Ginkgolide B protects isolated hearts against arrhythmias induced by ischemia but not reperfusion.
The effect of ginkgolide B (BN 52021), a specific platelet-activating factor (PAF) antagonist, applied in doses of 1.5, 3.0, 6.0 X 10(-5) and 1.2 X 10(-4) mol/l, in comparison to that of metoprolol (10(-5) mol/l) and diltiazem (10(-7) mol/l), two widely used antiarrhythmic agents, on ischemia- and reperfusion-induced arrhythmias and heart functions, such as heart rate (HR), coronary flow (CF), aortic flow (AF), left ventricular developed pressure (LVDP), its first derivative (LVdp/dtmax), and left ventricular end-diastolic pressure (LVEDP) in isolated working rat hearts was examined. BN 52021 caused a dose-related protection against dysrhythmias, such as ventricular fibrillation, ventricular tachycardia, and premature ventricular beats induced by ischemia (30 min ligation of the left anterior descending coronary artery). The antiarrhythmic effect of BN 52021 given in a dose of 6.0 X 10(-5) mol/l was comparable to that of diltiazem and superior to the activity of metoprolol. None of the drugs influenced reperfusion-induced rhythm disturbances. BN 52021 did not alter heart functions, while metoprolol reduced (LVEDP only, and diltiazem increased CF, decreased AF, LVDP, and LVdp/dtmax during regional ischemia, indicating a negative inotropic effect. The antiarrhythmic effect of BN 52021 appears to be related to an antagonism of an increase in slow calcium influx induced by PAF in myocardial cells. Similarly to the mechanism of action of established antiarrhythmic drugs, BN 52021 can presumably prevent the re-entry mechanism involved in the development of ischemia-induced rhythm disturbances.


Quantitative immunohistochemistry of metallothionein in rat placenta.
The presence of metallothionein (MT) was demonstrated in placentae from cadmium-exposed and control rats by an immunohistochemical technique, using peroxidase as label and the diaminobenzidine procedure for the staining reaction. The protein was found in different regions of the placenta, i.e. in trophoblastic labyrinth, in spongiotrophoblast and in visceral yolk sac. Cytophotometric analysis of the final reaction product revealed that the amount of MT was increased in the placental labyrinth of cadmium-exposed rats. Increases were found in both nuclei and cytoplasm of trophoblast cells in the labyrinth region. Possible roles of MT in the transport of zinc and in the carbohydrate metabolism are discussed.


Establishment and assessment of rat models of glucocorticoid-induced osteonecrosis.
To establish the rat models of glucocorticoid-induced osteonecrosis and evaluate the osteonecrosis by high-resolution micro-CT and histomorphology. Totally 30 Sprague-Dawley male adult rats (age:12 weeks; body weight:400-450 g) were randomized into two groups:one group received two doses of intraperitoneal injection of lipopolysaccharide (20 μg/kg) at an interval of 24 hours, 24 hours later, the rats received three doses of intramuscular injection of methylprednisolone (40 mg/kg) at an interval of 24 hours; in the control group,the rats received same amount of normal saline. Four weeks later, 5 rats in each group were sacrificed randomly.Eight weeks later, all the remaining rats were sacrificed and the femur specimens were scanned by micro-CT. The trabeculae parameters of the femoral head were calculated. The hematoxylin and eosin staining were performed to calculated the success rate. The incidence of osteonecrosis was 80% in the experimental group. The micro-CT demonstrated broken and cystic degeneration. The quantitative analysis showed that the bone volume/total volume (experimental group:0.55 ± 0.13 vs. 0.68 ± 0.12;P<0.05), bone surface area / bone volume (experimental group:20.45 ± 5.13 vs. 24.00 ± 5.20;P<0.05), and trabeculae number(experimental group: 5.67 ± 0.50 vs. 6.24 ± 0.96; P<0.05) were significantly lower in experimental group than those in control group. A rat model of glucocorticoid-induced osteonecrosis was successfully established by lipopolysaccharide and methylpredniso- lone. High-resolution micro-CT is useful for the qualitative and quantitative analyses of the morphology and structure of trabeculae, showing good consistence with the histomorphological findings.


Assessment of biological community in riparian zone contaminated by PAHs: Linking source apportionment to biodiversity.
Riparian zone, an important land-water interface, plays an essential role in maintaining the ecological health of rivers, whereas the effects of Polycyclic aromatic hydrocarbons (PAHs) on the health of biological communities in riparian groundwater remain undetermined. To understand the responses of multiple communities to environmental variables, the distribution and ecosystem risk of 16 PAHs have been investigated in the Beiluo River, China. The distribution of multiple communities in riparian groundwater was investigated by environmental DNA metabarcoding, including 16S rRNA, 18S rRNA, and COI gene sequencing for bacteria, microbial eukaryotes (including algae, fungi, and protozoa), and metazoan, respectively, followed by correlation analysis between multiple communities and PAH contamination levels. The concentration of PAHs in the Beiluo River ranged largely from 35.32 to 728.59 ng/L. Here, the Shannon's diversity index of bacteria (Firmicutes) decreased possibly due to the occurrence of Pyrene, which mainly derives from coal and biomass combustion. Furthermore, the reduced richness of fungi (Ascomycota, Basidiomycota) and algae (Chlorophyta, Chrysophyceae) can be attributed to the presence of medium molecular weight (MMW) PAHs (Pyrene, Benz(a)anthracene, Chrysene), and low molecular weight (LMW) PAHs (Naphthalene, Fluorene, Phenanthrene). The richness and Shannon's diversity index of metazoan (Arthropoda) were promoted owing to MMW PAHs (Chrysene, Fluoranthene) generated from coal and biomass combustion and traffic emission. The ecological risk of PAHs in the groundwater environment of the Beiluo River was characterized as low to medium, where LMW and MMW PAHs posed higher risk than the high molecular weight (HMW) compounds. Overall, this study provides insights into the structures of riparian multi-biological communities altered by PAHs.


Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits.
A colony of New Zealand white rabbits has been developed which, when fed a cholesterol-supplemented diet, exhibit unusual resistance to hypercholesterolemia and atherosclerosis, disorders usually observed in normal cholesterol-fed rabbits. When resistant rabbits (RT) were fed a normal low cholesterol diet (ND), their plasma lipoprotein patterns were significantly different from those of normal rabbits (NR) fed the same diet. The low density lipoprotein cholesterol (LDL-c)/high density lipoprotein cholesterol (HDL-c) ratio and LDL-c/very low density lipoprotein cholesterol (VLDL-c) ratio were lower in the resistant rabbits. The hydrated density of HDL of the normal-responsive rabbits was greater than that of the resistant rabbits. LDL from resistant rabbits contained a lower proportion of esterified cholesterol and protein than LDL from normal rabbits. Peripheral mononuclear cells from resistant rabbits bound about 30% more 125I-labeled rabbit LDL than mononuclear cells from normal rabbits. These results demonstrate that the plasma cholesterol levels of these animals is at least partly under genetic control and that compositional differences exist between the major plasma lipoprotein classes of normal and resistant rabbits even during the ingestion of low-cholesterol diet. The results indicate that at least a part of the difference in the cholesterolemic responses between the two rabbit groups is due to an enhanced LDL uptake by the mononuclear cells, and presumably by other somatic cells of the resistant group.


Significant reduction of ketoacidosis at diabetes onset in children and adolescents with type 1 diabetes-The Stuttgart Diabetes Awareness Campaign, Germany.
To prevent the potentially life-threatening complication, diabetic ketoacidosis (DKA) at type 1 diabetes onset in children and adolescents, awareness campaigns can lead to a significant reduction of DKA. As in Germany, the incidence of DKA at diabetes onset had remained at a constant rate over the last 15 years and increasing numbers of very young children present with higher risk for DKA we decided to set up the Stuttgart Ketoacidosis Awareness Campaign. Over 3 years (2015-2017) the campaign was conducted using information flyers and posters illustrating the typical symptoms of diabetes at school entry health examinations at the Public Health Department, in day-care facilities, in all pediatric practices and by regular public activities. The period between 2011 and 2013 was selected as a reference period. Approximately 17 000 children, median age 4.5 years, and their families were informed about the campaign during the preschool health examination. A total of 118 children and adolescents were treated with newly diagnosed type 1 diabetes compared with 127 during the reference period. During the campaign the incidence of DKA decreased significantly from 28% to 16%. Awareness campaigns like the Stuttgart Ketoacidosis Awareness Campaign about the typical clinical symptoms of type 1 diabetes can significantly reduce the risk for DKA at diabetes onset. Important factors for the success of our campaign were the close cooperation between the children's hospital and the public health department, the targeted approach of families, teachers, and pediatricians and the duration of the campaign over 3 years.


RNase III enzymes and the initiation of gene silencing.
Our understanding of RNA interference has been enhanced by new data concerning RNase III molecules. The role of Dicer has previously been established in RNAi as the originator of 22-mers characteristic of silencing phenomena. Recently, a related RNAse III enzyme, Drosha, has surfaced as another component of the RNAi pathway. In addition to biochemistry, protein structures have proven to be helpful in deciphering the enzymology of RNase III molecules.


Effect of aspirin therapy on photodynamic therapy with verteporfin for choroidal neovascularization.
Photodynamic therapy (PDT) with verteporfin is used for treatment of choroidal neovascularization in several conditions. Platelet aggregation is one of the mechanisms by which PDT is thought to work. This study sought to examine the hypothesis that systemic use of aspirin, an inhibitor of platelet aggregation, affects the efficacy of PDT. A retrospective review was conducted of data for patients treated with PDT at one institution between 2001 and 2004. End points included total number of PDT treatments, mean time between PDT treatments, change in visual acuity from baseline to 3 months after last PDT treatment, and concurrent or subsequent treatments other than PDT. A total of 244 eyes of 222 patients met inclusion criteria, of which 102 eyes from 92 patients were included in the aspirin taking group. Aspirin takers received an average of 3.11 PDT treatments compared with 2.39 PDT treatments for nonaspirin takers (P = 0.001). Decrease in logMAR visual acuity was greater for aspirin takers (P = 0.0003), and a loss of > or =3 lines was seen in 58% of aspirin takers compared with 35% of nonaspirin takers (P = 0.0003). These differences remained statistically significant after controlling for patient age, lesion type, and lesion size. Patients taking aspirin required more PDT treatments and had worse visual outcomes than patients not taking aspirin, possibly due to aspirin's ability to inhibit platelet aggregation and thereby diminish the efficacy of PDT.


