Removal of heavy metals from sewage sludge by chemical leaching with biodegradable chelator methyl glycine diacetic acid.
The heavy metals (HMs) contained in sewage sludge are some of the largest obstacles that hamper the usage of sewage sludge in land application (e.g. fertilizer, soil improver). The conventional chelators, e.g., ethylenediaminetetraacetic acid (EDTA), were effective in the remediation of HMs polluted sewage sludge, but suffered from an evident drawback of low biodegradability. Therefore, the applicability of a new biodegradable chelator, methyl glycine diacetic acid (MGDA), to extract HMs from sewage sludge was carried out and compared with EDTA. The experimental parameters affecting the performance of MGDA were optimized. Leaching results showed that in general, MGDA exhibited higher Zn leaching efficiency and similar Cu, Ni and Cr leaching efficiencies with EDTA at same pH and dosage conditions. The maximum Zn, Cu, Ni and Cr leaching efficiencies of MGDA were 94.1% ± 4.5%, 58.2% ± 3.1%, 78.2% ± 2.3% and 54.6% ± 2.5%, respectively. The leaching efficiency plateaued within a reaction time of 4 h, but that of Cu and Ni showed a slightly decreasing trend during hours 4 to 10. In raw sewage sludge, the Zn and Cu were mainly presented in the organically bound fraction, i.e., 45.3 ± 3.2% of total Zn and 48.3 ± 1.4% of total Cu. The addition of MGDA and EDTA caused obvious distribution transformations in Zn and Cu from the organically bound fraction to soluble fraction. According to the reduced partition index calculation, the mobility of Zn, Cu, Ni, and Cr was not significantly lowered after the MGDA treatment. However, the HMs secondary pollution risk of the sludge was reduced due to the drop of the total HMs content after chelator leaching. Findings from this study suggest that MGDA could be a potential environment-friendly alternative for refractory chelators (e.g. EDTA) in the decontamination of HMs from sludge.


[Targeted systemic treatments and locoregional radiotherapy for breast cancer: Can we expect a benefit from the potentiation of local treatment?]
Breast cancer is the first most common cancer worldwide, and radiation therapy has a major role to play in locoregional adjuvant treatment. In recent years, we have seen the emergence of adjuvant targeted systemic therapies improving the prognosis of patients at high risk of recurrence. Practices concerning combinations of targeted therapies and locoregional radiation therapy for non-metastatic breast cancers often remain heterogeneous due to the low level of evidence and lack of validated recommendations. This literature review covers immunotherapy, CDK 4/6 inhibitors, PARP inhibitors and anti-Her2 therapies. Combining these targeted systemic therapies with radiation therapy could potentiate local treatment. The optimal therapeutic sequence and fractionation for maximum synergistic effect remain to be defined. However, while efficacy may be enhanced, radiosensitization of healthy tissue may also lead to increased toxicity. It appears possible to continue immunotherapy, trastuzumab, pertuzumab, TDM-1 or lapatinib during locoregional breast and lymph node irradiation. PARP inhibitors and CDK4/6 inhibitors are still to be suspended, due to the lack of data in the adjuvant setting and their short half-life, which does not necessitate prolonged discontinuation. As with the new antibody-drug conjugates, prospective data are needed in conjunction with adjuvant radiation therapy.


The effect of risperidone on behavioral reactions and gene expression of pro- and anti-inflammatory cytokines in neuropathic pain model induced by chronic constriction injury of the sciatic nerve in rat.
Neuropathic pain results from lesions or diseases affecting the somatosensory system. The management of a patient with chronic neuropathic pain remains a challenge several studies report the analgesic effect of serotonin receptor antagonists in different models of experimental pain. The present study was designed to study the effect of systemic administration of risperidone, on behavioral scores of neuropathic pains in chronic constriction (CCI) model in rats. Inducing neuropathic pain with the CCI model which causes heat hyperalgesia, heat, and mechanical allodynia was performed on rats, and then, in two phases, risperidone effect was determined. In the acute phase, risperidone 1, 2, 4 mg was administered for three groups half an hour before behavioral tests on the 7th, 14th, and 21st day after surgery, and in the chronic phase, risperidone 1, 2, and 4 mg was administered for three different groups from the 1st to 14th days after surgery than on 14th-day behavioral scores were performed. For gene expression analysis, samples are taken from spinal cord tissues in lumbar segments. This study shows chronic administration of risperidone as an antipsychotic drug was effective on heat hyperalgesia and allodynia. However, only the max dosage (4 mg) of risperidone showed meaningful improvement in increasing mechanical allodynia. However, acute administering of risperidone did not show any meaningful changes in behavioral tests on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. In addition, gene expression results showed an increase in IL-4 and IL-10 gene expression in the risperidone group compared to the sham group. This study suggests the helpful preventive effects of risperidone in developing and increasing neuropathic pain, but it does not have any instant effect.


Sialyltransferase levels and sialic acid concentrations in sera of patients with malignant melanomas.
Serum levels of sialyltransferase and sialic acid were measured in patients with malignant melanomas (n = 49), healthy control persons (n = 20), and patients with non-malignant skin disorders (n = 30). Both parameters were found to be higher in malignant melanoma patients than in healthy control persons, but they were not significantly higher in melanoma patients than in patients with benign skin disorders, unless widespread dissemination of metastases had occurred. The highest values were measured in patients with liver and lung metastases. No general correlation was found between sialyltransferase activities and sialic acid concentrations. Sialic acid concentrations seem to be a better index for tumor spreading than sialyltransferase activities. In early stages of the disease, shedding from tumor cells is not the major source of elevated serum levels of sialyltransferase and sialic acid, respectively.


Novel systemic therapies for breast cancer.
The rapid expansion in our knowledge of the molecular pathogenesis of cancer has created several opportunities for novel strategies in anti-cancer drug design and development. Recent developments have included a series of new endocrine therapies such as pure anti-oestrogens and selective oestrogen receptor modulators, and trials are in progress to determine their role in the sequence of therapies given the first-line role now occupied by the aromatase inhibitors. Novel cytotoxic drugs have been developed with an improved toxicity profile, including oral prodrugs that are activated within tumour cells, and liposomal delivery mechanisms for conventional drugs that reduce some of the systemic toxicities. There has been much success with monoclonal antibodies targeted against growth factor receptors, both as monotherapy and in enhancing the efficacy of cytotoxic drugs. A number of small molecule signal transduction inhibitors are in early stages of clinical development for breast cancer, including tyrosine-kinase inhibitors and farnesyl transferase inhibitors. Emerging pre-clinical evidence suggests that these drugs may best be used in combination with endocrine therapy. Other novel strategies that are being tested include vaccines and anti-angiogenesis drugs. As these new therapies evolve towards the clinic, the challenge to oncologists is whether their potential seen in the laboratory can be matched by further substantial improvements in clinical outcome.


Pediatric Telemedicine: Lessons Learned During the Coronavirus Disease 2019 Pandemic and Opportunities for Growth.
The accelerated uptake of telemedicine during the coronavirus disease 2019 pandemic has resulted in valuable experience and evidence on the delivery of telemedicine for pediatric patients. The pandemic has also highlighted inequities and opportunities for improvement. This review discusses lessons learned during the pandemic, focusing on provider-to-patient virtual encounters. Recent evidence on education and training, developing and adapting clinical workflows, patient assessment and treatment, and family-centered care is reviewed. Opportunities for future research in pediatric telemedicine are discussed, specifically with regard to engaging pediatric patients, improving and measuring access to care, addressing health equity, and expanding the evidence base.


Quality Indices and Outcomes of a Neonatology Telerounding Program in a Level II Neonatal Intensive Care Unit: Single-Center Experience during the COVID-19 Pandemic.
The objective of this program evaluation was to describe the outcomes of daily neonatologist telerounding with the onsite advanced practice provider (APP) in a Level II neonatal intensive care unit (NICU), before and during the coronavirus disease 2019 (COVID-19) pandemic. Bedside telerounding occurred with an onsite APP using a telehealth cart and paired Bluetooth stethoscope. Data collected by longitudinal and cross-sectional surveys and chart review before (May 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic were analyzed using descriptive statistics and thematic analysis. A total of 258 patients were admitted to the Level II NICU before (May 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. Demographic characteristics and outcomes, including breastfeeding at discharge and length of stay were similar pre- and postonset of the COVID-19 pandemic. Postrounding surveys by 10 (response rate 83%) neonatologists indicated parents were present in 80 (77%) of rounds and video was at least somewhat helpful in 94% of cases. Cross-sectional survey responses of 23 neonatologists and APPs (response rate 62%) indicated satisfaction with the program. Common themes on qualitative analysis of open-ended survey responses were "need for goodness of fit" and "another set of eyes" and "opportunities for use." Daily telerounding with neonatologists and APPs in a Level II NICU supported neonatal care. Quality metrics and clinical outcomes are described with no differences seen before and during the COVID-19 pandemic. · Little is known about Level II NICU quality metrics and outcomes.. · Daily bedside telerounding with neonatologists and APPs is described.. · Telerounding supported neonatal care before and during the COVID-19 pandemic.. · Neonatologists found visual exam helpful in the majority of cases.. · No differences in NICU clinical outcomes were seen during the COVID-19 pandemic..


Sonochemical Synthesized Manganese Oxide Nanoparticles as Fluorescent Sensor for Selenium (IV) Quantification. Application to Food and Drink Samples.
Manganese oxide nanoparticles (MnO Nps), sonochemical synthesized and characterized in our laboratory, are proposed as fluorescent sensor for selenium (Se) determination. The new methodology has been developed based on the enhancing effect of the Se(IV) on fluorescent emission of MnO Nps. Experimental variables that influence on fluorimetric sensitivity were optimized. The calibration graph using zeroth order regression was linear from 0.189 ng L-1 to 8.00 × 103 µg L-1, with correlation coefficient better than 0.99. Under the optimal conditions, the limits of detection and quantification were of 0.062 ng L-1 and 0.189 ng L-1, respectively. The trueness of the methodology was assessed through standard addition method obtaining recovery near to 100%. This method showed good tolerance to foreign ions, particularly to Se(VI), and was applied to determination of Se(IV) trace in food and drink samples with satisfactory results. With the intention of preserving the environment from harmful effects, a degradation study of the used nanomaterials has been included for their subsequent disposal.


