saliva still significantly reduced progressive motility parameters, while KY jelly diminished head movement parameters. Hence, even at these very low concentrations, coital lubricants impair sperm motility and thus may adversely affect fertility.


The spatial pattern of Enchytraeidae (Oligochaeta).
Spatial pattern of enchytraeids (Oligochaeta: Enchytraeidae) was studied in an experimental plot in an apple orchard near Bavorov, South Bohemia, Czechoslovakia. A total of 450 soil cores were taken in 1982, all individuals were determined (juveniles to genus, mature individuals to species) and counted. In total, 17 species of 4 genera were found. Both juveniles and mature individuals exhibited a distinctly aggregated spatial pattern. The distribution of the number of individuals in a sampling unit may be effectively fitted by the negative binomial distribution. The fit of Neyman type A distribution was considerably poorer. Comparing juveniles and mature individuals of the same genus using Lloyd's index of patchiness we found mature individuals to be slightly more aggregated than juveniles. Comparing the observed distribution of species number with that expected under the assumption of independence we may conclude that individuals appear in multispecies aggregation centres. These two conclusions support the hypothesis that aggregations are environmentally conditioned (abiotic factors and/or food availability) rather than caused by the type of reproduction.


Use of Tri-Ponderal Mass Index in Predicting Late Adolescent Overweight and Obesity in Children Aged 7-18.
Current reference systems using body mass index (BMI) or BMI z-scores to estimate overweight and obesity risk in adolescents are complex to use. An easy and effective measure and cutoffs such as the tri-ponderal mass index (TMI) are in need for parents and grassroots health workers. The aim of this study was to test whether cohort-derived TMI could be efficient for obesity prediction and to find out whether simplified TMI cutoffs could be used in the prediction. Data were obtained from a 12-year retrospective growth cohort generated in Guangdong, China. A total of 17,815 children (53.9% were boys) with 151,879 follow-ups conducted annually between 2005 and 2016 were involved. Late adolescent overweight and obesity were defined based on the BMI z-score (WHO 2007 growth reference) of the last measurement, which happened at the mean age of 17.2 (SD: 0.7) for both sexes. Analysis of the area under the curve (AUC) of the receiver operating characteristic curves was used to find the most appropriate cutoff. In total, 9,604 boys and 8,211 girls were included in the final analysis. TMI cutoffs performed better than WHO BMI cutoffs in the prediction of late adolescent overweight and obesity, with all corresponding AUCs <0.7. The simplified TMI cutoffs used to predict late adolescent overweight and obesity were 13.1 and 14.1 kg/m3 for children aged 7 to 15 years, respectively, with the corresponding AUCs ranging from 0.7315 (standard error, SE: 0.0132) to 0.9367 (SE: 0.0052). The cutoffs for predicting late adolescent overweight and obesity for children aged 16 to 18 years were 14.0 and 15.8 kg/m3, respectively, with the corresponding AUCs ranging from 0.9189 (SE: 0.0048) to 0.9841 (95% CI: 0.0027). Tri-ponderal mass index with the ease of administration in practice could be a promising alternative screening tool to BMI for the prediction of late adolescent overweight and obesity.


Current Approaches to Neuromodulation in Primary Headaches: Focus on Vagal Nerve and Sphenopalatine Ganglion Stimulation.
Neuromodulation is a promising, novel approach for the treatment of primary headache disorders. Neuromodulation offers a new dimension in the treatment that is both easily reversible and tends to be very well tolerated. The autonomic nervous system is a logical target given the neurobiology of common primary headache disorders, such as migraine and the trigeminal autonomic cephalalgias (TACs). This article will review new encouraging results of studies from the most recent literature on neuromodulation as acute and preventive treatment in primary headache disorders, and cover some possible underlying mechanisms. We will especially focus on vagus nerve stimulation (VNS) and sphenopalatine ganglion (SPG) since they have targeted autonomic pathways that are cranial and can modulate relevant pathophysiological mechanisms. The initial data suggests these approaches will find an important role in headache disorder management going forward.


Calcium Hypochlorite Solutions: Evaluation of Surface Tension and Effect of Different Storage Conditions and Time Periods over pH and Available Chlorine Content.
The aim of this study was to evaluate the pH and the available chlorine content from sodium hypochlorite (NaOCl) and calcium hypochlorite (Ca[OCl]2) solutions stored in different conditions and time periods and the surface tension of Ca(OCl)2 solutions in comparison with NaOCl. Solutions at 0.5%, 1%, 2.5%, and 5.25% concentrations were prepared. The pH level and the available chlorine content of freshly prepared solutions and solutions stored for 30, 60, and 90 days at 25°C, 4°C, or 37°C were evaluated in a digital pH meter and by titration, respectively. Surface tension was tested using a Du Nouy tensiometer (Sigma 702, Force Tensiometer; Attension, Espoo, Finland). Descriptive and inferential statistical analyses were performed. A precipitate formed by 2.5% and 5.25% Ca(OCl)2 solutions was observed. Ca(OCl)2 showed a higher concentration of available chlorine than NaOCl. Both 2.5% and 5.25% NaOCl and Ca(OCl)2 had a decrease in the available chlorine content when compared with freshly prepared solutions; 0.5% and 1% NaOCl tend to have a lower pH compared with 0.5% and 1% Ca(OCl)2. NaOCl, 5.25%, showed higher pH compared with 5.25% Ca(OCl)2. NaOCl and Ca(OCl)2 in 0.5% and 1% concentrations tend to show a reduced pH level, whereas 2.5% and 5.25% solutions showed an increase in pH. The heat contributed to the instability of the solutions. NaOCl showed lower surface tension values than Ca(OCl)2. Ca(OCl)2 solutions are extremely alkaline and tend to have more available chlorine content than NaOCl but have a higher surface tension than NaOCl. Regarding the available chlorine content, these solutions tend to be stable to 30 days of storage when kept at 4°C or at 25°C.