Gayet Wernicke's encephalopathy with cortical damage following a subtotal gastrectomy: An uncommon association.
Wernicke's encephalopathy is a pathological entity caused by Vitamin B1 (Thiamine) deficiency in malnourished individuals, especially alcoholics, patients operated for digestive surgery or suffering from gastrointestinal tract's diseases or incoercible vomiting. Classically it manifests by confusion with oculomotor disorders and ataxia. However, other neurological manifestations are possible. Magnetic resonance imaging is the gold standard imaging technique for diagnosis. It shows signal abnormality on periventricular area around the third and fourth ventricles and on mammillary bodies in the most common cases, however other localizations are possible, in particular the cerebral cortex, which can explain the occurrence of epileptic seizures in some patients. Early administration of Thiamine, intravenously or intramuscularly, allows ad-integrum recovery, while delayed treatment is associated with serious consequences in terms of mortality and morbidity with debilitating neurological sequelae. The presence of cortical lesions is of poor prognosis despite a well-managed treatment. In this article, we report a nonalcoholic Wernicke's encephalopathy case, following a subtotal gastrectomy. Epileptic seizures were the major clinical manifestation, related to the associated cortical lesions. Despite early and well-managed treatment, the patient had a poor prognosis, with progression, after one month, to a persistent chronic vegetative state.


Lifestyle behavior change and repeat health risk appraisal participation: a structural equation modeling approach.
Health risk appraisals (HRAs) have been used to address multiple health concerns and lifestyle behaviors. We explore the longitudinal relationship between emotional health, stage of change for five lifestyle behaviors, and lifestyle risks using HRA-generated data. Secondary analysis of 3 years of HRA data. A large health care management services provider. A total of 7535 adults employed across three companies who completed consecutive HRAs over a 3-year period. Self-report items concerning participant health, lifestyle behaviors, disease risk factors, job/life satisfaction, safety, and biometrics. Structural equation modeling tested a hypothesized longitudinal, fully cross-lagged panel design. Results indicated that greater numbers of physical and behavioral risks classified as high risk were associated with greater intention to change or an actual change in lifestyle behavior in the following year. In addition, poorer emotional health was associated with a higher number of risks. Data from repeat participation in HRAs can be useful in studying multiple risk behaviors and related health measures, supporting the design and evaluation of effective, individualized, and responsive health promotion activities for working adults.


Spontaneous dislocation of posterior chamber intraocular lenses (PC IOLs) in patients with retinitis pigmentosa - Case series.
To report the outcomes of intraocular lens (IOL) dislocation management in 6 cases with Retinitis Pigmentosa (RP). Private practice, Los Angeles, USA. Retrospective interventional case series. The medical reports of six eyes of four RP patients with capsule bag fixated posterior chamber IOL dislocation were retrospectively reviewed. Pre-operative data included demographics, systemic or ocular disorders, history of trauma, previous intraocular surgery and pre-operative visual acuity. Outcome measures included the type of surgery, surgical complications, elevation of intraocular pressure (IOP), ocular inflammation, cystoid macular edema (CME) and IOL dislocation at 3 months or greater post-operatively. The medical records of six eyes of four patients operated on between December 2009 and May 2011 were evaluated. In four cases, dislocated PC IOL implants were sutured to the sclera. In two eyes of one patient anterior chamber IOLs (AC IOLs) were implanted after PC IOLs were explanted. One eye developed CME during the follow-up period. Despite modest tilt in one case and modest decentration in another, stability and centration of the IOLs was excellent during the follow-up period. No eyes had intraocular inflammation requiring long term medical treatment, new onset glaucoma or retinal detachment. Mean follow-up time was 6.9 months (range 3-20). Cataract surgeons should be aware of the increased risk for decentration and malposition of PC IOLs in patients with RP. Satisfactory results can be achieved by fixation of the PC IOL or AC IOL implantation.


Clinical and laboratory features of murine typhus in central Tunisia: a report of seven cases.
Murine or endemic typhus, caused by Rickettsia typhi, has been reported in all continents. In the 1970s, no cases of murine typhus were diagnosed in Tunisia. The clinico-epidemiological characteristics of seven cases of murine typhus diagnosed at our hospitals since 1993 are reported. Diagnosis was confirmed by indirect fluorescence assay detecting specific R. typhi antibodies. Murine typhus occurred in all ages from 18-80 years during the hot season in rural areas. Clinical features were: sudden onset of fever and absence of eschar in all cases, with maculo-papular rash (five cases), prostration (four cases), meningism (three cases) and pneumonia (four cases). Frequent laboratory findings were moderate thrombopenia (four cases) and elevated transaminases (four cases). Before the results of serology, clinical diagnoses were Mediterranean Spotted Fever (four cases), Q fever (one case), pneumonia (one case), and lymphocytic meningitis (one case). Serology confirmed all diagnoses with cross-reactivity with Rickettsia conorii. Murine typhus exists in Tunisia and its prevalence is underestimated. Further, more specific studies are needed to evaluate the true prevalence.


A phase III trial evaluating the efficacy and tolerability of nimesulide 1% spray in patients with soft-tissue injuries.
To evaluate the efficacy and safety of nimesulide 1% w/w spray in minor soft-tissue injuries in adult Indians through a multicentric, open-labeled, phase III trial. 125 eligible patients, who met the selection criteria and gave written informed consent, were screened, enrolled, and treated with nimesulide 1% spray for seven days. Patients were assessed at baseline, day 1, day 4, and day 8 for efficacy and safety. Primary efficacy variable pain intensity, was measured using a NRS 1-100 mm (numerical rating scale). Secondary efficacy variables were degree of inflammation and edema and degree of functional impairment; overall assessment of efficacy was done by patient (patient global assessment - PGA) and by investigator (investigator global assessment - IGA) on days 4 and 8. There was a statistically significant reduction in the NRS score, degree of pain, edema (inflammation), and improvement in functional impairment on days 4 and 8 and in serum creatine kinase levels on day 8 in comparison with baseline. Global assessment of efficacy on day 8 was rated as "very good (21%)," "good (67.70%)," and "fair (11.30%)" by investigators and "very good (25%)," "good (58.90%)," and "fair (16.1%)" by patients. Two mild adverse events were reported in two patients, which resolved without any intervention. One (local irritation) was reported as not related, while the other (itching sensation) was probably related to the study drug. Nimesulide 1% spray was effective with a good safety profile and can be considered is a good alternative to oral analgesic therapy in minor soft-tissue injuries.


Effect of photic injury on the retinal tissues.
In order to study the tissue damages in photic injury of the retina, the macula and posterior pole of the rhesus monkey were exposed to the light of an indirect ophthalmoscope. During the acute phase of the injury, disruption of the blood-retinal barrier appeared to be an early and sensitive indicator of retinal pigment epithelial damage and cyclic-GMP-phosphodiesterase of the photoreceptor lamella was inactivated. These lesions were followed for 2 to 5 years. Focal chronic decompensation of the blood-retinal barrier and subretinal pigment epithelial neovascularization were noted in the chronic degenerative phase of this photic maculopathy. A possible protective role of ascorbic acid in mild photic injury was proposed.


Strategies for Tumor Hypoxia Imaging Based on Aggregation-Induced Emission Fluorogens.
Hypoxia, as a crucial characteristic of cancer, has become an extremely significant direction for researchers to construct fluorescent probes for early diagnosis of tumors. Aggregation-induced emission fluorogens (AIEgens) possess many superior properties to those of conventional fluorophores due to aggregation-induced emission (AIE) features, such as a linear concentration-dependent increase in brightness, remarkable resistance to photobleaching, and the long-term tracking and imaging of cells. Constructing hypoxic response AIEgen-based probes will be very useful for the early diagnosis of tumors. Herein, several hypoxia-responsive probes based on AIEgens reported in the last three years are reported; these examples may lead to the construction of hypoxia-responsive AIE probes used for tumor hypoxia imaging in the future. In addition, typical, conventional hypoxia-responsive bioprobes are presented to further understand hypoxia-responsive fluorescent probes based on AIEgens.


Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and impaired cardiac adaptation.
Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (muscle enriched A-type lamin-interacting protein), a unique protein of unknown function, is required for proper cardiac adaptation. Mlip(-/-) mice exhibited normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of Akt/mTOR pathways. Cardiac-specific MLIP overexpression led to an inhibition of Akt/mTOR, providing evidence of a direct impact of MLIP on these key signaling pathways. Mlip(-/-) hearts showed an impaired capacity to adapt to stress (isoproterenol-induced hypertrophy), likely because of deregulated Akt/mTOR activity. Genome-wide association studies showed a genetic association between Mlip and early response to cardiac stress, supporting the role of MLIP in cardiac adaptation. Together, these results revealed that MLIP is required for normal myocardial adaptation to stress through integrated regulation of the Akt/mTOR pathways.


Preparation of a paclitaxel-loaded cationic nanoemulsome and its biodistribution via direct intratumoral injection.
In this study, a nano-preparation based on nanoemulsome (NES) modified with cetyltrimethylammonium bromide (CTAB) loading paclitaxel (PTX) was designed, and its biodistribution were explored after intratumoral (i.t.) administration on Heps tumor-bearing mice. The PTX-loaded nanoemulsome (PTX-NES) was prepared by using a solvent evaporation method and CTAB, chosen as a cationic material, was absorbed onto the surface of the NES via electrostatic interaction to yield paclitaxel-loaded cationic nanoemulsome (PTX-CTAB-NES). The MTT results exhibited that PTX-CTAB-NES (IC50: 0.50±0.035μg/mL in MCF-7 cells and 0.13±0.048μg/mL in SMMC-7721 cells) had the strongest cytotoxicity compared to Taxol (IC50: 0.88±0.054μg/mL in MCF-7 and 0.15±0.011μg/mL in SMMC-7721) and PTX-NES (IC50: 1.93±0.062μg/mL in MCF-7 and 0.32±0.027μg/mL in SMMC-7721). Body distribution of PTX revealed that the percent of PTX retained in the tumor after i.t. administration of PTX-CTAB-NES (approximately 92.99% at 0.167h and 15.35% at 48h) was higher when compared to that after i.t. injection of Taxol (approximately 58.94% at 0.167h and 0.83% at 48h) or PTX-NES (approximately 83.63% at 0.167h and 6.52% at 48h). Moreover, less PTX accumulated in liver, spleen, kidney, lung and heart after i.t. administration of PTX-CTAB-NES when compared with that after i.v. administration of PTX-CTAB-NES. In conclusion, PTX-CTAB-NES was a prospective in-situ delivery system for the therapy of tumor.


