Single-Nucleotide Variations, Insertions/Deletions and Copy Number Variations in Myelodysplastic Syndrome during Disease Progression Revealed by a Single-Cell DNA Sequencing Platform.
Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective hematopoiesis, cytopenia, dysplasia, and clonal instability, leading to leukemic transformation. Hypomethylating agents are the mainstay of treatment in higher-risk MDS. However, treatment resistance and disease transformation into acute myeloid leukemia (AML) is observed in the majority of patients and is indicative of a dismal outcome. The residual cell clones resistant to therapy or cell clones acquiring new genetic aberrations are two of the key events responsible for drug resistance. Bulk tumor sequencing often fails to detect these rare subclones that confer resistance to therapy. In this study, we employed a single-cell DNA (sc-DNA) sequencing approach to study the clonal heterogeneity and clonal evolution in two MDS patients refractory to HMA. In both patients, different single nucleotide variations (SNVs) or insertions and deletions (INDELs) were detected with bulk tumor sequencing. Rare cell clones with mutations that are undetectable by bulk tumor sequencing were detected by sc-DNA sequencing. In addition to SNVs and short INDELs, this study also revealed the presence of a clonal copy number loss of DNMT3A, TET2, and GATA2 as standalone events or in association with the small SNVs or INDELs detected during HMA resistance and disease progression.


The Clinical Dilemma of Anticoagulation Use in Patients with Cerebral Amyloid Angiopathy and Atrial Fibrillation.
This review highlights current management of patients with concomitant cerebral amyloid angiopathy (CAA) and atrial fibrillation (AF). We review quantifying risk of ischemic and hemorrhagic stroke as well as treatments to minimize future risk. Ischemic stroke risk in AF can be quantified by CHA2DS2-VASc and assessing left atrial echocardiographic characteristics. Patients deemed not low risk by CHA2DS2-VASC should be anticoagulated. CAA increases intracranial hemorrhage risk. CAA biomarkers include cortical microbleeds (CMBs), cortical superficial siderosis (cSS), convexal subarachnoid hemorrhage (cSAH), and lobar intracerebral hemorrhage (ICH). CAA with prior lobar ICH has an annual recurrence rate of 8.9%. CAA with cSAH carries an even higher annual lobar ICH risk of 19%. CMBs are associated with a dose-dependent risk of ICH, which rises with OACs. In patients with AF, antithrombotics should be avoided in CAA with predominant ICH, cSS, or cSAH features. Those with ≥ 2 CMB require in-depth risk-benefit analysis using a multidisciplinary approach.


Glucose transporter GLUT12-functional characterization in Xenopus laevis oocytes.
We have recently identified and cloned the cDNA of a new member of the glucose transporter family that has been designated GLUT12. GLUT12 possesses the structural features critical to facilitative transport of glucose but the key to understanding the possible physiological roles of this novel protein requires analysis of functional glucose transport. In the current study, we have utilized the Xenopus laevis oocyte expression system to assay transport of the glucose analog 2-deoxy-D-glucose and characterize the glucose transport properties and hexose affinities of GLUT12. Our results demonstrate that GLUT12 facilitates transport of glucose with an apparent preferential substrate affinity for glucose over other hexoses assayed. The results are significant to understanding the potential role and importance of GLUT12 in insulin-sensitive tissues and also cells with high glucose utilization such as cancer cells.


Association between prenatal exposure to bisphenol a and birth outcomes: A systematic review with meta-analysis.
Previous studies investigated the relation of prenatal exposure to bisphenol A (BPA) and birth outcomes, but these results were inconsistent. The aim of this study was to investigate the relation of prenatal exposure to BPA and birth outcomes, provide comprehensive results based on current studies. The PubMed, Cochrane databases, and Web of Science databases were searched systematically by two researchers respectively from their inceptions to Oct. 2018, using the following keywords "bisphenol A, birth weight, birth length, head circumference, gestational age, birth outcomes". We extracted β coefficient and 95% confidence interval (CI) or β coefficient and standard deviation (SD) from included study. The subgroup analysis was performed to evaluate the potential heterogeneity between studies. We conducted sensitivity analysis by excluding the each individual study to assess the results whether were stable. Finally, the publication bias was performed by accumulative forest plot. Seven studies with 3004 participants met the inclusion criteria. BPA had significant positively association with birth weight (β = 21.92, 95%CI: 1.50-42.35, P = .04). No significant associations were found between BPA and birth length, head circumference and gestational age (All of P > .05). This meta-analysis demonstrated that the BPA was positively associated with birth weight. Therefore, further studies are needed to investigate the critical sensitive period of influencing fetal development and to investigate the difference on gender.


Identification of oxygen responsive elements in the 5'-flanking region of the human glutathione peroxidase gene.
The -1389 to +588 region of the human genomic glutathione peroxidase gene (hgpx1) was amplified using the polymerase chain reaction. This DNA fragment was cloned and sequenced, and various deletion constructs derived from the hgpx1 5'-flanking region were fused to the chloramphenicol acetyltransferase gene. These reporter genes were analyzed in transient transfection assays using primary cultured human ventricular cardiomyocytes obtained from patients with tetralogy of Fallot. Two distinct regions upstream from the transcription start site, which was determined using S1 nuclease analysis, were identified to be responsive to the oxygen tension in culture (pO2 values of 150 or 40 mm Hg). Methylation interference footprinting assays revealed proteins closely apposed to two sequences located at -1232 to -1213 and -282 to -275. We have designated these oxygen responsive elements ORE1 and ORE2, respectively. Gel mobility shift assays using double-stranded oligonucleotides corresponding to each site have demonstrated the formation of specific complexes using both cultured human cardiomyocyte and HeLa nuclear extracts. ORE1 and ORE2 bind disparate proteins with equal precision as bound complexes could be competed away with identical sequences but not with either the other ORE or an unrelated sequence. Insertion of these oxygen responsive elements into a reporter gene governed by a SV40 promoter similarly regulated chloramphenicol acetyltransferase activity according to the oxygen tension in culture.


Effects of riboflavin-2',3',4',5'-tetrabutyrate and flavin adenine dinucleotide on the platelet aggregation induced by hydrogen peroxide.
Both riboflavin-2',3',4',5'-tetrabutyrate and flavin adenine dinucleotide (FAD), especially the latter, could inhibit H2O2-induced platelet aggregation. FAD enhanced the glutathione reductase activity of platelets. FAD might exert its inhibitory effect on the H2O2-induced platelet aggregation via the glutathione reductase and peroxidase system.


Cytotoxicity and genotoxicity induced by the photochemical alkoxyl radical source N-tert-butoxypyridine-2-thione in L5178Y mouse lymphoma cells under UVA irradiation.
The cell-damaging effects of N-tert-butoxypyridine-2-thione (tBuOPT), which generates alkoxyl and thiyl radicals on photolysis, have been investigated in L5178Y mouse lymphoma cells. The UVA irradiation of 2.5 microM tBuOPT inhibits strongly cell growth and cell viability, causes pronounced membrane damage, and induces micronuclei. Without irradiation, tBuOPT does not cause any cell damage at 2.5 microM concentration. The phototoxicity of tBuOPT is effectively inhibited by the radical scavenger glutathione, while the photogenotoxicity (micronuclei induction) is not affected by this strong hydrogen-atom donor. Thus, for the cytotoxicity and genotoxicity different reactive species seems to be responsible. The cytotoxicity is presumably caused by oxyl radicals, which are derived from tert-butoxyl radicals generated by photocleavage of tBuOPT, while in the genotoxicity the less reactive pyridyl-2-thiyl radicals appear to play a role. These results demonstrate that N-alkoxypyridinethiones are useful photochemical sources of oxyl and thiyl radicals to elucidate biological effects caused by these free radicals.


Role of biomarkers in the diagnosis of invasive aspergillosis in immunocompromised patients.
Invasive aspergillosis is one of the important causes of infection in immunocompromised patients. This study aimed to evaluate the roles of biomarkers in the diagnosis of invasive aspergillosis and their relationship with antifungal stewardship programs. 190 sera from 52 immunocompromised patients and volunteer individuals were included in this study. 18 immunocompromised volunteers without IA and 34 patients with probable and proven aspergillosis according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group consensus definitions were entered in this study. The respective sera were evaluated for procalcitonin, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels; white blood cells count (WBC) count, C reactive protein (CRP), lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) values. Demographic data and clinical characteristics of patients were extracted from their files. The male-to-female ratio and mean age of patients were 22/12 and 38.9 years, respectively. The hematologic disorder was the most predisposing factor (29/34, 85.3%). Sensitivity of biomarkers for diagnosis of invasive aspergillosis was 70.6% (cut off value > 190 pg/mL for sTREM-1, 71% (cut off value > 260 pg/mL) for PCT, 85.3% (cut off value > 193 U/L) for LDH, 94.1% (cut off value > 8 mg/l) for CRP, 64.7% (cut off value < 5200 cells/ml) for WBC, and 85.3% (cut off value > 23 mm/h) for ESR. Twelve patients died, with significantly increased sTREM-1 levels and decreased WBC count in them. According to our data, evaluation of the biomarkers can help in the diagnosis, management, and prediction of the severity of Aspergillus infection, and the rational use of antifungal agents in immunocompromised patients.


Decrease in triglyceride level by bezafibrate is related to reduction of recurrent coronary events: a Bezafibrate Infarction Prevention substudy.
Fibrates were reported to be effective in reducing recurrent coronary events in coronary heart disease patients with elevated triglycerides. It is not known whether this effect is related to the extent of triglyceride reduction. Participants comprised 3090 coronary heart disease patients enrolled in the Bezafibrate Infarction Prevention study, which showed a nonsignificant reduction (9.4%; P=0.26) in fatal or nonfatal myocardial infarction and sudden death during a mean follow-up time of 6.2 years. Significant reduction in triglyceride serum level was evident only among patients allocated to bezafibrate, ranging between 0.06 mmol/l (5 mg/dl) in the lowest decile of baseline triglycerides level and 0.68 mmol/l (60 mg/dl) in the highest baseline decile. The extent of triglyceride reduction with bezafibrate was significantly associated with the reduction of risk; relative risk reduction of 55% (hazards ratio: 0.45; 95% confidence interval: 0.24-0.84) was observed among patients with baseline triglycerides>or=2.26 mmol/l who reduced triglyceride level to >0.50 mmol/l (>44.3 mg/dl). In contrast, the risk of recurrent events among patients treated with bezafibrate and achieving less triglyceride reduction or failing to reduce triglyceride level was not significantly different from that of patients treated with placebo. Bezafibrate treatment was associated with significant risk reduction among coronary heart disease patients with elevated triglyceride levels that substantially reduced their triglyceride level with treatment.


