Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance.
Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (delta 0-10 min insulin area divided by delta 0-10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2-19.4] vs 9.1 [2.6-14.5] mU.mmol-1; p < 0.01). During the clamp, circulating insulin (93 +/- 8 [mean +/- SEM] and 81 +/- 10 mU.l-1) and glucagon (54 +/- 4 and 44 +/- 6 ng.l-1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 +/- 0.27 vs 4.47 +/- 0.53 mg.kg-1.min-1; p < 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 +/- 0.10 and 0.30 +/- 0.18 mg.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)


Transplantation versus dialysis in diabetic patients with renal failure.
Studies suggesting that transplantation is better than dialysis for diabetic patients with renal failure may be biased by the more favorable pretreatment prognosis of transplanted patients. Therefore, to provide a fairer comparison we controlled for pretreatment clinical state, categorized treatment received, and assessed mortality, major morbid events, and hospitalization in 51 diabetic patients who began therapy between 1970 and 1980. Fourteen patients were treated by transplantation and 37 by dialysis. The mean waiting period for transplantation was 5 months. The average age of transplanted patients was 40.9 years and of dialyzed patients 59.6 years. When we controlled for this age disparity and other factors (duration of diabetes and heart failure) that affect prognosis in end-stage renal disease (ESRD), the mortality with both transplantation and dialysis was similar to that expected from the overall mortality rate of the 51 study patients. Treatment received had no effect on mortality; the observed deaths compared with deaths expected from pretreatment status were 8 and 7.3 for transplantation and 30 and 30.7 for dialysis. We also compared major morbid events (blindness, amputation, stroke, severe heart failure, and myocardial infarction) and hospitalization in transplanted patients with the 24 dialyzed patients who survived long enough (5 months) to be eligible for transplantation. The number of major morbid events was 2.7 per 10 patient-years in the transplanted group and 3.4 in the dialyzed group. Hospitalization was 151.3 d/yr in transplanted patients and 55.6 d/yr in dialyzed patients (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


The use of sulthiame- in myoclonic epilepsy of childhood and adolescence.
Sulthiame has been used by most investigators in psychomotor seizures, other focal seizures and grand-mal, usually in conjuction with other anticonvulsants. Reports on its use in myoclonic epilepsy and as a sole anti-convulsant are few and inconclusive. The present report presents the results of a study carried out on the use of sulthiame in 54 cases of myoclonic epilepsies originating in infancy, childhood and adolescence. The different types of myoclonic epilepsy are defined. An illustrative case report is included. Results indicated that sulthiame is the drug of choice, often as the sole anti-convulsive agent, in cases of "juvenile myoclonic epilepsy". In the myoclonic encephalopathies of childhood (the so-called "minor motor epilepsy" or Lennox-Gastaut syndrome), which are notoriously refractory to therapy, sulthiame appears to be an efficacious adjunct to currently-used agents, including benzodiazepines, succinimides, dipropyl acetate, steriods and a ketogenic diet.


Annual variation of dissolved free primary amines in estuarine water and sediment.
The concentration of dissolved free primary amines (DFPA), determined as fluorescamine positive material, was quantified during a one year period of a small estuary. In the water, the concentration of DFPA ranged from 1.8 μM in winter, to 26.5 μM in summer. In the sediment, from 16 to 56 μM of DFPA occurred. The concentration varied with depth and season, and in summer months a maximum of DFPA was observed in the redox discontinuity layer. The DFPA peak in water and sediment coincided with maximum of the macrophytal biomass. About 80% of the fluorescamine positive material was identified as amino acids. Origin and distribution of primary amines in the estuarine environment are discussed.


Cholinergic nerve development of fetal lung in vitro.
The development of the cholinergic or parasympathetic nervous system was studied in embryonic lung dissociated from the central nervous system and placed in organ culture. In vitro development was similar to that seen in vivo. This study demonstrated that migration of neuroblasts from the central nervous system to the trachea takes place before day 12. Neuroblasts differentiate to small immature ganglia and then to larger more mature ganglia that give off nerve fibers to the submucosa and the epithelium. This isolated lung preparation was used to study neurostimulators. Thyroxine (T4) was found to accelerate nerve fiber growth and differentiation of ganglia in vitro. The neuroepithelial body, an epithelial cell with acetylcholine-esterase-positive granules, also differentiated in vitro. This cell may fill the morphologic criteria of an intrapulmonary chemoreceptor.


[Effect of thermal mud baths on normal, dry and seborrheic skin].
To investigate the curative effects of thermal water and thermal muds in various cutaneous pathologies. Modifications of phmetry and sebometry using sulphur thermal muds in normal, dry and seborrheic skin have been studied. The three groups of patients have been submitted to a 14 day treatment with thermal muds. The application of thermal mud normalized the value of cutaneous pH and sebometry. These beneficial effects are long-lasting in individuals who have a prolonged treatment with thermal muds.


Retardation of gastric emptying of solid food by secretin.
The effect of secretin at nearly physiologic plasma concentrations on the gastric emptying rate of solid food was studied in 12 healthy men. A 99mTc colloid-labeled pancake was used as the test meal. The gastric emptying rate was measured during 1 h using a dual-headed gamma-camera, and was expressed as the half-time of the emptying curve. To prevent endogenous secretin release, 400 mg of cimetidine was given before the meal. Subjects were studied under three conditions: (1) during infusion of saline; (2) during continuous infusion of secretin, 6.6 pmol/kg.h; and (3) during three intermittent 10-min periods of secretin infusion, 7.6 pmol/kg.h during each period. Both continuous and intermittent infusion of secretin increased half-emptying time, by 133% and 55%, respectively. The plasma secretin concentration in condition 1 was 0.8 pM; plateau concentration in condition 2 was 9.8 pM; and integrated mean concentration in condition 3 was 4.8 pM. It is concluded that secretin at approximately physiologic plasma concentrations retards gastric emptying of solid food in humans.


Time window of autoreceptor-mediated inhibition of limbic and striatal dopamine release.
Forebrain dopamine release is under the local control of D2 family (D2 and D3) autoreceptors. In this study, autoreceptor-mediated modulation of forebrain dopamine release was investigated using amperometry in brain slices following local electrical stimulation. 350 microm-thick slices of nucleus accumbens or dorsolateral neostriatum were prepared from male Wistar rats (150-200 g) and superfused with artificial cerebrospinal fluid at 32 degrees C. Dopamine release was evoked by electrical pulses (0.1 ms, 10 mA) across bipolar tungsten stimulating electrodes and measured at carbon fibre microelectrodes using fixed potential amperometry (+300 mV vs. Ag/AgCl). Peak dopamine release on stimulation (single pulse) was 0.75 microM (neostriatum) and 1.37 microM (nucleus accumbens). Metoclopramide (1 microM) had no significant effect on DA efflux from a single pulse in either region. Using paired pulse stimuli, dopamine release on the second pulse varied according to the interval between the two pulses. At very long intervals (>20 sec), dopamine release was similar to that for the first pulse. At shorter intervals, dopamine efflux was attenuated. Metoclopramide had no effect on second pulse dopamine release when the pulse was applied at short (<0.1 sec) or long (>5.0 sec) intervals after the first. At intermediate intervals, metoclopramide significantly increased second pulse dopamine release. The peak dopamine autoreceptor effect occurred at approximately 550 ms in neostriatum and approximately 700 ms in nucleus accumbens. The onset time is due both to diffusion of dopamine from the release sites to the autoreceptors and receptor-effector mechanisms. These findings may have implications for the local control of forebrain dopamine function in physiological and pathological states.


From basic science to clinical practice: Can cognitive behavioural therapy tasks be augmented with enhanced episodic specificity?
Individuals with depression typically remember their past in a generalised manner, at the cost of retrieving specific event memories. This may impair engagement with cognitive behavioural therapy (CBT) tasks that use concrete episodic information to challenge maladaptive beliefs, potentially limiting their therapeutic benefit. Study 1 demonstrated that an episodic specificity induction increased detail and specificity of autobiographical memory in people with major depression, relative to control conditions (N = 88). We therefore examined whether the induction enhanced the efficacy of CBT tasks that depend on episodic memory - cognitive reappraisal (Study 2, N = 30), evidence gathering (Study 2, N = 30), and planning behavioural experiments (Study 3a, N = 30). Across all three tasks, there were no significant differences in emotion- or belief-change between the specificity and control conditions. Although the induction temporarily enhanced specificity in depressed individuals, it did not significantly augment the efficacy of CBT tasks theorised to benefit from the use of specific mnemonic information.


