Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer.
Pancreatic cancer still has a poor prognosis, even if aggressive therapy is pursued. Currently, new modalities of oncolytic virus therapy are being tested against this cancer. The combination of one of two representative mutant herpes simplex viruses (R3616: gamma(1)34.5 inactivated, hrR3: UL39 inactivated) with a standard anti-pancreatic cancer chemotherapy drug (gemcitabine), was investigated in this study. The intracellular concentration of ribonucleotide reductase was estimated by Western blotting. The effect of gemcitabine on viral replication and the total cytotoxic effect of the combination therapy were investigated on pancreatic cancer cell lines. We compared the results of two oncolytic viruses, R3616 and hrR3. A mouse model of pancreatic cancer with peritoneal dissemination was used to evaluate the in vivo effect of the combination therapy. Although the replication of both viruses was inhibited by gemcitabine, the combination caused more tumor cell cytotoxicity than did virus alone in vitro. The results with R3616 were more striking. Although the difference was not statistically significant, R3616 with gemcitabine had a greater effect than did R3616 alone, while hrR3 with gemcitabine had a weaker effect than did hrR3 alone in vivo experiments. The combination of oncolytic virus with gemcitabine is a promising new strategy against advanced pancreatic cancer. Each virus has different functional characteristics, and can affect the results of the combination of viruses and chemotherapy drugs. The results indicate that there is a complicated interaction among viruses, cells, and chemotherapy drugs and that the best combination of oncolytic virus and chemotherapeutic agents should be studied more extensively before embarking on a clinical trial.


Virus induced diabetes and the immune system. II -- Evidence for an immune pathogenesis of the acute phase of diabetes.
The infection of normal DBA2 and BALB/C nu/ + mice with 2 X 10(2,6) TCID50 of the M variant of the EMC virus induced pathological mean glucose values of 426 +/- 99 mg/100 ml in DBA2 mice and 292 +/- 130 mg/100 ml in BALB/C nu/ + mice on day five following infection. As diabetic animals died afterwards, mean glucose values decreased in the surviving animals on day seven and fourteen. The infected immunodeficient BALB/C nu/nu mice with thymus aplasia did not show abnormal mean glucose values or higher standard deviation of the means (114 +/- 37 mg/100 ml) when compared to uninfected controls (117 +/- 23 mg/100 ml). This demonstrates that a complete thymus-dependent immune system seems to be necessary for the development of the acute stage of virus-induced diabetes in the mouse.


Predicting the need for hospital admission in patients with intentional drug overdose.
Self-poisoned patients are often admitted to a medical unit. However, often no treatment is given. We have developed a model to predict those patients who will not be treated and how long patients should be observed before this prediction can be safely made. In this retrospective study a model to predict treatment was developed based on cases of self-poisoning in 1996 and validated on cases between 1997 and 1999. In a teaching hospital in The Netherlands 299 adults performing 353 episodes of self-poisoning were studied. The main outcome measures were predicted versus initiated medical treatment, time to prediction and time to initiation of treatment. The model predicted that in 51% (156/307) of all autointoxications no treatment would be given. In 2% (6/307) of all cases, treatment was incorrectly not predicted. All but one of these were preventive treatments based on the ingested compound. 4.5 hours after admission no additional patients fulfilled the criteria for prediction of treatment and all treatments were started within 4.5 hours. In 51% of patients that present with an autointoxication the model accurately predicts that no treatment will be initiated. This decision can be made in the first 4.5 hours after presentation. This model can be used for a first screening of patients. It can also be used as a basis for a further prospective study to establish rational guidelines in the management of these patients.


The use of Streptococcus zymogenes for estimating tryptophan and methionine bioavailability in 17 foods.
As part of a cooperative study assessing amino acid bioavailability and/or protein quality, the provisional method of Boyne et al. (Brit J Nutr 21: 181-206) was used to assay 17 protein sources for methionine and tryptophan availability with S. zymogenes. Pronase was used as the predigesting enzyme. Product composition was found to affect reproducibility. The microbial assay results correlated positively with results from rat growth studies on the same foods (p = 0.05), and were generally accurate in identifying products of lower protein quality. Defatting four high-fat products increased microbial values in the methionine assay, but only the chicken franks and the sausage values in the tryptophan assay. Heating non-fat milk increased methionine values slightly. Low values for rolled oats were further reduced by finer grinding.


The tick saliva peptide HIDfsin2 promotes the tick-borne virus SFTSV replication in vitro by enhancing p38 signal pathway.
Pathogens co-evolved with ticks to facilitate blood collection and pathogen transmission. Although tick saliva was recently found to be rich in bioactive peptides, it is still elusive which saliva peptide promotes virus transmission and which pathways are invovled. Here, we used a saliva peptide HIDfsin2 and a severe fever with thrombocytopenia syndrome virus (SFTSV) both carried by the tick Haemaphysalis longicornis to elucidate the relationship between tick saliva components and tick-borne viruses. HIDfsin2 was found to promote the replication of SFTSV in a dose-dependent manner in vitro. HIDfsin2 was further revealed to MKK3/6-dependently magnify the activation of p38 MAPK. The overexpression, knockdown and phosphorylation site mutation of p38α indicated that p38 MAPK activation facilitated SFTSV infection in A549 cells. Moreover, the blockade of p38 MAPK activation significantly suppressed SFTSV replication. Differently, HIDfsin2 or pharmacological inhibition of p38 MAPK activation had no effect on a mosquito-borne Zika virus (ZIKV). All these results showed that HIDfsin2 specifically promoted SFTSV replication through the MKK3/6-dependent enhancement of p38 MAPK activation. Our study provides a new perspective on the transmission of tick-borne viruses under natural conditions, and supports that the blockade of p38 MAPK activation can be a promising strategy against the mortal tick-borne virus SFTSV.


Parameters of production and partial characterization of feline interleukin 2.
The conditions for the production of feline interleukin 2 (IL-2) from peripheral blood leukocytes (PBL) and splenocytes by concanavalin A (Con A) stimulation are described. Feline IL-2 was quantitated by measuring DNA synthesis in the murine IL-2-dependent cell line, CTLL-20. In addition, feline IL-2 was generated for the maintenance of long-term cultures of Con A-stimulated feline PBL and for biochemical characterization. Finally, IL-2 production was evaluated from the PBL of feline leukemia virus (FeLV)-infected cats. Con A at 9.6 micrograms/ml produced a plateau of peak IL-2 activity from 24 to 48 h following stimulation. The tumor promoter, phorbol myristic acetate, stimulated feline IL-2 production and enhanced Con A-stimulated feline IL-2 production. Fetal calf serum (FCS) was not required for IL-2 production; however, FCS at 5% (v/v) allowed for maximal Con A-stimulated IL-2 production. Feline IL-2 generated from Con A-stimulated splenocytes migrated with an apparent molecular size of 13.7 to 23 kD by gel filtration chromatography and supported the proliferation of Con A-activated feline PBL at a final concentration of 0.3 to 0.9 units/ml.


Modeling Tiered Pricing Frameworks: A Simulation Approach.
Drug plans take different approaches to determining reimbursement prices for generic drugs. One common approach is to set the maximum reimbursement price as a percentage of the price of the interchangeable branded drug. In many countries this percentage depends on the number of generic entrants, a model we call "tiered pricing." This paper seeks to enhance understanding of how to set the tiers. We construct a simple model of tiered pricing and set parameters to match evidence on generic drug costs and the distribution of revenues. Using simulation methods, we then assess different tier structures in terms of total surplus and average drug cost. We find when tiers are bunched tightly together welfare outcomes are poor. Moreover, there are large welfare gains from increasing the number of tiers from one to two, and only small welfare gains from increasing the number of tiers beyond four. The choice of tiers has substantial welfare and cost implications. While it is possible to refine the simulation analysis based on specific market characteristics, an optimal tier structure, such as the one we propose in the paper, should have at least two tiers.


Effects of endogenous hyperglucagonemia on lower esophageal sphincter pressure and gastric acid secretion.
Lower esophageal sphincter function and gastric acid secretion were studied in a patient with endogenous hyperglucagonemia due to a functioning islet cell carcinoma. Complete resection of the tumor resulted in a fall of the serum concentration of immunoreactive glucagon to a normal level. Pre- and postoperative resting lower esophageal sphincter pressures and lower esophageal sphincter pressure responses to administration of pentagastrin, edrophonium, and bethanechol were unchanged. After surgery, preoperative immunoreactive glucagon concentrations were reproduced by intravenous infusion or intramuscular injection of exogenous glucagon. Lower esophageal sphincter resting pressures and responses to agonists were unchanged. In contrast, glucagon administered at 36 micrograms/kg/hr, which produced a serum concentration of immunoreactive glucagon (32,000 pg/ml) much greater than observed preoperatively (1200 pg/ml), diminished resting lower esophageal sphincter pressure and sphincter responses to pentagastrin, edrophonium, and bethanechol. Similarly, pentagastrin-stimulated gastric acid secretion was unaffected by tumor resection or low-dose glucagon infusion but was decreased at a glucagon infusion rate of 36 micrograms/kg/hr. This series of observations supports the thesis that endogenous glucagon plays no physiological role in the regulation of lower esophageal sphincter pressure or gastric acid secretion.


