Manganese chloride (MnCl2) induced novel model of Parkinson's disease in adult Zebrafish; Involvement of oxidative stress, neuroinflammation and apoptosis pathway.
Parkinson's disease (PD) is a progressive neurodegenerative disorder imposing a severe health and socioeconomic burden worldwide. Existing pharmacological approaches for developing PD are poorly developed and do not represent all the characteristics of disease pathology. Developing cost-effective, reliable Zebrafish (ZF) model will meet this gap. The present study was conceived to develop a reliable PD model in the ZF using manganese chloride (MnCl2). Here, we report that chronic exposure to 2 mM MnCl2 for 21 days produced non-motor and motor PD-like symptoms in adult ZF. Compared with control fish, MnCl2-treated fish showed reduced locomotory activity, indicating a deficit in motor function. In the light-dark box test, MnCl2-treated fish exhibited anxiety and depression-like behavior. MnCl2-treated fish exhibited a less olfactory preference for amino acids, indicating olfactory dysfunction. These behavioral symptoms were associated with decreased dopamine and increased DOPAC levels. Furthermore, oxidative stress-mediated apoptotic pathway, decreased brain derived neurotropic factor (BDNF) and increased pro-inflammatory cytokines levels were observed upon chronic exposure to MnCl2 in the brain of ZF. Thus, MnCl2-induced PD in ZF can be a cost-effective PD model in the drug discovery process. Moreover, this model could be potentially utilized to investigate the molecular pathways underlying the multifaceted pathophysiology which leads to PD using relatively inexpensive species. MnCl2 being heavy metal may have other side effects in addition to neurotoxicity. Our model recapitulates most of the hallmarks of PD, but not all pathological processes are involved. Future studies are required to recapitulate the complete pathophysiology of PD.


Transformation of pulp and paper mill sludge (PPMS) into a glucose-rich hydrolysate using green chemistry: Assessing pretreatment methods for enhanced hydrolysis.
Pulp and paper mill sludge is a waste stream derived from the pulp and paper making industry, comprised of organic and inorganic material in the form of cellulose, hemicellulose, lignin and ash. In South Africa, approximately fivefour hundred thousand wet tonnes are produced per annum and is currently disposed via landfilling or incineration. However, these disposal methods raise environmental and financial concerns. This waste stream is an attractive feedstock for fermentable sugars, mainly glucose, recovery and can be redirected for valorisation as a feedstock for microbial fermentation to produce value-added products. Sugar recovery by enzymatic hydrolysis, as opposed to acidic hydrolysis, is a promising approach but is hampered by the lignin and inorganic material found in pulp and paper mill sludge. Several treatment steps to reduce or remove these components prior to enzymatic hydrolysis are assessed in this review. Pretreatment improves hydrolysis of cellulosic fibres and ensures a substantial yield of sugars.


Acute cerebral infarction and extra pontine myelinolysis in children with new onset type 1 diabetes mellitus.
Neurological complications of diabetic ketoacidosis (DKA) are still associated with significant mortality and morbidity. We report on two children who suffered from acute cerebral infarction (CI) and extra pontine myelinolysis (EPM) at onset of type 1 diabetes. Initially, clinical management had not been performed according to generally accepted guidelines. Putative risk factors that may have predisposed for the development of acute cerebrovascular complications are discussed. Not only cerebral edema (CE) but also other severe neurological complications such as CI should be suspected when neurological deterioration occurs during DKA. We conclude that not only an exceeded rehydration therapy but also a rapidly reduced serum osmolality due to an unbalanced rapid blood sugar decrease and serum sodium increase may have lead to the neurological disease. We propose that a reserved and well-defined rehydration strategy in the first 6 (-12) h of therapy is crucial for recovery and can reduce neurological complications of patients with DKA.


Dehydration assessment via a portable, single sided magnetic resonance sensor.
Undiagnosed dehydration compromises health outcomes across many populations. Existing dehydration diagnostics require invasive bodily fluid sampling or are easily confounded by fluid and electrolyte intake, environment, and physical activity limiting widespread adoption. We present a portable MR sensor designed to measure intramuscular fluid shifts to identify volume depletion. Fluid loss is induced via a mouse model of thermal dehydration (37°C; 15-20% relative humidity). We demonstrate quantification of fluid loss induced by hyperosmotic dehydration with multicomponent T2 relaxometry using both a benchtop NMR system and MRI localized to skeletal muscle tissue. We then describe a miniaturized (~1000 cm3 ) portable (~4 kg) MR sensor (0.28 T) designed to identify dehydration-induced fluid loss. T2 relaxometry measurements were performed using a Carr-Purcell-Meiboom-Gill pulse sequence in ~4 min. T2 values from the portable MR sensor exhibited strong (R2 = 0.996) agreement with benchtop NMR spectrometer. Thermal dehydration induced weight loss of 4 to 11% over 5 to 10 h. Fluid loss induced by thermal dehydration was accurately identified via whole-animal NMR and skeletal muscle. The portable MR sensor accurately identified dehydration via multicomponent T2 relaxometry. Performing multicomponent T2 relaxometry localized to the skeletal muscle with a miniaturized MR sensor provides a noninvasive, physiologically relevant measure of dehydration induced fluid loss in a mouse model. This approach offers sensor portability, reduced system complexity, fully automated operation, and low cost compared with MRI. This approach may serve as a versatile and portable point of care technique for dehydration monitoring.


Physiological response to heat stress and ingestive behavior of lactating Jersey cows in silvopasture and conventional pasture grazing systems in a Brazilian subtropical climate zone.
The aim of this study was to evaluate the physiological response to heat stress and ingestive behavior of Jersey cows in silvopasture and conventional pasture grazing systems. The experiment was carried out during the warm season, spanning spring, summer, and fall seasons in the Brazilian subtropical climate zone. Twelve lactating Jersey cows were observed in rotational grazing on Cynodon nlemfuensis Vanderyst and Panicum maximum Jacq. Treatments were composed of different grazing systems (silvopasture and conventional pasture). The silvopasture grazing system had eucalyptus trees (Eucalyptus grandis Hill ex Maiden) with an average height of ≈ 10 m and row spacing of 20 m. In the conventional pasture grazing system, there were no rows of eucalyptus and no other type of tree or structure to provide shade to the animals. During the summer and fall periods of evaluation, the silvopasture animals presented a lower respiratory rate, whereas during the spring and fall evaluation periods, these animals presented a lower rectal temperature. Cattle in the silvopasture showed longer grazing times at night (+21.65 min) and overall (+36.00 min) and remained lying down (ruminating and resting) for longer (+ 73.07 min) than conventional pasture grazing system animals. In addition, the animals in the silvopasture had a lower water intake (3.12 L/100 kg BW). The silvopasture grazing system improved the welfare of the grazing Jersey cows, as evidenced by the improvement in physiological response to heat stress, increased grazing time and decreased standing time (resting + ruminanting) when compared to cows in the conventional pasture grazing system.


Case report: An epidural cavernous hemangioma mimicking a dumbbell-shaped neuroma.
Spinal epidural cavernous hemangiomas are a rare occurrence. This particular case is made even more distinctive by the fact that the lesion mimicked a dumbbell-shaped neuroma. Moreover, it had a very unique localization (wholly epidural, at cervical-thoracic -C7-D1- level). The importance of this case is linked not only to its remarkable rarity, but also to the diagnostic avenues explored. The surgery was carried out by Prof. Riccardo Caruso, Head of the Neurosurgical Department of the Military Hospital of Rome and Professor of Neurosurgery of Sapienza University of Rome, assisted by Dr. Luigi Marrocco, Senior Neurosurgeon of the Military Hospital of Rome. Postsurgical recovery was managed by Dr. Venceslao Wierzbicki, Senior Neurosurgeon of the Military Hospital of Rome. In 2020, a 71 year-old man, suffering from intense pain in the left scapular region and in the ulnar area of the left forearm, underwent surgery for the removal of a spinal epidural cavernous hemangioma involving the left C7-D1 foramen. Prior to surgery, the lesion had been misdiagnosed as a neuroma by a radiologist. In the Literature there are other, rare cases of hemangiomas partly located in the spinal canal, and partly located intra and extra foramen. In the case here presented, differential diagnosis as well as a potential Schwannoma, suggested by the dumbbell shape of the lesion, should have considered also the possibility of a meningioma. Two teams of radiologists examined the images, the radiologists of our team, Dr. Valentina Martines and Dr. Emanuele Piccione, thanks to a close inspection of the features of the lesion, postulated the extra-dural position. Other aspects of the scans were then analyzed to help guide future diagnosis of similar lesions. With a spinal tumor affecting the foramen, a close examination of the images allows for accurate presurgical differential diagnosis, differentiating between the more frequent neuroma and other rarer tumors, such as a hemangioma.


Effect of 2% chlorhexidine on dentin microtensile bond strengths and nanoleakage of luting cements.
The aim of this study was to investigate the effect of pre-treatment by chlorhexidine on the microtensile bond strength (mTBS) of resin cements and nanoleakage at the resin-dentine interfaces. Cylindrical composite blocks were luted to human dentine using resin cements (RelyX ARC, 3M ESPE: ARC; Panavia F, Kuraray Medical Inc.: PF; RelyX Unicem, 3M ESPE: UN) with/without pre-treatment by 2% chlorhexidine digluconate (CAVITY CLEANSER, Bisco, Inc., Schaumburg, IL, USA). CAVITY CLEANSER was applied on the acid etched dentine for 60s in the ARC group, and on smear layer-covered dentine in the PF and UN groups. After storage in water for 24h, the bonded teeth were sectioned into 1mm thick slabs and further into 0.9mm x 0.9mm beams. After immersion in water or ammoniacal silver nitrate for 24h, the beams were stressed to failure in tension. The fractured surfaces were examined by field-emission scanning electron microscopy (FE-SEM) using backscattered electron mode. The silver-stained slabs were used to examine nanoleakage within the bonded interface by FE-SEM. The resin cement and chlorhexidine treatment had significant effects (p<0.0001) on mTBS; while the storage media had no significant effect (p=0.435). The mTBS of ARC was significantly higher than the other cements. Chlorhexidine reduced mTBS and produced pronounced nanoleakage when PF and UC were luted to dentine. Pre-treatment with chlorhexidine affected the integrity of dentine bonding with PF and UC, while there was no adverse effect on coupling of ARC.