Apposition and resorption of bone during oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD).
The effects of 1.5-2 years oral administration of disodium (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) on bone metabolism were studied in male and female rats. APD was mixed in the food at levels of 500, 2,000 and 10,000 ppm. A dose-dependent increase in metaphyseal bone was found, indicative of continued inhibition of bone and cartilage resorption. APD did not affect mineralization of bone and cartilage, primary bone formation, or periosteal apposition. A short-term metabolic balance study was performed to compare the effects of oral with subcutaneous APD. Absorption of APD was in the order of 0.2%. Oral APD increased absorption of phosphate, probably by complexation of calcium with APD. The excess absorbed phosphate increased phosphaturia and decreased urinary calcium.


Natural Biowaste Derived Fluorescent Carbon Quantum Dots: Synthesis, Characterization and Biocompatibility Study.
In this present study, a straightforward and affordable method for the environmentally safe synthesis of carbon quantum dots (CQDs) by employing human hair as the carbon source without any need of chemicals was synthesized. CQDs obtained from human hair was further functionalized with Poly-L-Lysine to form PLLCQDs. The synthesized PLLCQDs was demonstrated numerous advantageous characteristics like strong fluorescence intensity, superior photostability, and outstanding water solubility. Various physicochemical characterization was employed to confirm successful formation of PLLCQDs including UV-vis Spectroscopy, Fluorescence Spectroscopy, Fourier Transform Infrared (FTIR) Spectroscopy, Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). The size of synthesized PLLCQDs is 3 nm. The resultant PLLCQDs exhibited strong blue emission with a quantum yield of 28%. Under UV light, the synthesized PLLCQDs emit blue (at 365nm) fluorescence. The optimization of synthesis parameters including synthesis method, effect of reaction temperature, effect of reaction time and effect of reaction concentration have a significant impact on the quality and quantity of synthesized PLLCQDs, as well as their properties and applications. The effect of pH and UV radiation on synthesized PLLCQDs exhibited excellent photo and chemical stability. The cytotoxicity of bulk system (Hair precursor) and PLLCQDs was evaluated using fibroblast cell line (L929). The cell viabilities of 99.47% was obtained from L929 cells using MTT assay and it can applicably function as agents for cell labelling as a good bioimaging probe.


The RAGE pathway: activation and perpetuation in the pathogenesis of diabetic neuropathy.
The molecular mechanisms underlying loss of pain perception in diabetic neuropathy are poorly understood. Experimental diabetic neuropathy models recently provided evidence that engagement of the receptor for advanced glycation end products (RAGE) and RAGE-dependent sustained activation of the proinflammatory transcription factor nuclear factor kappa B might significantly contribute to reduced nociception. Most importantly, diabetes-induced loss of pain perception is largely prevented in RAGE-deficient mice compared to RAGE-bearing wild-type mice. Identifying RAGE-dependent inflammation as one pathomechanism underlying neuronal dysfunction might provide the basis for new therapeutic approaches.


Effects of MCI-225 on memory and glucose utilization in basal forebrain-lesioned rats.
The effects of MCI-225 on amnesia, the cerebral glucose metabolism, and choline acetyltransferase (ChAT) activity in basal forebrain (BF)-lesioned rats were studied in comparison with those of tacrine. Bilateral BF lesions with ibotenic acid impaired the performance in passive avoidance (PA) tasks. Single administration of MCI-225 (10 mg/kg, PO) after a 2-week postoperative recovery period, increased the escape latencies in the PA task, but was not statistically significant. Repeated administration of MCI-225 (0.3 and 1 mg/kg, PO for 6 days) significantly reversed the PA failure. The BF-lesioned rat exhibited a marked decrease in the local cerebral glucose utilization (LCGU) in the frontal cortex, parietal cortex, and caudate-putamen. MCI-225 (1 mg/kg, PO for 5 days) significantly ameliorated the reduction of the LCGU in the parietal cortex. MCI-225 did not change the decrease in the cortical ChAT activity induced by the BF lesion. Repeated administration of tacrine reversed the PA failure (0.3 mg/kg, PO) but failed to prevent the decrement in the LCGU and the ChAT activity. These results suggest that MCI-225 could be effective in the treatment of senile dementia of the Alzheimer type, which is accompanied with both deficit in the BF-cortex cholinergic neuron and cerebral glucose hypometabolism.


Measurement of background gamma radiation in the northern Marshall Islands.
We report measurements of background gamma radiation levels on six islands in the northern Marshall Islands (Enewetak, Medren, and Runit onEnewetak Atoll; Bikini and Nam on Bikini Atoll; and Rongelap on Rongelap Atoll). Measurable excess radiation could be expected from the decay of (137)Cs produced by the US nuclear testing program there from 1946 to 1958. These recordings are of relevance to safety of human habitation and resettlement. We find low levels of gamma radiation for the settled island of Enewetak [mean = 7.6 millirem/year (mrem/y) = 0.076 millisievert/year (mSv/y)], larger levels of gamma radiation for the island of Rongelap (mean = 19.8 mrem/y = 0.198 mSv/y), and relatively high gamma radiation on the island of Bikini (mean = 184 mrem/y = 1.84 mSv/y). Distributions of gamma radiation levels are provided, and hot spots are discussed. We provide interpolated maps for four islands (Enewetak, Medren, Bikini, and Rongelap), and make comparisons to control measurements performed on the island of Majuro in the southern Marshall Islands, measurements made in Central Park in New York City, and the standard agreed upon by the United States and the Republic of the Marshall Islands (RMI) governments (100 mrem/y = 1 mSv/y). External gamma radiation levels on Bikini Island significantly exceed this standard (P = <<0.01), and external gamma radiation levels on the other islands are below the standard. To determine conclusively whether these islands are safe for habitation, radiation exposure through additional pathways such as food ingestion must be considered.


Recent advances in auxin biosynthesis and homeostasis.
The plant proliferation is linked with auxins which in turn play a pivotal role in the rate of growth. Also, auxin concentrations could provide insights into the age, stress, and events leading to flowering and fruiting in the sessile plant kingdom. The role in rejuvenation and plasticity is now evidenced. Interest in plant auxins spans many decades, information from different plant families for auxin concentrations, transcriptional, and epigenetic evidences for gene regulation is evaluated here, for getting an insight into pattern of auxin biosynthesis. This biosynthesis takes place via an tryptophan-independent and tryptophan-dependent pathway. The independent pathway initiated before the tryptophan (trp) production involves indole as the primary substrate. On the other hand, the trp-dependent IAA pathway passes through the indole pyruvic acid (IPyA), indole-3-acetaldoxime (IAOx), and indole acetamide (IAM) pathways. Investigations on trp-dependent pathways involved mutants, namely yucca (1-11), taa1, nit1, cyp79b and cyp79b2, vt2 and crd, and independent mutants of tryptophan, ins are compiled here. The auxin conjugates of the IAA amide and ester-linked mutant gh3, iar, ilr, ill, iamt1, ugt, and dao are remarkable and could facilitate the assimilation of auxins. Efforts are made herein to provide an up-to-date detailed information about biosynthesis leading to plant sustenance. The vast information about auxin biosynthesis and homeostasis is consolidated in this review with a simplified model of auxin biosynthesis with keys and clues for important missing links since auxins can enable the plants to proliferate and override the environmental influence and needs to be probed for applications in sustainable agriculture. The online version contains supplementary material available at 10.1007/s13205-023-03709-6.


Maintenance and distribution of transgenic mice susceptible to human viruses: memorandum from a WHO meeting.
This Memorandum discusses the use of transgenic mice in poliovirus research and the potential risks to public health. General and specific recommendations are given concerning the maintenance, containment and transport of transgenic animals which are susceptible to pathogenic human viruses, with special attention to transgenic mice susceptible to polioviruses.


The Effect of Progressive Muscle Relaxation on Abdominal Pain and Distension in Colonoscopy Patients.
This study was conducted to examine the effect of progressive muscle relaxation on abdominal pain and distension in colonoscopy patients. A randomized controlled experimental design. The experimental group was informed about progressive muscle relaxation (PMR) and an audio recording was provided. After the colonoscopy, abdominal pain (Visual Analogue Scale (VAS) pain) and distension (VAS distension) scores were assessed, then PMR was applied for 30 minutes and pain scores were determined again. VAS pain and VAS distension scores of the control group were determined after colonoscopy and 30 minutes later. VAS abdominal pain and VAS distension scores were evaluated at the 2nd, 4th, 8th, 12th, 16th, and 24th hour after the procedure on all patients. The day after the colonoscopy, post-test data were collected. The pretest VAS pain and VAS distension mean scores were similar in the intervention and control groups (P > .05). The mean VAS pain and VAS distension scores decreased significantly in the intervention group post procedure (P < .05). PMR was determined to be effective in reducing abdominal pain and distension after colonoscopy.


Development of an adapted version of polar organic chemical integrative samplers (POCIS-Nylon).
POCIS (polar organic chemical integrative samplers) are increasingly used for sampling polar compounds. Although very efficient for a wide range of pollutants, the classic configuration of the device has a number of limitations, in particular for the sampling of highly polar analytes and hydrophobic compounds. This study presents a new version of the POCIS passive sampler which uses a highly porous Nylon membrane of 30 μm pore size, enabling the sampling of hydrophobic pollutants and improving the accumulation rate of other pollutants. This newly designed tool and the classic POCIS were both tested during a laboratory experiment to evaluate the accumulation kinetics of a selection of pesticides and pharmaceuticals. The observed results show unexpected accumulation kinetics for the new version of POCIS. To explain the data, the use of an intraparticulate diffusion model was required, which also enabled us to propose another explanation of the burst effect observed with the classic POCIS, primarily related to the potential wetting of the device as the first step in the accumulation of compounds.


Panhypopituitarism after traumatic head injury.
We describe a case report of panhypopituitarism after traumatic head injury. A previously healthy young man suffered a closed head injury and multiple spinal fractures after a motorcycle accident. His treatment in the intensive care unit was prolonged because of numerous problems with raised intracranial pressure, hemodynamics, and electrolyte balance. Eventually, hypocortisolism and other pituitary hormone deficiencies were diagnosed. Magnetic resonance images showed incoherent pituitary stalk and re-review of the first computed tomography scans of the day of the accident confirmed hemorrhage in the infundibulum. This case and review of the literature suggests that hormone deficiencies are not uncommon after head injuries.