Whole body glucose kinetics in type I diabetes studied with [6,6-2H] and [U-13C]-glucose and the artificial B-cell.
Dynamic aspects of whole body glucose metabolism were assessed in ten young adult insulin-dependent (type I) diabetic men. Using a primed, continuous intravenous infusion of [6,6-2H]glucose and [U-13C]glucose, endogenous production, tissue uptake, carbon recycling, and oxidation of glucose were measured in the postabsorptive state. These studies were undertaken after blood glucose had been maintained overnight at 5.9 +/- 0.4 mmol/L (n = 10), and on another night at 10.5 +/- 0.4 mmol/L (n = 4) or 15.2 +/- 0.6 mmol/L (n = 6). In the normoglycemic state, endogenous glucose production averaged 2.15 +/- 0.13 mg x kg-1 x min-1. This value, as well as the rate of glucose carbon recycling (0.16 +/- 0.04 mg x kg-1 x min-1) and glucose oxidation (1.52 +/- 0.16 mg x kg-1 x min-1) are comparable to those found in nondiabetic controls. In the hyperglycemic states at 10 or 15 mmol/L, endogenous glucose production was increased by 11% (P less than .01) and 60% (P less than .01) compared to the normoglycemic states, respectively. Glucose carbon recycling contributed only a small percentage to this variation in glucose production (15% at the 15 mmol/L glucose level). This suggests that if gluconeogenesis participates in the increased glucose output, it is not dependent on a greater systemic supply of three-carbon precursors. The increased rate of glucose production in the hyperglycemic state was quantitatively offset by a rise in urinary glucose excretion. Glucose tissue uptake, as well as glucose oxidation, did not vary between normoglycemic and hyperglycemic states.(ABSTRACT TRUNCATED AT 250 WORDS)


Multivariate analysis of clinical prognostic factors in patients with glioblastoma multiforme treated with a combined modality approach.
We investigated the influence of various clinical prognostic factors in patients with glioblastoma multiforme (GBM) treated with a combined modality approach. A total of 175 patients with GBM was treated in four consecutive prospective phase II studies using surgery, hyperfractionated or accelerated hyperfractionated radiotherapy (RT) and either adjuvant or concurrent or pre-irradiation chemotherapy (CHT) between January 1988 and December 1993. The median survival time for all 175 patients was 14 months and 1-3-year survival (OS) rates were 57%, 34% and 24%, respectively. The median time to tumour progression was 12 months, and 1-3-year progression-free survival (PFS) rates were 43%, 11% and 7%, respectively. Survival analysis showed that of all investigated prognostic factors, only gender did not influence survival. Patients </=55 years did better than those >55 years; patients with KPS 80-100 did better than those with KPS 50-70; patients with frontal tumours did better than those with tumours in other locations; patients with tumours up to 4 cm did better than those with larger tumours, as did patients with either subtotal or gross total tumour resection when compared to those undergoing biopsy only. Multivariate analysis showed that gender and tumour location did not independently influence survival. When PFS was used as the endpoint, only gender did not influence PFS, as confirmed by multivariate analysis.


Dietary nano-silver: Does support or discourage thermal tolerance and biochemical status in air-breathing fish reared under multiple stressors?
Unexpected fluctuations in weather parameters due to global climate change have been observed in all ecosystems worldwide. The aquatic ecosystem shelters a great diversity of fishes in the upper region of the ecosystem which adversely get affected due to their poikilothermic nature. The present study was designed to elucidate the impact of critical temperature minima (CTMin), lethal temperature minima (LTMin), critical temperature maxima (CTMax), and lethal temperature maxima (LTMax) on Channa striatus. Biologically synthesized silver nanoparticles (Ag-NPs) were evaluated for their potential to enhance thermal tolerance and improve the activities of biochemical enzymes of C. striatus reared under lead (Pb) and high temperature (34 °C) for 50 days. Three iso-caloric and iso-nitrogenous diets which included a basal diet and two supplemented diets with Ag-NPs @ 0.5 mg/kg, and 1 mg/kg were used in the study. Results suggested that CTMin and LTMin were significantly (p < 0.01) reduced and CTMax and LTMax were enhanced in the group fed with 0.5 mg/kg Ag-NPs supplemented feed. Pre-exposure to high temperature led to enhanced CTMax and LTMax in C. striatus. The biochemical enzymes involved in protein metabolism, carbohydrate metabolism, acetylcholine esterase and antioxidant activities were found to be normal in fish fed with 0.5 mg/kg Ag-NPs supplemented diet. Bioaccumulation of silver and Pb was determined in different fish tissues and experimental water. Overall, the incorporation of Ag-NPs at 0.5 mg/kg in diet can confer protection to fish against Pb and thermal stress and enhance thermal tolerance of C. striatus.


Phase II trial of edatrexate in patients with metastatic colorectal cancer.
Edatrexate is an analog of methotrexate which in vitro demonstrated activity against human colon cancer xenografts grown in nude mice. In a phase II trial, 12 patients with metastatic colorectal cancer and no prior chemotherapy were treated with Edatrexate 80 mg/m2/week for an initial period of 8 weeks. No objective responses were observed. Edatrexate is inactive against colon cancer at the dose and schedule used in this trial.


Ductility improvement due to martensite α' decomposition in porous Ti-6Al-4V parts produced by selective laser melting for orthopedic implants.
Ti-6Al-4V parts obtained by selective laser melting typically have an acicular α' martensitic microstructure whose ductility is low. Thus, post-heat treatments are useful for increasing ductility. In this work, the effects of sub-β-transus heat treatments on the mechanical properties of Ti-6Al-4V parts with porous structures are correlated with martensite α' phase decomposition. The precipitation of β phase and the gradual transformation of α' into α phase by the diffusion of excess vanadium from α' to β phase are proposed to be the main events of martensite α' phase decomposition in parts fabricated by selective laser melting. The heat treatment performed at 650°C for 1h produced no microstructural changes, but the samples treated for at the same temperature 2h showed a fine precipitation of β phase along the α' needle boundaries. The heat treatment performed at 800°C for 1 or 2h produced a fine α+β microstructure, in which β phase are present as particles fewer in number and larger in size, when compared with the ones present in the sample heat-treated at 650°C for 2h. Heat-treatment of the parts at 800°C for 2h proved to be the best condition, which improved the ductility of the samples while only slightly reducing their strength.


Monitoring exposure of northern cardinals, Cardinalis cardinalis, to cholinesterase-inhibiting pesticides: enzyme activity, reactivations, and indicators of environmental stress.
Northern cardinals (Cardinalis cardinalis) frequently use agricultural field edges in northeast Arkansas, USA, and may be at risk of exposure to cholinesterase (ChE)-inhibiting pesticides. We monitored northern cardinal exposure to ChE-inhibiting pesticides by comparing plasma total ChE (TChE) activity to reference-derived benchmarks and TChE reactivations. Total ChE and acetylcholinesterase (AChE) were measured for 128 plasma samples from 104 northern cardinals from nine study sites. Of birds sampled from sites treated with ChE-inhibiting pesticides, 4.3% of the samples had TChE activities below the diagnostic threshold (2 standard deviations [SD] below the reference mean) and 8.7% of the samples had TChE reactivations. No difference was found in TChE (p = 0.553) and AChE (p = 0.288) activity between treated and reference sites; however, activity varied among treated sites (p = 0.003). These data do not suggest uniform exposure to individuals, but rather exposure was variable and likely influenced by mitigating factors at individual and site scales. Furthermore, monitoring of TChE reactivation appeared to be a more sensitive indicator of exposure than the diagnostic threshold. Fluctuating asymmetry (FA) was greater at agricultural sites than reference sites (p = 0.016), supporting the hypothesis that FA may be useful for assessing a combination of habitat- and contaminant-related environmental stress.


The separation and analysis of symmetric and asymmetric dimethylarginine and other hydrophilic isobaric compounds using aqueous normal phase chromatography.
Two biologically important compounds with clinical relevance, asymmetric dimethylarginine and symmetric dimethylarginine, are analyzed using aqueous normal phase chromatography on silica hydride-based columns. Two different stationary phases were tested, a commercially available Diamond Hydride™ and a 2-acrylamido-2-methylpropane sulfonic acid experimental column. Two types of analytical protocols were investigated: analysis of the compounds when separation was achieved and analysis of the compounds with partial chromatographic separation. Urine samples from tuberculosis patients were tested for levels of asymmetric and symmetric dimethylarginine. The mass spectrometric technique of in-source fragmentation that can provide data similar to a tandem mass analyzer was evaluated as a means of identification and quantitation of the two compounds when complete separation is not achieved. This same protocol was also evaluated for two other isobaric compounds, glucose-1 and glucose-6 phohsphate, and leucine and isoleucine.


Interaction of Mesna (2-mercaptoethane sulfonate) with the mutagenicity of cyclophosphamide in vitro and in vivo.
The effects of sodium 2-mercaptoethane sulfonate (Mesna) on the mutagenicity of cyclophosphamide (CP) were assessed in vitro by the Ames test and in vivo in rats by analyzing micronuclei in bone marrow and mutagenic activity in urine. Mesna alone was negative in all test systems, while CP gave a positive response in all of them. In a combined treatment there was no significant reduction of the CP-induced mutagenicity in Salmonella. In rats the frequency of bone marrow micronuclei was not diminished when Mesna was given together with CP. May-Grunwald-Giemsa staining and Hoechst-Pyronin fluorescent staining techniques for micronuclei yielded similar results. The urine of rats treated with CP was mutagenic to Salmonella and no significant difference was observed when the rats had received both Mesna and CP. The results give support to the theory that Mesna acts primarily by reducing the toxicity of metabolites of CP, particularly acrolein, in the urinary tract and not by suppressing the mutagenicity of the active metabolites of CP.


Does coagulation differ between elderly and younger patients undergoing cardiac surgery?
Multiple improvements allow cardiac surgery in an increasingly older population. It is still unclear whether perioperative hemostasis differs between elderly and younger patients. Prospective, observational study. Single institutional study at an urban, university-affiliated hospital. Twenty-one consecutive patients aged over 80 years and 21 consecutive patients aged under 60 years undergoing first-time elective aortocoronary bypass grafting. None. Modified thromboelastography (TEG) using different activators [intrinsic TEG (InTEG); extrinsic TEG (ExTEG); fibrinogen TEG (fibTEG)] was carried out to measure coagulation time [CT = reaction time (r)], clot formation time [CFT = coagulation time (k)], and maximum clot firmness [MCF = maximal amplitude (MA)]. Measurements were performed before surgery, at the end and 5 h after surgery on the intensive care unit (ICU), and on the morning of the 1st postoperative day (POD). Blood loss was slightly higher in the elderly than in the younger patients. Most TEG data were already significantly different between elderly and younger patients at baseline, indicating altered coagulation in the elderly prior to surgery (hypocoagulability). After surgery and on the ICU, elderly patients showed similar alterations in TEG to those of the younger patients (e.g. InTEG-CT: from 183+/-21 to 239+/-28 s versus from 146+/-15 to 186+/-26 s). On the 1st POD, most TEG data had returned almost to baseline values, however, they were still different between elderly and younger patients. Elderly cardiac surgery patients already showed moderately altered coagulation prior to surgery. Thus elderly patients may be at risk of developing postoperative alterations in hemostasis on the ICU. The exact reasons for the impaired coagulation in the elderly remains to be determined.