The ontogeny of seizures in a rat model of limbic epilepsy: evidence for a kindling process in the development of chronic spontaneous seizures.
Kindling is an experimental model for epilepsy in which repeated stimuli induce longer electrographic seizures and eventually cause behavioral convulsions. Although kindling has some features that are similar to chronic human epilepsy, it is not known whether this process plays a role in the development of chronic seizure disorders. We have recently described a rat model of chronic spontaneous limbic seizures that has a number of similarities to human limbic epilepsy. To determine whether a kindling process is involved in the ontogeny of the seizures in this animal model, we continuously monitored 16 rats with EEG and closed circuit television until they had experienced a minimum of 5 and as many as 10 seizures following the first motor seizure. All animals had at least one non-motor seizure before the first motor event (mean 5.1 +/- 0.9 S.E.M. initial non-motor seizures, range 1-12). In addition the seizures significantly lengthened in duration with succeeding events (mean 90 s for the first motor seizure to mean 110 s for the tenth subsequent seizure). These data demonstrate that there is a kindling process involved in the early development of chronic limbic seizures.


A modified beam-walking apparatus for assessment of anxiety in a rodent model of blast traumatic brain injury.
The elevated plus maze (EPM) is used to assess anxiety in rodents. Beam-walking tasks are used to assess vestibulomotor function. Brain injury in rodents can disrupt performance on both of these tasks. Developing novel paradigms that integrate tasks like these can reduce the need for multiple tests when attempting to assess multiple behaviors in the same animal. Using adult male rats, we evaluated the use of a modified beam-walking (MBW) apparatus as a surrogate indicator for anxiety. We used a model of blast-induced traumatic brain injury (bTBI). A total of 39 rats were assessed before and at 3, 6, 24, 72, and 168h either post- bTBI (n=33) or no-injury (n=6) using both EPM and MBW. A novel anxiety index was calculated that encompassed peeks and re-emergences on MBW. The proposed MBW anxiety index was compared with the standard anxiety index calculated from exploration into different sections of EPM. Post- bTBI, rats had an increased anxiety index when measured using EPM. Similarly, they peeked or fully emerged less out of the safe box on MBW. It was found that this novel MBW anxiety index captured similar aspects of behavior when compared to the standard anxiety index obtained from EPM. Further, these effects were dissociated from the effects of bTBI on motor function simultaneously measured on MBW. Over the course of 168h post-bTBI, rats gradually recovered on both EPM and MBW. The MBW apparatus succeeded at capturing and dissociating two separate facets of rat behavior, motor function and anxiety, simultaneously.


Carotid endarterectomy with local anesthesia: results and advantages.
In a collaborative prospective study from two institutions, we reviewed the clinical course of 969 consecutive patients who had 1200 carotid endarterectomies (CEs) for the treatment of occlusive arterial disease during the period 1977 to 1987. The indications for CE comprised transient ischemic attacks (TIAs) in 581 cases (48.4%), cerebral infarction (CI) in 170 (14.2%), monocular blindness in 166 (13.8%), and asymptomatic stenosis in 283 (23.6%). Neurologic monitoring of the awake patient provided more reliable indication of the need for brain protection during operative arterial clamping than did electroencephalography or carotid stump pressure measurement. Of the 1200 cases, 113 (9%) required a shunt as determined by this method. Patients with contralateral carotid occlusion or severe stenosis required shunting six times more frequently than those with a unilateral lesion. Among all procedures, there were nine cases of transient neurologic deficit (0.9%), 11 cases of permanent neurologic deficit (0.9%), and eight deaths (0.67%). Among 283 CEs performed to treat asymptomatic lesions, no strokes and only one death (0.4%) occurred. One hundred sixty-six cases with amaurosis fugax were operated on without stroke or death. In the age group of 70 to 90 years, 508 procedures were carried out with four deaths (0.8%) and three strokes (0.6%). We conclude that CE performed with the patient under local anesthesia is safe and effective and permits satisfactory management of old and high-risk patients.


Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue.
The GABRP gene has been previously identified by in silico analysis of four million ESTs as a candidate gene differentially expressed in breast cancer. GABRP is located on chromosome 5q34 and it encodes the pi-subunit of the gamma-aminobutyric acid (GABA) receptor, a transmembrane protein expressed in the brain and several nonneuronal tissues. Using cDNA dot blot hybridisation (cancer profiling array), quantitative RT-PCR and non-radioisotopic in situ hybridisation (ISH), we have analysed GABRP expression in breast cancer and normal breast tissues as well as in nontumorigenic and tumorigenic breast cell lines. Analysis of the cancer profiling array revealed a more than 2-fold downregulation of GABRP (p < 0.001) in 76% of primary breast carcinomas (n = 50) compared to corresponding normal tissues. Quantitative RT-PCR in a panel of 23 normal human tissues showed that the GABRP expression level was most abundant in the normal breast tissues compared to other human tissues. GABRP downregulation in breast cancer was confirmed by quantitative RT-PCR in cryopreserved breast tumour and normal breast tissue specimens (n = 22), in archival formalin-fixed, paraffin-embedded tissue specimens (n = 32), as well as in breast cancer cell lines (n = 8). Furthermore, a significant downregulation of GABRP was noted in large (pT3-pT4) (p = 0.044) primary breast tumours. Non-radioisotopic ISH showed strong GABRP expression in normal epithelial and benign papilloma breast cells, but no signal could be detected in invasive ductal carcinoma. Altogether, these data suggest that GABRP is progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer.


In vivo tyrosine phosphorylations of the Abelson virus transforming protein are absent in its normal cellular homolog.
The transforming gene product of the Abelson murine leukemia virus (A-MuLV) is a phosphoprotein encoded by combined viral and cellular sequences. Previous work has shown the existence of a serologically crossreactive normal cellular phosphoprotein called NCP150. We have utilized two-dimensional phosphopeptide mapping and phosphoamino acid analysis to compare the structures of NCP150 and wild-type and mutant forms of the A-MuLV protein labeled in vivo with 32P-orthophosphate. This analysis demonstrated clear homology between NCP150 and wild-type A-MuLV protein, but a number of phosphorylation differences were seen. Among them, two specific tyrosine phosphorylations present in all transformation-competent Abelson proteins were not observed in NCP150. No other phosphotyrosine-containing peptides were detected. In addition, transformation-defective mutants isolated from either the P120 or P160 wild-type strain lack phosphotyrosine-containing peptides. Double-infection studies with such transformation-defective and transformation-competent A-MuLV strains show that Abelson viral proteins may be substrates for their own tyrosine-specific kinase activity in vivo. These observations suggest that the phosphotyrosine kinase activity of the abl region may be controlled, and may function, differently in its viral and cellular forms.


Silicon Supply Improves Leaf Gas Exchange, Antioxidant Defense System and Growth in Saccharum officinarum Responsive to Water Limitation.
Silicon (Si) is not categorized as a biologically essential element for plants, yet a great number of scientific reports have shown its significant effects in various crop plants and environmental variables. Plant Si plays biologically active role in plant life cycle, and the significant impact depends on its bioaccumulation in plant tissues or parts. In particular, it has been investigated for its involvement in limited irrigation management. Therefore, this experiment was conducted to examine the effect of Si application in eco-physiological, enzymatic and non-enzymatic activities of sugarcane plants against water stress. Four irrigation levels, i.e., normal (100-95% of soil moisture), 80-75, 55-50, and 35-30% of soil moisture were treated for the sugarcane cultivar GT 42 plants supplied with 0, 100, 200, 300, 400 and 500 mg Si L-1 and exposed for 60 days after Si application. Under stress, reduction in plant length (~26-67%), leaf area-expansion (~7-51%), relative water content (~18-57%), leaf greenness (~12-35%), photosynthetic pigments (~12-67%), physiological responses such as photosynthesis (22-63%), stomatal conductance (~25-61%), and transpiration rate (~32-63%), and biomass production were observed in the plants without Si application. The drought condition also inhibited the activities of antioxidant enzymes like catalase (~10-52%), peroxidase (ca. 4-35), superoxide dismutase (10-44%) and enhanced proline (~73-410%), and malondialdehyde content (ca. 15-158%), respectively. However, addition of Si ameliorated drought induced damage in sugarcane plants. The findings suggest that the active involvement of Si in sugarcane responsive to water stress ranges from plant performance and physiological processes, to antioxidant defense systems.


Combination of Pioglitazone and Metformin Actions on Liver Lipid Metabolism in Obese Mice.
Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.


Two-dimensional topological insulators with tunable band gaps: Single-layer HgTe and HgSe.
Two-dimensional (2D) topological insulators (TIs) with large band gaps are of great importance for the future applications of quantum spin Hall (QSH) effect. Employing ab initio electronic calculations we propose a novel type of 2D topological insulators, the monolayer (ML) low-buckled (LB) mercury telluride (HgTe) and mercury selenide (HgSe), with tunable band gap. We demonstrate that LB HgTe (HgSe) monolayers undergo a trivial insulator to topological insulator transition under in-plane tensile strain of 2.6% (3.1%) due to the combination of the strain and the spin orbital coupling (SOC) effects. Furthermore, the band gaps can be tuned up to large values (0.2 eV for HgTe and 0.05 eV for HgSe) by tensile strain, which far exceed those of current experimentally realized 2D quantum spin Hall insulators. Our results suggest a new type of material suitable for practical applications of 2D TI at room-temperature.