Harnessing nucleic acid technologies for human health on earth and in space.
Nucleic acid therapeutics are a versatile class of sequence-programmable drugs that offer a robust and clinically viable strategy to modulate expression or correct genetic defects contributing to disease. The majority of drugs currently on the market target proteins; however, proteins only represent a subset of possible disease targets. Nucleic acid therapeutics allow intuitive engagement with genome sequences providing a more direct way to target many diseases at their genetic root cause. Their clinical success depends on platform technologies which can support durable and well tolerated pharmacological activity in a given tissue. Nucleic acid drugs possess a potent combination of target specificity and adaptability required to advance drug development for many diseases. As these therapeutic technologies mature, their clinical applications can also expand access to personalized therapies for patients with rare or solo genetic diseases. Spaceflight crew members exposed to the unique hazards of spaceflight, especially those related to galactic cosmic radiation (GCR) exposure, represent another patient subset who may also benefit from nucleic acid drugs as countermeasures. In this review, we will discuss the various classes of RNA- and DNA-targeted nucleic acid drugs, provide an overview of their present-day clinical applications, and describe major strategies to improve their delivery, safety, and overall efficacy.


Femoral neuropathy caused by iliacus hematoma.
Two cases of femoral neuropathy caused by iliacus hematoma occurring during anticoagulant therapy are described. The pathogenesis and the clinical picture of this particular pathology are discussed and the necessity of early surgical decompression is emphasized.


Deficit of preparatory attention in children with frontal lobe epilepsy.
We compared the performance of a sustained attention task by children with epilepsy in either the frontal or temporal lobe. In a new simple task that specifically measures preparatory attention, developed recently by LaBerge, Auclair, and Siéroff [LaBerge, D., Auclair, L., & Siéroff, E. (2000). Preparatory attention: Experiment and theory. Consciousness and Cognition, 9, 396-434], patients responded to a target presented in the centre of the display and ignored a distracter presented at locations to the right or the left side of the target. The distracter was presented prior to the onset of the target and the relative frequency of the distracter to target was varied within a block of trials (from 0% to 67%). Children with frontal lobe epilepsy showed a higher mean slope of response time to the target as a function of distracter probability compared to children with temporal lobe epilepsy or compared to the response time slope of control subjects. The response time slope of children with temporal lobe epilepsy did not differ from that of control subjects. These results indicate that the presence of frontal lobe epilepsy selectively affects the capacity of these patients to resist the interference a distracter.


Tailored Double-Barrel Bypass Surgery Using an Occipital Artery Graft for Unstable Intracranial Vascular Occlusive Disease.
This report describes the need for a tailored approach for intracranial vascular occlusive disease and introduces the usefulness of the OA as a donor artery for interposition graft. A 65-year-old male patient suffered from repeated transient ischemic attack (TIA). Imaging studies revealed complete occlusion of the proximal left side of the internal carotid artery (ICA) and multiple infarction in the watershed zone. We planned superficial temporal artery-middle cerebral artery (STA-MCA) bypass to restore cerebral blood flow and to prevent the progression of infarction. However, the parietal branch of the STA was too small in diameter and not suitable as a single donor for the bypass in order to supply sufficient blood flow. Moreover, the frontal branch of the STA had collateral channels through the periorbital anastomosis into the cerebral cortex that could result in infarction during clamping for anastomosis. We determined that tailored treatment planning was necessary for successful revascularization under these conditions. Thus, we performed a bypass between the parietal branch of the STA and a cortical branch of the MCA as an "insurance bypass." Then we performed another bypass between the frontal branch of the STA and a cortical branch of the MCA using an ipsilateral occipital artery (OA) interposition graft. The patient had no perioperative complications, and postoperative imaging confirmed the restoration of cerebral blood flow. When end-to-side anastomosis in single-branch bypass is not appropriate for cerebral revascularization, a tailored double-barrel "insurance bypass" with an OA interposed graft could be a good alternative treatment modality. In addition, an OA interposition graft is a useful option for double-barrel bypass surgery in such cases of intracranial vascular occlusive disease.


Renal primitive neuroectodermal tumor as a second malignancy after chemotherapy and radiation for Non-Hodgkin's Lymphoma--treatment-related or just poor old bad luck?: A case report.
Peripheral primitive neuroectodermal tumor (PNET) is a rare histology to be found in primary tumors of the kidney. There are less than a hundred cases reported in the English literature. Most of these have been diagnosed after surgery for a renal neoplasm diagnosed on imaging. PNET has rarely been reported as a second malignancy, and has never been reported as a second malignancy after non-Hodgkin's lymphoma (NHL). Herein, we present our case of a 38-year-old female who developed a second malignancy in the kidney after the treatment for NHL.


Induction of preneoplastic hyperplasia and carcinoma by N-methyl-N'-nitro-N-nitrosoguanidine from regenerated mucosa of ulcers induced by iodoacetamide in fundus of rat stomach.
Differences in susceptibility to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of fundic mucosa in various states of regeneration after induction of ulcer with iodoacetamide were examined histologically in male Wistar rats. Iodoacetamide was given to rats in their drinking water, before (Group 1), with (Group 2), or after (Group 3) MNNG. Atypical hyperplasia in the renewed mucosa and pyloric gland metaplasia were observed on the ulcers in Group 1 in higher incidence than in Groups 2 and 3. In addition, adenocarcinoma developed in the ulcer of 2 of 17 effective animals in Group 1. These observations suggest that the mucosa showing pyloric gland metaplasia is more susceptible to MNNG than the young rapidly regenerating mucosa at the margin of ulcers.


The levels of galactosyl diglycerides and the composition of fatty acids of Spirodela oligorrhiza (Lemnaceae) plants cultivated on a nutrient containing 1% glucose were studied. Controls were grown on a medium without glucose. Between the 10(th) and the 25(th) day of growth the ether-soluble lipids of glucose-stimulated plants contained less monogalactosyl diglyceride (MG) but more digalactosyl diglyceride (DG) than controls. In the same time a marked decrease of the relative amount of C(18:3) acid and an increase of that of C(18:2) and C(16:0) acids was observed. These changes of the lipid composition might be one reason for the structural changes in the chloroplast fine structure of glucose-stimulated Spirodela plants.


Depression, Anxiety, Stress and Distress Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Results of a Prospective Cohort Study.
The aim of this study was to describe the levels of depression, anxiety, stress, and distress in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The 21-item Depression, Anxiety and Stress Scale (DASS-21) and Distress Thermometer were administered preoperatively, postoperatively day 10, and at hospital discharge to 169 patients with peritoneal carcinomatosis undergoing CRS and HIPEC. The mean preoperative values for DASS-21 subscale scores were 4.7 (depression), 4.2 (anxiety), and 8.4 (stress), and the mean preoperative Distress Thermometer rating was 4.0. No significant changes in levels of depression, stress, or distress were noted thereafter. The DASS-21 anxiety subscale score significantly increased at hospital discharge (p = .005). Higher levels of preoperative psychological depression, anxiety, stress and distress were associated with worse mental component scores. Higher preoperative depression levels were associated with the provision of more clinical psychologist occasions of service, and higher preoperative distress levels were associated with younger age. Preoperative psychological measures are important for ensuring CRS and HIPEC patients that require additional support are identified and provided with ongoing psychological interventions.


The management of hemorrhage from severe missile injuries using Foley catheter balloon tamponade.
Foley catheter tamponade is introduced as a method of arresting hemorrhage from maxillofacial wounds due to war missiles. Three cases representing severe casualties are presented and the technique described.


The vanadium chloroperoxidase from the fungus, Curvularia inaequalis. Evidence for the involvement of a histidine residue in the binding of vanadate.
The binding of vanadate to the novel vanadium chloroperoxidase from C. inaequalis was investigated. Reconstitution experiments of apo-chloroperoxidase by vanadate at different pH values showed that in the pH 6-7 range an acid/base group is present which affects the binding of the vanadate. It is proposed that this group is a histidine. This hypothesis was tested by specifically modifying this residue using diethylpyrocarbonate. In the apo-enzyme 9 histidines were modified, whereas in the holo-enzyme 6 histidines were modified. Modification with diethylpyrocarbonate had no effect on the chlorinating activity of the holo-enzyme, but when the apo-enzyme was modified the reactivation by vanadate was strongly inhibited. We conclude that histidine in the active site of chloroperoxidase is involved in the binding of vanadate.


A practical approach to evidence-based dentistry: X: How to avoid being misled by clinical studies' results in dentistry.
Clinicians using evidence to inform decisions on a daily basis have access to a number of tools to help them judge the importance of discriminating studies conducted using suboptimal methods from more rigorous ones. Many checklists have been developed to facilitate and guide clinicians to identify and critically appraise clinical studies. However, only limited guidance is available addressing how clinicians can identify misleading claims from those that can be supported reliably by study results. In this final article of a series of 10, the authors provide key concepts that clinicians can use to help them avoid using biased inferences or statements that are "too good to be true."


Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents.
In trying to develop new anticancer agents, a series of 1H-pyrazolo[3,4-b]pyridine derivatives was designed and synthesized. Fifteen compounds were evaluated in vitro for their anti-proliferative activity against HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Additionally, DNA binding affinity of the synthesized derivatives was investigated as a potential mechanism for the anticancer activity using DNA/methyl green assay and association constants assay. Compounds 19, 20, 21, 24 and 25 exhibited good activity against the four cancer cells comparable to that of doxorubicin. Interestingly, DNA binding assay results were in agreement with that of the cytotoxicity assays where the most potent anticancer compounds showed good DNA binding affinity comparable to that of doxorubicin and daunorubicin. Furthermore, a molecular docking of the tested compounds was carried out to investigate their binding pattern with the prospective target, DNA (PDB-code: 152d).