Chemical modification of bovine heart mitochondrial malate dehydrogenase. Selective modification of cysteine and histidine.
Bovine mitochondrial malate dehydrogenase (EC 126.96.36.199) was inactivated by the specific modifications of a single histidine residue upon reaction with iodoacetamide. NADH protected against this loss of activity and reaction with the histidine residue, suggesting that the histidine is at the NADH binding site. N-Ethylmaleimide also modified the enzyme by reacting with 1 sulfhydryl residue. The reaction rate with N-ethylmaleimide was increased by decreasing the pH from neutrality or by the addition of urea. NADH protected against the modification of the sulfhydryl group under all the conditions tested, again suggesting active site specificity for this inactivation. This enzyme has a subunit weight of 33,000 and is a dimer. The native malate dehydrogenase will bind only 1 mol of NADH and it is thus assumed that there is only a single active site per dimer.


Regulation of human Fc epsilon RI alpha-chain gene expression by multiple transcription factors.
Transcriptional regulation of the gene-encoding human Fc epsilon RI alpha-chain was analyzed in detail. EMSA revealed that either YY1 or PU.1 bound to the region close to that recognized by Elf-1. The alpha-chain promoter activity was up-regulated approximately 2-fold by exogenously expressed YY1 or PU.1 and approximately 7-fold by GATA-1, respectively, in KU812 cells. In contrast, coexpression of GATA-1 with either of PU.1 or YY1 dramatically activated the promoter approximately 41- or approximately 27-fold, respectively. Especially synergic activation by GATA-1 and PU.1 was surprising, because these transcription factors are known to inhibit the respective transactivating activities of each other. These up-regulating effects of PU.1 and YY1 with GATA-1 were inhibited by overexpression of Elf-1, indicating that Elf-1 serves as a repressor for the alpha-chain gene expression. Transcriptional regulation of the alpha-chain gene through four transcriptional factors is discussed.


Unstable nucleotide repeat minireview series: a molecular biography of unstable repeat disorders.
Expansion of an unstable nucleotide repeat is a mutational mechanism that is apparently unique to humans and is known to cause a variety of neurological disorders. This collection of minireviews examines several of these unstable repeats, focusing on those where there is considerable molecular information on how the mutation alters function.


Iron regulates Bacillus thuringiensis haemolysin hlyII gene expression during insect infection.
Bacillus thuringiensis (Bt) is a spore-forming entomopathogen broadly used in agriculture crop. The haemolysin HlyII is an important Bt virulence factor responsible for insect death. In this work, we focused on the regulation of the hlyII gene throughout the bacterial growth in vitro and in vivo during insect infection. We show that hlyII regulation depends on the global regulator Fur. This regulation occurs independently of HlyIIR, the other known regulator of hlyII gene expression. Moreover, we show that hlyII is highly expressed when iron is depleted in vivo. As HlyII induces haemocyte and macrophage death, which are involved in the sequestration of iron upon infection, HlyII may induce host cell death to allow bacteria to gain access to iron.


Different cystic fibrosis transmembrane conductance regulator mutations in Chinese men with congenital bilateral absence of vas deferens and other acquired obstructive azoospermia.
To investigate cystic fibrosis transmembrane conductance regulator (CFTR) gene in Chinese men with congenital bilateral absence of vas deferens (CBAVD) and other obstructive azoospermia. Four hundred one patients with obstructive azoospermia were included. Patients were grouped as 158 with CBAVD and 243 with other acquired obstructive azoospermia. Another 200 fertile men were used as controls. Genomic deoxyribonucleic acid was isolated from peripheral blood lymphocytes for all men. The exon 10 and 11 CFTR genes were amplified and sequenced. The frequency of CFTR gene mutations was compared among 3 groups. Six heterozygous mutations (+/-), I556V, M469V, E527N, F508del, S485C, and I558S, were found in 30 patients, and 1 homozygous mutation (+/+), I556V, was found in 1 patient. The overall frequency of CFTR mutations was 31 of 401 (7.7%). Of these mutations, I556V was the most common type with 24 of 31 (77.4%). In CBAVD group, 20 of 158 patients were identified with 6 different heterozygous mutations (I556V, M469V, E527N, F508del, S485C, and I558S) and 1 homozygous mutation (I556V). The rate of CFTR mutations was 12.7%. In acquired obstructive group, 11 of 243 patients were identified with 2 different heterozygous mutations, I556V and M469V; the rate of mutations was 4.5%. No CFTR mutations were identified in controls. There was significant difference among 3 groups (P = .000). The frequency of CFTR mutations in CBAVD is 2-fold higher than in other acquired obstructive group. Different CFTR mutations are observed in Chinese patients with CBAVD. I556V is the major common type of CFTR mutations in Chinese patients with CBAVD.


Substrate induction of isomaltulose synthase in a newly isolated Klebsiella sp. LX3.
Production of isomaltulose by newly isolated Klebsiella sp. LX3. The bacterial isolate LX3, which transforms sucrose to isomaltulose and trehalulose, has been isolated from a soil sample in Singapore. Morphological and biochemical analysis, as well as 16s rRNA sequence demonstrated that the isolate could represent a new member of genus Klebsiella. The strain has several interesting features. The immobilized cells of Klebsiella sp. LX3 convert more than 99% of sucrose to products that consist of more than 87% of isomaltulose, 11.6% of trehalulose, and <1% of glucose. The production of isomaltulose synthase in isolate LX3 is inducible by its substrate sucrose and the sugars containing a fructofuranosyl group. It would be useful for future biotechnological applications to understand the structural features or motifs of the isomaltulose synthases that determine the sucrose conversion efficiency and the ratio of the conversion products.


[Action of oxygen under increased pressure on the neutrophil metabolism in the peripheral blood].
The effect of hyperbaric oxygen (1--5 ata for 1 hr) on the activity of cytochrome oxidase, peroxidase, lipid content and phagocytic activity of neutrophils was studied. The dynamics of the recovery of those parameters was followed. A multimodal relationship between the pressure level and changes in the enzyme activity and lipid content was noted. The decrease in the activity of peroxidase was more pronounced than that of cytochrome oxidase in all cases. The dynamics of the recovery of the above parameters was shown to depend on the pressure level. The cytochemical parameters returned to the normal within 24 hours. The decline in the activity of cytochrome oxidase, peroxidase and in the lipid content of peripheral neutrophils was followed by a decrease in the phagocytic activity. These changes were closely correlated.


The route of Ca2+ entry during reloading of the intracellular Ca2+ pool in pancreatic acini.
To trace the route of Ca2+ entry and the role of the cytosolic Ca2+ pool in reloading of the internal stores of pancreatic acinar cells, Mn2+ influx into Fura 2-loaded cells and the effect of 1,2-bis(2-aminophenoxyethane-N,N,N',N'-tetraacetic acid (BAPTA) on Ca2+ storage in intracellular stores and reloading were examined. Treatment of acini suspended in Ca2(+)-free medium with carbachol (cell stimulation) or carbachol and atropine (reloading period) resulted in 2-fold increase in the rate of Mn2+ influx. Increasing Ca2+ permeability of the plasma membrane by elevation of extracellular pH from 7.4 to 8.2 further increased the rate of Mn2+ influx observed during cell stimulation and the reloading period. Loading the acini with BAPTA by incubation with 50 microM of the acetomethoxy form of BAPTA (BAPTA/AM) was followed by a transient reduction in free cytosolic Ca2+ concentration ((Ca2+]i). To compensate for the increased Ca2+ buffering capacity in the cytosol the acini incorporated Ca2+ from the external medium. Although BAPTA prevented changes in free cytosolic Ca2+ concentration during carbachol and atropine treatment, it had no apparent effect on Ca2+ content of the internal stores or the ability of agonists to release Ca2+ from these stores. Loading the cytosol with BAPTA considerably reduced the rate of Ca2+ reloading. These observations are not compatible with direct communication between the medium and the inositol 1,4,5-trisphosphate releasable pool and provide direct evidence for Ca2+ entry into the cytosol prior to its uptake into the intracellular pool, both during cell stimulation and the Ca2+ reloading.


Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men.
Our aim was to investigate the predictive power of a panel of variables in glucose and insulin metabolism for the incidence of stroke or transient ischaemic attacks (TIA). We hypothesised that proinsulin and insulin resistance contributes to an increase of risk for fatal and non-fatal stroke/TIA, independently of diabetes and established risk factors. The study is based on the Uppsala Longitudinal Study of Adult Men cohort. The examinations were performed at age 70 years. In 1,151 men free from stroke at baseline, 150 developed stroke or TIA during a median follow-up of 8.8 years. In unadjusted Cox proportional hazards analyses, a 1 SD increase of a predictor variable was associated with an increased risk for stroke/TIA, e.g. plasma insulin (HR 1.19, 95% CI 1.01-1.40), fasting intact proinsulin (HR 1.28, 95% CI 1.09-1.49); whereas a 1 SD increase in insulin sensitivity measured by the euglycaemic insulin clamp method decreased the risk for stroke/TIA (HR 0.81, 95% CI 0.68-0.96). The predictive values of fasting intact proinsulin and insulin sensitivity endured but not that of plasma insulin when adjusting for diabetes. In models adjusting for diabetes, hypertension, atrial fibrillation, electrocardiographic left ventricular hypertrophy, serum cholesterol and smoking, proinsulin remained as a significant predictor of later stroke/TIA (HR 1.22, 95% CI 1.00-1.48) whereas clamp insulin sensitivity did not (HR 0.87, 95% CI 0.71-1.07). Fasting intact proinsulin level and insulin sensitivity at clamp predicted subsequent fatal and non-fatal stroke/TIA, independently of diabetes in elderly men whereas fasting insulin did not.


[Therapeutic approach to actinomycosis--experience gained at the department of infectious and tropical diseases].
Actinomycosis is a chronic infectious disease caused by anaerobic, gram-positive microorganisms from the order of Actinomyce or Propionobacterium. The disease manifests iself mostly in cervicofacial form and less frequently in thoracic and abdominal form. The study was aimed at reviewing clinical manifestations and therapeutic approaches in treatment of patients with Actinomycosis. The study sample consisted of four patients with different clinical manifestations of Actinomycosis, who had been treated at the Institute for Infectious and Tropical Diseases in Belgrade in 2002, 2003, 2006 and 2008. Four patients with Actinomycosis were treated during the above mentioned periods of time. One patient had kidney Actinomycosis, which developed into generalized Actinomycosis. Two patients had the most common cervical form, while the forth one had abdominal form; all patients received Penicillin G followed by Ampicillin, during the period of four weeks to up to a year. Actinomycosis is a rare disease, which imposes great diagnostic dilemmas. The treatment of this disease requires long term use of antibiotics.


