Dopaminergic innervation and inhibition of ciliary movement in the ciliated epithelium of frog palatine mucosa.
The effect of dopamine on ciliary movement and the existence of dopamine-containing cells in the ciliated epithelium of frog palatine mucosa were investigated pharmacologically and by means of electron and fluorescence microscopy, respectively. Ciliary movement was suppressed markedly when the perfusion medium contained 10(-6) M dopamine, thereby indicating that dopamine has a suppressive effect on ciliary movement. Electron microscopy revealed at least two types of granule-containing (GC) cells, type 1 cells containing small spherical granular vesicles (about 100-150 nm in diameter) and type 2 cells containing elongated dense granules (about 150 X 250 nm in diameter). One hour after systemic administration of dihydroxyphenylalanine-[3H(G)] [( 3H]DOPA), a large number of silver grains appeared only in type 2 GC cells, thus indicating that type 2 cells are catecholamine-storing. Blue-green fluorescent cells were detected in the ciliated epithelium. On microspectrofluorometry, catecholamine fluorescence in the cells showed a main excitation and emission maxima at 415 and 480 nm, respectively. When the fluorescent cells were exposed to HCl vapor for several s, the excitation peak shifted to 380 nm and this peak was unchanged after treatment for an additional 5 min. It may be considered that these fluorescent cells contain dopamine and correspond to type 2 GC cells. A possible functional relationship between regulation of ciliary movement and dopamine-containing cells was also discussed.


Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone.
The impact of AGEs on human MSCs was studied. AGEs inhibited the proliferation of MSCs, induced apoptosis, and prevented cognate differentiation into adipose tissue, cartilage, and bone, suggesting a deleterious effect of AGEs in the pathogenesis of musculoskeletal disorders in aged and diabetic patients. Advanced glycation end-products (AGEs) are accumulated on long-lived proteins of various tissues in advanced age and diabetes mellitus and have been implicated in chronic complication, including musculoskeletal disorders. Human mesenchymal stem cells (MSCs) potentially differentiate into mature musculoskeletal tissues during tissue repair, but the pathogenetic role of AGEs on MSCs is unclear. AGEs were prepared by incubating BSA with glucose, glyceraldehydes, or glycolaldehyde (designated as AGE-1, AGE-2, or AGE-3, respectively). Proliferation, apoptosis, and reactive oxygen species (ROS) generation were assayed in AGE-treated cells. The expression of the receptor for AGE (RAGE) was examined by immunohistochemistry and Western blotting. Involvement of RAGE-mediated signaling was examined using a neutralizing antiserum against RAGE. Differentiation into adipose tissue, cartilage, and bone were morphologically and biochemically monitored with specific markers for each. AGE-2 and AGE-3, but not control nonglycated BSA and AGE-1, reduced the viable cell number and 5-bromo-2'deoxyuridine (BrdU) incorporation with increased intracellular ROS generation and the percentage of apoptotic cells. MSCs expressed RAGE and its induction was stimulated by AGE-2 and AGE-3. These AGEs inhibited adipogenic differentiation (assayed by oil red O staining, lipoprotein lipase production, and intracellular triglyceride content) and chondrogenic differentiation (assayed by safranin O staining and type II collagen production). On osteogenic differentiation, AGE-2 and AGE-3 increased alkaline phosphatase activity and intracellular calcium content; however, von Kossa staining revealed the loss of mineralization and mature bone nodule formation. The antiserum against RAGE partially prevented AGE-induced cellular events. AGE-2 and AGE-3 may lead to the in vivo loss of MSC mass and the delay of tissue repair by inhibiting the maturation of MSC-derived cells. The AGE-RAGE interaction may be involved in the deleterious effect of AGEs on MSCs.


Developing prognostic nomograms to predict overall survival and cancer-specific survival in synchronous multiple primary colorectal cancer based on the SEER database.
Synchronous multiple primary colorectal cancer (SMPCC) is a rare subtype of CRC, characterized by the presence of two or more primary CRC lesions simultaneously or within 6 months from the detection of the first lesion. We aim to develop a novel nomogram to predict OS and CSS for SMPCC patients using data from the SEER database. The clinical variables and survival data of SMPCC patients between 2004 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Appropriate inclusion and exclusion criteria were established to screen the enrolled patients. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors for OS and CSS. The performance of the nomogram was evaluated using the concordance index (C-index), calibration curves, and the area under the curve (AUC) of a receiver operating characteristics curve (ROC). A decision curve analysis (DCA) was generated to compare the net benefits of the nomogram with those of the TNM staging system. A total of 6772 SMPCC patients were enrolled in the study and randomly assigned to the training (n = 4670) and validation (n = 2002) cohorts. Multivariate Cox analysis confirmed that race, marital status, age, histology, tumor position, T stage, N stage, M stage, chemotherapy, and the number of dissected LNs were independent prognostic factors.The C-index values for OS and CSS prediction were 0.716 (95% CI 0.705-0.727) and 0.718 (95% CI 0.702-0.734) in the training cohort, and 0.760 (95% CI 0.747-0.773) and 0.749 (95% CI 0.728-0.769) in the validation cohort. The ROC and calibration curves indicated that the model had good stability and reliability. Decision curve analysis revealed that the nomograms provided a more significant clinical net benefit than the TNM staging system. We developed a novel nomogram for clinicians to predict OS and CSS, which could be used to optimize the treatment in SMPCC patients.


ABCC2 c.-24 C>T single-nucleotide polymorphism was associated with the pharmacokinetic variability of deferasirox in Chinese subjects.
Our aim was to evaluate the influence of genetic polymorphisms involved in the metabolism and transportation of deferasirox on deferasirox pharmacokinetics in the Chinese population. Thirty-eight healthy Chinese subjects were administered with a single dose of 20 mg kg-1 deferasirox. Allelic discriminations for eight single-nucleotide polymorphisms (SNPs) in UDP-glucuronosyltransferase 1A1, 1A3 (UGT1A1, UGT1A3), multidrug resistance protein 2 (MRP2, ABCC2), and breast cancer resistance protein (BCRP, ABCG2) were performed. The concentrations of deferasirox in the plasma were determined by UPLC-MS/MS. Subjects carrying ABCC2 c.-24 T allele had a 65% higher clearance (CL/F) and 42% lower area under the concentration-time curve from 0 to 72 h (AUC0-72h) as compared with non-carriers (P = 0.008, P = 0.011, respectively). ABCC2 c.-24 T was also associated with 59% shorter half-life (T1/2) and 17% shorter mean residence time (MRT) (P = 0.030, P = 0.014, respectively). ABCC2 1249A was associated with a marginal increase in deferasirox Cmax (P = 0.07). Genetic polymorphisms of UGT1A1, UGT1A3, and ABCG2 did not significantly influence the pharmacokinetics of deferasirox. Subjects with UGT1A1 211GG-(-1352)CC-(-3156)GG haplotype had higher AUC0-72h than others. Since only two subjects were recruited in the GG-CC-GG group, further confirmative studies were warranted. ABCC2 c.-24 C>T was associated with the pharmacokinetic variability of deferasirox in Chinese subjects. This study revealed an important role of MRP2 in the pharmacokinetics of deferasirox and drew attention to drug combination with MRP2 inhibitors like cyclosporine and methotrexate in deferasirox therapy.


Glucose Binding Drives Reconfiguration of a Dynamic Library of Urea-Containing Metal-Organic Assemblies.
A bis-urea-functionalized ditopic subcomponent assembled with 2-formylpyridine and FeII , resulting in a dynamic library of metal-organic assemblies: an irregular FeII4 L6 structure and three FeII2 L3 stereoisomers: left- and right-handed helicates and a meso-structure. This library reconfigured in response to the addition of monosaccharide derivatives, which served as guests for specific library members, and the rate of saccharide mutarotation was also enhanced by the library. The (P) enantiomer of the FeII2 L3 helical structure bound β-D-glucose selectively over α-D-glucose. As a consequence, the library collapsed into the (P)-FeII2 L3 helicate following glucose addition. The α-D-glucose was likewise transformed into the β-D-anomer during equilibration and binding. Thus, β-D-glucose and (P)-3 amplified each other in the product mixture, as metal-organic and saccharide libraries geared together into a single equilibrating system.


Gut microbiota regulates key modulators of social behavior.
Social behavior plays a pivotal role in the mental well-being of an individual. Continuous efforts in the past have led to advancements in the area of how the brain regulates emotion and cognition, while the understanding of human social behavior still remains eluded. A major breakthrough in understanding the etiology of neurological disorders is the recent insight on the role of the gut microbiota (GM). Human GM also referred to as the "forgotten organ" is home to 10(13-14) microorganisms, which is 10 times the number of cells present in the human body. In addition, the gut microbiome (total genome of GM) is 150 times greater as compared to the human genome. An emerging concept gaining worldwide focus and acceptance is that, this much big genome can potentially control human behavior and other biological functions. Herein we hypothesize on the basis of GM's ability to modify brain and behavior and that it can directly or indirectly control social behavior. This review focuses on the association of GM with various domains of social behavior like stress, cognition and anxiety.