Molecular phylogeny and a modified approach of character-based barcoding refining the taxonomy of New Caledonian freshwater gastropods (Caenogastropoda, Truncatelloidea, Tateidae).
The islands of New Caledonia represent one of the world's biodiversity hotspots with many endemic species including freshwater gastropods of the family Tateidae. A phylogenetic analysis based on the mitochondrial COI and 16S rRNA and the nuclear ITS2 genes revealed two cryptic genera, Crosseana gen. n. and Novacaledonia gen. n. In order to provide character-based diagnoses we modified a DNA barcoding approach identifying strings of pairwise diagnostic characters, i.e. alignment positions, at which two genera are alternatively fixed for different nucleotides. The combination or string of all pairwise diagnostic characters was unique for each genus. Inconsistent mitochondrial and nuclear topologies suggest that Hemistomia cockerelli Haase and Bouchet, 1998 and H. fabrorum Haase and Bouchet, 1998, two morphologically well-defined species, hybridize. The age of the most recent common ancestor of the New Caledonian radiation of Tateidae was estimated at 24.6±9.5 MY. These findings are in line with the notion that New Caledonia is rather a Darwinian island that was colonized after an extended phase of submergence - in case of the tateids probably from Australia - despite being a fragment of Gondwanaland.


Academic and professional paths of narcoleptic patients: the Narcowork study.
To study educational and professional pathways of narcoleptic patients and examine demographic, disease-related and environmental factors associated with a better academic and professional prognosis. In sum, 69 narcoleptic patients (51 narcolepsy type 1 and 18 narcolepsy type 2, age 42.5 ± 18.2 years) were enrolled in this pilot monocentric cross-sectional study with a comparison group (80 age- and sex-matched controls) between October 2017 and July 2018 in Lyon Center for Sleep Medicine. They completed questionnaires about their academic and professional trajectories and specific scales of quality of life (EuroQol quality of life scale EQ-5D-3L), depression (beck depression inventory, BDI), sleepiness (Epworth Sleepiness Scale, ESS) and narcoleptic symptoms severity (narcolepsy severity scale, NSS). No difference in grade repetition or final obtained diploma was observed between patients and controls, but patients evaluated their academic curricula as more difficult (45.5% vs 16.9%, p = 0.0007), complained for more attentional deficits (75% vs 22.1%, p < 0.0001), and had needed more educational reorientation (28.6% vs 9.9%, p = 0.01). Even if no difference was observed in occupational category and professional status, patients expressed significantly less satisfaction about their work. Patients had more signs of depression [OR severe depression = 4.4 (1.6-12.6), p = 0.02] and their quality of life was significantly decreased (67.3 ± 18.4 vs 80.6 ± 13.2, p = 0.0007) as compared to controls. Multivariate analysis showed that a more favorable professional career was associated with a better quality of life. Educational and professional pathways do not seem to be significantly impaired in narcoleptic patients, but their experience and quality of life are affected. These findings may allow to reassure patients and should lead to a more comprehensive management of the disease. Narcowork, https://clinicaltrials.gov/ct2/show/NCT03173378, N° NCT03173378.


Climatic correlates of live-bearing in squamate reptiles.
We use a stepwise multiple regression procedure to correlate geographic patterns in the distribution of live-bearing reptilian species with patterns in climatic variables, in both Australia and North America. Previous authors have interpreted reptilian live-bearing as an evolutionary adaptation to cold climates. Our results indicate that environmental temperature and irradiance measures are no more highly correlated with the percent live-bearing species than are measures of precipitation, evaporation and humidity. We conclude that, except in very cold environments in North America, environmental temperatures seem to play little role in the relative success of live-bearing versus egg-laying reptilian reproductive strategies. It appears from previous work that reptilian live-bearing evolves mainly, or exclusively, because of the advantage it confers in enabling successful reproduction in cold climates. The present study suggests that the subsequent radiation of live-bearing reptilian species may be due to entirely different selective forces.


Extremely elevated activity of serum alkaline phosphatase in gestational diabetes: a case report.
We report a case of a 25-year-old pregnant woman with gestational diabetes and increased activity (25-fold) of placental isozyme of alkaline phosphatase. Abdominal ultrasonographic scan revealed no hepatobiliary disease. After delivery, the alkaline phosphatase level decreased but did not return to the reference range. Similar abnormalities were found in the patient's first-degree relatives, which included a mother and a sister.


The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies.
To determine whether intake of tomato products reduces the risk of prostate cancer using a meta-analysis. We systematically searched MEDLINE and EMBASE and contacted authors to identify potential studies. Log relative risks (RRs) were weighed by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). Logistic regression and Poisson regression analyses were used to determine the effect produced by a daily intake of one serving of tomato product. Eleven case-control studies and 10 cohort studies or nested case-control studies presented data on the use of tomato, tomato products, or lycopene and met our inclusion criteria. Compared with nonfrequent users of tomato products (1st quartile of intake), the RR of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89 (95% CI 0.80-1.00). For high intake of cooked tomato products, this RR was 0.81 (95% CI 0.71-0.92). The RR of prostate cancer related to an intake of one serving/day of raw tomato (200 g) was 0.97 (95% CI 0.85-1.10) for the case-control studies and 0.78 (95% CI 0.66-0.92) for cohort studies. Our results show that tomato products may play a role in the prevention of prostate cancer. However, this effect is modest and restricted to high amounts of tomato intake. Further research is needed to determine the type and quantity of tomato products with respect to their role in preventing prostate cancer.


Deciphering the transcriptomic insight during organogenesis in Castor (Ricinus communis L.), Jatropha (Jatropha curcas L.) and Sunflower (Helianthus annuus L.).
Cultivation of the castor crop is hindered by various factors and one of the approaches for genetic improvement of the crop is through exploitation of biotechnological tools. Response of castor tissues to in vitro culture is poor which necessitated this study on understanding the molecular basis of organogenesis in cultured tissues of castor, through de novo transcriptome analysis and by comparing with jatropha and sunflower having good regeneration ability. Transcriptome profiling analysis was carried out with hypocotyl explants from castor, jatropha and cotyledons from sunflower cultured on MS media supplemented with different concentrations of hormones. Differentially expressed genes during dedifferentiation and organogenic differentiation stages of callus included components of auxin and cytokinin signaling, secondary metabolite synthesis, genes encoding transcription factors, receptor kinases and protein kinases. In castor, many genes involved in auxin biosynthesis and homeostasis like WAT1, vacuolar transporter genes, transcription factors like short root like protein were down-regulated while genes like DELLA were up-regulated accounting for regeneration recalcitrance. Validation of 62 DEGs through qRT-PCR showed a consensus of 77.4% of the genes expressed. Overall study provides set of genes involved in the process of organogenesis in three oilseed crops which forms a basis for understanding and improving the efficiency of plant regeneration and genetic transformation in castor.


Diethyldithiocarbamate (ditiocarb sodium) effect on arachidonic acid metabolism in human mononuclear cells. Glutathione peroxidase-like activity.
Diethyldithiocarbamate (DTC), a thiol delivery agent, has been shown to significantly reduce the frequency of primary opportunistic infections in HIV-infected patients. This therapeutic effect has been related to the capacity of DTC to reverse the deleterious effects of the oxidative stress occurring in HIV infection. The influence of DTC on the oxygenated metabolism of arachidonic acid (AA) was investigated in mitogen-stimulated human peripheral blood mononuclear cells (PBMC). Upon incubation with PBMC previously labelled with [3H]AA, Concanavalin A (Con A) markedly increased cyclooxygenase and lipoxygenase activities, within 30 min, as judged by thromboxane B2 (TxB2) and hydroxyeicosatetraenoic acid (HETE) production. Con A activation of [3H]AA platelets also increased 12-HETE production but did not induce any TxB2 synthesis. Micromolar concentrations of DTC, added simultaneously with the mitogen, significantly enhanced the synthesis of HETEs above the Con A-induced level while TxB2-induced synthesis was inhibited but only at DTC concentrations higher than 50 microM. In the presence of nordihydroguaiaretic acid, a lipoxygenase inhibitor, which inhibited the Con A-induced synthesis of HETEs by 78%, DTC no longer stimulated HETE production above the Con A-induced level. Reverse phase HPLC analysis showed that Con A increased the PBMC production of 5-, 12- and 15-HETEs. In the presence of 5 microM DTC, 5-HETE production was entirely suppressed whereas the 15-HETE level was markedly enhanced, 12-HETE production by the contaminating platelets remained unchanged. In vitro experiments indicated that DTC alone did not significantly influence 15-hydroperoxyeicosatetraenoic (15-HPETE) production by the soybean 15-lipoxygenase but, in the presence of added reduced glutathione, DTC markedly reduced 15-HPETE into 15-HETE. In addition, DTC was able to substitute for cellular extract in the glutathione peroxidase (GPx) assay system. Taken together, these results indicate that DTC, through its "GPx-like" activity is able to modify the lipoxygenase cascade. Its ability to selectively reduce 15-HPETE known to stimulate immunosuppressive T-cells might help to explain its positive regulatory effect upon the immune system.


Exploring the effects of palm kernel meal feeding on the meat quality and rumen microorganisms of Qinghai Tibetan sheep.
Palm kernel meal (PKM) has been shown to be a high-quality protein source in ruminant feeds. This study focused on the effects of feed, supplemented with different amounts of PKM (ZL-0 as blank group, and ZL-15, ZL-18, and ZL-21 as treatment group), on the quality and flavor profile of Tibetan sheep meat. Furthermore, the deposition of beneficial metabolites in Tibetan sheep and the composition of rumen microorganisms on underlying regulatory mechanisms of meat quality were studied based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry as well as 16S rDNA sequencing. The results of the study showed that Tibetan sheep in the ZL-18 group exhibited superior eating quality and flavor profile while depositing more protein and fat relative to the other groups. The ZL-18 group also changed significantly in terms of the concentration and metabolic pathways of meat metabolites, as revealed by metabolomics. Metabolomics and correlation analyses finally showed that PKM feed mainly affected carbohydrate metabolism in muscle, which in turn affects meat pH, tenderness, and flavor. In addition, 18% of PKM increased the abundance of Christensenellaceae R-7 group, Ruminococcaceae UCG-013, Lachnospiraceae UCG-002, and Family XIII AD3011 group in the rumen but decreased the abundance of Prevotella 1; the above bacteria groups regulate meat quality by regulating rumen metabolites (succinic acid, DL-glutamic acid, etc.). Overall, the addition of PKM may improve the quality and flavor of the meat by affecting muscle metabolism and microorganisms in the rumen.