CO-OP for Children with DCD: Goals Addressed and Strategies Used.
Developmental coordination disorder (DCD) is a neurodevelopmental disorder that impacts motor coordination and interferes with participation in everyday activities. Cognitive Orientation to Occupational Performance (CO-OP) is a client-centered treatment approach that focuses on skill acquisition through cognitive strategy use. To determine which types of goals a sample of children with DCD choose most frequently and which domain-specific strategies were most commonly used to address these goals. Retrospective chart review of 50 children (8-12 years) with DCD who completed CO-OP intervention was conducted to identify goal types and strategy use. Leisure was the most common goal type. Supplementing task knowledge, body position, and task modification were the most frequently used strategies. Results confirm the types of goals that are commonly selected by children with DCD and highlight commonly used strategies used to meet these goals. Findings will help guide occupational therapists in selecting appropriate strategies to meet children's goals.


Surface-confined supramolecular coordination chemistry.
The non-covalent synthesis of coordination compounds and networks provides promising avenues towardsmetal-containing supermolecules and nanostructured materials with ultimate feature definition. An importantfactor for their further development, and their integration and exploitation in nanoscale functional systems,is the capability to prepare or organize them at well-defined substrates or templated environments. Supramolecularengineering on atomistically controlled surfaces has been propelled by the direct insight into low-dimensionalcoordination systems provided by scanning tunneling microscopy observations. Here we discuss the principlesof surface-confined supramolecular coordination chemistry, emphasizingself-assembly protocols conducted on surface atomic lattices employing metal centers to direct the organizationof molecular ligands and the template-induced organization of prefabricated metallosupramolecular species.The presented exemplary molecular-level studies elucidate the arrangement of organic adsorbates and transitionmetal adatoms on low-index metal and graphite surfaces. They reveal the interplay between molecule-adatom,intermolecular, and adsorbate-substrate interactions, which need to be balanced for the fabricationof low-dimensional nanostructures. The control and understanding of both the nature of metal-ligandinteractions and the resulting supramolecular organization on solid surfaces is decisive for the designof advanced architectures with concomitant functions. The realized metallosupramolecular compounds andarrays combine the properties of their constituent metal ions and organic ligands, and feature versatilestructural characteristics as well as attractive functional aspects: their redox, magnetic, spin-state,and electronic transitions.


Specificity of the cholesterol side-chain cleavage enzyme system of adrenal cortex.
Incubation of lanosta-8, 24-dien-3beta-o1-1,2-3H and lanost-8-en-3beta-o1-1,2-3H with an adrenocortical bovine mitochondrial acetone-dried preparation did not yield any significant (less than 0.01%) 3beta-hydroxy-4, 4, 14-trimethyl-5alpha-pregn-8-en-20-one. Under the same conditions cholesterol-1,2-3H yielded 8.3% pregnenolone. Incubation of (20S)-17alpha, 20-di-hydroxycholesterol-7-3H yielded 0.6 to 1.6% (20S,22R)-17alpha, 20, 22-trihydroxycholesterol, 1.0 to 3.2% of 17alpha-hydroxy-pregnenolone, but no significant (less than 0.02%) (20S,22S)-17alpha,20,22-trihydroxycholesterol. In another experiment incubation of cholesterol-1,2-3H yielded 5% pregnenolone, 0.5% 17alpha-hydroxypregnenolone, 0.2% (20R,22R)-20,22-dihydroxy-cholesterol, but no significant ( less than 0.01%) 17alpha-hydroxy-cholesterol, (20S)-17alpha, 20-dihydroxycholesterol or (20S,22R)-17alpha, 20,22-trihydroxycholesterol.


Vibration characteristics of dental high-speed turbines and speed-increasing handpieces.
Vibrations of dental handpieces may contribute to symptoms of hand-arm vibration syndrome in dental personnel and iatrogenic enamel cracking in teeth. However, methods for measuring dental handpiece vibrations have previously been limited and information about vibration characteristics is sparse. This preliminary study aimed to use a novel approach to assess the vibrations of unloaded high-speed handpieces in vitro. Maximum vibration displacement amplitudes of five air turbines and two speed-increasing handpieces were recorded whilst they were operated with and without a rotary cutting instrument (RCI) using a scanning laser vibrometer (SLV). RCI rotation speeds, calculated from frequency peaks, were consistent with expected values. ANOVA statistical analysis indicated significant differences in vibrations between handpiece models (p<0.01), although post hoc tests revealed that differences between most individual models were not significant (p>0.11). Operating handpieces with a RCI resulted in greater vibrations than with no RCI (p<0.01). Points on the head of the handpiece showed greater vibration displacement amplitudes than points along the body (p<0.01). Although no single measurement exceeded 4 microm for the handpieces in the current test setup (implying that these vibrations may be unlikely to cause adverse effects), this study has formed the basis for future work which will include handpiece vibration measurements whilst cutting under clinically representative loads.


DNA damage response and repair pathway modulation by non-histone protein methylation: implications in neurodegeneration.
Protein post-translational modifications (PTMs) have emerged to be combinatorial, essential mechanisms used by eukaryotic cells to regulate local chromatin structure, diversify and extend their protein functions and dynamically coordinate complex intracellular signalling processes. Most common types of PTMs include enzymatic addition of small chemical groups resulting in phosphorylation, glycosylation, poly(ADP-ribosyl)ation, nitrosylation, methylation, acetylation or covalent attachment of complete proteins such as ubiquitin and SUMO. Protein arginine methyltransferases (PRMTs) and protein lysine methyltransferases (PKMTs) enzymes catalyse the methylation of arginine and lysine residues in target proteins, respectively. Rapid progress in quantitative proteomic analysis and functional assays have not only documented the methylation of histone proteins post-translationally but also identified their occurrence in non-histone proteins which dynamically regulate a plethora of cellular functions including DNA damage response and repair. Emerging advances have now revealed the role of both histone and non-histone methylations in the regulating the DNA damage response (DDR) proteins, thereby modulating the DNA repair pathways both in proliferating and post-mitotic neuronal cells. Defects in many cellular DNA repair processes have been found primarily manifested in neuronal tissues. Moreover, fine tuning of the dynamicity of methylation of non-histone proteins as well as the perturbations in this dynamic methylation processes have recently been implicated in neuronal genomic stability maintenance. Considering the impact of methylation on chromatin associated pathways, in this review we attempt to link the evidences in non-histone protein methylation and DDR with neurodegenerative research.


Evaluation of intestinal viability using 3-charge coupled device image enhancement technology in a pediatric laparoscopic appendectomy model.
Intraoperative laparoscopic determination of intestinal viability is currently limited to subjective visible cues. Adjunctive modalities are neither widely available nor practical. Three-charge coupled device (3-CCD) imaging directly correlates the amount of light detected by CCDs to tissue oxygenation. We hypothesize that application of 3-CCD image enhancement detects bowel ischemia in a pediatric laparoscopic appendectomy model. We recorded 10 laparoscopic appendectomies for appendicitis. Offline analysis involved selecting regions of interest (ROIs) in the appendix, adjacent colon, and nonappendiceal fat and calculating mean intensity values in selected images before and after division of the mesoappendix. The colon was used as a control, and the intensity values were normalized to fat. As an indicator of decreased perfusion, the mean appendix ROI intensity values decreased over time (R(2) = 0.92) compared with the colon mean ROI intensity values, which remained stable. There was a statistically significant difference between fat-normalized intensity values for ischemic and nonischemic appendix after 1 minute. We have demonstrated proof of principle for the determination of bowel ischemia using 3-CCD image enhancement. By quantitatively identifying areas of ischemia, this technique has the potential to significantly change the management of ischemic bowel in the future.


Comparative review of ambient air PM2.5 source apportioning studies in Tehran.
Rapid urbanization and consuming lifestyles have intensified air pollution in urban areas. Air pollution in megacities has imposed severe environmental damages to human health. Proper management of the issue necessitates identification of the share of emission sources. Therefore, numerous research works have studied the apportionment of the total emissions and observed concentrations among different emissions sources. In this research, a comprehensive review is conducted to compare the source apportioning results for ambient air PM2.5 in the megacity of Tehran, the capital of Iran. One hundred seventy-seven pieces of scientific literatures, published between 2005 and 2021, were reviewed. The reviewed research are categorized according to the source apportioning methods: emission inventory (EI), source apportionment (SA), and sensitivity analysis of the concentration to the emission sources (SNA). The possible reasons for inconsistency among the results are discussed according to the scope of the studies and the implemented methods. Although 85% of the reviewed original estimates identify that mobile sources contribute to more thant 60% of Tehran air pollution, the distribution of vehicle types and modes are clearly inconsistent among the EI studies. Our review suggests that consistent results in the SA studies in different locations in central Tehran may indicate the reliability of this method for the identification of the type and share of the emission sources. In contrast, differences among the geographical and sectoral coverage of the EI studies and the disparities among the emission factors and activity data have caused significant deviations among the reviewed EI studies. Also, it is shown that the results of the SNA studies are highly dependent on the categorization type, model capabilities and EI presumptions and data input to the pollutant dispersion modelings. As a result, integrated source apportioning in which the three methods complement each other's results is necessary for consistent air pollution management in megacities. The online version contains supplementary material available at 10.1007/s40201-023-00855-0.


Correlation of disease activity with circulating immune complexes (C1qbA) and complement breakdown products (C3D) in patients with systemic lupus erythematosus. A prospective study.
Most biologic effects of immune complexes are mediated through the activation of the complement system. The relationship between lupus disease activity and the presence of C3 breakdown products (C3d) and circulating immune complexes (CIC) as demonstrated with the C1q binding assay (C1qbA), was evaluated. Nearly all 13 systemic lupus erythematosus (SLE) patients had a stable disease course in this prospective study, nevertheless, in each patient the profiles of the serologic parameters were quite different. Despite the small number of investigated patients (13), it is concluded that irrespective of the disease activity, the serologic parameters could be either positive or negative. No relationship could be obtained between disease activity and the presence of C3d and/or CIC. Nor was there any evidence that the presence of CIC would indicate increased levels of C3 breakdown products (C3d). This observation argues against a pathogenetic significance of CIC detected by the C1qbA in SLE. In conclusion, the supposed link between the presence of CIC, consumption and activation of the complement system, and the activity of SLE needs further study.


Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma.
Basal cell carcinoma (BCC) of the skin is the most common malignant neoplasm in humans. BCC is primarily driven by the Sonic Hedgehog (Hh) pathway. However, its phenotypic variation remains unexplained. Our genetic profiling of 293 BCCs found the highest mutation rate in cancer (65 mutations/Mb). Eighty-five percent of the BCCs harbored mutations in Hh pathway genes (PTCH1, 73% or SMO, 20% (P = 6.6 × 10(-8)) and SUFU, 8%) and in TP53 (61%). However, 85% of the BCCs also harbored additional driver mutations in other cancer-related genes. We observed recurrent mutations in MYCN (30%), PPP6C (15%), STK19 (10%), LATS1 (8%), ERBB2 (4%), PIK3CA (2%), and NRAS, KRAS or HRAS (2%), and loss-of-function and deleterious missense mutations were present in PTPN14 (23%), RB1 (8%) and FBXW7 (5%). Consistent with the mutational profiles, N-Myc and Hippo-YAP pathway target genes were upregulated. Functional analysis of the mutations in MYCN, PTPN14 and LATS1 suggested their potential relevance in BCC tumorigenesis.


Injuries caused by home-made explosives.
Eighty-six cases of injuries caused by home-made unconventional explosives were studied. The use of this type of explosive is common in India, Sri Lanka and other Eastern countries. Injuries are due to the blast effect, shrapnel and flash. The blast effect is seen only when the explosion occurs at close range. Accidental injuries to handlers and manufacturers conform to a particular pattern.


Fine structural changes in cat L7 ventral horn neurones after chronic sub LD50 DFP.
The fine structural changes in the ventral anterior horn of spinal segment L7, have been studied in adult cats after single and chronic sub LD50 (0.1 to 0.75 mg/kg SC with a cumulative range of 1.3 mg/kg to 10.5 mg/kg) low dose exposure to diisopropylfluorophosphate (DFP). Only the motoneurons of the chronically treated animals show an increase in the number of lysosomes, neurofilaments and vesicle-like structures. A large number of coated vesicles is observed within axons and axon terminals of both acute and chronically treated animals. Morphological evidence of axon and terminal degeneration is seen only in chronically treated animals. The present study shows that chronic sub LD50 low dose administration of DFP over periods from 5 to 21 days results in degenerative changes of presynaptic terminals and axons, with the severity of the changes being dependent on dose and duration of treatment. The data are interpreted by comparison with single high dose exposure reported in the literature with a discussion of acute and delayed neurotoxic effects of DFP, on the central nervous system.


Isolation and characterization of human CapG expressed and post-translationally modified in Pichia pastoris.
CapG is an actin-binding protein, which is overexpressed in a variety of tumors, i.e. breast, ovarian, pancreatic and lung carcinoma. We successfully expressed human CapG in the wild type strain X-33 of the methylotrophic yeast Pichia pastoris (P. pastoris), which does not express endogenous CapG, in order to characterize this protein in more detail. After mechanical cell lysis, debris was centrifuged and the soluble protein was precipitated with ammonium sulfate. This protein pellet was dialyzed and used for CapG purification. Ca2+-dependent exposure of hydrophobic sites allowed single step and selective elution from a Phenyl Sepharose™ matrix. 3.5 mg CapG/10 g wet biomass were isolated and showed a Ca2+-sensitive and dose-dependent capping activity of actin in a fluorometric assay. In P. pastoris, CapG is located at actin patches, actin cables and arranges along the budding neck. The proliferation rate and morphology of the yeast cells are not influenced by the interaction of CapG with actin. The modification pattern of human CapG from P. pastoris and human carcinoma cells is highly similar. We validated most of the known post-translational modifications and found three new phosphorylation and nine new acetylation sites by mass spectrometry. The N-terminus is acetylated or truncated. Truncated CapG is not phosphorylated at the residues S10, T212 and S337. First mutagenesis experiments indicate an N-terminal acetylation dependent C-terminal phosphorylation.


Neonatal Abstinence Syndrome.
This review examines the continuum of care of opioid-exposed infants, including the assessment of the neonate, diagnosis of neonatal abstinence syndrome, management of the syndrome including nonpharmacologic and pharmacologic care, approach to breastfeeding, pediatric follow-up care, and integration of care of the mother-infant dyad.


Metagenomics revealing molecular profiles of microbial community structure and metabolic capacity in Bamucuo lake, Tibet.
Microorganisms play critical ecological roles in the global biogeochemical cycles. However, extensive information on the microbial communities in Qinghai-Tibet Plateau (QTP), which is the highest plateau in the world, is still lacking, particularly in high elevation locations above 4500 m. Here, we performed a survey of th e soil and water microbial communities in Bamucuo Lake, Tibet, by using shotgun metagenomic methods. In the soil and water samples, we reconstructed 75 almost complete metagenomic assembly genomes, and 74 of the metagenomic assembly genomes from the water sample represented novel species. Proteobacteria and Actinobacteria were found to be the dominant bacterial phyla, while Euryarchaeota was the dominant archaeal phylum. The largest virus, Pandoravirus salinus, was found in the soil microbial community. We concluded that the microorganisms in Bamucuo Lake are most likely to fix carbon mainly through the 3-hydroxypropionic bi-cycle pathway. This study, for the first time, characterized the microbial community composition and metabolic capacity in QTP high-elevation locations with 4555 m, confirming that QTP is a vast and valuable resource pool, in which many microorganisms can be used to develop new bioactive substances and new antibiotics to which pathogenic microorganisms have not yet developed resistance.


Physicochemical and rheological properties of pomelo albedo pectin and its interaction with konjac glucomannan.
Pomelo albedo was extracted with water to obtain the high methoxyl pectin, labeled as PAP. The physicochemical and rheological properties of PAP were determined. The effects of PAP addition on rheological property and thermal stability of konjac glucomannan (KGM) were evaluated. Results indicated that PAP was composed of arabinose, glucose and galacturonic acid with a relative mass percentage of 7.2%: 9.5%: 83.3%, and exhibited an average molecular weight of 56.6 kDa. The degree of esterification of PAP was 65.5%, showing PAP was a kind of high methoxyl pectin. Apparent viscosity of PAP was concentration-dependently increased, while it was slightly enhanced with salt (NaCl or CaCl2) addition. Moreover, the addition of PAP declined the apparent viscosity, elastic property and thermal stability of KGM. It can be concluded that interaction was occurred between KGM and PAP. Meanwhile, the interaction mechanism between KGM and PAP has been preliminarily proposed. The present study can provide some references for the application of PAP and support the combination usage of this pectin and KGM in food and other industries.


Isolation of myelin basic protein-specific T cells predominantly from the memory T-cell compartment in multiple sclerosis.
Myelin antigen-reactive T cells have been implicated in the pathogenesis of multiple sclerosis (MS). Myelin-reactive T cells can be isolated from control subjects as well as individuals who have MS. Experimental models of MS indicate that recently stimulated, myelin-reactive T cells have greater encephalitogenic potential than resting T cells. Activation induces changes in T-cell surface antigens that may distinguish previously stimulated, memory T cells from naive T cells. Therefore, we examined 108 myelin basic protein (MBP)-reactive T-cell lines from 7 MS and 8 control subjects to determine whether MBP-reactive T cells originated in the memory T-cell subset or in the naive subset. Isotypes of CD45 were used that designate memory or naive T cells. In subjects having MS, 84% of the MBP-reactive T cells resided in the memory T-cell subset. However, in control subjects, only 13% of MBP-specific T cells originated from the memory T-cell subset. This result suggests that a substantial proportion of MBP-reactive T cells from some individuals with MS have been previously activated in vivo. This difference provides additional support for the hypothesis that myelin antigen-specific T cells are involved in the pathogenesis of MS.


Intestinal specific overexpression of interleukin-7 attenuates the alternation of intestinal intraepithelial lymphocytes after total parenteral nutrition administration.
Total parenteral nutrition (TPN), with the complete removal of enteral nutrition, results in marked changes in intestinal intraepithelial lymphocyte (IEL) function and phenotype. Previous work shows that TPN results in a loss of intestinal epithelial cell-derived interleukin-7 (IL-7), and this loss may play an important role in development of such TPN-associated IEL changes. To further understand this relation, we generated a transgenic mouse (IL-7), which overexpresses IL-7 specifically in intestinal epithelial cells. We hypothesized that this localized overexpression would attenuate many of the observed TPN-associated IEL changes. Our study showed that TPN administration led to significant changes in IEL phenotype, including a marked decline in the CD8alphabeta+, CD4+, and alphabeta-TCR+ populations. IEL basal proliferation decreased 1.7-fold compared with wild-type TPN mice. TPN administration in wild-type mice resulted in several changes in IEL-derived cytokine expression. IL-7 mice given TPN, however, maintained IEL proliferation, and sustained normal IEL numbers and phenotype. We conclude that specific intestinal IL-7 overexpression significantly attenuated many IEL changes in phenotype and function after TPN administration. These findings suggest a mechanism by which TPN results in observed IEL changes.


A comparison of two methods to investigate the metabolism of human apolipoproteins A-I and and A-II.
Two methods are compared for measuring the kinetic parameters of apolipoprotein A-I and A-II metabolism in human plasma. In the first, high density lipoprotein apoproteins were radioiodinated in situ in the lipoprotein particle (endogenous apoprotein labeling) while in the second, individually labeled apolipoprotein A-I or A-II was incorporated into the particle by in vitro incubation (exogenous apoprotein labeling). The catabolic clearance rate of exogenously labeled apolipoprotein A-I was consistently faster than that of endogenous apolipoprotein A-I. Conversely, endogenously and exogenously labeled apolipoprotein A-II were catabolized at identical rates. The fractional plasma clearance rates of endogenous apolipoproteins A-I and A-II were the same.


Non-canonical roles of lysyl-tRNA synthetase in health and disease.
Lysyl-tRNA synthetase (LysRS) is a highly conserved enzyme that is part of the translational machinery in all living cells. Besides its canonical role in translation, LysRS gained additional domains and functions throughout evolution. These include its essential role in HIV replication and its roles in transcriptional regulation, cytokine-like signaling, and transport of proteins to the cell membrane. These diverse processes are tightly regulated through post-transcriptional modifications, interactions with other proteins, and targeting to the various cell compartments. The emerging variety of tasks performed by LysRS may therefore be utilized by various processes and pathological conditions that are described in this review, and their ongoing investigation is of extreme importance for our understanding of basic cellular regulatory mechanisms.