Incomplete activation of Alyref and Gabpb1 leads to preimplantation arrest in cloned mouse embryos.
Differentiated cell nuclei can be reprogrammed after nuclear transfer (NT) to oocytes and the produced NT embryos can give rise to cloned animals. However, development of NT embryos is often hampered by recurrent reprogramming failures, including the incomplete activation of developmental genes, yet specific genes responsible for the arrest of NT embryos are not well understood. Here, we searched for developmentally important genes among the reprogramming-resistant H3K9me3-repressed genes and identified Alyref and Gabpb1 by siRNA screening. Gene knockout of Alyref and Gabpb1 by the CRISPR/Cas9 system resulted in early developmental arrest in mice. Alyref was needed for the proper formation of inner cell mass by regulating Nanog, whereas Gabpb1 deficiency led to apoptosis. The supplement of Alyref and Gabpb1 mRNA supported efficient preimplantation development of cloned embryos. Alyref and Gabpb1 were silenced in NT embryos partially because of the repressed expression of Klf16 by H3K9me3. Thus, our study shows that the H3K9me3-repressed genes contain developmentally required genes, and the incomplete activation of such genes results in preimplantation arrest of cloned embryos.


On the VC-Dimension of Unique Round-Trip Shortest Path Systems.
The VC-dimension, which has wide uses in learning theory, has been used in the analysis and design of graph algorithms recently. In this paper, we study the problem of bounding the VC-dimension of unique round-trip shortest path set systems (URTSP), which are set systems induced by sets of vertices in unique round-trip shortest paths in directed graphs. We first show that different from the VC-dimensions of set systems induced by unique undirected and directed shortest paths in undirected and directed graphs respectively, the VC-dimension of URTSP can be larger than 3. We then prove that the VC-dimension of URTSP is at most 32. Furthermore, we apply the VC-dimension result to the minimum k-round-trip shortest path cover problem (k-RTSPC), which is to find for a directed graph a minimum vertex set to intersect every round-trip shortest path containing at least k vertices, and derive an upper bound on the size of the vertex set. The k-RTSPC problem can be useful in many real-world applications, including optimal placement of facilities.


Insights into Bacterial Community Structure and Metabolic Diversity of Mercury-Contaminated Sediments from Hyeongsan River, Pohang, South Korea.
This study investigated the bacterial community structure and metabolic diversity and their relationship with Hg and other environmental variables in sediments collected from different locations (HSR-1-HSR-6) in the Hyeongsan River estuary in South Korea. The results showed that the highest total mercury (THg) and methylmercury (MeHg) concentrations were in HSR-2, with values of 4585.3 µg/kg and 13.4 µg/kg, respectively. The lowest THg (31.9 µg/kg) and MeHg (0.1 µg/kg) concentrations were found in HSR-1. Sulfate and organic matter (OM) were more influential environmental variables, revealing a positive association with THg and MeHg and negatively affecting bacterial and metabolic diversities. Bacterial and metabolic diversities were also negatively impacted by the THg and MeHg concentrations. Proteobacteria and Bacteroidetes were abundantly distributed in all the sediments. The dominance of Proteobacteria was upscaled in all the heavily Hg-contaminated sites (HSR-2-HSR-6), and it was the only phylum that showed a significant positive correlation with THg, MeHg, and OM. The genera Sulfurovum and Sulfurimonas were abundantly observed in sites with high Hg contamination, whereas Congregibacter, Gaetbulibacter, Ilumatobacter, Methylotenera, Nevskia, and Sediminibacter were only detected in low Hg-contaminated sites (HSR-1). The community-level physiological profile data showed the highest (1.0) average well color development (AWCD) value in HSR-1 and the lowest (0.45) AWCD value in HSR-2. Overall, these results demonstrated the inhibitory effects of THg, MeHg, and other environmental variables on microbial communities and metabolic diversity. These findings broaden the current knowledge on the dynamics of bacterial and metabolic diversities in Hg-contaminated sediments and might be useful in the management of Hg pollution.


Purification and characterization of DNA polymerases from Plasmodium falciparum.
Fractionation of Plasmodium falciparum cellular extracts by fast protein liquid chromatography (FPLC) identified at least two different DNA polymerases. An aphidicolin-sensitive activity co-purified with a primase activity. This, in combination with other characteristics (processivity, sensitivity to other inhibitors), most likely classifies this enzyme as an alpha-like DNA polymerase. It was, however, relatively resistant to N2-(p-n-butylphenyl)deoxyguanosine 5'-triphosphate (IC50 = 6.6 microM) and differs in this aspect from the host homologue, possibly indicating structural differences between host and parasite DNA polymerase alpha. The other DNA polymerase matched eukaryotic DNA polymerase gamma in all properties tested.


Improving mass spectrometer sensitivity using a high-pressure electrodynamic ion funnel interface.
We report on a new electrodynamic ion funnel that operates at a pressure of 30 torr with no loss of ion transmission. The enhanced performance compared with previous ion funnel designs optimized for pressures of <5 torr was achieved by reducing the ion funnel capacitance and increasing the RF drive frequency (1.7 MHz) and amplitude (100-170 V peak-to-peak). No degradation of ion transmission was observed for pressures from 2 to 30 torr. The ability to operate at higher pressure enabled a new tandem ion funnel mass spectrometer interface design that can accommodate a greater gas load (e.g., from an ESI source). When combined with a multicapillary inlet, the interface provided more efficient introduction of ions, resulting in a significant enhancement in mass spectrometer sensitivity and detection limits.


A New and Unexpected Complication After Arch Stent Grafting for Residual Dissection.
This report describes a complication after stent grafting of the aortic arch for residual dissection after ascending aorta and aortic arch replacement for acute type A dissection. One year later, a pseudoaneurysm originating from the proximal suture line and therefore far from the stent graft landing zone developed and fistulized into the pulmonary artery. Possible causes were suture damage during stent deployment and change of system forces after stent placement leading to high tension on the suture line. Emergency surgery was performed. Aortic arch stent grafting is a new and promising technique, but its complications are still not completely known.


Neurohypophyseal peptides and the eye: use of synthetic analogs in analyzing effects on the pupil.
Effects of neurohypophyseal (NHP) and synthetic analogs on the pupil of the rabbit were explored. This was prompted by the recent emergence of synthetic analogs with selective agonist and antagonist properties. The miotic effect of the NHP was examined in an isolated iris preparation. Minimum concentrations of arginine-vasopressin (AVP) needed to cause threshold pupillary constriction were approximately 10(-10) M. The miotic potency of several NHP analogs correlated best with their pressor activity. In addition, the synthetic NHP pressor antagonist d(CH2)5 Tyr(Me)AVP specifically antagonized the miotic effect, confirming that a pressorlike receptor mediates this pharmacologic action of the NHP. We also employed the technique of in vivo intravitreal administration of pharmacologic doses of the NHP in the rabbit. Once again, potent miotic activity was demonstrated. The relative miotic potency of the NHP in vivo provided further support to the relationship between the NHP "pressor" receptor and pupillary constriction. We believe that the use of a variety of NHP natural and synthetic analogs may also prove helpful in investigating potential physiological effects of the NHP on other intraocular smooth muscle.


Femoral Neck Anteversion and Lesser Trochanteric Retroversion in Patients With Ischiofemoral Impingement: A Case-Control Magnetic Resonance Imaging Study.
To assess the relationship between the femoral neck version (FNV) and lesser trochanteric version (LTV) in symptomatic patients with ischiofemoral impingement (IFI) as compared with asymptomatic hips. The FNV and LTV of patients with symptomatic IFI who underwent magnetic resonance imaging assessment including a standardized femoral version study protocol were compared with those of patients with asymptomatic hips in this retrospective, observational study. Patients with isolated intra-articular pathology, prior hip fracture, and lesser trochanter deformity were excluded. The FNV, LTV, ischiofemoral space, and quadratus femoris space were evaluated on axial magnetic resonance imaging, as well as the angle between the LTV and the FNV. Independent t-tests were used to determine differences between groups. Data from 11 out 15 symptomatic patients and 250 out of 320 asymptomatic patients were analyzed. The mean ischiofemoral space (11.9 v 22.9 mm; P < .001; 95% confidence interval [CI], 6.9 to 15.2) and mean quadratus femoris space (7.2 mm v 14.9 mm; P < .001; 95% CI, 5.4 to 8.6) were significantly smaller in symptomatic patients versus asymptomatic patients. There was no difference in mean LTV between groups (-23.6° v -24.2°; P = .8; 95% CI, -7.5 to 6.4), however, the mean FNV (21.7° v 14.1°; P = .02; 95% CI, -14.2 to -1.1) and the angle between the FNV and LTV on average (45.4° v 38.3°; P = .01; 95% CI, -12.9 to -1.3) were higher in symptomatic than in asymptomatic patients, with statistical significance. The femoral mean neck anteversion and the mean angle between the FNV and LTV are significantly higher in patients with symptomatic IFI. The mean LTV is not increased in patients with symptomatic ischiofemoral impingement as compared with those patients with asymptomatic hips. Level III, diagnostic study.


Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.
Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.


Incorporating feature selection methods into a machine learning-based neonatal seizure diagnosis.
The present study developed a feature selection (FS)-based decision support system using the electroencephalography (EEG) signals recorded from neonates with and without seizures. The study employed 10 different FS algorithms to reduce the classification cost by using fewer features and to improve the classification performance of the model by removing the irrelevant features. In doing so, the classification performance of each FS algorithm on each EEG channel difference was also evaluated. The dataset used in the study included EEG measurements and visual EEG annotations that were recorded from 79 term neonates. Multiple features were extracted from each channel difference using the Feature extraction (FE). Subsequently, a novel feature subset was generated for the classification using FS algorithms. The classification performance of each selected feature was assessed based on multiple criteria. The use of features extracted by the combined use of FS algorithms showed higher performance compared to the use of all features. In this study, 18 channel differences were analyzed. Better performance was achieved by using 3 of the selected 14 features or 2 of the selected features. The C4-P4 channel difference showed the highest classification performance (98.8%) among all channel differences. In the literature, FE has already been performed for the classification of the dataset used in the present study. The primary aim of the present study was to perform the same classification with the minimum number of features. The results indicated that feature reduction reduced the cost and also improved the performance of the classification. These results seem to be highly promising and thus can be used in clinical practice and shed light for future studies.


