Characteristics of the nocturnal desaturation waveform pattern of SpO2 in COPD patients: an observational study.
Nocturnal desaturation is common in patients with chronic obstructive pulmonary disease (COPD) and impacts disease exacerbation and prognosis. In our previous study, we developed a diagnostic algorithm to classify nocturnal desaturation from SpO2 waveform patterns based on data from patients receiving home oxygen therapy. In this study, we aimed to investigate nocturnal desaturation in patients with COPD based on SpO2 waveform patterns and the associations between the waveforms and clinical data. We investigated patients diagnosed with COPD and measured SpO2 and nasal airflow with a type 4 portable long-term recordable pulse oximeter. Then, we classified the SpO2 waveforms with the algorithm and compared the clinical data. One hundred fifty-three patients (136 male and 17 female) were analysed. One hundred twenty-eight of the 153 (83.7%) patients had nocturnal desaturation, with an intermittent pattern (70.6%), sustained pattern (13.1%) and periodic pattern (68.0%). Intriguingly, desaturation with an intermittent pattern was associated with the apnoea-hypopnea index obtained with the portable monitor, and desaturation with a sustained pattern was associated with the cumulative percentage of time at a SpO2 below 90%. We found that nocturnal desaturation was frequently observed in patients with COPD and could be classified into 3 types of waveform patterns.


Facile analysis of short-chain fatty acids as 4-nitrophenyl esters in complex anaerobic fermentation samples by high performance liquid chromatography.
Short-chain fatty acids are crucial intermediates in the conversion of biomass to methane. Due to the complexity of raw biomass, volatile fatty acids (including n- and branched-chain compounds) as well as arylacetic and arylpropionic acids arise from digestion of carbohydrates, proteins and lipids. The development of a simple extraction procedure in combination with internal standardization and facile 4-nitrophenyl-labelling via oxalylchloride-generated acylchlorides enabled robust separation and quantification of the target compounds in crude biological samples like raw cattle manure and biogas fermenter contents. Detection limits of <100 μM and error rates of less than 4% for the quantification of individual compounds in a concentration range up to 50 mM for non-diluted samples suggest that the novel method might be of general advantage for the routine quantification of short-chain fatty acids in complex biological samples including complex fermentation media.


One-stage midline unifocalization and complete repair in infancy versus multiple-stage unifocalization followed by repair for complex heart disease with major aortopulmonary collaterals.
Patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have traditionally required multiple unifocalization staging operations before undergoing complete repair. Recently, the feasibility of a single-stage unifocalization and repair was demonstrated by Hanley. In this report, we describe our experience with each approach. Since 1989, 11 of 12 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have undergone complete surgical correction. The first seven patients were subjected to staged bilateral unifocalizations, with repair being achieved in six (group I). The last five patients have undergone a single-stage midline unifocalization and repair via a sternotomy (group II). Four of these were infants (2 weeks to 9 months) and one was 13 years old. All patients in group I had tetralogy of Fallot, whereas in group II three patients had tetralogy of Fallot, one patient had double-outlet right ventricle, and one patient had complete atrioventricular canal and transposition. In group I, the median age at the first operation was 43 weeks. Complete repair was performed at a median age of 3.5 years, with a mean number of 3.3 operations required. In group II, only one operation was required to achieve complete repair at a median age of 28 weeks. The postoperative right ventricular/left ventricular pressure ratio was 0.49 in group I and 0.45 in group II. One intraoperative death and one late death occurred in group I and no early or late deaths in group II. Currently, four patients in group I and all five patients in group II are alive and well. Early intervention with both surgical approaches can lead to complete biventricular repair in most patients. Because the single-stage midline unifocalization and repair can achieve a completely repaired heart in infancy with one operation, it is currently our approach of choice.


The response to valve injury. A paradigm to understand the pathogenesis of heart valve disease.
Human heart valve diseases have become an important topic in cardiovascular pathology and medicine. These diseases have different etiologies and manifestations. However, the most common ones including calcific aortic stenosis have histopathological features that are best characterized as a "response to tissue injury" similar to ones seen in numerous tissues and organs. The valve interstitial cell is the prevalent cell type in the valve and is likely the master cell which ultimately regulates cell and molecular repair processes within the valve that involve autocrine and paracrine processes as well as interactions with the matrix components of the valve. This presentation explores the concept of "response to tissue injury" in understanding the pathogenesis of calcific aortic stenosis.


Influence of surface groups of proteins on water studied by freezing/thawing hysteresis and infrared spectroscopy.
The influence of proteins and solutes on hysteresis of freezing and melting of water was measured by infrared (IR) spectroscopy. Of the solutes examined, poly-L-arginine and flounder antifreeze protein produced the largest freezing point depression of water, with little effect on the melting temperature. Poly-L-lysine, poly-L-glutamate, cytochrome c and bovine serum albumin had less effect on the freezing of water. Small compounds used to mimic non-polar (trimethylamine N-oxide, methanol), positively charged (guanidinium chloride, NH(4)Cl, urea) and negatively charged (Na acetate) groups on protein surfaces were also examined. These molecules and ions depress water's freezing point and the melting profiles became broad. Since infrared absorption measures both bulk solvent and solvent bound to the solutes, this result is consistent with solutes interacting with liquid water. The amide I absorption bands of antifreeze protein and poly-L-arginine do not detectably change with the phase transition of water. An interpretation is that the antifreeze protein and poly-L-arginine order liquid water such that the water around the group is ice-like.


Probing the interaction mode in hydrophilic interaction chromatography.
This work aims at characterizing interactions between a select set of probes and 22 hydrophilic and polar commercial stationary phases, to develop an understanding of the relationship between the chemical properties of those phases and their interplay with the eluent and solutes in hydrophilic interaction chromatography. "Hydrophilic interaction" is a somewhat inexact term, and an attempt was therefore made to characterize the interactions involved in HILIC as hydrophilic, hydrophobic, electrostatic, hydrogen bonding, dipole-dipole, π-π interaction, and shape-selectivity. Each specific interaction was quantified from the separation factors of a pair of similar substances of which one had properties promoting the interaction mode being probed while the other did not. The effects of particle size and pore size of the phases on retention and selectivity were also studied. The phases investigated covered a wide range of surface functional groups including zwitterionic (sulfobetaine and phosphocholine), neutral (amide and hydroxyl), cationic (amine), and anionic (sulfonic acid and silanol). Principal component analysis of the data showed that partitioning was a dominating mechanism for uncharged solutes in HILIC. However, correlations between functional groups and interactions were also observed, which confirms that the HILIC retention mechanism is partly contributed by adsorption mechanisms involving electrostatic interaction and multipoint hydrogen bonding. Phases with smaller pore diameters yielded longer retention of solutes, but did not significantly change the column selectivities. The particle diameter had no significant effect, neither on retention, nor on the selectivities. An increased water content in the eluent reduced the multipoint hydrogen bonding interactions, while an increased electrolyte concentration lowered the selectivities of the tested columns and made their interaction patterns more similar.


Microbial production of building block chemicals and polymers.
Owing to our increasing concerns on the environment, climate change, and limited natural resources, there has recently been considerable effort exerted to produce chemicals and materials from renewable biomass. Polymers we use everyday can also be produced either by direct fermentation or by polymerization of monomers that are produced by fermentation. Recent advances in metabolic engineering combined with systems biology and synthetic biology are allowing us to more systematically develop superior strains and bioprocesses for the efficient production of polymers and monomers. Here, we review recent trends in microbial production of building block chemicals that can be subsequently used for the synthesis of polymers. Also, recent successful cases of direct one-step production of polymers are reviewed. General strategies for the production of natural and unnatural platform chemicals are described together with representative examples.


Protein inheritance: lambda plasmid replication perpetuated by the heritable replication complex.
Replication of a plasmid derived from the Escherichia coli phage lambda initiates by binding of the lambda O protein initiator to the origin of lambda DNA replication, ori lambda. The lambda P protein participates in subsequent steps of assembly of the lambda replication complex. A function of lambda P required for replication complex assembly is inactivated at 43 degrees C by the ts1 mutation. We found that the lambda replication complex assembled at 30 degrees C survives the temperature upshift in lambda crotsPts1 plasmid-harbouring bacteria. We present several lines of evidence that in this system (in which the replication complex assembly does not occur), the replication complex assembled prior to the temperature upshift is inherited by one of two daughter plasmid copies at each replication round for more than 30 cell generations. The 'old' replication complex-driven replication is chloramphenicol-resistant and rifampicin-sensitive. This replication is dependent on lambda O and host dnaK, dnaJ and grpE chaperone gene functions. The lambda O-containing replication complex is inherited together with DNA and bears information how to initiate the next round of replication at ori lambda; thus, we consider that this phenomenon deserves to be called protein inheritance.


Immunocytochemical study of macrophages and microglial cells and extracellular matrix components in human CNS disease. 2. Non-neoplastic diseases.
For comparison with an earlier paper on gliomas (Morris and Esiri, J. Neurol. Sci., 101 (1991) 47-58), we have used an immunocytochemical approach to examine the reactions of astrocytes, macrophages and microglia and alterations to the extracellular matrix components fibonectin and laminin in 15 cases of non-neoplastic CNS disease. We compared recently available markers for the detection of macrophages and microglia (monoclonals Mac387, KP1 and the lectin RCA-1) and also used antisera to GFAP, fibronectin and laminin. RCA-1 was the superior marker for detecting macrophages and microglia but it also reacted with endothelial cells in normal and reactive brain. The numbers of macrophages and microglia were highly variable, depending on the type of lesion. Fibronectin and laminin were largely confined to the vasculature and leptomeninges. The relationship between the extracellular matrix and the astrocyte, macrophage and microglial reactions is discussed.