Attenuation of morphine withdrawal signs by low level laser therapy in rats.
In the present study, the effects of low-intensity laser therapy (LILT) on naloxone-induced withdrawal signs of morphine-dependent rats were examined. Low-intensity lasers with a power density of 12.5J/cm(2) have been used by a Ga-Al-As laser. One-way ANOVA showed that the LILT which applied immediately or 15min prior to naloxone injection significantly decreased total withdrawal score (TWS). These results suggest that LILT prior to naloxone injection attenuates the expression of withdrawal signs in morphine-dependent rats. Further studies may elucidate the likely role of LILT in clinical management of opioid withdrawal syndrome.


Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses.
Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body.


Spinal imaging and intervention: 1998.
Imaging of the lumbar spine is the most common application of magnetic resonance (MR) imaging in many radiologic practices. MR imaging has replaced computed tomography (CT) and CT myelography as the primary mode of spinal imaging and has relegated myelography to a secondary role in the evaluation of lumbar spinal disorders. At the same time, however, it has become evident that the correlation between gross anatomic findings as depicted on MR images and the clinical signs and symptoms detected by the clinician may be lacking. Defining the precise anatomic source of patients' complaints on the basis of imaging studies must be approached judiciously because a significant proportion of the population has disc disease as depicted on imaging studies, yet many have no clinical findings.


Normative FJS-12 scores for the knee in an Asian population: a cross-sectional study.
The Forgotten Joint Score is a patient-reported outcome measure validated in assessing patients post knee arthroplasty, anterior cruciate ligament (ACL) reconstruction surgery and patellar dislocation. A previous study had established the normative scores of a population in the USA but included knees with pathology. The aim of our study is to obtain normative Forgotten Joint Scores in young Asian adults without any pre-existing knee pathologies to increase the interpretability of the Forgotten Joint Score-12 (FJS-12) score. We conducted a cross-sectional study across young healthy Asian adults via electronic platforms. Participants who had sought either Western medical consultation, physiotherapy or traditional medical therapies were excluded. Demographic data, occupation, type of sport played, and FJS-12 scores were collected. Scores were stratified into subgroups and analysed. There were 172 participants who met our inclusion criteria for this study. The average age of participants in our study was 28.1 ± 10.5 years (range 14-70 years), with 83 (47.7%) participants falling into the ages 21-25 years. Average body mass index (BMI) was 21.9 ± 3.3 kg/m2 (range 14.7-36.3 kg/m2). The average FJS-12 score was 62.8 ± 25.6. The median FJS-12 was 63.5 with a range of 4.2-100. Nine participants (5.2%) scored the maximum score possible, and 56 (32.6%) participants scored below the midpoint score of 50. The percentiles for each subgroup of participants were tabulated and reported. Notably, males aged 46-70 years old scored the highest average FJS-12 score of 73.4 ± 5.5, and females aged 31-45 years old scored the lowest FJS-12 score of 57.1 ± 25.1. Females scored lower than males, although the difference was not statistically significant (p = 0.157). There were no significant correlations between BMI, age, or type of sport played with FJS-12; however, interestingly, we observed that women reported similar FJS-12 scores across all age groups, while men reported better scores with increasing age.Interestingly, we observed that women reported similar FJS-12 scores across all age groups, while men reported better scores with increasing age. CONCLUSION: Having normative values provides opportunities for benchmarking and comparing individuals against age- and gender-matched peers in the general population. Knowledge of normative values for FJS-12 scores would aid evaluating and tracking progress in patients recovering from injuries or undergoing post-surgery rehabilitation. This would help clinicians determine if they return to 'normal' post intervention.


[Locking plate fixation of distal periprosthetic femoral fractures : Clinical outcome and mortality].
The care of distal periprosthetic femoral fractures (PFF) is becoming a major interdisciplinary challenge due to demographic developments. The operative treatment is often performed (depending on the type of fracture) by means of locking plate fixation (LPF), although little data on the clinical outcome exist by now. The aim of the study is to identify risk factors for a poor outcome and increased mortality METHODS: In this retrospective study, 36 cases with distal PFF were examined. Exclusively treatment with LPF were included. Relevant previous illnesses (ASA score, Charlson index), fracture morphology and major complications were recorded as well as 1- and 3- year mortality. The clinical outcome was detected by using the Lysholm score. The 1- and 3- year mortality were 9% and 26% - exclusively affecting ASA 3 and 4 patients. The Lysholm Score showed a high variability (65 ± 27 points) with higher values in the ASA 1-2 subgroup (82 vs. 63 points) but independent of fracture type. The preoperative ASA score, the Charlson comorbidity index, and the patient age were determined to be decisive for 3-year mortality. This case series displayed a high absolute mortality even if the rate was slightly lower compared to previously published data. The rate of secondary dislocations, lack of fracture healing or follow-up operations were also low. The LPF therefore appears to be a suitable treatment for fractures with a stable prosthesis. However, there is a high variability in the clinical outcome regardless of the type of fracture and significantly increased mortality rates in previously ill patients.