Does exposure of preovulatory oocytes to ultrasonic radiation affect reproductive performance?
Ultrasonography of preovulatory oocytes has been reported to lead to reduced litter size in rats. Because of the growing popularity of ultrasound-guided follicular aspiration in human in vitro fertilization programs, further study of ultrasonic radiation's effect on the preovulatory oocyte is warranted. We used 106 virgin Sprague-Dawley rats which, on the evening of proestrus, received ultrasonic radiation of sham treatment after the onset of the luteinizing hormone (LH) surge. No differences were found between control (C) and experimental (US) animals in pregnancy rate, number of corpora lutea, implantations, pups, and mean pup and placental weights at autopsy on day 22 of pregnancy. Ultrasonic radiation applied to meiotically active, preovulatory oocytes did not affect the reproductive performance of these rats.


Our survey reinforces the low morale mantra, but Hunt is still not listening.
It has almost become a cliché to say that morale among nurses is at 'rock bottom', given the number of surveys over the years that have come to this conclusion.


Does space in the jaw influence the timing of molar crown initiation? A model using baboons (Papio anubis) and great apes (Pan troglodytes, Pan paniscus).
Radiographic and histological studies of baboon (Papio hamadryas, P. anubis) and chimpanzee (Pan troglodytes) permanent tooth development have found that periods of molar crown mineralization overlap markedly in chimpanzees but are staggered in baboons. Here we test the hypothesis that these intertaxon differences in molar initiation are primarily due to the space available in the mandibles of each species for these teeth. This study includes radiographic, linear measurement, and three-dimensional (3D) coordinate landmark data taken from baboon (Papio anubis n=51) and great ape (Pan paniscus n=43, P. troglodytes n=60) mandibles and permanent molars across a broad developmental range for each taxon. Unexpectedly, 3D multivariate statistical shape analysis of the molar crypt, crown, and root data shows that all three species trajectories of molar row shape change are indistinguishable from each other. Qualitative analysis of these 3D data reveals subtle and inconclusive intergeneric differences in the space maintained between adjacent molars during growth. The space distal to each newly initiated molar is slightly greater in the baboon. Bivariate analyses comparing molar row and mandibular corpus proportions in Papio and Pan fail to show clear or consistent taxonomic differences in the ratio of space afforded developing molars in the alveolar bone. Thus, there is a poor correlation between mandibular proportion and both intermolar spacing and 3D molar development pattern. Contrary to earlier studies, these results suggest that pattern of molar crown initiation and temporal overlap of adjacent mineralizing crowns is not significantly different between Papio and Pan. This may be due in part to the inclusion here of not only 3D molar crown data but also 3D molar crypt data. This study strongly refutes the hypothesis that space available in the mandible directly underlies different times of permanent molar crown initiation between Papio and Pan.


Optimised extraction of folic acid from multivitamin-mineral preparations for liquid chromatographic analysis.
Degradation of folic acid may occur during extraction of multivitamin-mineral preparations. The degradation may be caused by presence of ions such as Fe3+ and Cu2+, however, the buffer composition may also be critical. This study presents an optimised extraction procedure tested on 24 different products of multivitamin-mineral tablets. The present method yielded mean recoveries of 97% (n = 20) for folic acid and prevented degradation of folic acid in at least 24 h in extracts from multivitamin-mineral tablets.


Proliferation and differentiation potential of cryopreserved human skin-derived precursors.
Skin-derived precursors are recognized to be a potentially autologous and accessible source of neural precursor cells for drug screening or cell-based treatments, in many neurological disorders. Thus, it is necessary to investigate appropriate methods for cryopreservation of such human skin-derived precursors (hSKPs). The aim of this study was to evaluate different cryopreservation techniques for retention of hSKPs to discover an optimized protocol. We cryopreserved hSKPs treated with 0%, 10%, 20%, 30% and 40% foetal bovine serum (FBS) and three concentrations of dimethylsulphoxide (DMSO) 5%, 10% and 15%, with two different storage periods in liquid nitrogen (2 days: short-term storage; and 2 months: long-term storage). Then, we assessed survival and proliferation levels of the cells after freeze-thaw processes, by viability measurement and colony-forming assay. For detecting hSKPs, we used immunocytochemistry and RT-PCR assessments. Our findings indicated that hSKPs cryopreserved in 5% DMSO without FBS, had better survival and proliferation potentials compared to other working formulations. With various concentrations of cryoprotectants over different time periods, hSKPs retained their differentiation potentiality and were able to differentiate into neurons (NFM and βΙΙΙ tubulin-positive), glial cells (GFAP-positive) and smooth muscle cells (SMA-positive). Results revealed that in only 5% DMSO, hSKPs could be cryopreserved for long-term storage with considerable survival and proliferation levels, without losing multipotency.


Homogeneous immunoglobulins in the sera of lung carcinoma patients receiving cytotoxic chemotherapy--detection with the use of isoelectric focusing and immunoblotting.
Using isoelectric focusing (IEF) with immunoblotting, we have analysed serum immunoglobulins of 15 lung cancer patients on cytotoxic chemotherapy. In five of the patients homogeneous immunoglobulins were found which appeared between 9 and 18 months after beginning of treatment and were monoclonal in two and oligoclonal in three cases. These abnormalities were only partially shown by zonal electrophoresis with immunofixation and not detected by immune electrophoresis. Examination of 10 normal and 10 myeloma sera by the three techniques in parallel confirmed the competence and sensitivity of IEF with immunoblotting in detecting homogeneous immunoglobulins. Thus, this method provides a valuable tool for investigating an abnormal regulation of the immunoglobulin synthesis.


Elevated expression of RNA methyltransferase BCDIN3D predicts poor prognosis in breast cancer.
BCDIN3D is a member of the Bin3 methyl-transferase family that targets the 5' mono-phosphate of nucleic acids. Although BCDIN3D has been shown to increase tumorigenic phenotypes and invasiveness in MDA-MB-231 cells, its the clinical implications in breast cancer remain unclear. We screened for BCDIN3D using tissue microarrays constructed from 250 patients who were histologically confirmed to have invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center. The survival analysis by Kaplan-Meier and Cox regression showed that BCDIN3D expression level served as a prognostic factor for disease-free survival (P = 0.042). The prognostic value of BCDIN3D was most significant in triple-negative breast cancer (TNBC) patients (P = 0.007). BCDIN3D might serve as an important prognostic factor for TNBC patients.


The soluble transhydrogenase UdhA affecting the glutamate-dependent acid resistance system of Escherichia coli under acetate stress.
The soluble transhydrogenase (UdhA) is one of two transhydrogenases that play a role in maintaining the balance between NAD(H) pools and NADP(H) pools in Escherichia coli Although UdhA has been extensively used in metabolic engineering and biocatalysis for cofactor regeneration, its role in acid resistance has not been reported. Here we used DNA microarray to explore the impact of UdhA on transcript levels. We demonstrated that during growth on acetate, the expression of genes involved in the respiratory chain and Gad acid resistance system was inhibited in the udhA-knockout strain. The deletion of udhA significantly repressed the expression of six genes (gadA, gadB, gadC, gadE, hdeA and hdeB) which are involved in Gad acid resistance and resulted in low survival of the bacterium at a low pH of 4.9. Moreover, UdhA was essential for NADH production which is important for the adaptive growth of E. coli on acetate, while NADH concentration in the udhA-knockout strain was quite low and supplemental NADH significantly increased the expression of acid resistance genes and survival of the udhA-knockout strain. These results demonstrated that UdhA is an important source of NADH of E. coli growth on acetate and affects Gad acid resistance system under acetate stress.


The interaction of HMGB1 and linker histones occurs through their acidic and basic tails.
H1 and HMGB1 bind to linker DNA in chromatin, in the vicinity of the nucleosome dyad. They appear to have opposing effects on the nucleosome, H1 stabilising it by "sealing" two turns of DNA around the octamer, and HMGB1 destabilising it, probably by bending the adjacent DNA. Their presence in chromatin might be mutually exclusive. Displacement/replacement of one by the other as a result of their highly dynamic binding in vivo might, in principle, involve interactions between them. Chemical cross-linking and gel-filtration show that a 1:1 linker histone/HMGB1 complex is formed, which persists at physiological ionic strength, and that complex formation requires the acidic tail of HMGB1. NMR spectroscopy shows that the linker histone binds, predominantly through its basic C-terminal domain, to the acidic tail of HMGB1, thereby disrupting the interaction of the tail with the DNA-binding faces of the HMG boxes. A potential consequence of this interaction is enhanced DNA binding by HMGB1, and concomitantly lowered affinity of H1 for DNA. In a chromatin context, this might facilitate displacement of H1 by HMGB1.


UV Light as an Efficient Tool for Reducing Surface Defects of ZnSe-MSA Quantum Dots.
Defects in ZnSe quantum dots are responsible for increasing the trap states, which can lead to the drastic reduction of their fluorescence output, being one of the major drawbacks of these materials. As surface atoms become more relevant in these nanoscale structures, energy traps due to surface vacancies, play a very definite role in the final emission quantum yield. In the present study, we report the use of photoactivation procedures to decrease surface defects of ZnSe QDs stabilized with mercaptosuccinic acid (MSA), in order to improve the radiative pathways. We applied the colloidal precipitation procedure in a hydrophilic medium and evaluated the role of Zn/Se molar ratios as well as the Zn2+ precursors (nitrate and chloride salts) on their optical properties. Best results (i.e. increment of 400% of the final fluorescence intensity) were obtained for nitrate precursor and a Zn/Se = 1.2 ratio. Thus, we suggest that the chloride ions may compete more efficiently than nitrate ions with MSA molecules decreasing the passivation capability of this molecule. The improvement in ZnSe QDs fluorescence can potentialize their use for biomedical applications.