Dietary patterns and associations between air pollution and gestational diabetes mellitus.
The prevalence of gestational diabetes mellitus (GDM) has been increasing worldwide. Dietary patterns and air pollution are closely related to the occurrence of GDM. No previous study has explored the interaction effect of air pollution exposure and dietary patterns on GDM. We explored the interaction effect between main dietary patterns and pre-pregnancy exposure to air pollution on the development of GDM based on a prospective birth cohort in Northeast China. A total of 2244 participants were included in this study. Factor analysis was used to identify dietary patterns. We found that long-term exposure to nitrogen dioxide (NO2) and carbon monoxide (CO) before pregnancy was significantly associated with an increased risk of GDM; the animal foods pattern significantly modified these associations. The sub-group analysis showed that compared with a lower intake in the animal foods pattern (NO2, odds ratio [OR] = 1.07, 95% confidence interval [CI]: 0.84, 1.35; CO, OR = 1.05, 95% CI: 0.81, 1.34), higher intake in the animal foods pattern (NO2, OR = 1.41, 95% CI: 1.09, 1.83; CO, OR = 1.36, 95% CI: 1.05, 1.76) before pregnancy increased the hazardous effects of NO2 and CO on GDM development. The intake of animal blood, animal organs, preserved eggs, and processed meat products in animal food pattern could all aggravate the effect of exposure to air pollution due to NO2 and CO on GDM. Our study demonstrated that there was a significant interaction effect between animal foods pattern and exposure to air pollution on GDM. These results provide further scientific evidence of the associations among air pollution, dietary intake, and GDM, and may help as well as the prevention of GDM.


Cervical cancer incidence in young women: a historical and geographic controlled UK regional population study.
The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening. We measured if the relative risk of cervical cancer in younger women (20-29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20yrs. Cervical cancer incidence in women aged 20-29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30-39 was less steep (3.5%/year) but no significant rise was observed in women aged 40-49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results. The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25-29 years are recommended.


Stepwise evolution of therapy resistance in AML.
Relapse of AML patients to FLT3i treatment is the result of a long-term and stepwise process leading to resistance, whereby residual cancer cells initially survive and subsequently expand. Here, Joshi et al. use a multifaceted approach to characterize how microenvironment-driven early resistance to gilteritinib evolves into mutation-driven late resistance.


Glutamate and GABA in lateral hypothalamic mechanisms controlling food intake.
By the 1990s a convergence of evidence had accumulated to suggest that neurons within the lateral hypothalamus (LH) play important roles in the stimulation of feeding behavior. However, there was little direct evidence demonstrating that neurotransmitters in the LH could, like electrical stimulation, elicit feeding in satiated animals. The present paper is a brief review in honor of Bartley Hoebel's scientific contributions, emphasizing the evidence from my lab that the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in the LH mediate feeding stimulation and feeding inhibition respectively. Specifically, we summarize evidence that LH injection of glutamate, or agonists of its N-methyl-D-aspartate (NMDA) and non-NMDA receptors, elicits feeding in satiated rats, that NMDA receptor antagonists block the eating elicited by NMDA and, more importantly, that NMDA blockade suppresses natural feeding and can reduce body weight. Conversely, GABA(A) agonists injected into the LH suppress feeding and can also reduce body weight, while GABA(A) receptor antagonists actually elicit eating when injected into the LH of satiated rats. It is suggested that natural feeding may reflect the moment-to-moment balance in the activity of glutamate and GABA within the LH.


Attenuation of murine acute lethal graft-versus-host disease by the administration of DL-alpha-difluoromethylornithine.
Intravenous injection of 5 x 10(7) C57BL/6 (B6) lymphocytes into adult (C57BL/6 x DBA/2)F1 recipient mice results in acute lethal graft-versus-host (ALGVH) disease. This disorder is characterized by anemia, a diminished number of splenocytes, impaired cytotoxicity (CTX) against third party alloantigen, and impaired natural killer cell (NK) activity. Parental anti-F1 CTX is critical to the induction of ALGVH disease, and CTX in general has been reported to be dependent upon the presence of the low molecular weight polyamines essential for cell growth and differentiation. We now report that DL-alpha-difluoromethylornithine, a specific inhibitor of polyamine biosynthesis, attenuates the clinical expression of disease in mice undergoing ALGVH disease.


Renal cell carcinoma in a lumbar ectopic kidney.
Lumbar ectopic kidney is a rare developmental renal anomaly. We report a case of renal cell carcinoma in lumbar ectopic kidney with an abnormality of the main renal artery piercing the renal parenchyma. A 70-year-old female was referred to our division with an incidentally diagnosed ectopic kidney. Computed tomography angiography detected the right kidney at the lumbar (L3-L4) level with an early-enhanced 44-mm-diameter mass. The kidney had a laterally facing renal hilum and renal arteries piercing the renal parenchyma from the medial side. An open radical nephrectomy was performed using a peritoneal approach, and no perioperative complications were observed. The pathological diagnosis was clear cell carcinoma (pT1). This is the first case report of renal cell carcinoma in a lumbar ectopic kidney. It highlights the importance of preoperational imaging for aberrant artery and careful surgical management.


Ultrasonic-assisted transesterification of Jatropha curcus oil using solid catalyst, Na/SiO2.
The production of biodiesel from non-edible vegetable oil using ultrasonication, calls for an efficient solid catalyst to make the process fully ecologically and economically friendly. The methodology allows for the reaction to be run under atmospheric conditions. Solid catalyst and ultrasonication reduced the reaction time comparing to the conventional batch processes and we found 98.53% biodiesel yield. The optimal conditions for biodiesel production is the molar ratio oil to methanol 1:9, Catalyst conc. 3 wt.% of oil and 15 min reaction time.


Aligned silk fibroin/poly-3-hydroxybutyrate nanofibrous scaffolds seeded with adipose-derived stem cells for tendon tissue engineering.
In this work we investigated tenogenic differentiation of adipose-derived mesenchymal stem cells (AdMSCs), which were seeded onto silk fibroin/poly-3-hydroxybutyrate (SF/P3HB) scaffolds with aligned topography, and high mechanical strength. The electrospinning process was optimized by using the response surface method (RSM) and SF/P3HB nanofibrous matrices with a total polymer concentration of 5% (SF: PHB = 3: 1), flow rate 1 mL/h, collector rotation speed 2000 rpm, applied voltage 14 kV, and collector distance 25 cm were obtained. The average fiber diameter was 699 ± 203 nm and 80% of the nanofibers were aligned within the ±15o range. SF reinforcement reduced the crystallinity of P3HB, and the elastic modulus was found to be 197.0 ± 7.7 MPa. The scaffolds showed bacteriostatic effect. A 21-day of cell culture study was performed with rat rAdMSCs in the absence and presence of tenogenic differentiation factor-5 (GDF-5). The results demonstrated that SF/P3HB scaffolds allow the cells to proliferate and differentiate to the tenocytes. However, no significant effect of GDF-5 on the differentiation of cells was observed. These findings indicated that our aligned SF/P3HB scaffolds have a significant potential to be used for tendon tissue engineering.


Laboratory behavioral measures of impulsivity.
Previous research and theory have conceptualized impulsivity as a multifaceted construct that requires multiple modes of measurement for accurate assessment. This article describes a software package that includes four paradigms for measuring multiple and unique aspects of impulsivity. Specifically, four tasks are described: (1) the two choice impulsivity paradigm, (2) the single key impulsivity paradigm, (3) the GoStop impulsivity paradigm, and (4) the time paradigm. These tasks measure processes related to the capacity to tolerate delay for reward, to inhibit an already initiated response, and to estimate the passage of time. These processes have been found to be important to the understanding of impulsive behaviors. The programs are flexible and allow the experimenter to manipulate a number of parameters related to delay-reward contingencies, timing, performance feedback/payment, and data output variables. Manipulation of these parameters makes the paradigms scalable to a wide range of ability levels and appropriate for samples ranging from children to adults. The four paradigms in this software package are available at no cost and can be obtained by contacting the corresponding author.


Device closure of perimembranous ventricular septal defects with a minimally invasive technique in 12 patients.
Both surgical management and percutaneous device closure of perimembranous ventricular septal defects without cardiopulmonary bypass have drawbacks and limitations. This report describes the experience with intraoperative device closure of perimembranous ventricular septal defects without cardiopulmonary bypass by a minimally invasive technique. Twelve patients who had perimembranous ventricular septal defects underwent perventricular closure by a minimally invasive incision without cardiopulmonary bypass. A subxiphoid minimally invasive incision was performed. The right ventricle free wall was punctured, and a guidewire was introduced into the right ventricular cavity. A delivery sheath was advanced over the wire and through the defect into the left ventricular cavity under the guidance of transesophageal echocardiography. The device was released under the guidance of transesophageal echocardiography without cardiopulmonary bypass. The procedure was successful in the 12 patients. Patients stayed in the intensive care unit 1 day and were in the hospital 4 days. At follow-up of 2 to 4 months, there was no operative mortality, atrioventricular block, new aortic incompetence, or residual shunt. The minimally invasive technique appeared to be safe and efficacious for closure of perimembranous ventricular septal defects in the operating room with acceptable short-term outcomes.


Executive functions and attention 7years after severe childhood traumatic brain injury: Results of the Traumatisme Grave de l'Enfant (TGE) cohort.
Severe childhood traumatic brain injury (TBI) leads to long-standing executive function and attention deficits, with negative consequences for participation, academic outcome and independence. This study aimed to assess executive function and attention 7 years after severe childhood TBI in comparison with a matched control group and to investigate associated factors. Children (<15years) with severe accidental TBI consecutively admitted in a single trauma center over 3years were included in the Traumatisme Grave de l'Enfant (TGE) prospective longitudinal study. Of the 81children initially included, 65survived. At 7years post-TBI, executive functions and attention were assessed in 27participants (42 % of the 65 survivors) by using a combination of computerized tasks from the Test of Attentional Performance (TAP) and the Behavioral Rating of Executive Functions (BRIEF) questionnaire. Patients were compared to a group of 27typically developing controls who were matched for sex, age and parental education level. Among the 27participants, mean (SD) age at injury was 7.7 (4.6)years, and mean length of coma 5.6 (4.6) days. Regarding the TAP, the number of errors was significantly higher (P=0.003) and reaction time marginally slower (P=0.08) in the TBI than control group. The BRIEF questionnaire completed by parents indicated significantly more executive difficulties in the TBI than control group (Behavior Regulation Index, P=0.005; Metacognitive index, P=0.02; Global Executive Composite, P=0.012). Correlations between BRIEF and TAP scores did not reach statistical significance. BRIEF total score was correlated moderately with length of coma (r=0.40, P=0.037), and TAP scores were correlated with the Full-Scale Intellectual Quotient (total number of errors: r=-0.48; P=0.01; mean reaction time: r=-0.51; P=0.009). Executive and attention deficits were evident 7 years after severe childhood TBI. Computerized tasks and questionnaires provide complementary and non-redundant information. Systematic long-term follow-up should be provided until the transition to adulthood, to assess ongoing development and to implement timely tailored interventions.


