Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries.
Intimal hyperplasia plays an important role in a variety of types of vascular remodeling, particularly luminal narrowing after vascular injury. The vascular smooth muscle cells (VSMCs) in the neointimal area are a synthetic phenotype and have different epitopes from VSMCs in the normal media. The synthetic VSMCs in the neointima contain various possible antigens that can be targeted by the immune system. In this study, we tried to develop a new immunotherapy, which targets the synthetic VSMCs, for prevention of neointimal formation after angioplasty. Rabbits were repeatedly immunized with fixed xenogenic rat cultured VSMCs suspended in adjuvant as immunogens or injected with adjuvant and phosphate-buffered saline (PBS) or rat hepatocytes as controls every 2 weeks for 3 times. One week after the last immunization/injection, balloon injury of the left common carotid artery was performed. Four weeks after the injury, rabbits were euthanized and the neointimal lesion formation was assessed. The mean neointimal area of the PBS-injected, non-immunized group and the rat hepatocyte-immunized, control group was not statistically different (0.339 +/- 0.036 and 0.350 +/- 0.041 mm(2), P = NS). However, immunization with rat VSMCs significantly reduced the intimal lesion area (0.219 +/- 0.0286 mm(2); P < 0.05 vs. PBS-injected, non-immunized group and rat hepatocyte-immunized group.) PCNA-immunopositive proliferating VSMCs in the neointima were suppressed by the rat VSMC immunization (1.34 +/- 0.49% vs. 5.78 +/- 0.47%; P < 0.05 vs. PBS-injected, non-immunized group). Rat VSMC immunization induced antibodies which had strong cross-reactivity against rabbit synthetic VSMCs. In experiments in vitro, proliferation and migration of rabbit VSMCs that were stimulated by serum, angiotensin (AT) II, platelet-derived growth factor (PDGF)-BB, fibroblast growth factor (FGF), and the phorbol ester PMA were significantly suppressed by treatment with immunoglobulin extracted from the VSMC-immunized rabbit plasma, implying that the immunoglobulin had some global effects on VSMCs. The rat VSMC-immunized rabbit immunoglobulin bound the rabbit AT1a receptor protein, which was expressed in COS7 cells by transfection of rabbit AT1a receptor pcDNA3. This binding to AT1a receptor may be one of mechanisms of the effects of VSMC-immunized immunoglobulin. Xenogenic, synthetic rat VSMC immunization in rabbits induced auto-antibodies against synthetic rabbit VSMCs in a cross-reaction. The induced auto-antibodies against synthetic VSMCs may provide a possibility of new immunotherapy for vascular remodeling that forms neointimal lesions.


Prevalence of fungi in the vagina, rectum and oral cavity in pregnant diabetic women: relation to gestational age and symptoms.
To estimate the prevalence of fungi in the vagina, rectum and oral cavity in pregnant women with diabetes mellitus (DM) type I or gestational diabetes mellitus (GDM) and in healthy controls; to assess the influence of gestational age on the prevalence of fungi; to compare the vaginal symptoms within the groups; and to analyze the multifocality of fungal invasions. A total of 251 women were examined: 47 with DM, 72 with GDM and 132 controls. Samples were collected from the vagina, rectum and oral cavity of all women and cultured on Sabouraud media. Fungi were found in 59.8% in at least one of the three locations in all women. Vaginal mycosis was diagnosed more often (p < 0.001) in pregnancies with DM [40.4%, odds ratio (OR) 4.3, confidence interval (CI) 2.41-4.85] than with GDM (22.2%, OR 1.84, CI 0.99-2.12) and nondiabetics (13.6%, OR 1.0). The risk of trifocal mycosis was higher in DM women (OR 2.7, CI 1.72-4.45), than in the controls. Only in 27.6% of symptomatic women were fungi detected in vagina. However, 60.4% of women with vaginal mycosis had symptoms. Among women without mycosis, 42.4% were symptomatic, and discharge was more common in the DM group (50%) than in the GDM group (21.4%) and the controls (28.1%; p < 0.002). The prevalence of fungi in the groups was not influenced by gestational age. The risk of vaginal mycoses in DM women is more that four times higher and in pregnancies with GDM nearly two times higher than in controls. The risk of trifocal mycosis in DM women is nearly three times higher than in nondiabetics. There is a poor correlation between symptoms of vaginitis and fungal infection. We did not confirm the influence of the gestational age on the prevalence of fungi.


Hormone replacement therapy in women treated for breast cancer.
We must still maintain the conventional advice that unopposed low dosages of oestrogen should not be used for the treatment of menopausal symptoms in women treated previously for breast cancer. There is, however, epidemiological, laboratory and clinical evidence that certain combinations of oestrogen and progestagen are more likely to be beneficial than harmful, in respect to the risk of reactivating subclinical residual breast cancer or causing progression in premalignant lesions. It is no longer justifiable to deprive a woman with a history of breast cancer treatment of a hormonal therapy capable of safely relieving symptoms which are making her life intolerable. A clinical trial of such treatment is reported.


Accuracy of Transthoracic Echocardiogram as a Screening Method in the Clinical Practice of Pulmonary Hypertension Investigation.
The transthoracic echocardiogram (TTE) plays a screening role in the diagnostic algorithm of pulmonary hypertension (PH). Studies have shown a significant disagreement between TTE measurements of the systolic pulmonary artery pressure (sPAP) and right atrial pressure (RAP) and those obtained by right heart catheterization (RHC). To compare TTE measurements of sPAP and RAP with those obtained by RHC in patients being investigated for PH. Patients referred to a PH reference center with a high or intermediate TTE probability of PH upon admission were submitted to RHC. The agreement between sPAP and RAP from both procedures was assessed through the Bland-Altman test. Differences of up to 10 mmHg for sPAP and 5 mmHg for RAP were considered within the variability of the test. Receiver Operating Characteristic (ROC) curve was constructed to determine the most accurate sPAP and Tricuspid regurgitation maximal velocity (TRV)values associated with the diagnosis of PH by RHC. The adopted level of statistical significance was 5%. Ninety-five patients were included. The Bland-Altman analysis showed a bias of 8.03 mmHg (95% CI:-34.9-50.9) for sPAP and -3.30 mmHg (95% CI:-15.9-9.3) for RAP. AUC for sPAP and TRV measured by TTE for discrimination of probable PH were 0.936 (95% CI: 0.836-1.0) and 0.919 (95% CI: 0.837-1.0), respectively. However, only 33.4% of the echocardiographic estimate of sPAP and 55.1% of RAP were accurate, as compared to the measurements obtained by RHC. TTE has a high discriminatory power as a screening diagnostic method for PH despite presenting disagreements between sPAP and RAP absolute values when compared to RHC measurements.


Systemic and local release of inflammatory cytokines regulates hepatobiliary excretion of 99mTc-mebrofenin.
Imaging agents capable of providing cell compartment-specific information will facilitate studies of pathophysiological mechanisms, natural history of diseases, and therapeutic development. To demonstrate the effects of liver injury on the disposal of the organic anion mebrofenin, we performed animal studies. Acute liver injury was induced in Fischer 344 rats with 0.25-1 ml/kg single doses of carbon tetrachloride followed by studies of animals over 4 weeks. The liver injury was analyzed by blood tests and histological grading. Additional rats were treated with lipopolysaccharide, interleukin-6 or tumor necrosis factor-alpha to activate inflammatory events. Hepatic clearance of Tc-mebrofenin was studied with dynamic imaging and fractional retention after 60 min of peak hepatic mebrofenin activity was determined. In healthy rats, only 24+/-2% of peak mebrofenin activity was retained in the liver after 60 min. By contrast, 24 h after carbon tetrachloride, virtually all mebrofenin activity was retained in the liver (P<0.001). Three weeks were required for mebrofenin excretion to become normal after carbon tetrachloride administration. In this situation, we found that Kupffer cell activity was increased. In addition, the abnormality in mebrofenin excretion was reproduced by lipopolysaccharide, which activates Kupffer cells. Moreover, mebrofenin excretion was highly sensitive to interleukin-6 and/or tumor necrosis factor-alpha, which help mediate the Kupffer cell response. Hepatobiliary excretion of mebrofenin was affected rapidly and over an extended period by inflammatory cytokines released after liver injury. The remarkable sensitivity of mebrofenin excretion to cytokines suggests that Tc-mebrofenin imaging will be helpful for assessing cytokine-mediated liver inflammation.


Infectivity, pathogenicity, and genetic characteristics of mammalian gastric Cryptosporidium spp. in domestic ruminants.
Farm ruminants were infected experimentally with four mammalian gastric Cryptosporidium, namely Cryptosporidium andersoni LI03 originated from cattle and three isolates of Cryptosporidium muris from brown rat (isolate RN66), Bactrian camel (isolate CB03) and firstly characterized isolate from East African mole rat (isolate TS03). Sequence characterizations of the small-subunit rRNA gene showed that the LI03 isolate was C. andersoni and the other three isolates belonged to C. muris, although the TS03 isolate showed unique sequence variations (one single nucleotide change and four nucleotide insertions). C. andersoni LI03 was infectious for calves only, whereas lambs and kids were susceptible to C. muris CB03. C. muris TS03 and RN66 were not infectious for any farm ruminants. Infection dynamics including prepatent and patent period and infection intensity of the isolates used differed depending on the host species, but no clinical signs of cryptosporidiosis were observed in any of experimentally infected hosts. Cryptosporidium developmental stages were only detected in infected animals in the abomasum region. Histopathological changes were characterized by dilatation and epithelial metaplasia of infected gastric glands with no significant inflammatory responses in the lamina propria.