Optic flow induces spatial filtering in fruit flies.
The discrete and random nature of light absorption dictates that, when photons are scarce, images suffer from low signal-to-noise ratios [1]. Nocturnal animals combat this by increasing photon catch, either optically, with large pupils, photoreceptors, and ever larger eyes [2], or neurally, with summation strategies, which sacrifice acuity and leave images blurry and slow [3]. Fast image motion produces the same problems as dim light: photon noise and low signal-to-noise ratio. As a result, fast animals often exhibit optical adaptations comparable to nocturnal animals, but pronounced in lateral regions of the eye where images move quickly [4]. For example, flying insects typically increase equatorial curvature between the front and side of the eye, which increases interommatidial angle and improves light capture. Drosophila, curiously, show only minor changes in interommatidial angle [5]; but even without optical adaptations, they could potentially achieve a similar effect with neural summation. The optimal strategy would manifest as acuity loss, specifically in regions of fast motion, and only parallel to motion. Photoreceptors need quick temporal dynamics to cope with fast motion [6], so the ideal filtering would additionally be spatial. To determine if fruit flies implement filtering driven by background optic flow, I tested their frequency-dependent steering and found that flow transiently eliminates high spatial frequency responses. This effect increases from forward to lateral visual regions, acts only parallel to flow direction, and filters only high spatial, not temporal, responses. Facultative summation may maximize visual information by improving sensitivity during fast flight, but limiting acuity loss when the fly is still.


Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group.
This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma. This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naive patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m(2) for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progression-free survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS). Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile. Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.


Guidelines for the diagnosis and treatment of acute and subacute rhinosinusitis in children.
The importance of rhinosinusitis finally reached pediatricians' attention a few years ago, and it has now been demonstrated that it is medically important and has a considerable socioeconomic impact in childhood. These guidelines, which have been prepared with and approved by many Italian Scientific Societies, are based on the most recent findings in the fields of clinical symptoms, imaging and microbiology tests for the diagnosis of acute rhinosinusitis, and efficacy evidence concerning antibiotic treatment and non-antibiotic adjuvant treatment. A Pubmed search using the key words "sinusitis", "rhinosinusitis", "child" and "antibiotic treatment", and the limits "human studies" and "English language", led to the selection of more than 2,700 articles published between 1966 and 2007. These guidelines are based on the 125 that were considered truly relevant and reflect the most widely shared positions concerning the diagnosis and treatment of acute, subacute and recurrent rhinosinusitis in children.


Inhibitory responses to exogenous adenosine in murine proximal and distal colon.
The aims of the present study were firstly, to characterize pharmacologically the subtypes of P(1) purinoreceptors involved in the inhibitory effects induced by exogenous adenosine in longitudinal smooth muscle of mouse colon, and secondly, to examine differences in the function and distribution of these receptors between proximal and distal colon. Adenosine (100 microM-3 mM) caused a concentration-dependent reduction of the amplitude of spontaneous contractions in the proximal colon, and muscular relaxation in the distal colon. In the proximal colon, adenosine effects were antagonized by a selective A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM), but were not modified by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM) or by 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino)- [1,2,4]triazolo[1,5-c]quinazoline (MRS 1220, 0.1 microM), selective A(2) and A(3) receptor antagonists, respectively. In the distal colon, adenosine effects were antagonized by DPCPX, DMPX, and by a selective A(2B) receptor antagonist, 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl) xanthine (MRS 1754, 10 microM), but not by 8-(3-chlorostyryl)-caffeine (CSC, 10 microM), a selective A(2A) receptor antagonist, or by MRS 1220. Tetrodotoxin (TTX 1 microM), the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM), an inhibitor of soluble guanylyl cyclase, reduced adenosine effects only in distal colon. In addition, L-NAME induced a further reduction of adenosine relaxation in the presence of DPCPX, but not in the presence of MRS 1754. From these results we conclude that, in the murine proximal colon, adenosine induces inhibitory effects via TTX-insensitive activation of A(1) receptor. In the distal colon, adenosine activates both A(1) and A(2B) receptors, the latter located on enteric inhibitory neurons releasing NO.


Discovery of arylsulfonamides as a novel class of allosteric integrase inhibitors with antiviral activity.
Lens epithelial-derived growth factor (LEDGF) increases the efficiency of proviral DNA integration into the host genome by interacting with HIV integrase (IN) and directing it to a chromatin environment that favors viral transcription. Allosteric integrase inhibitors (ALLINIs), such as known 2-(tert-butoxy)acetic acid (1), bind to the LEDGF pocket on the catalytic core domain (CCD) of IN, but exert more potent antiviral activities by inhibition of late-stage HIV-1 replication events than through disruption of proviral integration at an earlier phase. A high-throughput screen (HTS) for compounds that disrupt IN-LEDGF interaction led to the identification of a novel arylsulfonamide series, as exemplified by 2, possessing ALLINI-like properties. Further SAR studies led to more potent compound 21 and provided key chemical biology probes revealing that arylsulfonamides are a novel class of ALLINIs with a distinct binding mode than that of 2-(tert-butoxy)acetic acids.


Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients with ovarian endometriomas.
To determine whether serum interleukin (IL)-6 can be measured in patients with ovarian endometriomas and whether these measurements are useful in managing this disease. A controlled clinical study and an in vitro study. Department of Obstetrics and Gynecology, Tottori University, Japan.Twenty-two patients with ovarian endometriomas. Laparoscopic cystectomy for ovarian endometriomas was performed. Gonadotropin-releasing hormone (GnRH) agonist was administered for 3 months in nine patients before laparoscopic surgery. Endometriotic stromal cells obtained from patients with endometriomas with or without GnRH agonist treatment were cultured. IL-6 concentrations in serum or supernatant of the cell culture were measured using ELISA. The serum concentration of IL-6 in patients with endometriomas was higher at the time of diagnosis than in those without endometriomas. Laparoscopic surgery significantly reduced serum levels of IL-6. Serum IL-6 concentrations also decreased after treatment with GnRH agonist. IL-6 production was attenuated in the endometriotic stromal cells obtained from patients with GnRH agonist treatment compared with patients without such treatment. GnRH agonist treatment may decrease IL-6 production in endometriotic cells. Measurement of serum IL-6 concentrations may be of value in managing patients with endometriomas.


Equivalence of the standard monophasic waveform shocks delivered by automated external defibrillators?
To study whether two different types of monophasic waveform shocks (i.e. monophasic damped sinusoidal [MDS] and monophasic truncated exponential [MTE] waveform shocks) are of equivalent efficacy. Retrospective review of defibrillation efficacy and outcome in ventricular fibrillation/ventricular tachycardia (VF/VT) patients treated in the same EMS system with AEDs delivering either MDS waveform shocks (n=40) or MTE waveform shocks (n=40). Defibrillation efficacy of the first shock was 82.5% in the MDS group and 70% in the MTE group (P=0.19). Termination of VF by at least one of the first three shocks was found in 95 and 85% of the patients treated with MDS and MTE waveform shocks, respectively (P=0.22). Restoration of spontaneous circulation occurred in 75% of the MDS group and 30% of the MTE group (P=0.0001). Hospital admission rates were 52.5% in the MDS group and 17.5% in the MTE group (P=0.001). Hospital discharge rates were 17.5% in the MDS group and 7.5% in the MTE group (P=0.18). Our data suggest disparity in efficacy between MDS waveform shocks and MTE waveform shocks. Furthermore, our findings should be taken into consideration when the issue of the control group(s) in future clinical trials on new waveforms is discussed.


Different degrees of processing of secretogranin II in large dense core vesicles of bovine adrenal medulla and sympathetic axons correlate with their content of soluble PC1 and PC2.
We investigated the processing of secretogranin II in large dense core vesicles of adrenal medulla and sympathetic nerve. Despite the fact that both types of vesicles have a very similar biochemical composition, the degree of processing of secretogranin II in vesicles from splenic nerve was significantly higher. The endoproteases PC1 and PC2, two likely candidates for secretogranin II cleavage, are found in both types of vesicles, however, relative to secretogranin II the nerve vesicles have a much higher content of these enzymes. This probably explains the fast and more extensive processing of secretogranin II in these vesicles.


The impact of improving access to primary care.
To measure the size and timing of changes in utilization and costs for employees and dependents who had major access barriers to primary care removed, across an 8-year period (2007 to 2014). Retrospective observational study examining patterns of utilization and costs before and after the implementation of a worksite medical office in 2010. The worksite office offered convenient primary care services with no travel from work, essentially guaranteed same day access, and no co-pay. Trends in visit rates and costs were compared for an intervention fixed cohort group (employees and dependents) at the employer (n = 1211) with a control fixed cohort group (n = 542 162) for 6 types of visits (primary, urgent, emergency, inpatient, specialty, and other outpatient). Difference-in-differences methods assessed the significance of between-group changes in utilization and costs. The worksite medical office intervention group had an increase in primary care visits relative to the control group (+43% vs +4%, P < 0.001). This was accompanied by a reduction in urgent care visits by the intervention group compared with the control group (-43% vs -5%, P < 0.001). There were no differences in the other types of visits, and the total visit costs for the intervention group increased 5.7% versus 2.7% for the control group (P = 0.008). A sub-group analysis of the intervention group (comparing dependents to employees) found that that the dependents achieved a reduction in costs of 2.7% (P < 0.001) across the study period. The potential for long-term reduction in utilization and costs with better access to primary care is significant, but not easily nor automatically achieved.