Resuscitation of older adults in Norway; a comparison of survival and outcome after out-of-hospital cardiac arrest in healthcare institutions and at home.
Perceptions about expected outcome after out-of-hospital cardiac arrest (OHCA) influence treatment decisions, and there is a need for updated evidence about outcomes for the elderly. We conducted a cross-sectional study of cases reported to the Norwegian Cardiac Arrest Registry from 2015 through 2021 of patients 60 years and older, suffering cardiac arrest in healthcare institutions or at home. We examined reasons for emergency medical service (EMS) withholding or withdrawing resuscitation. We compared survival and neurological outcome for EMS-treated patients and explored factors associated with survival using multivariate logistic regression. We included 12,191 cases and the EMS started resuscitation in 10,340 (85%). The incidence per capita of OHCA the EMS were alerted to was 267/100,000 in healthcare institutions and 134/100,000 at home. Resuscitation was most frequently withdrawn due to medical history (n = 1251). In healthcare institutions, 72 of 1503 (4.8%) patients survived to 30 days compared to 752 of 8837 (8.5%) at home (P <.001). We found survivors in all age cohorts both in healthcare institutions and at home, and most of the 824 survivors had a good neurological outcome with a Cerebral Performance Category ≤2 (88%). Medical history was the most frequent reason for EMS not to start or continue resuscitation, indicating a need for a discussion about, and documentation of, advance directives in this age group. When EMS attempted resuscitation, most survivors had a good neurological outcome, both in healthcare institutions and at home.


Nonvisual feeding in a visual planktivore, Xenomelaniris venezuelae.
Studies of the diel feeding patterns of the planktivorous fish, Xenomelaniris venezuelae, in Lake Valencia, Venezuela, revealed that, although the fish is primarily a diurnal feeder, it consumes substantial numbers of Chaoborus larvae and pupae at night. A number of fish species are known which feed on plankton at night, but these fish are filter feeders and their diets largely consist of relatively small, nonevasive prey. Chaoborus, however, is large and agile. Predation by Xenomelaniris in the dark was also studied experimentally. Captured fish were placed in completely darkened aquaria with zooplankton from Lake Valencia. After several hours the plankton was removed and examined for evidence of feeding. The fish were found to consume Chaoborus pupae and fourth instar larvae but not other types of prey. The mode of feeding by Xenomelaniris in the dark is unknown.


Population genetics of Cryptosporidium meleagridis in humans and birds: evidence for cross-species transmission.
Population genetic studies have been used to understand the transmission of pathogens in humans and animals, especially the role of zoonotic infections and evolution and dispersal of virulent subtypes. In this study, we analysed the genetic diversity and population structure of Cryptosporidium meleagridis, the only known Cryptosporidium species that infects both avian and mammalian hosts and is responsible for approximately 10% of human cryptosporidiosis in some areas. A total of 62 C. meleagridis specimens from children, AIDS patients, and birds in Lima, Peru were characterised by sequence analysis of the ssrRNA gene and five minisatellite, microsatellite and polymorphic markers in chromosome 6, including the 60 kDa glycoprotein (gp60), 47 kDa glycoprotein (CP47), a serine repeat antigen (MSC6-5), retinitis pigmentosa GTPase regulator (RPGR) and thrombospondin protein 8 (TSP8). The multilocus sequence analysis identified concurrent infections with Cryptosporidium hominis in four AIDS patients and three children. Unique subtypes of C. meleagridis ranged from eight at the gp60 locus (gene diversity -Hd=0.651), three at the RPGR (Hd=0.556), three at the MSC6-5 locus (Hd=0.242), two at TSP8 (Hd=0.198), to one at CP47 (monomorphic), much lower than that of C. hominis in the same area. Intragenic linkage disequilibrium was strong and complete at all gene loci. Intergenic linkage disequilibrium was highly significant (P<0.001) for all pairs of polymorphic loci. Two major groups of subtypes were seen, with most subtypes belonging to group 1. Within group 1, there was no clear population segregation, and two of the 14 multilocus subtypes of C. meleagridis were found in both AIDS patients and birds. We believe that these results provide the first evidence of a clonal population structure of C. meleagridis and the likely occurrence of cross-species transmission of C. meleagridis between birds and humans.


Eye stabilization reflexes in traumatic and non-traumatic chronic neck pain patients.
Many chronic neck pain patients experience problems with vision. These problems are possibly induced by deviations of the eye stabilization reflexes. It is not known whether these eye reflex alterations occur both in traumatic and non-traumatic neck pain patients. To investigate if the cervico-ocular reflex (COR) and the vestibulo-ocular reflex (VOR) are changed in tertiary care patients with prolonged, chronic neck pain with various origin of complaints. Cross sectional study. Ninety-one chronic neck pain patients were subdivided into three groups by origin of complaints, and compared with healthy controls. COR and VOR gains were measured with an infrared eye tracking device with the subject sitting on a rotating chair in a darkened room and with the head fixed. Neck pain patients had a higher COR gain (median 0.41, IQR 0.289) compared with healthy controls (median 0.231, IQR 0.179). The mean COR gain did not differ between the three patient groups (Whiplash Associated Disorders 0.444 (SD 0.221); traumatic 0.397 (SD0.205); non-traumatic 0.468 (SD0.236)). There was no difference in VOR gain between the groups. Chronic neck pain patients, who already received primary care, still have an elevated cervico-ocular reflex. The origin of complaints did not seem to be associated with this deviant oculomotor behavior.


[Protein and peptide factors from Bacillus sp.739 inhibit the growth of phytopathogenic fungi].
Thermolabile peptides inhibiting the growth of Helminthosporium sativum, a facultative phytopathogen, have been isolated from the low-molecular-weight fraction of extracellular metabolites of the strain Bacillus sp. 739. Paper chromatography of the fraction, followed by bioautography, revealed the presence of three components exhibiting antifungal activity. These components were separated by gel chromatography on Toyopearl HW-40. SDS-PAGE (the Laemmli procedure) demonstrated that only one component was a protein (MW, approximately 14 kDa). The other two substances were polypeptides with molecular weights less than 6 kDa each. The protein factor inhibited the growth of H. sativum with a minimum effective concentration of 0.1 to 0.2 mg/ml.


Plasma lipoproteins in posttraumatic stress disorder patients compared to healthy controls and their associations with the HPA- and HPT-axis.
Based on studies among primarily male veteran subjects, lipoproteins are thought to mediate the association of posttraumatic stress disorder (PTSD) with cardiovascular disease (CVD). However, recent civilian studies with female samples or samples with both sexes represented provide little evidence for this association. Gender, diet and sex-specific effects of stress hormones on lipoproteins may explain this dissociation in findings. Cross-sectional analysis of plasma concentrations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG) in a male and female sample of 49 PTSD-patients due to civilian trauma and 45 healthy controls. Second, we related these lipoproteins to several stress hormones (prolactin, cortisol, DHEA(S), TSH, T4). Patients showed lower LDL (p=0.033) and LDL:HDL ratio (p=0.038) compared to controls, also when adjusting for diet. Sex influenced the effect of having PTSD on LDL with only male patients having lower values than male controls (p=0.012). All stress hormones were associated with several lipoproteins, mostly in a sex-dependent manner. For LDL, a significant sex-by-cortisol effect (p<0.001), having PTSD-by-sex-by-DHEA (p<0.001), having PTSD-by-sex-by-DHEAS (p=0.016) and having PTSD-by-sex-by-prolactin (p=0.003) was found. In this male and female civilian sample we found a somewhat more favorable lipoprotein profile in PTSD-patients in contrast to evidence from strictly male veteran samples exhibiting a less favorable lipoprotein profile. Male patients did not exhibit a worse lipoprotein profile than female patients and therefore gender cannot explain the contradiction in evidence. Additionally, we found that PTSD-related stress hormones are associated with lipoproteins levels in patients in a sex-specific manner. Specific configurations of stress hormones may contribute to CVD in male patients or protect in female patients. Further research on these configurations could indicate which PTSD-patients are especially at risk for CVD and which are not. This could guide future precision medicine efforts to prevent and treat the still growing burden of CVD morbidity and mortality in PTSD.


Characterizing the potential estrogenic and androgenic activities of two disinfection byproducts, mono-haloacetic acids and haloacetamides, using in vitro bioassays.
Exposure to disinfection byproducts (DBPs) is potentially related to cytotoxic, genotoxic, mutagenic, and tumorigenic effects in humans, in addition to their adverse effects on the environment. However, their impacts on endocrine disruption, especially reproductive toxicity, remain largely unknown. In this study, the estrogenic and androgenic activities of DBPs and corresponding antagonistic activities were investigated using a yeast-based reporter assay, focusing on haloacetic acids and haloacetamides. We also examined the cytotoxicity of DBPs and mechanisms of antagonistic activities. Of the DBPs assayed, iodoacetamide (IAM) and bromoacetamide (BAM) were the most cytotoxic, with LC50 values of 0.0462 and 0.0537 mM, respectively, followed by chloroacetic acid (CAA; LC50 = 4.87 mM) and chloroacetamide (CAM; LC50 = 5.28 mM). Iodoacetic acid (IAA) and bromoacetic acid (BAA) were the least cytotoxic, with LC50 values of 5.52 and 6.35 mM, respectively. IAA (EC10 = 0.00573 mM; EC50 = 0.0215 mM) exhibited most potent estrogenic activity, and CAA (EC10 = 0.0434 mM) and BAM (EC10 = 0.0150 mM) showed weak estrogenic and androgenic activities, respectively. By contrast, IAM exhibited anti-estrogenic effects. These results suggest that DBPs interact with hormone receptors.


ATP synthesis associated with the conversion of hexachlorocyclohexane related compounds.
Clostridium rectum strain S-17 converts gamma-1,2,3,4,5,6-hexachlorocyclohexane (HCH) related compounds to chlorobenzenes. The metabolites from gamma-1,2,3,4,5,6-hexachlorocyclohexene and gamma-1,3,4,5,6-pentachlorocyclohexene are identified as 1,2,4-trichlorobenzene and 1,4-dichlorobenzene, respectively. ATP synthesis, converting these chlorinated compounds, is observed in the cell suspension of C.rectum as indicated by luciferase-luciferin reaction and phosphorylation of 32P-labeled phosphate. These observation lead to the conclusion that HCH and related compounds serve as artificial electron acceptors of the Stickland reaction, and therefore, the reductive dechlorination is associated with ATP synthesis.