The global response to the COVID-19 pandemic: how have immunology societies contributed?
The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed, Nature Reviews Immunology invited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


Unplanned admission after gastrectomy as a consequence of fast-track surgery: a comparative risk analysis.
The objectives of this study were to evaluate the incidence of and the risk factors for readmission after gastrectomy. Our hypothesis was that early discharge may be related to an increase in the incidence of readmission. This was a retrospective, single-center, observational study of 1442 patients who underwent gastrectomy for stage I gastric cancer. The main outcome was the incidence of early readmission after gastrectomy, which was defined as an admission within 6 months after the first discharge day. A stepwise logistic regression analysis was conducted to identify the risk factors for readmission after gastrectomy. The surgical procedures performed were total gastrectomy in 217 patients (15.0 %), distal gastrectomy in 845 patients (58.6 %), pylorus-preserving gastrectomy in 342 patients (23.7 %), and proximal gastrectomy in 37 patients (2.6 %). The median hospital stay was 11 days, and there were 63 readmissions for a total of 56 patients (3.8 %). The main reasons for readmission were poor food intake in 14 patients (22.2 %), anastomotic stricture in nine patients (14.3 %), small bowel obstruction in eight patients (12.7 %), and an abdominal distension in seven patients (11.1 %). Endoscopic balloon dilation was performed for the nine patients with anastomotic stricture, drainage was needed for the four patients with an intra-abdominal abscess, and laparotomy was performed for one patient with adhesion-associated bowel obstruction. The long hospitalization during the primary admission and patients who underwent total gastrectomy were risk factors for readmission. Patients with a long hospital stay after gastrectomy are at an increased risk of early readmission, which was likely related to the incidence of severe sequelae specific to gastrectomy.


Safety and feasibility report on nonimplantable endovenous valve formation for the treatment of deep vein reflux.
Definitive treatment techniques for symptomatic deep venous reflux have been relegated to complex and invasive open surgery which is rarely performed today. The BlueLeaf System provides an endovenous method for the formation of deep venous valves without an implant, avoiding the complications associated with permanent foreign materials. The system has the adaptability to form valves within the femoral and popliteal veins at multiple levels in a single procedure. The aim was to determine the midterm safety and efficacy of this novel device in an early feasibility study. Feasibility of endovenous deep venous valve formation was assessed in patients with chronic venous insufficiency (Clinical, Etiologic, Anatomic, Pathophysiologic [CEAP] 4-6). Follow-up was completed through 1 year, assessing vein patency and reflux time (RT) with duplex ultrasound examination. Venous clinical improvement was evaluated using the revised Venous Clinical Severity Scale. Of the 14 patients, 13 (93%) had successful formation of at least one monocuspid valve, with a mean number of 1.4 valves (range, 0-3 valves) per patient. There were no device-related serious adverse events during the index procedure. There were no deep venous thromboses reported at any time point, including 10 patients through the 1-year follow-up. In patients with at least one valve formed, site reported duplex ultrasound examination measured the average RT in the popliteal vein below valve formations, was 3.0 ± 1.0 seconds at baseline, 3.9 ± 3.1 seconds at 30 days, and 3.6 ± 2.1 seconds at 360 days. The revised Venous Clinical Severity Scale improved in all 13 successfully treated patients, decreasing from 15.0 ± 6.0 at baseline to 11.6 ± 5.5 at 30 days, 10.7 ± 5.3 at 210 days, and 9.4 ± 5.0 at 360 days (P = .0002; baseline to 360 days). Among the five patients with an ulcer who reached the 360-day follow-up visit, all (100%) healed at least one ulcer. Two patients (40%) healed all ulcers and three patients (60%) had a decrease in ulcers number but remained at C6 at 360 days. The five patients with a total of nine active ulcers at baseline had four active ulcers at 360 days. The BlueLeaf System holds promise as a minimally invasive means to safely form fully autogenous deep venous valves. Reconstructed deep veins remained patent, without deep venous thrombosis and symptomatic improvement was consistently observed; however, a decrease in the RT was not. Incremental device design improvements have been undertaken to improve valve function. The results of these iterations await further clinical evaluation.


Exon shuffling by recombination between self-splicing introns of bacteriophage T4.
The organization of genes into exons separated by introns may permit rapid evolution of protein-coding sequences by exon shuffling. Introns could provide non-coding targets for recombination, which would then give rise to novel combinations of exons. Evidence to support this theory is indirect and consists of examples of homologous domains of protein structure encoded in different genes, with introns in conserved positions at the boundaries of these domains. Here, we report the first direct evidence for exon shuffling. Two spontaneous deletion mutations of phage T4 have been characterized by sequencing, and they are clearly the result of recombination between homologous regions of two self-splicing group I introns. As a result of the recombination, exons of different genes are transcribed together, with a hybrid intron between them. One of these introns is proficient in self-splicing.


Variability in PolyIC induced immune response: Implications for preclinical maternal immune activation models.
Maternal infection during pregnancy may increase the risk of offspring neurodevelopmental disorders. The preclinical Polyinosinic-polycytidylic acid (PolyIC) model has become one of the most widely used approaches in maternal immune activation (MIA) research. However, variability in molecular weight may impact the immune activating potential of PolyIC. Nulliparous rats injected with high molecular weight PolyIC exhibit pronounced cytokine response and sickness behavior that was not observed in rats injected low molecular weight PolyIC. Although an essential next step is to extend these studies to pregnant animals, the preliminary results suggest that PolyIC molecular weight is an important experimental design consideration.


Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet's disease. Does interleukin-1beta play a major role in Behçet's synovitis?
The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1beta, TNF-alpha and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet's disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1beta, TNF-alpha and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-alpha and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1beta levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1beta between BD and RA patients. Among patients with RA, positive correlations were found between TNF-alpha and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1beta, were expressed in relatively small quantities in Behçet's synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet's arthritis. We suggest that IL-1beta may be involved in the pathogenesis of Behçet's synovitis.


Molecular cloning and characterization of a novel human gene (HSPBAP1) from human fetal brain.
Rat PASS1 is a novel protein binding specifically to hsp27 and thus plays a role in regulating stress response in the living cell. Here we report on a human homologue of PASS1, encoded by the gene HSPBAP1. The gene was cloned and identified during a large-scale sequencing analysis of a human fetal brain cDNA library. The human protein shared 80% amino acid identity with rat PASS1. According to bioinformatics analysis, the HSPBAP1 gene is located on chromosome 3q21. RT-PCR analysis indicated that HSPBAP1 was abundant in thymus and pancreas but had a ubiquitously low expression pattern in other human adult tissues except for brain where it was absent.


A distal lung organoid model to study interstitial lung disease, viral infection and human lung development.
Organoids have been an exciting advancement in stem cell research. Here we describe a strategy for directed differentiation of human pluripotent stem cells into distal lung organoids. This protocol recapitulates lung development by sequentially specifying human pluripotent stem cells to definitive endoderm, anterior foregut endoderm, ventral anterior foregut endoderm, lung bud organoids and finally lung organoids. The organoids take ~40 d to generate and can be maintained more than 180 d, while progressively maturing up to a stage consistent with the second trimester of human gestation. They are unique because of their branching morphology, the near absence of non-lung endodermal lineages, presence of mesenchyme and capacity to recapitulate interstitial lung diseases. This protocol can be performed by anyone familiar with cell culture techniques, is conducted in serum-free conditions and does not require lineage-specific reporters or enrichment steps. We also provide a protocol for the generation of single-cell suspensions for single-cell RNA sequencing.


Potential Therapeutic Strategy for EGFR-Mutant Lung Cancer With Concomitant EML4-ALK Rearrangement-Combination of EGFR Tyrosine Kinase Inhibitors and ALK Inhibitors.
Although driver gene mutations have been believed to be mutually exclusive, some patients with NSCLC and concomitant EGFR mutations and EML4-ALK rearrangements have been reported. In this study, we reported a case of a patient with lung cancer who harbored both EGFR mutation and the EML4-ALK rearrangement after acquiring resistance to the EGFR tyrosine kinase inhibitor treatment. EGFR-mutant and ALK fusion proteins were detected in the same tumor cells through immunohistochemical analysis. Investigation of the molecular mechanisms of concomitant EGFR mutation and the EML4-ALK rearrangement in the same tumor cell can help discover an appropriate treatment for these patients. PC-9 cells, expressing EGFR exon 19 deletion, were transfected with EML4-ALK variant 3a (v3a) and variant 3b (v3b) separately and selected, and the effect of EGFR and ALK inhibitors was evaluated in vitro and in vivo. PC-9_v3a-gef and PC-9_v3b-gef cells were resistant to gefitinib and ALK inhibitors alone, but ALK inhibitors enhanced gefitinib-induced cytotoxicity. In animal studies, gefitinib completely inhibited the tumor growth in PC-9_vector cells but not in PC-9_v3a-gef and PC-9_v3b-gef cells. A combination of ALK inhibitor and gefitinib was found to be more potent than gefitinib alone in PC-9_v3a-gef and PC-9_v3b-gef cells. Furthermore, combination treatment with osimertinib and ceritinib caused a decrease in liver tumor size of the patient with liver metastases. Our data suggest that combination treatment with EGFR and ALK inhibitors can be a therapeutic strategy for treating NSCLC with concomitant EGFR mutation and EML4-ALK rearrangement.


Changes of profiles of neutrophil granulocytes induced with the administration of L-DOPA and prednisolone.
Morphological changes of granulocytes following combined treatment with L-DOPA and prednisolone were elucidated at the electron microscopic level. Neutrophil granulocytes exhibited marked changes in their surface as evidenced by scanning electron microscope. It is suggested that neutrophil granulocytes are sensitive to some biogenic amines.