A Descriptive Study of United States-Based Human Trafficking Specialty Clinics.
Human trafficking is a crime associated with serious adverse health and mental health outcomes. It has been estimated that more than 40 million people worldwide have been victimized, which has resulted in high rates of traumatic injuries, unwanted and high-risk pregnancies, mental illness, substance use disorders; and suicidality among trafficked persons. Little is known as to what models of health care delivery are best in engaging and sustaining the involvement of trafficked individuals with health care and trafficked individuals have reported discouragement and/or re-traumatization as a result of inadequate or fragmented care. To address the gap in knowledge regarding best practices for engaging and sustaining trafficked patients with health care, the authors of this study set out to identify and describe medical and mental health specialty clinics that work exclusively with trafficked adults, with the goal of assisting organizations and health care providers in program development and to improve clinical outcomes. A patient-centered, comprehensive, interdisciplinary, and trauma informed approach to clinical care is recommended for the treatment of trafficked patients. The authors strongly suggest that human trafficking specialty clinics prioritize psychiatric care and mental health services given the high rate of trauma and mental health issues among trafficked persons.


Effects of sex, age, choice of surgical orthodontic treatment, and skeletal pattern on the psychological assessments of orthodontic patients.
We aimed to examine the effects of sex, age, choice of surgical orthodontic treatment, and skeletal pattern on psychological assessment scores of orthodontic patients before edgewise treatment. They completed the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI)-II, and the psychological domain of the World Health Organization Quality of Life 26 (Psych-QOL) for assessment of anxiety, depression, and body image, respectively. No significant effects on psychological assessment scores due to sex or age differences were found. Surgical orthodontic treatment patients and patients with skeletal Class III had significantly higher STAI-Trait and/or BDI-II scores and lower Psych-QOL score. Based on the linear mixed-effects model, the choice of surgical orthodontic treatment had a significant effect on the STAI-Trait, BDI-II, and Psych-QOL scores. No significant interaction effect was found between the choice of surgical orthodontic treatment and the skeletal pattern by ANB angle. Patients with skeletal Class I or III who chose surgical orthodontic treatment had higher STAI-Trait and/or BDI-II scores and/or lower body image score, respectively. These results suggest that patients who chose surgical orthodontic treatment, particularly those with skeletal Class I and III, may be more prone to experience anxiety and depression and have body image dissatisfaction.


Immobilisation of contaminants by 'green'-synthesized magnetite as a remediation approach to the phosphogypsum waste leachates model solution.
Contaminant removal from (waste)waters by magnetite is a promising technology. In the present experimental study, a magnetite recycled from the steel industry waste (zero-valent iron powder) was used to investigate the sorption of As, Sb and U in phosphate-free and -rich suspensions, i.e. as a remediation for the acidic phosphogypsum leachates derived from the phosphate fertilizer industry. The results showed up to 98% U removal under controlled pH conditions, while phosphate did not hinder this immobilisation. In contrast, the results confirmed the limited uptake of As and Sb oxyanions by magnetite in presence of phosphate as the competing anion, displaying only 7-11% removal, compared to 83-87% in the phosphate-free sorption experiments. To limit this wastewater problem, raw ZVI anaerobic oxidation was examined as mechanism to increase the pH and as a source of Fe2+ in a first step, and in a second step to remove phosphate via vivianite precipitation, therefore prior to the reaction with magnetite. UV-Vis, XRD and SEM-EDS showed that vivianite precipitation is feasible at pH > 4.5, mainly depending on the phosphate concentration. The higher the [PO43-], the lower is the pH at which vivianite precipitates and the higher the % removal of phosphate from solution. It is anticipated that an optimum 3-steps design with separate reactors controlling the conditions of ZVI oxidation, followed by vivianite precipitation and finally, reaction with magnetite, can achieve high contaminant uptake in field applications.


Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma.
To determine (1) the reliability of sentinel lymph node (SLN) biopsy and (2) the need for cytokeratin 20 (CK-20) immunostaining in the staging of head and neck Merkel cell carcinoma (MCC). Retrospective cohort study (median follow-up of 34.5 months). Tertiary care center. Ten patients with head and neck MCC who underwent regional staging with SLN biopsy (SLNB) and CK-20 immunostaining. Sentinel lymph nodes were identified using preoperative lymphoscintigraphy, intraoperative gamma probe, and isosulfan blue dye. The SLNs were evaluated with hematoxylin-eosin and CK-20 immunostaining. Patients with negative SLNB results were followed up clinically. Percentage of positive SLNs, regional recurrence in the setting of a negative finding from SLNB, and percentage of positive SLNs requiring CK-20 immunostaining for diagnosis of micrometastatic MCC. At least 1 SLN was identified in every patient. Of 24 nodes, 19 (79%) were from the neck region and 5 (21%) were from the parotid basin. Two of the 24 SLNs, in 2 (20%) of 10 patients, were positive for metastatic disease. Both positive SLNs appeared negative on hematoxylin-eosin-stained sections, but small foci of micrometastatic MCC were identified with CK-20 immunostaining. No cranial nerve complications occurred. Regional failure in the setting of a negative finding on SLNB was observed in 1 (12%) of 8 patients. Biopsy of SLNs represents a safe and reliable technique for regional staging of MCC of the head and neck. It provides pathologists with a limited number of SLNs for focused analysis, which is imperative because hematoxylin-eosin immunostaining is often insufficient for identifying micrometastatic MCC. The use of anti-CK-20 antibody allows accurate identification of micrometastatic MCC.