Standardized Opioid Counseling Is Underperformed Before and After Anterior Cruciate Ligament Reconstruction.
To characterize contemporary pain management strategies after anterior cruciate ligament reconstruction (ACLR) within the US and international orthopaedic community. This was a cross-sectional survey-based study disseminated to a consortium of expert orthopaedic surgeons in the management of anterior cruciate ligament injuries. The survey was a 27-question, multiple choice-style questionnaire with question topics ranging from demographic characteristics and practice characteristics to surgeon-specific pain management strategies in the postoperative period after ACLR. Specific topics of interest included the use of preoperative opioid education and/or counseling sessions, implementation of standardized pain management regimens, use of pain tracking systems, and use of any adjunct non-narcotic analgesic modalities. A total of 34 completed surveys were collected, representing a 73.9% response rate. Over 85% of respondents reported prescribing opioids as a standardized postoperative regimen after ACLR. Surgeons reported prescribing 5- to 10-mg doses, with the tablet count ranging anywhere from fewer than 10 tablets to more than 20 tablets, often instructing their patients to stop opioid use 2 to 4 days postoperatively. Prescribed dosages remained stable or decreased over the past 6 months with increased use of non-narcotic adjuncts. Only one-third of respondents reported using standardized preoperative opioid counseling, with even fewer discussing postoperative discontinuation protocols. Over 85% of respondents prescribe opioids as a standardized postoperative regimen after ACLR, with only 15% providing non-narcotic pain regimens. However, prescribed dosages have remained stable or decreased over the past 6 months with increased use of non-narcotic adjuncts. Only one-third of respondents use standardized preoperative opioid counseling, with even fewer discussing postoperative discontinuation protocols. The ongoing opioid epidemic has created an urgent need to identify the most effective pain management strategies after orthopaedic procedures, especially ACLR. This study provides important information about current pain management practices for patients who have undergone ACLR.


Functional significance of post-myocardial infarction inflammation evaluated by 18F-fluorodeoxyglucose imaging in swine model.
The aim of the study was to investigate the relationship between post-myocardial infarction (MI) inflammation and left ventricular (LV) remodeling in a swine model by 18F-fluorodeoxyglucose (FDG) imaging. MI was induced in swine by balloon occlusion of the left anterior descending coronary artery. A series of FDG positron emission tomography (PET) images were taken within 2 weeks post-MI, employing a comprehensive strategy to suppress the physiological uptake of cardiomyocytes. Echocardiography was applied to evaluate LV volume, global and regional function. CD68+ macrophage and glucose transporters (GLUT-1, -3 and -4) were investigated by immunostaining. The physiological uptake of myocardium was adequately suppressed in 92.3% of PET scans verified by visual analysis, which was further confirmed by the minimal expression of myocardial GLUT-4. Higher FDG uptake was observed in the infarct than in the remote area and persisted within the observational period of 2 weeks. The FDG uptake of infarcted myocardium on day 1 post-MI was correlated with LV global remodeling, and the FDG uptake of infarcted myocardium on days 1 and 8 post-MI had a trend of correlating with regional remodeling of the infarct area. We here report a feasible swine model for investigating post-MI inflammation. FDG signal in the infarct area of swine persisted for a longer duration than has been reported in small animals. FDG activity in the infarct area could predict LV remodeling.


Synthesis of blood group A and B (type 2) tetrasaccharides. A strategy with fucosylation at the last stage.
The traditionally used strategy for the synthesis of blood group A and B tetrasaccharides includes 2'-O-fucosylation of lactosamine followed by insertion of an α1-3 linked N-acetylgalactosamine or a galactose moiety. Here, we report the synthesis of 3-aminopropyl glycosides of A (type 2) and B (type 2) tetrasaccharides via an alternative sequence, i.e. α-galactosaminylation (or α-galactosylation) followed by α-fucosylation. This strategy allows us to synthesize fucose-free trisaccharides GalNAcα1-3Galβ1-4GlcNAc and Galα1-3Galβ1-4GlcNAc, which are promising targets for immunotherapy utilising human natural antibodies against the trisaccharides. The key stage in this scheme was the selective chloroacetylation of the 2'-OH group of βGal in the intermediate trisaccharides having the second (3-OH) unprotected group.The protocol is suitable for multigram syntheses and its further scaling up.


Probiotic-related Clostridium butyricum bacteremia: a case report and literature review.
We report three cases of Clostridium butyricum bacteremia associated with taking C. butyricum-related probiotics. We performed a literature review and found 11 cases of C. butyricum bacteremia including our cases. Nine cases related to probiotics. We should consider that probiotics may infect clinically unstable patients.


Excellent clinical outcomes of renal transplant from pediatric deceased donors with acute kidney injury.
The use of kidneys from deceased donors with acute kidney injury (AKI) to expand the donor pool is an ongoing trend. Prior research on the utilization of AKI donor kidneys, especially from pediatric AKI donors, was limited and has been subject to small sample sizes. In this study, we aimed to evaluate the safety and effectiveness of early post-transplantation outcomes in pediatric deceased donors with AKI. This retrospective study compared the clinical results (including delayed graft function [DGF], acute rejection, patient and death-censored graft survival rates and renal function post-transplant) of kidney transplantation from deceased donors who were categorized as pediatric donors and adult donors with or without AKI, as defined by the Kidney Disease: Improving Global Outcomes (KIDGO) criteria, at our center between January 2018 and December 2020. Of the 740 patients, 154 received kidneys from pediatric donors (with AKI group [n = 41]; without AKI group [n = 113]), and 586 received kidneys from adult donors (with AKI group [n = 218]; without AKI group [n = 368]). The baseline characteristics were similar in both cohorts. No significant difference was observed in 1-year patient survival, death-censored graft survival, or acute rejection between the AKI and non-AKI groups in both the pediatric and adult cohorts. However, compared with those transplanted with adult AKI kidneys, those transplanted with pediatric AKI kidneys showed a superior recovery of allograft function. In pediatric cohorts, no significant difference was found in serum creatinine/estimated glomerular filtration rate (SCr/eGFR) between the AKI and non-AKI groups, even in the first week post-transplant. In contrast, the post-transplant SCr/eGFR level of the AKI group recipients in adult cohorts did not recover to a level statistically similar to that of non-AKI recipients, even at 6-months post-transplant. Nonetheless, AKI kidney recipients were at an increased risk of DGF in both pediatric (34.1% vs. 16.8%) and adult (38.5% vs. 17.4%) cohorts. Kidney transplantation from deceased donors with AKI has short-term clinical outcomes comparable to those of non-AKI kidney transplantation. Pediatric AKI kidneys have a superior recovery of allograft function. The transplant community should utilize this donor pool to minimize waiting-list-related mortalities.


Predicting mutagenicity of chemicals using topological and quantum chemical parameters: a similarity based study.
Five molecular similarity methods have been used to estimate mutagenicity of a set of 73 aromatic and heteroaromatic amines. Two of the similarity methods (AP, PCTI) are based on topological parameters. Two other methods (PCPROP, PROP) are derived from physicochemical and electronic parameters. The fifth method, PCALL, is based on a combination of both topological and physicochemical parameters. The effectiveness of the five similarity methods in the rapid evaluation of mutagenicity is discussed.


Combined urinary and fecal diversion using a no bowel anastomosis technique.
We present the experience at our institution with combined fecal and urinary diversion using 3 variations of a no anastomosis technique that avoids bowel anastomosis. The charts of 10 female and 2 male patients who underwent the no bowel anastomosis technique were identified and reviewed. Information on the etiology of urination and defecation abnormalities, surgical resolution, complications, hospital stay and other pertinent aspects of management were retrospectively reviewed. Mean patient age was 64 years (range 36 to 83). Of the 12 patients 7 had a history of cancer treated with external beam radiotherapy, while 4 had neurological disorders with combined fecal and urinary incontinence or a history of colostomy. Mean hospital stay was 14.6 days (range 6 to 31) and mean followup was 26.6 months (range 14 to 52). There were no postoperative deaths, although a nonQ wave myocardial infarction occurred in 1 patient. The no anastomosis technique of combined diversion is recommended in patients with preexisting or planned diversion of the fecal stream. Avoidance of bowel anastomosis makes this technique especially advantageous in those with a history of radiotherapy.


The frequency of non-epileptic spells in children: results of video-EEG monitoring in a tertiary care center.
the diagnosis of non-epileptic spells (NES) in children can be challenging, even for experienced clinicians. Our objective was to describe the characteristics of such events. this was a retrospective study conducted from January 2004 to December 2006. Inclusion criteria were age >1 month and <18 years and the diagnosis of NES established by video-EEG monitoring. among 746 monitored children (1203 recorded video-EEG sessions), 109 (14.6%) had NES. The mean age of patients with NES was 6.6 years (range 0.1-18). Seventy patients were diagnosed with NES alone; the remaining 39 with both NES and epilepsy. Developmental delay was more frequent among patients with a co-morbid diagnosis of epilepsy (p<0.001). Similar clinical events were reported in both of these groups, save for crying spells/irritability which was more common in children with epilepsy. Frequent manifestations of NES included staring spells in preschool children, crying/irritability, tremor and eye deviation in young children and preschoolers, and limb shaking in adolescents. All of the patients with epilepsy and 19 (27%) of those without epilepsy were receiving antiepileptic drugs. our data highlights the importance of accurate diagnosis of NES toward the appropriate treatment of affected children.


Diastereoselective reversible C-C bond exchange of oxindole-thiazolidienediones for dynamic combinatorial chemistry.
We herein describe a diastereoselective aldol exchange involving isatins and thiazolidinediones, providing oxindolyl-thiazolidienediones in aqueous media at pH 6. This equilibrium can also be achieved with oxindole exchange as well as cross-exchange within reasonable timescales. These metal and organic catalyst free reversible reactions provide a unique opportunity for the evolution of dynamic combinatorial libraries (DCLs) for target directed dynamic combinatorial chemistry (DCC) and system chemistry.


Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Acute Myeloid Leukemia: A Single-Centre Experience.
Patients with relapsed/refractory acute myeloid leukemia (r/r AML) are characterized as having a poor prognosis. The only viable option of treatment for these patients is allogenic stem cell transplantation (allo-HSCT). Therefore, we have attempted to analyse factors related to both the disease itself and the transplantation procedure that could have an influence on the improvement of outcomes in this group of patients. Sixty-four patients with r/r AML underwent allo-HSCT at our center in 2012 to 2021. Fifty-two had active disease at the beginning of theallo-HSCT procedure, with amedian number of blasts in bone marrow (BM) of 18, and 12 had therapeutic aplasia after the last reinduction (blasts < 5% in BM). The probability of overall survival (OS) at 2 years was 25%. The median follow-up for survivors was 21.5 months. Progression-free survival (PFS) estimates were above 46%. The main cause of death was disease progression (49%). A statistically significant effect on premature death was reported for the diagnosis of secondary AML (sAML) and cytomelovirus (CMV) reactivation post allo-HSCT. On the other hand, chronic graft versus host disease (cGVHD) decreased the risk of disease progression. sAML and CMV reactivation were found to have opposite effects.


Comparative analysis of the DNA staining efficiencies of different fluorescent dyes in preparative agarose gel electrophoresis.
Ethidium bromide (EB) is a mutagen and toxin that is widely used in the laboratory for visualization of nucleic acids. Safer nucleic acid stains, such as SYBR Gold, SYBR Green, GoldView, GeneFinder, and GoldStar, have been developed. However, there has been no systematic comparative analysis of the staining efficiencies of these dyes. In the present study, SYBR Gold, SYBR Green I, GoldView and EB were compared. Although both SYBR Gold and SYBR Green alter electrophoretic mobility and thus DNA size estimates, they are cost-effective alternatives to EB. SYBR Gold was more sensitive than SYBR Green I at detecting short fragments, but 50-bp bands were clearly visible using either dye when visualized with a long integration time. SYBR Gold or SYBR Green I are sensitive and relatively safe alternatives to EB. In our laboratory, the SYBR Gold method is now used routinely by all members of our group with great consistency and success.


Human Digested Dentin Matrix for Dentin Regeneration and the Applicative Potential in Vital Pulp Therapy.
Human dentin is a natural acellular matrix with excellent reported biocompatibility. The aim was to fabricate a novel dentin matrix material from human dentin and investigate its applicative potential for vital pulp therapy. Digested dentin matrix extract (DDME) was fabricated using controlled enzymatic digestion under acidic conditions. The surfaces and biocompatibility of DDME were then investigated, with its effects on the odontogenic differentiation of human dental pulp cells (hDPCs) also studied. The ability of DDME to induce mineralization was assessed in a nude mouse model. The performance of DDME as a pulp capping agent was evaluated in an in situ rat model. The molecular mechanism was verified by mRNA sequencing. A novel type of dentin matrix material with a uniform size of 8 μm was fabricated. DDME had a similar band compared with grinded dentin matrix, with a smaller size, and more uneven surface, as detected by Fourier-transform infrared spectrometer and X-ray photoelectron spectroscopy. DDME at low concentrations did not affect hDPC viability or proliferation, but enhanced runt-related transcription factor 2, dentin matrix acidic phosphoprotein 1, and COL1A1 (collagen type I alpha 1 chain) expression in hDPCs in vitro. DDME was superior to HA-TCP (hydroxyapatite-tricalcium phosphate) in dentin-like mineralized tissue formation after subcutaneous transplantation. In the rat model of pulpotomy, DDME showed visible curative effects. The underlying mechanism may be the inhibition of Hippo signaling following DDME treatment. DDME promoted Yes-associated protein (YAP) 1 nuclear influx, thereby enhancing the expression of DMP-1 (dentin matrix acidic phosphoprotein 1), which was reversed by YAP inhibitor treatment. Human DDME can be used as a biomaterial for dentin regeneration. The combined application of DDME and current pulp capping agents is a potential choice for vital pulp therapy.


Cardiac drug-drug interaction between HCV-NS5B pronucleotide inhibitors and amiodarone is determined by their specific diastereochemistry.
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not. Stereochemical selectivity on emerging bradycardia was confirmed in vivo. Diastereomer pairs entered cells equally well, and there was no difference in intracellular accumulation of L-ala,SP metabolites ± amiodarone, but no D-ala,RP metabolites were detected. Cathepsin A (CatA) inhibitors attenuated L-ala,SP prodrug metabolite formation, yet exacerbated L-ala,SP + amiodarone effects, implicating the prodrugs in these effects. Experiments indicate that pharmacological effects and metabolic conversion to UTP analog are L-ala,SP prodrug-dependent in cardiomyocytes.


A mobile genetic element with unknown function found in distantly related viruses.
The genetic element s2m seems to represent one of very few examples of mobile genetic elements in viruses. The function remains obscure and a scattered taxonomical distribution has been reported by numerous groups. We have searched GenBank in order to identify all viral accessions that have s2m(-like) sequence motifs. Rigorous phylogenetic analyses and constrained tree topology testing were also performed in order to investigate the apparently mobile nature of s2m. The stem-loop s2m structure can be found in four families of + ssRNA viruses; Astroviridae, Caliciviridae, Picornaviridae and Coronaviridae. In all of these virus families, with the possible exception of Caliciviridae, multiple gains and/or losses of s2m would have to be postulated in order to explain the distribution of this character. s2m appears to be a mobile genetic element with a unique evolutionary history in all of the four virus families where it can be found. Based on our findings and a review of the current literature on s2m, a hypothesis implying an RNAi-like function for the s2m element is also outlined.


Cognitive consequences of sleep and sleep loss.
Although we still lack any consensus function(s) for sleep, accumulating evidence suggests it plays an important role in homeostatic restoration, thermoregulation, tissue repair, immune control and memory processing. In the last decade an increasing number of reports continue to support a bidirectional and symbiotic relationship between sleep and memory. Studies using procedural and declarative learning tasks have demonstrated the need for sleep after learning in the offline consolidation of new memories. Furthermore, these consolidation benefits appear to be mediated by an overnight neural reorganization of memory that may result in a more efficient storage of information, affording improved next-day recall. Sleep before learning also appears to be critical for brain functioning. Specifically, one night of sleep deprivation markedly impairs hippocampal function, imposing a deficit in the ability to commit new experiences to memory. Taken together, these observations are of particular ecologic importance from a professional and education perspective when considering that sleep time continues to decrease across all age ranges throughout industrialized nations.


Comparison of the osteogenic potential of bone dust and iliac bone chip.
There is no comparative study of the in vitro and in vivo osteogenic potential of iliac bone chips (autogenous iliac cancellous bone chips) compared with bone dusts generated during the decortication process with a high-speed burr in spine fracture or fusion surgery. To compare the osteogenic potential of three sizes of bone dusts with iliac bone chips and to determine whether bone dusts can be used as a bone graft substitute. In vitro and in vivo study. Bone chips were harvested from the posterior superior iliac spine and bone dusts from the vertebrae of 15 patients who underwent spinal fracture surgery. Bone dust was divided into three groups: small (3 mm), middle (4 mm), and large (5 mm) according to the size of the burr tip. A comparison was made using a cell proliferation assay, alkaline phosphatase (ALP) activity, the degree of mineralization in an in vitro model, and radiographic and histologic studies (the change of absorbable area and tissue density) after implantation of the various materials into back muscles of nude mice. Although all three bone dust groups were less active with regard to cell proliferation, ALP activity, and the degree of mineralization, than were bone chips, they still exhibited osteogenic potential. Furthermore, there was no significant difference among the three bone dust groups. The three bone dust groups did show greater absorbable area and change of the tissue density than did the iliac bone chip group. Again, there was no significant difference among the three bone dust groups in this regard. Histologically, specimens from the bone dust groups had a higher osteoclast cell number than specimens from the iliac bone chip group. The osteogenic potential of bone dusts is lower than that of iliac bone chips, and the absorption speed of bone dusts in vivo is faster than that of iliac bone chips. The increased resorption speed appeared to result from an increase in osteoclast cell number. Therefore, caution needs to be used when surgeons employ bone dust as a bone graft substitute.


Chemical Biology of Mitotic Spindle Assembly Motors.
Mitotic kinesins play essential roles during mitotic spindle assembly and in ensuring proper chromosome segregation. Chemical inhibitors of mitotic kinesins are therefore valuable tools to study kinesin function in vitro and in cells. Because cancer is a disease of unregulated cell division, inhibitors also represent potential chemotherapeutic agents. Here, we present assays that can be used to evaluate the potency and specificity of mitotic kinesin inhibitors identified from high-throughput screening. By evaluating their effects in a variety of in vitro, fixed-cell, and live cell assays, screening hits can be prioritized and optimized to produce effective, on-target inhibitors.


Comparative study of phacoemulsification-subscleral trabeculectomy versus phacoemulsification-deep sclerectomy.
To compare the surgical outcomes of phacoemulsification-subscleral trabeculectomy versus phacoemulsification-deep sclerectomy with intraoperative mitomycin C in open-angle glaucoma. The study was conducted on 40 chronic primary open-angle glaucomatous eyes with senile cataract. They were divided into two groups: group I (n = 20): eyes undergoing phacoemulsification with subscleral trabeculectomy, and group II (n = 20): eyes undergoing phacoemulsification with deep sclerectomy. Intraoperative mitomycin C (0.4 mg/ml for 3 min) was applied in both groups. Postoperative intraocular pressure (IOP), complications, glaucoma medications, visual outcomes, and the bleb appearance were assessed for 12 months. The mean postoperative IOP was significantly lower (P < 0.05) in both groups in all time intervals in comparison to their preoperative values. The mean postoperative IOP was 14.1 ± 5.4 mmHg in group I, and 14.8 ± 3.1 mmHg in group II. No major complications were encountered in either procedure, but complications such as shallow anterior chamber, hypotony, and delayed bleb leaks were common in group I, whereas intraoperative perforation of Descemet's membrane occurred in group II. No significant difference in visual acuity improvement, visual field changes, and surgical success outcome were found between both groups. There was no significant difference in IOP reduction, surgical complications and visual outcomes between subscleral trabeculectomy, or deep sclerectomy with intraoperative mitomycin C in combination with phacoemulsification and intraocular lens implantations in patients with primary open-angle glaucoma.