The Toxicology Investigators Consortium 2022 Annual Report.
Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments.


Emerging issues of the expression profiling technologies for the study of gynecologic cancer.
Evaluation of the prognostic parameters of gynecologic cancer has shown their failure for classification according to the clinical behavior or the prediction of its outcome. This weakness has important implications on prognosis and treatment. The increasing understanding of the complexity of the human genome, coupled with the development of high throughput analysis techniques and bioinformatics tools, has changed our concepts on cancer biology, by shifting our targets to a global analysis of the transcriptome and the proteome, linking genes and their products into functional pathways. These approaches permit the documentation of expression patterns of thousands of genes within a cell. With the use of DNA microarray technology, it is feasible to identify signature patterns of expression in tumor samples that faithfully correlate with its biology, providing accurate prognosis for each cancer patient and thus a rational customized treatment. At this stage, there is a need for systematic studies for the validation of these novel approaches. In this review, we provide a basic background of the concept of the technology, highlight several emerging issues from their applications on gynecologic cancer, discuss a series of important themes and problems regarding their interpretation and relevance for the clinicians, and comment on future areas of research.


Tension pneumocephalus: case report and review.
Tension pneumocephalus is a rare complication of frontal sinus fracture or neurosurgical intervention resulting from compression of the brain by entrapped air, leading to seizure, altered mental status, brain herniation, and death. This report presents a case of traumatic tension pneumocephalus associated with an anterior and posterior table frontal sinus fracture in a patient with pneumosinus dilatans and osteogenesis imperfecta.


The myoplasm of ascidian eggs: a localized cytoskeletal domain with multiple roles in embryonic development.
The myoplasm of ascidian eggs is a localized cytoplasmic region containing a unique cytoskeletal domain. During ooplasmic segregation, the myoplasm moves first to the vegetal pole and then to the future posterior region of the fertilized egg, where it subsequently enters the muscle cell lineage during cleavage. In the vegetal pole region, the myoplasm defines a developmental center which later controls gastrulation and embryonic axis formation. In the posterior region, the myoplasm defines another developmental center, which specifies muscle cell development. Evidence is described suggesting that the integrity of the myoplasmic cytoskeletal domain is required for normal embryonic functions of the myoplasm.


Diet may influence the oral microbiome composition in cats.
Periodontal disease is highly prevalent amongst domestic cats, causing pain, gingival bleeding, reduced food intake, loss of teeth and possibly impacts on overall systemic health. Diet has been suggested to play a role in the development of periodontal disease in cats. There is a complete lack of information about how diet (composition and texture) affects the feline oral microbiome, the composition of which may influence oral health and the development of periodontal disease. We undertook a pilot study to assess if lifelong feeding of dry extruded kibble or wet (canned and/or fresh meat combinations) diets to cats (n = 10) with variable oral health affected the microbiome. Oral microbiome composition was assessed by amplifying the V1-V3 region of the 16S gene from supragingival dental plaque DNA extracts. These amplicons were sequenced using Illumina technology. This deep sequencing revealed the feline oral microbiome to be diverse, containing 411 bacterial species from 14 phyla. We found that diet had a significant influence on the overall diversity and abundance of specific bacteria in the oral environment. Cats fed a dry diet exclusively had higher bacterial diversity in their oral microbiome than wet-food diet cats (p < 0.001). Amongst this higher diversity, cats on dry-food diets had a higher abundance of Porphyromonas spp. (p < 0.01) and Treponema spp. (p < 0.01). While we observed differences in the oral microbiome between cats on the two diets assessed, the relationship between these differences and gingival health was unclear. Our preliminary results indicate that further analysis of the influence of dietary constituents and texture on the feline oral microbiome is required to reveal the relationship between diet, the oral microbiome and gingival health in cats.


Impact of astaxanthin-enriched algal powder of Haematococcus pluvialis on memory improvement in BALB/c mice.
The impact of astaxanthin-enriched algal powder on auxiliary memory improvement was assessed in BALB/c mice pre-supplemented with different dosages of cracked green algal (Haematococcus pluvialis) powder daily for 30 days. The supplemented mice were first tested over 8 days to find a hidden platform by swimming in a Morris water maze. Then, for 5 days, the mice were used to search for a visible platform in a Morris water maze. After that, the mice practised finding a safe place--an insulated platform in a chamber--for 2 days. During these animal experimental periods, similar algal meals containing astaxanthin at 0, 0.26, 1.3 and 6.4 mg/kg body weight were continuously fed to each group of tested mice. Profiles of latency, distance, speed and the direction angle to the platforms as well as the diving frequency in each group were measured and analyzed. The process of mice jumping up onto the insulated platform and diving down to the copper-shuttered bottom with a 36 V electrical charge were also monitored by automatic video recording. The results of the Morris maze experiment showed that middle dosage of H. pluvialis meals (1.3 mg astaxanthin/kg body weight) significantly shortened the latency and distance required for mice to find a hidden platform. However, there was no obvious change in swim velocity in any of the supplemented groups. In contrast, the visible platform test showed a significant increase in latency and swim distance, and a significant decrease in swim speed for all groups of mice orally supplemented with H. pluvialis powder compared to the placebo group (P < 0.05 or P < 0.01). Mice supplemented with the algal meal hesitantly turned around the original hidden platform, in contract to mice supplemented with placebo, who easily forgot the original location and accepted the visible platform as a new safe place. These results illustrate that astaxanthin-enriched H. pluvialis powder has the auxiliary property of memory improvement. The results from the platform diving test showed that the low and middle dosage of H. pluvialis powder, rather that the high dosage, increased the latency and reduced the frequency of diving from the safe insulated platform to the electrically stimulated copper shutter, especially in the low treatment group (P < 0.05). These results indicate that H. pluvialis powder is associated with dose-dependent memory improvement and that a low dosage of algal powder (<or=middle treatment group) is really good for improving the memory.


Efficient photoconductive terahertz source using line excitation.
We report significant improvement in terahertz (THz) power and efficiency using photoconductive sources by use of a spatially extended line source excitation and the trap enhanced field effect that occurs in sources made on semi-insulating GaAs. The combination of high electric fields and reduced screening effects allows 10 microW of THz power to be generated with 14 mW of absorbed optical power, demonstrating nearly 0.1% optical-to-THz conversion efficiency.


Product activation of human erythrocyte AMP deaminase.
IMP was found to activate AMP deaminase in crude glucose-depleted human erythrocyte lysates. Activation of the enzyme by IMP is due to prevention of the inhibitory effect of inorganic phosphate. At 1 mM AMP and 2-3 mM phosphate the addition of 2-5 mM IMP accelerates the AMP deamination two to three times.


[If digital clubbing appears bear Marie-Bamberger disease in mind].
Secondary hypertrophic osteoarthropathy, also known as Marie-Bamberger disease, occurs in up to 5 % of patients with non-small cell lung cancer (NSCLC). If the syndrome constellation of finger clubbing and bone pain on palpation is recognized early, lung cancer can be diagnosed at an early stage. This article reports the case of a 52-year-old male patient with knee pain, distal edema, watchglass nails and finger clubbing which first appeared in August 2013. Following angiologic, cardiologic and orthopedic consultations radiographs of the hands, feet and lungs were taken. Following the presumptive diagnosis of hypertrophic osteoarthropathy, the patient was referred to a specialist pulmonary clinic where an adenocarcinoma of the lungs was diagnosed.


Macrophage infiltration and renal damage are independent of matrix metalloproteinase 12 in the obstructed kidney.
To determine whether matrix metalloproteinase-12 (MMP-12) plays a functional role in renal interstitial macrophage accumulation, interstitial fibrosis or tubular apoptosis in the unilateral ureteric obstruction (UUO) model. MMP-12 is an enzyme that can cleave a number of extracellular matrix proteins and plays a role in macrophage-mediated injury in experimental models of emphysema and antibody-dependent glomerular disease. Macrophages are thought to promote renal fibrosis and tubular damage in the obstructed kidney. Furthermore, upregulation of MMP-12 expression by infiltrating macrophages in the obstructed kidney has been described, but the potential role of MMP-12 in renal injury induced by this non-immune insult is unknown. Groups of eight MMP-12 gene deficient (MMP-12(-/-)) and wild type (WT) C57BL/6J mice were killed 3, 7 or 14 days after UUO. Analysis of three different lineage markers found no difference in the degree of interstitial macrophage accumulation between MMP-12(-/-) and WT UUO groups at any time point. Examination of renal fibrosis by total collagen staining, α-SMA + myofibroblast accumulation, and TGF-β1, PAI-1 and collagen IV mRNA levels showed no difference between MMP-12(-/-) and WT UUO groups. Finally, tubular damage (KIM-1 levels) and tubular apoptosis (cleaved caspase-3) in the obstructed kidney was not affected by MMP-12 gene deletion. In contrast to lung injury and antibody-dependent glomerular injury, MMP-12 is not required for renal interstitial macrophage accumulation, interstitial fibrosis or tubular damage in the obstructed kidney.


An Initiative to Reduce Routine Viral Diagnostic Testing in Pediatric Patients Admitted with Bronchiolitis.
Bronchiolitis is a viral lower respiratory tract infection that causes significant morbidity and mortality in the pediatric population. Viral diagnostic testing (VDT) has been used to identify specific viral pathogens. However, current guidelines suggest that routine use of this testing is not advisable. For children admitted to a children's hospital from the pediatric emergency department (PED), the rate of VDT was 63%, which was higher than the national rate. A quality improvement project was conducted to reduce the use of routine VDT. Key drivers of VDT were identified, and interventions, which included staff education about the cost and use of VDT and dissemination of a simplified cohorting policy aimed to eliminate VDT without medical necessity, were implemented through the PED and inpatient unit settings. Between January 2017 and April 2017, VDT use in all non-ICU patients admitted from the PED with bronchiolitis decreased from 63% to 12%. In the same time period, patients with VDT sent from the PED fell from 53% to 14%. A reduction in VDT for patients admitted with asthma exacerbation was also observed-from 24% to 0%-demonstrating early spread of these effects. Cost savings of approximately $8,584 per year in direct supply costs alone was documented. Using simple, low-cost interventions, including education and guideline refinement, the rate of VDT use for bronchiolitis was significantly reduced. Further directions for this project include the reduction of routine testing for patients with bronchiolitis who are admitted to the ICU or discharged for outpatient care.