Deconstructing the liquid architecture of human herpesvirus 8 diseases.
Human herpesvirus 8 (HHV-8), also called Kaposi sarcoma herspesvirus (KSHV), causes several human tumours, which may be associated with systemic inflammation and body cavity effusions, including a form of multicentric Castleman disease (MCD) and a novel inflammatory syndrome, KSHV inflammatory cytokine syndrome (KICS). In this issue, Zhou et al. demonstrate that HHV-8-infected lambda-restricted plasmablasts can be detected in these effusions and can be used to distinguish MCD from other HHV-8 tumours as well as to categorise KICS into distinct clinicopathological groups. These findings open a path to an integrated clinicopathological approach to HHV-8-associated inflammatory diseases and may have clinical implications. Commentary on: Zhou et al. A novel approach for characterisation of KSHV-associated multicentric Castleman disease from effusions. Br J Haematol 2023;200:462-475.


Sexually disrupting effects of nonylphenol and diethylstilbestrol on male silver carp (Carassius auratus) in aquatic microcosms.
Based on detected nonylphenol (NP) levels in aquaculture water, this study investigated sexually disrupting effects in mature male silver carp (Carassius auratus) exposed to NP and a positive control diethylstilbestrol (DES). The combined evidences of steroid hormone (17beta-estradiol, estrone and testosterone) levels and hispathological pictures showed that NP (10 microg/L) and DES could exert estrogenic effects through indirect mechanisms [i.e. increased estrogens levels (up to two times) and decreased androgen level in serum (down to 20-30%)], which might subsequently induce vitellogenin synthesis in liver. Environmental realistic concentrations of NP might be on the verge of inducing significant estrogenic effects in male silver carps. High amounts of NP and DES might be accumulated in fish serum, and the uptake by fish was possibly responsible for their quick attenuation in experimental tank water. NP and DES might have different metabolic mechanisms, the estrogenic effects of DES were more significant than those of NP.


The effect of MK-801 on cortical spreading depression in the penumbral zone following focal ischaemia in the rat.
Cortical spreading depression (CSD) is a transient depression of neuronal activity that spreads across the cortical surface. In the present studies, we have investigated CSD activity in the penumbral zone following permanent middle cerebral artery (MCA) occlusion in the rat (n = 16/group), using double-barreled Ca(2+)-sensitive microelectrodes. Measurements of CSD activity were made for 3 h in each animal. During this time, a varying number of spontaneous CSDs were seen in the control group (total was 30, with a range of 0-7/rat). These CSDs were of varying duration: "small" (approximately 1 min) and "big" (5-45 min) CSDs. During a CSD, the extracellular [Ca2+] decreased to 0.11 +/- 0.07 mM (mean +/- SD). After 3 h, the extracellular [Ca2+] in the cortex (penumbral zone) was either normal (10/16 rats) or lowered to 0.5 mM (2/16 rats) or to 0.1 mM (4/16 rats). In the caudate nucleus (ischaemic core area), all rats had an extracellular [Ca2+] of approximately 0.1 mM when measured after the 3 h recording period. Neuropathological evaluation of the brains of the animals, which had been allowed to survive for 24 h after MCA occlusion, revealed ischaemic damage in the dorsolateral cortex and caudate nucleus. Administration of the noncompetitive NMDA antagonist, MK-801 (3 mg/kg i.p.), 30 min after MCA occlusion resulted in 24 and 29% reductions in the volume of hemispheric and cortical damage, respectively, which was highly significant (p less than 0.0001); no protection was seen against caudate damage.(ABSTRACT TRUNCATED AT 250 WORDS)


Systemic use of spinosad to control the two-spotted spider mite (Acari: Tetranychidae) on tomatoes grown in rockwool.
Spinosad is a reduced-risk insecticide derived as a fermentation product from the soil actinomycete Saccharopolyspora spinosa. It is toxic by ingestion and contact and has a unique mode of action on the insect nervous system. Spinosad exhibits a high degree of selective toxicity towards the insect orders Lepidoptera, Diptera and Thysanoptera, but is less toxic to many beneficial arthropods. To determine if spinosad could be valuable as an alternative acaricide for the control of Tetranychus urticae, laboratory toxicity experiments with leaf-disk bio-assays were performed on a laboratory susceptible and several resistant strains. LC50 values were rather high in comparison with newly developed commercial acaricides. Surprisingly, when spinosad was applied to the roots of tomato plants in rock wool, excellent control of spider mites was obtained. Apparently, spinosad has systemic properties and quantities as low as 1 mg/plant could protect tomato plants from mite infestation. Different substrates with varying percentage of clay and organic matter were tested in comparison with rockwool and showed that sufficient control was restricted to the rockwool substrate. Consequently, a dose-response experiment with tomato plants grown in rockwool was set up. The persistence of spinosad toxicity when applied via the roots was determined, and pointed to a long lasting control (up to 30 DAT). Spinosad amounts in leaves after systemic application were determined with an immunological technique to quantify spinosad uptake. Correlations between mite control, spinosad uptake and leaf concentrations can be helpful to determine the necessary dose in field situations.