Demonstration that a chemically synthesized BPV1 oncoprotein and its C-terminal domain function to induce cellular DNA synthesis.
Bovine papillomavirus type 1 contains the smallest known oncogene (ORF E5), encoding a hydrophobic 44 amino acid protein. To study the biochemical functions of the E5 oncoprotein, we have chemically synthesized it and several deletion mutant peptides. We demonstrate induction of cellular DNA synthesis in growth-arrested cells by microinjection of E5 oncoprotein. This activity can be broken down into two functionally distinguishable domains. Remarkably, the first domain, which alone is sufficient to induce cellular DNA synthesis, contains only the C-terminal 13 amino acids. This is the smallest known protein fragment that can autonomously activate cellular DNA synthesis. The second domain is the hydrophobic middle region, which by itself fails to induce cellular DNA synthesis but confers a 1000-fold increase in specific activity. The N-terminal one-third of the molecule is dispensable for induction of DNA synthesis.


Improvement of catalytic activity of sorbose dehydrogenase for deoxynivalenol degradation by rational design.
Deoxynivalenol (DON) is the most frequently contaminated mycotoxin in food and feed worldwide, causing significant economic losses and health risks. Physical and chemical detoxification methods are widely used, but they cannot efficiently and specifically remove DON. In the study, the combination of bioinformatics screening and experimental verification confirmed that sorbose dehydrogenase (SDH) can effectively convert DON to 3-keto-DON and a substance that removes four hydrogen atoms for DON. Through rational design, the Vmax of the mutants F103L and F103A were increased by 5 and 23 times, respectively. Furthermore, we identified catalytic sites W218 and D281. SDH and its mutants have broad application conditions, including temperature ranges of 10-45 °C and pH levels of 4-9. Additionally, the half-lives of F103A at 90 °C (processing temperature) and 30 °C (storage temperature) were 60.1 min and 100.5 d, respectively. These results suggest that F103A has significant potential in the detoxification application of DON.


Histochemical demonstration of non-specific esterases and non-specific acid phosphatases using menadiol substrates.
Although many synthetic substrates and methods are available for the histochemical detection of non-specific esterases and non-specific acid phosphatase, there are still further possibilities to investigate these hydrolases histochemically. This was shown for menadiol diacetate and menadiol diphosphate using tetrazolium salt, simultaneous azo-dye as well as metal salt methods in many rat tissues. In comparison, the azo-dye procedure with various Fast salts or hexazonium Pararosaniline or New Fuchsin delivered less satisfactory results; precisely localized stain in sufficient amounts was obtained for non-specific esterases using nitro BT, tetranitro BT or benzothiazolystyrylphthalhydrazidyl tetrazolium (BSPT) and for non-specific acid phosphatase with BSPT in the tetrazolium salt method or using cerium ions for phosphate trapping in the diaminobenzidine-nickel-hydrogen peroxide procedure.


Cadmium-induced serotonergic neuron and reproduction damages conferred lethality in the nematode Caenorhabditis elegans.
Cadmium is a ubiquitous environmental toxicant. The use of Caenorhabditis elegans as a model for monitoring cadmium exposure has revealed several conserved signaling pathways. However, little is known about the killing process during lethality assay. In the present study, we investigated the effects serotonergic neuronal and reproductive damages on cadmium exposure in C. elegans. We found that sterile hermaphrodites, males and worms that passed reproduction span presented high cadmium resistance compared to those of young adults. The results demonstrated that reproduction process other than reproduction capacity conferred cadmium sensitivity. Cadmium exposure resulted in high ratio bagging phenotype, which was a severe reproductive deficit with embryos hatched internally that could cause worms to die early. The mechanism of bagging formation was ascribed to cadmium-induced egg laying deficiency that led embryos to retain and hatch in uterus. The addition of serotonin and imipramine promoted egg laying and thereby increased cadmium resistance. The results demonstrated that vulval muscles responsible for egg laying were still functional, while the serotonergic hermaphrodite specific neurons might be dysfunctional under cadmium exposure. Cadmium exposure resulted in shrinkage of serotonergic neuronal body and reduced expressions of tryptophan hydroxylase, the key enzyme for serotonin synthesis. The protection of serotonergic neuron through transient thermal preconditioning improved survival rate. In conclusion, our study demonstrated that damages of serotonergic neurons and reproduction conferred to cadmium-induced lethality.


Porous Ni/β-Ni(OH)2 superstructures: rapid solvothermal synthesis, characterization, and electrochemical property.
The porous Ni/β-Ni(OH)2 superstructures have been successfully prepared via a simple, fast one-pot solvothermal route in the presence of cetyltrimethyl ammonium bromide (CTAB), using NiCl2·6H2O and NaBH4 as the original reactants. The reaction was carried out in ethylene glycol at 170°C for 1h. The morphology of the obtained product could be controlled by adjusting the reaction time and the surfactant. The products were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectrometry (EDS), Infrared (IR) spectrometry, and Brunauer-Emmett-Teller (BET). The electrochemical property of the as-obtained superstructures was investigated through the cyclic voltammogram (CV) measurements. It was found that the as-obtained porous Ni/β-Ni(OH)2 superstructures exhibited good electrochemical properties and could be used as electrochemical sensors for the detection of some organic small molecules such as hydrochinone, pyrocatechol, and glucose.


Benchmarking the diagnostic test accuracy of certified AI products for screening pulmonary tuberculosis in digital chest radiographs: Preliminary evidence from a rapid review and meta-analysis.
The global market for AI systems used in lung tuberculosis (TB) detection has expanded significantly in recent years. Verifying their performance across diverse settings is crucial before medical organisations can invest in them and pursue safe, wide-scale deployment. The goal of this research was to synthesise the clinical evidence for the diagnostic accuracy of certified AI products designed for screening TB in chest X-rays (CXRs) compared to a microbiological reference standard. Four databases were searched between June to September 2022. Data concerning study methodology, system characteristics, and diagnostic accuracy metrics was extracted and summarised. Study bias was evaluated using QUADAS-2 and by examining sources of funding. Forest plots for diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves were constructed for the AI products individually and collectively. 10 out of 3642 studies satisfied the review criteria however only 8 were subject to meta-analysis following bias assessment. Three AI products were evaluated with a 95 % confidence interval producing the following pooled estimates for accuracy rankings: qXR v2 (sensitivity of 0.944 [0.887-0.973], specificity of 0.692 [0.549-0.805], DOR of 3.63 [3.17-4.09], Lunit INSIGHT CXR v3.1 (sensitivity of 0.853 [0.787-0.901], specificity of 0.646 [0.627-0.665], DOR of 2.37 [1.96-2.78]), and CAD4TB v3.07 (sensitivity of 0.917 [0.848-0.956], specificity of 0.371 [0.336-0.408], DOR of 1.91 [1.4-2.47]). Overall, the products had a sensitivity of 0.903 (0.859-0.934), specificity of 0.526 (0.409-0.641), and DOR of 2.31 (1.78-2.84). Current publicly available evidence indicates considerable variability in the diagnostic accuracy of available AI products although overall they have high sensitivity and modest specificity which is improving with time. These preliminary results are limited by the small number of studies and poor coverage for low TB burden settings. More research is needed to expand the clinical evidence base for the performance of AI products.


Comparison of the cerebroside sulphatase and the arylsulphatase activity of human sulphatase A in the absence of activators.
A cerebroside sulphatase (cerebroside-3-sulphate 3 sulphohydrolase, EC 22.214.171.124) assay based on radio thin-layer chromatography is described. The substrate was labelled by the catalytic addition of tritium to cerebroside sulphate. Using this assay the cerebroside sulphatase activity of sulphatase A (Aryl-sulphate sulphohydrolase, EC 126.96.36.199) from human liver and kidney in the absence of activators was investigated. The pH optimum of this reaction depends on the buffer concentration, being pH 4.5 at 50 mM and 5.3 at 10 mM sodium formate. With the latter concentration the apparent Km for cerebroside sulphate is 0.06 mM; SO2-4 and nitrocatechol sulphate inhibit noncompetitively with a Ki of 4.51 mM for Na2SO4 and 0.43 mM for nitrocatechol sulphate. The cerebroside sulphatase activity of sulphatase A is highly dependent on the ionic strength. The optimum sodium formate concentration is 10 mM, and the cerebroside suophatase activity decreases rapidly with increasing buffer concentration. The same concentration dependence is observed in the inhibitory effect of cerebroside sulphate on the arylsulphatase reaction. The inhibition decreases at increasing buffer concentrations, becoming an activation at 70 mM sodium formate. The progress curve of the cerebroside sulphatase reaction shows a deviation from linearity similar to that of the arylsulphatase reaction. Investigation of the effect of preincubation with cerebroside sulphate on the arylsulphatase activity of the enzyme shows that cerebroside sluphatase activity and inactivation of the enzyme by cerebroside sulphate occur simultaneously. These observations are interpreted as supporting the assumption that cerebroside suophate and arylsulphates are degraded at an identical active site on the same enzyme. Differences in the properties of the cerebroside sulphatase and the arylsulphatase reaction of the enzyme may be attributed to the differences in the physiocochemical state of the two substrates.


Post-Discharge Mortality and Rehospitalization among Participants in a Comprehensive Acute Kidney Injury Rehabilitation Program.
Hospitalization-associated AKI is common and is associated with markedly increased mortality and morbidity. This prospective cohort study examined the feasibility and association of an AKI rehabilitation program with postdischarge outcomes. Adult patients hospitalized from September 1, 2019 to February 29, 2020 in a large health system in Pennsylvania with stage 2-3 AKI who were alive and not on dialysis or hospice at discharge were evaluated for enrollment. The intervention included patient education, case manager services, and expedited nephrology appointments starting within 1-3 weeks of discharge. We examined the association between AKI rehabilitation program participation and risks of rehospitalization or mortality in logistic regression analyses adjusting for comorbidities, discharge disposition, and sociodemographic and kidney parameters. Sensitivity analysis was performed using propensity score matching. Among the high-risk patients with AKI who were evaluated, 77 of 183 were suitable for inclusion. Out of these, 52 (68%) patients were enrolled and compared with 400 contemporary, nonparticipant survivors of stage 2/3 AKI. Crude postdischarge rates of rehospitalization or death were lower for participants versus nonparticipants at 30 days (15% versus 34%; P=0.01) and at 90 days (31% versus 51%; P=0.01). After multivariable adjustment, participation in the AKI rehabilitation program was associated with lower risk of rehospitalization or mortality at 30 days (OR, 0.41; 95% CI, 0.16 to 0.93), with similar findings at 90 days (OR, 0.52; 95% CI, 0.25 to 1.05). Due to small sample size, propensity-matched analyses were limited. The participants' rehospitalization or mortality was numerically lower but not statistically significant at 30 days (18% versus 31%; P=0.22) or at 90 days (47% versus 58%; P=0.4). The AKI rehabilitation program was feasible and potentially associated with improved 30-day rehospitalization or mortality. Our interventions present a roadmap to improve enrollment in future randomized trials.