[Counter-lateral compression in oblique pseudarthroses of diaphyses of the tubular bones of the lower limbs].
The author reports the results of treatment in 58 patients with oblique aplastic pseudarthrosis of tubular bones diaphyses of the lower limbs. For treatment extrafocal with counter-lateral compression by means of pins with bearing surfaces. By the present time nearly in all patients (52 of 58) with the mentioned complications such kind of treatment resulted in rehabilitation of the main motion-bearing function of the extremity.


Beyond scene gist: Objects guide search more than scene background.
Although the facilitation of visual search by contextual information is well established, there is little understanding of the independent contributions of different types of contextual cues in scenes. Here we manipulated 3 types of contextual information: object co-occurrence, multiple object configurations, and background category. We isolated the benefits of each contextual cue to target detectability, its impact on decision bias, confidence, and the guidance of eye movements. We find that object-based information guides eye movements and facilitates perceptual judgments more than scene background. The degree of guidance and facilitation of each contextual cue can be related to its inherent informativeness about the target spatial location as measured by human explicit judgments about likely target locations. Our results improve the understanding of the contributions of distinct contextual scene components to search and suggest that the brain's utilization of cues to guide eye movements is linked to the cue's informativeness about the target's location. (PsycINFO Database Record


Greenhouse gas emissions and wastewater treatment performance by three plant species in subsurface flow constructed wetland mesocosms.
Greenhouse gas (GHG) emissions from constructed wetlands (CWs) have raised environmental concern and thus offset their environmental and ecological benefits. This study evaluated the influence of plant species, i.e., Canna indica (C. indica), Cyperus alternifolius (C. alternifolius), Phragmites australis (P. australis) and unplanted control, on GHG emissions, pollutant removal and associated microbial abundance in subsurface flow constructed wetland (SSFCW) mesocosms. C. indica outperformed the other tested plant species in pollutant removal, and the presence of plants irrespective of species enhanced the removal efficiencies of nitrogen, phosphorus and organics in SSFCW mesocosms compared to unplanted control. The greatest carbon dioxide (CO2) flux (582.01 ± 89.25 mg/m2/h), methane (CH4) flux (21.88 ± 2.51 μg/m2/h) and nitrous oxide (N2O) flux (37.27 ± 15.82 μg/m2/h) were observed in mesocosms planted with C. indica, P. australis and C.alternifolius, respectively. Unexpectedly, the mcrA and pmoA genes were not detected in any mesocosms. For denitrifiers, the N2O fluxes showed a significantly (p < 0.05) positive correlation with nirS and nirK genes abundance. The abundance of nosZ gene (ranged from 0.18 × 104 to 0.75 × 104 copies/mg gravel) and nosZ/(nirS + nirK) (ranged from 1.29 × 10-4 to 2.12 × 10-4 copies/mg gravel) in this study was lower than that in most reported studies. Regarding the global warming potential (GWP), the lowest value was observed in mesocosms planted with C. indica. In conclusion, C. indica is selected as the optimal plant species in this study due to its lower GWP and excellent pollutant removal performance.


γ-Aminobutyric acid transporters as relevant biological target: Their function, structure, inhibitors and role in the therapy of different diseases.
γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the nervous system. It plays a crucial role in many physiological processes. Upon release from the presynaptic element, it is removed from the synaptic cleft by reuptake due to the action of GABA transporters (GATs). GATs belong to a large SLC6 protein family whose characteristic feature is sodium-dependent relocation of neurotransmitters through the cell membrane. GABA transporters are characterized in many contexts, but their spatial structure is not fully known. They are divided into four types, which differ in occurrence and role. Herein, the special attention was paid to these transporting proteins. This comprehensive review presents the current knowledge about GABA transporters. Their distribution in the body, physiological functions and possible utilization in the therapy of different diseases were fully discussed. The important structural features were described based on published data, including sequence analysis, mutagenesis studies, and comparison with known SLC6 transporters for leucine (LeuT), dopamine (DAT) and serotonin (SERT). Moreover, the most important inhibitors of GABA transporters of various basic scaffolds, diverse selectivity and potency were presented.


Polymorphisms of the MDR1 and MIF genes in children with nephrotic syndrome.
Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). Nonetheless, some patients are resistant to this treatment. Many efforts have been made to explain the differences in the response to steroid treatment in patients with NS based on the genetic background. We have investigated single nucleotide polymorphisms of the MDR1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and MIF (G-173C, rs755622) genes in 170 children with NS. Of these children, 69 (40.6%) were initial steroid non-responders, and 23 (13.5% of total) developed chronic kidney disease. Renal biopsy findings, which were available for 101 patients, showed that 35 patients had minimal change lesion and 66 had focal segmental glomerulosclerosis. The frequencies of the MDR1 1236 CC (18.8 vs 7.2%) or TC (53.5 vs 43.5%) genotype and C allele (45.5 vs 29.0%) were significantly higher in the initial steroid responders than in the non-responders. Analysis of MDR1 three-marker haplotypes revealed that the frequency of the TGC haplotype was significantly lower in the initial steroid responders than in the non-responders (15.8 vs 29.0%). There was no association between the MIF G-173C polymorphism and clinical parameters, renal histological findings, and steroid responsiveness. These data suggest that the initial steroid response in children with NS may be influenced by genetic variations in the MDR1 gene.


Effect of soft tissue noise on trabecular bone score in postmenopausal women with diabetes: A cross sectional study.
Type 2 diabetes (T2D) is associated with increased fracture risk, despite similar or greater BMD compared to nondiabetics. TBS predicts fracture risk in T2D and nondiabetics. However, increased abdominal thickness, a common feature in T2D, may reduce TBS values. To study the relationship among glycemic status, BMD and TBS, considering abdominal soft tissue thickness (STT) interference. Cross-sectional analysis of 493 women ≥65 years, with simultaneous DXA scans and HbA1c measures. STT and TBS (iNsight Software, v3.0) were derived from lumbar spine (LS) scans. Subjects were divided according to HbA1c levels: 1 (≥6.5%; n = 116), 2 (5.7-6.4%; n = 217) and 3 (≤5.6%; n = 160). Group 1 was further divided based on HbA1c and/or disease duration: 1a (HbA1c ≥ 7.5%; n = 42), 1b (HbA1c ≥ 6.5% and disease duration ≥5 years; n = 63) and 1c (HbA1c ≥ 7.5% and disease duration ≥5 years; n = 30). For the entire cohort, mean age, TBS, BMI and STT were 71.8 ± 6.0 years, 1.299 ± 0.101, 26.9 ± 4.1 kg/m2, and 21.4 ± 2.9 cm, respectively. LS-BMD was similar among groups. BMD in hip sites and STT were higher in group 1. TBS was lower in patients with higher HbA1c (P = 0.020), with a mean TBS in groups 1, 2, and 3 of 1.280, 1.299 and 1.314, respectively. This difference remained after adjusting for age, LS-BMD and BMI (P = 0.010). After replacing BMI with STT, TBS differences were no longer significant (P = 0.270). The same was observed when subgroups 1a and 1b were compared to group 3. However, for subgroup 1c, TBS remained lower compared to group 3, even after adjusting for age, LS-BMD and STT, with a borderline P-value (1.275 vs. 1.308; P = 0.047). Higher HbA1c levels were associated with greater BMD in hip sites, higher abdominal STT and lower TBS values. However, after including the STT in the adjustment, TBS differences among groups disappeared, except in women with higher HbA1c levels and longer disease duration.


Potential of Pichia pastoris for the production of industrial penicillin G acylase.
This study deals with the potential of Pichia pastoris X-33 for the production of penicillin G acylase (PGAA) from Achromobacter sp. CCM 4824. Synthetic gene matching the codon usage of P. pastoris was designed for intracellular and secretion-based production strategies and cloned into vectors pPICZ and pPICZα under the control of AOX1 promoter. The simple method was developed to screen Pichia transformants with the intracellularly produced enzyme. The positive correlation between acylase production and pga gene dosage for both expression systems was demonstrated in small scale experiments. In fed-batch bioreactor cultures of X-33/PENS2, an extracellular expression system, total PGAA expressed from five copies reached 14,880 U/L of an active enzyme after 142 h; however, 60% of this amount retained in the cytosol. The maximum PGAA production of 31,000 U/L was achieved intracellularly from nine integrated gene copies of X-33/PINS2 after 90 h under methanol induction. The results indicate that in both expression systems the production level of PGAA is similar but there is a limitation in secretion efficiency.


Virus-like particles as powerful vaccination strategy against human viruses.
Nowadays, viruses are not only seen as causative agents of viral infectious diseases but also as valuable research materials for various biomedical purposes, including recombinant protein production. When expressed in living or cell-free expression systems, viral structural proteins self-assemble into virus-like particles (VLPs). Mimicking the native form and size of viruses and lacking the genetic material, VLPs are safe and highly immunogenic and thus can be exploited to develop antiviral vaccines. Some vaccines based on VLPs against various infectious pathogens have already been licenced for human use and are available in the commercial market, the latest of which is a VLP-based vaccine to protect against the novel Coronavirus. Despite the success and popularity of VLP subunit vaccines, many more VLPs are still in different stages of design, production, and approval. There are still many challenges that require to be addressed in the future before this surface display system can be widely used as an effective vaccine strategy in combating infectious diseases. In this review, we highlight the use of structural viral proteins to produce VLPs, emphasising their intrinsic properties, structural classification, and main expression host systems. We also compiled the recent scientific literature about VLP-based vaccines to underline the recent advances in their application as a vaccine strategy for preventing and fighting virulent human pathogens. Finally, we presented the key challenges and possible solutions for VLP-based vaccine production.