A case report of 2 distinct primary sarcomas arising in an extremity in rapid succession.
A 59-year-old male presented with a primary synovial sarcoma around his knee. Two months after resection, he presented with a new, rapidly-growing mass in the ipsilateral proximal thigh. A biopsy of the new mass demonstrated a pleomorphic liposarcoma, distinct from the prior synovial sarcoma. He underwent neoadjuvant radiation, followed by wide resection. He is now undergoing surveillance for recurrence. While 2 distinct primary sarcomas developing in rapid succession is rare, this case emphasizes the need for a complete work-up, including obtaining a tissue diagnosis for suspected recurrent lesions as this may alter treatment and follow-up recommendations.


Quantitative Anatomic Analysis of the Native Ligamentum Teres.
While recent studies have addressed the biomechanical function of the ligamentum teres and provided descriptions of ligamentum teres reconstruction techniques, its detailed quantitative anatomy remains relatively undocumented. Moreover, there is a lack of consensus in the literature regarding the number and morphology of the acetabular attachments of the ligamentum teres. To provide a clinically relevant quantitative anatomic description of the native human ligamentum teres. Descriptive laboratory study. Ten human cadaveric hemipelvises, complete with femurs (mean age, 59.6 years; range, 47-65 years), were dissected free of all extra-articular soft tissues to isolate the ligamentum teres and its attachments. A coordinate measuring device was used to quantify the attachment areas and their relationships to pertinent open and arthroscopic landmarks on both the acetabulum and the femur. The clock face reference system was utilized to describe acetabular anatomy, and all anatomic relationships were described using the mean and 95% confidence intervals. There were 6 distinct attachments to the acetabulum and 1 to the femur. The areas of the acetabular and femoral attachment footprints of the ligamentum teres were 434 mm2 (95% CI, 320-549 mm2) and 84 mm2 (95% CI, 65-104 mm2), respectively. The 6 acetabular clock face locations were as follows: anterior attachment, 4:53 o'clock (95% CI, 4:45-5:02); posterior attachment, 6:33 o'clock (95% CI, 6:23-6:43); ischial attachment, 8:07 o'clock (95% CI, 7:47-8:26); iliac attachment, 1:49 o'clock (95% CI, 1:04-2:34); and a smaller pubic attachment that was located at 3:50 o'clock (95% CI, 3:41-4:00). The ischial attachment possessed the largest cross-sectional attachment area (127.3 mm2; 95% CI, 103.0-151.7 mm2) of all the acetabular attachments of the ligamentum teres. The most important finding of this study was that the human ligamentum teres had 6 distinct points of attachment on the acetabulum (transverse, anterior, and posterior margins of the acetabular notch and cotyloid fossa attachments: ilium, ischium, and pubis) and 1 on the femur. On the acetabulum, the anterior attachment was substantially larger than the posterior attachment and was located at a mean clock face position of 4:53 o'clock. These quantitative descriptions of the ligamentum teres can be used by clinicians to arthroscopically identify the attachments of the ligamentum teres, guiding arthroscopic surgical interventions designed to address ligamentum teres pathology.


Evidence for the overestimation of molecular masses of proteins after chemical modification and chemical crosslinks on sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE).
Human trypsin inhibitor (home prepared), lactalbumin, trypsinogen, carbonic anhydrase, and bovine serum albumin were submitted to succinylation and their molecular masses were determined by SDS-PAGE according to the method of Weber and Osborn (1969 J. Biol. Chem. 244, 4406) before and after chemical modification. High estimates of their molecular masses were obtained. The monomer and dimer of arrowhead inhibitor proteinase-B (Chinese vegetable legume) obtained after chemical crosslink(s) were also submitted to SDS-PAGE and their apparent molecular masses were also determined and compared to the native arrowhead inhibitor proteinase-B. Abnormally high estimates of their molecular masses were obtained. Our results agree with those in the literature.


The 6S RNA transcribed from rodent total DNA in vitro is the transcript of the type 2 Alu family.
We have performed in vitro transcription, using total DNA isolated from mouse and a cloned mouse DNA fragment containing a representative type 2 Alu sequence characterized by Kominami et al. (1983) as templates. From each template, 6S RNA was transcribed. The fingerprint of the 6S RNA produced from in vitro transcription of total DNA showed a very clear pattern of oligonucleotides. By comparing the oligonucleotides of the 6S RNA produced from each template, we demonstrated that the 6S RNA transcribed from mouse total DNA is the in fact the transcript of type 2 Alu sequences. The composition of the oligonucleotides of the 6S RNA transcribed from mouse total DNA seems to reflect well that of the consensus sequence of the type 2 Alu family proposed by Krayev et al. (1982). In vitro transcripts of rat or hamster total DNA showed fingerprint patterns nearly identical to that of mouse DNA, confirming that rodents have equivalent type 2 Alu sequences whose transcripts have the same length and similar compositions of oligonucleotides. Thus total DNA transcription provides a novel approach to the detection and analysis of type 2 Alu sequences transcribed in vitro.


Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate chemicals classified as reactive.
The evaluation of chemicals for their skin sensitising potential is an essential step in ensuring the safety of ingredients in consumer products. Similar to the Threshold of Toxicological Concern, the Dermal Sensitisation Threshold (DST) has been demonstrated to provide effective risk assessments for skin sensitisation in cases where human exposure is low. The DST was originally developed based on a Local Lymph Node Assay (LLNA) dataset and applied to chemicals that were not considered to be directly reactive to skin proteins, and unlikely to initiate the first mechanistic steps leading to the induction of sensitisation. Here we have extended the DST concept to protein reactive chemicals. A probabilistic assessment of the original DST dataset was conducted and a threshold of 64 μg/cm(2) was derived. In our accompanying publication, a set of structural chemistry based rules was developed to proactively identify highly reactive and potentially highly potent materials which should be excluded from the DST approach. The DST and rule set were benchmarked against a test set of chemicals with LLNA/human data. It is concluded that by combining the reactive DST with knowledge of chemistry a threshold can be established below which there is no appreciable risk of sensitisation for protein-reactive chemicals.


Formation and reactivity of novel pyranosidic nicholas oxocarbenium ions: access to C-ketosides and branched-chain C-ketosides.
[Structure: see text] Dicobalt hexacarbonyl propargyl complexes, prepared from alkynyl ketoses, display an unexpected reactivity when treated with Lewis acids in the presence of nucleophiles and furnish C-ketosides, branched-chain C-ketosides, or branched-chain C-glycals depending on the nucleophile and the carbohydrate starting material.


Tumor host relations. II. Influence of tumor extent and tumor site on plasma cortisol of patients with malignant diseases.
The increase of plasma cortisol in patients with tumors of five different sites compared with a control group of patients with benign surgical diseases amounted to: +39% (breast), +34% (stomach), +86% (intestine), +60% (skin) and +194% (gall bladder). The first detectable increase of cortisol occurred in patients with tumors classified T 2 according to the TNM scheme (+27% above the control). Highly significant increases were observed for T 3 (+82%) and T 4 (+77%) patients. Patients with palpable lymph nodes showed a most significantly increased cortisol mean value compared with patients without palpable lymph nodes. Similarly, the cortisol mean value of patients with distant metastases was significantly higher than the corresponding value of tumor patients without distant metastases. The question remains open, whether the primary site, the extent of the tumor or the occurrence of metastases is the main determinant for the cortisol increase.


Decreased fructose concentrations in coagulating glands of prepuberal rats treated with testosterone and LH.
Doses of testosterone propionate from 2.5 to 320 microgram and doses of LH from 2 to 360 microgram given over 1--3 days generally decreased fructose/body weight ratios in the coagulating glands of late prepuberal rats. The ratios of testes, seminal vesicles, coagulating glands and ventral prostates to body weight were increased after different treatment regimes with testosterone propionate. These changes in the variables measured could be detected by computer analysis in spite of the rapid growth rates of organs of rats of this age. LH increased the weights of only the seminal vesicles and coagulating glands, and then, only at the highest doses given.


Afzelin positively regulates melanogenesis through the p38 MAPK pathway.
Melanogenesis refers to synthesis of the skin pigment melanin, which plays a critical role in the protection of skin against ultraviolet irradiation and oxidative stressors. We investigated the effects of afzelin on melanogenesis and its mechanisms of action in human epidermal melanocytes. In this study, we found that afzelin increased both melanin content and tyrosinase activity in a concentration-dependent manner. While the mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein (TRP)-1 increased following afzelin treatment, the mRNA levels of TRP-2 were not affected by afzelin. Likewise, afzelin increased the protein levels of MITF, TRP-1, and tyrosinase but not TRP-2. Mechanistically, we found that afzelin regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK), independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. Taken together, these findings indicate that the promotion of melanogenesis by afzelin occurs through increased MITF gene expression, which is mediated by activation of p38 MAPK, and suggest that afzelin may be useful as a protective agent against ultraviolet irradiation.


Divergent Enzymatic Assembly of a Comprehensive 64-Membered IgG N-Glycan Library for Functional Glycomics.
N-Glycosylation, a main post-translational modification of Immunoglobulin G (IgG), plays a significant role in modulating the immune functions of IgG. However, the precise function elucidation of IgG N-glycosylation remains impeded due to the obstacles in obtaining comprehensive and well-defined N-glycans. Here, an easy-to-implement divergent approach is described to synthesize a 64-membered IgG N-glycan library covering all possible biantennary and bisected N-glycans by reprogramming biosynthetic assembly lines based on the inherent branch selectivity and substrate specificity of enzymes. The unique binding specificities of 64 N-glycans with different proteins are deciphered by glycan microarray technology. This unprecedented collection of synthetic IgG N-glycans can serve as standards for N-glycan structure identification in complex biological samples and the microarray data enrich N-glycan glycomics to facilitate biomedical applications.


Restricted accumulation of globotriaosylceramide in the hearts of atypical cases of Fabry's disease.
Immunohistochemical and biochemical analyses of several tissues were performed in two unusual cases of Fabry's disease which showed accumulation of globotriaosylceramide (Gal alpha 1-4Gal beta 1-4 Glc-Cer, Gb3Cer) only in the hearts, but no clinical signs of the disease. Immunohistochemical study revealed that the hearts from our cases (cases no. 1 and 2) contained large amounts of anti-Gb3Cer antibody-positive granules in cytoplasms as in typical Fabry's disease. The contents of accumulated Gb3Cer in the hearts from case no. 1, case no. 2, and a typical Fabry's disease case were approximately 100, 340, and 100 times higher than those from normal controls, respectively. While typical Fabry's diseased kidney and liver contained approximately 40 and 50 times higher amounts of Gb3Cer than did controls, no accumulation of Gb3Cer was observed in kidney and liver of our cases. The only exception was a slight increase of Gb3Cer in kidney of case no. 2 (about two times higher than controls), in which epithelial cells of the glomeruli but not of other types of cells were positively stained by anti-Gb3Cer antibody. Case no. 1 kidney and liver were not stained by the antibody. The glomerular endothelium and epithelium, tubular epithelium, smooth muscle of renal arteries, and several hepatocytes were Gb3Cer-positive in the typical Fabry's disease case. The involvements of our cases differed distinctly from the typical Fabry's disease case.


Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification.
Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.


Enhancement of cytomegalovirus detection in mink lung cells using CMV Turbo.
Detection of HCMV from clinical specimens was a slow process until the development of shell vial method with staining for immediate early antigen (IEA). Culture though still considered insensitive is widely used for other than blood samples. A method to improve culture sensitivity is desirable. TurboTreat, a CMV pretreatment medium from Diagnostic Hybrids Inc., was evaluated on Mv1Lu, R-Mix and MRC-5 cells for improved sensitivity for HCMV detection. Monolayers of Mv1Lu, R-Mix and MRC-5 cells in 48-well plates were treated with TurboTreat for overnight (o/n), 4 h or left untreated and then inoculated with previously positive HCMV specimens. After o/n incubation, cells were fixed, stained and positive cells counted. CMV TurboTreat enhanced detection 2-3-fold after 4 h treatment and 4-6-fold after o/n treatment in Mv1Lu and R-Mix cells and to a lesser extend in MRC-5 cells with clinical isolates of HCMV. With frozen clinical specimens, Mv1Lu cells treated o/n, 4 h or untreated detected 23, 21 and 15 positive specimens, respectively. R-Mix cells detected 19, 18, and 14 positives, respectively and MRC-5 cells detected 16, 15 and 15 positives, respectively. In no case was a positive detected in another cell line regardless of treatment that was not detected in Mv1Lu treated o/n. The o/n pretreatment with CMV TurboTreat on Mv1Lu cells is the optimum condition of treatment and significantly enhanced the detection of HCMV. Even 4 h pretreatment of Mv1Lu cells showed significant enhancement over untreated Mv1Lu, R-Mix and MRC-5 cells. Pretreatment of Mv1Lu cells with CMV TurboTreat for 4 h or longer increased the sensitivity of rapid HCMV detection.


Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non-small cell lung carcinoma.
We assessed the impact of coverage of the mediastinum with a local hemostyptic agent as well as the impact of perioperative thromboembolic prophylaxis on cumulative chest drain volume and on the duration of chest tubes after surgical resection with complete mediastinal lymph node dissection for stage I or II non-small cell lung cancer. In a prospective, randomized two-by-two factorial design, 80 patients with clinical stage I or II non-small cell lung cancer were allocated to one of two surgical therapy arms (TachoComb or conventional surgical hemostasis) and one of two anticoagulation arms (enoxaparin 4,000 IU or dalteparin 5,000 IU). Primary end point was cumulative chest drain volume; secondary end point was duration of chest tubes. Additionally clinical data were obtained. Comparison of the surgical arms revealed significantly lower cumulative chest drain volumes and thereby an earlier chest tube removal in the TachoComb group (p = 0.045). With regard to thromboembolic prophylaxis, a significantly earlier chest tube removal was found for patients treated with dalteparin (p = 0.039). Analysis of the interaction of surgical and anticoagulation treatment revealed the combined use of TachoComb and dalteparin was superior to other combinations (cumulative chest drain volumes 498 +/- 67 mL versus 1,000 +/- 88 mL, 924 +/- 87 mL, and 895 +/- 118 mL; p = 0.008; mean duration of chest tubes 1.78 +/- 0.15 days versus 2.96 +/- 0.21 days, 2.93 +/- 0.17 days, and 3.06 +/- 0.27 days; p = 0.019). The combined use of a local hemostyptic agent and dalteparin seems superior as compared with other regimens of hemostasis and thromboembolic prophylaxis in patients undergoing surgical resection and complete mediastinal lymph node dissection for stage I and II non-small cell lung cancer with regard to cumulative chest drain volume as well as duration of chest tubes.


The effect of TNF-alpha, FcγR and CD1 polymorphisms on Guillain-Barré syndrome risk: evidences from a meta-analysis.
The findings on the associations between potential genetic variants and risk of Guillain-Barré syndrome (GBS) are controversial. We conducted a meta-analysis for candidate genes to provide the evidences for the current understanding of the genetic association with GBS. We searched relevant studies without language restriction in PubMed, Embase and Cochrane library through May 2011. The strengths of the associations between genetic variants and GBS risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Random-effects models or fixed effects model was applied based on the heterogeneity test. We identified 12 case-control studies involving 1,590 GBS cases and 2,154 controls for the analysis. Because of limited eligible data, our meta-analysis specifically focused on 6 genetic variants of 3 candidate genes, TNF-α, FcγR and CD1. We found that TNF-α 308 G/A polymorphism was significantly associated with the risk of GBS in the overall population (GG+GA vs. AA: OR=0.32, 95%CI=0.16-0.62; GG vs. AA: OR=0.36, 95%CI=0.19-0.68). Subgroup analysis further provided evidence of significant association between TNF-α 308 G/A and risk of the GBS in Asian population (GG+GA vs. AA: OR=32, 95%CI=0.11-0.93; GG vs. AA: OR=0.32, 95%CI=0.15-0.68). In addition, we did not observe significant associations between FcγRIIA R/H, FcγRIIIA F/V, FcγRIIIB NA1/NA2, CD1A 1/2 and CD1E 1/2 polymorphisms and susceptibility for developing GBS. Our findings showed that TNF-α 308A allele might be a moderate risk factor for GBS. However, the results should be interpreted with caution due to the limited number of studies available.


Design and preparation of quantum dots fluorescent probes for in situ identification of Microthrix parvicella in bulking sludge.
A series of quantum dots (QDs) fluorescent probes for the in situ identification of Microthrix parvicella (M. parvicella) in bulking sludge were designed and prepared. In the preparation of CdTe/CdS QDs, the 11-mercaptoundecanoic acid (11-acid) and 16-mercaptohexadecanoic acid (16-acid) were used as the stabilizer. The prepared QDs probes were characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and transmission electron microscopy (TEM), and the results showed that the CdTe/CdS QDs formed a core-shell structure and the long carbon chain was successfully grafted onto its surface. And the three QDs probes had different crystallinity and particle size, which was due to the inhibition effect of long carbon chain. The optical properties test results showed that although the formed core-shell structure and long carbon chain affected the fluorescent intensity, adsorption, and emission spectra of the QDs probes, the probes B and C had a large stokes-shift of 82 and 101 nm, which was a benefit for their fluorescent labeling property. In the fluorescent identification of M. parvicella, the probes B and C effectively adsorbed onto the surface of M. parvicella through a hydrophobic bond, and then identified M. parvicella by their unique fluorescence. In addition, it was found that a better hydrophobic property resulted in better identification efficiency.


[Revised WHO classification and new developments in diagnosis of central nervous system tumors].
In recent years there has been considerable progress in brain tumor neuropathology. Several new diagnostic entities have been recognized, subclassification schemes have been modified, and new concepts on the histogenesis and cell biology of brain tumors have emerged. In 1993, a revised WHO classification of brain tumors was published by an international committee. This article summarizes the pertinent new aspects. As novel tumor entities, the central neurocytoma, the dysembryoplastic neuroepithelial tumor (DNT), desmoplastic infantile ganglioglioma (DIG) and pleomorphic xanthoastrocytoma (PXA) have been included. Several histopathological variants of meningiomas have been added of which only the papillary meningioma and the atypical meningioma are characterized by an increased rate of recurrence. Meningeal hemangiopericytomas and hemangioblastomas are classified as tumors of non-meningothelial origin. The glioblastoma multiforme, which had previously been listed as an embryonal tumor, is now recognized as an astrocytic glioma. Immunohistochemistry has greatly advanced the practical diagnosis and classification of brain tumors. There are specific markers for all normal and neoplastic cell types except for oligodendroglioma cells. The prognosis of and therapeutic approaches to brain tumors greatly depend on histopathological grading. The WHO proposes four tumor grades, i.e., I, II, III, and IV. As a rule, grades I and II tumors are viewed as benign or semi-benign neoplasms and grades III and IV tumors as malignant. There are attempts to use new biological parameters for the grading of brain tumors. Antibodies to proliferation-associated proteins reflect tumor growth. Molecular genetic approaches to tumor-associated genes and gene loci are particularly promising new tools for the future.


The activity of temocillin against Enterobacteriaceae, Pseudomonas and Haemophilus influenzae.
The in vitro antimicrobial activity of temocillin against 130 strains of Enterobacteriaceae and 27 strains of Pseudomonas and other related Gram-negative organisms was compared with carbenicillin, mezlocillin and piperacillin. Temocillin was compared with ampicillin against 76 strains of Haemophilus influenzae. More than 90% of Enterobacteriaceae including 65 carbenicillin-resistant strains were inhibited by 8 mg/L of temocillin. Pseudomonas spp. were less susceptible to temocillin than to the other 3 penicillins. 35 out of 38 strains of beta-lactamase-producing H. influenzae were inhibited by 2 mg/L of temocillin. But with 38 ampicillin-sensitive and non-beta-lactamase-producing ampicillin-resistant strains, temocillin was slightly less active than ampicillin. There was no significant enhancement of temocillin activity by clavulanic acid against 20 strains of Gram-negative rods producing characterised beta-lactamases. The resistance to plasmid-mediated and chromosomal beta-lactamase extracts was also studied by bioassay method. No enzyme extracts tested could hydrolyse temocillin except that from one Flavobacterium strain.


Recent evolution of living donor liver transplantation at Kyoto University: How to achieve a one-year overall survival rate of 99%?
Previously, living donor liver transplantation was considered as a "high-risk, high-return" medical treatment due to the relatively high short-term mortality. It is our task to change "high-risk, high-return" into a "low-risk, high-return" situation. In this review article, the recent evolutions in living donor liver transplantation for both donors and recipients at Kyoto University such as portal vein pressure modulation, hybrid donor operation, and perioperative management considering sarcopenia, focusing on improvement of short-term outcomes are described. Under a paradigm of "marketing and innovation", various innovations and efforts have been made over the last decade aiming at improving the short-term outcomes of both donors and recipients. By doing so, excellent short-term results after living donor liver transplantation have been achieved, along with a potentially epoch-making discoveries.