Nrf2: An all-rounder in depression.
The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes and diseases, such as depression. Oxidative stress can result in or aggravate a battery of pathological processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder and ferroptosis, which have been found to be involved in the development of depression. Inhibition of oxidative stress and related pathological processes can help improve depression. In this regard, the nuclear factor erythroid 2-related factor 2 (Nrf2) in the antioxidant defense system may play a pivotal role. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damages, but also directly regulate the genes related to the above pathological processes to combat the corresponding alterations. Therefore, targeting Nrf2 has great potential for the treatment of depression. Activation of Nrf2 has antidepressant effect, but the specific mechanism remains to be elucidated. This article reviews the key role of Nrf2 in depression, focusing on the possible mechanisms of Nrf2 regulating oxidative stress and related pathological processes in depression treatment. Meanwhile, we summarize some natural and synthetic compounds targeting Nrf2 in depression therapy. All the above may provide new insights into targeting Nrf2 for the treatment of depression and provide a broad basis for clinical transformation.


QSAR study on toxicity to aqueous organisms using the PI index.
We have attempted to develop quantitative structure-toxicity relationships (QSTRs) to predict hydrophobicity (logP) as well as toxicity (pEC50 microm) of benzene derivatives using recently introduced Padmakar-Ivan (PI) index. The results have shown that both logP as well as pEC50 of benzene derivatives can be modelled excellently in multiparametric models in that the PI index and some indicator parameters are involved. The predictive ability of the models is discussed on the basis of the cross-validation method. The superiority of the PI index over several other topological indices is critically examined.


Double network hydrophobic starch based amphoteric hydrogel as an effective adsorbent for both cationic and anionic dyes.
A double-network hydrophobic-hydrogel was successfully synthesized. Here epichlorohydrin (ECH) and N, N-methylene bis-acrylamide act as the crosslinkers for starch and poly(acrylic acid), respectively. The synthesized hydrogel having both positive and negative charge exhibited amphoteric properties and employed for the exclusion of anionic and cationic dyes from waste aqueous solution. The formation of positive charge occurs via reaction of triethylamine with the open up epoxy ring of ECH while carboxylate ion of poly(acrylic acid) gives the negative charge in the hydrogel. The formation of double cross-linking and the presence of quaternized alkyl chains lead towards hydrophobicity with much lower swelling ability. As an adsorbent, the hydrogel was able to remove both cationic dye (methylene blue) and anionic dye (congo red) with adsorption maxima of 133.65 mg/g and 64.73 mg/g, respectively. This study showed that the synthesized hydrogel offers enormous potential as the toxic dye adsorbent for effluent treatment of industrial wastewater.


In vivo anti-inflammatory effect of a new steroidal saponin, mannioside A, and its derivatives isolated from Dracaena mannii.
A new steroidal saponin, mannioside A (1), was isolated from the stem bark of Dracaena mannii, together with the known pennogenin (2), pennogenin-3-O-beta-D-glucopyranoside (3) and pennogenin-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->3)]-beta-D-glucopyranoside (4). Their structures were determined using 1D-and 2D-NMR spectroscopy and mass spectrometry. Compounds 1 and 3 significantly inhibited carrageenan-induced paw edema in the rat; compound 4 was moderately active whereas 2 showed very weak activity.


Characterization of cachexia in the human fibrosarcoma HT-1080 mouse tumour model.
Cancer cachexia is a complex metabolic disease with unmet medical need. Although many rodent models are available, none are identical to the human disease. Therefore, the development of new preclinical models that simulate some of the physiological, biochemical, and clinical characteristics of the human disease is valuable. The HT-1080 human fibrosarcoma tumour cell line was reported to induce cachexia in mice. Therefore, the purpose of this work was to determine how well the HT-1080 tumour model could recapitulate human cachexia and to examine its technical performance. Furthermore, the efficacy of ghrelin receptor activation via anamorelin treatment was evaluated, because it is one of few clinically validated mechanisms. Female severe combined immunodeficient mice were implanted subcutaneously or heterotopically (renal capsule) with HT-1080 tumour cells. The cachectic phenotype was evaluated during tumour development, including body weight, body composition, food intake, muscle function (force and fatigue), grip strength, and physical activity measurements. Heterotopic and subcutaneous tumour histology was also compared. Energy balance was evaluated at standard and thermoneutral housing temperatures in the subcutaneous model. The effect of anamorelin (ghrelin analogue) treatment was also examined. The HT-1080 tumour model had excellent technical performance and was reproducible across multiple experimental conditions. Heterotopic and subcutaneous tumour cell implantation resulted in similar cachexia phenotypes independent of housing temperature. Tumour weight and histology was comparable between both routes of administration with minimal inflammation. Subcutaneous HT-1080 tumour-bearing mice presented with weight loss (decreased fat mass and skeletal muscle mass/fibre cross-sectional area), reduced food intake, impaired muscle function (reduced force and grip strength), and decreased spontaneous activity and voluntary wheel running. Key circulating inflammatory biomarkers were produced by the tumour, including growth differentiation factor 15, Activin A, interleukin 6, and TNF alpha. Anamorelin prevented but did not reverse anorexia and weight loss in the subcutaneous model. The subcutaneous HT-1080 tumour model displays many of the perturbations of energy balance and physical performance described in human cachexia, consistent with the production of key inflammatory factors. Anamorelin was most effective when administered early in disease progression. The HT-1080 tumour model is valuable for studying potential therapeutic targets for the treatment of cachexia.


Characterization of a new cell line from ornamental fish Amphiprion ocellaris (Cuvier, 1830) and its susceptibility to nervous necrosis virus.
Amphiprion ocellaris (ocellaris clownfish) is one of the most commercially important marine ornamental fish. A cell line designated as OCF was developed for the first time from the caudal fin of this fish species. The cell line was maintained in Leibovitz's-15 medium supplemented with 15% FBS (Fetal Bovine Serum) and was successfully subcultured up to 34 passages. The cell line was authenticated by sequencing mitochondrial cytochrome C oxidase subunit I (COI) and 16S rRNA genes. The growth rate of the OCF cell line was maximum in medium containing 20% FBS and 1% of 0.2 M NaCl at 28 °C. Chromosome analysis revealed 48 diploid chromosomes. The OCF cell line was transfected with the pMaxGFP plasmid vector with 7% efficiency and GFP expression was observed. The OCF cell line was used for testing nervous necrosis virus (NNV) susceptibility. Cytopathic effect (CPE) was observed in terms of plaque formation after virus inoculation. Nested PCR confirmed the susceptibility of the OCF cell line to NNV. The cell line was successfully cryopreserved by a slow freezing procedure at - 80 °C with a revival efficiency of 70-75%. The study revealed that the OCF cell line would be useful for virological studies. In addition, the cell line would play an important role as an in vitro tool for carrying out toxicological and biotechnological studies.


A comparison of formic acid or monoglycerides to formaldehyde on production efficiency, nutrient absorption, and meat yield and quality of Cobb 700 broilers.
After being banned by the European Commission in 2018, the use of formaldehyde as a feed amendment in the United States has come into question. Therefore, this study was conducted to explore alternatives to formaldehyde, such as formic acid and monoglycerides, and their effects on poultry production. In total, 1,728 Cobb 700 broilers were randomly assigned to 96-floor pens on day of hatch (18 birds/pen). Using a randomized complete block design (4 blocks), treatments were assigned to pens with blocking based on location within the barn, with the eastern half of the barn designated for digestibility and the western half designated for production (per experiment: 8 control pens and 10 pens per treatment). All diets were based on a negative control (NC), basal diet. Dietary treatments consisted of: NC, NC + 0.25% formalin (F), NC + 0.25 and 0.50% Amasil NA (AML and AMH; 61% formic acid and 20.5% Na-formate), and NC + SILO Health 104L (SILO; mixture of monoglycerides; 0.5% from 0 to 14 d, 0.4% from 14 to 28 d, and 0.2% from 28 to 42 d). Water and feed were provided ad libitum. Performance data were collected during feed changes on d 0, 14, 28, and 42, with digestibility data collected at d 14 (2 per pen) and carcass quality (6 per pen) assessed at d 46 with a randomly selected group of broilers. A one-way ANOVA followed by Dunnett's multiple comparison, where treatments were evaluated against F were conducted using JMP 14.0 (P ≤ 0.05). Main effect of treatment was significant for performance, nutrient digestibility, and carcass quality. Differences in body weight and ADG were observed from d 14 to d 28, resulting in a trending improvement in lysine digestibility on d 14 and carcass quality on d 46 of birds fed AML and AMH in comparison to those fed F (P < 0.05). Whereas birds fed SILO had reduced digestibility of methionine on d 14 and a decrease in meat quality on d 46 in comparison to those fed F (P < 0.05). Therefore, Amasil NA at 0.25 or 0.50% may be an effective alternative to formaldehyde as a feed amendment for poultry production.