Administering Antibiotics for Less Than Four Weeks Increases the Risk of Relapse in Culture-Positive Septic Arthritis of Native Joints.
(1) Objectives: This study investigated the optimal duration of antibiotic therapy and determined the risk factors associated with relapse in patients with culture-proven septic arthritis of native joints. (2) Methods: A retrospective review was conducted on patients aged ≥18 years diagnosed with native joint septic arthritis, with bacteria isolated from joints and/or blood. The exclusion criteria were prosthetic joint infections and cases with no identified microorganisms. The outcomes were assessed in the remission and relapse groups. (3) Results: Among 479 patients with native joint septic arthritis, 137 met the inclusion criteria, with a median follow-up duration of 2.7 years. The relapse rate was 9.5%, which mainly occurred within 30 days after antibiotic treatment completion. Compared with the remission group, the relapse group showed a significantly higher proportion of cases that received antibiotic therapy for ≤ 4 weeks (4.8% vs. 46.2%, p < 0.001), synovial fluid white blood cell (WBC) counts ≥150 × 103/mm3 (25.3% vs. 60.0%, p = 0.030), acute kidney injury (19.2% vs. 50%, p = 0.024), and extended-spectrum beta-lactamases-producing Enterobacteriaceae (0.8 vs. 15.4%, p = 0.024). Independent risk factors for relapse were determined as antibiotic therapy duration of ≤ 4 weeks (odds ratio (OR), 25.47; 95% confidence interval (CI), 1.57-412.33; p = 0.023) and synovial fluid WBC counts ≥150 × 103/mm3 (OR, 17.46; 95% CI, 1.74-175.62; p = 0.015). (4) Conclusions: Patients with native joint septic arthritis require vigilant monitoring for relapse, particularly when treated with antibiotic regimens administered for less than four weeks or when synovial aspirates exhibit elevated WBC counts at diagnosis.


Assessment of Post-Vaccination Phagocytic Activation Using Candida albicans Killing Assays.
Candida albicans is an important opportunistic fungal pathogen. It is now the fourth leading cause of nosocomial bloodstream infections and a great threat to the immuncompromised patients attributed to the disseminated candidiasis with the mortality up to 40%. Phagocytic cells are the first line of defense against Candida infections. Antibodies induced by vaccination can effectively enhance the capacities of phagocytosis and killing of neutrophils and macrophages. In this chapter, flow cytometric analysis (FACS) and killing assay by plate culture methods are introduced to evaluate the phagocytosis and killing of strains of Candida albicans opsonized with immune serum obtained from mice vaccinated with yeast and recombinant enolase.


Prognostic value of FDG-PET in patients with ovarian carcinoma following surgical treatment.
[corrected] To determine the prognostic value of FDG-PET after surgical resection in patients with ovarian carcinoma, we compared the results of FDG-PET and serum CA-125 level and prognosis of patients. Eighteen patients underwent a total of 32 FDG-PET examinations following surgery for ovarian carcinoma from October 2001 to December 2002 at our hospital (median follow-up period, 31 months). Age of the patients at the time of the initial FDG-PET examination ranged from 31 to 73 years (mean 52 years) and the period from surgery to the initial FDG-PET examination ranged from 5 to 109 months (mean 30 months). Serum CA-125 levels were determined on the occasion of each FDG-PET examination. Recurrent tumors were treated with surgery in 5 cases, radiotherapy in 2 cases, and chemotherapy in 9 cases. The initial FDG-PET examinations revealed that 13 cases had positive and 5 cases had negative findings, which included 2 false positive cases. The survival rate for all patients at 1 year and 2 years after the initial examination was 82% and 63%, respectively. Two-year survival rates in patients with positive and negative FDG-PET findings were 51% and 83%, respectively, and the difference was not statistically significant (p = 0.19). Furthermore, 4 patients with normal CA-125 levels and 14 patients with elevated CA-125 levels showed 2-year survival rates of 100% and 51%, respectively, and they were not significantly different (p = 0.11). For all 32 examinations, the 2-year survival rates for patients with normal CA-125 levels (100%) were significantly higher (p = 0.025) than that for patients with elevated CA-125 levels (47%), however there was no significant difference (p = 0.20) between FDG-PET positive cases (53%) and negative cases (83%). CONCLUSION The prognosis of patients with positive FDG-PET findings was less favorable than that of patients with negative findings. However, over the mean extended observation period of about 2.5 years, no significant difference in the prognosis of patients was observed between the two groups. The results of the present study indicate that elevated serum CA-125 levels may be more useful for evaluating the prognosis of ovarian cancer during the post-operative follow-up than FDG-PET findings.


Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease.
In the gastrointestinal neural system, the emergence of Lewy Body (LB) is usually earlier than the clinical diagnosis of Parkinson (PD) motor symptoms. Therefore, this study is aimed to explore whether the LB in the gastrointestinal tract of prodromal PD patients. 98 paraffin embedded tissue specimens from 57 PD patients were collected in the Second Affiliated Hospital of Soochow University archives, as well as 98 tissue specimens of 90 non-PD patients undergone surgical resection. The pathological sections were stained by the immune-histochemistry method. The positive staining of aggregated a-Synuclein (a-a-syn) and phosphorylated a-Synuclein (p-a-syn) in gastrointestinal tract were counted to analyze the distribution of the expression of a/p-a-syn in the prodromal PD patients before diagnosis (0-5 years, 6-10 years, 11-20 years). According to results from the immunohistochemical staining of a/p-α-syn, 35 (52.23%) and 30 (44.78%) tissue blocks were positively stained respectively in total 67 tissue blocks provided from 39 prodromal PD patients. And there were 46 (46.94%) and 25 (25.51%) positive staining in 98 tissue blocks from the control group. In 31 tissue blocks collected from 18 PD patients, there were 19 (61.29%) and 15 (48.39%) tissue blocks with the a/p-a-syn positive staining. Compared with non-PD patients from the control group, the a-a-syn positive rate was not significantly increased in the pre- and post-diagnosis PD patients (p>0.05). However, p-a-syn of both groups increased significantly (p<0.05). Also, the positive expression rate of a/p-a-syn in the 6-10-year group was lower than that in the 0-5-year and 11-20-year, and the positive rate of the 0-5-year group was the highest (p<0.05). p-a-syn as the main component of Lewy body of nervous system in the gastrointestinal track may be used as a characteristic predictive marker of PD and the prevention of PD disease.


Neonatal myotonic dystrophy as a cause of hydramnios and neonatal death. A case report and literature review.
A woman had three consecutive pregnancies complicated by hydramnios and early neonatal death. The identical prenatal and neonatal course, family history and, ultimately, maternal diagnosis supported the diagnosis of recurrent severe neonatal myotonic dystrophy. Ultrasonographic observation of the last fetus affected suggested and predicted the neonatal features of the disease.


Health risk assessment of heavy metals in marine fish to the population in Zhejiang, China.
Environmental pollution with toxic metals can lead to the possible contamination of the marine fish. We investigated the levels of As, Cd, Cr, Hg and Pb in 652 marine fish samples (15 species) collected from coastal areas of Zhejiang, China and estimated their health risk. Mean concentrations of As, Cd, Cr, Hg and Pb were 0.783, 0.009, 0.114, 0.031, 0.043 mg/kg wet weight. The average estimated daily intakes (EDIs) for As, Cd, Cr, Hg and Pb were 1.214, 0.014, 0.177, 0.048 and 0.067 μg/kg bw/day. The risk assessment at mean exposure level showed that there was no health risk associated with these elements through consumption of marine fish. However, potential health risk may exist for high exposure consumers considering the possible contamination of As and Hg. Given that the different levels of certain elements in marine fish in China, this study provides a scientific basis for food safety assessment and suggestions for risk management.


Eta polycaprolactone (ε-PCL) implants appear to cause a partial differentiation of breast cancer lung metastasis in a murine model.
Cells in every epithelium can be roughly divided in three compartments: stem cell (SC) compartment, transient amplifying cell (TA) compartment and terminally differentiated (TD) compartment. Maturation of stem cells is characterized by epithelial stromal interaction and sequential maturational movement of stem cell's progeny through those compartments. In this work we hypothesize that providing an artificial stroma, which murine breast cancer metastatic cells can infiltrate, will induce their differentiation. BALB/c female mice were injected with 106 isogenic 4T1 breast cancer cells labeled with GFP. After 20 days primary tumors were removed, and artificial ε-PCL implants were implanted on the contralateral side. After 10 more days mice were sacrificed and implants along with lung tissue were harvested. Mice were divided in four groups: tumor removal with sham implantation surgery (n = 5), tumor removal with ε-PCL implant (n = 5), tumor removal with VEGF enriched ε-PCL implant (n = 7) and mice without tumor with VEGF enriched ε-PCL implant (n = 3). Differentiational status of GFP + cells was assessed by Ki67 and activated caspase 3 expression, thus dividing the population in SC like cells (Ki67+/dim aCasp3-), TA like cells (Ki67+/dim aCasp3+/dim) and TD like cells (Ki67- aCasp3+/dim) on flow cytometry. Lung metastatic load was reduced by 33% in mice with simple ε-PCL implant when compared to tumor bearing group with no implant. Mice with VEGF enriched implants had 108% increase in lung metastatic load in comparison to tumor bearing mice with no implants. Likewise, amount of GFP + cells was higher in simple ε-PCL implant in comparison to VEGF enriched implants. Differentiation-wise, process of metastasizing to lungs reduces the average fraction of SC like cells when compared to primary tumor. This effect is made more uniform by both kinds of ε-PCL implants. The opposite process is mirrored in TA like cells compartment when it comes to averages. Effects of both types of implants on TD like cells were negligible. Furthermore, if gene expression signatures that mimic tissue compartments are analyzed in human breast cancer metastases, it turns out that TA signature is associated with increased survival probability. ε-PCL implants without VEGF can reduce metastatic loads in lungs, after primary tumor removal. Both types of implants cause lung metastasis differentiation by shifting cancer cells from SC to TA compartment, leaving the TD compartment unaffected.