Effects of piclozotan (SUN N4057), a partial serotonin 1A receptor agonist, on motor complications induced by repeated administration of levodopa in parkinsonian rats.
Serotonin 1A receptor agonists have attracted much interest recently as potential therapeutic agents for levodopa-induced motor complications, such as dyskinesia and motor fluctuations. The effects of piclozotan (SUN N4057) on a rat model of advanced Parkinson's disease were investigated. Parkinsonian rats, unilaterally 6-hydroxydopamine-lesioned rats, were administered levodopa for 8 to 9 weeks. Based on the results of rotational behavior and forelimb hyperkinesia in Week 5, the rats were allocated to three treatment groups (saline and two dosing rates of piclozotan set at 0.018 and 0.036 mg/kg/h). Piclozotan was administered via continuous subcutaneous infusion using an osmotic pump for 3 to 4 weeks. At Week 7 of repeated levodopa dosing, the effects of piclozotan on levodopa-induced behavior were evaluated. In addition, extracellular levels of levodopa-derived dopamine in the striatum were measured using microdialysis in Weeks 8 to 9 after completion of the respective behavioral studies. Chronic treatment with levodopa-induced forelimb hyperkinesia and shortened the duration of rotational behavior. Piclozotan (0.018 and 0.036 mg/kg/h, plasma concentrations 5.3±0.7 and 14.3±2.9 ng/ml) reduced levodopa-induced forelimb hyperkinesia by 55% and 69%, respectively, at 1h relative to the control. Piclozotan (0.036 mg/kg/h) significantly lengthened the duration of rotational behavior by 26% versus the control and attenuated the increase in striatal levodopa-derived extracellular dopamine levels. These findings suggest that piclozotan, a serotonin 1A agonist, can improve motor complications in patients with advanced Parkinson's disease.


Functional hand development in tetraplegia.
The development of the 'functional hand' in tetraplegics has been historically facilitated through specialized hand positioning schemes. However, clinical experience at the University Hospital Heidelberg demonstrates no direct relationship between various hand positioning techniques and the probability of functional hand development. The aim of this study was to document the various methods of hand positioning and the resulting functional outcome. In a multi-center study, the paralysed thumb and finger positioning of 64 tetraplegics and the resultant functional outcome was evaluated with a specially developed survey form. Results indicated that the functional outcome of the tetraplegic hand was highly dependent on the level of the spinal cord injury and only to a minor degree dependent upon the different methods of hand positioning employed. The conclusion drawn is that remaining neurologic function after injury determines the final functional outcome of the tetraplegic hand.


Longitudinal Treatment Outcomes of Microsurgical Treatment of Neurosensory Deficit after Lower Third Molar Surgery: A Prospective Case Series.
To prospectively evaluate the longitudinal subjective and objective outcomes of the microsurgical treatment of lingual nerve (LN) and inferior alveolar nerve (IAN) injury after third molar surgery. A 1-year longitudinal observational study was conducted on patients who received LN or IAN repair after third molar surgery-induced nerve injury. Subjective assessments ("numbness", "hyperaesthesia", "pain", "taste disturbance", "speech" and "social life impact") and objective assessments (light touch threshold, two-point discrimination, pain threshold, and taste discrimination) were recorded. 12 patients (10 females) with 10 LN and 2 IAN repairs were recruited. The subjective outcomes at post-operative 12 months for LN and IAN repair were improved. "Pain" and "hyperaesthesia" were most drastically improved. Light touch threshold improved from 44.7 g to 1.2 g for LN repair and 2 g to 0.5 g for IAN repair. Microsurgical treatment of moderate to severe LN injury after lower third molar surgery offered significant subjective and objective sensory improvements. 100% FSR was achieved at post-operative 6 months.


Results of sole postoperative interstitial, high-dose-rate brachytherapy of T1-2 tongue tumours.
To describe the results of treating tongue cancer patients with single postoperative interstitial, high-dose-rate (HDR) brachytherapy (BT) after resection. Between January 1998 and April 2019, 45 patients with squamous cell histology, stage T1-2N0-1M0 tongue tumours were treated by surgery followed by a single HDR BT in case of negative prognostic factors (close or positive surgical margin, lymphovascular and/or perineural invasion). The average dose was 29 Gy (range: 10-45 Gy) and rigid metal needles were used in 11 (24%) and flexible plastic catheters in 34 cases (76%). Survival parameters, toxicities and the prognostic factors influencing survival were analysed. During a mean follow-up of 103 months (range: 16-260 months) for surviving patients, the 10-year local and regional control (LC, RC), overall survival (OS), and disease-specific survival (DSS) probabilities were 85, 73, 34 and 63%, respectively. The incidence of local grade 1, 2 and 3 mucositis was 23, 73 and 4%, respectively. As a serious (grade 4), late side effect, soft tissue necrosis developed in 3 cases (7%). In a univariate analysis, there was a significant correlation between lymphovascular invasion and RC (p = 0.0118) as well as cervical recurrence and DSS (p < 0.0001). Sole postoperative HDR brachytherapy can be an effective method in case of negative prognostic factors in the treatment of early, resectable tongue tumours. Comparing the results of patients treated with postoperative BT to those who were managed with surgery or BT alone known from the literature, a slightly more favourable LC can be achieved with the combination therapy, demonstrating the potential compensating effect of BT on adverse prognostic factors, while the developing severe, grade 4 toxicity rate remains low.


Mixed pollutants adsorption potential of Eichhornia crassipes biochar on Manihot esculenta processing industry effluents.
The starch is one of the most essential food stuff and serves as a raw material for number of food products for the welfare of human. During the production process enormous volume of effluents are being released into the environment. In this regard, this study was performed to evaluate the physicochemical traits of Manihot esculenta processing effluent and possible sustainable approach to treat this issue using Eichhornia crassipes based biochar. The standard physicochemical properties analysis revealed that the most the parameters (EC was recorded as 4143.17 ± 67.12 mhom-1, TDS: 5825.62 ± 72.14 mg L-1, TS: 7489.21 ± 165.24 mg L-1, DO: 2.12 ± 0.21 mg L-1, BOD 2673.74 ± 153.53 mg L-1, COD: 6672.66 ± 131.21 mg L-1, and so on) were beyond the permissible limits and which can facilitate eutrophication. Notably, the DO level was considerably poor and thus can support the eutrophication. The trouble causing E. crassipes biomass was used as raw material for biochar preparation through pyrolysis process. The temperature ranging from 250 to 350 °C with residence time of 20-60 min were found as suitable temperature to provide high yield (56-33%). Furthermore, 10 g L-1 concentration of biochar showed maximum pollutant adsorption than other concentrations (5 g L-1 and 15 g L-1) from 1 L of effluent. The suitable temperature required to remediate the pollutants from the effluent by biochar was found as 45 °C and 35 °C at 10 g L-1 concentration. These results conclude that at such optimized condition, the E. crassipes effectively adsorbed most of the pollutants from the M. esculenta processing effluent. Furthermore, such pollutants adsorption pattern on biochar was confirmed by SEM analysis.


Effect of PSC 833, a potent inhibitor of P-glycoprotein, on the growth of astrocytoma cells in vitro.
Malignant astrocytomas have been found to express P-glycoprotein (Pgp, mdr1 gene product). It was hypothesized that in addition to conferring multidrug resistance, Pgp is intimately associated with the development of astrocytomas. Accordingly, we studied the effect of PSC 833 (PSC, Novartis), a potent inhibitor of Pgp, on the growth of Pgp-expressing astrocytoma cells. The results showed that in all the cell lines tested, PSC (10-60 microM) inhibited the growth as well as induced cell death. Cells exposed to PSC exhibited DNA ladder characteristic of apoptosis. PSC-induced cell death could be reversed by Z-VAD-fmk, a general caspase inhibitor, indicating that PSC-induced cell death was characteristic of caspase-mediated apoptosis. These results suggest a novel therapeutic strategy in the treatment of malignant astrocytomas by inhibitors of Pgp.


Measuring health in patients with cervical and lumbosacral spinal disorders: is the 12-item short-form health survey a valid alternative for the 36-item short-form health survey?
To determine the convergent validity of the 12-Item Short-Form Health Survey, version 2 (SF-12v2), with 36-Item Short-Form Health Survey, version 2 (SF-36v2), in patients with spinal disorders, and to determine other key factors that might further explain the variances between the 2 surveys. Cross-sectional study. Orthopedic ambulatory care. Eligible participants (N=98; 24 with cervical, 74 with lumbosacral disorders) who were aged 18 years and older, scheduled to undergo spinal surgery, and completed the SF-36v2. Not applicable. SF-36v2 and SF-12v2 (extracted from the SF-36v2). The 2 summary scores, physical and mental component scores (r range, .88-.97), and most of the scale scores (r range, .81-.99) correlated strongly between the SF-12v2 and SF-36v2, except for the general health score (cervical group, r=.69; lumbosacral group, r=.76). Stepwise linear regression analyses showed the SF-12v2 general health scores (cervical: beta=.61, P<.001; lumbosacral: beta=.68, P<.001) and the level of comorbidities (cervical: beta=-.37, P=.014; lumbosacral: beta=-.18, P=.039) were significant predictors of the SF-36v2 general health score in both groups, whereas age (beta=.32, P<.001) and smoking history (beta=-.22, P=.005) were additional predictors in the lumbosacral group. SF-12v2 is a practical and valid alternative for the SF-36v2 in measuring health of patients with cervical or lumbosacral spinal disorders. The validity of the SF-12v2 general health score interpretation is further improved when the level of comorbidities, age, and smoking history are taken into consideration.


Clinical accuracy of malaria loop-mediated isothermal amplification assay as a stand-alone screening tool at a non-endemic Northern California regional health system.
Malaria is critical to rule out in febrile returned travelers. We evaluated the performance of the Alethia Malaria loop-mediated isothermal amplification (LAMP) assay for rapid one-time malaria screening using nucleic acid amplification testing. Retrospective analysis of 51 archival blood specimens collected from 32 patients with malaria and 25 uninfected controls showed Malaria LAMP assay to have sensitivity of 100% (95% CI 93.0-100) and specificity of 100% (95% CI 86.7-100) using blood smear microscopy as the reference standard. Prospective evaluation of Malaria LAMP as a single screening test in 205 patients identified 4 (1.95%) positives which were all confirmed as Plasmodium falciparum by PCR, with parasitemia quantified as <0.1% (n = 2), 1.0% (n = 1), and 4.6% (n = 1). Alternative diagnoses were found in 129 of 201 (64.2%) of LAMP-negative patients, and no patient was subsequently diagnosed with malaria. The Malaria LAMP offers a sensitive and rapid stand-alone screening alternative in non-endemic settings.


Nonpharmacologic labor analgesia.
A supportive medical team should be well informed on the various pharmacologic and nonpharmacologic modalities of coping with or mitigating labor pain to appropriately support and respectfully care for parturients. Using the methodical rigor of previously published Cochrane systematic reviews, this summary evaluates and discusses the efficacy of nonpharmacologic labor analgesic interventions.