Effects of water cooling on laser-induced thermal damage in rat hepatectomy.
High-powered lasers are commonly used for tissue resection in surgeries, including liver resection, medically known as hepatectomy; however, such lasers inevitably induce thermal damage that causes postoperative complications. This study aims to explore the effects of water cooling and different laser output modes on laser-induced thermal damage during hepatectomy. To avoid the influence of superposition, a 980-nm diode laser was used for a single-point hepatectomy. Eighteen Sprague-Dawley rats were used to explore the effects of water cooling and different laser output modes. A constant energy 10-J laser was used to cut the liver tissue with a power of 10 W and time of 1 second. The rats were randomly divided into six groups. The first three groups were assigned as test subjects for different laser output modes. Group 1 was operated with a continuous laser output for a duration of 1 second. Groups 2 and 3 were operated with a pulsed laser output for a duration of 1 second and a pulse width of 0.5 and 0.25 seconds, respectively. Groups 4, 5, and 6 were assigned for the water cooling test. Water cooling was performed based on the parameters of the first three groups. Medical saline (0.9% NaCl) was used for water cooling. The main observation indicators were resection efficiency and thermal damage, including the area of the thermal damage zone. Resection efficiency is calculated by dividing the resection area by the total thermal damage area. In the three water cooling groups, the area of the resection, carbonized, sub-boiling coagulated, and total thermal damage zones were 0.0677, 0.00, 1.7293, and 2.2982 mm2 in Group 4; 0.0465, 0.00, 1.3205, and 1.8414 mm2 in Group 5; and 0.0565, 0.00, 1.4301, and 1.9650 mm2 in Group 6, respectively. Compared with the first three groups, the water cooling groups exhibited significantly reduced thermal damage areas of in the carbonized, sub-boiling coagulated, and total thermal damage zones (p < 0.001 for all). In addition, there was no statistical difference in the resection area, vacuolated area, and resection efficiency. Furthermore, there was no statistical difference in the area of each thermal damage zone between the continuous and pulsed output groups. The resection efficiencies were 4.82%, 3.34%, 3.73%, 3.93%, 3.36%, and 3.01% in Groups 1 to 6, respectively. Moreover, there was no statistical difference (p > 0.05) in the resection efficiencies. Water cooling can reduce the total laser-induced thermal damage area and prevent tissue carbonization. Therefore, this cooling method can be used as a simple and safe strategy for controlling thermal damage during hepatectomy.


Serum CXC chemokine ligand-12 as a potential predictor for in-hospital major adverse events after severe traumatic brain injury.
CXC chemokine ligand-12 (CXCL12) is associated with brain inflammation. We attempted to discern whether serum CXCL12 is a promising predictor for in-hospital major adverse events (IMAEs) after traumatic brain injury (TBI), including death, acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction. In this prospective, observational study, serum CXCL12 levels were quantified among 117 severe TBI patients. We investigated the relation of CXCL12 levels to IMAEs using a multivariate analysis. Median value of serum CXCL12 concentrations was substantially higher in patients with IMAEs than in other remainders (21.1 vs. 11.6 ng/ml). With an increasing number of IMAEs, serum CXCL12 concentrations were significantly increased (r = 0.702). Serum CXCL12 independently predicted IMAEs (odds ratio, 1.253; 95% CI, 1.100-1.428). Serum CXCL12 concentrations discriminated risk of IMAEs with area under receiver operating characteristic curve of 0.759 (95% CI, 0.672-0.834), its concentrations >16.0 ng/ml distinguished IMAEs with 83.9% sensitivity and 67.2% specificity and its combination with Glasgow coma scale scores produced the best predictive ability compared with each one alone (p = 0.0116 or 0.0004). Serum CXCL12 concentrations are independently associated with IMAEs following TBI, substantializing serum CXCL12 as a useful prognostic biomarker for head trauma patients.


Allogeneic CD34+ -selected peripheral stem cell transplantation from parental donors in children with non-malignant diseases.
Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+ cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11 (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival.


Cesarean section and childhood infections: Causality for concern?
In this Perspective, Gordon Smith discusses the findings of Miller et al, and the balance of risks and benefits associated with different modes of delivery.


Effect of gamma interferon on HLA class-I and -II transcription and protein expression in human breast adenocarcinoma cell lines.
The spontaneous expression of HLA class-I and class-II molecules in 5 human breast carcinoma cell lines, MCF-7, T47D, ZR75-1, HSL-53, MDA-MB 231, and their modulation during IFN-gamma treatment, are reported. The expression of cell-surface determinants was examined by indirect immunofluorescence using monoclonal antibodies (MAbs) specific for HLA class-I and class-II (DR, DQ and DP) antigens. The biosynthesis and maturation of these molecules were analyzed by 2-dimensional gel electrophoresis analysis (2D-PAGE) of class I, DR alpha, beta and invariant immunoprecipitates. Transcription was analyzed by Northern blot hybridization with HLA class-I and -II cDNA-specific probes. In all cell lines, more than 80% of cells expressed HLA class-I antigens at their surface. 2D-PAGE and mRNA studies showed a variable basal level of HLA class-I biosynthesis and transcription with a constant increase after 1,000 U/ml IFN-gamma treatment. HLA class-II determinants were totally absent from the surface of MCF-7, MDA MB231, ZR75-1 and T47D but they were detected in a small subpopulation of HSL-53 cells (DR 6%, DQ 6%, DP 20%). Spontaneous biosynthesis of HLA-DR molecules in immunoprecipitates analyzed by 2D-PAGE or transcripts in Northern blot were not detected in the 5 cell lines. Treatment with 1000 U/ml IFN-gamma induced or increased the expression of HLA class-II molecules in all cell lines but DQ expression was variable. While T47D, ZR75-1 and HSL-53 increased their transcripts and antigen expression, MDA, MB231 and MCF-7 showed no DQ mRNA transcript. Biochemical analysis of the DR products revealed a classical alpha, beta and invariant (li) chain pattern, but indicated a constant glycosylation defect in the invariant chain in all cell lines, associated with weak expression of the beta chain and the presence of an extra spot of low molecular weight in the acidic part of the gel. Thus, post-transcriptional events did not appear to be totally controlled by IFN-gamma in the different cell lines. These differences in DQ expression and glycosylation process in different breast cancer cells may be important in the activation of the immune response among different individuals.


Monitoring endoscopic treatment of superficial bladder carcinoma by postoperative urinary cytology.
Transurethral resection was the only modality of treatment in 39 patients with long-standing, recurrent, superficial bladder carcinoma. Postoperative urinary cytology was performed within 3 days of each endoscopy. Tumor recurrence was defined by the presence of a positive biopsy or visible papillary tumors on followup cystoscopic examination. Tumor recurred in 38 patients (97.4 per cent) and 1 patient (2.6 per cent) has remained free of disease 74 months following transient positive postoperative cytology. Among the 38 recurrences 15 (39.5 per cent) were positive, 3 (7.9 per cent) suspicious and 20 (52.6 per cent) negative at the postoperative cytological examination. The interval to recurrence did not differ significantly among the 3 groups. The failure of a negative postoperative cytology study to predict a durable response to treatment by transurethral resection reflects the polychronotopic nature of superficial bladder tumors in this select patient population and suggests the need for adjuvant therapy.


Long-term follow-up after stroke in childhood.
Over the last few years, the importance of paediatric stroke has become more and more evident; however, there is still little known about long-term neurological and especially neuropsychological outcome of these children. By retrospective chart review, questionnaire and clinical examination with structured interview, we analysed initial presentation, aetiology and long-term outcome of children suffering ischaemic childhood stroke between 1985 and 1999. A total of 20 children (13 boys) suffered acute arterial ischaemic events. Aetiology was detected in 14, and suspected in another five. Follow-up after 1-15 years (mean 7 years) was possible for 16 children; two had died and two were lost to follow-up. Only two were completely healthy, five suffered mild, six moderate, and three severe handicap. Eleven children presented with combined neurological and neuropsychological problems. Neurological problems were mild to moderate hemisyndrome in 11, dysphasia, epilepsy and other in six each. Mild to severe neuropsychological problems were detected in 13 children, school problems in eight, attention deficits in nine and behaviour problems in seven, increased fatigability and headache in six each. Recurrence was observed in three children, all due to progressive underlying disease. Outcome was most affected by the presence of combined cortical/subcortical and least affected by subcortical infarction. Epilepsy affected neuropsychological outcome. although prognosis of paediatric stroke is better than for adult stroke, neurological and especially neuropsychological long-term problems significantly influence the lives of these children. Careful long-term follow-up to support these children in their school career and integration into professional life is necessary. Future studies should evaluate whether specific treatments during the acute episode could improve outcome for these children.


Using pharmacokinetic-pharmacodynamic relationships to predict the effect of poor compliance.
Since it is difficult to improve patient compliance to drug prescriptions, an alternative is to select a drug with less consequences for poor compliance, that is, a drug that has the capacity of 'forgiveness'. Forgiveness is the property of a drug which, when compared with another medicine with different pharmacokinetics and/or concentration-effect relationships, blunts the consequences of missing one or two doses in a row, or has a greater variability in the timing of intake. Simulations show that drugs with a concentration-effect relationship modelled with an effect compartment, for example a delayed response, have more forgiveness. A marker of forgiveness would be of some help for doctors deciding which drug to prescribe to patients who are poor compliers.


A case of incidental infection of Hepatitis E virus (HEV) genotype 1 in a domestic pig.
Hepatitis E virus (HEV) infection involving zoonotic genotypes is a public health problem in high-income and non-endemic developing countries. Herein we report the detection of a human genotype 1 (HEV-1) strain infecting a domestic pig, which is not considered a natural reservoir of this genotype. Viral load was quantified in stool by Real-Time qPCR and sequence analyses were performed. Infectivity of the HEV-1 strain was assesed by in vitro isolation in A549 cell line. Results suggest that certain epidemiological settings might favour accidental spillover infection and thus influence the host range restriction of HEV.


Inclusion complexation of doxorubicin and daunorubicin with cyclodextrins.
The interaction of alpha-, beta- and gamma-cyclodextrins with the anthracycline antibiotics doxorubicin and daunorubicin was investigated by LC, circular dichroism (CD) and absorption spectroscopy. All studies were performed in aqueous media at different temperatures and pH values. The anthracyclines complex only with gamma-cyclodextrin. Lineweaver-Burk and Scott's plots were used to calculate the stability constants of the anthracycline-gamma-cyclodextrin inclusion complexes.


Vessel reactivity and prejunctional modulatory changes in the portal vein of mature spontaneously hypertensive rats.
The prejunctional effects of 2-chloroadenosine on the contractile responses to perivascular nerve stimulation were studied in conjunction with vessel reactivity in portal veins from mature (45-60 weeks) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls. It was found that the contractility of the portal veins to exogenous noradrenaline was enhanced in SHR, while the sensitivity to noradrenaline, as seen from the EC50 values, was not altered. Responses to perivascular nerve stimulation (supramaximal voltage, 0.7 ms pulse duration for 10 s) were also enhanced in spontaneously hypertensive rats compared to WKY controls at all frequencies of stimulation tested (2-64 Hz), although the sensitivity to perivascular nerve stimulation was not changed since a response of 50% of the maximal obtainable was achieved at 8 Hz in both SHR and WKY. However, no evidence for change in the level of prejunctional modulation of nerve stimulation responses or postjunctional modulation of noradrenaline responses by 2-chloroadenosine (0.1-100 microM) was found. In conclusion, in mature SHR, responses to perivascular nerve stimulation and exogenous noradrenaline were found to be enhanced compared to responses in WKY, although there was no difference in the modulatory action of 2-chloroadenosine between SHR and WKY.