Preventing Transmission of Mycobacterium Tuberculosis-A Refocused Approach.
Traditional tuberculosis (TB) infection control focuses on the known patient with TB, usually on appropriate treatment. A refocused, intensified TB infection control approach is presented. Combined with active case finding and rapid molecular diagnostics, an approach called FAST is described as a convenient way to call attention to the untreated patient. Natural ventilation is the mainstay of air disinfection in much of the world. Germicidal ultraviolet technology is the most sustainable approach to air disinfection under resource-limited conditions. Testing and treatment of latent TB infection works to prevent reactivation but requires greater risk targeting in both low- and high-risk settings.


Affinity purification of tissue plasminogen activator using transition-state analogues.
The search for a simple affinity ligand to purify tissue plasminogen activator (tPA) was facilitated by a solid-phase synthesis approach. A large variety of tripeptide ligands containing argininal were synthesized on agarose gels containing a spacer with carboxy terminal. The immobilized ligands were easy to test with urokinase, and tPA. While a number of sequence combinations showed initial binding by tPA, only a few resulted in tight binding corresponding to a hemiacetal linkage with the active site serine. Hydrophobic residues, especially aromatics, flanking the N-side of argininal gave rise to ligands which were bound strongly by tPA. A gel containing D-Phe-D-Phe-Argal (an aldehyde derivative of arginine) was very effective in purifying tPA derived from cell culture media at small scale (milligrams) and at large (multi-grams).


Cotrimoxazole as a Preventative Intervention for Pneumocystis Pneumonia in Pemphigus Patients Treated with Rituximab: A Retrospective Study.
Pneumocystis jirovecii pneumonia (PJP) is a severe, life-threatening complication in patients treated with rituximab. However, there is no consensus on the primary prophylaxis for it in rituximab-treated pemphigus patients. Therefore, we sought to investigate the prophylactic efficacy and safety profile of cotrimoxazole for reducing the risk of developing PJP in pemphigus patients receiving rituximab. This single-center retrospective study investigated 148 pemphigus patients undergoing a first cycle of rituximab between 2008 and 2021 at a tertiary referral center in northern Taiwan. Patients were divided into the prophylaxis group (N = 113) and the control group (N = 35) according to whether or not cotrimoxazole was administered. The primary outcome was the 1-year incidence of PJP in the two groups, while the secondary outcome was the incidence of cotrimoxazole-related adverse events. Of the 148 patients enrolled in this study, three patients, all in the control group, developed PJP during the 1-year follow-up. The incidence of PJP (8.6%) in the control group was significantly higher than that in the prophylaxis group (0%) (p = 0.012). The incidence of cotrimoxazole-related adverse events was 2.7%, and none of the cases were associated with life-threatening conditions. In addition, the cumulative prednisolone dose was associated with a trend of a higher risk of PJP (p = 0.0483). Prophylactic cotrimoxazole significantly reduces the risk of PJP in a certain high-risk population and has a tolerable safety profile.


Independence levels and social adjustment of poststroke patients.
A study of 52 poststroke patients found that patients who lived alone reported more independence in their life-styles than those who lived with family members. Family members of male patients were more likely to experience guilt, irritation, restrictions, and relationship difficulties than family members of female patients.


[Modification of repair DNA synthesis in mutagen-treated human fibroblasts during adaptive response and the antimutagenic effect of garlic extract].
Repair DNA synthesis (RDS) in human fibroblasts during the adaptive responses (ARs) induced by cadmium chloride (CdCl2), gamma-radiation, and 4-nitroquinoline-1-oxide (4NQO) was compared in cells pretreated and not pretreated with garlic extract. The RDS was increased during the ARs induced CdCl2 and gamma-irradiation. Garlic extract stimulated RDS in cells treated by the same mutagens. 3-Aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) polymerase, decreased the RDS rate in cells treated with CdCl2 and gamma-irradiation but had no significant effect on cells treated with 4NQO. It was demonstrated that DNA repair was involved into cell protection in different ways in the cases of antimutagen treatment and AR.