Recent progress in metabolic engineering of microbial formate assimilation.
Formate can be efficiently produced via electrochemical or photochemical catalytic conversion of CO2, and it can be directly used as an organic carbon source by microorganisms. In theory, formate can be used as the sole carbon source for the microbial production of high-value-added chemicals. Consequently, the construction of efficient formate-assimilation pathways in microorganisms is essential for the utilization of cheap, renewable one-carbon compounds. This paper summarizes new methods of formate synthesis, as well as the natural formate utilization pathways of microorganisms with their advantages and disadvantages. Furthermore, it reviews recent progress in the design of utilization pathways for formate in microbial cells through metabolic engineering and synthetic biology. Besides, we also use the pathway-prediction algorithm comb-FBA to rationally design completely new one-carbon compounds utilization pathways. The pathway with the highest efficiency, named GAA, was corroborated by the in vitro experiments showing a carbon molar yield up to 88%. Finally, it discusses the main problems and challenges presently existing in the pathway design and strain improvement for microbial utilization of formate. KEY POINTS: • Natural and artificial design pathways of formate-assimilation was summarized. • Recent progresses in different hosts and approaches of using one-carbon compounds was reviewed. • Metabolic engineering and synthetic biology methods to improve formate utilization were discussed.


Synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme.
The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, (1)H NMR, (13)C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H 37 Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562-3.125 μg/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues.


Growth of the facultative chemolithoautotroph Ralstonia eutropha on organic waste materials: growth characteristics, redox regulation and hydrogenase activity.
The chemolithoautotrophic β-proteobacterium Ralstonia eutropha H16 (Cupriavidus necator) is one of the most studied model organisms for growth on H2 and CO2. R. eutropha H16 is also a biologically significant bacterium capable of synthesizing O2-tolerant [NiFe]-hydrogenases (Hyds), which can be used as anode biocatalysts in enzyme fuel cells. For heterotrophic growth of R. eutropha, various sources of organic carbon and energy can be used. Growth, bioenergetic properties, and oxidation-reduction potential (ORP) kinetics were investigated during cultivation of R. eutropha H16 on fructose and glycerol or lignocellulose-containing brewery spent grain hydrolysate (BSGH). BSGH was used as carbon and energy source by R. eutropha H16, and the activities of the membrane-bound hydrogenase (MBH) and cytoplasmic, soluble hydrogenase (SH) were measured in different growth phases. Growth of R. eutropha H16 on optimized BSGH medium yielded ~ 0.7 g cell dry weight L-1 with 3.50 ± 0.02 (SH) and 2.3 ± 0.03 (MBH) U (mg protein)-1 activities. Upon growth on fructose and glycerol, a pH drop from 7.0 to 6.7 and a concomitant decrease of ORP was observed. During growth on BSGH, in contrast, the pH and ORP stayed constant. The growth rate was slightly stimulated through addition of 1 mM K3[Fe(CN)6], whereas temporarily reduced growth was observed upon addition of 3 mM dithiothreitol. The overall and N,N'-dicyclohexylcarbodiimide-sensitive ATPase activities of membrane vesicles were ~ 4- and ~ 2.5-fold lower, respectively, upon growth on fructose and glycerol (FGN) compared with only fructose utilization (FN). Compared to FN, ORP was lower upon bacterial growth on FGN, GFN, and BSGH. Our results suggest that reductive conditions and low ATPase activity might be signals for energy depletion, which, in turn, leads to increased hydrogenase biosynthesis to overcome this unfavorable situation. Addition of fructose or microelements have no, or a negative, influence on hydrogenase activity. Organic wastes (glycerol, BSGH) are promising carbon and energy sources for the formation of biomass harboring significant amounts of the biotechnologically relevant hydrogenases MBH and SH. The results are valuable for using microbial cells as producers of hydrogenase enzymes as catalysts in enzymatic fuel cells.


The Identification of Two New Races of Pyrenophora tritici-repentis from the Host Center of Diversity Confirms a One-to-One Relationship in Tan Spot of Wheat.
ABSTRACT Pyrenophora tritici-repentis, causal agent of tan spot, induces necrosis and chlorosis in its wheat host. The tan spot system conforms to the toxin model and three host-specific toxins have been identified (Ptr ToxA, Ptr ToxB, and putative Ptr ToxC). Processing of a collection of isolates, obtained in the Fertile Crescent and Caucasus regions, yielded two new virulence patterns. Isolate Az35-5 combined the virulences of races 2 and 5 and was classified in the new race 7. Isolates TS93-71B and TS93-71F had a virulence pattern that combined those of races 2, 3, and 5 and were grouped in the new race 8. Southern analysis revealed that all three isolates possessed copies of the ToxA and ToxB genes, the first time the genes were found in a common background. The production of Ptr ToxA and Ptr ToxB by the isolates was confirmed by western blotting. Virulence patterns suggested that TS93-71B and TS93-71F may also produce Ptr ToxC, even though it was not present at detectable levels in culture filtrates. The identification of races 7 and 8 complete the theoretical maximum number of races that can be differentiated by three loci in the host (2(3) = 8), assuming a one-to-one relationship. It appears that the wheat/P. tritici-repentis system is a mirror image of the classical gene-for-gene relationship.


Evaluation of antipyretic potential of Vernonia cinerea extract in rats.
The methanol extract of the whole plant of Vernonia cinerea (MEVC) was evaluated for its antipyretic potential on normal body temperature and yeast-induced pyrexia in rats. MEVC significantly reduced the normal body temperature at doses of 250 and 500 mg/kg body weight p.o. MEVC also lowered the elevated body temperature in the case of yeast-induced pyrexia in a dose dependent manner. The antipyretic effect of the extract at a dose of 500 mg/kg was identical to that of the standard drug paracetamol.


Estimating the burden of hypertension and its significant risk factors among male commercial drivers in sub-Saharan Africa: A systematic review and meta-analysis.
The study was designed to assess the burden and significant risk factors among male commercial drivers in sub-Saharan Africa (SSA). Systematic review and meta-analysis. Medline via PubMed, Google Scholar, Cochrane databases and Africa Journal Online were searched from January 2010 to December 2020. The authors included observational studies reporting on the burden and/or risk factors for hypertension among commercial drivers in SSA. Male adult population ≥18 years working as a commercial driver in SSA as well articles published in English. Two independent coauthors used a prepared data extraction form to extract data from the eligible published papers and assessed the risk of bias. DerSimonian and Laird random effects model was used to pool the burden of hypertension and significant risk factors among male commercial drivers in SSA. The presence of heterogeneity among studies was quantified by estimating variance using both Cochrane's Q statistics and the I2 statistics. A subgroup and sensitivity analyses were performed. Overall, 14 articles met the inclusion criteria involving a total of 4285 male commercial drivers in SSA. The estimated pooled burden of hypertension among the male commercial drivers in SSA was 32% (95% CI 24% to 39%). The risk factors identified were age OR=1.10 (95% CI 1.06 to 1.15), overweight/obese OR=3.38 (95% CI 2.46 to 4.29), alcohol consumption OR=3.00 (95% CI 2.05 to 3.95) and duration of driving (≥5 years) OR=1.83 (95% CI 1.03 to 2.63). Funnel plot inspection and Egger's regression test of small effect (0.5838) showed no evidence of publication bias. Our review showed that nearly one-third of male commercial drivers in SSA have hypertension. Reduction of modifiable risk factors such as overweight/obesity, alcohol consumption and long-term driving through multifaceted implementation strategies are recommended for prevention and control of hypertension among male commercial drivers in SSA. CRD42021250910.


Inching Toward a Unified Metatheory for Psychology.
Zagaria et al. (2020) have aptly suggested that as a discipline, psychology is a giant with feet of clay. Drawing on the content of introductory textbooks, the authors show that there is little coherence and consensus about the meaning of key psychological terms - including such terms as psychology, mind, behavior. Drawing on evidence marking psychology is a "soft" science, the authors suggest that psychology can profit by adopting the "hard" foundation of evolutionary psychology as its metatheory. While Zagaria et al.'s characterization of psychology's fractious foundation has deep merit, their desire to erect a psychological metatheory on evolutionary psychology is unlikely to solve the problem they so aptly identify. At the least, I suggest a unified metatheory must: (a) establish a shared psychological lexicon; (b) elaborate a methodology that coordinates first-, second- and third-person modes of inquiry, and (c) develop a process model that describes psychological functioning at the biological, psychological and socio-cultural levels of analysis. To illustrate, I describe how contemporary relational and systems frameworks provide a framework that can move us in these directions.


Fate of respiratory droplets in tropical vs temperate environments and implications for SARS-CoV-2 transmission.
The new pandemic of SARS-CoV-2 has shown stark differences in number of affected patients between countries in the tropics and those with temperate environments. Though there have been many theories on reasons for these differences, we hypothesise that this could be due to differences in the fate of respiratory droplets in the two environments. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. This paper discusses the possibility of differences in number of infections and spread between different countries based on the spread of droplets.