Appearance of killer (K) cells in the mesenteric lymph nodes in Crohn's disease.
The local lymph node in Crohn's disease contains killer (K) cells which are able to lyse antibody-coated heterologous target cells. K cells are not found in mesenteric lymph nodes from control patients not suffering from Crohn's disease, whereas they are regularly found in similar amounts in the peripheral blood of both control and patients with Crohn's disease. Even mesenteric lymph node cells from areas not macroscopically affected by inflammatory disease show increased K cell activity as compared to control lymph node lymphocytes, suggesting a generalized mesenteric lymph node involvement with regard to K activity in Crohn's disease.


Native-like secondary structure of molten globules.
The most common evidence for the existence of secondary structure in a globular protein is the presence of a strongly pronounced far-UV circular dichroism (CD) spectrum. Although CD spectra of native proteins are well described and their quantitative analysis is widely used, similar studies for denatured proteins have still to be done. Far-UV CD spectra of nine proteins in the native and the pH-induced molten globule states were acquired and analyzed. Singular value decomposition showed that the spectra of molten globules could be described as a superposition of at least three independent components (most likely alpha-, beta- and irregular structure). A self-consistent procedure of CD spectra analysis revealed the existence of a clear correlation between the shape of the molten globule spectra and the content of secondary structure elements in the corresponding native proteins, as determined from X-ray data. A mathematical expression of this correlation in terms of the Pierson coefficient amounts to the value of 0.9 for both the alpha-helix and the beta-structure. Thus, the secondary structure of proteins in the molten globule state is close to that in the native state.


Association of genetic and environmental factors with dental caries among adolescents in south China: A cross-sectional study.
The objective of this study was to investigative genetic and environmental factors that contribute to caries susceptibility among adolescents in south China. A cross-sectional study was conducted among 1055 adolescents aged 13-14 years old in south China. The International Caries Detection and Assessment System (ICDAS) was used to identify caries. Environmental variables were analysed by regression models. Twenty-three single nucleotide polymorphisms (SNPs) in 14 genes were identified from saliva samples. Regression analysis was used for the evaluation of effects of SNP markers using the minor allele as the effect allele. Our results suggest that gender, Cariostat score and Plaque Index were associated with dental caries. After the adjustment by age and gender, the G allele in AMBN (rs13115627) nominally was a protective factor for caries under additive model (P=0.028; OR=0.782; 95% CI, 0.627-0.974). However, the association did not meet the Bonferroni correction significance cut-off for multiple testing. Gender, Cariostat score and Plaque Index were associated with dental caries in this population. No selected SNPs showed a significant association with dental caries under either additive model or dominance model.


Combined medical and surgical approach in the management of ligneous conjunctivitis in a pediatric patient: A case report.
Ligneous conjunctivitis (LC), a rare chronic conjunctivitis linked to plasminogen deficiency, poses challenges in research and management due to its complexity. This case report details the combined medical and surgical approach in managing LC in a 1.5-year-old female with congenital hydrocephalus, plasminogen deficiency, and glaucoma. The patient's LC required a comprehensive treatment plan involving systemic and topical therapies, surgical intervention, and fresh frozen plasma (FFP) infusions via a central line. Managing LC necessitates a comprehensive, individualized approach due to its rarity and lack of standardized treatments. Various therapies have shown promise, but their availability, cost, and potential side effects vary. FFP infusions played a crucial role in managing plasminogen deficiency, but the potential complications associated with central lines must be considered. Ongoing clinical trials aim to improve LC treatment, but until results are available, clinicians must rely on existing evidence and clinical judgment. This case underscores the complexity of managing LC and the significance of adopting an individualized treatment strategy. Regular follow-ups are crucial for flexibility and adaptability in treatment plans to address potential recurrences. Further research is necessary to validate these findings and assess the long-term effectiveness of the combined approach.


Dorsal lumbotomy for surgery of the upper urinary tract.
Between July 1978 and December 1985, 100 patients underwent an operation on the kidneys and ureter through the dorsal lumbotomy approach. A total of 12 patients underwent dismembered pyeloplasty for ureteropelvic junction obstruction. Compared to patients who underwent an operation via the standard flank incision, these 12 patients had significantly shorter hospitalization and fewer doses of analgesics. The treatment demonstrated improved cost-effectiveness. Similar advantages were noted in the remaining patients in whom removal of calculi (78), open renal biopsy (5), simple nephrectomy (4) and removal of a foreign body in the ureter (1) were done through the dorsal lumbotomy approach. We appeal for a renaissance of the dorsal lumbotomy approach in urological teaching and practice.


Clinical outcomes of different types of tooth-supported bilayer lithium disilicate all-ceramic restorations after functioning up to 5 years: A retrospective study.
The aim of this retrospective study with large sample was to assess the 5-year clinical outcomes of four different types of restorations made from IPS e.max Press. A total of 6855 restorations containing veneers (Vs), single crowns (SCs), 2-unit or multiple-unit combined crowns (CCs) and 3-unit or multiple-unit fixed dental prostheses (FDPs) from 4634 patients were included. Data collection were performed through scrutiny and registration of the records of all patients. The cumulative survival rates (CSRs) and their differences were calculated according to the Kaplan-Meier analysis and Log-Rank test. The differences among the failure rates of different restorations were evaluated according to the Chi-squared test. The 5-year CSR of all restorations was 96.6%. The 5-year CSRs of CCs (94.4%) and FDPs (90.6%) were both significantly lower than those of SCs (96.5%) and Vs (97.2%). A total failure rate was 3.2%. The failure rate of FDPs was 9.0%, which was significantly higher than those of Vs (2.5%) and SCs (3.3%), and was similar to that of CCs (5.2%). The failure rate of molar SCs (8.2%) was significantly higher than those of anterior (3.2%) and premolar SCs (2.5%). 83.0% of failed restorations happened in the 1st year after cementation and 50.6% happened in the first 3 months. Moreover, ceramic chipping (41.5%) and fracture (37.3%) were the top two reasons. In anterior tooth region, the ceramic damage rate of Vs (1.7%) was significantly lower than those of FDPs (8.1%) and CCs (4.8%), and that of SCs (2.6%) was significantly lower than that of FDPs (8.1%). IPS e.max Press has an ideal medium-term outcome. The failures mainly occurred in the first 3 months after cementation and the main reasons were ceramic chipping and fracture. Due to higher failure risk, we suggest dentists should be cautious to apply FDPs, CCs and molar SCs.


[Pregnancy without medical monitoring: obstetrical and neonatal prognosis. A retrospective study of 88 cases].
Unregistered and unmonitored pregnancies account for 0.2 to 0.6 p. cent of all pregnancies. They essentially concern young, single, primiparous mothers from disadvantaged social backgrounds. Labour and delivery are generally without difficulty but the neonatal prognosis is impaired by a high proportion of premature and underdeveloped infants, often requiring a long stay in a pediatric unit.


Dynamic light-scattering evidence for the flexibility of native muscle thin filaments.
We have obtained clear evidence for the flexibility of native scallop adductor thin filaments by studying the temperature and ionic strength dependence of the average decay constants obtained from intensity fluctuation spectroscopic (IFS) measurements. The low-angle (10-25 degrees ), average decay constants obtained from time autocorrelation functions of scattered light were independent of concentration (0.08-1.3 mg/ml), scaled with the ratio of temperature to solvent viscosity, T/eta, over a range of 4-45 degrees C, and yielded a value for the translational diffusion coefficient of D(T) (5 degrees C) = (1.24 +/- 0.06) x 10(-8) cm(2)/s. From this value and the Broersma relation for rigid rods, we find an average filament length of 1.06 +/- 0.06 mum. Quantitative sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that at high temperatures (> 35 degrees C) or in 0.6 M NaCl, tropomyosin completely dissociates from native thin filaments. Decay constants from high-angle (60-150 degrees C) IFS temperature dependence measurements do not scale with T/eta and hence do not show the temperature dependence expected for rigid rods. The differences are not due to any change in length distribution of filaments with temperature or to the free tropomyosin in solution, but are attributed to nonrigid motions of the filaments. Similar experiments on samples in high- and low-salt solvents gave results consistent with this interpretation.


Distribution of two distinct messenger ribonucleic acids encoding gastrin-releasing peptide in rat brain.
There are two distinct mRNAs that encode the precursor to gastrin-releasing peptide (GRP) in rat brain. These two messages arise from separate transcription initiation sites located approximately 400 base pairs apart, which are presumably regulated by separate promoters. In the present study, we mapped the distribution of neurons containing GRP mRNAs by in situ hybridization using cRNA and synthetic DNA probes specific for the 1.5 kb GRP transcript and probes complementary to both the 1.5 kb and 1.1 kb transcripts. The distribution of neurons expressing GRP mRNA appears to be wider than that previously observed by immunohistochemical studies, suggesting an important functional role for this neuropeptide in a number of brain regions. We detected the 1.5 kb transcript only in cingulate cortex, Ammon's horn of the hippocampus and in subiculum. In contrast, the probe which hybridized to both GRP mRNAs labeled a broad range of brain areas, including those containing the 1.5 kb mRNA. These data suggest that the 1.5 kb mRNA encoding rat GRP is expressed only in specific parts of the limbic system, whereas the expression of the 1.1 kb GRP message is more widespread.


[Severe tooth agenesis. Presentation of a case].
In the present work the Authors describe a case of a patient affected by Duchenne disease as well as by dental multiple agenesis. It is a particular case of such rare syndromes in the same subject.