Synthesis, characterization, and antimicrobial activity of some new N-aryl-N'-(2-oxoindolin-3-ylidene)-benzohydrazonamides.
A green approach was developed for synthesizing a series of (isatin-3-ylidene)-hydrazonamides 3a-j from the reaction between isatin, (isatin-3-ylidene)malononitrile, or 2-cyano-2-(2-isatin-3-ylidene)acetate and benzohydrazonamide in ethyl acetate solutions at ambient temperature. The structures of the new compounds were confirmed on the basis of spectral data. In this eco-friendly medium, a variety of (isatin-3-ylidene)hydrazonamides were obtained free of catalyst in good to excellent yields. All the synthesized products were evaluated for their antimicrobial activity. Among the compounds tested, 3b and 3d exhibited good antibacterial activity against Staphylococcus aureus, whereas others responded moderately with reference to the standard drug ciprofloxacin.


Association between thrombophilia gene polymorphisms and preeclampsia: a meta-analysis.
To estimate the relationship between the risk of preeclampsia and two thrombophilia gene single-nucleotide polymorphisms (SNPs), the factor V G1691A SNP and the prothrombin G20210A SNP. A systematic search of the English-language literature up to November 2012 was performed using Medline and EMBASE. Search terms included "preeclampsia," "thrombophilia," "factor V Leiden," "prothrombin gene 20210," and their combinations. Thirty-seven studies with 5048 preeclampsia patients and 6796 controls were included in the meta-analysis. We found that the prothrombin G20210A polymorphism was associated with an increased risk of all preeclampsia (pooled odds ratio (OR) = 1.81, 95% confidence interval (CI) 1.25-2.63) and severe preeclampsia (pooled OR = 3.02, 95%CI 2.06-4.45). Meanwhile, the pooled OR for the association between factor V Leiden and all preeclampsia was 1.60 (95%CI 1.28-2.00) and 2.45 (95%CI 1.63-3.69) for the cases of severe preeclampsia. This meta-analysis supports that the factor V G1691A SNP and the prothrombin G20210A SNP are associated with an increased risk for both preeclampsia overall and severe preeclampsia.


Utilizing participants' strengths to reduce risk of harm in a study of family estrangement.
In this article I examine some issues involved in researching vulnerable populations and sensitive issues, and the challenges and risks of researching issues of a deeply personal nature. Participants might have complex needs and vulnerabilities, but they also have many resources to ensure their own well-being. I ask researchers to move beyond the minimum standards espoused by human ethics committees, and utilize participant strengths to further reduce the risk of harm. My reflections on a study of older people who were experiencing family estrangement highlight some of the actions that participants used to increase their personal safety. I discuss the usefulness of "strengths" questions in assessing risk and facilitating participant strengths to minimize harm. Finally, I propose a three-way model for reducing risk that involves the "lessons learned" from ethics committees, researchers, and the participants themselves.


Effects of key operational parameters on biohydrogen production via anaerobic fermentation in a sequencing batch reactor.
In this study, a series of tests were conducted in a 6L anaerobic sequencing batch reactor (ASBR) to investigate the effect of pH, hydraulic retention time (HRT) and organic loading rate on biohydrogen production at 28°C. Sucrose was used as the main substrate to mimic carbohydrate-rich wastewater and inoculum was prepared from anaerobic digested sludge without pretreatment. The reactor was operated initially with nitrogen sparging to form anaerobic condition. Results showed that methanogens were effectively suppressed. The optimum pH value would vary depending on the HRT. Maximum hydrogen production rate and yield of 3.04 L H(2)/L reactor d and 2.16 mol H(2)/mol hexose respectively were achieved at pH 4.5, HRT 30 h, and OLR 11.0 kg/m(3)d. Two relationships involving the propionic acid/acetic acid ratio and ethanol/acetic acid ratio were derived from the analysis of the metabolites of fermentation. Ethanol/acetic acid ratio of 1.25 was found to be a threshold value for higher hydrogen production.


Rectal stenosis due to Veganine suppositories.
A new case of rectal stenosis due to the chronic use of suppositories of associated analgesic drugs is reported. Surgical treatment was conservative. This observation outlines the dramatic consequences of chronic self-treatment and the difficulties of ensuring long-term withdrawal.


Basal transcription is regulated by lipopolysaccharide and glucosamine via the regulation of DNA binding of RNA polymerase II in RAW264.7 cells.
The objective of this study is to investigate glucosamine (GlcN) as a transcriptional regulator of iNOS and other genes in association with the dynamic O-GlcNAcylation of RNA polymerase II (RNAPII). The LPS- and/or GlcN-stimulated transcriptional activities of various Gal4-binding site/TATA-box-containing reporter constructs were measured. Basal transcriptional activities of nuclear factor-κB (NF-κB) and nitric oxide synthase (iNOS) reporter plasmids are inhibited by GlcN in RAW264.7 cells. Furthermore, GlcN suppressed whereas lipopolysaccharide (LPS) stimulated the basal activity of Gal4-binding site/TATA-box-containing reporter constructs. LPS reduced the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of RNAPII, but enhanced the binding of this enzyme to the iNOS promoter. In contrast, GlcN enhanced RNAPII O-GlcNAcylation, but inhibited iNOS promoter binding. Furthermore, the basal activities of reporter plasmids containing activator protein 1 (AP1), E2F, or cyclic AMP response element (CRE) binding sites were consistently inhibited by GlcN in a dose-dependent manner. However, GlcN did not inhibit the phorbol 12-myristate 13-acetate- (PMA-) or forskolin-induced transcriptional activities of AP1 and CRE. The transcriptional activity of transforming growth factor alpha (TGF-α) was slightly increased by both LPS and GlcN. In conclusion, our data demonstrate that LPS activates, whereas GlcN suppresses, basal activities of transcription through the regulation of RNAPII O-GlcNAcylation and DNA binding.


Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia.
Drug resistance is an obstacle in the treatment of chronic myelogenous leukemia (CML), and is a common reason for treatment failure or disease progression. However, the underlying mechanisms of cyclophosphamide resistance remain poorly defined. In the present study, microarray data concerning cyclophosphamide‑sensitive and ‑resistant chronic myelogenous leukemia cell lines were analyzed. A total of 258 differentially‑expressed genes (DEGs) were identified between these two groups, from which 139 DEGs were upregulated and 119 were downregulated. Several candidate genes that were associated with cyclophosphamide resistance were also identified. These DEGs were subsequently classified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis. A total of 487 biological processes and 17 KEGG pathways were revealed to be enriched. Furthermore, an interaction network was established to identify the core genes that regulated cyclophosphamide resistance. Signal transducer and activator of transcription 5A (STAT5A), FYN proto‑oncogene, Src family tyrosine kinase and spleen associated tyrosine kinase were revealed to be the hub genes in multiple enriched biological processes and signaling pathways, indicating that these were involved in mediating cyclophosphamide sensitivity in CML cells. The expression levels of 5 DEGs were also confirmed in two human CML cell lines (K‑562 and KU812) by reverse transcription‑quantitative polymerase chain reaction. Furthermore, selective knockdown of STAT5A and S100 calcium binding protein A4 (S100A4) recovered cyclophosphamide sensitivity in K‑562 cells, suggesting their involvement in drug resistance. The present study identified several potential genes and pathways contributing to cyclophosphamide resistance, and confirmed the involvement of STAT5A and S100A4 in drug resistance. These results enable improved understanding of the mechanisms underlying drug resistance in CML cells.


Outcomes of a combination of augmented MicroPulse and limited Continuous Wave Cyclophotocoagulation in patients with refractory glaucoma.
To assess the safety and effectiveness of augmented MicroPulse (MP-TSCPC) with limited Continuous Wave Transscleral Cyclophotocoagulation (CW-TSCPC) in patients with refractory glaucoma. Thirty-eight eyes of 38 patients underwent combined MP-TSCPC and CW-TSCPC at Massachusetts Eye and Ear. Kaplan-Meier survival curves and Wilcoxon paired sign rank tests were performed to evaluate intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity (BCVA), and adverse events. With success defined as IOP reduction ≥ 30% and IOP between 5 and 18 mmHg, the cumulative probability of success at 1 year and 1.5 years were 0.81 (95% confidence interval (CI), 0.68-0.96) and 0.65 (95% CI, 0.50-0.86), respectively. With success defined as IOP reduction ≥ 50% and IOP between 5 and 18 mmHg, the success probability at 1 year and 1.5 years were 0.72 (95% CI, 0.57-0.89) and 0.56 (95% CI, 0.40-0.78), respectively. IOP and medication burden reductions were significant at all follow-up visits compared to baseline. Average IOP decreased from 27.9 mmHg at baseline to 11.4 mmHg at 1 year (p < 0.001) and 10.0 mmHg at 1.5 years (p < 0.001). Average medication burden decreased from 3.8 to 1.7 at 1.5 years (p = 0.001). No significant differences in visual acuity were observed at any time point. No long-term sight-threatening complications due to the combined procedure were observed, and most of the complications observed were mild and transient. In patients with refractory glaucoma, the combination of augmented MP-TSCPC with limited CW-TSCPC provides a significant IOP-lowering effect and decrease in medication burden without increased risk of postoperative complications.