The quality of great scallop (Pecten maximus) sperm after thawing.
Most publications devoted to the cryopreservation of mollusc sperm have focused on the definition of technical protocols, avoiding the description of sperm quality after thawing. The present study investigated the effects of cryopreservation on sperm quality in the great scallop. Wild scallop were fished during the natural spawning period and conditioned in the hatchery before use. Sperm samples were obtained after intragonadal injection of serotonin and cryopreserved using a previously published protocol. Sperm quality was assessed using a panel of four parameters: sperm motility characteristics, using a computer assisted sperm analysis plugin with Image J, intracellular ATP content using an ATP-Lite kit, sperm integrity, using flow cytometry and sperm morphology, using transmission electron microscopy. For each parameter, fresh (control) and thawed spermatozoa were compared. A significant decrease of both the percentage of motile spermatozoa (reduction: 75%) and sperm swimming speed (86%) were observed for thawed sperm compared with fresh sperm. The percentage of living spermatozoa, as assessed using flow cytometry, was significantly lower for thawed sperm (72.4±2.5%) compared with fresh sperm (86.4±1.1). However, no significant difference of intracellular sperm ATP content was observed between fresh and thawed sperm. Post thawing, while some spermatozoa showed little or no morphological differences compared with fresh sperm, others had undergone drastic changes, including swelling of the plasma membrane, structural alterations of the chromatin and damage to mitochondria. In conclusion, the descriptive parameters studied in the present work showed that the quality of thawed great scallop sperm was lower than that of fresh cells but was still sufficient for use in aquaculture programs and sperm cryobanking for this species.


Implication of RPA32 phosphorylation in S-phase checkpoint signalling at replication forks stalled with aphidicolin in Xenopus egg extracts.
Activation of the replication checkpoint relies upon uncoupling of DNA polymerases and helicase activities at replication forks, which in multicellular organism results in production of long stretches of single-stranded DNA bound by the trimeric, single stranded DNA binding protein, the RPA complex. Binding of RPA to this substrate promotes synthesis of replication intermediates that contributes to checkpoint activation by allowing binding of the 9-1-1 checkpoint clamp. The RPA32kDa subunit is also phosphorylated during this process but its role in checkpoint signalling is unclear. Here we have investigated the requirement for RPA32 phosphorylation in checkpoint activation in Xenopus egg extracts. We show that phospho-deficient mutants of RPA32 stimulate checkpoint signalling at replication forks arrested with aphidicolin at both the initiation and the elongation step of DNA replication, without affecting DNA synthesis. In contrast, we show that phospho-mimetic RPA32 mutants do not stimulate checkpoint activation at unwound forks. These results indicate that the hypophosphorylated, replication fork-associated form of RPA32 functions in S-phase-dependent checkpoint signalling at unwound forks in Xenopus egg extracts while RPA32 phosphorylation may be implicated in other pathways such as repair or restart of arrested replication forks.


Renal amyloidosis complicating a recessive epidermolysis bullosa in childhood.
A case of recessive epidermolysis bullosa and secondary renal amyloidosis in a nine-year-old boy is reported. The first case observed in childhood. The clinical relationships of the two conditions are briefly discussed.


Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies.
Cytosine arabinoside (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m2 as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9-12 and 21-24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m2 X 2 doses of ara-C and 50 mg/m2 of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.


Coconut milk treated by atmospheric cold plasma: Effect on quality and stability.
Commercial sterilization plays an important role in extending the shelf-life of coconut milk. However, thermal sterilization affects the quality of coconut milk. This study was initiated to evaluate the effects of atmospheric cold plasma (ACP) treatment on some important quality parameters of coconut milk. ACP treatment had a slight effect on physicochemical characteristics and nutritional ingredients while it obviously reduced the colony count. Furthermore, ACP treatment obviously promoted the formation of lactone, an indispensable volatile substance in coconut milk. Insufficient or moderate ACP treatment had subtle effect on the sensory quality. Notably, moderate ACP treatment reduced the droplet size from 28.0 μm to 18.6 μm, and improved the stability during storage and centrifugation, especially at 60 kV 60 s. Overall, sterilization of coconut milk by ACP at 60 kV 60 s was the most ideal. This study can provide theoretical guidance for the application of ACP in liquid food.


A randomized controlled pilot trial to improve advance care planning for LVAD patients and their surrogates.
To examine feasibility, acceptability and preliminary effects of an advance care planning (ACP) intervention, SPIRIT-HF, in LVAD patients and their surrogates. LVADs may improve HF symptoms but they are not curative. Thus, ACP is needed to prepare patients and surrogates for end-of-life (EOL) decision-making. Bridge to transplant and destination therapy LVAD patient-surrogate dyads were randomized to either SPIRIT-HF or usual care. Percentages of eligible dyads who were enrolled and completed the study determined feasibility. Analysis of interviews with SPIRIT dyads determined acceptability. Group comparisons of dyad congruence, patient's decisional conflict, and surrogate's decision-making confidence determined preliminary effects. Of 38 eligible dyads, 29 (76%) were enrolled, randomized, and completed the study. The 14 intervention dyads characterized SPIRIT-HF as beneficial. All dyads demonstrated improvement in outcomes. However, SPIRIT-HF dyads tended toward greater congruence on patient EOL treatment goals. SPIRIT-HF is feasible and acceptable. Results will inform future trials.


Six new species of the genus Laena Dejean from China (Coleoptera, Tenebrionidae, Lagriinae).
Six new species of Laena Dejean, Laena quadratasp. n. and Laena motoganasp. n.(China: Xizang), Laena chiloriluxasp. n., Laena dentatasp. n. and Laena liangisp. n. (China: Yunnan), Laena dentatocrassasp. n. (China: Hainan Island, representing new province record of the genus) are described, complemented with photos of habitus, illustrations of legs, antenna, aedeagus and last abdominal ventrite of male and female. Type specimens are deposited in both the Museum of Hebei University, Baoding, China and the Natural History Museum of Stuttgart, Germany.A key to the 102 Chinese species of genus Laena is provided.


The key values and factors identified by older adults to promote physical activity and reduce sedentary behaviour using co-production approaches: a scoping review.
Inactivity and sedentary behaviour in older adults adversely impacts physical function, reduces social networks, and could contribute to population healthcare costs. To encourage and support the planning and uptake of physical activity by older adults, it is important to understand what physical activity means to older adults. Therefore, the aim of this scoping review was to collate what older adults have self-identified as the key factors for sustaining and increasing their physical activities. Arksey and O'Malley's Scoping Review framework was used to guide the review process. SCOPUS, ASSIA, PsychINFO and MEDLINE databases were searched. Studies were eligible for inclusion if they were peer-reviewed, the target population were older adults (aged 55 and above), co-production related research approaches were explicitly stated in the methods and there was a focus on design of physical activity interventions or products to support or enhance physical activity. Assets and values important for physical activity were first extracted from included studies and were subsequently thematically analysed. Themes are presented to provide an overview of the literature synthesis. Sixteen papers were included in the analysis. Data from these papers were gathered via designing interventions or services (n = 8), products (n = 2), 'exergames' (n = 2) or mobile applications (n = 4). Outcomes were varied but common themes emerged across papers. Overarching themes identified by older adults were associated with a desire to increase activity when it was accessible, motivational, and safe. In addition, older adults want to enjoy their activities, want independence and representation, want to stay connected with families and friends, be outdoors, familiarity, activities to be tailored and resulting in measurable/observed progress. Population demographics, personal attributes, and life experiences all affect preferences for physical activity. However, the key factors identified by older adults for increasing physical activity were common-even in separate co-production contexts. To promote physical activities in older adults, activities must fundamentally feel safe, provide a sense of social connectedness, be enjoyable and be accessible in terms of cost and ability.


Pancreatoblastomas and mixed and pure acinar cell carcinomas share epigenetic signatures distinct from other neoplasms of the pancreas.
Pancreatic neoplasms are heterogenous and have traditionally been classified by assessing their lines of cellular differentiation using histopathologic methods, particularly morphologic and immunohistochemical evaluation. These methods frequently identify overlapping differentiation along ductal, acinar, and neuroendocrine lines, raising diagnostic challenges as well as questions regarding the relationship of these neoplasms. Neoplasms with acinar differentiation, in particular, frequently show more than one line of differentiation based on immunolabeling. Genome methylation signatures, in contrast, are better conserved within cellular lineages, and are increasingly used to support the classification of neoplasms. We characterized the epigenetic relationships between pancreatoblastomas, acinar cell carcinomas (including mixed variants), pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, and pancreatic ductal adenocarcinomas using a genome-wide array platform. Using unsupervised learning approaches, pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, ductal adenocarcinomas, and normal pancreatic tissue samples all localized to distinct clusters based on their methylation profiles, whereas all neoplasms with acinar differentiation occupied a broad overlapping region located between the predominantly acinar normal pancreatic tissue and ductal adenocarcinoma clusters. Our data provide evidence to suggest that acinar cell carcinomas and pancreatoblastomas are similar at the epigenetic level. These findings are consistent with genomic and clinical observations that mixed acinar neoplasms are closely related to pure acinar cell carcinomas rather than to neuroendocrine tumors or ductal adenocarcinomas.