Everything is a carcinogen?
The public has developed the impression that in an industrialized society environmental carcinogens are ubiquitous and that all chemical exposures, irrespective of the dose, influence carcinogenesis. Such impressions are influenced by many nonscientific considerations and often reflect insufficient knowledge of scientific data and methods. Such misconceptions are thus partly explained by the multistage nature of carcinogenesis, the absence of a clear understanding, and definition of the multiple factors which influence cancer induction. It is obvious that not all chemicals are carcinogenic and it is reasonable to accept that not all substances (including primary chemical carcinogens) that are found to enhance carcinogens in animals are necessarily carcinogenic to humans under conditions of usual human exposure.


The potential of curcumin-based co-delivery systems for applications in the food industry: Food preservation, freshness monitoring, and functional food.
Currently, curcumin-based co-delivery systems are receiving widespread attention. However, a systematic summary of the possibility of curcumin-based co-delivery systems used for the food industry from multiple directions based on the functional characteristics of curcumin is lacking. This review details the different forms of curcumin-based co-delivery systems including the single system of nanoparticle, liposome, double emulsion, and multiple systems composed of different hydrocolloids. The structural composition, stability, encapsulation efficiency, and protective effects of these forms are discussed comprehensively. The functional characteristics of curcumin-based co-delivery systems are summarized, involving biological activity (antimicrobial and antioxidant), pH-responsive discoloration, and bioaccessibility/bioavailability. Correspondingly, potential applications for food preservation, freshness detection, and functional foods are introduced. In the future, more novel co-delivery systems for active ingredients and food matrices should be developed. Besides, the synergistic mechanisms between active ingredients, delivery carrier/active ingredient, and external physical condition/active ingredient should be explored. In conclusion, curcumin-based co-delivery systems have the potential to be widely used in the food industry.


Physical Activity, Sedentary Behavior, and Sleep on Twitter: Multicountry and Fully Labeled Public Data Set for Digital Public Health Surveillance Research.
Advances in automated data processing and machine learning (ML) models, together with the unprecedented growth in the number of social media users who publicly share and discuss health-related information, have made public health surveillance (PHS) one of the long-lasting social media applications. However, the existing PHS systems feeding on social media data have not been widely deployed in national surveillance systems, which appears to stem from the lack of practitioners and the public's trust in social media data. More robust and reliable data sets over which supervised ML models can be trained and tested reliably is a significant step toward overcoming this hurdle. The health implications of daily behaviors (physical activity, sedentary behavior, and sleep [PASS]), as an evergreen topic in PHS, are widely studied through traditional data sources such as surveillance surveys and administrative databases, which are often several months out-of-date by the time they are used, costly to collect, and thus limited in quantity and coverage. The main objective of this study is to present a large-scale, multicountry, longitudinal, and fully labeled data set to enable and support digital PASS surveillance research in PHS. To support high-quality surveillance research using our data set, we have conducted further analysis on the data set to supplement it with additional PHS-related metadata. We collected the data of this study from Twitter using the Twitter livestream application programming interface between November 28, 2018, and June 19, 2020. To obtain PASS-related tweets for manual annotation, we iteratively used regular expressions, unsupervised natural language processing, domain-specific ontologies, and linguistic analysis. We used Amazon Mechanical Turk to label the collected data to self-reported PASS categories and implemented a quality control pipeline to monitor and manage the validity of crowd-generated labels. Moreover, we used ML, latent semantic analysis, linguistic analysis, and label inference analysis to validate the different components of the data set. LPHEADA (Labelled Digital Public Health Dataset) contains 366,405 crowd-generated labels (3 labels per tweet) for 122,135 PASS-related tweets that originated in Australia, Canada, the United Kingdom, or the United States, labeled by 708 unique annotators on Amazon Mechanical Turk. In addition to crowd-generated labels, LPHEADA provides details about the three critical components of any PHS system: place, time, and demographics (ie, gender and age range) associated with each tweet. Publicly available data sets for digital PASS surveillance are usually isolated and only provide labels for small subsets of the data. We believe that the novelty and comprehensiveness of the data set provided in this study will help develop, evaluate, and deploy digital PASS surveillance systems. LPHEADA will be an invaluable resource for both public health researchers and practitioners.


In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipase.
As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced than that in mildly HTG plasma, but they became highly pronounced upon increase of its TG-rich lipoprotein level by the addition of preisolated VLDL or by the induction of postprandial lipemia. Although the effect of LCAT, CETP and LpL reactions in non-circulating plasma in vitro may be different from that in vivo, the above data suggests that the plasma TG-rich lipoprotein level and the extent of intraplasma LCAT, CETP, LpL and likely hepatic lipase (HL) reactions in vivo may play a role in determining the LDL phenotype.


Single-Crystal to Single-Crystal Uptake of Volatile Solids and Associated Chromatic Response in a Porous Metallocycle.
Guest molecules have been absorbed into crystals of a metallocyclic host by sublimation of volatile solids at room temperature. The guest exchanges are accompanied by color changes. Since the crystals remain intact, evidence of guest inclusion could be obtained using single-crystal X-ray diffraction. The results are also supported by thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet-visible spectroscopy (UV-vis).


Genotypic screening of pseudorabies virus strains for thymidine kinase deletions by use of the polymerase chain reaction.
Genetic recombination between field strains and vaccine strains of pseudorabies virus (PRV) has been suggested as a scenario that might arise from use of deletion-mutant modified-live vaccine strains, particularly those strains attenuated by deletions within the thymidine kinase (TK-) gene locus. To address this hypothesis experimentally, it is necessary to screen large numbers of PRV isolates for their TK genotype. Techniques to detect the native TK genotype are routinely used in molecular virology laboratories, but are time-consuming. We adapted the polymerase chain reaction to define the genotypic status of PRV isolates with regard to the presence or absence of deletions in the TK gene locus. Used in tandem with the existing glycoprotein-specific ELISA that discriminate between PRV-vaccinated and field strain-infected swine populations, the described technique may help to clarify whether vaccine-derived recombinants are generated under natural conditions and after normal vaccine usage.


The effect of cul length and hippocampal lesions on maze learning in the rat.
Twenty-four rats, 8 with bilateral hippocampal lesions, 8 with cortical lesions and 8 unoperated rats, were tested on one of 2 mazes. Half of each group were run in a conventional 5 choice multiple Y maze. The other half were run in a symetrical, long cul maze in which distance and number of successive choice point were equal for a right or wrong choice before the animal reached an cul end or the goal box. The correct path in the long cul maze was identical to that of the short cul maze. S's were run one trial a day for 15 days. On the symetrical, long cul maze there were no differences between groups. On the short cul maze, hippocampals were significantly worse than control S's and looked similar to control S's on the long cul maze. The results are interpreted in terms of frustration theory.


Effects of moderate sleep deprivation and low-dose alcohol on driving simulator performance and perception in young men.
To determine the combined effects of sleep restriction and low-dose alcohol on driving simulator performance, EEG, and subjective levels of sleepiness and performance in the mid-afternoon. Repeated measures with 4 experimental conditions. Normal sleep without alcohol, sleep restriction alone (4 hours) and sleep restriction in combination with 2 different low blood alcohol concentrations (0.025 g/dL and 0.035 g/dL). Sleep Laboratory, Adelaide Institute for Sleep Health. Twenty-one healthy young men, aged 18-30 years, mean (+/-SD) = 22.5(+/-3.7) years, BMI = 25(+/-6.7) kg/m2; all had normal sleep patterns and were free of sleep disorders. Participants completed a 70-minute simulated driving session, commencing at 14:00. Driving parameters included steering deviation, braking reaction time, and number of collisions. Alpha and theta EEG activity and subjective driving performance and sleepiness were also measured throughout the driving task. All measures were significantly affected by time. Steering deviation increased significantly when sleep restriction was combined with the higher dose alcohol. This combination also resulted in a significant increase in alpha/theta EEG activity throughout the drive, as well as greater subjective sleepiness and negative driving performance ratings compared to control or sleep restriction alone. These data indicate that combining low-dose alcohol with moderate sleep restriction results in significant decrements to subjective alertness and performance as well as to some driving performance and EEG parameters. This highlights the potential risks of driving after consumption of low and legal doses of alcohol when also sleep restricted.


Multi-stage sampling for large scale natural resources surveys: a case study of rice and waterfowl.
Large-scale sample surveys to estimate abundance and distribution of organisms and their habitats are increasingly important in ecological studies. Multi-stage sampling (MSS) is especially suited to large-scale surveys because of the natural clustering of resources. To illustrate an application, we: (1) designed a stratified MSS to estimate late autumn abundance (kg/ha) of rice seeds in harvested fields as food for waterfowl wintering in the Mississippi Alluvial Valley (MAV); (2) investigated options for improving the MSS design; and (3) compared statistical and cost efficiency of MSS to simulated simple random sampling (SRS). During 2000-2002, we sampled 25-35 landowners per year, 1 or 2 fields per landowner per year, and measured seed mass in 10 soil cores collected within each field. Analysis of variance components and costs for each stage of the survey design indicated that collecting 10 soil cores per field was near the optimum of 11-15, whereas sampling >1 field per landowner provided few benefits because data from fields within landowners were highly correlated. Coefficients of variation (CV) of annual estimates of rice abundance ranged from 0.23 to 0.31 and were limited by variation among landowners and the number of landowners sampled. Design effects representing the statistical efficiency of MSS relative to SRS ranged from 3.2 to 9.0, and simulations indicated SRS would cost, on average, 1.4 times more than MSS because clustering of sample units in MSS decreased travel costs. We recommend MSS as a potential sampling strategy for large-scale natural resource surveys and specifically for future surveys of the availability of rice as food for waterfowl in the MAV and similar areas.


Interactions between T-2 toxin and its metabolites in HepG2 cells and in silico approach.
The T-2 toxin (T-2) is commonly metabolized to HT-2 toxin (HT-2), Neosolaniol (NEO), T2-triol and T2-tetraol and they can modify the toxicity of T-2. In this study, T-2 and its modified forms were evaluated by in vitro and in silico methods. The in vitro cytotoxicity individually was evaluated by MTT and Total Protein Content (PC) assays in human hepatocarcinoma (HepG2) cells. The order of IC50 was T-2 tetraol > T-2 triol > NEO > T-2 = HT-2. The T-2 and HT-2 evidenced the highest cytotoxic effect in HepG2 cells individually. No differences were observed in binary combinations tested and the two mycotoxins in the mixture tested individually. The T-2+HT-2 combination showed the highest toxic potential with the lowest IC50 value of 34.42 ± 0.58 nM at 24 h. All binary combinations exhibited antagonistic interactions. The ADME and toxicity profile of mycotoxins were obtained by the in silico admetSAR predictive model which determines the metabolic and toxicological approaches in order to know if these mycotoxins might be taken into consideration to support a more realistic and adequate risk assessment.