Production, transportation and milling costs of sweet sorghum as a feedstock for centralized bioethanol production in the upper Midwest.
Sweet sorghum has been identified as a possible ethanol feedstock because of its biomass yield and high concentration of readily fermentable sugars. It has found limited use, however, because of poor post-harvest storage characteristics and short harvest window in cooler climates. Previous research (Bennett, A.S., Anex, R.P., 2008. Farm-gate production costs of sweet sorghum as a bioethanol feedstock. Transactions of the ASABE 51(2), 603-613) indicates that fermentable carbohydrates (FC) can be produced at less expense from sweet sorghum than from corn grain. Previous research, however, did not include costs associated with off-farm transportation, storage, or capital costs associated with milling and energy recovery equipment that are required to provide FC suitable for biological conversion. This study includes these additional costs and reevaluates sweet sorghum as a biocommodity feedstock. A total of eight harvest-transport-processing options are modeled, including 4-row self-propelled and 2-row tractor-pulled forage harvesters, two different modes of in-field transport, fresh processing, on-farm ensilage and at-plant ensilage. Monte Carlo simulation and sensitivity analysis are used to account for system variability and compare scenarios. Transportation costs are found to be significant ranging from $33 to $71 Mg (-1) FC, with highest costs associated with at-plant ensilage scenarios. Economies of scale benefit larger milling equipment and boiler systems reducing FC costs by more than 50% when increasing annual plant capacity from 37.9 to 379 million liters. Ensiled storage of high moisture sweet sorghum in bunkers can lead to significant losses of FC (>20%) and result in systems with net FC costs well above those of corn-derived FC. Despite relatively high transport costs, seasonal, fresh processed sweet sorghum is found to produce FC at costs competitive with corn grain derived FC.


An Insight Into the Impact of Polymers on the Hydrate Conversion of Olanzapine Form I in Aqueous Suspensions.
The potential of polyethyleneglycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropylcellulose (HPC) to inhibit the hydration of olanzapine (OLZ) in aqueous environments was assessed. OLZ Form I (OLZ) suspended in water (A) or in aqueous polymer solutions (2%, 0.2%, 0.02%, and 0.002%) (PEG 6000 [B], PEG 40,000 [C], HPC LF [D], or PVP K30 [E]). Filtered samples were analyzed by different techniques (X-ray powder diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, 1H-nuclear magnetic resonance spectroscopy). OLZ hydration showed to be faster in water than in PEG solutions, regardless of the polymer molecular weight. OLZ in D and E suspensions remained anhydrous at concentrations of 2%-0.02%. The NMR measurements revealed that all of these polymers were able to establish hydrogen bonds with the OLZ molecule and increased its saturation solubility, but only D and E showed to increase the wettability of the OLZ particles due to binding of these polymers to the surface of hydrate nuclei/first crystals OLZ crystals. This study provided an insight into the mechanisms of OLZ hydrate protection by polymers. It confirmed the advantage of using PVP K30 or HPC LF in wet granulation in concentrations as low as 0.02% to prevent formation of OLZ hydrates, due to the combined effect of H-bond ability and the strong bonding of these polymers to the surface of the crystals.


Impact of postoperative telemedicine visit versus in-person visit on patient satisfaction: A randomized clinical trial.
Although telemedicine use has increased dramatically during the COVID-19 pandemic and beyond, the impact of telemedicine versus in-person postoperative visits on patient satisfaction has not been studied prospectively. We hypothesized that telemedicine visits would be noninferior to in-person visits in terms of postoperative colorectal surgery patient satisfaction. We conducted a randomized trial of consecutive adult patients undergoing transabdominal colorectal surgery from September 2020 to February 2021. Eligible participants were randomized 1:1 to either receive a telemedicine visit (Arm T) or an in-person visit (Arm I) for their first postoperative appointment. Subsequently, participants in Arm T completed a second postoperative visit in person, and participants in Arm I completed a second postoperative visit via telemedicine. All participants completed a patient satisfaction survey electronically within 24 hours after each postoperative visit. The primary endpoint was total patient satisfaction score. Secondary endpoints included patient-reported safety score, length of visit, and willingness of patients to recommend the practice to their peers. Fisher's exact test, χ2 analysis, and Student's t test were used to compare outcomes. A total of 46 patients were analyzed with 23 each in Arm T and Arm I. The mean age of our study cohort was 50.6 (standard deviation 17.7) years and 52% were female. No significant differences were found between groups in terms of baseline characteristics. With respect to our primary endpoint of total satisfaction score, patient satisfaction scores in Arm T were non-inferior to those in Arm I. Similarly, there was no significant difference in satisfaction scores after the second postoperative visit when the visit types were reversed. We did not find any significant differences between groups in terms of our secondary endpoints. Postoperative telemedicine visits were a safe and time-efficient option that maintained high patient satisfaction compared with in-person postoperative visits.


[A neurophysiological analysis of the forms of wakefulness and rest in the toad Bufo bufo and the frog Rana ridibunda in the circadian cycle].
Studies have been made on the spectral EEG parameters in the forebrain and midbrain of the toad and frog during active and passive forms of natural behaviour within a diurnal cycle. Basing on evaluation of animal reactivity and on EEG analysis performed by presentation of the power of EEG signals via the frequency spectrum, it is possible to obtain a reliable identification of functional condition of amphibians. Behavioural and EEG patterns of 3 forms of wakefulness and 2 forms of rest are presented for frogs and toads.


Cellular injuries upon exposure of Escherichia coli and Lactobacillus rhamnosus to high-intensity ultrasound.
To examine cellular injuries occurring in cells of Escherichia coli (Gram-negative bacteria) and Lactobacillus rhamnosus (Gram-positive bacteria) in response to a high-intensity ultrasound treatment using classical plate count technique and flow cytometry. According to plate count results, E. coli (D-value 8.3 min) was far more sensitive than L. rhamnosus (D-value 18.1 min) in their response to the ultrasound intensity applied (20 kHz, 17.6 W). The dye precursor carboxyfluorescein diacetate (cFDA) could freely diffuse across the cytoplasmic membrane of intact cells of Gram-positive bacteria L. rhamnosus, resulting in its intracellular enzymatic conversion and emission of green fluorescence. In contrast, the presence of an outer membrane on E. coli, which represents the class of Gram-negative bacteria, apparently disabled the penetration of viability marker cFDA. Ultrasound application on E. coli yielded in an increasing population with disintegrated outer membrane, which allowed penetration of cFDA and its intracellular enzymatic conversion as well as accumulation. In both organisms evaluated only a small population was labelled by propidium iodide upon exposure to ultrasound for up to 20 min. Within the experimental conditions investigated ultrasound did not considerably affect the cytoplasmic membrane, although according to plate count results viability loss occurred. The results compiled suggest, that ultrasound induced cell death, which may not be related to membrane damage. Limitation on the use of bacteriocins, which are aimed on destabilization of cytoplasmic membrane but inhibited by the outer membrane, could be overcome by ultrasound-assisted physical disruption of the outer membrane.


Hydrodynamic properties of water in contractile system.
When muscle fragments are compressed, intracellular water leaks out. Unexpectedly, y-intercepts of regression lines in resting and active states become negative, implying "negative compression". It seems that in resting state there is a kind of mechanical equilibrium between proteins and water. This protein-water complex in muscle behaves like a synthesized elastomer under moderate extension, (less than 10%). Employing the data presented by Richie & Wilkie (1958), validity of elastomer model is examined. Compression study also shows that in active state a frictional drag of intracellular water decreases markedly. It leads to the assumption that the negative mechanical resistance may play a role in regenerative activation.


Responses in glabrous skin mechanoreceptors during precision grip in humans.
Impulses in single tactile units innervating the human glabrous skin were recorded percutaneously from the median nerve using tungsten electrodes. The units were classified as belonging to one of the four categories: fast adapting with small receptive fields (FA I), fast adapting with large receptive fields (FA II), slowly adapting with small fields (SA I), and slowly adapting with large fields (SA II). A small test object was lifted, positioned in space and replaced using the precision grip between fingers and thumb. The grip force, the load force (vertical lifting force), the vertical movements of the object and vibrations (accelerations) in the object were recorded. After being virtually silent between lifts, the FA I units whose fields contacted the object became highly active during the initial period of grip force increase (initial response). This was also true for most SA I units. Accordingly, most of the skin deformation changes took place at low grip forces (below ca. 1 N). Later, while the load and grip forces increased in parallel during isometric conditions, the FA I and SA I units continued firing but generally at declining impulse rates. As long as the object was held in the air, the SA I units generally maintained firing with a tendency to adaptation. A minority of the FA I unit also discharged, especially during periods of pronounced physiological muscle tremor. The SA I units usually became silent when the grip and load forces in parallel declined to zero during isometric conditions after the object had contacted the table. However, during the very release of the grip the FA I units and some SA I units showed brief burst discharges (release response). The FA II units responded distinctly to the mechanical transients associated with the start of the vertical movement and especially with the sudden cessation of movement at the terminal table contact. FA II units whose end organs were remotely located in relation to the skin areas in contact with the object also responded. Most FA II units also discharged at the initial touch and at the release of the object, albeit less reliably than the type I units. In addition to weak dynamic responses during the phase of isometric force increase, the SA II units showed comparatively strong tonic responses while the object was held during static conditions. High firing rates also were maintained during long-lasting lifts. Moreover, it was established that the signals in SA II afferents were related to the three dimensional force profile in the grip.(ABSTRACT TRUNCATED AT 400 WORDS)


Immunization of monkeys with recombinant complimentary deoxyribonucleic acid expressed zona pellucida proteins.
To evaluate the effects of immunization with zona pellucida (ZP) proteins produced by recombinant complementary DNA (cDNA) technology for the elicitation and antibodies that inhibit sperm binding without altering ovarian function in the nonhuman primate. Controlled nonhuman primate study. Controlled environment with individual housing of monkeys in facility approved by National Institutes of Health (NIH) guidelines. Monkeys housed and treated according to NIH regulations. Monkeys immunized and boosted at regular intervals with ZP proteins produced using recombinant cDNA techniques. Urinary estrogen, P, serum antibody levels, sperm-ZP binding, and ovarian morphology. Monkeys immunized with a recombinant rabbit 75-kd ZP protein expressed from a partial cDNA in the pEX bacteria expression system produce antibodies that interfere with ovarian follicular development and ovarian cyclicity. On the contrary, monkeys immunized with a recombinant rabbit 55-kd ZP protein develop antibodies that inhibit homologous sperm binding but do not affect ovarian follicular development or subsequent ovarian hormonal cyclicity. Monkey antibodies to the rabbit 75-kd ZP recombinant protein can be generated that inhibit ovarian cyclicity as desired for animal sterilization vaccines. Antibodies to the 55-kd ZP recombinant protein inhibit homologous monkey sperm binding to the ZP without altering ovarian endocrine function or morphology as is desired for human immunocontraception.