Control of HIV during a structured treatment interruption in chronically infected individuals with vigorous T cell responses.
To study whether and under what circumstances HIV can be controlled in chronically infected patients. Nine patients treated with hydroxyurea and didanosine (PANDAs) were compared with 7 patients on highly active antiretroviral therapy (HAART) during an 8-week treatment interruption. Both groups had similar baseline viral load, CD4 count, and length of treatment. Treatment was resumed if viral rebound >10,000 copies/mL (virological failure) or CD4 count decrease below 200 cells/mm(3) (immunological failure) occurred in two consecutive measurements. None of the PANDAs failed. Viral rebound was spontaneously contained, and CD4 count remained stable. Four out of 7 patients in the HAART group failed to control HIV by week 6 and had to restart therapy due to either viremia rebound or CD4 decrease. Before therapy interruption, the PANDAs had a vigorous HIV-specific T cell immune response (median CD4VIR 1.2%), while the HAART-treated patients did not (median CD4VIR 0.2%) (CD4VIR represents the percentage of HIV-specific CD4 subpopulation expressing IFN-gamma within the total CD4 population [CD3+, CD4+, IFN-gamma+]). This difference was statistically significant (p =.002). This study shows that HIV can be controlled during therapy interruption in patients with established infection, and that control of viral replication correlates with vigorous anti-HIV specific immune responses.


Correlates of participation in a pediatric primary care-based obesity prevention intervention.
The purpose of this study was to examine the correlates of participation in a childhood obesity prevention trial. We sampled parents of children recruited to participate in a randomized controlled trial. Eligible children were 2.0-6.9 years with BMI ≥ 95th percentile or 85th to <95th percentile if at least one parent was overweight. We attempted contact with parents of children who were potentially eligible. We recruited 475 parents via telephone following an introductory letter. We also interviewed 329 parents who refused participation. Parents who refused participation (n = 329) did not differ from those who participated (n = 475) by number of children at home (OR 0.94 per child; 95% CI: 0.77-1.15) or by child age (OR 1.07 per year; 95% CI: 0.95-1.20) or sex (OR 1.06 for females vs. males; 95% CI: 0.80-1.41). After multivariate adjustment, parents who were college graduates vs. <college graduates were less likely to participate (OR 0.62; 95% CI: 0.46-0.83). In addition, parents were less likely (OR 0.41; 95% CI: 0.31-0.56) to participate if their child was overweight vs. obese. Among the 115 refusers with obese children, 21% cited as a reason for refusal that their children did not have a weight problem, vs. 30% among the 214 refusers with overweight children. In conclusion, parents of preschool-age children with a BMI 85-95th%ile are less likely to have their children participate in an obesity prevention trial than parents of children with BMI > 95th%ile. One reason appears to be that they less frequently consider their children to have a weight problem.


The effects of UV filters on health and the environment.
Sunscreens are an important means of protection against sunburns, dyspigmentation, photoaging, and photocarcinogenesis. Sunscreens come in a variety of formulations that can protect against ultraviolet B (UVB) radiation, both UVB and ultraviolet A (UVA) radiation (broad-spectrum sunscreens), and UVB, UVA, and visible light (tinted broad-spectrum sunscreens). In the USA, there is currently a paucity of FDA-approved broad-spectrum filters on the market. Studies have identified the presence of multiple UV filters in water sources globally. Many laboratory studies have implicated the potential impact of UV filters on coral reef bleaching, the food chain, and human health. However, many of these studies are performed at concentrations that are much higher than those present in the natural environment. With increasing discussion surrounding the role of organic and inorganic UV filters as potential environmental pollutants over the past decade, approval of additional broad-spectrum filters would be an important means of alleviating the use of more controversial filters. The aim of this article is to review the effects of UV filters on health and the environment and explore potential adjunctive agents for photoprotection.


Prevalence and clinical correlates of vitamin D inadequacy among patients with chronic pain.
Vitamin D inadequacy is associated with medication refractory musculoskeletal pain and neuromuscular dysfunction. This vitamin deficiency could subsist as an unrecognized comorbid condition among patients with chronic pain. The primary objective of this study was to determine the prevalence and clinical correlates of vitamin D inadequacy in patients seeking treatment for chronic pain. Retrospective case series. Multidisciplinary pain rehabilitation center at a tertiary referral medical center. The study involved 267 chronic pain patients admitted from February to December 2006. Serum 25-hydroxyvitamin D (25[OH]D) was drawn at admission. Patients with serum 25[OH]D levels < or=20 ng/mL were considered to have inadequate levels and those with levels >20 ng/mL were considered to have adequate levels. Upon admission, opioid intake was documented and patients completed the Short Form-36 Health Status Questionnaire. The prevalence of vitamin D inadequacy was 26% (95% confidence interval, 20.6-31.1%). Among patients using opioids, the mean morphine equivalent dose for the inadequate vitamin D group was 133.5 mg/day compared with 70.0 mg/day for the adequate group (P = 0.001). The mean duration of opioid use for the inadequate and adequate groups were 71.1 months and 43.8 months, respectively (P = 0.023). Opioid users with inadequate levels reported worse physical functioning (P = 0.041) and health perception (P = 0.003) than opioid users with adequate levels. The prevalence and clinical correlates identified in this pilot study provide the basis for the assertion that vitamin D inadequacy may represent an under-recognized source of nociception and impaired neuromuscular functioning among patients with chronic pain.


Outcome after veno-arterial extracorporeal membrane oxygenation in elderly patients: A 14-year single-center experience.
Use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in elderly patients is controversial because of presumed poor outcome. Our primary aim was to determine the influence of advanced age on short- and long-term outcome; the secondary aim was to analyze risk factors for impaired outcome. Between January 2006 and June 2020, 645 patients underwent VA-ECMO implantation in our department. The patients were categorized into four groups:<50, 50-59.9, 60-69.9 and ≥70 years old. Data were retrospectively analyzed for short- and long-term outcome. Risk factors for in-hospital mortality and mortality during follow-up were assessed using multivariate regression analysis. VA-ECMO support duration was comparable in all age groups (median 3 days). Weaning rates were 60.8%/n = 104 (<50 years), 51.4%/n = 90 (50-59.9 years), 58.8%/n = 107 (60-69.9), and 67.5%/n = 79 (≥70, p = 0.048). Hospital mortality was highest in the patients aged 50-59.9 years (68%/n = 119), but not in the elderly patients (60-69.9, ≥70:62.1%/n = 113, 58,1%/n = 68). At discharge, the cerebral performance category scores were superior in the patients <50 years. Multivariate logistic regression analysis revealed chronic kidney failure requiring hemodialysis, duration of cardiopulmonary resuscitation, and elevated blood lactate levels before VA-ECMO, but not age as predictors of in-hospital mortality. Cox's regression disclosed age as relevant risk factor for death during follow-up. The patients' physical ability was comparable in all age groups. VA-ECMO support should not be declined in patients only because of advanced age. Mortality and neurological status at hospital discharge and during follow-up were comparable in all age groups.


Exposure to antenatal corticosteroids and infant cortisol regulation.
Administration of antenatal corticosteroids (AC) is the standard of care during pregnancy for women who are at risk of early delivery. Evidence indicates that AC improve survival and reduce morbidity for preterm infants. However, research suggests that infants whose mothers receive AC have an altered hypothalamic-pituitary-axis (HPA) response to stressors in early life. Results are mixed regarding the nature of these effects, with studies showing both suppressed and augmented HPA activity. In addition, research is very limited beyond the 4th month of life. The purpose of this study was to determine if AC exposure was associated with infant cortisol levels in a resting state or in response to a stressor at 1, 6 and 12 months postnatal. We also evaluated the moderating role of preterm birth in this association. 181 women and their infants participated in the study. Women were recruited during the 3rd trimester of pregnancy; at this time, they completed the Perceived Stress Scale and provided 8 salivary samples over a 2-day period for cortisol assay. They provided these data again at 6 and 12 months postnatal. At 1, 6, and 12 months postnatal, salivary samples were collected from infants to examine their cortisol levels before and after participation in a 'stressor protocol'. Data were extracted from the medical record on AC exposure, gestational age, maternal obstetric risk, and neonatal morbidity. Mixed effects multilevel regression modeling was used to examine the aims. Infants whose mothers received AC had significantly lower resting state (B = -2.47, CI: -3.691, -0.0484) and post-stressor (B = -2.51, CI: -4.283, -0.4276) cortisol levels across the first year of life than infants whose mothers did not receive AC. There was no moderating effect of preterm birth on the relationship between AC exposure and cortisol. Results indicate a state of dampened HPA activation and cortisol hypo-arousal that persists across the first year of life among infants who were exposed to corticosteroids in utero. Further research is needed to examine mechanisms responsible for any alterations that occur during development of the fetal HPA axis, including epigenetic and biochemical factors that control hormonal secretion, negative feedback, and glucocorticoid receptor function throughout the HPA axis. Findings warrant careful consideration by obstetric clinicians of the benefits and risks of prescribing AC.