Role for caveolin-mediated transcytosis in facilitating transport of large cargoes into the brain via ultrasound.
The blood-brain barrier (BBB) is a dynamic diffusional barrier regulating the molecular and chemical flux between the blood and brain, thereby preserving cerebral homeostasis. Endothelial cells form the core anatomical component of the BBB based on properties such as specialized junctional complexes between cells, which restricts paracellular transport, and extremely low levels of vesicular transport, restricting transcytosis. In performing its protective function, the BBB also constrains the entry of therapeutics into the brain, hampering the treatment of various neurological disorders. Focused ultrasound is a novel therapeutic modality that has shown efficacy in transiently and non-invasively opening the BBB for the targeted delivery of therapeutics to the brain. Although the ability of ultrasound to disrupt the junctional assembly of endothelial cells has been partially investigated, its effect on the transcellular mode of transport has been largely neglected. In this study, we found that ultrasound induces a pronounced increase in the levels of the vesicle-forming protein caveolin-1. In order to investigate the role of vesicle-mediated transcytoplasmic transport, we compared the leakage of various cargo sizes between a mouse model that lacks caveolin-1 and wild-type mice following sonication of the hippocampus. The absence of caveolin-1 did not lead to overt abnormalities in the cerebral vasculature in the mice. We found that caveolin-1 has a critical role specifically in the transport of large (500 kDa), but not smaller (3 and 70 kDa) cargoes. Our findings indicate differential effects of therapeutic ultrasound on cellular transport mechanisms, with implications for therapeutic interventions.


Engineering a potent and long-acting GLP-1/Y2 receptor dual agonist as a multi-agonist therapy for diabetes and obesity.
Novel dual agonists for the glucagon-like peptide-1 (GLP-1) and Y2 receptor hold the potential for enhanced efficacy over GLP-1 receptor (GLP-1R) agonists in treating obesity and diabetes. In this study, we aimed to improve the stability and increase the drug development success rate of our previously identified GLP-1/Y2 receptor dual agonist, 6q. To achieve this, we first optimized the structure of the linker within 6q. Additionally, we explored various fatty acid albumin binders to further enhance the stability of 6q. These binders were mainly selected from approved or clinically developed GLP-1R agonists or GLP-1-based multi-agonists. Through this process, we were able to identify a lead peptide, xGLP/PYY-6, that exhibited comparable in vitro potency toward the GLP-1 and Y2 receptors as 6q but with significantly improved stability compared to 6q. In Kunming and DIO mice, xGLP/PYY-6 showed a comparable hypoglycemic effect to semaglutide, and a significantly better effect on inhibiting food intake than semaglutide. In a chronic study in DIO mice, xGLP/PYY-6 exhibited significant metabolic benefits, as reflected by regulation of lipid levels, improved glucose tolerance, weight loss, decreased hepatocellular vacuolation, and the reversal of steatosis effects caused by xGLP/PYY-6. These results indicate the potential of developing xGLP/PYY-6 as an antiobesity, lipid regulation, antisteatotic, and antidiabetic agent.


Confocal fluorescence microscopy: some applications in bone cell biology.
Three-dimensional information is necessary for the proper investigation of the interrelationships of bone cells, and of the complex interface between these cells and the bone matrix they form and destroy. The use of fluorescence confocal microscopy was explored in the determination of the distribution of immunolabelled actin and vinculin--cytoskeletal and attachment proteins--in isolated chick bone cells cultured on dentine, and in neonate rat and rabbit calvaria. Confocal imaging, compared with conventional fluorescence imaging, greatly enhanced the interpretation possible.


Acute coronary syndromes: unstable angina/non-ST elevation myocardial infarction.
Acute coronary syndrome is a major health problem affecting approximately 1.5 million individuals a year. Early diagnosis and appropriate evidence-based therapies improve clinical outcomes significantly. Current data suggest that an early invasive therapy may improve intermediate-term and long-term outcomes, particularly in high-risk individuals. The last few years also have seen significant advances in antiplatelet and antithrombotic therapies for the management of patients who have acute coronary syndrome.


Narrow plasmon mode in 2D arrays of silver nanoparticles self-assembled on thin silver films.
Extinction spectra of 2D arrays of silver nanoparticles self-assembled on 5-20-nm-thick vacuum-deposited silver films exhibit extremely narrow plasmon mode in the blue spectral region, whereas the same particles self-assembled on thin films of Au, Cu, Cr and Ti damp the plasmon resonance. The observed narrowing was attributed to the plasmon coupling between the nanoparticles and between the nanoparticles and surface modes in the underlying silver film.


Mycoplasma hyopneumoniae and Mycoplasma flocculare differential domains from orthologous surface proteins induce distinct cellular immune responses in mice.
Mycoplasma hyopneumoniae and Mycoplasma flocculare are two genetically close species found in the swine respiratory tract. Despite their similarities, while M. hyopneumoniae is the causative agent of porcine enzootic pneumonia, M. flocculare is a commensal bacterium. Genomic and transcriptional comparative analyses so far failed to explain the difference in pathogenicity between these two species. We then hypothesized that such difference might be, at least in part, explained by amino acid sequence and immunological or functional differences between ortholog surface proteins. In line with that, it was verified that approximately 85% of the ortholog surface proteins from M. hyopneumoniae 7448 and M. flocculare present one or more differential domains. To experimentally assess possible immunological implications of this kind of difference, the extracellular differential domains from one pair of orthologous surface proteins (MHP7448_0612, from M. hyopneumoniae, and MF_00357, from M. flocculare) were expressed in E. coli and used to immunize mice. The recombinant polypeptides (rMHP61267-169 and rMF35767-196, respectively) induced distinct cellular immune responses. While, rMHP61267-169 induced both Th1 and Th2 responses, rMF35767-196 induced just an early pro-inflammatory response. These results indicate that immunological properties determined by differential domains in orthologous surface protein might play a role in pathogenicity, contributing to elicit specific and differential immune responses against each species.


Cellular Therapies in Systemic Sclerosis: Recent Progress.
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with a high mortality and morbidity. While progress has been made in terms of identifying high-risk patients and implementing new treatment strategies, therapeutic options remain limited. In the past few decades, various cellular therapies have emerged, which have been studied in SSc and other conditions. Here, we provide a comprehensive review of currently available cellular therapies and critically assess their merit as disease-modifying treatment for SSc. Currently, hematopoietic stem cell transplantation is the only cellular therapy that has demonstrated clinical effects on the immune system, neoangiogenesis, and fibrosis. Robust mechanistic studies as well as clinical trials are essential to move the field forward.


Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth.
The NF-AT transcription factors regulated by the phosphatase calcineurin play a role in breast cancer metastasis-promoting tumor cell invasion. Metastasis is a multistep process requiring angiogenesis and endothelial activation. NF-AT is also expressed in endothelial cells, and calcineurin-NF-AT signaling is an important downstream effector of the proangiogenic cytokine VEGF. One isoform of the endogenous calcineurin regulator, Down syndrome candidate region-1 (DSCR1.Ex4), suppresses calcineurin-NFAT signaling blocking endothelial proliferation. However, overexpression of the other DSCR1 isoform (DSCR1.Ex1) may promote angiogenesis. We report that targeted deletion of both isoforms leads to hyperactivated calcineurin and precocious endothelial apoptosis, inhibiting formation of an effective tumor vasculature and suppressing tumorigenesis. Treatment with the specific pharmacological calcineurin inhibitor cyclosporin A rescues this endothelial defect in DSCR1(-/-) mice, restoring tumor growth.


Dosimetry verification of radioactive seed implantation for malignant tumors assisted by 3D printing individual templates and CT guidance.
We compared the dose distributions of postoperative plans with preoperative plans for 3D printing template-assisted radioactive seed implantations. A total of 14 patients with malignant tumors enrolled in the study. The dose parameters included D90, minimum peripheral dose, V100, V150, and V200. The statistical method was the paired t-test. There was no significant difference in P values between the two groups for all parameters except for V100. The 3D printing guide template can provide good accuracy for radioactive seed implantation.


CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation.
T cells dynamically rewire their metabolism during an immune response. We applied single-cell RNA sequencing to CD8+ T cells activated and differentiated in vitro in physiological medium to resolve these metabolic dynamics. We identify a differential time-dependent reliance of activating T cells on the synthesis versus uptake of various non-essential amino acids, which we corroborate with functional assays. We also identify metabolic genes that potentially dictate the outcome of T cell differentiation, by ranking them based on their expression dynamics. Among them, we find asparagine synthetase (Asns), whose expression peaks for effector T cells and decays toward memory formation. Disrupting these expression dynamics by ASNS overexpression promotes an effector phenotype, enhancing the anti-tumor response of adoptively transferred CD8+ T cells in a mouse melanoma model. We thus provide a resource of dynamic expression changes during CD8+ T cell activation and differentiation, and identify ASNS expression dynamics as a modulator of CD8+ T cell differentiation.


Penalized logistic regressions with technical indicators predict up and down trends.
Correctly predicting up and down trends for stock prices is of immense important in the financial market. To further improve the prediction performance, in this paper we introduce five penalties: ridge, least absolute shrinkage and selection operator, elastic net, smoothly clipped absolute deviation and minimax concave penalty to logistic regressions with 19 technical indicators, and propose the five penalized logistic regressions to predict up and down trends for stock prices. Firstly, we translate the five penalized logistic log-likelihood functions into the five penalized weighted least squares functions and combine them with the tenfold cross-validation method to calculate the solution path to parameter estimators. Secondly, we combine the binomial deviation with cross-validation error as a risk measure to choose an appropriate tuning parameter for the penalty functions and apply the training set and the coordinate descent algorithm to obtain parameter estimators and probability estimators. Thirdly, we employ the testing set and the chosen optimal thresholds to construct two-class confusion matrices and receiver operating characteristic curves to assess the prediction performances to the five regressions. Finally, we compare the proposed five penalized logistic regressions with logistic regression, support vector machine and artificial neural network and found that the minimax concave penalty logistic regression performs the best in terms of the prediction performance to up and down trends for Google's stock prices. Therefore, in this paper we propose the five new prediction methods to improve the prediction accuracy of stock returns and bring economic benefits for investors.