Choledochocele, an overlooked diagnosis: report of 15 cases and review of 56 published reports from 1984 to 1992.
Choledochocele (CDCL) is still regarded as being a rare abnormality, despite the increasing number of case reports published in the last ten years. The aim of this prospective study was to investigate the prevalence rate of CDCL in patients referred for endoscopic retrograde cholangiopancreatography (ERCP), as well as the short-term and long-term complications of endoscopic treatment. Over a seven-year period, fifteen symptomatic patients (ten male, five female, age range 47-93 years) were identified as having CDCL out of a total of 1019 ERCP referrals to our unit. The diagnosis of CDCL was made by both duodenoscopy and ERCP. All 15 patients had small (4-25 mm) CDCLs associated with pancreatic (n = 1) or biliary (n = 14) disorders. Ten of the 15 patients (67%) had choledocholithiasis as well. Twelve patients were treated by endoscopic sphincterotomy (ES), and three by surgery. The immediate post-ES complications (2 of 12, 16.7%) were acute cholangitis (n = 1) and acute pancreatitis (n = 1). Eleven (76%) of the 14 patients who had a complete follow-up were symptom-free, with normal liver function tests at a median of 18 months (range 12-97). Two patients reported episodes of acute cholangitis, and one patient died of a misdiagnosed ampullary carcinoma arising in the CDCL. These results suggest that CDCL is probably an overlooked diagnosis in patients with pancreaticobiliary symptoms. It should be readily recognized and treated, preferably by endoscopic sphincterotomy. The endoscopist must be aware that an ampullary carcinoma may develop in a CDCL.


Unit activity in the nucleus triangularis septi of the rat following blood pressure changes or vasoactive peptides, and electrically stimulated blood pressure decreases.
The nucleus Triangularis Septi (TS) of anesthetized rats was studied using iontophoretic application of various vasoactive peptides (vasopressin and angiotensin) to a small number of the cells in this nucleus and blood pressure recordings during electrical stimulation of the nucleus. In the iontophoretic study 83% of the cells investigated were found to be sensitive to iontophoretic application or intracerebroventricular infusion of angiotensin II and vasopressin and that 40% of these cells were sensitive to spontaneous or induced increases of blood pressure. Electrical stimulation of the nucleus produced a reliable and reproducible decrease in blood pressure without any change in heart rate. Therefore the possible role of the TS in blood pressure regulation is discussed.


The impacts of brewing in glass tumblers and thermos vacuum mugs on the aromas of green tea (Camellia sinensis).
This study investigated the effect of brewing apparatus on the aromatic feature of tea infusion. Huangshan Maofeng tea infusion was brewed under glass tumblers (GT) or thermos vacuum mugs (TVM) for up to 180 min. Tea infusion sensory attributes were evaluated using quantitative descriptive analysis and the composition of volatiles were analyzed using headspace solid phase microextraction coupled with gas chromatography-mass spectrometry. Results showed that GT tea infusion at each brewing duration possessed stronger 'Pure', 'Fresh' and 'Grassy' attributes than TVM tea infusion, whereas TVM tea infusion showed a higher intensity on 'Steamed' aroma. A total of 74 volatiles were detected in tea infusion, and aldehydes and alcohols appeared to be the major volatiles. Total aldehydes concentration percentage decreased in tea infusion with brewing process, whereas an increase on total alcohol percentage was found. Principal component analysis indicated that brewing duration and apparatus played vital roles in altering the volatile composition in tea infusion, whereas orthogonal partial least squares discriminant analysis (OPLS-DA) revealed that GT tea infusion samples were separated from TVM tea infusion samples. OPLS-DA also screened 20 volatiles that significantly contributed to the differentiation of GT and TVM tea infusion.


Late Balloon Valvuloplasty for Transcatheter Heart Valve Dysfunction.
Transcatheter heart valve (THV) dysfunction with an elevated gradient or paravalvular leak (PVL) may be documented late after THV implantation. Medical management, paravalvular plugs, redo THV replacement, or surgical valve replacement may be considered. However, late balloon dilatation is rarely utilized because of concerns about safety or lack of efficacy. We aimed to evaluate the safety and efficacy of late dilatation in the management of THV dysfunction. All patients who underwent late dilatation for symptomatic THV dysfunction at 2 institutions between 2016 and 2021 were identified. Baseline, procedural characteristics, and clinical and echocardiographic outcomes were documented. THV frame expansion was assessed by multislice computed tomography before and after late dilatation. Late dilatation was performed in 30 patients a median of 4.6 months (IQR: 2.3-11.0 months) after THV implantation in the aortic (n = 25; 83.3%), mitral (n = 2; 6.7%), tricuspid (n = 2; 6.7%) and pulmonary (n = 1; 3.3%) position. THV underexpansion was documented at baseline, and frame expansion substantially improved after late dilatation. The mean transvalvular gradient fell in all patients. For aortic THVs specifically, mean transaortic gradient fell from 25.4 ± 13.9 mm Hg to 10.8 ± 4.1 mm Hg; P < 0.001. PVL was reduced to ≤mild in all 11 patients with a previous >mild PVL. Embolic events, stroke, annular injury, and bioprosthetic leaflet injury were not observed. Symptomatic benefit was durable at 19.6 months (IQR: 14.8-36.1 months) follow-up. Balloon dilatation late after THV implantation appears feasible and safe in appropriately selected patients and may result in THV frame expansion resulting in improvements in hemodynamic performance and PVL.


Molecular modeling, design, synthesis, and biological evaluation of novel 3',4'-dicamphanoyl-(+)-cis-khellactone (DCK) analogs as potent anti-HIV agents.
Our current studies aimed at developing new potential anti-AIDS drug candidates have focused on the design and synthesis of new DCK analogs with improved molecular water solubility. Based on the structures and biodata of previous DCK analogs, 3D-QSAR studies have been performed which resulted in two reliable computational models, CoMFA and CoMSIA, with r(2) values of 0.995 and 0.987, and q(2) values of 0.662 and 0.657, respectively. In accord with these 3D-QSAR models, 15 new DCK analogs with polar functional groups at the 3-position were subsequently designed, synthesized, and evaluated against HIV-1 replication in H9 and MT4 cell lines. New DCK analogs 3b, 3c, 4b, 4c, 6a, 7c, and 9a showed promising potency with EC(50) values ranging from 0.09 to 0.0002 microM in both assays. Meanwhile, these promising compounds also showed a wide range of predicted logP values from 0.90 to 5.19, which increased the probability of identifying anti-HIV drug candidates from this class of compounds for clinical trials. Furthermore, both experimental and predicted values matched well, corroborating the reliability of the established 3D-QSAR models.


Problems in the clinical assessment of memory.
The purpose of this paper is to examine the current state of clinical memory testing in the light of recent theoretical and experimental advances in the study of human memory. It recounts some of the purposes of memory testing and inadequacies in the tests currently available. A brief review of information processing theory and experimental findings with Korsakoff patients and aged normals provides a number of considerations that must be attended to in developing more adequate memory tests in the future.


[The Relationship of Work Stress and Somatic Symptoms Among Early Childhood Professionals During the COVID-19 Pandemic].
The COVID-19 pandemic has changed the world of work. Due to additional occupational health and safety measures early childhood professionals were faced with an increased workload, which may lead to an increased risk for their individual health. The aim of this cross-sectional study was to obtain updated prevalences of psychosocial work stress (effort-reward imbalance, ERI), overcommitment as well as somatic symptoms and their association during the COVID-19 pandemic. Early childhood professionals from a large city in North Rhine-Westphalia (N=1009) participated in the survey between June 2020 and May 2021. The Effort-Reward Imbalance at work questionnaire (16 items version) was used to assess work stress, and the Patient Health Questionnaire (PHQ-15) was used to assess somatic symptoms. A multiple logistic regression tested the association between work stress and somatic health. In total, 72.3% of the sample showed an effort-reward imbalance, 25.0% showed a high overcommitment. The overall prevalence of somatization at a moderate to high level was 45.2%. Effort-reward imbalance and high overcommitment increased the odds of severe symptom presence by a factor of 4.12 and 5.20, respectively. This study shows the high number of effort-reward imbalances, the high overcommitment and the above-average prevalence of somatic complaints among early childhood professionals during the COVID-19 pandemic. In view of these high prevalences and their relationships, there is still a strong need for action and research to reduce work-related stress in this occupational group as well as to investigate the persistence of and the management of somatic symptoms in order to develop long-term preventive measures.


Partial purification and characterization of neutrophic substance affecting tetrodotoxin sensitivity of organ-cultured mouse muscle.
From mouse spinal cord homogenate, we isolated a trophic substance which reverses the post-denervation decrease in tetrodotoxin sensitivity of action potential in organ-cultured extensor digitorum longus muscle of mouse and characterized its physicochemical properties. The trophic substance was separated from macromolecules in homogenate by gel filtration on Biogel P2 column. The partially purified trophic substance was heat-stable, acid-stable and alkaline-labile. The trophic activity was destroyed by lyophilization at neutral pH but not at acidic pH. The trophic activity was abolished by incubation with pronase or leucine aminopeptidase, but not by trypsin, chymotrypsin, thermolysin or carboxypeptidase A. The trophic substance passed through an ultrafiltration membrane UM10 freely. A small part of the trophic activity passed through a UM2 or UM05, and the rest was retained on the membranes. The trophic substance adsorbed on CM-Sephadex at pH 7.2 but passed through DEAE-Sephadex at pH 8.4. These results suggest that the trophic substance regulating tetrodotoxin sensitivity of action potential in mouse skeletal muscle is a peptide with a rather low molecular weight of less than 10,000 and that while the N-terminus of the peptide is free, the C-terminus is probably blocked. This peptide differs from other trophic substances reported previously by other investigators.