MK886, a potent and specific leukotriene biosynthesis inhibitor blocks and reverses the membrane association of 5-lipoxygenase in ionophore-challenged leukocytes.
Recently, we have shown that ionophore activation of human leukocytes results in leukotriene synthesis and a translocation of 5-lipoxygenase from the cytosol to cellular membrane. This membrane translocation was postulated to be an important early activation step for the enzyme. 3-[1-(p-Chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2, 2- dimethylpropanoic acid (MK886) is a potent and specific inhibitor of leukotriene biosynthesis in vivo and in intact cells, but has no direct effect on 5-lipoxygenase activity in cell-free systems. In this report, we show that MK886 can both prevent and reverse the membrane translocation of 5-lipoxygenase, in conjunction with the inhibition of leukotriene synthesis. Similar compounds of the indole class could also inhibit the membrane translocation of 5-lipoxygenase in a rank order of potency that correlated with their potencies for leukotriene synthesis inhibition. In contrast L-656,224, a direct 5-lipoxygenase inhibitor, had no effect on the translocation of the enzyme. Attempts to demonstrate the effects of MK886 on the association of 5-lipoxygenase with membrane in cell-free preparations failed due to a nonspecific Ca2+-dependent sedimentation of the enzyme. The mechanism of action of MK-886 is therefore to block translocation, prevent subsequent activation of 5-lipoxygenase, and hence block cellular leukotriene biosynthesis.


B-lymphocyte-induced maturation protein-1 (Blimp-1) gene of torafugu (Takifugu rubripes).
Homologous gene of B-lymphocyte-induced maturation protein-1 (Blimp-1) of torafugu (Takifugu rubripes) was identified by tblast search analysis. RT-PCR and 5'RACE clearly defined the sequence of the UTR and coding region which has been ambiguously determined by tblast analysis. Fugu Blimp-1 was mainly expressed in the lymphoid organs. These finding imply that Blimp-1 would take a major role in the terminal differentiation of B-cells to plasma cells in fish.


Urethral prosthesis for treatment of prostatic abscess in a dog.
A dog with a prostatic abscess was treated successfully with surgical implantation of a urethral prosthesis after 6 recurring episodes of abscess formation failed to respond to antibiotic therapy, surgical drainage, and bilateral marsupialization.


Cinnamoyl coA: NADP oxidoreductase-like 1 regulates abscisic acid response by modulating phaseic acid homeostasis in Arabidopsis thaliana.
Phaseic acid (PA), a main catabolite of abscisic acid (ABA), is structurally related to ABA and possesses ABA-like hormonal activity. However, the comprehensive metabolism pathway and roles of PA are not well understood. Here, using homologous alignment and expression pattern analysis, we identified in Arabidopsis the previously named CRL1 (Cinnamoyl coA: NADP oxidoreductase-like 1) as a PA reductase that catalyses PA to dihydrophaseic acid. The function of CRL1 and the potential role of PA were studied in transgenic CRL1 plants. Overexpression of CRL1 resulted in decreased ABA sensitivity in seed germination and attenuated drought tolerance. In contrast, increased ABA sensitivity and elevated drought tolerance was observed in down-regulated and loss-of-function crl1 mutants. Tyr162 in the conserved motif is the key residue in CRL1 to catalyse PA. Accelerated seed germination and earlier flowering phenotype were also observed in overexpressing lines, while retarded seed germination and delayed flowering occurred in crl1 mutants which accumulated more PA, but less dihydrophaseic acid than the wild type. This study demonstrates that PA plays diverse functions in drought tolerance, seed germination and flowering in an ABA-like manner, which may increase the adaptive plasticity of plants.


2019 in review: FDA approvals of new medicines.
The US Food and Drug Administration (FDA) green-lighted the marketing of 53 therapeutic agents in 2019. This rate of approvals was consistent with the 5-year running average. Nonetheless, a few changes are worth noting. The rate of medicines first approved using an orphan drug designation declined from 56% in 2018 to 41% in 2019, which mirrored a comparable decline in the use of priority review. A second notable feature was an uptick in industry consolidation. Twenty-five companies were lost, primarily because of mergers, leaving only 146 extant companies that have contributed to the research or development of an innovative FDA-approved medicine.


Comparative and phylogenetic analyses of six Kenya Polystachya (Orchidaceae) species based on the complete chloroplast genome sequences.
Polystachya Hook. is a large pantropical orchid genus (c. 240 species) distributed in Africa, southern Asia and the Americas, with the center of diversity in Africa. Previous studies on species of this genus have not obtained the complete chloroplast genomes, structures and variations. Additionally, the phylogenetic position of the genus in the Orchidaceae is still controversial and uncertain. Therefore, in this study, we sequenced the complete plastomes of six Kenya Polystachya species based on genome skimming, subjected them to comparative genomic analysis, and reconstructed the phylogenetic relationships with other Orchidaceae species. The results exhibited that the chloroplast genomes had a typical quadripartite structure with conserved genome arrangement and moderate divergence. The plastomes of the six Polystachya species ranged from 145,484 bp to 149,274 bp in length and had an almost similar GC content of 36.9-37.0%. Gene annotation revealed 106-109 single-copy genes. In addition, 19 genes are duplicated in the inverted regions, and 16 genes each possessd one or more introns. Although no large structural variations were observed among the Polystachya plastomes, about 1 kb inversion was found in Polystachya modesta and all 11 ndh genes in the Polystachya plastomes were lost or pseudogenized. Comparative analysis of the overall sequence identity among six complete chloroplast genomes confirmed that for both coding and non-coding regions in Polystachya, SC regions exhibit higher sequence variation than IRs. Furthermore, there were various amplifications in the IR regions among the six Polystachya species. Most of the protein-coding genes of these species had a high degree of codon preference. We screened out SSRs and found seven relatively highly variable loci. Moreover, 13 genes were discovered with significant positive selection. Phylogenetic analysis showed that the six Polystachya species formed a monophyletic clade and were more closely related to the tribe Vandeae. Phylogenetic relationships of the family Orchidaceae inferred from the 85 chloroplast genome sequences were generally consistent with previous studies and robust. Our study is the initial report of the complete chloroplast genomes of the six Polystachya species, elucidates the structural characteristics of the chloroplast genome of Polystachya, and filters out highly variable sequences that can contribute to the development of DNA markers for use in the study of genetic variability and evolutionary studies in Polystachya. In addition, the phylogenetic results strongly support that the genus of Polystachya is a part of the tribe Vandeae.


In vivo responses of rat intestinal epithelium to intraluminal dietary lectins.
Although a variety of plant lectins are consumed as part of the normal human diet and are capable of binding to intestinal cell surfaces in vitro, little information exists on their effects on intact intestine. We have studied the acute effects of intraluminal administration of wheat germ agglutinin and concanavalin A in normal rats. Both lectins caused increased shedding of brush border membrane and, at higher concentrations, reduction in surface area, acceleration of cell loss, and shortening of villi. These changes were prevented by simultaneous administration of the appropriate sugar to inhibit binding, indicating that the effects were related to binding to carbohydrate residues of intestinal cells. Similar changes of brush borders were found after intraluminal administration of antiserum to sucrase-isomaltase, a surface protein of the brush border membrane, suggesting that the lectin effects resulted from cell surface receptor-lectin interaction rather than a primary intracellular effect. Our results suggest that dietary lectins may be in part responsible for normal turnover of brush border membrane, and support, in addition, the possibility that certain intestinal diseases such as celiac sprue may be the consequence of increased levels of lectin receptor allowing a dietary lectin to exert a toxic effect.


Everyday technology use among people with Parkinson's disease.
To explore the relevance of and ability to use everyday technology (ET) among people with Parkinson's Disease (PD) and to explore associations between ET use and global cognition and motor ability. Cross-sectional data was collected from 34 people with PD using the Short Everyday Technology Use Questionnaire+ (S-ETUQ+), the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and the Montreal Cognitive Assessment (MoCA). Out of 41 ETs in the S-ETUQ+, the mean number perceived as relevant was 27.5 (min-max 19-35, SD 3.6). A good ability to use ET was reported where many ETs had a challenge measure below participants' ability to use them. A strong positive correlation between the ability to use ET and global cognition (MoCA) (r = .676, p = <0.01) was shown. ET use has become integrated into everyday life and is important for participation. This study showed a high relevance of and good ability to use ET and a correlation between ET use and global cognition among people with mild-moderate PD. Evaluation and support to use ET in PD are important for maintaining independence and participation, especially among those with cognitive decline.


Functional disconnection of thalamic and cerebellar dentate nucleus networks in progressive supranuclear palsy and corticobasal syndrome.
To assess functional rearrangement following neurodegeneration in the thalamus and dentate nucleus in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We recruited 19 patients with PSP, 11 with CBS and 14 healthy subjects. All the subjects underwent resting-state (rs) fMRI using a 3T system. Whole brain functional connectivity of the thalamus and dentate nucleus were calculated by means of a seed-based approach with FEAT script in FSL toolbox. Thalamic volume was calculated by means of FIRST, and the dentate area by means of Jim software. Both thalamic volume and dentate area were significantly smaller in PSP and CBS patients than in healthy subjects. No significant difference emerged in thalamic volume between PSP and CBS patients, whereas dentate area was significantly smaller in PSP than in CBS. Thalamic functional connectivity was significantly reduced in both patient groups in various cortical, subcortical and cerebellar areas. By contrast, changes in dentate nucleus functional connectivity differed in PSP and CBS: it decreased in subcortical and prefrontal cortical areas in PSP, but increased asymmetrically in the frontal cortex in CBS. Evaluating the dentate nucleus size and its functional connectivity may help to differentiate patients with PSP from those with CBS.


Shear Wave Elastography and Quantitative Ultrasound as Biomarkers to Characterize Deep Vein Thrombosis In Vivo.
Investigate shear wave elastography (SWE) and quantitative ultrasound (QUS) parameters in patients hospitalized for lower limb deep vein thrombosis (DVT). Sixteen patients with DVT were recruited and underwent SWE and radiofrequency data acquisitions for QUS on day 0, day 7, and day 30 after the beginning of symptoms, in both proximal and distal zones of the clot identified on B-mode scan. SWE and QUS features were computed to differentiate between thrombi at day 0, day 7, and day 30 following treatment with heparin or oral anticoagulant. The Young's modulus from SWE was computed, as well as QUS homodyned K-distribution (HKD) parameters reflecting blood clot structure. Median and interquartile range of SWE and QUS parameters within clot were taken as features. In the proximal zone of the clot, the HKD ratio of coherent-to-diffuse backscatter median showed a significant decrease from day 7 to day 30 (P = .036), while the HKD ratio of diffuse-to-total backscatter median presented a significant increase from day 7 to day 30 (P = .0491). In the distal zone of the clot, the HKD normalized intensity of the echo envelope median showed a significant increase from day 0 to day 30 (P = .0062). No SWE features showed statistically significant differences over time. Nonetheless, a trend of lower median of Young's modulus within clot for patients who developed a pulmonary embolism was observed. QUS features may be relevant to characterize clot's evolution over time. Further analysis of their clinical interpretation and validation on a larger dataset would deserve to be studied.