Screening for genotoxic activity of amitraz with short-term bacterial assays.
Genotoxic effects of both amitraz and its metabolites made by S9 fraction were reevaluated in short-term bacterial assays. Neither amitraz nor its metabolites induced frameshift mutation or caused base-pair substitution as detected by the Ames test. They also did not introduce any damages into DNA recognized by correndonuclease II as shown by the repair test. Metabolites of amitraz (but not amitraz itself) induced the SOS-repair system in E. coli strain PQ 243 tagA, alkA which was deficient in N-glycosylases. It is concluded that neither amitraz nor its metabolites have mutagenic activity. In contrast to amitraz, its metabolites alkylate DNA in the N3-position of adenine.


Analysis of metabolite differences between South Korean and Chinese yellow goosefish (Lophius litulon) using capillary electrophoresis time-of-flight mass spectrometry.
The yellow goosefish is a benthic fish that belongs to the family Lophiidae and order Lophiiformes and is distributed in the Yellow and East China Seas. This study aimed to distinguish between yellow goosefish from different geographical origins by analyzing their metabolites. Capillary electrophoresis time-of-flight mass spectrometry was used to analyze metabolite profiles in the muscle tissues of yellow goosefish to distinguish between Korean and Chinese yellow goosefish. In total, 271 putative metabolites were extracted using 50% acetonitrile in water. Principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to distinguish different geographical origins using the metabolite profiles obtained. The R2 and Q2 values of the OPLS-DA model were 0.856 and 0.695, respectively, indicating that the model was well-fitted and had good predictability. The heat map revealed that nucleic acid and amino compounds differed between the Korean and Chinese fish, and the variable importance in the projection scores obtained from OPLS-DA showed that there were geographical differences in the primary metabolites (5'-methylthioadenosine, adenosine, uridine 5-diphosphate, guanosine 5-diphosphate, urea, homocarnosine, O-acetylcarnitine, cycloleucine, cycloleucine S-adenosylmethionine, S-adenosylhomocysteine, ethanolamine, myo-inositol 1-phosphate), which were identified as potential candidate biomarkers.


Growth management of white-rot fungus Phlebia brevispora improved degradation of high-molecular-weight polycyclic aromatic hydrocarbons.
The effect of co-culturing white-rot fungus Phlebia brevispora with growth-promoting bacterial strains Enterobacter sp. TN3W-14 and Pseudomonas sp. TN3W-8 on the degradation of polycyclic aromatic hydrocarbons (PAHs) was evaluated in liquid culture. In axenic cultures, P. brevispora strains TN3F and TMIC33929 showed high degradation of phenanthrene (> 98%) within 15 days, and degraded 65% and 63% of pyrene, and 12% and 8% of benzo(a)pyrene, respectively. This low level of degradation ability toward benzo(a)pyrene was improved significantly by co-culturing the fungi with a mixture of bacterial strains TN3W-8 and TN3W-14 (mixed bacterial co-culture; MBC). Within 15 days, P. brevispora TN3F with MBC achieved about 86% pyrene and 53% benzo(a)pyrene degradation; P. brevispora TMIC33929 with MBC showed 92% pyrene and 72% benzo(a)pyrene degradation. The MBC alone degraded little PAH, as its growth was inhibited by PAH; however, its co-culture with P. brevispora improved mycelial growth of the fungus, which led to improved degradation of the PAHs. A possible dihydrodiol metabolite of pyrene from fungal cultures suggests that hydroxylation was the first step in the degradation of pyrene by P. brevispora.


Potential of autochthonous fungal strains isolated from contaminated soils for degradation of polychlorinated biphenyls.
Up to now, most studies on polychlorinated biphenyl (PCB) bioremediation have examined the ability of model fungal strains to biodegrade PCBs. Yet, there is limited information concerning the potential of autochthonous filamentous fungal strains in the biodegradation of PCBs and their possible use in the environmental technologies. In this study, we investigated the capacity of autochthonous fungal strains in the biodegradation of PCBs by isolating 24 taxa from former industrial sites highly contaminated by PCBs. Microscopic and molecular analyses using the internal transcribed spacer (ITS) region revealed that the fungal strains belonged to the phyla Ascomycota (19 strains) and Zygomycota (five strains). The chromatography gas analysis revealed evidence of degradation of seven PCB congeners. With the exception of Circinella muscae which presented no degradation potential, the other fungal strains exhibited a rate of biodegradation ranging from 29 to 85 % after 7 d of incubation in liquid medium. Among these strains, Doratomyces nanus, Doratomyces purpureofuscus, Doratomyces verrucisporus, Myceliophthora thermophila, Phoma eupyrena, and Thermoascus crustaceus showed remarkable degradation ability (>70 %) regardless of the number of chlorine substituents on the biphenyl nucleus and a high tolerance towards PCBs. To our knowledge, this is the first study that demonstrates the ability of PCB degradation by these species and indicates the potential effectiveness of some autochthonous fungal strains in bioremediation systems.


Observations about subcalcaneal adventitial bursitis (heel fat pad inflammatory lesion) in rheumatoid arthritis. Comment on the article of Suzuki and Shirai.
Not available.


Diagnosis and Management of Classical Hodgkin Lymphoma During the COVID-19 Pandemic.
The coronavirus disease 2019 (COVID-19) pandemic has brought life to a standstill globally. Intermittent quarantines were applied to control the pandemic and reduce contamination. During the pandemic, patients with hematological malignancies were among the most vulnerable population. Our aim was to compare in terms of demographic data, disease-related factors, symptom-to-diagnosis interval, diagnosis-to-treatment interval , and interim and end-of-treatment response in classical Hodgkin lymphoma patients diagnosed during the pandemic and in the pre-pandemic periods. A total of 90 patients were included, of which 65 and 25 were diagnosed in the 2 years before the pandemic and the 12-month period during the pandemic, respectively. Demographic features were comparable in both groups. Although the percentage of patients with advanced-stage disease was higher during the pandemic (64% vs 53.8%), this difference did not reach statistical significance (P = 0.384). The median symptom-to-diagnosis interval was significantly longer during the pandemic than was observed within the pre-pandemic era (16 weeks vs 8 weeks, P = 0.042). The median diagnosis-to-treatment intervals was similar in both groups (13 days vs 15 days, P = 0.253). In the pre-pandemic and pandemic periods, 85.2% and 72.7% of the patients had complete response at end-of-treatment evaluation, respectively (P = 0.208). We found that symptom-to-diagnosis interval was significantly prolonged during the pandemic. Higher percentage of patients with advanced-stage disease during the pandemic might also be due to this delay, nevertheless, this difference did not reach to a significant difference regarding treatment response in both groups.


Nutrients enriched biochar production through Co-Pyrolysis of poultry litter with banana peduncle and phosphogypsum waste.
Poultry litter (PL) utilisation has been widely studied for production of phosphorus (P) rich biochars. Recent research documented co-pyrolysis of PL with nutrient rich chemical additives like rock phosphate, phosphoric acid and magnesium (Mg) salts for production of P-Mg enriched biochar with improved P use efficiency. However, research is highly scarce on utilisation of waste materials for production of PL biochar enriched in P, potassium (K) and sulphur (S). In this context, present work investigated co-pyrolysis (700°C, 10°C/min, 1h residence time) of PL with banana peduncle (BP) and phosphogypsum (PG) in different w/w ratios (1:1:1, 1:2:1, 1:3:1) of BP-PL-PG for production of K-P-S enriched biochars composites. These biochars mainly showed variations in their K-P-S contents. The K (5.1%) and S (11.35%) enrichment was relatively higher in BP-PL-PG (1:1:1) biochar than PL biochar (K-3.70% and S-0.96%). However, P content was higher in PL biochar (4.48%) and was reduced in biochar composites. The P contents were 3.84, 2.84, and 2.44% in BP-PL-PG (1:3:1), BP-PL-PG (1:2:1) and BP-PL-PG (1:1:1) composites respectively. In biochars, P was present predominantly as Ca-Mg bound form. Furthermore, best fit of second order kinetic model indicated slow-release behaviour of P from biochars and composites. These results highlight the scope of co-pyrolysis of PL with selected wastes for production of multi-nutrients enriched biochars with improved nutrient availability for soil application.


Developmental defects and impaired network excitability in a cerebral organoid model of KCNJ11 p.V59M-related neonatal diabetes.
The gene KCNJ11 encodes Kir6.2 a major subunit of the ATP-sensitive potassium channel (KATP) expressed in both the pancreas and brain. Heterozygous gain of function mutations in KCNJ11 can cause neonatal diabetes mellitus (NDM). In addition, many patients exhibit neurological defects ranging from modest learning disorders to severe cognitive dysfunction and seizures. However, it remains unclear to what extent these neurological deficits are due to direct brain-specific activity of mutant KATP. We have generated cerebral organoids derived from human induced pluripotent stem cells (hiPSCs) possessing the KCNJ11 mutation p.Val59Met (V59M) and from non-pathogenic/normal hiPSCs (i.e., control/WT). Control cerebral organoids developed neural networks that could generate stable synchronized bursting neuronal activity whereas those derived from V59M cerebral organoids showed reduced synchronization. Histocytochemical studies revealed a marked reduction in neurons localized to upper cortical layer-like structures in V59M cerebral organoids suggesting dysfunction in the development of cortical neuronal network. Examination of temporal transcriptional profiles of neural stem cell markers revealed an extended window of SOX2 expression in V59M cerebral organoids. Continuous treatment of V59M cerebral organoids with the KATP blocker tolbutamide partially rescued the neurodevelopmental differences. Our study demonstrates the utility of human cerebral organoids as an investigative platform for studying the effects of KCNJ11 mutations on neurophysiological outcome.


Protocol for the management of ankylosis of the temporomandibular joint.
Ankylosis of the temporomandibular joint (TMJ) is a severely deforming, disabling condition as a result of craniomandibular fusion caused mainly by condylar fractures with displacement of the meniscus. Ankylosis may be fibrous, fibro-osseous, or bony, and unilateral or bilateral. The severity of the deformity is based on the onset, duration, and type of ankylosis. Various surgical techniques have been described for treatment, but no single treatment is recommended because of inconsistent results and the high rate of failure. While our total experience extends to 300 cases, we have developed a protocol using the most recent 193 patients to address our earlier high failure rate. The onset was during childhood in 168 patients, and 25 were adults. We describe the protocol that we developed for these two groups. Our management included gap arthroplasty, costochondral grafting, temporalis flaps, ramus osteotomies, and transport distraction.