Predictive variables of sustained virological response after early discontinuation of triple therapy with telaprevir for genotype-1 HCV infection.
Pivotal phase studies of telaprevir (TLV) and boceprevir (BOV) showed 10-56% rates of early treatment interruption. However, there have been no reports on the sustained virological response (SVR) rates of these patients. To assess the SVR rate in a large cohort of patients who discontinued triple therapy with TLV or BOV for reasons other than stopping rules and to identify variables predicting SVR. A survey was sent to 15 hospitals in Catalonia asking them to report all TLV/BOV treatments finished by 31 May 2014. Demographic, clinical, laboratory, liver fibrosis and therapeutic data were recorded for treatments with early discontinuation. Logistic regression analysis, ROC curves and prognostic assessment of the variables identified were calculated. Twelve hospitals responded to the survey, representing 467 treatments and 121 (21.2%) early discontinuations, 76 (62.8%) due to stopping rules and 45 (37.2%) for other reasons. Early discontinuation was more frequent with BOV [38.2% (50/131) versus 21.1% (71/336) p<0.005], mainly due to stopping rules [78% (39/50) versus 52.1% (37/71); p=0.004]. SVR was achieved in 21/121 patients (17.4%), 19/71 (26.8%) treated with TLV and 2/50 (4.0%) treated with BOV. In patients discontinuing treatment for reasons other than stopping rules, SVR was achieved in 19/37 (55.9%) treated with TLV and in 2/11 (18.2%) treated with BOV. The SVR rate in patients treated with TLV who discontinued due to a severe adverse event was 61.5% (16/26). A logistic regression analysis was performed only with triple therapy with TLV and early discontinuation. The predictive variables of SVR were undetectable HCV-RNA at treatment week 4 and treatment length longer than 11 weeks. Treatment duration longer than 11 weeks showed the best accuracy (0.794), with a positive predictive value of 0.928. Early discontinuation of TLV-based triple therapy due to reasons other than stopping rules still have a significant SVR rate (55.9%). Undetectable HVC-RNA at week 4 of treatment and treatment duration longer than 11 weeks are predictive of SVR in this subset of patients.


Ratiometric fluorescent detection of intracellular hydroxyl radicals based on a hybrid coumarin-cyanine platform.
The first ratiometric fluorescent probe for hydroxyl radical ratiometric imaging in living cells was rationally designed based on a hybrid coumarin-cyanine platform.


Placement of the GaBP ring system in the banded gastric bypass operation.
Currently, bariatric surgeons fashion the band or ring reinforcement prosthesis, to control the stoma in the vertical banded gastroplasty and gastric bypass operations for morbid obesity. To meet this need, the GaBP Ring system has been developed in various sizes, and consists of 4 main parts to provide a means for inserting a ring around the gastric pouch in the banded gastric bypass or the vertical banded gastroplasty. The pre-manufactured and sterilized device provides for better standardization and quality control than individually surgeon-fashioned devices. The GaBP Ring system is described, and the technique of placement and the pertinent initial clinical results are presented.


Long-term effect of ovariectomy on dopamine-stimulated adenylate cyclase in rat striatum and nucleus accumbens.
The long-term effects on dopamine-sensitive adenylate cyclase of deprivation of gonadal steroids resulting from ovariectomy were studied in extrahypothalamic areas of the brain, i.e. corpus striatum and nucleus accumbens. The results obtained show that in both central nervous system areas dopamine- and apomorphine-stimulated adenylate cyclase were significantly reduced, suggesting that the function of dopamine receptors in these areas was depressed.


Boundary cue invariance in cortical orientation maps.
We effortlessly perceive oriented boundaries defined by either luminance changes ('first-order' cues) or texture variations ('second-order' cues). Many neurons in mammalian visual cortex show orientation preference to both types of boundaries, but it is uncertain how they contribute to perceptual orientation cue-invariance at the neuronal population level. Using optical imaging in cat A 18, we observed highly similar orientation preference maps to first-order and a variety of second-order visual stimuli. Thus the neuronal representation of coarse-scale boundary orientation appears to be invariant to the characteristics (including local orientation) of the fine-scale textures by which those boundaries are defined. A common feature of second-order visual stimuli is that modulation shifts their Fourier energy for boundary orientation to the higher spatial frequencies of their constituent textures - our results suggest a common neural mechanism (demodulation) mediating visual processing of many kinds of texture boundary. The similarity between orientation maps to different stimuli implies that second-order responsive neurons are homogeneously distributed across the cortical surface. Such homogeneously cue-invariant orientation representation could provide a neural substrate for perceptual form-cue invariance, and reflect an optimal organization for encoding orientation information in natural scenes.


Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review.
The effect of obesity on drug metabolism and pharmacokinetics is poorly understood, and this is particularly true in regard to contraceptive steroids. This article will review the known and theoretical physiologic and pharmacologic interactions between obesity and contraceptive steroids.


HPARSER: extracting formal patient data from free text history and physical reports using natural language processing software.
A prototype, HPARSER, processes a patient history and physical report such that specific data are obtained and stored in a patient data record. HPARSER is a recursive transition network (RTN) parser, and includes English and medical grammar rules, lexicon, and database constraints. Medical grammar rules augment the grammar rule base and specify common phrases seen in patient reports (e.g., "pupils are equal and reactive"). Each database constraint associates a grammar rule with a database table and attribute. Constraint behavior is such that if a rule is satisfied, data is extracted from the parse tree and stored into the database. Control reports guided construction of grammar and constraint rules. Test reports were processed with the control rules. 85% of test report sentences parsed and a 60% data capture rate, compared to controls, was achieved. HPARSER demonstrates use of an RTN to parse patient reports, and database constraints to transfer formal data from parse trees into a database.


The impact of smoking cessation on drug abuse treatment outcome.
Although cigarette smoking is endemic among illicit drug users, drug abuse treatment programs rarely encourage smoking cessation and often discourage it. The purpose of this study was to determine whether smoking cessation after entering drug abuse treatment influenced drug use 12 months after drug abuse treatment. We analyzed 2316 cigarette smokers in the Drug Abuse Treatment Outcome Study (DATOS), a national, longitudinal study of drug abuse treatment. Heckman probit selection models assessed the association of self-reported smoking cessation while in drug abuse treatment on self-reported drug abstinence in the year after treatment completion, while simultaneously accounting for possible nonparticipation bias. Controlling for multiple factors, smoking cessation was associated with greater abstinence from drug use after completion of drug abuse treatment (P=.04). Despite drug abuse treatment programs' hesitance to encourage smokers to quit, smoking cessation does not negatively impact drug use outcomes.


Type I interferons mediate pancreatic toxicities of PERK inhibition.
The great preclinical promise of the pancreatic endoplasmic reticulum kinase (PERK) inhibitors in neurodegenerative disorders and cancers is marred by pancreatic injury and diabetic syndrome observed in PERK knockout mice and humans lacking PERK function and suffering from Wolcott-Rallison syndrome. PERK mediates many of the unfolded protein response (UPR)-induced events, including degradation of the type 1 interferon (IFN) receptor IFNAR1 in vitro. Here we report that whole-body or pancreas-specific Perk ablation in mice leads to an increase in IFNAR1 protein levels and signaling in pancreatic tissues. Concurrent IFNAR1 deletion attenuated the loss of PERK-deficient exocrine and endocrine pancreatic tissues and prevented the development of diabetes. Experiments using pancreas-specific Perk knockouts, bone marrow transplantation, and cultured pancreatic islets demonstrated that stabilization of IFNAR1 and the ensuing increased IFN signaling in pancreatic tissues represents a major driver of injury triggered by Perk loss. Neutralization of IFNAR1 prevented pancreatic toxicity of PERK inhibitor, indicating that blocking the IFN pathway can mitigate human genetic disorders associated with PERK deficiency and help the clinical use of PERK inhibitors.


Evaluation of regional myocardial function in ischemic heart disease by echocardiography.
Echocardiography can display motion abnormalities of acutely or chronically ischemic myocardium. In experimental studies, this permits the evaluation of the effect on regional dyskinesis of potentially therapeutic interventions. In clinical studies, the demonstration of segmental dyskinesis has been primarily useful for diagnostic purposes. As more experience is gained with the newer two-dimensional cross-sectional ultrasound techniques, it appears likely that these will afford a major advance in the diagnosis of ischemic heart disease by permitting the routine noninvasive demonstration of segmental ventricular dyskinesis and assessment of regional myocardial function.


Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population.
Left ventricular hypertrophy (LVH) is a valid predictor for cardiovascular mortality and morbidity regardless of age, gender, and race. The HyperGEN study conducted a genome-wide association study and identified twelve single nucleotide polymorphisms (SNPs) associated with LVH. The aim of this study was to validate these candidate SNPs in the Korean population. Among 1637 individuals from the Korean Multi-Rural Communities Cohort Study (MRCohort) of the Korean Genome Epidemiology Study (KoGES), we carried out a linear regression analysis with left ventricular mass index (LVMI) and a logistic regression analysis for LVH status. The rs4129218 on chromosome 12 tended to be associated with LVM/body surface area (adjusted β = -0.023; p = 0.036) and LVM/height(2.7) (adjusted β = -0.027; p = 0.016), and was marginally protective against LVH after adjustment for age, sex, body mass index, serum creatinine, systolic blood pressure, heart rate and antihypertensive medication (adjusted odds ratio = 0.766 and 0.731; p = 0.027 and 0.007 according to indexation by BSA and height(2.7), respectively). In the Korean population, the minor allele of rs4129218 had borderline association with lower LVM. This study suggests that rs4129218 on chromosome 12 showed consistent tendency of possibly related loci for LVH independent of ethnic background.


Recombination of 2Fe-2S Ferredoxins Reveals Differences in the Inheritance of Thermostability and Midpoint Potential.
Recombination can be used in the laboratory to overcome component limitations in synthetic biology by creating enzymes that exhibit distinct activities and stabilities from native proteins. To investigate how recombination affects the properties of an oxidoreductase that transfers electrons in cells, we created ferredoxin (Fd) chimeras by recombining distantly related cyanobacterial and cyanomyophage Fds (53% identity) that present similar midpoint potentials but distinct thermostabilities. Fd chimeras having a wide range of amino acid substitutions retained the ability to coordinate an iron-sulfur cluster, although their thermostabilities varied with the fraction of residues inherited from each parent. The midpoint potentials of chimeric Fds also varied. However, all of the synthetic Fds exhibited midpoint potentials outside of the parental protein range. Each of the chimeric Fds could also support electron transfer between Fd-NADP reductase and sulfite reductase in Escherichia coli, although the chimeric Fds varied in the expression required for similar levels of cellular electron transfer. These results show how Fds can be diversified through recombination and reveal differences in the inheritance of thermostability and electrochemical properties. Furthermore, they illustrate how electron transfer efficiencies of chimeric Fds can be rapidly evaluated using a synthetic metabolic pathway.


Using an innovative flag element ratio approach to tracking potential sources of heavy metals on urban road surfaces.
Heavy metals deposited on urban road surfaces can be washed-off by stormwater runoff, undermining stormwater reuse safety due to their high toxicity to ecological and human health. Heavy metals on urban road surfaces come from diverse sources and tracking these sources is essential to effectively manage stormwater and hence its reuse safety. This research study developed an innovative approach to tracking sources of heavy metals using data collected in Shenzhen, China. This approach developed was based on a "flag element ratio" theory, where each source generally corresponds to a specific ratio of targeted pollutants to the flag element. It is noted that Cr, Cu, Pb, Ni, and Zn on urban roads were 19.05 mg/kg to 152.01 mg/kg, 25.66 mg/kg to 310.75 mg/kg, 15.61 mg/kg to 220.35 mg/kg, 10.65 mg/kg to 100.28 mg/kg, and 138.14 mg/kg to 1047.05 mg/kg, respectively. Gasoline emission was the main source for Cr, Ni and Pb, while braking wear and tyre wear were the major sources of Cu and Zn, respectively. Furthermore, the rankings of sources of each heavy metal in terms of their contributions were obtained by using this approach. Vehicle exhaust was found as the main contributor for all the heavy metals on urban road surfaces. This highlighted that vehicle exhaust should be seriously considered in terms of controlling heavy metal pollution on urban road surfaces and hence resulting urban road stormwater runoff.


Indirect organogenesis-mediated high frequency conversion of non-embryonic synthetic seeds, essential oil profiling and antibacterial activity in genetically stable plants of Patchouli.
Patchouli is a prized tropical medicinal herb with broad-spectrum therapeutic importance. The present research work describes development of an efficient callus-mediated plant regeneration protocol along with associated germplasm portability system (via alginate-encapsulation). Using 1.5 mg/l α-naphthalene acetic acid (NAA) and 1.0 mg/l 2, 4-dichlorophenoxy acetic acid (2, 4-D), highly proliferative friable calli were produced that subsequently underwent organogenesis in combinatorial cytokinin treatment to yield multiple shoot clusters. The highest frequency of shoot formation was achieved using 1.5 mg/l NAA with 1.5 mg/l 6-benzylaminopurine (BAP) in Murashige and Skoog (MS) medium. In vitro-derived shoot tips were encapsulated with 3% sodium alginate and 100 mM CaCl2 solution. The encapsulated beads were germinated in MS media with various concentrations of polyamines, where the highest regeneration frequency was observed with 1.5 mg/l spermidine. The regenerated shoots were rooted in basal MS medium and were successfully acclimatized with 96% survival rate. Genetic homogeneity amongst the regenerated plantlets was validated using Start Codon Targeted polymorphism (SCoT) and CAAT box-derived polymorphism (CBDP) ascertaining a high degree of clonal fidelity. The essential oil (EO) profiling of the donor plant and the in vitro-derived plantlets revealed identical composition. Furthermore, the antibacterial activities of various tissue extracts and extracted EOs were evaluated against the opportunistic pathogens viz. Klebsiella pneumoniae (MTCC 109), Salmonella typhii (MTCC 733), Micrococcus luteus (MTCC 2470) and Staphylococcus aureus (MTCC 96). The minimum inhibitory concentration (MIC) ranged from 0.31 to 5.0 mg/ml and 2.5 to 5.0 mg/ml against Gram-positive and Gram-negative bacteria, respectively. Eventually, the present research provides a holistic insight into the rapid regeneration of quality planting material as well as pharmacological bioprospection of patchouli along with the scope of further qualitative improvement via genetic transformation. The online version contains supplementary material available at 10.1007/s13205-022-03302-3.


Utilizing G2/M retention effect to enhance tumor accumulation of active targeting nanoparticles.
In recent years, active targeting strategies by ligand modification have emerged to enhance tumor accumulation of NP, but their clinical application was strictly restricted due to the complex preparation procedures, poor stability and serious toxicity. An effective and clinical translational strategy is required to satisfy the current problems. Interestingly, the internalization of NP is intimately related with cell cycle and the expression of receptors is not only related with cancer types but also cell cycle progression. So the cellular uptake of ligand modified NP may be related with cell cycle. However, few investigations were reported about the relationship between cell cycle and the internalization of ligand modified NP. Herein, cellular uptake of folic acid (FA) modified NP after utilizing chemotherapeutic to retain the tumor cells in G2/M phase was studied and a novel strategy was designed to enhance the active targeting effect. In our study, docetaxel (DTX) notably synchronized cells in G2/M phase and pretreatment with DTX highly improved in vitro and in vivo tumor cell targeting effect of FA decorated NP (FANP). Since FA was a most common used tumor active targeting ligand, we believe that this strategy possesses broader prospects in clinical application for its simplicity and effectiveness.


Combined analysis of lipidomics and transcriptomics revealed the key pathways and genes of lipids in light-sensitive albino tea plant (Camellia sinensis cv. Baijiguan).
Currently, the mechanism by which light-sensitive albino tea plants respond to light to regulate pigment synthesis has been only partially elucidated. However, few studies have focused on the role of lipid metabolism in the whitening of tea leaves. Therefore, in our study, the leaves of the Baijiguan (BJG) tea tree under shade and light restoration conditions were analyzed by a combination of lipidomics and transcriptomics. The leaf color of BJG was regulated by light intensity and responded to light changes in light by altering the contents and proportions of lipids. According to the correlation analysis, we found three key lipid components that were significantly associated with the chlorophyll SPAD value, namely, MGDG (36:6), DGDG (36:6) and DGDG (34:3). Further weighted gene coexpression network analysis (WGCNA) showed that HY5 TF and GLIP genes may be hub genes involved lipid regulation in albino tea leaves. Our results lay a foundation for further exploration of the color changes in albino tea leaves.