The evolution of cytoplasmic incompatibility or when spite can be successful.
It is proposed that the phenomena of cytoplasmic incompatibility is explicable in terms of the selfish interests of the prokaryotic symbionts associated with the phenomena. It is hypothesized that in males the symbionts produce a product, termed wolbachin, which is carried in sperm and has the capability of inhibiting zygotic development if not neutralized. Symbionts are capable of neutralizing wolbachin. If this is the correct mechanism then the symbionts by killing eggs incapable of neutralizing wolbachin are acting spitefully. A simple model demonstrates that spiteful symbionts can invade a population of non-spiteful symbionts. The resulting population of spiteful symbionts is capable of resisting invasion by other spiteful symbionts even if the invaders have more efficient vertical transmission. Spite is successful in this system because all of the costs of being spiteful are inflicted on the host and not on the symbionts. This is in contrast to other systems of spite.


JENNIFER M. BOSCO ANGELA CHUANG (2018) A new species of grass spider, Agelenopsis riechertii, from the Southwestern USA, with notes on its courtship behavior (Araneae: Agelenidae). Zootaxa, 4442: 579-583.
We made changes in the description of a new Agelenopsis spider species, Agelenopsis riechertae. Firstly, we declare the male holotype and a type repository to validate the species description, which was previously omitted. The original Latin name has been feminized from Agelenopsis riechertii to Agelenopsis riechertae.


Dengue and hantavirus coinfection with good outcomes: a clinical case from Panama.
Dengue and hantavirus are endemic in central Panama. We present a case report of a patient coinfected with dengue and hantavirus who presented overlapping clinical manifestations of both infections. The patient did not require intensive care-as it is commonplace during hantavirus pulmonary syndrome-and he had a good outcome. Patient's care was positively impacted due to correct diagnosis of coinfection. This case highlights that in endemic areas, coinfection with dengue virus and hantavirus should be suspected. To the best of our knowledge, this case is the first documented case of coinfection with dengue virus and hantavirus in Central America.


cT1N0M0 Esophageal Squamous Cell Carcinoma Invades the Muscularis Mucosa or Submucosa: Comparison of the Results of Endoscopic Submucosal Dissection and Esophagectomy.
Endoscopic submucosal dissection (ESD) combined with selective adjuvant chemoradiotherapy may be a new treatment option for cT1N0M0 esophageal squamous cell carcinoma (ESCC) invading muscularis mucosa or submucosa (pT1a-M3/pT1b). We aim to report the effectiveness of this treatment by comparing the results of esophagectomy. This retrospective single-center study included 72 patients with pT1a-M3/pT1b ESCC who received ESD combined with selective adjuvant chemoradiotherapy (n = 40) and esophagectomy (n = 32). The main outcome comparison was overall survival (OS). The secondary outcomes were treatment-related events, including operation time, complication rate, and length of hospital stay. Disease-specific survival (DSS) and progression-free survival (PFS) were also evaluated. There were no significant differences in the rates of OS, DSS, and PFS between the two groups (median follow-up time: 49.2 months vs. 50.9 months); these were also the same in the subgroup analysis of pT1b ESCC patients. In the ESD group, the procedure time, overall complication rates, and length of hospital stay were significantly reduced. However, the metachronous recurrence rate was significantly higher. In a multivariate analysis, tumor depth and R0 resection were the independent factors associated with OS. ESD combined with selective adjuvant chemoradiotherapy can be an alternative treatment to esophagectomy for cT1N0M0 ESCC invading muscularis mucosa or submucosa.


[Ureaplasma urealyticum in the male urethra. The assessment of the semiquantitative demonstration as exemplified in men with and without urethritis].
By means of wire-loops, smears were taken from the urethra of 117 male patients suffering from urethritis and of 236 healthy men. Ureaplasma urealyticum (U.u.) was isolated semiquantitatively on A7-medium agar. Large quantities of U.u. were found in 20.5% of the infected patients, but also in 7.6% of the healthy men; plenty of U.u. was isolated in 9.4% of the infected and in 7.2% of the healthy persons. U.u. could not be tracted out in 61% of the males suffering from urethritis and in 75.4% of those not infected. According to our findings, semiquantitative isolation of U.u. does not infer the etiopathogenetical role of U.u. in every single case. In addition, a broad spectrum of microbials, e.g. chlamydia trachomatis has to be excluded in order to be able to recognize U.u. as the cause for urethritis after successful antimicrobial therapy.


Effect of Nissen fundoplication on the lower esophageal sphincter pressure of children with gastroesophageal reflux.
Nine children (age range, 5 weeks to 13 years) with gastroesophageal reflux unresponsive to medical management were evaluated with esophageal manometry studies before and after Nissen fundoplications were performed. All patients had a postoperative increase in lower esophageal sphincter (LES) pressure. The mean preoperative LES pressure was 11.3 mm Hg and the mean postoperative pressure was 22.3 mm Hg. The mean LES pressure increase after surgery was 10.9 mm Hg (range: 5.3 to 22.5 mm Hg). All patients ceased vomiting immediately after surgery and have gained weight at a rate greater than that expected for their age.


The survivors of childhood solid tumors.
With the improvement in cancer therapy in recent years, the number of cancer survivors is rapidly increasing. Potential late medical and psychosocial sequelae of cancer therapy are reviewed. A practical guide for the primary health care giver is provided.


Randomized controlled trials of traditional, complementary, and integrative medicine-based interventions for coronavirus disease 2019 (COVID-19): A bibliometric analysis and review of study designs.
To date, the coronavirus disease 2019 (COVID-19) pandemic remains ongoing and continues to affect millions of people worldwide. In the effort of fighting this pandemic, there has been an increasing interest in the potential of traditional, complementary, and integrative medicines (TCIMs) in engaging COVID-19. This study presents a bibliometric analysis of the research trends of TCIMs for COVID-19. Six databases were searched on July 15, 2021, to retrieve all the citations on TCIM-focused randomized controlled trials (RCTs) available on COVID-19. Only RCTs that mentioned at least one TCIMs for the treatment and/or management or COVID-19 were eligible. Data such as number and countries of trials conducted, publication journal, research focus, study design, and sample size were extracted for analysis. The resulting 56 articles were authored by 553 unique authors, and included 28 English articles, 19 Chinese articles with English abstracts, and 9 Chinese articles without English abstract. Analyses had shown that China was the dominant country with TCIM related RCT publications, followed by India and the United States. The included articles were published across 24 English journals and 22 Chinese journals with a wide range of impact factors from 0.220 to 56.272. The most commonly studied TCIM modalities included Chinese herbal decoction (n=12) and Chinese patent medicine (n=16). In terms of study designs, TCIM interventions were integrated with standard medicine across the trials with most trials having a small to medium sample size and open-labeled. This bibliometric analysis of RCTs demonstrated the research trends and characteristics of TCIM utilized in COVID-19 research. Although there are still many research gaps and limitations for pandemic research, the publication of TCIM-focused RCTs is anticipated to show a continuously increasing trend.


Doppler echocardiographic assessment of changes in pulmonary artery pressure associated with vasodilating therapy in patients with congestive heart failure.
Transpulmonic pressure gradient and pulmonary artery pressures can be estimated from the Doppler pulmonary regurgitant flow velocities by applying the simplified Bernoulli equation. In this study, continuous-wave Doppler echocardiography was used to assess changes in pulmonary regurgitant flow velocities associated with administration of vasodilators in 10 patients with congestive heart failure. M-Mode echocardiographic parameters such as left ventricular end-systolic and end-diastolic dimension and fractional shortening did not change with administration of vasodilators. Pulmonary regurgitant flow velocity at end diastole decreased from 1.9 +/- 0.6 to 1.3 +/- 0.3 m/sec (p less than 0.01), and Doppler-estimated transpulmonic pressure gradient at end diastole decreased from 16 +/- 11 to 8 +/- 4 mm Hg (p less than 0.01). Doppler-estimated transpulmonic pressure gradient at end diastole was compared with catheterization-determined pulmonary arterial end-diastolic pressure before and after administration of vasodilators in three patients, and there was a good agreement between these measurements. Thus noninvasive and sensitive assessment of the effect of vasodilators on pulmonary arterial end-diastolic pressure in patients with congestive heart failure is possible with continuous-wave Doppler echocardiographic measurement of pulmonary regurgitant flow velocities.


Spatial Scale Effects of the Relationship between Fractional Vegetation Coverage and Land Surface Temperature in Horqin Sandy Land, North China.
Sandy range land refers to a major component of grassland area types in the semi-arid area of northern China. Monitoring of vegetation and land surface temperature (LST) using remote sensing technology can help determine the degree of desertification in a regional and/or sub regional scale, as in the Horqin Sandy Land selected in this study. Correlation analysis was performed to examine the relationship between the fractional vegetation coverage (FVC) and the LST within one growing season (from May to August 2017), at different spatial scales. The results showed that the FVC increased from 0.12 in May to 0.29 in August, and the LST increased first and then declined. The highest LST was 41.68 °C in July, while the lowest was 28.62 °C in August. At the grid scale, the LST increased first and then declined with the increase of the FVC on 25 May, 10 June, and 29 August; the FVC ranged from 0.29-0.38, 0.27-0.32, and 0.29-0.38 with the preference of the 'turning point', respectively. A negative correlation was identified between the FVC and the LST and without any 'turning point' in the fitting curve on 28 July. The correlation between FVC and LST complied with the grid scale at the sample area scale. The coupling analysis of landscape pattern expressed by FVC and LST showed that, the landscape evenness, Euclidean nearest neighbor distance, and landscape splitting degree all showed strong coupling correlation in any study period (P). The landscape aggregation of FVC and LST showed a good coupling at the relatively high and low air temperature conditions of P1 and P3. Landscape contagion showed a good coupling between FVC and LST at relatively moderate air temperature condition of P1 and P4. Air temperature conditions and characteristics of vegetation coverage should be considered for a more targeted analysis when analyzing the relationship between FVC and LST and attention should be paid to the timing and type of study area in practical application.


Effects of Chinese medicine shen-fu injection on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model.
To investigate the action of Shen-Fu Injection (SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation. Thirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC. Serum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation through 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups. SFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.