Influence of contrast enhancement at the contrast injection location for the arm or leg in neonatal and infant patients during cardiac computed tomography.
Obtaining CCTA images with optimal injection location such as the arm or leg is important to avoid the artifacts caused by the CM. This study compares the computed tomography (CT) numbers and visualization scores of the three-dimensional (3D) images of the lumens of the blood vessels in the arm or leg during cardiac computed tomography angiography (CCTA) in neonatal and infant patients. Between January 2017 and January 2020, 253 consecutive patients were considered for inclusion. We used the estimated propensity scores as a function of the demographic data, including age, body weight, and injection location (right or left side) in the arm (n = 58) and leg (n = 58) of neonatal and infant patients. We compared the mean CT numbers of the pulmonary artery, ascending aorta, and left superior vena cava; contrast-noise ratios (CNR); and visualization scores between the arm and leg as the injection locations. The mean CT numbers during CCTA for the arm and leg were 479.4 and 461.3 HU in the ascending aorta, 464.2 and 448.1 HU in the pulmonary artery, and 232.8 and 220.1 HU in the left superior vena cava, respectively. The mean image noise (SD) and CNR values, respectively, were 38.9 HU and 12.1 for the arm as the injection location and 39.1 HU and 12.3 for the leg as the injection location. The median visualization scores of volume rendering of the 3D images were 3.0 and 3.0 for the arm and leg injection sites, respectively. There were no significant differences in the mean CT numbers of the ascending aorta, pulmonary artery, and left superior vena cava; SD value; CNR; and visualization scores between the arm and leg injection locations. The CT numbers of the lumen of the blood vessel and visualization scores of the 3D images of the arm and leg injection locations are equal during CCTA in neonatal and infant patients with congenital heart disease.


Strontium as therapy for osteoporosis.
Osteoporosis is characterized by low bone mass and increased susceptibility to fracture. Recent in vitro studies showed that strontium ranelate, a novel agent containing two strontium atoms, acts as an effective anti-osteoporotic drug by inhibiting bone resorption by osteoclasts and promoting osteoblast replication and bone formation. Studies in animals demonstrated that strontium ranelate increases bone mass, microarchitecture and strength in intact rodents and prevents bone loss in osteopenic animals. Clinical studies show that strontium ranelate reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporosis. Together, these recent advances point to unique effects of strontium ranelate on bone cells and show that strontium ranelate has significant clinical benefits in the treatment of postmenopausal osteoporosis.


Identification and biological characterization of a new pathogen that causes potato scab in Gansu Province, China.
Potato scab caused by pathogenic Streptomyces is a serious soil-borne disease on potato. In this study, a new Streptomyces strain 5A-1 was isolated from potato samples in China. Based on morphological characteristics, 16S rDNA gene sequence analyses, it was identified as Streptomyces griseoplanus (Streptacidiphilus griseoplanus), pathogenicity of which was measured by the methods of small potato chips, radish slices and potato pot trial inoculation. Moreover, the pathogenic genes txtAB and tomA from the Streptomyces pathogenicity island (PAI) were detected. Determination of biological characteristics showed that the optimal temperature for the growth of S. griseoplanus strain 5A-1 was 25 °C, the optimal light condition was darkness, the optimal pH value was 8.5 and the most preferred carbon source and nitrogen source is glucose and aspartate, respectively. To our knowledge, it is the first report for S. griseoplanus, as a new pathogen, to cause potato scab.


Natural cytotoxicity of lymphocytes and monocytes and its augmentation by OK432 in melanoma patients.
Lymphocytes and monocytes from the peripheral blood of 30 patients with malignant melanoma were tested for natural cytotoxicity against K562 cells in a 3-h 51Cr-release assay, and the effects of OK432 (a streptococcal preparation) on the cytotoxicity were examined. The lymphocyte cytotoxicity of melanoma patients was similar to that of normal donors and control patients with benign skin disease. Furthermore, the lymphocyte cytotoxicity of melanoma patients was not correlated to the stage of the disease. Similarly, lysis of K562 cells by monocytes isolated by adherence to autologous serum-coated plastic dishes in melanoma patients was comparable to that of controls and not associated with the stage of the disease. Positive monocyte reactions were recorded in 10 of 30 (33%) melanoma patients, seven of 21 (33%) normal donors and three of 10 (30%) control patients. There was no correlation between lymphocyte cytotoxicity and monocyte cytotoxicity. Overnight treatment of monocytes and lymphocytes with OK432 resulted in an increase in cytotoxicity. Significant augmentation of cytotoxicity by OK432 was observed in 28% of the monocyte samples and 86% of the lymphocyte samples, while partially purified human interferon augmented cytotoxicity in 63% of the monocyte samples and all the lymphocyte samples. These results suggest that neither lymphocyte nor monocyte cytotoxicities are depressed in melanoma patients as compared with normal donors and patients with benign disease and that OK432 has a stronger stimulatory effect on lymphocytes than on monocytes.


Two-year follow-up of a thyroid cartilage metastasis from prostate cancer: A case report.
Few case reports describe metastatic prostate cancer to the thyroid cartilage. While earlier reports identified the metastatic lesions upon developing symptoms, more recent ones have detected them via prostate-specific membrane antigen positron emission tomography (PSMA PET). Herein, we report the case of a patient with metastatic castrate-resistant prostate cancer and a PSMA PET-detected lesion in the thyroid cartilage. Over the course of 2 years, he received multiple lines of chemotherapy and hormonal therapy, and his overall disease status fluctuated - some nodal and bony metastases resolved while others appeared anew. His thyroid cartilage lesion, however, slowly progressed in a consistent fashion with increasing uptake on successive PSMA PET images. Apart from mild dysphonia, the patient remained to be asymptomatic from this lesion, and no local therapies were used. To our knowledge, this is the first close follow-up of prostate cancer metastatic to the thyroid cartilage, shedding light on the course of such lesions and helping answer management-related questions, which are particularly relevant as more occult metastases are discovered in the PSMA PET era.