Superficial implantation in pigs is associated with decreased numbers and redistribution of endometrial NK-cell populations.
We evaluated implantation-associated quantitative changes in endometrial and peripheral natural killer (NK)-cell populations of pigs. Natural killer cell populations were investigated in 10, 15, 20, 30 and 40 days pregnant and non-pregnant (NP) sows by flow cytometry, immunohistochemistry and morphometry. The number of endometrial CD16(+) NK cells significantly declined at attachment phase of implantation and remained relatively low over the course of implantation. The CD16(+) NK cells in situ showed implantation-phase dependent density and localization. Prior to implantation, they substantially resided in the subepithelial stroma. As implantation advances, the density of NK cells into subepithelial stroma decreased while that of NK cells into glandular layer increased, suggesting implantation-induced re-location far from the attached conceptus. The number of CD56(+) lymphocytes was the greatest at pre-attachment phase of implantation, dropped at the time of attachment and increased up to end of early pregnancy period. The CD3(-) CD8(+) NK-cell number decreased significantly when the definitive placenta is established. No significant differences in the numbers of peripheral blood CD16(+), CD56(+) and CD3(-) CD8(+) NK cells between pregnant and NP animals as well as relative to the implantation phase were observed. Superficial and adeciduate implantation of pigs is associated with decreased numbers of endometrial NK-cell populations and specific spatiotemporal profile of classical NK cells.


Protease inhibitors: silver bullets for chronic hepatitis C infection?
Recent trials evaluated the safety and efficacy of two protease inhibitors, boceprevir (Victrelis) and telaprevir (Incivek), added to standard care with pegylated interferon and ribavirin, in patients with chronic hepatitis C virus (HCV) infection. These drugs open the door for triple therapy and other new therapies involving combinations of other direct-acting antiviral agents to become the new standard of care for this population.


Ethyl 2-(3,5-dinitro-benzamido)-benzoate.
The title mol-ecule, C(16)H(13)N(3)O(7), is slightly twisted, with the dihedral angle between the two benzene ring planes being 17.4 (1)°. An intra-molecular N-H⋯O hydrogen bond is observed. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into chains along the b axis.


Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis.
We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment. The trial was a prospective, randomized, and non-blinded study. The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands. Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis. Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients. Outcome measures were a complete or partial response, recrudescence and relapse. A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003). Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.


Sternal cavernous hemangioma and reconstruction of the anterior chest wall: a case report.
The sternum is considered an unusual tumor site, corresponding to 15% of all thoracic wall tumors. Primary sternal tumors are even rarer and most commonly malignant. We present the case of a young man who consulted with a painful sternal mass, which after its resection is confirmed to be a cavernous hemangioma. A 39-year-old man, with unremarkable medical history besides a 2-year-long sternal pain, non-irradiated, which worsens over the last few months and is accompanied by the appearance of a sternal palpable mass. On physical exam, there was a bulging of the sternal manubrium, with no inflammatory changes. Thoracic CT scan shows an expansive and lytic lesion of the sternum, compromising the manubrium and extending to the third sternocostal joint, without intrathoracic compromise nor cleavage plane with mediastinal vascular structures. The patient is taken to resection of the mass and sternal reconstruction using prosthetic material and pectoral and fasciocutaneous muscular flaps. Histopathological findings: cavernous hemangioma with negative borders and no other malignant findings. Sternal hemangiomas can cause defects in the bone structure and show an expansive growth, challenging the differentiation between a benign or malignant lesion. Therefore, they should be considered malignant until shown otherwise. Management involves radical surgery with curative purposes and posterior reconstruction to improve quality of life, as shown with our patient.


A Reflection of a Taiwanese Resident of Surgery in COVID-19 Pandemic.
In March 2020, the coronavirus disease 2019 (COVID-19) outbreak was declared as a pandemic by the World Health Organization. The COVID-19 breached the Taiwanese government's defense, and the Central Epidemic Command Center (CECC) announced a Nationwide Level 3 Alert on May 19, 2021. In summary, the residency training has been affected as follows: less exposure to elective surgeries and decreased training time. In the COVID-19 pandemic era, both my life and career as a surgical resident have been deeply affected. Worries, anxiety, and fear about insufficient training, unfulfilled career development, and unknown future have been prevalent daily. However, surgeons have always managed to confront and overcome difficulties and challenges with courage and fearlessness. Hence, it is also important that we face the COVID-19 pandemic situation and adapt wisely.


Removal mechanisms of Cr(VI) and Cr(III) by biochar supported nanosized zero-valent iron: Synergy of adsorption, reduction and transformation.
In this study, sludge-derived biochar was prepared and utilized to support nano-zero-valent iron (NZVI-SDBC) for removing Cr(VI) and Cr(III) from aqueous solution with the aim of investigating their removal and transformation. Under the conditions of initial pH of 4, dosage of 1 g/L, temperature of 25 °C, and rotational speed of 160 rpm, 64.13% Cr species could be removed by NZVI-SDBC from Cr(VI) solution and 28.89% from Cr(III) solution. Coexisting ions experiments showed that Cu(II) and humic acids dramatically affected the removal of Cr(VI) and Cr(III), while the effect of Na(I) and Ca(II) was almost negligible. Based on this, through the coexistence and pre-loaded Cr(III) experiments, the conversion from Cr(VI) to Cr(III) was demonstrated to enhance the further attraction on Cr(VI) and promote the subsequent removal of Cr(VI). The SDBC of NZVI-SDBC could serve as electron shuttle mediator to facilitate the electron transfer between adsorbed Cr(VI) and NZVI for ortho-reduction. The transformation and removal mechanisms were further discussed by various characterizations. The kinetics of Cr(VI) removal suggested that the removal process of Cr(VI) could be divided into three phases dominated by different mechanisms (adsorption, direct/ortho reduction, electrostatic attraction), in which Cr(VI) and Cr(III) showed different behaviors of interaction. The removal of Cr(III) mainly depended on sufficient adsorption sites and the direct complexation with Fe(II). Finally, the reusability of NZVI-SDBC was assessed by adsorption/desorption recycling test. These results provided new insights into the removal and transformation mechanisms of Cr(VI) and Cr(III) by biochar-based nanocomposites.


Thermal physiological ecology of Colias butterflies in flight.
As a comparison to the many studies of larger flying insects, we carried out an initial study of heat balance and thermal dependence of flight of a small butterfly (Colias) in a wind tunnel and in the wild.Unlike many larger, or facultatively endothermic insects, Colias do not regulate heat loss by altering hemolymph circulation between thorax and abdomen as a function of body temperature. During flight, thermal excess of the abdomen above ambient temperature is weakly but consistently coupled to that of the thorax. Total heat loss is best expressed as the sum of heat loss from the head and thorex combined plus heat loss from the abdomen because the whole body is not isothermal. Convective cooling is a simple linear function of the square root of air speed from 0.2 to 2.0 m/s in the wind tunnel. Solar heat flux is the main source of heat gain in flight, just as it is the exclusive source for warmup at rest. The balance of heat gain from sunlight versus heat loss from convection and radiation does not appear to change by more than a few percent between the wings-closed basking posture and the variable opening of wings in flight, although several aspects require further study. Heat generation by action of the flight muscles is small (on the order of 100 m W/g tissue) compared to values reported for other strongly flying insects. Colias appears to have only very limited capacity to modulate flight performance. Wing beat frequency varies from 12-19 Hz depending on body mass, air speed, and thoracic temperature. At suboptimal flight temperatures, wing beat frequency increases significantly with thoracic temperature and body mass but is independent of air speed. Within the reported thermal optimum of 35-39°C, wing beat frequency is negatively dependent on air speed at values above 1.5 m/s, but independent of mass and body temperature. Flight preference of butterflies in the wind tunnel is for air speeds of 0.5-1.5 m/s, and no flight occurs at or above 2.5 m/s. Voluntary flight initiation in the wild occurs only at air speeds ≦1.4 m/s.In the field, Colias fly just above the vegetation at body temperatures of 1-2°C greater than when basking at the top of the vegetation. These measurements are consistent with our findings on low heat gain from muscular activity during flight. Basking temperatures of butterflies sheltered from the wind within the vegetation were 1-2°C greater than flight temperatures at vegetation height.


Interleukin-12 augments cytolytic activity of peripheral blood mononuclear cells against autologous lung cancer cells in combination with IL-2.
The majority of patients with advanced lung cancer die within a few years. Accordingly, new therapeutic modalities need to be developed. Interleukin (IL)-12 was previously known as natural killer (NK) cell stimulatory factor or cytotoxic lymphocyte maturation factor. By virtue of its effects on T cells and NK cells, IL-12 seems to be one of the key cytokines that regulates cell-mediated anti tumor immune responses. Recently, there has been a substantial interest in the potential applications of IL-12 in the treatment of lung cancer. However, there have been no reports about the effect of IL-12 on peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients in an autologous setting. In this study, we examined the cytotoxicity of PBMC activated by IL-2, IL-12 or both against K562 or autologous lung cancer cells. In contrast to the effect of IL-2 on NK activity, IL-12 alone augmented NK activity against K562 cells, but not against autologous lung cancer cells. IL-12 augmented the IL-2 mediated cytotoxicity of PBMC against both K562 and autologous lung cancer cells. In the absence of IL-2, IL-12 alone cannot induce an autologous anti-tumor effect in vivo. In summary, our results clearly demonstrated that IL-12 can augment the cytolytic activity of PBMC against K562 and autologous lung cancer cells when combined with IL-2, although, IL-12 alone was unable to induce a marked increase in the cytotoxicity against autologous lung cancer cells. These results suggest that an administration of IL-12 in combination with IL-2 may be a useful therapeutic option for solid tumors.