Candy twists as an alternative to the glucola beverage in gestational diabetes mellitus screening.
Screening for gestational diabetes mellitus commonly uses an oral glucose challenge test with a 50-g glucola beverage and subsequent venous puncture. However, up to 30% of pregnant women report significant side-effects, and the beverage is costly. We hypothesized that equivalent glucose loads could be achieved from a popular candy twist (Twizzlers; The Hershey Company, Hershey, PA) and tested it as cost-effective, tolerable alternative with a test of equivalency. The glucose equivalent of the 50-g glucola was calculated as 10 candy twists. We initially used a triple crossover design in nonpregnant patients whereby each subject served as her own control; this ensured the safety and equivalency of this load before using it among pregnant subjects. We then recruited pregnant women with an abnormal screening at 1 hour (glucose challenge test) in a double crossover design study. Subjects consumed 10 candy twists with a 1-hour venous blood glucose assessment. All subjects subsequently completed the confirmatory 3-hour glucose tolerance test. Sensitivity, specificity, positive predictive values, negative predictive values, false-referral rates, and detection rates were calculated. At ≥130 mg/dL, the sensitivity (100%) was the same for candy twists and glucola. However, the false-referral rate (82% vs 90%), positive predictive value (18% vs 10%), and detection rate (18% vs 10%) were improved for candy twists when compared with the 50-g glucola beverage. Our results indicate that strawberry-flavored candy twists are potentially an equally effective screening test, compared with the gold standard glucola beverage but lead to fewer false-positive screens and therefore could be a cost-effective alternative.


Omega-3 fatty acids for the treatment of depressive disorders in children and adolescents: a meta-analysis of randomized placebo-controlled trials.
To investigate the efficacy and safety of omega-3 fatty acids (O3FA) in treating depressive disorders in children and adolescents. We conducted a comprehensive search in electronic databases and hand-searched articles included for relevant studies. We included randomized controlled trials which studied on O3FA for treatment of children and adolescents with depression. The standard mean differences (SMDs) and the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by a random-effects model. The primary outcomes were end-point depressive symptoms scores (efficacy) and all-cause discontinuation (safety). The secondary outcome of response rate was also assessed. Subgroup analyses were performed by age, severity of depression and dosage. Risk of bias assessment was performed based on the Jadad score and the Cochrane Collaboration's risk-of-bias method. A total of four studies with 153 participants were included. In terms of efficacy, there was no significant difference of end-point depressive symptoms scores between O3FA and placebo (SMD = - 0.12, 95% CI - 0.53 to 0.30, P = 0.58; I 2= 30%). In terms of safety, the all-cause discontinuation showed no statistical significance between O3FA and placebo (OR = 1.3, 95% CI 0.58 to 2.93, P = 0.53; I 2= 0%). The response rate of O3FA was also not significant better than that of placebo (OR = 1.57, 95% CI 0.26 to 9.39, P = 0.62; I 2= 71%). Besides, there were also no significant differences in those subgroup analyses outcomes. The risk of bias of included trials were not high. Only considering the limited evidence of O3FA in the acute treatment of major depressive disorder, it did not seem to offer a clear advantage for children and adolescents.


Bacterial metal nanoparticles to develop new weapons against bacterial biofilms and infections.
The widespread use of antibiotics has resulted in the outbreak and spread of antibiotic-resistant pathogens. Bacterial antibiotic resistance may develop at cellular and community levels. In the latter case, it is based on tolerance which implicates the shift from a free-living form of life (i.e., planktonic) to a sessile multi-stratified community (i.e., biofilm). Metal nanoparticles (MNPs) have been shown to be promising candidates as antimicrobial agents. MNPs are able to interact with and penetrate bacterial biofilms, thus, resulting effective antibiofilm compounds. Another interesting aspect is the possibility of using plants, fungi, yeasts, and bacteria to obtain biogenic MNPs (BMNP). Bacteria are able to grow in presence of many different toxic heavy metal ions thanks to different metal resistance gene clusters that allow a variety of biochemical counters (formation of harmless complexes, efflux, precipitation, reduction, etc.). The formation of BMNPs by bacterial cells could be, in most cases, just a consequence of metal detoxification mechanisms. This review focuses on BMNPs from bacterial origin that may represent a good source of compounds with a broad spectrum of activity against common Gram-positive and Gram-negative pathogens and bacterial biofilms thereof. In particular, the state of art on BMNP synthesis by bacteria is presented and potential applications in the fight against biofilm-associated infections and resistant pathogens are highlighted. In addition, critical aspects on BMNP bacterial synthesis and utilization are commented.Key points• New antimicrobials to fight antibiotic-resistant pathogens are urgently needed.• Biogenic metal nanoparticles can efficiently hit biofilm-forming pathogens.• Metal-nanoparticle composition could confer specific antibiofilm activity.


Survival of Mycobacterium tuberculosis organisms for 8 days in fresh lung tissue from an exhumed body.
Mycobacterium tuberculosis was isolated from the lung tissue of an 86-year-old unembalmed woman who was exhumed for an autopsy 8 days after her death. Autopsy prosectors should consider performing microbiological culture in all cases with a history or gross pathological findings suggestive of an infection even if the postmortem interval is extended. In addition, prosectors should still adhere to biosafety precautions for airborne pathogens, because a long postmortem interval does not necessarily provide assurance that these organisms are not viable.


Small supraspinatus tears repaired by arthroscopy: are clinical results influenced by the integrity of the cuff after two years? Functional and anatomic results of forty-six consecutive cases.
We assessed cuff integrity after arthroscopic repair of small full-thickness supraspinatus tears (<2 cm) and the correlation with clinical results and predisposing factors for recurrence. We hypothesized that clinical results depend on tendon healing, which is obtained in almost all cases. The study included 46 small supraspinatus tears in 46 patients. Mean age was 56.8 years (range, 39-75 years). Preoperative and postoperative functions were assessed by the Constant-Murley (CM) score. The integrity of the repair was evaluated by ultrasonography. The average follow-up was 35 months (range, 24-60 months). The mean absolute CM score improved significantly (P < .001) from 46.8 points (range, 34-62 points) preoperatively to 76 (range, 51-98) at the last follow-up. The result was excellent or good in 76.1%, and 42 (91.3%) were subjectively very satisfied or satisfied with the final result. The supraspinatus was completely healed on imaging studies in 33 patients (71.8%). The presence of an intratendinous cleavage of the supraspinatus was the only factor associated with a postoperative rerupture (P = .044). There was no association between functional and anatomic results. Arthroscopic repair of small supraspinatus tears yields favorable clinical and anatomic results at a mean of 35 months after surgery. Retearing is relatively common, but has no effect on the clinical result except that patients with radiographic signs of tendon healing appear to have increased postoperative ability to perform activities of daily living (P = .022). An intratendinous cleavage is the only significant predisposing factor for recurrence.


Fingerprint comparison. II: On the development of a single fingerprint filing and searching system.
A FORTRAN program has been written to compare the minutiae coded in an"unknown" fingerprint with the minutiae of fingerprints stored in a data base. The criteria for matching are scores based on the type and number of minutiae matched. Minutiae of low relative frequency have higher scoring weights than those that are more common. The matching mechanism is tested by using a fingerprint coded several times, first by a single individual and then by six other individuals who have no previous knowledge about fingerprints. These tests yield satisfactory results.


Trace element studies in Karachi populations. Part III: Blood copper, zinc, magnesium and lead levels in psychiatric patients with disturbed behaviour.
Blood levels of copper, zinc, magnesium and lead were determined in 29 males and 15 females suffering from disturbed behaviour. As far as we could ascertain they were under no medication and belonged to low income groups. Male patients had significantly higher levels than female patients for zinc (0.05 greater than P greater than 0.01) but there was no sexual difference for magnesium or copper. In patients copper and lead levels were higher than for normals (P less than 0.01), but no difference could be found for Mg and Zn. At least one metal abnormality was observed in 19 (65.5%) of the males and 9 (60.0%) of the female patients.


Bilateral lesions of suprachiasmatic nucleus eliminate circadian rhythms of oxygen consumption and the respiratory quotient in rats.
Bilateral lesions of the suprachiasmatic nucleus of the hypothalamus of rats abolished circadian rhythms of oxygen consumption and of the respiratory quotient (RQ). The RQ remained constant at a level intermediate between the maximum (about 1.0) and minimum (about 0.9) values in control animals.


[Shoulder dystocia].
In the increasing number of plaintiffs against mal-practice shoulder dystocia and plexus paralysis take a special role. Legal decisions are leaning too one-sided on statistical experience of childrens weight. But form and diameter of the pelvis should also be considered and better registered in medical record. A catalog of risks is given to prevent obstetrical cause of shoulder dystocia and plexus paralysis. The paper refers to the social and psychological change in which the child-parents must have more right to decide between cesarean section or vaginal delivery to prevent injury of the baby.


A comparative analysis of the toxicity of eight common soil contaminants and their effects on drought tolerance in the collembolan Folsomia candida.
Previous exposure to contaminants can increase the susceptibility to drought stress in soil invertebrates. In the present study, the effects of eight common environmental contaminants on drought tolerance and reproduction were investigated using the collembolan Folsomia candida as a model organism. Four classes of chemicals were considered: polycyclic aromatic hydrocarbons (pyrene and fluorene), detergents (linear alkylbenzene sulfonate (LAS) and nonylphenol), insecticides (dimethoate and cypermethrin), and heavy metals (copper and cadmium). Previous exposure to nonylphenol, pyrene, and fluorene had significant effects on drought tolerance. LAS had a weak effect on drought tolerance, whereas the remaining chemicals had no such effects even at concentrations at which reproduction was considerably reduced. Reproduction and adult survival in F. candida were equally sensitive to dimethoate. However, for all other chemicals, reproduction was a considerably more sensitive parameter than adult survival. The results suggest that toxicants whose effects are associated with cell membrane function are the most potent with respect to effect on drought tolerance.


Appropriate radiation volume for stage IIA/B testicular seminoma.
Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution. Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (+/- contralateral) pelvic lymph nodes (dose: 25-35 Gy). With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged. Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only.