Docetaxel induced-JNK2/PHD1 signaling pathway increases degradation of HIF-1α and causes cancer cell death under hypoxia.
HIF-1 (hypoxia-inducible factor-1) regulates the expression of more than 70 genes involved in angiogenesis, tumor growth, metastasis, chemoresistance, and radioresistance. Thus, there is growing interest in using HIF-1 inhibitors as anticancer drugs. Docetaxel, a Food and Drug Administration-approved anticancer drug, is reported to enhance HIF-1α degradation. Here, we investigated the molecular mechanism underlying docetaxel-induced HIF-1α degradation and cancer cell death under hypoxic conditions. Docetaxel pretreatment enhanced the polyubiquitination and proteasome-mediated degradation of HIF-1α, and increased cancer cell death under hypoxic conditions. Docetaxel also activated the prolyl hydroxylase, PHD1, in hypoxia, and pharmacological inhibition or siRNA-mediated knockdown of PHD1 prevented docetaxel-induced HIF-1α degradation and cancer cell death. Additionally, siRNA-mediated JNK2 knockdown blocked docetaxel-induced HIF-1α degradation and cancer cell death by inhibiting PHD1 activation. A luciferase reporter assay revealed that inhibition of the JNK2/PHD1 signaling pathway significantly increased the transcriptional activity of HIF-1 in docetaxel-treated cancer cells under hypoxia. Consistent with these results, docetaxel-treated JNK2-knockdown tumors grew much faster than control tumors through inhibition of docetaxel-induced PHD1 activation and degradation of HIF-1α. Our results collectively show that, under hypoxic conditions, docetaxel induces apoptotic cell death through JNK2/PHD1 signaling-mediated HIF-1α degradation.


FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer.
Prostate cancer adeno-to-neuroendocrine lineage transition has emerged as a mechanism of targeted therapeutic resistance. Identifying the direct molecular drivers and developing pharmacological strategies using clinical-grade inhibitors to overcome lineage transition-induced therapeutic resistance are imperative. Here, using single-cell multiomics analyses, we investigate the dynamics of cellular heterogeneity, transcriptome regulation, and microenvironmental factors in 107,201 cells from genetically engineered mouse prostate cancer samples with complete time series of tumor evolution seen in patients. We identify that FOXA2 orchestrates prostate cancer adeno-to-neuroendocrine lineage transition and that Foxa2 expression is significantly induced by androgen deprivation. Moreover, Foxa2 knockdown induces the reversal of adeno-to-neuroendocrine transition. The KIT pathway is directly regulated by FOXA2 and specifically activated in neuroendocrine prostate cancer (NEPC). Pharmacologic inhibition of KIT pathway significantly suppresses mouse and human NEPC tumor growth. These findings reveal that FOXA2 drives adeno-to-neuroendocrine lineage plasticity in prostate cancer and provides a potential pharmacological strategy for castration-resistant NEPC.


Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia.
Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM).


Role of fascial collagen in stress urinary incontinence.
Our purpose was to determine whether collagen of the pubocervical fasciae that support the urethrovesical junction undergoes alterations that might contribute to incontinence. Pubocervical fascia was collected as a residual tissue in 82 patients, aged 25 to 73 years, during surgical treatment of cystocele (n = 26, no incontinence) or of stress urinary incontinence (n = 56). Measurements were made of collagen content, solubility, and cross-linking and of collagenase activity. Patients treated for incontinence had the same mean age and parity as the control cystocele group. There was a highly significant (20%, P <.0005) decrease in collagen content in fascial tissue from incontinent women. There was no difference in the percentage of acid-soluble (0.7%) and pepsin-soluble (17%) collagen in the 2 groups of patients; this agrees with the lack of significant change in the degree of collagen cross-linking by pyridinoline. Collagenase activity was significant in fascia but did not change in incontinence. Incontinent women had an increased body mass index. The pubocervical fasciae of incontinent women show a diminished content of collagen, but this is not accompanied by changes in collagen solubility or cross-linking or in collagenase activity. This decrease in collagen may contribute to the weakening of support of the bladder neck.


White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies.
Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions.


Go with the flow-hidden vascular passages in bone.
The circulatory system in long bones is incompletely understood. A new study published in Nature Metabolism unveils the presence of dense vascular networks in long bones that facilitate the egress of bone marrow cells and potentially the exchange of nutrients between the bone marrow and the systemic circulation.