Safety and effectiveness of lanthanum carbonate for hyperphosphatemia in chronic kidney disease (CKD) patients: a meta-analysis.
The aim of this study was to determine the efficacy and safety of lanthanum carbonate (LC) versus calcium salts, non-LC phosphate binders (PBs), sevelamer, or placebo in patients with chronic kidney disease (CKD). A literature search on PubMed, Embase, and Cochrane Library databases was conducted up to 18 June 2021. Data acquisition and quality assessment were performed by two reviewers. Meta-analysis was performed to evaluate the serum biochemical parameters, adverse events, and patient-level outcomes of LC, non-LC PBs, and sevelamer for hyperphosphatemia in patients with CKD. Heterogeneity across studies was assessed utilizing the I2 statistic and Q-test, and a random effect model was selected to calculate the pooled effect size. A total of 26 randomized, controlled trials and 3 observational studies were included. Compared to the other groups, better control effect of serum phosphorus (RR = 2.68, p < 0.001), reduction in serum phosphorus (95%CI = -1.93, -0.99; p < 0.001), Ca × P (95%CI = -13.89, -2.99; p = 0.002), serum intact parathyroid hormone levels (95%CI = -181.17, -3.96, p = 0.041) were found in LC group. Besides, reduced risk of various adverse effects, such as hypotension, abdominal pain, diarrhea, dyspepsia, and a score of coronary artery calcification were identified with LC in comparison to calcium salt, non-LC PBs, or placebo group. Significantly lower risk in mortality with LC treatment vs. non-LC PBs was observed, while no significant difference was identified between LC and calcium salt groups. LC might be an alternative treatment for hyperphosphatemia in patients with CKD considering its comprehensive curative effect.


Micronutrient status during paediatric critical illness: A scoping review.
No evidence based recommendations for micronutrient requirements during paediatric critical illness are available, other than those arising from recommended nutrient intakes (RNI) for healthy children and expert opinion. The objective of this review is to examine the available evidence from micronutrient status in critically ill children considering studies which describe 1) micronutrient levels, 2) associations between micronutrient levels and clinical outcome, and 3) impact on clinical outcome with micronutrient supplementation during PICU admission. Scoping review. Any study which used a qualitative and quantitative design considering causes and consequences of micronutrient levels or micronutrient supplementation during paediatric critical illness. NICE Healthcare Databases Advanced Search website (https://hdas.nice.org.uk/) was used as a tool for multiple searches, with a content analysis and charting of data extracted. 711 records were identified, 35 were included in the review. Studies evaluated serum micronutrient status was determined on admission day in majority of patients. A content analysis identified (n = 49) initial codes, (n = 14) sub-categories and (n = 5) overarching themes during critical illness, which were identified as: i) low levels of micronutrients, ii) causes of aberrant micronutrient levels, iii) associations between micronutrients levels and outcome, iv) supplementation of micronutrients. During critical illness, micronutrients should be provided in sufficient amounts to meet reference nutrient intakes for age. Although, there is insufficient data to recommend routine supplementations of micronutrients at higher doses during critical illness, the 'absence of evidence should not imply evidence of absence', and well designed prospective studies are urgently needed to elucidate paediatric micronutrient requirements during critical illness. The absence of reliable biomarkers make it challenging to determine whether low serum levels are reflective of a true deficiency or as a result redistribution, particularly during the acute phase of critical illness. As more children continue to survive a PICU admission, particularly those with complex diseases micronutrient supplementation research should also be inclusive of the recovery phase following critical illness.


Factors associated with tuberculosis cases in Semarang District, Indonesia: case-control study performed in the area where case detection rate was extremely low.
Indonesia is ranked as the 4th highest contributor to tuberculosis (TB) in the world. Semarang District in Central Java displays extremely low case detection rate (CDR), possibly contributing to the local prevalence of TB. A case-control study was performed to explore the factors that cause such low CDR. We recruited 129 TB cases and 83 controls that visited the same centers and were not diagnosed with TB. The cases had 7.5 ± 2.3 symptoms/person on average, indicating the delay in diagnosis because the controls only displayed 1.0 ± 1.7. The multiple logistic regression analysis comparing the cases/controls extracted following factors as a risk to have TB: farmer, close contact with TB patients, ignorance of whether Bacillus Calmette-Guérin (BCG) was accepted or no, smoking, low income, a lot of people living in the same room, irregular hand wash before meals, not wash hands after blow, soil floor, and no sunlight and no ventilation in the house. Neither the cases nor the controls knew the symptoms and how to avoid TB infection, which probably caused the delay in diagnosis. It is difficult to change the current living conditions. Thus, the amendment of the community-based education program of TB seems to be required.


A re-assessment of the oldest therapsid Raranimus confirms its status as a basal member of the clade and fills Olson's gap.
The non-mammalian therapsids comprise a paraphyletic assemblage of Permian-Jurassic synapsids closely related to mammals that includes six major clades of largely unresolved phylogenetic affinity. Understanding the early evolutionary radiation of therapsids is complicated by a gap in the fossil record during the Roadian (middle Permian) known as Olson's gap. Because of its early stratigraphic occurrence and its primitive features, Raranimus dashankouensis, from the Dashankou fauna (Rodian), Qingtoushan Formation (China), is currently considered the best candidate to fill this gap. However, it is known from only a single specimen, an isolated snout, which limits the amount of usable phylogenetic characters to reconstruct its affinities. In addition, understanding of the stratigraphy of the Qingtoushan Formation is poor. Here, we used CT scanning techniques to digitally reconstruct the bones and trigeminal canals of the snout of Raranimus in 3D. We confirm that Raranimus shares a high number of synapomorphies with more derived therapsids and is the only therapsid known so far to display a "pelycosaur"-like maxillary canal bearing a long caudal alveolar canal that gives off branches at regular intervals. This plesiomorphic feature supports the idea that Raranimus is basal to other therapsids.


Evidence for a gene cluster involving trichothecene-pathway biosynthetic genes in Fusarium sporotrichioides.
Two overlapping cosmid clones (Cos1-1 and Cos9-1) carrying the Tox5 gene were isolated from a library of F. sporotrichioides strain NRRL 3299 genomic DNA. These cosmids were used to transform three T-2 toxin-deficient mutants that are blocked at different steps in the trichothecene pathway. Both cosmids restored T-2 toxin production to Tox3-1- or Tox4-1- mutants but neither restored T-2 toxin production to a Tox1-2- mutant. The production of T-2 toxin by the complemented Tox3-1- and Tox4-1- mutants, as well as the production of diacetoxycirpenol by the cosmid-transformed Tox1-2- mutant, were 2- to 10-fold higher than in strain NRRL 3299. In addition, those transformants carrying Cos9-1 produced significantly higher levels of trichothecenes than transformants carrying Cos1-1. Two different DNA fragments (FSC13-9 and FSC14-5), representing the region of overlap between the cosmid clones, were isolated. These fragments specifically complemented either the Tox3-1- mutant (FSC14-5) or the Tox4-1- mutant (FSC13-9). The trichothecene-production phenotype of these transformants was similar to NRRL 3299. These results suggest that two or more genes involved in the biosynthesis of trichothecenes are closely linked to Tox5.


Draft Genome Sequences of Lactobacillus plantarum Strain K03D08 and Acetobacter syzygii Strain K03D05, Isolated from a Kefir Beverage Collected in Chile.
Kefir is an ancestral food produced using microbial consortia whose composition varies depending on the geographical origin and the substrate used for fermentation. This dairy beverage is considered a probiotic food, and its consumption has been associated with several health benefits. This report describes the isolation of bacterial strains from Chilean kefir.


Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit.
Perfusates were taken from the superficial layers of the subnucleus caudalis of the trigeminal sensory nuclear complex (SpVc), the first relay station of dental pain, with a push-pull cannula system and were assayed for endogenous serotonin (5-HT) and catecholamines by high-pressure liquid chromatography with an electrochemical detection. Spontaneous release of 5-HT and epinephrine was observed, while that of norepinephrine was not. Tooth pulp stimulation (ST) tended to increase the level of 5-HT in the perfusates. Pretreatment with morphine at a dose of 10 mg/kg (i.v.) significantly enhanced the release of 5-HT. However, there was no significant difference in morphine effect on the 5-HT level between stimulated and non-stimulated animals. Systemic administration of morphine (10 mg/kg i.v.) completely inhibited the release of immunoreactive substance P from the superficial layers of SpVc evoked by ST, and this inhibition was antagonized by local application of methysergide (10(-4) M). These results suggest that in the superficial layers of SpVc, morphine may primarily activate the descending 5-HT pathway which serves to modulate dental pain transmission.


Limits of delocalization in through-conjugated dinitrenes: aromatization or bond formation?
[reaction: see text] Dinitrenes 4 and 5 both can form quinonoidal structures by conjugative bond formation. However, ESR spectroscopy detects a thermally populated, excited-state, triplet quinonoidal structure only for 4, with a zero-field splitting of |D/hc| = 0.0822 cm(-)(1), |E/hc| congruent with 0.0 cm(-)(1). The tendency to maintain aromaticity in the additional ring of 5 favors a dinitrene structure (with one less formal pi-bond) over a quinonoidal structure. The thermally populated quintet state of 5 has a zero-field splitting of |D/hc| = 0.287 cm(-)(1), |E/hc| <or= 0.002 cm(-)(1).


Role of functional fatty acids in modulation of reproductive potential in livestock.
Fatty acids are not only widely known as energy sources, but also play important roles in many metabolic pathways. The significance of fatty acids in modulating the reproductive potential of livestock has received greater recognition in recent years. Functional fatty acids and their metabolites improve follicular development, oocyte maturation and embryo development, as well as endometrial receptivity and placental vascular development, through enhancing energy supply and precursors for the synthesis of their productive hormones, such as steroid hormones and prostaglandins. However, many studies are focused on the impacts of individual functional fatty acids in the reproductive cycle, lacking studies involved in deeper mechanisms and optimal fatty acid requirements for specific physiological stages. Therefore, an overall consideration of the combination and synergy of functional fatty acids and the establishment of optimal fatty acid requirement for specific stages is needed to improve reproductive potential in livestock.