Hydrogel-coated needles prevent puncture site bleeding.
Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation. A hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate was coated onto the surface of suture needles. Needles were observed using scanning electronic microscopy (SEM) and immunofluorescence. Cannulation was performed in both mouse and rat models; the liver, kidney, jugular vein, inferior vena cava and aorta were punctured using uncoated and hydrogel-coated needles. Needles coated with a hydrogel with and without CD34 antibody were used to puncture the rat jugular vein and aorta. Tissues were examined by histology and immunofluorescence. The hydrogel was successfully coated onto the surface of 22G and 30G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after cannulation of the liver, kidney, jugular vein, inferior vena cava and aorta. Hydrogel-coated needles that contained CD34 antibody attracted vascular progenitor cells near the puncture site; there were fewer M1-type macrophages and more M2-type macrophages. Hydrogel-coated needles can effectively and rapidly stop puncture-site bleeding. The hydrogel that contains CD34 antibody attracted vascular progenitor cells, potentially promoting healing of the site after cannulation. Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm and remains a significant clinical problem. We developed a hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate; hydrogel-coated needles effectively and rapidly stopped bleeding after vascular cannulation. Interestingly, the hydrogel can also serve as a carrier for drugs that are delivered to the puncture site during the short time of cannulation that could additionally promote puncture site healing. Hydrogel-coated needles may be a new method for rapid hemostasis with application to patients especially at risk for bleeding.


Structural basis for plazomicin antibiotic action and resistance.
The approval of plazomicin broadened the clinical library of aminoglycosides available for use against emerging bacterial pathogens. Contrarily to other aminoglycosides, resistance to plazomicin is limited; still, instances of resistance have been reported in clinical settings. Here, we present structural insights into the mechanism of plazomicin action and the mechanisms of clinical resistance. The structural data reveal that plazomicin exclusively binds to the 16S ribosomal A site, where it likely interferes with the fidelity of mRNA translation. The unique extensions to the core aminoglycoside scaffold incorporated into the structure of plazomicin do not interfere with ribosome binding, which is analogously seen in the binding of this antibiotic to the AAC(2')-Ia resistance enzyme. The data provides a structural rationale for resistance conferred by drug acetylation and ribosome methylation, i.e., the two mechanisms of resistance observed clinically. Finally, the crystal structures of plazomicin in complex with both its target and the clinically relevant resistance factor provide a roadmap for next-generation drug development that aims to ameliorate the impact of antibiotic resistance.


Environmental correlates of sedentary behaviors and physical activity in Chinese preschool children: A cross-sectional study.
This cross-sectional study examined environmental correlates of sedentary behavior (SB) and physical activity (PA) in preschool children in the urban area of Tianjin, China. Data were collected from the Physical Activity and Health in Tianjin Chinese Children study, involving healthy children 3-6 years old and their families. In all children (n = 980), leisure-time SB (LTSB) and leisure-time PA (LTPA) were reported in min/day by parents. In a subgroup (n = 134), overall sedentary time, light PA, and moderate-to-vigorous PA (MVPA) were objectively measured using ActiGraph accelerometry (≥3 days, ≥10 h/day). Environmental correlates were collected using a questionnaire that included home and neighborhood characteristics (e.g., traffic safety, presence of physical activity facilities) and children's behaviors. Potential correlates were identified using linear regression analysis. Multiple linear regression analysis showed that "having grandparents as primary caregivers" (βs and 95% confidence intervals (95%CIs) for overall sedentary time: 29.7 (2.1-57.2); LTSB (ln): 0.19 (0.11-0.28)) and "having a television (for LTSB (ln): 0.13 (0.00-0.25)) or computer (for LTSB (ln): 0.13 (0.03-0.23)) in the child's bedroom" were both associated with higher SB. Furthermore, "having grandparents as primary caregivers" was associated with less MVPA (β (95%CI): -7.6 (-14.1 to -1.2)), and "active commuting to school by walking" correlated with more MVPA (β (95%CI): 9.8 (2.2-17.4)). The path model showed that "more neighborhood PA facilities close to home" was indirectly related to higher LTPA (ln), which was partly mediated by "outdoor play" (path coefficients (95%CI): 0.005 (0.002-0.008)) and "going to these facilities more often" (path coefficients (95%CI): 0.013 (0.008-0.018)). Traffic safety was not a correlate. Family structure and media exposure in the home maybe important factors in shaping preschoolers' PA patterns. Built environmental correlates could indirectly influence preschoolers' LTPA through parental help with engaging in active behaviors.


[Plastic surgery of lower lip defects (author's transl)].
A modification of the Hertig method for reconstruction of the lower lip is reported. The method is suitable for repair of lateral defects of the lower lip, and was performed in 10 patients. The procedure is technically simple to perform, and yeilds good functional and cosmetic results.


Preoperative heart rate variability analysis is as a potential simple and easy measure for predicting perioperative delirium in esophageal surgery.
Delirium is one of the most common but severe perioperative complications. Autonomic activity evaluated by heart rate variability (HRV) has been recently reported as a useful tool for prediction and for early detection of delirium in acute care medicine, especially in postoperative intensive care unit (ICU) patients. We hypothesized that HRV, by 3-lead electrocardiogram (ECG), one day prior to surgery might correlate with the presence of postoperative delirium. This study was cohort prospective pilot study. We measured preoperative HRV and postoperative delirium in patients who underwent surgery for elective esophageal cancer. ECG of the participants was performed for 10 min 6-12 h preceding surgery. Postoperatively, patients were admitted to the ICU or critical care unit and stayed for at least 3 days. Delirium was diagnosed by psychiatrist rounds twice a day. Delirium was assessed for 3 days after surgery and 30 patients performed the study. Seven patients developed delirium during their ICU stay, while the remaining twenty-three did not. After HRV analysis, the preoperative high frequency power in delirium patients was significantly lower than that in non-delirium patient. Other parameters of HRV, including lower frequency power, total power and the ratio showed no statistically significant difference between the groups. The results of current study demonstrated that preoperative measurement of HRV may be a useful predictor of delirium. Further investigation could pave the way to a non-invasive, minimally stressful method of predicting postoperative delirium.


The Intrinsic Enzyme Activities of the Classic Polyoxometalates.
The mimicking enzyme activities of eighteen classic POMs with different structures, Keggin (H3PW12O40, H4SiW12O40, H4GeW12O40, K4GeW12O40, H3PMo12O40, H4SiMo12O40 and Eu3PMo12O40), Wells-Dawson (H6P2Mo18O62, α-(NH4)6P2W18O62 and α-K6P2W18O62·14H2O), lacunary-Keggin (Na8H[α-PW9O34], Na10[α-SiW9O34], Na10[α-GeW9O34] and K8[γ-SiW10O36]), the transition-metal substituted-type (α-1,2,3-K6H[SiW9V3O34] and H5PMo10V2O40), sandwich-type (K10P2W18Fe4(H2O)2O68) and an isopolyoxotungstate (Na10H2W12O42) were screened and compared. The mechanisms and reaction conditions of POMs with mimicking enzyme-like activities were also analyzed. The results shown that the structures, the hybrid atoms, the coordination atoms, the substituted metal atoms, pH and substrate are the effect factors for the enzyme mimic activities of POM. Among the eighteen POMs, H3PW12O40, H4SiW12O40, H4GeW12O40, α-(NH4)6P2W18O62, α-K6P2W18O62·14H2O, Na8H[α-PW9O34], Na10[α-SiW9O34], Na10[α-GeW9O34], K8[γ-SiW10O36], K10P2W18Fe4(H2O)2O68 and Na10H2W12O42 had the peroxidase activities. Eu3PMo12O40, H3PMo12O40, H4SiMo12O40, α-1,2,3-K6H [SiW9V3O34], H6P2Mo18O62 and H5PMo10V2O40 showed the oxidase-like activities. K4GeW12O40 did not show the peroxidase and oxidase activities. The Na8H[α-PW9O34], Na10[α-SiW9O34] and Na10[α-GeW9O34] showed intrinsic enzyme activities at alkaline conditions, which were different from other type of POMs. The sandwich-type K10P2W18Fe4(H2O)2O68 displayed the strongest peroxidase activity, which is similar to natural horseradish peroxidase.


Cost effectiveness of percutaneous closure versus medical therapy for cryptogenic stroke in patients with a patent foramen ovale.
In patients with patent foramen ovales (PFOs) and cryptogenic stroke, observational studies have demonstrated reductions in recurrent neurologic events with transcatheter PFO closure compared with medical therapy. Randomized controlled trials and meta-analyses have shown a trend toward benefit with device closure. The cost-effectiveness of PFO closure has not been described. Therefore, a detailed cost analysis was performed using pooled weighted outcome and complication rates from published randomized controlled trials, Medicare cost tables, and wholesale medication prices. Incremental cost per life-year gained and per quality-adjusted life-year (QALY) gained by PFO closure was calculated. The commonly accepted cost-effectiveness threshold of <$50,000/quality-adjusted life-year gained was used. At 2.6 years (the mean duration of randomized controlled trial follow-up), PFO closure was more costly ($16,213, 95% confidence interval [CI] $15,753 to $16,749) per patient, with a cost of $103,607 (95% CI $5,826 to $2,544,750) per life-year gained. The expenditure to prevent 1 combined end point (transient ischemic attack, stroke, and death) at 2.6 years was $1.09 million (95% CI $1.04 million to $1.20 million). Modeling the costs of medical treatment prospectively, PFO closure reached cost-effectiveness (<$50,000/quality-adjusted life-year gained) at 2.6 years (95% CI 1.5 to 44.2). At 30.2 years (95% CI 28.2 to 36.2), the per patient mean cost of medical therapy exceeded that of PFO closure. In conclusion, PFO closure is associated with higher expenditures related to procedural costs; however, this increase may be offset over time by reduced event rates and costs of long-term medical treatment in patients who undergo transcatheter PFO closure. In younger patients typical of cryptogenic stroke, PFO closure may be cost effective in the long term.