Antibody functionalized intravascular devices combined with genetically engineered endothelial colony-forming cells for targeted drug delivery: A proof-of-concept study.
This study was designed to test the ability of ex vivo antibody-coated intravascular devices to capture genetically engineered pig endothelial colony-forming cells (ECFCs) as proof of concept for their potential for in vivo targeted drug delivery. Human α-calcitonin gene-related peptide (α-CGRP) was chosen as the therapeutic molecule as it is unsuitable for systemic administration due to its potent peripheral arterial vasodilatory effect and short half-life in blood, requiring local delivery to yield therapeutic benefit in a particular vascular bed. H-2Kk, a murine leukocyte surface antigen, served as the selection marker for genetically modified ECFCs. H-2Kk antibody was immobilized on electropolished cobalt-chromium (CC) discs, CC stents and ePTFE grafts through dopamine self-polymerization. The functionalized surface was integral and smooth, lacked or had significantly reduced chemical signals specific for substrates. Pig bone marrow-derived ECFCs transfected with a plasmid constructed for H-2Kk and α-CGRP expression produced H-2Kk on cell surface and biologically active α-CGRP in culture medium. H-2Kk antibody-coated substrates bound H-2Kk ECFCs but not control ECFCs in vitro. Bare or only dopamine-coated substrates did not bind H-2Kk ECFCs. These data suggest that implantation of antibody functionalized devices combined with injection of genetically modified ECFCs could be potentially applied for targeted drug delivery.


[Transcutaneous electric nerve stimulation in the treatment of placental insufficiency. 1. Methodologic principle and set of instruments].
Presentation of a set of generators for the transcutaneous electric nerve stimulation serving the treatment of placental insufficiency. First experiences confirm the proper practibility of the method in the variant of our generator set.


Duodenal complications in necrotizing pancreatitis: Challenges of an overlooked complication.
Duodenal complications of necrotizing pancreatitis (NP) are challenging and understudied. We sought to characterize the demographics and clinical course of NP patients with duodenal complications. Single institution retrospective review of 687 NP patients treated from 2005 to 2018. Duodenal complications developed in 40 (6%) patients including fistula in 11 (2%) and stricture in 29 (4%) patients. Patients with duodenal complications had increased computed tomography severity index (CTSI), degree of glandular necrosis, organ failure, infected necrosis, and disease duration. Mortality from NP was increased in patients with duodenal fistula (36%) compared to patients with duodenal stricture (7%) and patients without duodenal complications (9%). Surgical management of duodenal complications was required in 9/11 (82%) patients with fistula and 17/29 (59%) patients with stricture. Duodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.


Associations of dietary supplement use with all-cause and cause-specific mortality in patients diagnosed with cancer: a large prospective cohort study in the UK Biobank.
Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort. This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities). This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90-0.99) and cancer (aHR = 0.89, 95% CI = 0.83-0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83-0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87-0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82-0.94) were associated with a modest decrease in cancer mortality which were marginally significant. This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes.


ReachingBot: An automated and scalable benchtop device for highly parallel Single Pellet Reach-and-Grasp training and assessment in mice.
The single pellet reaching and grasp (SPRG) task is a behavioural assay widely used to study motor learning, control and recovery after nervous system injury in animals. The manual training and assessment of the SPRG is labour intensive and time consuming and has led to the development of multiple devices which automate the SPRG task. Here, using robotics, computer vision, and machine learning analysis of videos, we describe a device that can be left unattended, presents pellets to mice, and, using two supervised learning algorithms, classifies the outcome of each trial with an accuracy of greater than 94% without the use of graphical processing units (GPUs). Our devices can also be operated using our cross-platform Graphical User Interface (GUI). We show that these devices train and assess mice in parallel. 21 out of 30 mice retrieved > 40% of pellets successfully following the training period. Following ischaemic stroke; some mice showed large persistent deficits whilst others showed only transient deficits. This highlights the heterogeneity in reaching outcomes following stroke. Current state-of-the-art desktop methods either still require supervision, manual classification of trial outcome, or expensive locally-installed hardware such as graphical processing units (GPUs). ReachingBots successfully automated SPRG training and assessment and revealed the heterogeneity in reaching outcomes following stroke. We conjecture that reach-and-grasp is represented in motor cortex bilaterally but with greater asymmetry in some mice than in others.


Amelioration of radiation-induced liver damage by p-coumaric acid in mice.
Radiation-induced liver damage (RILD) is a spiny problem in radiotherapy or other circumstances that exposure to radiation. The need for radioprotective agent is increasing to protect liver tissue. This study aimed to explore the hepatoprotective effect of p-coumaric acid (CA) against RILD. C57BL/6 male mice were exposed to 4 Gy irradiation and administrated with CA for 4 days starting on the same day of irradiation. Mice were sacrificed to obtain blood and liver tissues on day 3.5 or 14 post irradiation, respectively. The blood and liver tissues were collected. As compared with the only irradiated group, CA supplementation improved liver morphology, decreased serum alanine aminotransferase and aspartate aminotransferase, inhibited BCL2-associated X (BAX) protein expression, and improved the mice hematopoietic function. CA at the dose of 100 mg/kg body weight showed better effect compared to the other doses. Thus, CA might possess potential to protect against RILD.


[Diagnosis of hemoglobinopathies in the clinical laboratory].
This paper describes the methods which are, at present, in common use in clinical laboratories to diagnose haemoglobinopathies. They include simple and more sophisticated techniques of conventional electrophoresis, isoelectric focusing, specific screening tests for certain haemoglobins or groups of haemoglobins and ion exchange chromatography. The value and limitations of these methods are discussed along with recent developments.


Saharan dust clouds and human health in the English-speaking Caribbean: what we know and don't know.
Dust clouds travel across the Atlantic to the Americas and the Caribbean Islands. This long-range transport of dust leads to clouds that are enriched with small particles less than 10 microm aerodynamic diameter (PM10) which can reach human airways. The dust clouds also bring pollen, microbes, insects and chemicals, all of which could potentially have a negative impact on human health. This has led to a small number of retrospective studies being conducted on the islands of Barbados and Trinidad to look at possible associations between dust cover and acute asthma admissions to Emergency Rooms. The results have been conflicting. This review examines these studies, offers possible explanations for the differences in results, and suggests that there is a need for a prospective Caribbean-wide study to assess fully any relationship between African dust clouds and human respiratory and cardiovascular diseases.


A dosing strategy model of deep deterministic policy gradient algorithm for sepsis patients.
A growing body of research suggests that the use of computerized decision support systems can better guide disease treatment and reduce the use of social and medical resources. Artificial intelligence (AI) technology is increasingly being used in medical decision-making systems to obtain optimal dosing combinations and improve the survival rate of sepsis patients. To meet the real-world requirements of medical applications and make the training model more robust, we replaced the core algorithm applied in an AI-based medical decision support system developed by research teams at the Massachusetts Institute of Technology (MIT) and IMPERIAL College London (ICL) with the deep deterministic policy gradient (DDPG) algorithm. The main objective of this study was to develop an AI-based medical decision-making system that makes decisions closer to those of professional human clinicians and effectively reduces the mortality rate of sepsis patients. We used the same public intensive care unit (ICU) dataset applied by the research teams at MIT and ICL, i.e., the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) dataset, which contains information on the hospitalizations of 38,600 adult sepsis patients over the age of 15. We applied the DDPG algorithm as a strategy-based reinforcement learning approach to construct an AI-based medical decision-making system and analyzed the model results within a two-dimensional space to obtain the optimal dosing combination decision for sepsis patients. The results show that when the clinician administered the exact same dose as that recommended by the AI model, the mortality of the patients reached the lowest rate at 11.59%. At the same time, according to the database, the baseline mortality rate of the patients was calculated as 15.7%. This indicates that the patient mortality rate when difference between the doses administered by clinicians and those determined by the AI model was zero was approximately 4.2% lower than the baseline patient mortality rate found in the dataset. The results also illustrate that when a clinician administered a different dose than that recommended by the AI model, the patient mortality rate increased, and the greater the difference in dose, the higher the patient mortality rate. Furthermore, compared with the medical decision-making system based on the Deep-Q Learning Network (DQN) algorithm developed by the research teams at MIT and ICL, the optimal dosing combination recommended by our model is closer to that given by professional clinicians. Specifically, the number of patient samples administered by clinicians with the exact same dose recommended by our AI model increased by 142.3% compared with the model based on the DQN algorithm, with a reduction in the patient mortality rate of 2.58%. The treatment plan generated by our medical decision-making system based on the DDPG algorithm is closer to that of a professional human clinician with a lower mortality rate in hospitalized sepsis patients, which can better help human clinicians deal with complex conditional changes in sepsis patients in an ICU. Our proposed AI-based medical decision-making system has the potential to provide the best reference dosing combinations for additional drugs.


Dimethylacetamide-induced toxic hepatitis in spandex workers: clinical presentation and treatment outcomes.
Dimethylacetamide (DMAc) exposure has been associated with toxic hepatitis, and no clinical treatment has been reported. To investigate the clinical manifestations of DMAc-induced symptoms and how to rescue the functional loss due to occupational exposure. Clinical observations of 60 spandex factory workers with the exposure to DMAc from January, 2017-19. Chinese drugs (reduced glutathione, polyene phosphatidylcholine, glycyrrhizin compound, Hugan tablets and ornithine aspartate) were used to evaluate the therapeutic improvements in DMAc-exposed patients. Our data found that 58.3% patients had no distinct clinical symptoms, but 41.7% patients felt fatigue, and 21.7% patients suffered abdominal discomfort and appetite loss, and 8.3% patients had yellow skin and sclera. The ultrasonic and CT imaging revealed that some patients have fatty livers, intrahepatic calcifications, hepatomegaly, gallbladder wall edema and abdominal effusions. Biochemical analysis showed that the alanine aminotransferase (ALT) (P < 0.001), aspartate aminotransferase (AST) (P < 0.001), lactate dehydrogenase (LDH) (P < 0.001) and bilirubin (P < 0.01) statistically decreased after the drug treatment, but alkaline phosphatase (P >0.05) and glutamyl transpeptidase (P> 0.05) did not decrease. Twenty-nine out of the thirty-one patients' abnormal blood ammonia recovered. The risk factor of ALT on hospitalization time was significantly related (P < 0.01). The drugs above are sufficient to rescue functional loss in DMAc-induced toxic hepatitis, in part via the regulations of ALT, AST, LDH, bilirubin and ammonia. Workers with the exposure to DMAc should receive specific drugs to maintain the health and prevent functional loss in the long term.