Thermal acclimation to cold alters myosin content and contractile properties of rainbow smelt, Osmerus mordax, red muscle.
Rainbow smelt (Osmerus mordax), a eurythermal fish, live in environments from -1.8 to 20°C, with some populations facing substantial annual variation in environmental temperature. These different temperature regimes pose distinct challenges to locomotion by smelt. Steady swimming performance, red muscle function and muscle myosin content were examined to assess the prediction that cold acclimation by smelt will lead to improved steady swimming performance and that any performance shift will be associated with changes in red muscle function and in its myosin heavy chain composition. Cold acclimated (4°C) smelt had a faster maximum steady swimming speed and swam with a higher tailbeat frequency than warm acclimated (10°C) smelt when tested at the same temperature (10°C). Muscle mechanics experiments demonstrated faster contractile properties in the cold acclimated fish when tested at 10°C. The red muscle of cold acclimated smelt had a shorter twitch times, a shorter relaxation times and a higher maximum shortening velocity. In addition, red muscle from cold acclimated fish displayed reduced thermal sensitivity to cold, maintaining higher force levels at 4°C compared to red muscle from warm acclimated fish. Immunohistochemistry suggests shifts in muscle myosin composition and a decrease in muscle cross-sectional area with cold acclimation. Dot blot analysis confirmed a shift in myosin content. Rainbow smelt do show a significant thermal acclimation response to cold. An examination of published values of maximum muscle shortening velocity in fishes suggests that smelt are particularly well suited to high levels of activity in very cold water.


Safety of vaginal delivery in women infected with COVID-19.
There is limited data regarding the safety of vaginal delivery in women infected with COVID-19. Our goal was to assess the safety of vaginal delivery in women infected with COVID-19 and the risk of neonatal infection. This was a single medical center cohort study. Data were collected about the outcome of twenty-one women with laboratory-confirmed COVID-19 infection who delivered between March 23, 2020, and May 8, 2020. Twenty-one gravidas were diagnosed with COVID-19 infection. None required admission to the intensive care unit (ICU) and there were no fatalities. Seventeen delivered vaginally and four by caesareans. Apgar scores of all neonates were 9 at 1 min and 10 at 5 min. One neonate was diagnosed with COVID-19 infection 24 h after birth. Vaginal delivery in women infected with COVID-19 is not associated with a significant risk of neonatal infection.


Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure.
Elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease (CVD) in patients with chronic renal failure (CRF). The phosphate-binder sevelamer has been shown to decrease both phosphate and FGF23, but limited data indicate that sevelamer improves CRF-related CVD, such as diastolic dysfunction, left ventricular hypertrophy (LVH), and aortic stiffness. To gain additional information, we measured the effects of sevelamer on CVD in a murine model of CRF. Groups of CRF and sham-operated mice received regular chow or 3% sevelamer-HCl in the chow for 14 weeks, starting 6 weeks after the initiation of CRF or sham operation. After the first 8 weeks of sevelamer treatment, CRF mice had decreased serum phosphate levels and an improved aortic systolic expansion rate, pulse-wave velocity, and diastolic function, although LVH remained unchanged. Following an additional 6-week course of sevelamer, LVH had not progressed. The FGF23 serum level was not reduced by sevelamer until after 14 weeks of treatment. In multiple regression analysis, serum phosphate, but not FGF23, was independently correlated with LV diastolic function and mass. Thus, sevelamer first improved aortic stiffness and diastolic dysfunction and secondarily prevented LVH in mice with CRF. The phosphate-lowering, rather than FGF23-lowering, effect appears to be responsible for the observed cardiovascular improvement.


Delirium on stroke units: a prospective, multicentric quality-improvement project.
Post-stroke delirium (POD) in patients on stroke units (SU) is associated with an increased risk for complications and poorer clinical outcome. The objective was to reduce the severity of POD by implementing an interprofessional delirium-management. Multicentric quality-improvement project on five SU implementing a delirium-management with pre/post-comparison. Primary outcome was severity of POD, assessed with the Nursing Delirium Screening Scale (Nu-DESC). Secondary outcome parameters were POD incidence, duration, modified Rankin Scale (mRS), length of stay in SU and hospital, mortality, and others. Out of a total of 799 patients, 59.4% (n = 475) could be included with 9.5% (n = 45) being delirious. Implementation of a delirium-management led to reduced POD severity; Nu-DESC median: pre: 3.5 (interquartile range 2.6-4.7) vs. post 3.0 (2.2-4.0), albeit not significant (p = 0.154). Other outcome parameters were not meaningful different. In the post-period, delirium-management could be delivered to 75% (n = 18) of delirious patients, and only 24 (53.3%) of delirious patients required pharmacological treatments. Patients with a more severe stroke and POD remained on their disability levels, compared to similar affected, non-delirious patients who improved. Implementation of delirium-management on SU is feasible and can be delivered to most patients, but with limited effects. Nursing interventions as first choice could be delivered to the majority of patients, and only the half required pharmacological treatments. Delirium-management may lead to reduced severity of POD but had only partial effects on duration of POD or length of stay. POD hampers rehabilitation, especially in patients with more severe stroke. DRKS, DRKS00021436. Registered 04/17/2020, www.drks.de/DRKS00021436 .


Therapist personality and treatment outcome: a test of the interaction hypothesis using the Campbell A-B scale.
The A-B scale was developed to distinguish therapists with a high rate of therapeutic improvement with schizophrenic patients from those with a low rate. The present study tests the hypothesis, developed by Whitehorn and Betz, expanded by McNair and Lorr, of an interaction between a therapist factor, i.e. the A-B score (identified in this study by the Campbell et al. revision of the Whitehorn and Betz A-B scale), patient diagnosis, and treatment outcome. An automated data system identified all of the adult patients treated by 42 therapists during their training at a psychiatric center containing inpatient and outpatient facilities. The patient group was broken down according to diagnosis and whether or not psychotropic drugs were a major treatment modality. Using a linear logistic regression model, the slope of the line specifying log odds of improvement in relation to therapist A-B was found to be significantly different for schizophrenics and neurotics treated without drugs. (No relationship to A-B was found for drug-treated patients.) For those therapists who had treated both neurotic and schizophrenic patients (N = 19) without drugs, A-B was found to be significantly associated (p = .075) with a measure of dependence between patient type and outcome. These two findings were consistent with the hypothesized relationship between the A-B dimension, patient diagnosis, and case outcome.


Seasonal and age-related variation in the needle quality of five conifer species.
Age changes of foliage resource quality (water, nitrogen, fibre, phenolics and toughness) were studied in five species of conifer (Pinus sylvestris L.), Picea abies (L.) Karsten, Tsuga heterophylla (Rafinesque) Sargent (all Pinaceae), Chamaecyparis lawsonian (Murray) Parlatore and Thuja plicata D. Don (both Cupressaceae) over a 2-year period in an English forest.Mature foliage of Pinus sylvestris was characterized by higher levels of nitrogen, fibre and toughness, and lower phenolics, and that of Tsuga heterophylla by higher levels of phenolics, and lower fibre and toughness levels, than the mature needles of the other species studied. Immature needles had higher levels of water and nitrogen, and lower levels of fibre and toughness, than older needles. Immature needles of Picea abies and Tsuga heterophylla had a high concentration of phenolics, which decreased with needle maturity. By mid-August, the levels of most of the foliar constituents in current-year needles had stabilized at levels maintained for the next year. Sampling revealed a fall in the concentration of phenolics, fibre and water in mature needles between March and June. Possible reasons for this seasonal trend are discussed. The levels of conifer foliar constituents were compared with levels recorded in broadleaf trees. Conifers had greater concentrations of all measured foliar constituents, but, with the exception of the six fold greater toughness of conifer needles, the differences between broadleaves and conifers were less than those between the immature and mature conifer needles. Previous studies have related the abundance of Lepidoptera on conifers to hostplant taxonomic relationships. However, the foliar constituents measured in this study were poor predictors of taxonomic relationships between the conifers. It is suggested that the abundance of Lepidoptera on conifers is not determined by levels of general foliar constituents and the role of other hostplant factors in shaping lepidopteran utilization of conifers is discussed.


Successful Removal of a Bullet from the Spinal Canal of a GSW Victim in the Level of L5: Case Report.
Gunshot wounds (GSWs), for increasing violence in urban areas globally and especially among the young population, have been significant causes of morbidity and mortality. These are the most common cause of spinal cord injuries, followed by traffic accidents. The priority of the therapeutic team is to save the victim and then minimise the permanent neural deficits. The indications for lumbosacral decompressive spinal surgery have remained challenging. A 25-year-old man victim of a gunshot in his left flank presented to the emergency department in hemodynamic shock and lethargy status. Resuscitating with fluids, he underwent damage control surgery (DCS). Sources of 2.5 l of intra-abdominal blood were detected of multiple intestinal and mesentery perforations beside the left ureter complete cut. The left psoas muscle was through and through perforated, too, and the bullet was stuck between the vertebrae. On the fifth day after DCS, the bullet surgical removal of the bullet was done in which L2-S1 laminectomy approaching the crushed Conus terminalis was completed. After the operation, his left foot drop and walking ability were improved. Surgical treatment for gunshot wounds in the spinal column is controversial, but the emphasis is on providing advanced trauma life support. Definite treatment of such lesions mainly focuses on maintaining spinal stability, decreasing neurologic deficits as much as possible, and preventing complications. A patient indicates neurological surgery who is young with incomplete or progressive neurology deficits, unstable spine, or complete injury with persistent neural compression.


I see what you are saying.
The motor cortex in the brain tracks lip movements to help with speech perception.