Occlusion-robust scene flow-based tissue deformation recovery incorporating a mesh optimization model.
Tissue deformation recovery is to reconstruct the change in shape and surface strain caused by tool-tissue interaction or respiration, which is essential for providing motion and shape information that benefits the improvement of the safety of minimally invasive surgery. The binocular vision-based approach is a practical candidate for deformation recovery as no extra devices are required. However, previous methods suffer from limitations such as the reliance on biomechanical priors and the vulnerability to the occlusion caused by surgical instruments. To address the issues, we propose a deformation recovery method incorporating mesh structures and scene flow. The method can be divided into three modules. The first one is the implementation of the two-step scene flow generation module to extract the 3D motion from the binocular sequence. Second, we propose a strain-based filtering method to denoise the original scene flow. Third, a mesh optimization model is proposed that strengthens the robustness to occlusion by employing contextual connectivity. In a phantom and an in vivo experiment, the feasibility of the method in recovering surface deformation in the presence of tool-induced occlusion was demonstrated. Surface reconstruction accuracy was quantitatively evaluated by comparing the recovered mesh surface with the 3D scanned model in the phantom experiment. Results show that the overall error is 0.70 ± 0.55 mm. The method has been demonstrated to be capable of continuously recovering surface deformation using mesh representation with robustness to the occlusion caused by surgical forceps and promises to be suitable for the application in actual surgery.


The inferior olivary complex of guinea pig: cytoarchitecture and cellular morphology.
The inferior olivary complex (I.O.C.) of the guinea pig can be divided into three primary subdivisions: the principal olive (PO), the medial accessory olive (MAO), and the dorsal accessory olive (DAO). In Nissl-stained preparations, the PO possessed darker staining cells than did the MAO and DAO and was the most densely populated with cells. All neuronal somata in the I.O.C. were oblique-spheroid in profile (mean size: coronal = 18.3 microns, parasagittal = 15.8 microns). Based on Golgi impregnations, it was apparent that inferior olive cells were of two unique radiate-cell types (I and II). Type I neurons had relatively diffuse, sparsely branched dendritic arbors, whereas type II cells had dendrites which were highly branched and massed about the cell body, at times creating complex spirals. Type II cells were further categorized into types IIa and IIb based on geometric variations of the type II dendritic arbors. Indices of branching and tortuosity, together with estimates of dendritic arbor volume, were quite helpful in distinguishing cell types. The cell types were differentially distributed across the subdivisions with type I neurons being encountered in the MAO while type II cells were found in all three subdivisions. Within the neuropil of the I.O.C., three different afferent axonal arbors were identified, as was the presence of dendrites from surrounding reticular formation cells. Neuronal aggregates creating a possible electrical syncytium within the I.O.C. are consistent with the dendroarchitectonics of the cells.


Symptom clusters in advanced cancer.
Patients with advanced cancer often experience multiple concurrent symptoms. Few studies have explored symptom clusters (SCs) in this population. The aim of the present study was to explore SCs in advanced cancer, evaluate the characteristics associated with various clusters, and determine their relationship to survival. This study included patients in the palliative care program of the Hospital Universitario La Paz from 2003 to 2005. The Edmonton Symptom Assessment System and a supplement including 13 other symptoms were used to detect symptoms. Principal component analysis was performed to determine symptom relationships and compare SCs with associated parameters. In total, 406 patients were included, 61% men and 39% women. The median age was 66.4 (range 18-95). The most common primaries were gastrointestinal (35%), lung (25%), genitourinary (8%), breast (5%), and head and neck (5%) carcinomas. The following clusters were identified: confusion (cognitive impairment, agitation, urinary incontinence), neuropsychological (anxiety, depression, and insomnia), anorexia-cachexia (anorexia, weight loss, and tiredness), and gastrointestinal (nausea and vomiting). The presence of these SCs was influenced by primary cancer site, gender, age, and performance status. Survival was related to the number of SCs present in a given patient: zero SC, 52 days; one SC, 38 days; two SCs, 23 days; and three to four SCs, 19 days; P < 0.001. Different SCs can be identified in patients with advanced cancer. These SCs are influenced by primary cancer site, gender, age, and Eastern Cooperative Oncology Group performance status, and they can have prognostic value.


Diversity of Rickettsia in ticks collected from wild animals in Panama.
This paper presents new data about Rickettsia species detected in ticks collected from wild animals, using 16S rRNA, gltA and ompA. Rickettsia DNA was found in 66 of 101 ticks. Using EZ BioCloud libraries were produced reads that identified Rickettsia aeschlimannii, and Illumina BaseSpace produced reads of Rickettsia rickettsii group, Rickettsia bellii group, and unclassified Rickettsia. Using gltA and ompA gene-specific primers, R. aeschlimannii could not be confirmed, but detection of Rickettsia amblyommatis was achieved in Amblyomma auricularium, Amblyomma geayi, Amblyomma mixtum, and Amblyomma pacae; R. bellii from Amblyomma dissimile, "Candidatus Rickettsia colombianensi" from A. dissimile, Rickettsia spp. closely related to R. raoultii from A. geayi, Rickettsia tamurae from A. dissimile, and Rickettsia endosymbionts of Ixodes from Ixodes affinis. There were no databases available specifically for 16S rRNA of Neotropical Rickettsia, highlighting the need to use species primers over only 16S rRNA primers to achieve more accurate interpretations and identifications. These findings increase the number of Rickettsia species detected in Panama and highlight the need to establish isolates to further characterize the nature of Rickettsia in the area.


Association of nocturia and cardiovascular disease: Data from the National Health and Nutrition Examination Survey.
To investigate the association of nocturia with the prevalence of cardiovascular disease (CVD) using the National Health and Nutrition Examination Survey (NHANES) data. Among the 40 790 individuals who participated in NHANES from 2005 to 2012, 14 114 adults were analyzed in this study. A participant was considered to have nocturia if they have two or more voiding episodes nightly. In addition, participants with nocturia more than four times in a day were considered to have severe nocturia. A multivariate logistic regression analysis with adjustment for confounding variables, including age, sex, race, body mass index (BMI), smoking status, alcohol consumption, sleeping time, dyslipidemia, hypertension, and diabetes mellitus was performed with 1:1 propensity score matching (PSM). Nocturia occurred in 4610 individuals (32.7%). The prevalence of CVD was significantly higher in men, older individuals, those with higher BMI, smokers, and those with diabetes, hypertension, and hyperlipidemia. There was also a significantly higher prevalence of nocturia in the participants with CVD. Multivariate analysis showed that odds ratios (ORs) of mild and severe nocturia for CVD were 1.23 (95% confidence interval [CI]: 1.08-1.39) and 1.74 (95% CI: 1.39-2.17), respectively. After 1:1 PSM, the ORs of mild and severe nocturia were 1.27 (95% CI: 1.10-1.48) and 1.73 (95% CI: 1.33-2.26), respectively, showing statistical significance. Data from the NHANES indicate that CVD was significantly associated with the prevalence of nocturia, after taking major confounding factors into account. Furthermore, the risk for CVD increases with increasing nocturia severity.


In-situ growth of zeolitic imidazolate frameworks into a cellulosic filter paper for the reduction of 4-nitrophenol.
Whatman® cellulosic filter paper was used as a substrate for the synthesis of two zeolitic imidazolate frameworks (ZIFs); ZIF-8 and ZIF-67 with and without 2,2,6,6-tetramethyl-1-piperidine oxoammonium salt (TEMPO)-oxidized cellulose nanofibril (TOCNF). All synthesis procedures take place at room temperature via a one-pot procedure. The synthesis steps were followed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transforms infrared (FT-IR). Data indicated the formation of metal oxide that converted to a pure phase of ZIFs after the addition of the organic linker i.e. 2-methyl imidazole (Hmim). The materials were characterized using XRD, FT-IR, SEM, energy dispersive X-ray (EDX), nitrogen adsorption-desorption isotherms, and X-ray photoelectron microscope (XPS). Data analysis confirms the synthesis of ZIFs into Whatman® filter paper. The materials were used for the reduction of pollutants such as 4-nitrophenol (4-NP) compound to 4-aminophenol (4-AP). The materials exhibit high potential for water treatment and may open new exploration for hybrid materials consisting of cellulose and ZIFs.


Rapamycin Attenuates Acute Seizure-induced Astrocyte Injury in Mice in Vivo.
Astrocytes have been implicated in epileptogenesis and seizure-induced brain injury. Pathological studies reveal a variety of structural abnormalities in astrocytes, such as vacuolization and astrogliosis. While in vivo imaging methods have demonstrated rapid changes in astrocytes under a variety of physiological and pathological conditions, the acute effects of seizures on astrocyte morphology in vivo and corresponding mechanisms of seizure-induced astrocytic injury have not been documented. In this study, we utilized in vivo two-photon imaging to directly monitor the acute structural effects of kainate-induced seizures on cortical astrocytes. Kainate seizures cause an immediate, but transient, vacuolization of astrocytes, followed over several days by astrogliosis. These effects are prevented by pre- or post-treatment with rapamycin, indicating the mTOR pathway is involved in mediating seizure-induced astrocyte injury. These finding have clinical implications for mechanisms of seizure-induced astrocyte injury and potential therapeutic applications with mTOR inhibitors.


The NAM/ATAF1/2/CUC2 transcription factor PpNAC.A59 enhances PpERF.A16 expression to promote ethylene biosynthesis during peach fruit ripening.
Peach is a typical climacteric fruit that releases ethylene during fruit ripening. Several studies have been conducted on the transcriptional regulation of ethylene biosynthesis in peach fruit. Herein, an ethylene response factor, PpERF.A16, which was induced by exogenous ethylene, could enhance ethylene biosynthesis by directly inducing the expression of 1-aminocyclopropane-1-carboxylic acid synthase (PpACS1) and 1-aminocyclopropane-1-carboxylic acid oxidase (PpACO1) genes. Moreover, the NAM/ATAF1/2/CUC2 (NAC) transcription factor (TF) PpNAC.A59 was coexpressed with PpERF.A16 in all tested peach cultivars. Interestingly, PpNAC.A59 can directly interact with the promoter of PpERF.A16 to induce its expression but not enhance LUC activity driven by any promoter of PpACS1 or PpACO1. Thus, PpNAC.A59 can indirectly mediate ethylene biosynthesis via the NAC-ERF signaling cascade to induce the expression of both PpACS1 and PpACO1. These results enrich the genetic network of fruit ripening in peach and provide new insight into the ripening mechanism of other perennial fruits.