Pericentric inversions in man: personal experience and review of the literature.
The Leuven cytogenetic centre experience on pericentric inversion in man is discussed with exclusion of the pericentric inversions of the heterochromatic blocks of chromosomes 1 and 9. In a total of 51,500 patients, referred for constitutional chromosome analysis during the period 1970-1985, pericentric inversions were found in 24 index patients. The breakpoints detected in these different pericentric inversions are summarized and compared to those found in previous reports. Bands 2p13, 2q21, 5q31, 6q21, 10q22, and 12q13 were shown to be repeatedly involved in the different studies and, furthermore, breakpoints at bands 2q11, 5p13, 5p15, 5q13, 7q11, 11q25, and 14p11 were present in this study as well as in our previous review on reciprocal autosomal translocations. In 13 familial pericentric inversions, even after exclusion of all inversion carrier probands, a 1.6:1 excess of pericentric inversion carriers versus karyotypically normal progeny was observed. While chromosomally unbalanced offspring represent 3.5% of all chromosomally investigated liveborns of the present study, 7.1% of all liveborn inversion carrier offspring presented with a mental retardation and/or multiple congenital anomalies (MR/MCA) problem. Additional chromosomal abnormalities, i.e. a 21 trisomy and an accessory small ring chromosome were observed in two pericentric inversion carriers. These data and results are discussed and compared to the data available in the literature.


The cell biology of genomes: bringing the double helix to life.
The recent ability to routinely probe genome function at a global scale has revolutionized our view of genomes. One of the most important realizations from these approaches is that the functional output of genomes is affected by the nuclear environment in which they exist. Integration of sequence information with molecular and cellular features of the genome promises a fuller understanding of genome function.


Towards human motor augmentation by voluntary decoupling beta activity in the neural drive to muscle and force production.
Objective.Effective human motor augmentation should rely on biological signals that can be volitionally modulated without compromising natural motor control.Approach.We provided human subjects with real-time information on the power of two separate spectral bands of the spiking activity of motor neurons innervating the tibialis anterior muscle: the low-frequency band (<7 Hz), which is directly translated into natural force control, and the beta band (13-30 Hz), which is outside the dynamics of the neuromuscular system.Main Results.Subjects could gain control over the powers in these two bands to navigate a cursor towards specific targets in a 2D space (experiment 1) and to up- and down-modulate beta activity while keeping steady force contractions (experiment 2).Significance.Results indicate that beta projections to the spinal motor neuron pool can be voluntarily controlled partially decoupled from natural muscle contractions and, therefore, they could be valid control signals for implementing effective human motor augmentation platforms.


The 'common knowledge' of Quebecers: quantifying the evidence of historians testifying for defendant tobacco companies.
The 'common knowledge' defence is a legal strategy which has been successfully used by defendant tobacco companies to avoid legal responsibility for the harms caused by smoking. Tobacco companies have hired professional historians to try to persuade courts about a longstanding high level of public awareness regarding the risks of tobacco use. To support this argument, they have used archival news clippings and media reports. Two historians were hired by tobacco companies to offer this defence during a recent class action trial in Canada, following which they were required to submit to the court the collection of media materials which had been gathered by history students to assist their testimony. Included in this collection were tobacco advertisements and other news items about tobacco products which the students had inadvertently also collected. Quantifying this collection reveals that even by the tobacco industry's own construct, the information environment surrounding Quebec smokers in the middle 20th century included more prosmoking messages than information about the risks of smoking.


Marital interactions in the process of dietary change for type 2 diabetes.
To explore how couples adjust to dietary management of type 2 diabetes. Couples were interviewed, first together and then separately, during the first year after diagnosis and 1 year later. Qualitative interviews conducted in hospital classrooms using a semistructured interview guide. Couples (N = 20) with a recently diagnosed spouse who met the study criteria were purposefully selected from volunteers solicited from hospital-based diabetes classes. Processes used by the couple to address the prescribed diet. Thematic analysis of interview transcripts using grounded theory to identify patterns of adaptation processes used over time. Three couple categories emerged (cohesive, enmeshed, and disengaged), representing adaptation to the diabetic diet. Initially, 5 couples were cohesive (teamwork approach), 7 were enmeshed (nondiabetic spouse responsible for the diet; spouse was dependent), and 8 were disengaged (spouses functionally separate; spouse was solely responsible for the diet management). A year later, the majority of couples were disengaged (n = 14), 1 couple remained cohesive, and 4 couples remained enmeshed. Themes of flexibility, roles, rules, and communication varied across categories. Understanding categories of marital adjustment to the diabetic diet may improve nutrition-based diabetes interventions. Further study is needed to verify these findings in larger and more diverse populations.


Functional differences in type-I fibres from two slow skeletal muscles of rabbit.
The present study addressed the question of whether the slow fibres of mammalian skeletal muscle, containing the myosin heavy chain MHCI (type-I fibres), are a functionally homogeneous population. We compared various properties of Ca(2+)-activated, skinned, type-I fibres from the soleus and semitendinosus muscles of a rabbit. Soleus type-I fibres showed significantly faster kinetics of stretch activation, measured as the time-to-peak of the stretch-induced, delayed force increase, t(3), than semitendinosus fibres (1239+/-438 ms, n=136, vs. 1600+/-409 ms, n=208 respectively) (means+/-SD, 22 degrees C). Similarly, the speed of unloaded shortening at 15 degrees C was faster in soleus than in semitendinosus fibres [0.79+/-0.16 fibre lengths (FL) s(-1), n=44, vs. 0.65+/-0.15 FL s(-1), n=35 respectively]. The kinetics of stretch activation were more temperature sensitive in semitendinosus than in soleus fibres. Finally, the generation of steady-state isometric force was more sensitive to Ca(2+) in semitendinosus than in soleus fibres: [pCa(50) (-log [Ca(2+)] for half-maximal activation) at 22 degrees C: 6.29+/-0.15, n=28, vs. 6.19+/-0.10, n=18 respectively]. These results suggest strongly that there is no functional homogeneity within type-I fibres of different muscles. The observed differences might reflect the existence of more than one functionally different slow myosin heavy chain isoforms or other modifications of contractile proteins.


Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide.
After hematopoietic stem cell transplantation (HSCT), patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI) which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa) and octreotide infusion.


Fetal hypothalamic transplants promote survival and functional regeneration of axotomized adult supraoptic magnocellular neurons.
This study investigated the mechanisms by which fetal hypothalamic transplants promote functional recovery in neurohypophysectomized rats. Seven days after neurohypophysectomy (resulting in urine osmolalities of about 800 mOsm), young adult male Long-Evans rats received either fetal hypothalamic grafts (n = 10) or sham transplants (n = 7). Recovery from the lesioned-induced diabetes insipidus was monitored for 6 months and then the transplant sites were evaluated by immunocytochemistry. Surviving host supraoptic magnocellular neurons and neurophysin-positive grafted neurons were counted and their formation of neurohemal contacts evaluated by retrograde transport of systemically injected horseradish peroxidase (HRP). There were significantly more surviving supraoptic magnocellular neurons in neurohypophysectomized animals with median eminence-placed grafts (2236 +/- 261 neurons/animal) than in animals with ectopic tissue grafts (895 +/- 142 neurons/animal) or sham implants (1052 +/- 92 neurons/animal). Almost all surviving host magnocellular neurons were labeled with retrogradely transported HRP while virtually none of the grafted neurophysin positive cells showed evidence of HRP uptake. The degree of functional recovery was directly correlated with the increased survival of host neurons. By 8 weeks post-transplantation, animals with median eminence-placed grafts had recovered from their diabetes insipidus and could concentrate their urine to within normal limits (2,120 +/- 110 mOsm). This recovery was stable for the remainder of the 6 month test period. In contrast, animals with ectopic grafts and sham transplants had permanent deficits in fluid regulation. Our results provide evidence for the long-term capacity of fetal neural tissue implants to rescue host neurons from the cell death that typically occurs in the mature central nervous system after axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)


Life-threatening hypophosphataemia secondary to zoledronic acid implementation in a middle-age patient who presented with advanced osteolysis in the course of multiple myeloma.
Not required for Clinical Vignette.


Ocean inherent optical property determination from in-water light field measurements.
An algorithm is described and evaluated for determining the absorption and backscattering coefficients a(z) and bb(z) from measurements of the nadir-viewing radiance Lu(z) and downward irradiance Ed(z). The method, derived from radiative transfer theory, is similar to a previously proposed one for Eu(z) and Ed(z)and both methods are demonstrated with numerical simulations and field data. Numerical simulations and a sensitivity analysis show that good estimates of a(z) and bb(z) can be obtained if the assumed scattering phase function is approximately correct. In an experiment in Long Island Sound, estimates of a(z) derived with these methods agreed well with those obtained from an in situ reflecting tube instrument.