Depression, anxiety, stress, and suicide risk in patients with functional seizures vs. those with epilepsy.
We aimed to investigate the rates of positive screening for depression, anxiety, stress, and suicide risk in adults with seizures [i.e., well-matched groups of patients with focal epilepsy vs. idiopathic generalized epilepsy (IGE) vs. functional seizures (FS)]. This was a cross sectional study. Patients, 19-55 years of age, with a diagnosis of IGE, focal epilepsy or FS were investigated at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from September 2022 until January 2023 and during their follow-up visits. We used the validated Farsi version of DASS-21 (Depression-Anxiety-Stress Scale) to investigate and screen for depression, anxiety, and stress in these patients. We also used the Beck Scale for Suicide Ideation (BSSI). Forty patients with focal epilepsy, 40 persons with IGE, and 40 individuals with FS were included. Depression and anxiety were more prevalent among patients with FS compared with those with epilepsy. The rate of stress among patients with FS was not significantly different compared with that in patients with epilepsy. The suicide risks were not significantly different between the groups either. Patients with FS are at high risk for psychiatric comorbidities that is comparable or even worse than that in patients with epilepsy. Specific validated scales to screen for psychiatric comorbidities and suicide risk should be integral components of the evaluation and treatment of all patients with seizures.


Synthesis and Biological Evaluation of Three New Chitosan Schiff Base Derivatives.
Recently, chemical modifications of chitosan (CS) have attracted the attention of scientific researchers due to its wide range of applications. In this research, chitin (CH) was extracted from the scales of Cyprinus carpio fish and converted to CS by three chemical steps: (i) demineralization, (ii) deprotonation, and (iii) deacetylation. The degree (measured as a percentage) of deacetylation (DD %) was calculated utilizing the acid-base titration method. The structure of CS was characterized by Fourier transform infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA). Three new CS Schiff bases (CSSBs) (CS-P1, CS-P2, and CS-P3) were synthesized via coupling of CS with 2-chloroquinoline-3-carbaldehyde, quinazoline-6-carbaldehyde, and oxazole-4-carbaldehyde, respectively. The newly prepared derivatives were verified, structurally, by nuclear magnetic resonance (1H and 13C NMR) and FT-IR spectroscopy. Antimicrobial activity was evaluated for the prepared compounds against both "Gram-negative" and "Gram-positive" bacteria, namely, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, in addition to two kinds of fungi, Candida albicans and Aspergillus fumigates. Cytotoxicity of the synthesized CSSBs was evaluated via a MTT screening test. The results indicated a critical activity increase of the synthesized compound rather than CS generally tested bacteria and fungi and the absence of cytotoxic activity. These findings suggested that these new CSSBs are novel biomaterial candidates with enhanced antibacterial and nontoxic characteristics for applications in areas of both biology and medicine.


Bacillus piliformis infection (Tyzzer's disease) in a calf.
A 1-week-old Jersey bull calf with a history of diarrhea, weakness, and lethargy was submitted for necropsy. Principal macroscopic findings were enteritis and multifocal necrotizing hepatitis. Histologically and ultrastructurally, organisms with characteristics of Bacillus piliformis were associated with the foci of necrosis in the liver.


Aesthetic Units and Zones of Adherence, Relevance to Planning Incisions in Body Contouring Surgery.
Aesthetic units (AUs) and zones of adherence (ZAs) have been previously noted in the face and torso. A systematic classification of common AUs and ZAs has not been previously described for the torso and extremities. Contour and scars are equally important in obtaining the best result. Therefore, the six principles to consider in body contouring surgery (BCS) are that the resulting scar be anchored at a zone of adhesion; at the interface of AUs; concealed within flexion or extension skin creases, or placed according to conventional usage and experience; positioned on the medial aspect of a limb; hidden when nude, topless, or in a variety of clothing such as one-piece and two-piece swimsuits, crop tops, short sleeves, etc; and positioned to avoid a contracture across a flexion joint crease or a dehiscence across the extension aspect of a joint. Images of male and female massive weight loss (MWL) patients with a history of MWL were reviewed and analyzed. AUs and Zas are described and codified. An algorithm is provided to aid in planning incisions for BCS. With the increase in BCS after MWL, a classification of AUs and ZAs is considered useful in planning surgery and optimizing the aesthetic result.


Case-control comparison brain lesion segmentation for early infarct detection.
Computed Tomography (CT) images are widely used for the identification of abnormal brain tissues following infarct and hemorrhage of a stroke. The treatment of this medical condition mainly depends on doctors' experience. While manual lesion delineation by medical doctors is currently considered as the standard approach, it is time-consuming and dependent on each doctor's expertise and experience. In this study, a case-control comparison brain lesion segmentation (CCBLS) method is proposed to segment the region pertaining to brain injury by comparing the voxel intensity of CT images between control subjects and stroke patients. The method is able to segment the brain lesion from the stacked CT images automatically without prior knowledge of the location or the presence of the lesion. The aim is to reduce medical doctors' burden and assist them in making an accurate diagnosis. A case study with 300 sets of CT images from control subjects and stroke patients is conducted. Comparing with other existing methods, the outcome ascertains the effectiveness of the proposed method in detecting brain infarct of stroke patients.


The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.
Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.


The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters.
Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast were involved in this study. The expressions of ER, PR, c-erbB-2 and p53 were immunostained in tumor tissues and serum p53 Abs were assayed using ELISA method. The correlations between p53 Abs and other clinical and biological markers were analyzed. Among 144 patients, 31 (21.5%) had positive p53 Abs, which was associated with several poor prognostic parameters including higher clinical stage (p = 0.0233), lymph nodes metastasis (p = 0.0033), negative ER expression (p = 0.0250) and positive c-erbB-2 status (p = 0.0227). There was also a strong correlation between p53 Abs and tumor p53 positivity (p < 0.0001). These results indicated that the presence of p53 Abs is probably triggered by the accumulation of tumor p53 protein, and it could be a useful marker to complement routine prognostic factors in breast cancer patients.


Statin effects on atherosclerotic plaques: regression or healing?
Despite the well-documented improved survival of coronary heart disease with the use of statins, their effects on atherosclerotic plaques are not yet fully understood. While some studies suggest statins may reduce plaque volume, the reduction is small even with the use of high-dose statins. Due to this small change in plaque volume, other effects of statin therapy on plaques have been proposed. A large meta-analysis by Banach et al. explored statin effects on plaque composition detected by intravascular ultrasound (IVUS). We discuss the mechanisms of plaque composition modification demonstrated in their study and its implications on atherosclerotic plaque stabilization. Please see related article: http://www.biomedcentral.com/1741-7015/13/229.


A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective.
To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1 ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.


[Studies on the larval trematodes from brackish water fishes: I. Observation of Centrocestus asadai Mishima, 1959]
1. Metacercariae of Centrocestus species were found from a brackish water fish, Tribolodon taczanowskii Steindachner in the downstream of Hyungsan river. 2. Thirty one fishes out of 154 examined (31.8 per cent) were infected with the metacercariae of Centrocestus. sp. 3. Metacercariae were fed to the mouse experimentally and adult worms were recovered from the intestinal mucosa. And they were identified C. asadai Mishima and compared with the prereported Centrocestus sp.


Occurrence, temporal variation, quality and safety assessment of pesticide residues on citrus fruits in China.
Citrus is highly consumed in China and considered a major source of pesticide carrier in human diet. In this paper, pesticide residues in mandarins, tangerines and oranges from China were evaluated, as well as the quality and long-term dietary risks for the Chinese consumers. Temporal variations for eight MRL non-compliant pesticides were also investigated. 106 pesticides were analyzed using QuEChERS procedure and UPLC-MS/MS, GC-MS and GC methods. Forty different pesticides were detected in 86% of the 2922 samples from 2013 to 2018. Chlorpyrifos was the most frequently detected pesticide with a detection rate of 40%. Residues of eight pesticides in 3.8% of the total samples exceeded their MRLs. The most severely excessive pesticide was bifenthrin with 283% MRL. The occurrences and exceeding rates of eight pesticides presented clear temporal variations during the six harvesting years. Isocarbophos, carbofuran and triazophos were the main risk factors threatening the citrus safety pre-2015, whereas profenofos and bifenthrin gradually became dominant after 2016, coinciding with government control measures. The index of quality for residues (IqR) levels of 88% of the samples were below 1.0, which indicated a satisfactory quality of citrus fruits in China, although 70% of the samples contained two or more residues. The cumulative chronic dietary risks were acceptable for both the Chinese general population and children and would not pose health risks. However, more strictly enforced control measures for methidathion and isocarbophos, and reduced usage of triazophos, quinalphos, profenofos and bifenthrin should be pursued to further improve the safety of citrus fruits.