Relative associations of fitness and fatness to fibrinogen, white blood cell count, uric acid and metabolic syndrome.
To examine the relation between fitness and fibrinogen, white blood cell count, uric acid and metabolic syndrome across levels of adiposity in apparently healthy, nonsmoking men. Cross-sectional study of 4057 men from the Aerobics Center Longitudinal Study examining the age-adjusted resting levels and risk of having a clinically significant elevation of fibrinogen, white blood cell count, uric acid and metabolic syndrome score across nine fitness-body fatness combinations. Fitness categories (low fitness, moderately fit or high fitness) were based on a maximal treadmill test. Body mass index (BMI) <25.0 was classified as normal weight, BMI > or = 25.0 but <30.0 as overweight and BMI > or = 30.0 as obese. Fitness (inversely) and BMI (directly) were independently related to the age-adjusted values of all four variables (P for trend P<0.0001 for each). For all four variables, the greatest age-adjusted risk of having a clinically relevant value was found in the low fitness-obese category and the lowest age-adjusted risk was found in the high fitness-normal weight group. Fibrinogen, white blood cells, uric acid and metabolic syndrome score are independently related to both fitness (inversely) and fatness (directly). Within levels of fatness, risk for significant elevations in fibrinogen, white blood cells, uric acid and metabolic syndrome score is lower for the higher fitness groups.


Resource recovery in life cycle assessment of sludge treatment: Contribution, sensitivity, and uncertainty.
This study focused on the resource recovery of sludge treatment by quantifying the environmental contributions, identifying the influential factors, and comparing different scenarios. Life cycle assessment (LCA) of sewage sludge treatment was carried out to estimate the environmental impacts of six scenarios: (1) co-digestion of sludge and food waste; (2) co-gasification of sludge and woody waste; (3) co-incineration of sludge and used oil; (4) landfilling; (5) incineration; and (6) anaerobic digestion combined with incineration. Results demonstrate that the resource recovery had a substantial contribution to the environmental performance of the sludge treatment, while the degree of contribution was largely affected by various treatment scenarios and diverse impact categories. To gain deep insight into the parameters related to resource recovery, sensitivity analysis was performed to investigate the influence of the parameters on the LCA results, including the organic content, conversion efficiency of organic matter to methane, and other energy conversion efficiencies. After integrating the inventory variation of those parameters into the decision process via the Monte Carlo simulation, results indicate that no obviously superior scenario could be identified. Conversely, when parameter uncertainty was not considered, co-gasification of sludge and woody waste exhibited the most preferable environmental performance. Overall, this study demonstrates that considering the parameter uncertainty of resource recovery will contribute to a more transparent evaluation process, but will inevitably increase the complexity of the decision-making process based on LCA results because it is difficult to determine a sludge treatment scenario that decisively outperforms the others.


Identification of a heparin activated amidolytic enzyme in carp (Cyprinus carpio) plasma.
A heparin activated amidolytic enzyme capable of cleaving synthetic thrombin sensitive chromogenic substrates was identified from the plasma of the carp (Cyprinus carpio). Activation was inhibited by KCl, protamine sulphate and human plasma. Heparin was not required for the continued action of the enzyme. Active enzyme was irreversibly inhibited by DFP. The pH and temperature optima was studied and the enzyme semi purified by Sephadex G100 superfine and Sephadex A50 chromatography. An approximate MW of 62,000 was found. Activity generated by as little as 0.002 units of heparin per ml carp plasma was detected. The trivial name carpamidase is proposed for the enzyme.


Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor.
Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.


Liberation, purification, and properties of thioesterase component of pigeon liver fatty acid synthetase complex.
Proteolysis of pigeon liver fatty acid synthetase with elastase results in the quantitative cleavage of the thioesterase component from the enzyme complex. This thioesterase component is two or three times more active catalytically in the isolated state than in the native fatty acid synthetase, and its activity is not affected by the presence or absence of reducing thiols. The proteolytically cleaved thioesterase is separated from the core enzyme in one step by size-exclusion chromatography on a Sephadex G-75 column. The peptide obtained by gel permeation is homogeneous with respect to size and charge, as shown by polyacrylamide gel electrophoresis in the presence and absence of SDS. Size-exclusion chromatography on Bio-Gel A 0.5 m and Sephadex G-75 columns, sucrose density gradient ultracentrifugation, and N-terminal amino acid analysis also indicate that the proteolytically cleaved thioesterase is homogeneous. The sedimentation coefficient of the thioesterase is approximately 2.9 S. Proteolytic cleavage with elastase also quantitatively releases the [1,3-14C]- or [1,3-3H]diisopropylphosphofluoridate-labeled thioesterase component from the correspondingly labeled fatty acid synthetase. Binding studies with 14C- or 3H-labelled diisopropylphosphofluoridate and fatty acid synthetase show that 2 mol of the label are bound per mol of the enzyme when complete loss of fatty acid-synthesizing activity occurs. The molecular weight of the thioesterase component is estimated to be 36000 by size-exclusion chromatography, SDS-polyacrylamide gel electrophoresis and amino acid analysis.


B. G. Johns and his "famous blind men" the genesis of heroic blindness in Victorian England.
In 1876, Bennett George Johns, a minister and chaplain at the school for the blind in St George's Field, published Blind People: Their Works and Ways; with Sketches of the Lives of Some Famous Blind Men. The book provided a window into the lives of the blind in Victorian England, with an emphasis on their education-or lack thereof. Johns was an observer of the blind and sympathetic to their plight. His depictions of schools were dispassionate, yet gently argued for improvement. Rather than rely on pity, he emphasized the benefits of institutionalized life and recounted the extraordinary achievements of four blind men. The creation of heroic historical figures had traditionally been employed to venerate political, military, or religious personages. Its use in shaping public perception of blindness was novel. This paper explores Johns's book as an early example of the innocent, myth-building of the blind and considers whether the process is always harmless.


Prokineticin 2 promotes and sustains neuroinflammation in vincristine treated mice: Focus on pain and emotional like behavior.
Vincristine (VCR) treatment is often associated to painful neuropathy. Its development is independent from antitumoral mechanism and involves neuroinflammation. We investigated the role of the chemokine prokineticin (PK)2 in a mouse model of VCR induced neuropathy using a PK-receptors (PK-R) antagonist to counteract its development. We also evaluated emotional like deficits in VCR mice. VCR (0,1 mg/kg) was i.p. injected in C57BL/6J male mice once a day for 14 consecutive days. Pain, anxiety and depressive like behaviors were assessed in animals. PK2, PK-Rs, cytokines, neuroinflammatory markers (CD68, CD11b, GFAP, TLR4) and ATF3 were evaluated in DRG, spinal cord, prefrontal cortex and hippocampus. The PK-Rs antagonist PC1, was s.c. injected (150 μg/kg) twice a day from day 7 (hypersensitivity state) until day 14. Its effect on pain and neuroinflammation was evaluated. VCR mice developed neuropathic pain but not mood alterations. After 7 days of VCR treatment we observed a neuroinflammatory condition in DRG with high levels of PK-Rs, TLR4, CD68, ATF3 and IL-1β without relevant alterations in spinal cord. At day 14, an upregulation of PK system and a marked neuroinflammation was evident also in spinal cord. Moreover, at the same time, we observed initial alterations in supraspinal brain areas. PC1 treatment significantly counteracted neuropathic pain and blunted neuroinflammation.


Early reactions of brain-derived neurotrophic factor in plasma (pBDNF) and outcome to acute antidepressant treatment in patients with Major Depression.
In Major Depressive Disorder, a growing data base suggests that the onset of antidepressants' action can be detected by improvement of depressive symptoms in the first 10-14 days of treatment. Previous studies showed that the mean concentration of the brain-derived neurotrophic factor (BDNF) in blood increases during antidepressant treatment and positively correlates with amelioration of MDD symptoms. We previously showed an association between very early changes of the serum BDNF concentration and treatment outcome (Tadić et al., 2011. Prog Neuropsychopharmacol Biol Psychiatry 35, 415-420). However, no study has yet investigated whether BDNF concentration in plasma increases in the early course of treatment and enables the prediction of final treatment outcome. The goal of this study was to investigate in MDD patients, whether the change of pBDNF in the early course of treatment is a specific and sensitive marker for final treatment outcome. For this purpose, we performed a naturalistic pilot study with 39 inpatients with MDD according to DSM-IV. Depression severity and pBDNF were measured in weekly intervals from baseline (EP) to endpoint (EP, max. week six) with the 21-item Hamilton Depression Rating Scale (HAMD-21) and enzyme-linked immunosorbent assay (ELISA), respectively. According to ROC-analysis, the best cut-off value for the prediction of response at EP is an increase of 338 pg/ml or 126%, respectively, of pBDNF between BL and day 7. The single markers pBDNF change and HAMD-21 improvement from BL-d7 predicted later treatment outcome with moderate to high sensitivity and specificity (pBDNF: 42% and 96%, resp.; HAMD improvement: 83% and 65%, resp.). The combined marker early pBDNF change plus HAMD-21 improvement at day 7 increased the specificity for response to 100%. Our data provide first preliminary evidence that an early change of pBDNF in conjunction with early improvement might be a peripheral marker predictive for treatment outcome in patients with MDD. This has to be confirmed in further investigations. This article is part of a Special Issue entitled 'Anxiety and Depression'.


Corrigendum to "Application of Minocycline-Containing Bismuth Quadruple Therapies as First-Line Regimens in the Treatment of Helicobacter pylori".
[This corrects the article DOI: 10.1155/2019/9251879.].