Long-term strontium ranelate administration in monkeys preserves characteristics of bone mineral crystals and degree of mineralization of bone.
In monkeys, long-term strontium ranelate administration results in a dose-dependent bone strontium uptake (mainly into newly formed bone) that preserves the degree of mineralization of bone and the bone mineral at the crystal level, showing its safety at bone mineral level. Strontium ranelate simultaneously increases bone formation and decreases bone resorption, leading to prevention of bone loss and increase in bone mass and bone strength in normal and ovariectomized rats. This study investigated the interactions of stable strontium (Sr) with bone mineral in monkeys after long-term strontium ranelate treatment and after a period of treatment withdrawal. Iliac bone was obtained from untreated monkeys, monkeys at the end of a 52-week strontium ranelate administration (200, 500, 1250 mg/kg/day orally), and in parallel groups 10 weeks after the end of strontium ranelate administration (same three doses; n = 3-7). Sr uptake and distribution in bone mineral were quantified by X-ray microanalysis, changes at the crystal level by X-ray diffraction, and the degree of mineralization of bone (DMB) by quantitative microradiography. After strontium ranelate administration, dose-dependent Sr uptake occurred into cortical and cancellous bone, with higher content (1.6 times) in new than in old bone. This Sr uptake decreased (50%) 10 weeks after treatment withdrawal; the decrease occurred almost exclusively in new bone. At the end of strontium ranelate treatment and after its withdrawal, a preservation of crystal characteristics was observed, suggesting that Sr was only faintly linked to crystals by ionic substitution and of DMB. These results show the absence of a deleterious effect of long-term strontium ranelate treatment on bone mineralization, confirming the histomorphometric observations made in postmenopausal osteoporotic women treated with strontium ranelate.


Effects of sodium, potassium and calcium ions on the slow wave in the circular muscle of the guinea-pig stomach.
1. The contribution of Na, K and Ca ions to the generation of slow waves in the circular muscle of the guinea-pig stomach was studied.2. The slow waves had a lower, potential-independent (first) and an upper, potential-dependent (second) component. Reduction of the external Na prolonged the first component, but complete removal of Na depolarized the membrane and caused deterioration of the slow wave.3. Readmission of Na (5-10 mM) restored the slow wave; this action was not abolished by ouabain.4. Removal of K depolarized the membrane and slightly reduced the amplitude and duration of the slow waves. Readmission of K hyperpolarized the membrane and increased the amplitude and duration of the slow waves, particularly of the first component. Ouabain blocked the effects on the membrane potential, but not the effects on the slow waves.5. An increase in extracellular Ca prolonged the first component and reduced the frequency. Removal of extracellular Ca abolished the slow wave activity. Excess Ca enhanced, and low Ca reduced the effects of altering the concentrations of external K.6. It is concluded that the ouabain-sensitive Na-K pump may not be directly involved in generating slow waves, but that some other metabolic process is involved, which is regulated to a large extent by Ca, and possibly also by Na and K.


Effects of ultrasound-assisted high temperature-pressure treatment on the structure and allergenicity of tropomyosin from clam (Mactra veneriformis).
Tropomyosin (TM) is the major allergen in clams. This study aimed to evaluate the effects of ultrasound-assisted high temperature-pressure treatment on the structure and allergenicity of TM from clams. The results showed that the combined treatment significantly affected the structure of TM-converting the α-helix to β-sheet and random coil, and decreasing the sulfhydryl group content, surface hydrophobicity, and particle size. These structural changes caused the unfolding of the protein, disrupting and modifying the allergenic epitopes. The significant reduction in the allergenicity of TM was approximately 68.1% when treated with combined processing (P < 0.05). Notably, an increase in the content of the relevant amino acids and a smaller particle size accelerated the penetration of the enzyme into the protein matrix, resulting in strengthening the gastrointestinal digestibility of TM. These results prove that ultrasound-assisted high temperature-pressure treatment has great potential in reducing allergenicity, benefiting the development of hypoallergenic clam products.


Tumor tropic delivery of FU.FA@NSs using mesenchymal stem cells for synergistic chemo-photodynamic therapy of colorectal cancer.
To overcome the limitations associated with the targeting abilities of nanotherapeutics and drug loading capacity of mesenchymal stem cells (MSCs), the present study relies on the combination of MSCs tumor tropism with the controlled release function of nano-based drug delivery platforms to achieve tumor-specific accumulation of chemotherapeutics with minimal off-target effects. 5-fluorouracil (5-FU)-containing ceria (CeNPs) coated calcium carbonate nanoparticles (CaNPs) were functionalized with folinic acid (FA) to develop drug-containing nanocomposites (Ca.FU.Ce.FA NCs). NCs were then conjugated with graphene oxide (GO) and decorated with silver nanoparticles (Ag°NPs) to form FU.FA@NS, a rationally designed drug delivery system with O2 generation capacity that alleviates tumor hypoxia for improved photodynamic therapy. Engineering of MSCs with FU.FA@NSs provided successful loading and long-term retention of therapeutics on the surface membrane with minimal changes to the functional properties of MSCs. Co-culturing of email@example.com with CT26 cells upon UVA exposure revealed enhanced apoptosis in tumor cells through ROS-mediated mitochondrial pathway. FU.FA@NSs released from MSCs were effectively taken up by CT26 cells via a clathrin-mediated endocytosis pathway and distributed their drug depots in a pH, H2O2, and UVA-stimulated fashion. Therefore, the cell-based biomimetic drug delivery platform formulated in the current study could be considered a promising strategy for targeted chemo-photodynamic therapy of colorectal cancer.


Communication: thermodynamics of condensed matter with strong pressure-energy correlations.
We show that for any liquid or solid with strong correlation between its NVT virial and potential-energy equilibrium fluctuations, the temperature is a product of a function of excess entropy per particle and a function of density, T = f(s)h(ρ). This implies that (1) the system's isomorphs (curves in the phase diagram of invariant structure and dynamics) are described by h(ρ)/T = Const., (2) the density-scaling exponent is a function of density only, and (3) a Grüneisen-type equation of state applies for the configurational degrees of freedom. For strongly correlating atomic systems one has h(ρ) = ∑(n)C(n)ρ(n/3) in which the only non-zero terms are those appearing in the pair potential expanded as ν(r) = ∑(n)ν(n)r(-n). Molecular dynamics simulations of Lennard-Jones type systems confirm the theory.


Psychological stress delays periodontitis healing in rats: the involvement of basic fibroblast growth factor.
To evaluate the effects of psychological stress on periodontitis healing in rats and the contribution of basic fibroblast growth factor (bFGF) expression to the healing process. Ninety-six rats were randomly distributed into control group, periodontitis group, and periodontitis plus stress group. Then, the rats were sacrificed at baseline and week(s) 1, 2, and 4. The periodontitis healing condition was assessed, and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and bFGF were tested by immunohistochemistry. The stressed rats showed reduced body weight gain, behavioral changes, and increased serum corticosterone and ACTH levels (P < 0.05). The surface of inflammatory infiltrate, alveolar bone loss, attachment loss, and expression of IL-1β and TNF-α in the stress group were higher than those in the periodontitis group at weeks 2 and 4 (P < 0.05). Rats with experimental periodontitis showed decreased bFGF expression (P < 0.05), and the recovery of bFGF expression in the stress group was slower than that in the periodontitis group (P < 0.05). Negative correlations between inflammatory cytokines and bFGF were detected. Psychological stress could delay periodontitis healing in rats, which may be partly mediated by downregulation of the expression of bFGF in the periodontal ligament.


Tiring job and work related injury road crashes in the GAZEL cohort.
The objective was to describe at-work and commuting crashes occurring in a cohort of French employees and to investigate occupational risk factors. The subjects were employees of the French national electricity and gas companies, Electricité de France and Gaz de France (EDF-GDF), who volunteered to join a research cohort (the GAZEL cohort which included 20,625 participants in 1989). Only crashes with injuries were considered. Crashes for the periods 1989--2001 were recorded together with the type of journey (commuting, work, private), the type of road-user, self-estimated responsibility, and injuries sustained by the subject. Annual incidences for gender/age groups and socio-occupational groups were computed for each of the two types of work related crashes. Occupational risk factor analyses were conducted using a Cox proportional hazards regression model with time-dependent covariates adjusting for the main confounders. A total of 146,285 person years at work were observed. Two indicators of self-reported work fatigue were associated with the occurrence of at-work crashes: "nervously tiring work" for males (RR=1.6, 95% CI [1.1; 2.3]), sustained standing for females (RR=3.0, 95% CI [1.0; 8.4]), adjusting for health status, location of residence, type of family, transport mode and mileage. As regards crashes while commuting, a self-reported uncomfortable position at work was a risk factor among women (RR=1.9, 95% CI [1.1; 3.3]). On the other hand, these occupational factors were not linked to road crashes in private trips. Work related road crashes seem then to be a matter for a specific prevention. Preventing employees from becoming exhausted should be considered as the first way to initiate such a prevention.


Deletion of the SAPS1 subunit of protein phosphatase 6 in mice increases radiosensitivity and impairs the cellular DNA damage response.
Cellular responses to DNA damage include activation of DNA-dependent protein kinase (DNA-PK) through, among others, the serine/threonine protein phosphatase 6 (PP6). We previously showed that recognition of DNA-PKcs is mediated by the SAPS1 PP6 regulatory subunit. Here, we report and characterize a SAPS1 null mouse and investigate the effects of deletion on DNA damage signaling and repair. Strikingly, neither SAPS1-null animals nor cells derived from them show gross defects, unless subjected to DNA damage by radiation or chemical agents. The overall survival of SAPS1-null animals following whole body irradiation is significantly shortened as compared to wild-type mice, and the clonogenic survival of null cells subjected to ionizing radiation is reduced. The dephosphorylation of DNA damage/repair markers, such as γH2AX, p53 and Kap1, is diminished in SAPS1-null cells as compared to wild-type controls. Our results demonstrate that loss of SAPS1 confers sensitivity to DNA damage and confirms previously reported cellular phenotypes of SAPS1 knock-down in human glioma cells. The results support a role for PP6 regulatory subunit SAPS1 in DNA damage responses, and offer a novel target for sensitization to enhance current tumor therapies, with a potential for limited deleterious side effects.