Anticonvulsant effects of phencynonate hydrochloride and other anticholinergic drugs in soman poisoning: neurochemical mechanisms.
Previous studies have paid little attention to the anticonvulsant effect of anticholinergic drugs that act on both muscarinic (M) and nicotinic (N) receptors during soman-induced seizures. Therefore, with the establishment of a soman-induced seizures model in rats, this study evaluated the efficacy in preventing soman-induced convulsions of two antagonists of both the M and N receptors, phencynonate hydrochloride (PCH) and penehyclidine hydrochloride (8018), which were synthesized by our institute, and of other anticholinergic drugs, and investigated the mechanisms of their antiseizures responses. Male rats, previously prepared with electrodes to record electroencephalographic (EEG) activity, were pretreated with the oxime HI-6 (125 mg kg-1, i.p.) 30 min before they were administered soman (180 microg kg-1, s.c.). All animals developed seizures subsequent to this treatment. Different drugs were given at different times (5, 20 and 40 min after seizures onset) and their anticonvulsant effects were monitored and compared using the two variables, i.e. the dose that could totally control the ongoing seizures, as well as the speed of seizures control. The anticonvulsant effects of atropine, scopolamine and 8018 decreased with the progression of the seizures, and they eventually lost their anticonvulsant activity when the seizures had progressed for 40 min. In contrast, PCH showed good anticonvulsant effectiveness at 5 and 20 min, and especially at 40 min after seizures onset. Of the anticholinergic drugs tested, atropine, scopolamine, and 8018 showed no obvious protection against pentylenetetrazol (PTZ)-induced convulsions or N-methyl-D-aspartate (NMDA)-induced lethality in mice. However, PCH antagonized the PTZ-induced convulsions in a dose-dependant manner with an ED50 of 10.8 mg kg-1, i.p. (range of 7.1-15.2 mg kg-1) and partly blocked the lethal effects of NMDA in mice. PCH also dose-dependently inhibited NMDA-induced injury in rat primary hippocampal neuronal cultures, suggesting a possible neuroprotective action in vivo. In conclusion, our study suggests that the mechanisms of PCH action against soman-induced seizures might differ from those of the M receptor antagonists atropine and scopolamine, and that of the antagonist of both the M and N receptors, 8018. The pharmacological profile of PCH might include anticholinergic and anti-NMDA properties. Compared with the currently recommended anticonvulsant drug diazepam, with known NMDA receptor antagonists such as MK-801 and with conventional anticholinergics such as scopolamine and atropine, the potent anticonvulsant effects of PCH during the entire initial 40 min period of soman poisoning, and its fewer adverse effects, all suggest that PCH might serve as a new type of anticonvulsant for the treatment of seizures induced by soman.


Anemia in male adolescents in Singapore.
Among 990 young male adolescents studied, only 7 were anemic. Three of the anemics had beta-thalassemia trait and 4 had probable alpha-thalassemia trait. Forty-six individuals with hemoglobinopathies were detected: 29 with probable alpha-thalassemia trait, 10 with beta-thalassemia trait and 7 with heterozygous HbE. Heterozygous alpha and beta-thalassemia occurred predominantly in Chinese while heterozygous HbE was found entirely in Malays. There were no cases of established iron deficiency anemia and only 1 had iron deficient erythropoiesis. Folate deficiency occurred only in 8 subjects with thalassemia traits, and no vitamin B12 deficiency was detected.


Criteria to recognize the structure and micropolarity of pyridoxal 5'-phosphate-binding sites in proteins.
We show that polarography can be a useful tool for the recognition of the mode of binding of pyridoxal 5'-phosphate to proteins. Furthermore we discuss the possibilities of other techniques that can be used to study this subject.


Surface functionalization of twisted graphene C32H15 and C104H52 derivatives with alkalis and superalkalis for NLO response; a DFT study.
Herein, we present the detailed comparative study on geometric, electronic, optical and non-linear optical response of alkalis and superalkalis doped twisted graphene. The results illustrate that alkali metals and superalkalis interact with the central ring of the twisted graphene through non-covalent interactions which demonstrate the stability of the resultant complexes. NBO charges indicate the transfer of electrons from dopant (alkali metal atoms and superalkalis) towards twisted graphene sheet. Superalkalis doped twisted graphene complexes exhibit higher first hyperpolarizability values compared to alkali metals analogues. Among superalkalis doped complexes, K3O@C104H52 shows the highest βo value of 1.68 × 105 au. In frequency dependent first hyperpolarizability analysis, strong second harmonic generation (SHG) response of K3O@C32H15 complex is observed at both selected resonance frequency values (532 nm and1064 nm) whereas EOPE value of K3O@C32H15 complex shows higher induced response at 1064 nm wavelength. The static hyperpolarizability (βo) further increases under the influence of applied electric field. Among all complexes, Li3O@C32H15 graphene complex has the highest βo value (1.40 × 105 au) under applied electric field along x axis when sheet is in y-z plane. This analysis will be an important guideline for future studies on twisted graphene based NLO materials.


Problematic behavior in children with epilepsy: issues and management.
This chapter is written on the premise the neurologist who will take on a new case of epilepsy or will have behavioral problems arise in an old case. "behavioral problems" is preferred to "psychiatric disorders" because the behavior is described by the parents and can be evident to the neurologist. All "behavior" is organized in the brain and can be dysfunctional if cerebral function is impaired by lesions, by genetic aberrations, or by medications. Epilepsy is also liable to give rise to prejudicial responses in all concerned. A detailed history of the family unit is essential from the start. The "illness" of epilepsy will arise from structural "disease" and will give rise to a painful "predicament"; anguish, distress. And all this is in a particular context. The best possible solution for the child will have to be "negotiated," rather than prescribed. Psychopathology also arises from "everyday life"; from the fact of chronic illness; and from alienation. These aspects are explored in detail. Mental handicap, specific learning difficulties, ADHD, and autism are frequently specifically associated with epilepsy.


"A Cold Spring Harbor in Europe." EURATOM, UNESCO and the Foundation of EMBO.
This article explores the problem of the foundation of the European Molecular Biology Organization (EMBO), by reconstructing a broader institutional framework, which includes other international actors--EURATOM, UNESCO and the International Laboratory of Genetics and Biophysics (ILGB) in Naples--and a relevant, but still neglected figure, the Italian geneticist Adriano Buzzati-Traverso (1913-1983). The article considers the tension between centralized and federal models of organization in the field of life sciences not just as an EMBO internal controversy, but rather as a structural issue of European scientific cooperation in fundamental biology in the early 1960s. Along with EMBO, the article analyzes in particular the EURATOM Biology Division Program and the constitution of UNESCO International Cell Research Organization (ICRO). Adriano Buzzati-Traverso, as founder of ILGB and scientific consultant of EURATOM and UNESCO, played a crucial role in the complex negotiation which ultimately led to the foundation of EMBO. A synchronic treatment of ILGB, EURATOM, UNESCO-ICRO and EMBO opens a window on the early 1960s institutional configuration of molecular biology in Europe, showing how it basically incorporated the "Cold Spring Harbor" decentralized model rather than reproducing the "CERN" centralized model.


Characterization of a newly established human urinary bladder cancer cell line (BT-1).
A new human transitonal cell carcinoma cell line has been established in long term tissue culture. The BT-1 cells were derived from a poorly differentiated human bladder cancer. The tumor cell line produces tumors in nude mice. BT-1 has been characterized by cytogenetic and flow cytometric analysis and by isoenzyme typing. As in direct preparations of human bladder tumors, an isochromosome 5p is a consistent marker of the newly established line. The BT-1 cells produce transforming growth factors but do not respond to exogeneous EGF.


Soluble expression, purification and functional characterization of a coil peptide composed of a positively charged and hydrophobic motif.
A de novo heterodimeric coiled-coil system formed by the association of two synthetic peptides, the Ecoil and Kcoil, has been previously designed and proven to be an excellent and versatile tool for various biotechnology applications. However, based on the challenges encountered during its chemical synthesis, the Kcoil peptide has been designated as a "difficult peptide". In this study, we explore the expression of the Kcoil peptide by a bacterial system as well as its subsequent purification. The maximum expression level was observed when the peptide was fused to thioredoxin and the optimized purification process consisted of three chromatographic steps: immobilized-metal affinity chromatography followed by cation-exchange chromatography and, finally, a reverse-phase high-performance liquid chromatography. This entire process led to a final volumetric production yield of 1.5 mg of pure Kcoil peptide per liter of bacterial culture, which represents a significant step towards the cost-effective production and application of coiled-coil motifs. Our results thus demonstrate for the first time that bacterial production is a viable alternative to the chemical synthesis of de novo designed coil peptides.


The segway personal transporter as an alternative mobility device for people with disabilities: a pilot study.
To determine the functional measures that best correlate with the skill levels of people with disabilities who operate a Segway Personal Transporter, and-using a qualitative analysis-to explore subjects' experience with the Segway. A prospective study encompassing 3 training sessions with the Segway to correlate subjects' functional ability (eg, cognition, balance, mobility, muscle strength) with their skill level on the device. A provincial adult rehabilitation center. Twenty-three subjects (age range, 19-65y) with a wide range of disabilities (eg, multiple sclerosis, spinal cord injury, amputation) who could walk at least 6m with or without assistance. Not applicable. Segway Task Assessment, Berg Balance Scale, and Timed Up & Go test. No correlation was found because all participants successfully completed the final Segway Task Assessment, regardless of scores on functional assessments. The Segway is a useful device for a broad range of populations with functional disabilities. Subjects found the Segway easy to use and were excited about its potential as an assistive device for use in their communities.