Gender differences in information and communication technology use & skills: a systematic review and meta-analysis.
Even though information and communication technology (ICT) is essential for everyday life and has gained considerable attention in education and other sectors, it also carries individual differences in its use and relevant skills. This systematic review aims to examine the gender differences in ICT use and skills for learning through technology. A comprehensive search of eight journal databases and a specific selection criterion was carried out to exclude articles that match our stated exclusion criteria. We included 42 peer-reviewed empirical publications and conference proceedings published between 2006 and 2020. For a subsample of studies, we performed a small-scale meta-analysis to quantify possible gender differences in ICT use and skills. A random-effects model uncovered a small and positive, yet not significant, effect size in favor of boys (g = 0.17, 95% CI [-0.01, 0.36]). However, this finding needs to be further backed by large-scale meta-analyses, including more study samples and a broader set of ICT use and skills measures. We highlight several concerns that should be addressed and more thoroughly in collaboration with one another to better IT skills and inspire new policies to increase the quality of ICT use. The findings from this review further suggest implications and present existing research challenges and point to future research directions.


Longitudinal Prediction of Transplant-Free Survival by Echocardiography in Pediatric Dilated Cardiomyopathy.
The prognostic significance of serial echocardiography and its rate of change in children with dilated cardiomyopathy (DCM) is incompletely defined. We retrospectively analysed up to 4 serial echocardiograms. Associations between mortality/transplant and echocardiographic parameters over time and between outcomes and the rate of change of echocardiographic parameters were analysed. Estimation of patient-specific intercepts and slopes was done using linear regression models. Fifty-seven DCM children were studied (50% male; median age, 0.6 year; average follow-up, 2.1 ± 2.4 years). The median time to transplant or death was 2.0 years. Increased left ventricular (LV) diastolic (LVEDD) and systolic (LVESD) dimensions and myocardial performance index (MPI) were associated with increased mortality and transplant risk. Increased LV ejection fraction, mitral E-deceleration time, right ventricular (RV) fractional area change, and tricuspid annular plane systolic excursion were associated with reduced mortality and transplant risk. Transplant/mortality likelihood increased by 41.6% and 19.8% for each unit increase in LVEDD and LVESD z scores, respectively (LVEDD: hazard ratio [HR], 1.416; 95% confidence interval [CI], 1.285-1.560; P < 0.001; LVESD: HR, 1.198; 95% CI, 1.147-1.251; P < 0.001). A higher monthly change in LVESD z score increased transplant/mortality likelihood by 85.6% (HR, 1.856; 95% CI, 1.572-2.191; P = 0.015). Greater changes in mitral E/e' (HR, 0.707; 95% CI, 0.636-0.786; P < 0.001) and RV MPI (HR, 0.412; 95% CI, 0.277-0.613; P < 0.001) were associated with reduced mortality and transplant risk. LV and RV systolic and diastolic dimensions and function over time and their rate of change are associated with risk for transplant and mortality in childhood DCM. Serial changes in these parameters may be useful to predict clinical outcomes.


Determination of base pairing in ribonucleic acid by Fourier-transform infrared spectrometry: yeast ribosomal 5S ribonucleic acid.
Fourier-transform infrared (FT-IR) spectra of yeast ribosomal 5S RNA have been acquired at several temperatures between 30 and 90 degrees C. The difference spectrum between 90 (bases unstacked) and 30 degrees C (bases stacked) provides a measure of base stacking in the RNA. Calibration difference spectra corresponding to stacking of G-C or A-U pairs are obtained from "reference" FT-IR spectra of poly(rG) X poly(rC) minus 5'-GMP and 5'-CMP or poly(rA) X poly(rU) minus 5'-AMP and 5'-UMP. The best fit linear combination of the calibration G-C and A-U difference spectra to the 5S RNA (90-30 degrees C) difference spectrum leads to a total of 25 +/- 3 base pairs (17 G-C pairs + 8 A-U pairs) for the native yeast 5S RNA in the absence of Mg2+. In the presence of Mg2+, an additional six base pairs are detected by FT-IR (one G-C and five A-U). FT-IR melting curve midpoints show that A-U and G-C pairs melt together (65 and 63 degrees C) in the presence of Mg2+ but A-U pairs melt before G-C pairs (47 vs. 54 degrees C) in the absence of Mg2+.


Simulated vehicle exhaust exposure induces sex-dependent behavioral deficits in rats.
Chronic exposure to vehicle exhaust emissions are known to cause several adverse health effects. In this study, we examined the impact of several parameters of behavioral, cardiovascular and biochemical functions upon exposure of pro-oxidants CO2, NO2 and CO (simulated vehicle exhaust exposure: SVEE) in male and female rats. Adult rats were subjected to SVEE or ambient air in whole body chambers (5 h/day, 2 weeks). Male, but not female, rats developed memory deficits, and exhibited anxiety- and depression-like behavior, accompanied with significantly high levels of serum corticosterone, oxidative stress, and inflammatory markers (CRP and TNFα), associated with lower levels of total antioxidant capacity, glutathione, glyoxalase and superoxide dismutase (SOD) activities. Brain region-specific downregulation of Cu/Zn SOD, Mn SOD, GSR, PKCα, ERK1/2, CaMKIV, CREB, BDNF and NMDAR subunit protein expression were also observed in male, but not female, rats. Blood pressure, heart rate and eGFR were not negatively impacted by SVEE. Our results suggest that SVEE, through its pro-oxidant content, induces oxido-inflammation in susceptible brain regions in a sex-dependent manner.


Cultivated and Wild Juvenile Thick-Lipped Grey Mullet, Chelon labrosus: A Comparison from a Nutritional Point of View.
The thick-lipped grey mullet (Chelon labrosus) is a nominee fish species for aquaculture diversification in Spain because it is an omnivore and euryhaline species, but limited knowledge about the nutritional attributes of this species is available. This study aimed to characterize the chemical composition of wild and cultured fish. The muscle proximate composition, and fatty acid and amino acid profiles were assessed. The cultivated specimens showed a higher lipid content and lower protein and ash contents compared with the wild specimens. The predominant tissue fatty acids in both the wild and cultivated fish were palmitic acid (16:0), oleic acid (18:1n-9) and docosahexaenoic acid (DHA, 22:6n-3). A higher content of arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (20:5n-3) and DHA were detected in the muscle of wild mullets, while the fish supplied with commercial pellets showed higher quantities of monounsaturated fatty acids, and lower quantities of saturated fatty acids and polyunsaturated fatty acids (PUFAs). Regarding PUFAs, n-3 fatty acids were predominant in wild mullets, while n-6 and n-9 were more abundant in farmed fish. In terms of amino acid composition, except for histidine in wild specimens, the amino acid amounts were higher than the FAO/WHO standard. In conclusion, C. labrosus may contribute to improving the dietary intake of highly polyunsaturated n-3 fatty acids, with a benefit to human health, owing to that fact that a 100-g fillet portion of cultivated and wild C. labrosus can provide 770 mg and 1160 mg of EPA and DHA, respectively, which exceeds the 250 mg dietary daily intake recommended by the FAO/WHO.


Breaking B and T cell tolerance using cationic lipid--DNA complexes (CLDC) as a vaccine adjuvant with hepatitis B virus (HBV) surface antigen in transgenic mice expressing HBV.
Cationic lipid DNA complexes (CLDC), referred to here as JVRS-100, were evaluated as an adjuvant for hepatitis B surface antigen (HBsAg) for eliciting B and T cell responses in transgenic mice expressing hepatitis B virus (HBV). To confirm the immunogenicity of HBsAg+JVRS-1000, a study was conducted in C57BL/6 mice, the genetic background of the HBV transgenic mice used in the study. HBsAg+JVRS-100 elicited a T cell response and B cell response as evidenced by interferon-gamma (IFN-γ) secretion by re-stimulated splenocytes and anti-HBsAg IgG induction, respectively, whereas, HBsAg only elicited a B cell response. In HBV transgenic mice, HBsAg did not elicit either T or B cell responses, unlike the HBsAg+JVRS-100 that elicited both. Energix-B vaccine did perform better than the HBsAg by eliciting a B cell response in the transgenic mice, but it did not perform as HBsAg+JVRS-100 since it did not elicit a T cell response. The response by HBsAg+JVRS-100 was not sufficient to cause destruction of infected liver cells, but it did suppress HBV DNA non-cytolytically. From these results, JVRS-100 might be considered for further development as an adjuvant for HBV therapeutic vaccines.


Involvement of cAMP- and IKK-2-dependent signal pathways in the growth capacity of mesenchymal progenitor cells under the influence of basic fibroblast growth factor.
We studied the role of cAMP- and IKK-2-dependent pathways under conditions of functional stimulation of mesenchymal progenitor cells by basic fibroblast growth factor. An adenylate cyclase inhibitor 2',5'-dideoxyadenosine had no effect on functional activity of early (primitive) mesenchymal precursors. This agent produced a stimulatory effect on proliferation of stromal precursor cells. Mitotic activity of mesenchymal progenitor cells was shown to decrease after treatment with a specific blocker of the IKK-2 kinase-inhibitor complex.


Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis.
Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5-20% for half of the patients if the treatment considered superior by the MS-TDS is used. Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established.


Enantioseparation of underivatised amino acids by ligand exchange capillary electrophoresis in a counter-electroosmotic mode.
Enantiomer separations of underivatised amino acids were carried out by using ligand exchange capillary electrophoresis (LECE). Chiral discrimination is based on the formation of ternary complexes between copper(II), a chiral selector (L-proline or trans-4-hydroxy-L-proline) and an amino acid. All amino acids containing aromatic moieties or not were detected at 214 nm because of their interactions with copper(II). In order to reduce copper(II) adsorption onto capillary walls, we used hexadimethrine bromide to reverse the electroosmotic flow. Using this original strategy, the studied enantiomers migrated in the opposite direction of the anodic electroosmosis. After optimising the analytical conditions taking into account the chiral resolution and the detection sensitivity, we performed very satisfactory enantioseparations not only of aromatic amino acids (tryptophan, tyrosine, phenylalanine and histidine) but also of aliphatic amino acids (threonine, serine, isoleucine and valine). These enantioseparations were performed in a short analysis time at 35 degrees C. In order to rationalise the obtained results, we evaluated the complexation constants corresponding to the formed ternary complexes by capillary electrophoresis and we used molecular mechanics modelling.