Detection of ophthalmoscopically occult maculopathy by focal electroretinography.
We performed focal electroretinography (FERG) in 10 patients with reduced vision of unknown cause. No patient gave a family history of uncorrectably reduced vision, and none had taken any drug known to damage the retina. Visual acuity claims ranged from 20/40 to finger counting. Color discrimination was reduced in all but one patient. Visual field sensitivity was reduced nonspecifically in five of the six patients who could perform perimetry reliably. Ophthalmoscopy showed no pertinent abnormality in four of 10 patients, mildly reduced foveal reflex in two of 10, arteriolar narrowing in two of 10, foveal pigment disturbance in one of 10, and preretinal gliosis in one of 10. Flash visual evoked potential (VEP) testing showed no abnormality in seven of 7 patients. The pattern VEP was reduced or delayed in five of 5 patients, only one of whom showed the expected amplitude loss with decreasing check size. Five patients completed full-field electroretinography, six patients completed fluorescein angiography, and none showed pertinent abnormality on either test. FERG was performed in both eyes of seven patients and in one eye of three others. Signals were non-recordable from four eyes, abnormal in nine, equivocal in three, and normal in one. The severity of FERG abnormality did not correlate with the severity of acuity loss. FERG abnormalities were found in fourteen of 17 eyes of 10 patients with vision loss out of proportion to clinical findings. In these patients only one of 5 pattern VEP tests, none of 5 full-field ERGs, and none of 7 fluorescein angiograms suggested correspondingly severe maculopathy. The FERG results in these cases mitigated suspicions of nonorganic vision loss and permitted speedier referral to retinal disease and low vision specialists.


Snowboarding injuries in Australia: investigating risk factors in wrist fractures to enhance injury prevention strategies.
To investigate risk factors associated with wrist fractures in snowboarders to inform future snowsport safety strategies. A prospective case-control study using a nonprobability convenience sample was conducted with data collected via a respondent-completed questionnaire. Subjects consisted of snowboarders with a snowboard-related injury who presented to one of 10 medical centers and physiotherapy clinics in resort medical centers and gateway communities across the Australian snowsport season in 2007. Those presenting with injuries other than wrist fractures acted as the control. The 611 respondents reported 802 injuries (61.3% were males and 51.5% were aged 16-25 years). Protective equipment was worn by 57.0% of respondents. The main reason for not wearing a wrist guard was that they did not see the need; of these, 12.9% experienced a wrist fracture. Most injuries occurred on-piste, in a terrain park, or in a lesson. The main mechanism of injury was falling. The major risk factors for wrist fractures were being less than 16 years of age (OR 3.97, CI 2.54-6.22), being in the alpine area for a holiday (OR 2.77, CI 1.47-5.21), and being a first-day snowboard participant (OR 2.02, CI 1.15-3.64). A direct logistic regression indicated that 3 variables had a statistically significant contribution to the model (being less than 16 years old, being on holidays in the region, and not wearing a wrist guard). The key risk factors in this Australian study reflect other international studies, providing a clear market segment for targeted snowsport safety messages: those less than 16 years old, visitors to the alpine regions, and those not wearing wrist guards.


A survey of the use of micro-computers in general dental practice in Scotland.
The aim of the study was to determine current and future use of micro-computers in general dental practice. A piloted questionnaire was sent to 736 general dental practitioners in Scotland, with the intention of contacting one principal from every dental practice known to the Scottish Dental Estimates Board. A total of 390 (53%) of the questionnaires were returned. If it is assumed that those dentists who did not reply have a low interest in computers then the results of the survey are not likely to lead to an overestimation of trends. Six per cent of the 736 practices that were contacted are using a micro-computer, mainly for practice management and particularly for word processing. In addition, 25% of the replies showed some interest in introducing micro-computers in the future. Thirty-four per cent of current users and 19% of prospective users indicated a high degree of interest in direct data transmission between the practice and the Scottish Dental Estimates Board.


Blastocystis hominis: evidence for human pathogenicity and effectiveness of metronidazole therapy.
1. Clinical symptoms and oral treatment with metronidazole were studied in 103 patients with pure infections by Blastocystis hominis. 2. The results showed that excessive flatulence is the chief gastrointestinal symptom associated occasionally with diarrhoea and abdominal cramps. All the patients showed good responses with treatment of metronidazole and 74 patients whose stools were reexamined 1-2 months after the treatment demonstrated no signs of infections. 3. It is concluded that B. hominis is a pathogenic intestinal parasite and the infection could be eradicated successfully by oral metronidazole.


Expression of Tryptophan Metabolism Enzymes in Patients with Diffuse Large B-cell Lymphoma and NK/T-cell Lymphoma.
Metabolites of tryptophan (Trp) metabolism in the tumor microenvironment play crucial immunosuppressive roles in various cancers. However, the role of Trp metabolism in diffuse large B-cell lymphoma (DLBCL) or natural killer/T-cell lymphoma (NK/TCL) remains unelucidated. We investigated the potential role of Trp metabolism in a cohort of 43 patients with DLBCL and 23 with NK/TCL. We constructed tissue microarrays and performed in situ staining of Trp-catabolizing enzymes and PD-L1 using immunohistochemistry (IHC). We observed 14.0% positive staining of IDO1 in DCBCL and 60.9% in NK/TCL; 55.8% of IDO2 in DCBCL and 95.7% in NK/TCL; 79.1% of TDO2 in DCBCL and 43.5% in NK/TCL; 29.7% of IL4I1 in DCBCL and 39.1% in NK/TCL. However, IDO1, IDO2, TDO2, and IL4I1 positivity did not significantly differ between PD-L1+ and PD-L1- biopsy tissue samples of NK/TCL; nonetheless, a positive correlation of IDO1 (r = 0.87, p < 0.001), IDO2 (r = 0.70, p < 0.001), TDO2 (r = 0.63, p < 0.001), and IL4I1 (r = 0.53, p < 0.05) with PD-L1 expression was observed in the TCGA-DLBCL dataset. Finally, immunohistochemical (IHC) analysis revealed the lack of superior prognostic effect with higher expression of Trp enzymes in DLBCL and NK/TCL. Furthermore, IDO1, IDO2, TDO2, and IL4I1 expression, as well as survival rates, did not significantly differ across all groups in the TCGA-DLBCL cohort. Collectively, our findings provide novel insights into the enzymes involved in Trp metabolism in DLBCL and NK/TCL and their association with PD-L1 expression, which offers potential strategies to combine Trp-metabolism enzyme inhibitors with anti-PD-L1 or other immunotherapeutic strategies in clinical DLBCL or NK/TCL treatment.


Administration sequence-dependent antitumor effects of paclitaxel and 5-fluorouracil in the human gastric cancer cell line MKN45.
The clinical outcome of gastric cancer patients has been improved by combination of 5-fluorouracil (5-FU) and paclitaxel (PXL). However, the optimal schedule of this combination has not been determined. The efficacies of sequential administrations of 5-FU and PXL on the gastric cancer cell line MKN45 were investigated using a WST-8 colorimetric assay. The cell cycle distribution of each drug was evaluated by flow-cytometry. Furthermore, the mechanism of antitumor activity enhancement by the administration sequence was investigated by western blotting. MKN45 cell growth was significantly inhibited by each drug in a dose- and time-dependent manner. The cytotoxicities of PXL followed by 5-FU were significantly greater than those of 5-FU followed by PXL. The flow-cytometric analysis revealed that PXL exposure caused viable cell accumulation in G2/M phase in a dose-dependent manner. Western blotting showed that PXL exposure followed by 5-FU up-regulated Chk1 and Wee1 protein expressions until PXL removal and 5-FU exposure, when these expressions gradually decreased to their basal levels. 14-3-3sigma protein expression was significantly up-regulated upon PXL treatment followed by 5-FU. Interestingly, Mad2 protein expression with PXL treatment followed by 5-FU gradually increased after the PXL removal and 5-FU exposure. PXL followed by 5-FU administration may be the optimal sequence for treatment of gastric cancer. The enhanced viable cell accumulation after PXL pretreatment may be related to G2 arrest. After PXL removal and 5-FU exposure, the cells progressing to M phase may undergo cell death by mitotic catastrophe due to DNA damage caused by 5-FU exposure.


Oral and dental manifestations in Rubinstein-Taybi syndrome: report of a rare case.
Rubinstein-Taybi syndrome, or broad thumb-hallux syndrome, is a well-defined rare congenital disorder characterised by postnatal growth deficiency, craniofacial dysmorphism, broad thumbs and great toes, and mental retardation (intellectual disability). Occurrence may be either sporadic or through autosomal dominant inheritance. Reports of Rubinstein-Taybi syndrome are scarce in the literature. This case report describes the oral and dentofacial findings of Rubinstein-Taybi syndrome affecting a 13-year-old Indian female, including the uncommon presence of talon cusps and an unerupted supernumerary tooth.


Highlighting adalimumab as a treatment option for systemic treatment of toxic epidermal necrolysis: A case series from a tertiary specialised burns centre.
Toxic epidermal necrolysis and Stevens-Johnson Syndrome describe a spectrum of severe cutaneous skin reactions constituting a medical emergency, and no formal treatment guidelines exist to direct systemic immunosuppressive therapy although referral to a burns unit and wound management remains a mainstay of treatment. We performed a retrospective chart review on all patients at a single centre with TEN between 2017 to 2021 to compare clinical characteristics and outcomes of those treated with the tumour necrosis factor-alpha (TNF-α) inhibitor adalimumab against non-TNF-α immunosuppressants such as glucocorticoids, intravenous immunoglobulin and cyclosporine. All patients treated with adalimumab had successful resolution of their TEN, resulting in a mean duration of hospital admission of 22.5 days compared to 33 days for patients treated with non-TNF-α inhibitors. We highlight adalimumab as a promising systemic immunomodulator in the treatment of TEN with efficacy comparable to other immunosuppressive agents and associated with a shorter duration of hospital admission.


Blood flow suspension in tapered stenosed arteries for Walter's B fluid model.
In the present article, I have studied the blood flow of a Walter's B fluid through a tapered artery with a stenosis. The problem is modeled in cylindrical coordinates system. The analytical solutions have been carried out using regular perturbation method by taking α as perturbation parameter. The expressions for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat have been evaluated. The graphical results of different types of tapered arteries (i.e. converging tapering, diverging tapering, non-tapered artery) have been examined for different parameters of interest.


Effect of non-select menus on weight and eating concern in adolescents hospitalized with anorexia nervosa.
The objective of this study was to assess the impact of food service menu type (i.e., non-select versus select) on weight restoration and eating concern for adolescent patients hospitalized with Anorexia Nervosa. Charts of 40 adolescents (mean age 13.3 +/- 2.2 years) were reviewed. Rate of weight gain was significantly increased when non-select menus were used (0.95 kg/wk versus 0.72 kg/wk [p < .03]). No significant differences in total weight gain, length of stay, or eating concern were observed. Non-select menus significantly increase rate of weight restoration in children and adolescents hospitalized with Anorexia Nervosa.