Five-year change of periodontal diseases in the Study of Health in Pomerania (SHIP).
To assess the extent of remission and progression of periodontal diseases among adults in a Northeast German Region. The Study of Health in Pomerania (SHIP) is a population-based cohort study with baseline examinations conducted in 1997-2001 and 5-year-follow-up in 2002-2006. The study comprised 2558 subjects aged 20-81 years. Periodontal status was assessed by probing depth (PD) and attachment level (AL), measured at four surfaces per tooth, half-mouth. An event was defined as AL progression or remission of ≥3 mm on ≥2 sites. Average change in mean AL (mean PD) was 0.10 mm (-0.05 mm) during follow-up, equalling 0.02 mm/year (-0.01 mm/year). Adjusted for gender and follow-up time, change in mean AL was significantly higher in 20-29- and 60-69-year-old patients compared with 50-59-year-old patients (p < 0.05). 6.5 (7.5) events of progression (remission) in AL per 100 person-years were observed. In multivariate models, risk factors for progression comprised current smoking, middle or low education, being single or divorced and diabetes (p < 0.05). Enhanced progressive attachment loss seen in 20-29- and 60-81-year-old patients was explained through unfavourable risk factors distributions. Periodontal progression was moderate. Periodontal prophylaxis and motivation to reduce risk factors should especially be addressed to patients having unfavourable risk factor distributions.


Age-related changes in body composition, hydroxyproline, and creatinine excretion in normal women.
We have made a cross-sectional study of relationships among age, whole body bone mineral content (WBBMC), and non-bone lean body mass (NBLBM) measured by dual energy X-ray absorptiometry (DXA), and daily excretion of hydroxyproline (OHP) and creatinine (Cr) in a group of normal women. WBBMC fell with age from the 6th decade, whereas NBLBM was almost constant. Creatinine excretion fell with age from the 5th decade until the 9th, to a much greater degree than NBLBM, reaching a nadir in the 8th decade. Daily excretion of hydroxyproline showed a peak in the 6th decade and fell moderately thereafter. The greater fall of creatinine compared with hydroxyproline resulted in rising OHP/Cr ratios with advancing age, in contrast to the pattern of hydroxyproline excretion. The use of creatinine as a correction for urine dilution or for lean body mass (LBM) in assays for markers of bone turnover must therefore be viewed with caution.


Effect of Surfosept and Deconex® 53 Disinfectant Agents on the Accuracy and Dimensional Stability of Panasil Dental Impression Materials: An Experimental Study.
This in vitro study was performed on 30 dental casts. The samples were divided into one control group and two experimental groups to be disinfected with Surfosept (1%) and Deconex® 53 (2%) using a sequential sampling method (10 per group). The impressions in the experimental groups (i.e., Surfosept and Deconex® 53) were rinsed and dried; then, the disinfectant was sprayed on the impressions and remained for 30 seconds before pouring with stone. In the control group, the impressions were only rinsed and dried and were poured in 10 minutes. Cast dimensions were measured by a profile projector device, and the mean values obtained from the experimental groups were compared with those of the control group. There were no significant differences among the groups regarding the height of the resulting dies without undercut (P=0.62). Moreover, there was no significant difference among the groups regarding the distance between the two dies (P=0.77). However, the diameter of the dies with undercut and without undercut was different significantly among the control and experimental groups (P < 0.005). In general, no significant difference was encountered between dimensional stability and accuracy of the dental impressions using Surfosept and Deconex® 53 in this study.


Twelve years of experience with cytotoxic therapy in malignant tumors of the neck and head.
Since 1968 we have treated with antiblastic drugs 164 malignant tumors recurrent or incurable by surgery or radiotherapy in 151 cases. Different therapeutic methods were employed. Today we have the possibility of selecting alternative options with incipient or relatively delimited carcinomas, principally the substitution of radical surgery by initial associated physical and chemical treatment, so that if there is a cure the consequences of radical surgery can be avoided. We emphasize the curve of two primary cancers of the uvula with 300 mg bleomycin exclusively and the results observed in oropharyngeal and laryngeal carcinomas by using three intermittent Schabel cycles and 4,000 rad Telecobalt, avoiding a radical surgery.


Deletion of psbJ leads to accumulation of Psb27-Psb28 photosystem II complexes in Thermosynechococcus elongatus.
The life cycle of Photosystem II (PSII) is embedded in a network of proteins that guides the complex through biogenesis, damage and repair. Some of these proteins, such as Psb27 and Psb28, are involved in cofactor assembly for which they are only transiently bound to the preassembled complex. In this work we isolated and analyzed PSII from a ΔpsbJ mutant of the thermophilic cyanobacterium Thermosynechococcus elongatus. From the four different PSII complexes that could be separated the most prominent one revealed a monomeric Psb27-Psb28 PSII complex with greatly diminished oxygen-evolving activity. The MALDI-ToF mass spectrometry analysis of intact low molecular weight subunits (<10kDa) depicted wild type PSII with the absence of PsbJ. Relative quantification of the PsbA1/PsbA3 ratio by LC-ESI mass spectrometry using (15)N labeled PsbA3-specific peptides indicated the complete replacement of PsbA1 by the stress copy PsbA3 in the mutant, even under standard growth conditions (50μmol photons m(-2) s(-1)). This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial.


The distribution of eutherian body weights.
The frequency distributions of eutherian body weights given by Caughley and Krebs (1983) are here corrected for an algebraic error in that publication. The distributions for hervibores and omnivores combined and for carnivores and insectivores combined are bimodal, the trough for the first group lying between 25 and 35 kg and for the second between 0.1 and 0.3 kg. The trough within the distribution of weights for herbivores and omnivores combined has been suggested (Caughley and Krebs 1983) as dividing those species whose populations are regulated intrinsically from the larger species whose populations are regulated extrinsically.


Abnormal chordal insertion: a cause of mitral valve prolapse.
Although the morphology of mitral valve prolapse (MVP) has been described, abnormalities of chordal arrangement and insertion have not been emphasized. We retrospectively reviewed 23 surgically-excised MVP and 10 control mitral valves removed at necropsy. Two-dimensional echocardiograms (2DE) were available in 10 MVP and in six additional controls. 2DE accurately assessed the length of anterior leaflet (AL) and posterior leaflet (PL) of the mitral valve (3.2 +/- 0.7 cm and 2.2 +/- 0.6 cm, respectively) as compared to morphologic measurements (3.0 +/- 0.4 cm and 2.1 +/- 0.4 cm, respectively). However, annular diameter as assessed by echocardiography was significantly less (4.6 +/- 0.7 cm) than that derived by morphologic measurements of annular circumference (AC) (5.3 +/- 0.7 cm). The AL and PL lengths and the mitral anuli were significantly larger in patients with MVP as compared to controls (p less than 0.01) when assessed both by 2DE and by morphology. The ratio of the maximum distance of chordal separation/AC was 0.11 +/- 0.04 in MVP and 0.13 +/- 0.02 in controls (p less than 0.05). Chordal divisions were increased in MVP (4.2) compared to controls (3.1, p less than 0.01). The most striking morphologic feature of MVP was abnormal chordal insertion and a random, unpredictable pattern of chordal distribution. We postulate that abnormal chordal architecture may be responsible for unequal stress on the valve leaflets and may thus lead to MVP.


Fibrinogen gene variation and ischemic stroke.
Plasma fibrinogen level and fibrin clot structure are heritable traits that may be of importance in the pathogenesis of ischemic stroke. To investigate associations between variation in the fibrinogen gamma (FGG), alpha (FGA) and beta (FGB) genes, fibrinogen level, and ischemic stroke. The Sahlgrenska Academy Study on Ischemic Stroke comprises 600 cases and 600 matched population controls. Stroke subtypes were defined according to TOAST criteria. Plasma fibrinogen level was measured by an automated clot-rate assay. Eight tagging single nucleotide polymorphisms (SNPs) were selected to capture genetic variation in the FGA, FGG, and FGB genes. Plasma fibrinogen was independently associated with overall ischemic stroke and all subtypes, both in the acute stage (P < 0.001) and at three-month follow-up (P < 0.05). SNPs belonged to two haplotype blocks, one containing the FGB gene and the other the FGG and FGA genes. FGB haplotypes were associated with fibrinogen level (P < 0.01), but not with ischemic stroke. In contrast, FGG/FGA haplotypes showed independent association to ischemic stroke but not to fibrinogen level. In an additive model with the most common FGG/FGA haplotype (A1) as reference, the adjusted odds ratios of ischemic stroke were 1.4 [95% confidence interval (95% CI) 1.1-1.8], P < 0.01, 1.4 (95% CI 1.0-1.8), P < 0.05, and 1.5 (95% CI 1.0-2.1), P < 0.05 for the A2, A3, and A4 FGG/FGA haplotypes, respectively. FGG/FGA haplotypes show association to ischemic stroke. This association is independent of fibrinogen level, thus suggesting that the association between ischemic stroke and variation at the FGG/FGA genes is mediated by qualitative rather than quantitative effects on fibrin(ogen).


Antiarrhythmic peptide has no direct cardiac actions.
The electrophysiologic, inotropic, and muscarinic effects of antiarrhythmic peptide (AAP) were examined in canine cardiac Purkinje fibers, ferret papillary muscle, and canine cardiac membranes, respectively. Aside from a prolongation of time to peak force in papillary muscle, no biologically significant effects of AAP could be determined in any preparation, suggesting that its antiarrhythmic effects are not mediated by direct membrane actions.