Countervailing effects of rapamycin (sirolimus) on nuclear factor-kappa B activities in neointimal and medial smooth muscle cells.
Local application of rapamycin (sirolimus) by drug-eluting stents prevents lumen obliteration after angioplasty by inhibition of neointimal hyperplasia. The effects of rapamycin on neointimal smooth muscle cells (niSMC) which are responsible for the occurrence of restenosis have not been investigated so far. Rat niSMC and medial SMC (mSMC) were obtained from balloon catheter-injured arteries. The niSMC exhibited higher basal NF-kappaB activity and TNF-alpha mRNA levels. Nuclear protein binding to NF-kappaB-DNA was attenuated in niSMC by incubation with rapamycin (0.1 and 1 microg/ml) for 24 and 48 h. In contrast in mSMC, 0.1 microg/ml rapamycin had no effect and at 1 microg/ml even increased nuclear protein binding to NF-kappaB-DNA. After 12 h incubation, rapamycin (0.001-10 microg/ml) induced IkappaB-alpha protein in niSMC, whereas in mSMC it stimulated IkappaB-alpha at much lower levels. Prolonged rapamycin treatment (1 microg/ml for 72 h) had no effect on TNF-alpha mRNA level and NF-kappaB activity in niSMC, whereas it led to their increase in mSMC. Vascular endothelial growth factor (VEGF) secretion was higher in mSMC than in niSMC; rapamycin decreased VEGF levels in both cell types. Ultrastructural analysis suggested that rapamycin caused early signs of degeneration in niSMC, but enhanced protein synthesis in mSMC. This study shows that rapamycin influences the inflammatory phenotypes of SMC in opposite directions: it reduces the high basal NF-kappaB activity in niSMC and enhances NF-kappaB activity and TNF-alpha expression in mSMC. In addition, rapamycin inhibits VEGF production regardless of the phenotype of SMC. These findings shed light on molecular mechanisms and structural changes underlying therapeutic applications of rapamycin in prevention of restenosis, inhibition of chronic transplant arteriosclerosis and reduction of secondary malignoma formation due to immunosuppression.


Differences between CS-DAVF and TCCF--to reveal and redefine CS-DAVF.
In the past, the cavernous dural arteriovenous fistula was categorized as spontaneous cavernous carotid fistula [1] due to the lack of knowledge and limitation of imaging equipment. In the recent time, with the accumulation of knowledge of DAVF's etiology, mechanism, physiology, clinical symptoms and imaging data, the diagnostic methods and treatment have achieved novel understandings and progresses. In fact, it's a specific type of dural arteriovenous fistula---- cavernous dural arteriovenous fistula. The purpose of this paper is to tell the difference between cavernous dural arteriovenous fistula and traumatic carotid cavernous fistula, and to redefine cavernous dural arteriovenous fistula from the aspects of etiology, mechanism, pathology, clinical symptoms, DSA characteristic and therapy. DAVF is an independent disease. The Cavernous dural arteriovenous fistula can not be classified as spontaneous CCF any longer, but a specific type of DAVF--- cavernous DAVF.


Preferential inhibition of ribonucleic acid synthesis by a new thiosemicarbazone possessing antibacterial and antiparasitic properties.
We determined the influence of the azacycloheptane derivative (H) of a 2-acetylpyridine thiosemicarbazone on growth and macromolecular synthesis in Escherichia coli AT-9. Thiosemicarbazone H caused bacteriostasis and a primary inhibition of ribonucleic acid synthesis; secondary effects included inhibition of deoxyribonucleic acid and protein synthesis. Addition of cooper or other transition elements was not necessary for these inhibitions.


Spontaneous enterocutaneous fistula in a patient with femoral hernia: a case report.
Enterocutaneous fistula commonly occurs in the post-operative setting. However, a handful of cases have been reported to occur secondary to strangulation of hernia, mostly femoral due to the narrow femoral ring through which this type of hernia passes through. We encountered a case of spontaneous fecal fistula, which occurred in the setting of an incarcerated femoral hernia. The patient did not develop peritonism, or obstruction, throughout the course of the disease. The hernia ruptured on day 7 of incarceration. Exploratory laparotomy under epidural anesthesia revealed a femoral hernia with ileum as content, arising approximately 20 cm from the ileocecal junction. Reduction of the contents was done, and a resection performed along with repair of the hernia. As very few literature describe the formation of spontaneous fecal fistula, we discuss the presentation in this report.


Endoscopic drainage with a metallic stent for obstructive jaundice caused by bile duct metastasis of breast cancer: A case report.
Bile duct metastasis of breast cancer is rare. It often causes obstructive jaundice which makes the patient interrupt state of treatment. Endoscopic drainage for obstructive jaundice is effective and less invasive treatment option also in this case. A 66-year-old breast ductal carcinoma patient developed obstructive jaundice, presenting with epigastric discomfort and dark-colored urine. Computed tomography and endoscopic retrograde cholangiopancreatography revealed bile duct stenosis. Brushing cytology and tissue biopsy confirmed bile duct metastasis, a self-expandable metallic stent was placed/replaced endoscopically, and chemotherapy was continued, extending the patient's life.


A prospective, randomized controlled trial of megestrol acetate among high-risk patients with resected malignant melanoma.
In light of some evidence that hormonal factors may impact on malignant melanoma, we performed a randomized trial of megestrol acetate versus observation among 67 patients with high-risk resected stage I or stage II (nodal) malignant melanoma. Following stratification by relevant prognostic factors, we observed a statistical significance in survival advantage for megestrol acetate that approached 7.6 versus 2.6 years, median survival; two-sided log rank p = 0.06. Disease-free survival was also greater for patients who received this hormonal therapy (3.4 versus 1.1 years, median disease-free survival), but the difference was not statistically significant (two-sided log rank p = 0.20). The most noteworthy side effects were weight gain (median 6-month gain of 8.2 kg) and impotence. Fully recognizing the hazards of limited sample analyses and the need for confirmatory trials, our findings suggest a possible role for megestrol acetate as adjuvant therapy for selected patients with malignant melanoma.