Membrane alterations in cerebral cortex when using PIPES buffer.
When used for vascular perfusion of brain, 0.1 M PIPES-buffered 3% glutaraldehyde resulted in the formation of expanded, vesicle-filled cell processes limited by multiple membrane layers. These structures, termed multivesicular myelin figures and interpreted as artefacts, were most common in layer 2 of the cerebral cortex. When cacodylate or phosphate buffer was used instead of PIPES buffer in the primary fixative, such structures were not seen. The use of a more concentrated initial aldehyde fixative, PIPES-buffered, markedly reduced the size and numbers of these artefacts when compared to PIPES-buffered 3% glutaraldehyde only. Slowing the initial perfusion rate increased the size and frequency of occurrence of multivesicular myelin figures with PIPES buffer when compared to optimum perfusions. Prolonged initial exposure to PIPES buffer by using it to wash out the blood and then perfusing with fixative 5 min later did not increase the number or size of multivesicular myelin figures but did reduce the multivesicular nature of the artefacts. We suggest that the non-toxic nature of PIPES buffer allowed the formation of these membranous artefacts, while phosphate and cacodylate interfered with the cellular activity during the process of fixation.


Metals in wine--impact on wine quality and health outcomes.
Metals in wine can originate from both natural and anthropogenic sources, and its concentration can be a significant parameter affecting consumption and conservation of wine. Since metallic ions have important role in oxide-reductive reactions resulting in wine browning, turbidity, cloudiness, and astringency, wine quality depends greatly on its metal composition. Moreover, metals in wine may affect human health. Consumption of wine may contribute to the daily dietary intake of essential metals (i.e., copper, iron, and zinc) but can also have potentially toxic effects if metal concentrations are not kept under allowable limits. Therefore, a strict analytical control of metal concentration is required during the whole process of wine production. This article presents a critical review of the existing literature regarding the measured metal concentration in wine, methods applied for their determination, and possible sources, as well as their impact on wine quality and human health. The main focus is set on aluminum, arsenic, cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc, as these elements most often affect wine quality and human health.


Endovascular isolated hepatic perfusion under pneumoperitoneum.
Isolated hepatic perfusion (IHP) allows loco-regional administration of high drug doses for cancer treatment. Minimally invasive endovascular occlusion techniques can be used for IHP, but control of leakage remains a major drawback. We hypothesized that the increased intraabdominal pressure generated by a CO(2)-pneumoperitoneum (PP) can reduce the leakage rate of hypoxic endovascular IHP by mechanical compression of the capillary beds connecting the liver to the systemic circulation. IHP was performed on adult pigs through laparotomy using a fenestrated double balloon-catheter placed into the retrohepatic vena cava to collect the hepatic outflow which was reinfused into the hepatic artery through an extracorporeal circulation system. Each pig underwent IHP during four consecutive phases: abdomen open (Phase I), abdomen closed under a 15 and 20 mmHg pneumoperitoneum (Phase II and III, respectively) and abdomen re-opened (Phase IV). The leakage rate from the liver to the systemic circulation was continuously monitored using a nuclear medicine technique. The systemic arterial pressure, the IHP inflow and outflow pressures and the flow rate were recorded. Leakage from the hepatic extracorporeal circulation to the systemic circulation occurred in all animals during Phase I. Under PP (Phases II and III), two leakage profiles were observed: (1) a major increase of the leakage rate in two animals with a high differential pressure (>50 mmHg) between the IHP inflow and the systemic pressures; (2) no change or a decrease of the leakage rate in the other three animals who had a low or negative differential pressure (<30 mmHg). Leakage was undetectable in all animals after exsufflation of the PP (Phase IV). IHP under PP is feasible. Leakage is not reduced during PP. A high gradient between the IHP inflow and the systemic pressure increases systemic leakage during PP. Upon release of the PP, the leakage is most likely redirected towards the volume depleted low resistance portal territory.


Muconaldehyde formation from 14C-benzene in a hydroxyl radical generating system.
It has recently been proposed that muconaldehyde, a six carbon, alpha, beta-unsaturated dialdehyde, may be a hematotoxic metabolite of benzene. The present studies indicate that trans, trans-muconaldehyde is formed from benzene in vitro in a hydroxyl radical (.OH) generating system containing ascorbate, ferrous sulfate and EDTA in phosphate buffer, pH 6.7. Muconaldehyde formed from benzene in the .OH generating system was identified by trapping it with thiobarbituric acid (TBA), which results in the formation of an adduct with a 495 nm absorption maximum and a 510 nm fluorescence emission maximum. These maxima were identical to those observed after reacting authentic trans, trans-muconaldehyde with TBA. This finding was supported by thin layer chromatography and solid phase extraction studies. In those studies benzene-derived muconaldehyde cochromatographed with the muconaldehyde/TBA standard. Analyses of the products from the .OH generating system using high performance liquid chromatography (HPLC) confirm that trans, trans-muconaldehyde is a product of benzene ring fission. Regardless of whether or not TBA was used for trapping, samples from the .OH system incubated with benzene contained a peak which cochromatographed with the muconaldehyde standard. The radioactivity profile of fractions collected during HPLC analysis demonstrates 14C-benzene to be the source of the trans, trans-muconaldehyde. The role of hydroxyl radicals in the formation of muconaldehyde was investigated by using dimethyl sulfoxide, mannitol, and ethanol as .OH scavengers. These scavengers, at concentrations of 10 and 100 mM, were found to cause a dose-dependent decrease in the formation of muconaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)


Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment.
We examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L-T4) treatment. This prospective study employing 1912 consecutive patients analyses the interacting equilibria of TSH and free triiodothyronine (FT3) and free thyroxine (FT4) in the circulation. The complex interrelations between FT3, FT4 and TSH were modulated by age, body mass, thyroid volume, antibody status and L-T4 treatment. By group comparison and confirmation by more individual TSH-related regression, FT3 levels were significantly lower in L-T4-treated vs untreated nonhypothyroid autoimmune thyroiditis (median 4·6 vs 4·9 pm, P < 0·001), despite lower TSH (1·49 vs 2·93 mU/l, P < 0·001) and higher FT4 levels (16·8 vs 13·8 pm, P < 0·001) in the treated group. Compared with disease-free controls, the FT3-TSH relationship was significantly displaced in treated patients with carcinoma, with median TSH of 0·21 vs 1·63 (P < 0·001) at a comparable FT3 of 5·0 pm in the groups. Disparities were reflected by calculated deiodinase activity and remained significant even after accounting for confounding influences in a multivariable model. TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.


Breast-conserving therapy is associated with better survival than mastectomy in Early-stage breast cancer: A propensity score analysis.
Recent retrospective studies have reported that breast-conserving therapy (BCT) led to improved overall survival (OS) than mastectomy in some populations. We aimed to compare the efficacy of BCT and mastectomy using the SEER database. Between 2010 and 2015, 99,790 eligible patients were identified. We included early-stage breast cancer patients with 5cm or smaller tumors and three or fewer positive lymph nodes in our study. We compared the OS and breast cancer-specific survival (BCSS) results among patients with BCT and those with mastectomy. Kaplan-Meier plots, Cox proportional hazard regressions, competing risk analysis, and multivariate regressions were used to evaluate the outcomes. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. In our study, 77,452 (77.6%) patients underwent BCT and 22,338 (22.4%) underwent mastectomy. The 5-year OS rate was 94.7% in the BCT group and 87.6% in the mastectomy group, and the 5-year BCSS was 97.2% in the BCT and 94.3% in the mastectomy group. Multivariate analysis in the matched cohort showed that women underwent mastectomy was associated with worse OS (Hazard ratio (HR) = 1.79; 95% confidence intervals (CIs) = 1.59-2.02, p < 0.001) and BCSS (HR = 1.88; 95% CIs = 1.61-2.18, p < 0.001) results compared with those underwent BCT. Patients with different subtypes and age group (>50 years old; ≤50 years old) received BCT showed significantly better OS and BCSS results than those received mastectomy. The effect of surgery choice on survival yielded similar results either for all patients or matched cohorts. Our study showed that BCT was associated with improved survival compared with mastectomy in early-stage breast cancer patients. It seems advisable to encourage patients to receive BCT rather than mastectomy in early-stage patients when feasible and appropriate.


Preparation and characterization of vaccarin, hypaphorine and chitosan nanoparticles and their promoting effects on chronic wounds healing.
Chronic wounds have become an important factor hindering human health, affecting tens of millions of people worldwide, especially diabetic wounds. Based on the antibacterial properties of chitosan, the angiogenesis promoting effect of vaccarin (VAC) and the anti-inflammatory effect of hypaphorine (HYP), nanoparticles with high bioavailability were prepared. VAC, HYP and chitosan nanoparticles (VAC + HYP-NPS) were used to the treatment of chronic wounds. Transmission electron microscopy (TEM) images showed the nanoparticles were spherical. ZetaPALS showed the potential of nanoparticles were -12.8 ± 5.53 mV and the size were 166.8 ± 29.95 nm. Methyl thiazolyl tetrazolium (MTT) assay showed that VAC + HYP-NPS had no toxicity and the biocompatibility was satisfactory. In the treatment of chronic wounds in diabetic rats, VAC + HYP-NPS significantly promoted the re-epithelialization of chronic wounds and accelerated the healing of chronic wounds. In the process of chronic wounds healing, VAC + HYP-NPS played the antibacterial effect of chitosan, the angiogenic effect of VAC and the anti-inflammatory effect of HYP, and finally promoted the chronic wounds healing. Overall, the developed VAC + HYP-NPS have potential application in chronic wounds healing. In view of the complexity of the causes of chronic wounds, multi-target drug administration may be an effective way to treat chronic wounds.


Autoinflammatory keratinitzation diseases (AIKDs.
Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years.


Deaths of British nationals abroad--a 10-year survey.
Details are presented of all deaths of British Nationals abroad where a post mortem examination after repatriation was carried out in what is now the Wales Institute of Forensic Medicine. The problems posed by such deaths are discussed and the conclusion is drawn that without international uniformity in technique and documentation of medico-legal post mortem examinations, H.M. Coroner cannot be confident that all pathological evidence has been gathered from such an examination carried out in another country. A plea is made for international uniformity in the criteria for selection of deaths which require post mortem examination.