Signals for the selection of a splice site in pre-mRNA. Computer analysis of splice junction sequences and like sequences.
To evaluate the importance of the surrounding nucleotide sequence in the selection of a splice site for mRNA, we have carried out computer studies of eukaryotic protein genes whose entire nucleotide sequences were available. A splice site-like sequence that has a significant homology to the consensus splice junction sequences is frequently found within an intron and exon. It is found that the higher the homology of a candidate donor site sequence to the nine-nucleotide consensus sequence, the higher is its probability of being a donor site. For most of the donors, the stability of presumed base-pairing with U1-RNA is higher than that of donor-like sequences, if any, in the adjacent exon and intron. However, homology of a candidate acceptor sequence to the 15-nucleotide consensus is a poor criterion of an acceptor site. The presence of a sequence that could serve as a branch-point 18 to 37 nucleotides before an acceptor does not seem to be critical in distinguishing it from an acceptor-like sequence. For genes of human, rat, mouse and chicken, respectively, nucleotide frequencies around splice junctions of many genes have been calculated. They seem to be different at some positions around a donor site from species to species. The acceptors for these vertebrates have longer pyrimidine-rich regions than the previous consensus sequence. The newly derived nucleotide frequencies were used as the standard to calculate the weighted homology score of a candidate splice site sequence in a gene of the four species. This weighted homology score of the 40 to 60-nucleotide intron-exon sequence is a much better criterion of an acceptor. These results suggest that the most important signal in the selection of a splice resides in the surrounding nucleotide sequence. It is also suggested that the surrounding nucleotide sequence alone is not generally sufficient for the selection.


Effects of Homocysteine on white matter diffusion parameters in Alzheimer's disease.
The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores. We enrolled 132 patients with AD and analyzed white matter (WM) macrostructural changes using diffusion tensor neuroimaging parameters including fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (axial-D) and radial diffusivity (RD). Two neuroimaging post-processing analyses were performed to provide complementary data. First, we calculated 11 major bundle microstructural integrities using a WM parcellation algorithm, and correlated them with serum homocysteine levels to explore whether the fiber bundles were affected by homocysteine. Second, we used tract-based spatial statistics to explore the anatomical regions associated with homocysteine levels. Changes in cognitive test scores caused by homocysteine served as the major outcome factor. The results suggested that homocysteine levels did not have a direct impact on cross-sectional cognitive test scores, but that they were inversely correlated with renal function, B12 and folate levels. Topographies showing independent correlations with homocysteine in FA and MD were more diffusely located compared to the posterior brain regions in axial-D and RD. In the association bundle analysis, homocysteine levels were significantly correlated with the four diffusion parameters even after correcting for confounders, however no association between homocysteine and WM to predict cognitive outcomes was established. In our patients with AD, homocysteine levels were associated with renal dysfunction and decreased levels of vitamin B12 and folate, all of which require clinical attention as they may have been associated with impaired WM microstructural integrity and modulated cognitive performance in cross-sectional observations.


Effects of postoperative environment on recovery of function after fimbria-fornix transection in the rat.
We have previously found that rats given dorsal hippocampus lesions show reduced deficits on maze learning, spontaneous alternation and extinction tasks when housed postoperatively in an "enriched" as opposed to an "impoverished" environment. In contrast, postoperative enriched conditions were ineffective in rats given bilateral entorhinal cortex lesions. In this study, we examined whether postoperative differential housing would reduce the impairment in radial maze performance induced by fimbria-fornix transections. Significant interactions were found between lesion state and housing condition for the total number of errors made, the number of errors on the first eight arms visited and for the number of arms visited before the first error in an 8-arm maze. The interaction was due to the fact that, in sham-operated rats, isolated ones made more errors than enriched counterparts whereas, in rats with lesions, enriched ones showed no improvement of performance in comparison to isolated counterparts. These data suggest that the integrity of fimbria-fornix pathways is an important factor for the expression of facilitated maze performance in intact enriched rats and in enriched rats with hippocampal system damage.


AAV2-Neurturin for Parkinson's Disease: What Lessons Have We Learned?
The dream that trophic factors could be effectively delivered and potently forestall and reverse the symptoms of Parkinson's disease (PD) has yet to be realized. Research in this area has been active for 20 years, but after much work, the prospects for utilizing trophic factors in the treatment of PD are currently dim. Millions of dollars have been spent, numerous academic, foundation, and government resources have been invested, and hundreds of patient research volunteers have contributed their time and hope to this effort without a therapeutic breakthrough. As a scientist who has journeyed these events from the beginning and participated in many of the decisions that navigated this field, I consider it important for the movement disorder scientific community to reflect on the evolution of thought and to participate in the dialog over whether the investments were worthwhile.The most studied group of trophic factor for PD is the glial cell derived family of ligands, of which glial cell derived neurotrophic factor (GDNF) and neurturin are members, and are the best studied. I trace the development of these factors chronologically with commentary on the key decision-making points. Before we collectively invest further, I offer this scientific reflection on the past and offer my own view on the next steps of research in the field of neurotrophins as potential therapeutic agents in PD.


Station in early labor in nulliparous women at term.
Several authors of standard obstetric texts state that engagement occurs before the onset of labor in a majority of nulliparas at term, and failure of the fetal head to engage in early labor is a greater indicator for operative birth. A pilot clinical descriptive study was done at University Hospital, University of Medicine and Dentistry of New Jersey, in Newark to examine the birth outcomes of nulliparous women who arrived in early labor with an unengaged vertex presentation at term. For the study, 146 births were reviewed, and data from 101 vertex deliveries that met the study's criteria were compiled to test this hypothesis. The study results showed that in approximately 31% of the nulliparas, the fetal head was engaged. The incidence of the unengaged vertex in early labor in nulliparous women who met the study's criteria was found to be 69%. This factor alone did not predict birth outcome.


Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11.
Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy that is characterized by poor prognosis. RNA-binding motif protein 15 (RBM15) has been identified as an oncogene in multiple tumors. Nevertheless, the function and mechanism of RBM15 in ccRCC are not clear. In this study, RBM15 was found to be upregulated in ccRCC cells and tissues. RBM15 enhanced the proliferation, clone formation, migration, invasion and epithelial-interstitial transition of ccRCC cells. Enhanced RBM15 was caused by the abundant histone 3 acetylation modification of the RBM15 promoter induced by EP300/CBP. RBM15 enhanced the stability of CXCL11 mRNA in an m6A-dependent manner. Moreover, RBM15 was found to promote macrophage infiltration and M2 polarization by promoting the secretion of CXCL11 in ccRCC cells in vitro and in vivo. Our findings highlight the function of RBM15 in ccRCC and reveal a novel identified EP300/CBP-RBM15-CXCL11 signaling axis, which promotes ccRCC progression and provides new insight into ccRCC therapy.


Adverse reaction to 99Tcm sulfur colloid in a routine examination. A case report.
The case of a patient in whom an allergic reaction developed after injecting 99Tcm sulfur colloid for a routine liver scan is herein presented. Since this reaction did not appear when injecting the same patient 99Tcm polyphosphate for a bone scan, it can be assumed that the allergic reaction was due to the stabilizer.


Experimental validation of the free-energy principle with in vitro neural networks.
Empirical applications of the free-energy principle are not straightforward because they entail a commitment to a particular process theory, especially at the cellular and synaptic levels. Using a recently established reverse engineering technique, we confirm the quantitative predictions of the free-energy principle using in vitro networks of rat cortical neurons that perform causal inference. Upon receiving electrical stimuli-generated by mixing two hidden sources-neurons self-organised to selectively encode the two sources. Pharmacological up- and downregulation of network excitability disrupted the ensuing inference, consistent with changes in prior beliefs about hidden sources. As predicted, changes in effective synaptic connectivity reduced variational free energy, where the connection strengths encoded parameters of the generative model. In short, we show that variational free energy minimisation can quantitatively predict the self-organisation of neuronal networks, in terms of their responses and plasticity. These results demonstrate the applicability of the free-energy principle to in vitro neural networks and establish its predictive validity in this setting.


Extractive spectrophotometric method for determination of metribuzin herbicide and application of factorial design in optimization of various factors.
A simple extractive spectrophotometric method has been described for the determination of metribuzin herbicide. Metribuzin was reacted with copper and a stable complex in the presence of ammonia (0.2M) at pH 10.5 was formed. The resulting yellow coloured complex was extracted in chloroform and showed absorption maxima at 340 nm. Beer's law was obeyed in the range of 0.8-25 microg mL(-1) with molar absorptivity of 5.67 x 10(3)L mol(-1)cm(-1). The composition of the complex was studied by Job's method of continuous variation and the results indicated that the mole ratio of metribuzin:Cu(2+) is 2:1. The optimum reaction conditions for complexation and other analytical parameters were evaluated. A two-level factorial design was also used to determine the effect of different parameters and their interaction on metribuzin:Cu(2+) complex formed. The method was successfully applied for the determination of metribuzin in commercial formulations and real samples.


Defective neutrophil chemotaxis resulting from thermal injury: restoration of directed migration by increasing Boyden chamber filter pore size.
Decreased chemotaxis of burn patient neutrophils has been observed in many studies. This study attempts to analyze the basis of this defect by determining the effect of filter pore size on chemotaxis, utilizing the Boyden chamber technique. Directed migration of burn patient neutrophils, as compared to normal controls, was greatly decreased when 3.0-micron filters were used. When 8.0-micron filters were used, however, the directed migration of burn patient neutrophils was identical to that of the normal controls. These findings indicate that the failure of burn patient neutrophils to undergo directed migration using Boyden chambers is not due to an inability to migrate toward a chemoattractant. Our data suggests that when utilizing the Boyden chamber technique to measure chemotaxis, the failure to give a normal response should not necessarily be interpreted as a chemotactic defect. In fact, mechanical impediments may play a major role in the decreased migration.


Measuring the route topography impact on real driving emissions based on neural network models.
Route topography is an important test boundary of real driving emission (RDE) tests. However, the RDE test boundaries, such as atmospheric environment, driver behavior, route topography, and traffic congestion, are random, uncertain, and completely coupled. It is difficult to know to what extent route topography can determine on-road emissions, especially in a region with hilly topography. In this regard, the neural network predictor importance algorithms were proposed to measure the importance of the route topography test boundary. Based on tens of thousands of data window samples from the RDE tests in Chongqing, factor analysis was performed to reduce the data dimensionality and eliminate information overlap, and neural network models were established to predict pollutant emissions and calculate the relative importance of input variables. The results show that route topography is comparable to trip dynamics for on-road emissions but the importance of the route topography test boundary is not fully appreciated in the existing RDE regulation, making mountain cities suffer from severe vehicle emissions that are not effectively controlled.