Profile of chronic kidney disease from a nephrology underserviced region in North Eastern India: a preliminary report from a single center in Assam.
Chronic kidney disease (CKD) is a worldwide health problem affecting at least 10% of the world's population. CKD represents especially a large burden in low- to middle-income countries that are ill equipped to deal with its consequences. The burden of CKD is increasing in India as well. Although diabetes and hypertension account for much of this burden of CKD, there are regions where a surprisingly high rate of CKD of undetermined etiology (CKD-U) has been described in certain areas of the country. In our observational cross-sectional study, we attempted to look at burden and etiology of CKD in a predominantly rural referral center. Out of 334 patients with diagnosed CKD, of whom 70% were male, included from Oct 2021 to July 2022, CKD-U was the single largest cause of CKD in 154 (46.1%) followed by diabetic nephropathy in 148 (44.3%). 80% of CKD patients presented initially with advanced CKD (stages 4 and 5). Approximately, 2/3rd of CKD patients reported a family income of less than 10,000 Rs/month (< 130USD). Hypertension was seen in 89% of patients in total (73% in CKD-U vs. 100% in other cause CKD). Our initial study brings to focus another new and as yet unrecognized hotspot for CKD-U in the Indian subcontinent. Given the vast diversity in the population in this region and variable delivery health care resources, we believe that concerted efforts should be made by governmental and other agencies to better understand the nature of this undiagnosed CKD epidemic so that adequate preventative strategies can be envisaged.


A weighted-sum chaotic sparrow search algorithm for interdisciplinary feature selection and data classification.
In today's data-driven digital culture, there is a critical demand for optimized solutions that essentially reduce operating expenses while attempting to increase productivity. The amount of memory and processing time that can be used to process enormous volumes of data are subject to a number of limitations. This would undoubtedly be more of a problem if a dataset contained redundant and uninteresting information. For instance, many datasets contain a number of non-informative features that primarily deceive a given classification algorithm. In order to tackle this, researchers have been developing a variety of feature selection (FS) techniques that aim to eliminate unnecessary information from the raw datasets before putting them in front of a machine learning (ML) algorithm. Meta-heuristic optimization algorithms are often a solid choice to solve NP-hard problems like FS. In this study, we present a wrapper FS technique based on the sparrow search algorithm (SSA), a type of meta-heuristic. SSA is a swarm intelligence (SI) method that stands out because of its quick convergence and improved stability. SSA does have some drawbacks, like lower swarm diversity and weak exploration ability in late iterations, like the majority of SI algorithms. So, using ten chaotic maps, we try to ameliorate SSA in three ways: (i) the initial swarm generation; (ii) the substitution of two random variables in SSA; and (iii) clamping the sparrows crossing the search range. As a result, we get CSSA, a chaotic form of SSA. Extensive comparisons show CSSA to be superior in terms of swarm diversity and convergence speed in solving various representative functions from the Institute of Electrical and Electronics Engineers (IEEE) Congress on Evolutionary Computation (CEC) benchmark set. Furthermore, experimental analysis of CSSA on eighteen interdisciplinary, multi-scale ML datasets from the University of California Irvine (UCI) data repository, as well as three high-dimensional microarray datasets, demonstrates that CSSA outperforms twelve state-of-the-art algorithms in a classification task based on FS discipline. Finally, a 5%-significance-level statistical post-hoc analysis based on Wilcoxon's signed-rank test, Friedman's rank test, and Nemenyi's test confirms CSSA's significance in terms of overall fitness, classification accuracy, selected feature size, computational time, convergence trace, and stability.


Institutional Delivery Among Young Women in Ethiopia: Further Analysis of Trends and Determinants, from the Four Consecutive Ethiopia Demographic and Health Survey.
Although young people have a right to sexual and reproductive health, they are facing inadequate access to information and services. The Ethiopian government has started implementing policies and strategies to eliminate inequalities in reproductive health service use. However, there are huge disparities in institutional delivery utilization between different age groups. Therefore, this study aimed to explore trends and factors associated with institutional childbirth among young women in Ethiopia. Ethiopian demographic and health survey data (EDHS) from 2000 to 2016 surveys were used. Data on the most recent births to women aged 15-24 years that occurred in the 5 years preceding the survey period were extracted. All the four EDHS data were used to examine trends of institutional delivery, whereas determinants for institutional delivery were analyzed from a 2016 dataset by using multivariable logistic regression analysis. Between 2000 and 2016, the proportion of institutional delivery among young women increased from 6% (95% CI=3.7-6.5%) to 40.1% (95% CI=30.6-44.3%). The odds of institutional delivery increased for young women who had attended secondary and above education (AOR=2.68; 95% CI=1.559-4.607), started ANC visits early (AOR=1.518; 95% CI=1.095-2.105) and received four or more ANC visits (AOR=1.87; 95% CI=1.370-2.561). However, the odds were lower among young women who had two (AOR=0.31; 95% CI=0.185-0.514), and three or more children (AOR=0.62; 95% CI=0.452-0.849). There is an increase in trend of institutional delivery among young women during the 2000 to 2016 EDHS. Having higher educational levels, early ANC booking, and attending four or more ANC visits were positively associated with institutional delivery. Increased number of children is negatively associated with institutional delivery. Strengthening strategies for improving girls' education and addressing their socioeconomic and demographic vulnerabilities, and strengthening strategies being implemented for encouraging early and recommended ANC visits is crucial.


Anthropogenic activities and environmental filtering have reshaped freshwater fish biodiversity patterns in China over the past 120 years.
Over the past centuries, freshwater fish introductions and extinctions have been the major environmental and ecological crises in various water bodies in China. However, consequences of such crises on freshwater fish biodiversity in China remain only partially or locally studied. Furthermore, identifications of relatively sensitive areas along with stressors (i.e., environmental and anthropogenic drivers) influencing freshwater fish biodiversity patterns are still pending. Taxonomic, functional, and phylogenetic facets of biodiversity can well describe and evaluate the underlying processes affecting freshwater fish biodiversity patterns under different dimensionalities. Here we thus evaluated temporal changes in these facets of freshwater fish biodiversity as well as a new developed biodiversity index, multifaceted changes in fish biodiversity, for over a century at the basin level throughout China using both alpha and beta diversity approaches. We also identified the drivers influencing the changes in fish biodiversity patterns using random forest models. The results showed that fish assemblages in Northwest and Southwest China (e.g., Ili River basin, Tarim basin, and Erhai Lake basin) experienced extreme temporal and multifaceted changes in the facets of biodiversity compared with other regions, and environmental factors (e.g., net primary productivity, average annual precipitation, and unit area) largely drove these changes. Since fish faunas in over 80% of China's water bodies covering more than 80% of China's surface were currently undergoing taxonomic, functional, and phylogenetic homogenization, targeted conservation and management strategies should be proposed and implemented, especially for the areas with relatively high changes in biodiversity.


Association between protective efficacy of antibodies to tumor necrosis factor and suppression of nitric oxide production in neonatal rats with fatal infection.
In a rat model of fatal infection caused by Pseudomonas aeruginosa, the circulating level of nitrite/nitrate (NO2-/NO3-), a good indicator for nitric oxide production, was remarkably increased after elevation of circulatory tumor necrosis factor (TNF). Anti-TNF MAb cotreatment was shown to blunt hypoglycemia and hyperlacticemia and was associated with decreased mortality of septic animals. Moreover, anti-TNF MAb significantly reduced not only plasma TNF but also plasma NO2-/NO3- levels. Dexamethasone had a similar effects, and when anti-TNF MAb was used in combination with dexamethasone, the suppression of nitric oxide production and the protective efficacy were more remarkable compared with therapy with either anti-TNF MAb or dexamethasone alone. Our present data suggested that the protective efficacy of anti-TNF MAb may correlate with the suppression of nitric oxide production and also with a modulation in metabolic abnormalities in the septic newborn rats.


State-level homelessness and drug overdose mortality: Evidence from US panel data.
Although homelessness is a well-documented risk factor for drug overdose at the individual level, less is known about state-level homelessness and overdose mortality in the United States (US). This study used 2007-2020 panel data for all US states and the District of Columbia, from the following sources: US Department of Housing and Urban Development (homelessness data); Centers for Disease Control and Prevention (drug overdose death counts, population estimates, and opioid prescribing rates); Bureau of Labor Statistics (unemployment rates); and the National Forensic Laboratory Information System (drug seizure data). Two-way (state and year) fixed effects models regressed log-transformed drug overdose mortality rates on homelessness prevalence, in nested models adding demographic composition and unemployment measures, as well as drug supply measures. Models were weighted by state population size, and standard errors (SEs) were clustered at the state level. Homelessness prevalence was significantly and positively associated with rates of drug overdose mortality after adjusting for nationwide trends, time-invariant differences between states, demographic composition, and unemployment rates (b[SE]=0.98[0.36], p=0.009). The positive association between homelessness prevalence and overdose mortality was attenuated at higher levels of fentanyl availability (fentanyl involvement in drug seizures; interaction term b[SE]=-0.02[0.01], p=0.001). The positive association between state-level homelessness and drug overdose mortality suggests that policies and programs to prevent and reduce homelessness represent fundamental elements of a comprehensive response to the US overdose crisis.


A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development.
Protein kinase C-associated kinase (PKK)/receptor interacting protein 4 (RIP4) is a protein kinase C (PKC) beta-associated kinase that links PKC to NF-kappaB activation. The kinase domain of PKK is similar to that of RIP, RIP2, and RIP3. We show in this study that PKK is expressed early during lymphocyte development and can be detected in common lymphoid progenitor cells. Targeting of a catalytically inactive version of PKK to lymphoid cells resulted in a marked impairment in pro-B cell generation in the bone marrow. Although peripheral B cell numbers were markedly reduced, differentiation into follicular and marginal zone B cells was not defective in these mice. B-1a and B-1b B cells could not be detected in these mice, but this might be a reflection of the overall defect in B cell production observed in these animals. In keeping with a possible link to PKCbeta, peripheral B cells in these mice exhibit a defect in anti-IgM-mediated proliferation. These studies suggest that PKK may be required early in B cell development and for BCR-mediated B cell proliferation.