Malignant autonomic dysreflexia in spinal cord injured men.
Case reports. To present a series of cases of protracted and severe autonomic dysreflexia (AD) in men with spinal cord injury (SCI), who sustained damage to their descending autonomic pathways. GF Strong Rehabilitation Centre, Sexual Health Rehabilitation Service, Vancouver Sperm Retrieval Clinic, Vancouver Coastal Health Authority, Vancouver, BC, Canada. AD is a serious complication of SCI triggered by a variety of noxious or non-noxious stimuli below the level of injury. However, we are presenting three cases of protracted, severe AD we have termed 'malignant', owing to the tendency of progressive worsening not usually seen with AD once the alleviating factor is removed. In all three individuals, AD was initially triggered by ejaculation and continued for a period of more than 1 week. Systolic blood pressure in these individuals increased above 220 mmHg and required either acute hospitalization or hospital assessment. Two of the individuals with malignant AD had American Spinal Injury Association (ASIA) B and C high cervical injury, respectively, with the third having a high thoracic ASIA A injury. In addition to detailed history and neurological examination, electrophysiological assessment of sympathetic skin responses (SSR) demonstrated a significant disruption of the descending autonomic pathways in these individuals. Our findings suggest that in addition to the severe injury of the motor and sensory pathways (assessed by ASIA score), these individuals sustained severe injury to the supraspinal autonomic control. A combination of strong triggers such as ejaculation and bladder or colono-rectal irritation with total loss of descending autonomic control to the spinal sympathetic circuits could therefore contribute to the unusual manifestation of AD.


Dance Intervention Using the Feldenkrais Method Improves Motor, and Non-Motor Symptoms and Gait in Parkinson's Disease: A 12-Month Study.
The aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period. This was a single-arm study in which 12 subjects with Parkinson's disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months. Dance intervention decreased motor scale (Unified Parkinson's Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL. Our findings suggest that dance intervention can be a complementary management method for PD patients.


Carbocyclic Ring Closure of Aryl C-Glycosides Promoted by Fluoroboric Acid.
A novel transformation from rhamnose-type C-glycosides to 2-cyclopentenones is described. With the promotion of fluoroboric acid, C-glycosides underwent ring opening and subsequent Nazarov cyclization to afford 2-cyclopentenones in good to excellent yields. The solvent and the concentration of acid are crucial to the yield of this transformation.


Effect of granulocytes on the microcirculation in free-flap surgery.
Impaired capillary perfusion may result in flap failure. Platelet emboli, vasospasm and/or polymorphonuclear leukocytes (PMNs) have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free-flap model. Sprague-Dawley rats were injected with either anti-neutrophil serum or saline. Their cremaster muscle was isolated on its pedicle. After arterial repair and reperfusion, capillary perfusion was counted each hour for 6 h. The number of PMNs was significantly reduced in the animals treated with anti-neutrophil serum. However, capillary perfusion did not improve in this group. These results demonstrate that depleting circulating PMNs does not counterbalance the reduction of perfused capillaries, i.e., does not increase their number. It is suggested that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.


Four factors of nurse caring in the ICU.
Phenomenological research is conducted to understand the lived experience of persons-patients, families, nurses. This research report describes the feelings of 15 critical care nurses about their experiences of caring. Four major factors (support, role modeling, patient and family interactions, and economic/bureaucratic forces) were identified as crucial aspects of caring in critical care by the nurses. These four factors can be used to increase caring behaviors of nurses in critical care.


Fibronectin network recovery in confluent PtK2 cells after acrylamide treatment.
Confluent PtK2 cells 4 hr treated with 5 mM acrylamide were FN-detected by indirect immunofluorescence. The initial fibrillar-FN network was replaced by an alveolar-type network located at the cell-cell contacts areas in the form of a thick frame with a lace-like appearance. Afterwards, acrylamide removal was obtained by several washes with fresh FCS-free culture medium. Then, PtK2 cells were returned to the incubator for 20 hr. Cell recovery was indicated by reversion of the initial fibrillar-FN network. These data show that FN reversion was possible without any changes in shape and cytoplasmic organization of non-motile growing cells.


The absolute counting of 166mHo, 58Co and 88Y.
In this study, absolute 4pi beta-gamma-coincidence counting was used to measure the mass activity of 166mHo, 58Co and 88Y. For 166mHo and 88Y, three gamma windows were set to study the systematic error caused by the different gamma window settings. To eliminate the effect arising from the large difference in counting efficiency of the 4pi beta counter between electron capture events and beta+ particles, the two-dimensional extrapolation method was used to measure 58Co. The measurement results for the three nuclides were linked with the BIPM SIR through two APMP regional comparisons, APMP.RI(II)-K2, Ho-166m and APMP.RI(II)K2.Co-58, Y-88. Results are presented.


Progressive plasmacytoid variant bladder cancer with retroperitoneal dissemination: An autopsy case report.
Plasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer. A 75-year-old woman presented with plasmacytoid urothelial carcinoma with retroperitoneal dissemination was treated with chemotherapy. After an unsuccessful first-line chemotherapy with gemcitabine and cisplatin, we assessed circulating tumor cells; one such cell was found to be positive for programmed death-ligand 1. The patient received second-line chemotherapy with pembrolizumab. However, the tumor extended to the retroperitoneal organs, and the patient eventually died. Autopsy revealed a widespread diffuse scirrhous infiltration of the carcinoma into the retroperitoneum. However, distant metastasis was not observed. The evaluation of circulating tumor cells and autopsy revealed a disease state of progressive plasmacytoid urothelial carcinoma treated with pembrolizumab.


A novel genetically modified oncolytic vaccinia virus in experimental models is effective against a wide range of human cancers.
Replication-competent oncolytic viruses have shown great promise as a potential cancer treatment. This study aimed to determine whether a novel vaccinia virus, GLV-1h151, with genetic modifications enhancing cancer specificity and enabling virus detection, is effective against a range of human cancers and is safe when administered in preclinical models. GLV-1h151 was modified with deletion of thymidine kinase enhancing specificity and insertion of the green fluorescent protein (GFP) gene. The virus was tested in several human cancer cell lines for cytotoxicity including breast, lung, pancreatic, and colorectal. Virus replication was assessed via visualization of GFP expression and bioluminescence, and viral plaque assays. Finally, GLV-1h151 was administered systemically or intratumorally in mice with pancreatic cancer xenografts (PANC-1) to assess virus biodistribution, toxicity, and effect on tumor growth. GLV-1h151 effectively infected, replicated in, and killed several cancer cell types. Detection and visualization of virus replication was successful via fluorescence imaging of GFP expression, which was dose dependent. When administered intravenously or intratumorally in vivo, GLV-1h151 regressed tumor growth (P < 0.001) and displayed a good biosafety profile. GLV-1h151 infection and replication in tumors was successfully visualized via GFP and bioluminescence, with virus presence in tumors confirmed histologically. GLV-1h151 is effective as an oncolytic agent against a wide range of cancers in cell culture and is effective against pancreatic human xenografts displaying a good biosafety profile and ability to be detected via optical imaging. GLV-1h151 thus adds another potential medium for the killing of cancer and detection of virus in infected tissue.


Infection control in neonatal intensive care units.
Healthcare-associated infection is a major problem in acute hospital settings. Hand decontamination is considered to be the most effective means of preventing healthcare-associated infection, but is poorly performed. Few studies have examined technique, which may be important in neonatal intensive care units (NICUs) where clinical procedures are intricate and could result in contamination of many areas of the hand, resulting in cross-infection. This study examined technique in six NICUs. Eighty-eight nurses were observed. A scoring system was developed so that technique could be quantified and subjected to statistical testing. The mean score was 6.29 out of 11 when hands were washed and 3.87 out of 7 when alcohol hand rub was used, indicating that performance was not optimal. Scores for technique were not significantly different in each NICU. Senior nurses achieved higher scores for handwashing (P<0.01), as did nurses holding positive feelings about the atmosphere in their NICU (P=0.04). Junior nurses scored less well on a knowledge questionnaire than senior nurses (P<0.01). Nurses who had been employed in the neonatal unit for less than one year also scored less well (P<0.01). Differences in technique were noted when comparing the beginning and end of long shifts. These differences were not noted at the beginning and end of standard shifts.


Changes in serum acute phase proteins in ovarian cancer patients receiving cis-diamminedichloroplatinum (CDDP) infusion therapy.
Nine patients with adenocarcinoma of the ovary were given a number of courses of Cisplatin, by I.V. infusion. In four patients a complete clinical response was observed and these patients are disease-free one year after treatment. There was no clinical response in the remaining five patients who have subsequently died. Serial determinations of three acute-phase reactant proteins (alpha 1-acid glycoprotein, haptoglobin, alpha 1-antitrypsin) were performed before every infusion and after therapy. Constantly high or rising serum levels of haptoglobin and alpha 1-acid glycoprotein were associated with progression of the cancer, whereas in patients who were disease-free after therapy, these glycoproteins remained essentially in the normal range. The results suggest that serial measurements of haptoglobin and alpha 1-acid glycoprotein may have clinical value as aids in deciding the effectiveness of drug therapy in these patients.


Effect of zinc and/or pyridoxine deficiency upon oestrogen retention and oestrogen receptor distribution in the rat uterus.
A deficiency of vitamin B6 has been reported to enhance oestrogen responsiveness of the uterus in rats whereas zinc deficiency provokes a syndrome suggestive of a diminution in oestrogen sensitivity. In this study [3H]oestrogen uptake by the uterus was increased in rats deficient in either nutrient and the differences were additive in the dually deficient animals. The total number of oestrogen receptors per g tissue was unaffected by either nutrient but the proportion of the receptors recovered from the nuclear fraction increased from about 6 to 74% when both nutrients were withheld. The results are consistent with the hypothesis that both zinc and pyridoxal phosphate play important metabolic roles in end-organ responsiveness to oestrogen.