TAZ is required for chondrogenesis and skeletal development.
Chondrogenesis is a major contributor to skeletal development and maintenance, as well as bone repair. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key regulator of osteogenesis and adipogenesis, but how TAZ regulates chondrogenesis and skeletal development remains undefined. Here, we found that TAZ expression is gradually increased during chondrogenic differentiation. Deletion of TAZ in chondrocyte lineage impaired articular and growth plate, as well as the bone development in TAZ-deficient mice. Consistently, loss of TAZ impaired fracture healing. Mechanistically, we found that ectopic expression of TAZ markedly promoted chondroprogenitor proliferation, while deletion of TAZ impaired chondrocyte proliferation and differentiation. TAZ associated with Sox5 to regulate the expression and stability of Sox5 and downstream chondrocyte marker genes' expression. In addition, overexpression of TAZ enhanced Col10a1 expression and promoted chondrocyte maturation, which was blocked by deletion of TAZ. Overall, our findings demonstrated that TAZ is required for skeletal development and joint maintenance that provided new insights into therapeutic strategies for fracture healing, heterotopic ossification, osteoarthritis, and other bone diseases.


Reversal of rest myocardial asynergy during exercise: a radionuclide scintigraphic study.
While exercise-induced segmental left ventricular wall motion abnormalities are well described, the phenomenon of improvement in certain asynergic segments during exercise in some patients remains a curiosity. To assess this unexpected finding, results were analyzed in 85 patients with wall motion abnormalities at rest who underwent two view (45 degrees left anterior oblique and anterior) exercise radionuclide ventriculography and exercise thallium-201 myocardial perfusion imaging. Wall motion was scored with a 5 point system (from 3 [normal] to - 1 [dyskinesia]); normalization or increase of 2 or more points with exercise signified improvement. Forty-eight patients (56%) had no change or further deterioration of wall motion at peak exercise, 15 (18%) showed both improvement of wall motion and deterioration and 22 (26%) showed only improvement of wall motion. Wall motion improvement during exercise was found in 57 (20%) of 279 segments with asynergy at rest. Of these 57 segments improving with exercise, 45 (79%) showed mild and 12 (21%) showed severe asynergy at rest. Only seven segments (12%) were associated with pathologic Q waves. Thallium-201 perfusion was normal in 44 segments (77%) while only 6 segments (11%) had reversible and only 7 (12%) had nonreversible thallium-201 defects. 1) wall motion that is abnormal at rest can sometimes improve with exercise; 2) this phenomenon generally occurs in zones without a Q wave or nonreversible thallium-201 defect. Hence, segments with abnormal wall motion at rest that show improvement with exercise appear to represent viable nonischemic segments.


Fetal bovine serum and other sera used in tissue culture increase epithelial permeability.
Fetal bovine serum (FBS) or heat-inactivated FBS (56 degrees C for 30 min, HFBS) caused a dose-dependent decrease in the transepithelial electrical resistance of an epithelial monolayer (MDCK). A saturating concentration of HFBS (30%) caused an average fall of 25 +/- 2% within 60 min. Upon removal of HFBS, the resistance returned to its starting value within 1 h. Flux studies with [3H]mannitol demonstrate that the fall in resistance is due to an increased permeability of the tight junctions. Thirty percent heat inactivated sera from goat, newborn calf, calf, bovine, and horse caused falls ranging from 26 to 47%. In contrast with the basolateral preference of human and bovine adult sera, fetal bovine and newborn calf sera elicit this response primarily by interacting with the apical surface of the epithelium. HFBS-treated monolayers show a significant increase in the condensation of F-actin at points where > or = 3 cells meet. These results demonstrate that FBS and other sera used as nutritional supplements can increase the permeability of the tight junctions of cultured epithelial cells.


Associated congenital anomalies in patients with anorectal malformations--a need for developing a uniform practical approach.
The aim of this study was to compare the incidences of various associated anomalies among subjects with high and low anorectal malformation (ARM), study the coexistence of these anomalies, and compare their frequency with those quoted in the existing literature. Ten years of data (from January 1993 through December 2002) on the 416 subjects from our center with anorectal malformations (ARM) were evaluated. The subjects with supra or translevator rectal pouch (radiologic or operative findings) were classified as high ARM and the rest as low ARM. The associated anomalies studied were vertebral, skeletal, renal, cardiac, vesicoureteric reflux (VUR), gastrointestinal, tracheoesophageal fistula, spinal, genital, and miscellaneous. For a detailed comparison, 4 subgroups were made: boys with high ARM, boys with low ARM, girls with high ARM, and girls with low ARM. Statistical methods were used for intergroup comparison. There were 68% male and 32% female subjects. Overall, 58% of subjects had high ARM (supralevator and translevator). Our attempt to compare the incidences of anomalies in our study population with those in other populations was defeated because of nonuniformity of classification and investigation of these anomalies in different studies. We found a frequent clubbing of anomalies affecting distantly developing anatomic regions in patients with ARM in many studies. The highest incidence of associated anomalies was found among boys with high ARM. The male subjects also had significantly more genital anomalies in association with low ARM and gastrointestinal tract anomalies in association with high ARM. On the other hand, girls had more urologic anomalies with high ARM and VUR with low ARM. Except for a low incidence of spinal anomalies (8%) and of VUR (1.7%), the incidences of most associated anomalies in our study were comparable with those of the earlier studies. Additionally, the girls with high ARM were observed to have significantly more urologic anomalies compared with the boys with high ARM in contrast to the results of the earlier reports. The existence of anomalies in distantly developing anatomic regions in patients with ARM supports the possibility of a "generalized" insult during embryogenesis rather than a ("localized") defect. It was observed that the boys with ARM are more likely to suffer morbidity because of frequent occurrence of multiple associated anomalies, and it may be worthwhile to evaluate of the role of sex chromosome in relation to ARM. The authors are also of the view that there is a need for more uniformity in classification of the anomalies and in their diagnostic approach because various reported studies have differed so widely on these aspects that any interstudy comparison is difficult or not feasible.


Emerging role of semaphorin-3A in autoimmune diseases.
Autoimmune diseases (ADs) are featured by the body's immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Currently, the exact pathogenesis of ADs remains not fully elucidated. Semaphorin-3A (Sema3A), a secreted member of semaphorin family, is a potent immunoregulator during all immune response stages. Sema3A has wide expression, such as in bone, connective tissue, kidney, neurons, and cartilage. Sema3A can downregulate ADs by suppressing the over-activity of both T-cell and B-cell autoimmunity. Moreover, Sema3A shows the ability to enhance T-cell and B-cell regulatory properties that control ADs, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis. However, it can also induce ADs when overexpressed. Together, these data strongly suggest that Sema3A plays a pivotal role in ADs, and it may be a promising treatment target for these diseases. In the present review, we focus on the immunological functions of Sema3A and summarize recent studies on the involvement of Sema3A in the pathogenesis of ADs; the discoveries obtained from recent findings may translate into novel therapeutic agent for ADs.


Gossypiboma of thigh mimicking soft tissue sarcoma: A case report and review of the literature.
Gossypiboma is a term used to describe a surgical error related to accidental retention of surgical material within the body. Gossypibomas of extremities are rare and not only lead to serious health problems (infection and organ damage), but also, they may mimic benign or malignant tumors, especially those affecting the thigh where they may mimic soft tissue sarcomas. A 50-year-old male, presented to the orthopedic department with a round palpable mass at mid-lateral of his right thigh region. The patient had history of surgical intervention on his femur due to femoral fracture 38-years ago. He had no sign of infection with normal laboratory workups. Radiological examinations suggested the possibility of a soft tissue sarcoma. Upon grossing, it revealed a white-tan and pink oval cystic mass with smooth surface. The cyst was filled with gauze fibers and creamy white-tan material. Histologically, the cystic wall of the mass revealed fibrocollagenous tissue, chronic inflammation and tiny foreign body materials, engulfed by the multinucleated giant cells, which was diagnosed as gossypiboma. Gossypiboma can mimic malignant soft tissue sarcomas. In most of the previously reported cases, the clinical and radiological findings suggested the possibility of malignant neoplasms. Considering the similarity between asymptomatic capsulated gossypiboma and soft tissue sarcomas radiologically, the possibility of gossypiboma should always be in the differential diagnosis, mainly in cases with presence of previous surgical scar or history of surgery at the affected area.


Referring patients with chronic kidney disease back to primary care: a criteria-based analysis in outpatient renal clinics.
The increased demand for nephrology care for patients with chronic kidney disease (CKD) necessitates a critical review of the need for secondary care facilities and the possibilities for referral back to primary care. This study aimed to evaluate the characteristics and numbers of patients who could potentially be referred back to primary care, using predefined criteria developed by nephrologists and general practitioners. We organised a consensus meeting with eight nephrologists and two general practitioners to define the back referral (BR) criteria, and performed a retrospective cohort study reviewing records from patients under nephrologist care in three hospitals. We reached a consensus about the BR criteria. Overall, 78 of the 300 patients (26%) in the outpatient clinics met the BR criteria. The characteristics of the patients who met the BR criteria were: 56.4% male, a median age of 70, an average of 3.0 outpatients visits per year, and a mean estimated glomerular filtration rate of 46 ml/min/1,73m2. Hypertension was present in 67.9% of this group, while 27.3% had diabetes and 16.9% had cancer. The patients who could be referred back represented all CKD stages except stage G5. The most common stage (16%) was G3bA2 (eGFR 30 ≤ 44 and ACR 3 ≤ 30). A substantial proportion of patients were eligible for referral back to primary care. These patients often have a comorbidity, such as hypertension or diabetes. Future research should focus on generalisability of the BR criteria, the feasibility of actual implementation of the back referral, follow-up assessments of renal function and patient satisfaction.