Biochar-amended composting of lincomycin fermentation dregs promoted microbial metabolism and reduced antibiotic resistance genes.
Improper disposal of antibiotic fermentation dregs poses a risk of releasing antibiotics and antibiotic resistant bacteria to the environment. Therefore, this study evaluated the effects of biochar addition to lincomycin fermentation dregs (LFDs) composting. Biochar increased compost temperature and enhanced organic matter decomposition and residual antibiotics removal. Moreover, a 1.5- to 17.0-fold reduction in antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) was observed. Adding biochar also reduced the abundances of persistent ARGs hosts (e.g., Streptomyces, Pseudomonas) and ARG-related metabolic pathways and genes (e.g., ATP-binding cassette type-2 transport, signal transduction and multidrug efflux pump genes). By contrast, compost decomposition improved due to enhanced metabolism of carbohydrates and amino acids. Overall, adding biochar into LFDs compost reduced the proliferation of ARGs and enhanced microbial community metabolism. These results demonstrate that adding biochar to LFDs compost is a simple and efficient way to decrease risks associated with LFDs composting.


Color tuning and white light emission by codoping in isostructural homochiral lanthanide metal-organic frameworks.
Four lanthanide-based homochiral metal-organic frameworks (Ln-HMOFs), {[Ln2(HL)2(H2O)4]·2Cl·5H2O} n [Ln = Gd (1), Eu (2), Tb (3) and Dy (4)], have been synthesized through solvothermal reactions of chiral ligand (S)-5-(((1-carboxyethyl)amino)methyl)isophthalic acid (H3L) with corresponding LnCl3·6H2O. They are binodal (3,6)-connected frameworks with kgd nets based on binuclear cluster units and zwitterionic (HL)2- linkers. Considering the isostructuralism of these Ln-HMOFs as well as the blue emission of compound 1 and the strong typical Eu3+ and Tb3+ emissions of compounds 2 and 3, single-phase mixed-lanthanide HMOFs have been prepared by doping of Ln3+ into the Ln-HMOFs to modulate light-emitting color. Interestingly, the bimetallic doped Eu/Tb-HMOFs [(Eu x Tb1-x )2(HL)2(H2O)4]·2Cl·5H2O display a fluent change of light-emitting color among green, yellow, orange, orange-red, and red by adjusting the doping concentration of Eu3+ ions into the Tb-HMOF. Very importantly, the trimetallic doped Eu/Gd/Tb-HMOF [(Eu0.1388Gd0.6108Tb0.2504)2(HL)2(H2O)4]·2Cl·5H2O emits white light upon excitation at 355 nm, whose emission can also be switched between different colors when excited with different ultraviolet light. Furthermore, the fluorescence response of Tb-HMOF to various usual metal ions, and especially fluorescent sensing behaviours to Fe3+, Cr3+ and Al3+ have been preliminarily investigated.


Management of physical health in schizophrenia: a stepping stone to treatment success.
While patients with schizophrenia are known to have an increased risk of physical health co-morbidity including coronary heart disease, diabetes, hypertension, stroke and emphysema, their physical wellbeing often goes unnoticed by health care professionals. In many cases the patient's only contact with the health service is through the mental health team. However, many psychiatrists consider their primary function to be the provision of clinical care in terms of symptom control and are reluctant to switch medication despite the presence of physical health issues. Nevertheless outcomes in schizophrenia may be improved by expanding the remit of the clinician to include assessments of both physical and mental health. Simple measurements such as waist circumference, weight, height, blood pressure and blood sampling would provide the psychiatrist with useful information that could be used to optimize treatment and improve overall quality of life for patients with schizophrenia.


Sarcolipin haploinsufficiency prevents dystrophic cardiomyopathy in mdx mice.
Sarcolipin (SLN) is an inhibitor of sarco/endoplasmic reticulum (SR) Ca2+-ATPase (SERCA) and expressed at high levels in the ventricles of animal models for and patients with Duchenne muscular dystrophy (DMD). The goal of this study was to determine whether the germline ablation of SLN expression improves cardiac SERCA function and intracellular Ca2+ (Ca2+i) handling and prevents cardiomyopathy in the mdx mouse model of DMD. Wild-type, mdx, SLN-haploinsufficient mdx (mdx:sln+/-), and SLN-deficient mdx (mdx:sln-/-) mice were used for this study. SERCA function and Ca2+i handling were determined by Ca2+ uptake assays and by measuring single-cell Ca2+ transients, respectively. Age-dependent disease progression was determined by histopathological examinations and by echocardiography in 6-, 12-, and 20-mo-old mice. Gene expression changes in the ventricles of mdx:sln+/- mice were determined by RNA-Seq analysis. SERCA function and Ca2+i cycling were improved in the ventricles of mdx:sln+/- mice. Fibrosis and necrosis were significantly decreased, and cardiac function was enhanced in the mdx:sln+/- mice until the study endpoint. The mdx:sln-/- mice also exhibited similar beneficial effects. RNA-Seq analysis identified distinct gene expression changes including the activation of the apelin pathway in the ventricles of mdx:sln+/- mice. Our findings suggest that reducing SLN expression is sufficient to improve cardiac SERCA function and Ca2+i cycling and prevent cardiomyopathy in mdx mice.NEW & NOTEWORTHY First, reducing sarcopolin (SLN) expression improves sarco/endoplasmic reticulum Ca2+ uptake and intracellular Ca2+ handling and prevents cardiomyopathy in mdx mice. Second, reducing SLN expression prevents diastolic dysfunction and improves cardiac contractility in mdx mice Third, reducing SLN expression activates apelin-mediated cardioprotective signaling pathways in mdx heart.


[D-Leu-4]-OB3, an orally bioavailable leptin-related synthetic peptide insulin sensitizer: a study comparing the efficacies of [D-Leu-4]-OB3 and metformin on energy balance and glycemic regulation in insulin-deficient male Swiss Webster mice.
The effects of oral delivery of exenatide or pramlintide acetate in dodecyl maltoside (DDM) on energy balance and glycemic control in insulin-resistant obese db/db mice are enhanced when given in combination with [D-Leu-4]-OB3. To examine the anti-hyperglycemic influence of [D-Leu-4]-OB3 in a non-obese insulin-deficient animal model, we compared the effects of metformin (200mg/kg) and [D-Leu-4]-OB3 (40 mg/kg) on energy balance and glycemic control in streptozotocin (STZ)-induced diabetic male Swiss Webster (SW) mice. Diabetic mice were given insulin (Levemir(®), sc) alone, or in combination with metformin or [D-Leu-4]-OB3 orally in DDM, for 14 days. Body weight and food and water intake were measured daily. Fasting blood glucose levels were determined every other day. Serum C-peptide was measured by ELISA. Diabetic mice receiving insulin alone for 14 days gained significantly more weight than DDM-treated control mice, or mice given insulin in combination with metformin or [D-Leu-4]-OB3. The weight gain seen in mice given insulin alone was accompanied by significant increases in both food and water intake. Mice treated with insulin in combination with metformin or [D-Leu-4]-OB3, consumed significantly less food and water. Blood glucose levels in STZ-treated mice receiving insulin alone were reduced to 65.3% of initial levels, while mice receiving insulin with metformin or [D-Leu-4]-OB3 were reduced to 44.5% and 38.9%, respectively. Our results indicate that [D-Leu-4]-OB3 is as effective as metformin in preventing the body weight gain associated with insulin therapy, and on a molar basis, that the efficacy of [D-Leu-4]-OB3 as an insulin sensitizer may equal or surpass that of metformin.


Somatosensory evoked potentials following posterior tibial nerve stimulation predict later motor outcome.
Posterior tibial nerve somatosensory evoked potentials (PTN-SEPs) were performed on 50 neonates at high risk of future neurodevelopmental impairment just before their discharge from the neonatal intensive-care unit. The close association of sensory pathways with motor tracts and the need for sensory input and integration for normal motor functioning would indicate that CNS lesions producing motor deficits may be detected by this method. Follow-up of these infants revealed a highly significant relationship between bilaterally abnormal PTN-SEPs and the presence of cerebral palsy at three years of age. Normal PTN-SEPs were associated with a normal outcome in 24 of 25 infants. In this group of neonates, PTN-SEPs were more predictive than cranial ultrasound.


Technique for isolating phage for Azotobacter vinelandii.
An enrichment technique was developed whereby azotophage could readily be isolated after inoculation of soil sites with Azotobacter vinelandii.


Biosynthetic trends and future aspects of bimetallic nanoparticles and its medicinal applications.
Recently, in all over the world, nanotechnology plays a major role in various applications. Most of the researchers focused their work on bimetallic nanoparticles due to their several modes or mechanisms of synthesis such as chemical, physical, and biosynthesis methods. These nanoparticles are of great interest due to their enormous applications and catalytic activities. Currently, syntheses of bimetallic nanoparticles using different sources of natural products are focused due to their advantage of being nontoxic to human and environment. To our knowledge, there is no report on the review of bimetallic nanoparticles and their medicinal applications. Taking this fact into account, we discussed the various synthesizing methods of bimetallic nanoparticles and their application related to biology.


Association of self-efficacy and mental toughness with sport performance in Brazilian futsal athletes.
Self-efficacy is considered a component of mental toughness, but there are few studies investigating the relationship of sport self-efficacy with mental toughness in performance athletes, especially in team sports. The objective was to examine the impact of sport self-efficacy mediated by mental toughness on the sport performance of Brazilian futsal athletes. The sample was composed of five adult male teams participating in the National Futsal League 2020, totaling 77 athletes. As instruments, we used: athlete identification sheet, Perceived Self-Efficacy Scale in Sports (PSES), Mental Toughness Index (MTI) questionnaire and the performance data from the National Futsal League 2020 (NFL). The data were analyzed using the Kolmogorov-Smirnov test, Mann-Whitney "U" test, Spearman's correlation, network analysis (LASSO), with the indicators of centrality: strength, proximity and degree of intermediation (p < 0.05). The results showed that the investigated sample presented high levels of Perceived Self-Efficacy Scale in Sports (PSES) (Md = 4.66) and mental toughness (MT) (Md = 6.44). PSES presented a positive relationship with the number of wins, and negative relationships with the number of red cards and wrong passes (r = -0.08). MT indirectly influenced these variables through its connection with PSES (r = 0.30). The best ranked teams presented higher amounts of goals for, fouls, shots on goal, tackles, assists, and wins. The time of practice revealed an inverse relationship with the number of defeats, while age was positively related to the number of wrong passes (r = 0.09). The centrality indicators showed that the number of games stood out as the most central variable in the network, due to its degree of strength, proximity and intermediation. Moreover, the high degree of proximity and intermediation of the tackles made presented a connection with the number of assists (γ = 0.25; n = 77). We can conclude that sport self-efficacy and mental toughness are intervening factors in the sport performance of Brazilian futsal athletes.