Chk1/2 inhibitor AZD7762 enhances the susceptibility of IDH-mutant brain cancer cells to temozolomide.
The IDH mutation initially exhibits chemosensitive properties, progression-free survival cannot be achieved in the later grades, and malignant transformation occurs as a result of TMZ-induced hypermutation profile and adaptation to this profile. In this study, we evaluated the potential of the combination of TMZ and AZD7762 at molecular level, to increase the anticancer activity of TMZ in IDH-mutant U87-mg cells. We used the WST-1 test to evaluate cytotoxic effect of TMZ and AZD7762 combination with dose-effect and isobologram curves. The effects of the inhibitory and effective concentrations of the combination on apoptosis, cell cycle and γ-H2AX phosphorylation were analyzed with flow cytometry. The expression of genes responsible for the DNA damage response was analyzed with qRT-PCR. The combination showed a synergistic effect with high dose reduction index. Single and combined administrations of TMZ and AZD7762 increased in G2/M arrest from 24 to 48 h, and cells in the G2/M phase shifted towards octaploidy at 72 h. While no double-strand breaks were detected after TMZ treatment, AZD7762 and combination treatments caused a significant increase in γ-H2AX phosphorylation and increased apoptotic stimulation towards 72 h although TMZ did not cause apoptotic effect in IDH-mutant U87-mg cells. The genes controlling the apoptosis were determined to be upregulated in all three groups, and genes regarding cell cycle checkpoints were downregulated. Targeting Chk1/2 with AZD7762 simultaneously with TMZ may be a potential therapeutic strategy for both increasing the sensitivity of IDH-mutant glioma cells to TMZ and reducing the dose of TMZ. In IDH-mutant glioma cells, AZD7762, the Chk1/2 inhibitor, can increase the efficacy of Temozolomide by (i) increasing mitotic chaos, and (ii) inhibiting double-strand break repair, (iii) thereby inducing cell death.


Selection response and genetic parameter estimation of feeding behavior traits in Pekin ducks.
Body weight-related traits and feeding behavior traits are important in poultry breeding and production. To investigate the heritability of feeding behavior and their genetic correlation with body weight-related traits in Pekin ducks, 5,594 Pekin ducks were selected. The information about body weight-related traits and feeding behavior from 3 to 6 wk of age were recorded by automatic electronic feeders. The heritability estimates for body weight, residual feed intake, and feeding behavior traits are relatively high (ranging from 0.29 to 0.65). We observed that total feed intake, meal feed intake, body weight at the age of 3 wk, and daily body weight gain had strong positive genetic correlations with body weight at the age of 6 wk. Moreover, body weight at the age of 3 wk also showed a positive genetic correlation with the feed conversion ratio (0.33). Total feeding time, daily feed intake, and feeding rate had significant positive phenotypic correlations with feed efficiency. However, the average interval between meals, the number of daily visits, and the number of meals all had a low genetic or phenotypic relationship with body weight and feed efficiency. In conclusion, our study revealed that body weight, residual feed intake, and feeding behavior traits were all highly heritable traits, and the selection for certain feeding behaviors could improve feed efficiency in Pekin ducks. This study is the first report about genetic parameter estimates about feeding behaviors in ducks based on large datasets and provides solid data for genetic study in ducks.


Outcome and treatment toxicity in east-indian versus white-canadian patients with oral cavity cancer following postoperative (chemo-)radiotherapy delivered under similar multidisciplinary care: A propensity-matched cohort study.
We compare clinical behaviour of East-Indians and White-Canadians with oral cavity squamous cell carcinoma (OSCC) treated at a Western institution within a uniform health care system. Newly diagnosed OSCC patients who underwent postoperative (chemo-)radiotherapy (PORT/POCRT) between 2005 and 2017 were included. Data on ethnicity and other variables were extracted from patient-questionnaires, a prospective database and supplemented by chart review. Baseline characteristics were compared between East-Indian versus White-Canadian groups. A propensity-matched (1:1 ratio) of East-Indian versus White-Canadian cohorts was generated to compare locoregional control (LRC), distant control (DC), overall survival (OS), and acute and late toxicities. A total of 53 East-Indian and 467 White-Canadian OSCC patients were identified. Compared to White-Canadians, East-Indian patients were younger, had less exposure to smoking and alcohol (p < 0.001), but more chewed betel (areca) nut /tobacco (43% vs 0.2%, p < 0.001). Buccal/retromolar-trigone/lower gingiva primaries were more common in East-Indians (49% vs 25%, p < 0.001). Median follow-up was 5.0 years. Propensity-score paired analysis revealed inferior 3-year LRC (68% vs 81%, p = 0.030), non-significantly lower OS (61% vs 75%, p = 0.257), but similar DC (81% vs 87%, p = 0.428) in East-Indian versus White-Canadian patients. Actuarial rate of toxicities was higher in East-Indians vs White-Canadians: acute toxicity at 6 weeks: 47% vs 30%, p = 0.012; chronic trismus at 5-years: 16% vs 2%, p = 0.013. East-Indian OSCC patients have a greater betel nut/ chewable tobacco exposure compared to White-Canadians and a different distribution of OSCC sites. Propensity-matched cohort analysis showed lower LRC and higher toxicities in East-Indian OSCC patients, suggesting a complicated interaction between genetic/biological and life-style factors.


Identification of the acidic and basic subunit complexes of glycinin.
Five complexes consisting of one acidic and one basic subunit that were linked via disulfide bonds were purified from unreduced S-alkylated glycinin. The acidic and basic subunits were identified unambiguously using NH2-terminal sequence analysis, sodium dodecyl sulfate (SDS)-electrophoresis, and analytical isoelectric focusing. The subunit pairings are A1aB2, A1bB1b, A2B1a, A3B4, and F2(2)B3. Polypeptide A4 was not linked to a corresponding basic subunit via a disulfide bond. The study shows that pairing between subunits is nonrandom, which is consistent with evidence that glycinin is synthesized as a Mr = 60,000 precursor that undergoes post-translational modification to form the individual linked subunits.


Surface-charging behavior of Zn-Cr layered double hydroxide.
A Zn-Cr layered double hydroxide (LDH) having the formula Zn(2)Cr(OH)(6)Cl(0.7)(CO(3))(0.15)2.1H(2)O was synthesized and characterized by powder X-ray diffraction, infrared spectroscopy, acid-base potentiometric titration, mass titration, electrophoretic mobility, and modeling of the electrical double layer. Adsorption of alizarin was also performed in order to show some particular features of the HDL. Net hydroxyl adsorption, which increases with increasing pH and decreasing supporting electrolyte concentration, takes place above pH 5. The electrophoretic mobility of the particles was always positive and it decreased when the pH was higher than 9. An isoelectric point of 12 could be estimated by extrapolating the data. The modified MUSIC model was used to estimate deprotonation constants of surface groups and different adsorption models were compared. Good fit of hydroxyl adsorption and electrophoresis could be achieved by considering both OH(-)/Cl(-) exchange at structural sites and proton desorption from surface hydroxyl groups. The modeling, in agreement with alizarin adsorption, indicates that most of the structural positive charge of the LDH is screened at the surface by exchanged anions and negatively charged surface groups. It also suggests that only structural charge sites initially neutralized by chloride ions are active for anion exchange. The remaining sites are blocked by carbonate and do not participate in the exchange.


Incidental detection of an aortic valve papillary fibroelastoma by echocardiography in an asymptomatic patient presenting with hypertension.
Papillary fibroelastomas are rare, frond-like tumours of uncertain etiology seen on cardiac valves, uncommonly found antemortem. They carry a significant risk of embolization, making their detection and excision during life an important issue. A case of an aortic valve papillary fibroelastoma is described, which was found at echocardiography in a patient being assessed for previously unrecognized, severe hypertension.


Karyotypic analysis in primary myelodysplastic syndromes.
Cytogenetics has provided new insights into the biology and pathogenesis of myelodysplastic syndromes. In patients with refractory anemia, it has provided proof of clonality and has helped differentiate chronic myelomonocytic leukemia from chronic myeloid leukemia. As a prognostic tool, cytogenetics has been predictive of duration of survival and leukemic transformation. However, its role as an independent prognostic factor compared with recent prognostic scoring systems remains to be determined. New techniques such as fluorescent in situ hybridization using chromosome-specific DNA probes may expand the usefulness of cytogenetics. The prognostic impact of cytogenetics may not be fully realized until more effective treatments become available.


Morale of mental health professionals in Community Mental Health Services of a Northern Italian Province.
To explore morale of psychiatrists and psychiatric nurses working in Community Mental Health Centres (CMHC) in an Italian Province, and identify influential factors. Thirty psychiatrists and 30 nurses working in CMHCs in Modena completed questionnaires on burnout, team identity and job satisfaction. They also answered open questions about different aspects of their work. Answers were subjected to content analysis. Regression analyses were used to identify factors that predicted morale across groups. Psychiatrists had higher scores on emotional exhaustion and depersonalisation. There were no significant differences between the two groups in job satisfaction and job or role perception. Professionals reported positive relationships with patients as the most enjoyable aspects of their job, whilst team conflicts and high workloads were seen as most difficult to cope with. Multivariate analyses showed that being a psychiatrist and perceiving team conflicts as a main cause of pressure in the job predicted higher burnout. Simple open questions coupled with quantitative measures appear a promising tool to investigate morale of mental health professionals and identify factors determining morale. Research, training and service development should focus on relationship aspects both with patients and within teams to reduce burnout in CMHCs.


Influence of low-level laser therapy on wound healing in nicotine-treated animals.
Low-level laser therapy (LLLT) has been shown to have several biological effects that favor the healing process, and nicotine has been shown to delay the healing process. In this study we investigated the healing of open wounds created on the back of rats treated with nicotine with or without LLLT. Of 115 animals, 59 received subcutaneous injections of saline solution, and the others received subcutaneous injections of nicotine (3 mg/kg body weight), twice a day throughout the study period. After 30 days, skin wounds were created on the back of the animals. The animals receiving saline injections were divided into two groups: group 1 (G1, n = 29), in which the wounds were left untreated, and group 2 (G2, n = 30), in which the wounds were treated with LLLT (GaAlAs, 660 nm, 30 mW, 5.57 J/cm(2) per point, 0.39 J, 13 s per point, 0.42 W/cm(2)). The animals receiving nicotine injections were also divided into two groups: group 3 (G3, n = 29), in which the wounds were left untreated, and group 4 (G4, n = 27), in which the wounds were treated with LLLT. The animals were killed 3, 7 or 14 days after surgery. Wound healing was evaluated histologically both qualitatively and semiquantitatively. Wounds of G2 showed a delay in epithelial migration and connective tissue organization compared to those of G1. Wounds of G2 showed faster healing than those of G1; similarly, wounds of G4 showed more advanced healing than those of G3. LLLT acted as a biostimulatory coadjuvant agent balancing the undesirable effects of nicotine on wound tissue healing.