Electrocatalytic CO2 Reduction by Molecular Ruthenium Complexes with Polypyridyl Ligands.
Two series of ruthenium complexes with various polypyridyl ligands have been prepared. One series of complexes (5 examples) are featured with tetradentate polypyridyl ligands and two acetonitrile molecules at the axial positions of the coordination sphere; the other series (3 examples) include combinations of a tridentate polypyridyl ligand, one 2,2'-bipyridine (bpy) or two picolines, and one acetonitrile ligand. All these complexes were fully characterized by their NMR spectra as well as X-ray single crystal structures. Their electronic absorption and redox data were measured and reported. Of the 8 complexes, three candidates effectively catalyze electrochemical CO2 reduction reaction (CO2 RR) in wet acetonitrile medium, generating CO as the major product. All these three catalytically active complexes contain a 2,2':6',2'':6'',2'''-quaterpyridine (qpy) ligand scaffold. A maximum turnover frequency (TOFmax ) of>1000 s-1 was achieved for the electrocatalytic CO2 reduction at a modest overpotential. On the basis of electrochemical and spectroelectrochemical evidences, the CO2 substrate was proposed to bind with the ruthenium center at the two-electron reduced state of the complex and then entered the catalytic cycle.


Quality of life following living donor nephrectomy comparing classical flank incision and anterior vertical mini-incision.
In this study we focused on the quality of life and satisfaction of living kidney donors comparing traditional lumbar (LDN) and mini-incision donor nephrectomy (MIDN). From May 1996 to December 2002, 174 donor nephrectomies including 127 cases of LDN and 47 cases of MIDN were performed. Donors were evaluated using the SF-36 quality-of-life survey as well as a questionnaire dealing with donors' attitude towards kidney donation, financial burdens, pain, cosmetic satisfaction and duration of sick leave. Our donors achieved comparable or even higher scores in all the SF-36 categories in comparison to the general US population. Following MIDN, quality of life tended to be superior compared to that of LDN donors; however, statistical significance was reached only in one of the eight categories. Duration of sick leave following surgery was in favor of MIDN compared to LDN donors. Statistically significant differences favoring MIDN were observed regarding postoperative hospital stay and cosmetic satisfaction. The procedure would be again undergone by 94 of LDN and 97% of MIDN donors. Open-donor nephrectomy is a safe and cost-effective procedure. Introduction of the here-described MIDN has led to comparable or even improved results compared to LDN.


Porous monoliths: sorbents for miniaturized extraction in biological analysis.
In this review the focus is on application of porous monoliths to miniaturized extraction of biological analysis, with emphasis on porous monolithic materials and different miniaturized extraction formats. The general approaches used to synthesize organic polymer and silica monolithic materials are highlighted, and their properties and applicability are described and compared. Several extraction formats, including in-tube microextraction, chip-based microextraction, tip-based microextraction, among others, are reviewed in depth.


Vagal postganglionic innervation of the canine sinoatrial node.
Differential, selective distribution of parasympathetic, postganglionic innervation to the atrioventricular nodal (AVN) region of the canine heart was recently described. Ablation of parasympathetic pathways to the AVN by disruption of the epicardial fat pad at the junction of the inferior vena cava and inferior left atrium did not interfere with normal vagal control of the sinoatrial node (SAN) function. In sharp contrast, surgical dissection of the fat pad overlying the right pulmonary vein-left atrial junction interrupted the major right and left vagal inputs to the SAN region. The pulmonary vein fat pad (PVFP) in the dog heart is triangular in shape with roughly equilateral dimensions of approximately 1 cm, its base extending from superior to inferior veins, and its apex extending nearly to the sinus nodal artery as it courses rostrally in the sulcus terminalis. Careful dissection of smaller fat pads around the circumference of the pulmonary veins and particularly over the rostral-dorsal surfaces of the right superior pulmonary vein and adjacent right atrium, completed SAN parasympathetic denervation. Care in making these dissections left the vagal supply to the AVN region essentially intact, and preserved the sympathetic supplies to both SAN and AVN regions. Autonomic ganglia, varying in size from 1 or 2 cells to 80-100 cells, were found scattered throughout the ventral PVFP (overlying and surrounding the right pulmonary vein-left atrial junction). The ganglia were generally imbedded in fatty connective tissue, although they commonly rested very close to, or were loosely surrounded by epicardial muscle. Ganglia were also found in smaller fat pads on the dorsal surfaces of the atrium between the azygos and the right superior pulmonary vein.


A virtual assessment of the suprainiac depressions on the Eyasi I (Tanzania) and Aduma ADU-VP-1/3 (Ethiopia) Pleistocene hominin crania.
Despite a steady increase in our understanding of the phenotypic variation of Pleistocene Homo, debate continues over phylogenetically informative features. One such trait is the suprainiac fossa, a depression on the occipital bone above inion that is commonly considered an autapomorphy of the Neanderthal lineage. Challenging this convention, depressions in the suprainiac region have also been described for two Pleistocene hominin crania from sub-Saharan Africa: Eyasi I (Tanzania) and ADU-VP-1/3 (Ethiopia). Here, we use a combined quantitative and qualitative approach, using μCT imaging, to investigate the occipital depressions on these specimens. The results show that neither the external nor the internal morphologies of these depressions bear any resemblance to the Neanderthal condition. A principal component analysis based on multiple thickness measurements along the occipital squama demonstrates that the relative thickness values for the internal structures in Eyasi I and ADU-VP-1/3 are within the range of Homo sapiens. Thus, our results support the autapomorphic status of the Neanderthal suprainiac fossa and highlight the need to use nuanced approaches and multiple lines of evidence.


Sugarcane productivity and sugar yield improvement: Selecting variety, nitrogen fertilizer rate, and bioregulator as a first-line treatment.
The improvement of sugarcane productivity depends on the crop varieties, growth environments, and management practices. In particular, the selection of the most productive variety and the use of an optimal fertilizer rate and plant bioregulator are critical for increasing sugarcane productivity and sugar yield. This study aimed to determine the high-performing sugarcane variety, optimal nitrogen rate, and potential bioregulator for improved sugarcane production, juice quality, and sugar yield. Two sugarcane varieties (D42/58 and NCo-334), three nitrogen (N) fertilizer rates (0, 100, and 150 kg/ha), and two bioregulators (Agrostemin and Crops®) were used for the study. The study revealed that sugarcane variety had a significant effect on all growth, yield, and quality parameters. Plant height was significantly influenced by variety and bioregulators, while stalk population was significantly influenced by two- and three-way interactions of varieties, bioregulators, and N fertilizer rates. Cane weight was significantly affected by variety, N fertilizer rate, and bioregulators, whereas cane yield was significantly affected by variety, N fertilizer, and their interaction effects. Sugar yield was similarly influenced by variety, bioregulator, and their interaction. The three main factors, as well as their two- and three-way interactions, had a considerable influence on cane quality parameters. Sugarcane variety D42/58 significantly outperformed variety NCo-334 in terms of sprouting, number of tillers, plant height, number of millable canes, and sucrose percentage by 7.49%, 9.50%, 12.80%, 10.50%, and 9.10%, respectively. The use of the D42/58 variety with N fertilizer (at 100 kg/ha) and/or the Agrostemin bioregulator also led to higher performance in cane population (107126), cane yield (153.34 tons/ha), Pol % (15.81%), and sugar yield (10.25 tons/ha). Most sugarcane growth, yield, juice quality, and sugar yield parameters were positively correlated; hence, high-performing varieties, appropriate N rates, and plant bioregulators could boost sugarcane productivity and sugar yield. Overall, the selection and combination of sugarcane variety D42/58 with 100 kg N/ha and/or Agrostemin bioregulator could maximize sugarcane production, juice quality, and sugar yield. To confirm the current findings, however, more research needs to be conducted across different agroecologies and seasons.


Cefepime, not Piperacillin/Tazobactam use, for empirical treatment of bloodstream infections caused by Enterobacter spp.: Results from a population pharmacokinetic/pharmacodynamic analysis.
There is a paucity of published data to evaluate the efficacy and safety of imipenem, cefepime and piperacillin/tazobactam dosing regimens against bloodstream infections caused by Klebsiella aerogenes (BSIs-Kae) and Enterobacter cloacae complex (BSIs-Ecc) in patients with various degrees of renal function. Pathogens were isolated from China's blood bacterial resistant investigation network. The dosing regimens of imipenem, cefepime and piperacillin were simulated with intermittent infusion and extended infusion. Monte Carlo simulation was performed to calculate the probability of target attainment and a cumulative fraction of response (CFR) against BSIs-Kae/Ecc. In total, 203 BSIs-Kae, and 785 BSIs-Ecc were isolated from the surveillance network. Imipenem showed the highest in vitro activity against BSIs-Kae/Ecc, followed by cefepime (85%) and piperacillin/tazobactam (70-80%). The MIC90 values of imipenem, cefepime and piperacillin/tazobactam aginst BSIs-Kae and BSIs-Ecc were 1/1 mg/L, 16/16 mg/L, and 64/128 mg/L, respectively. The simulation results showed imipenem achieved the highest CFRs in patients with normal or decreased renal function, with values of 91-99%, followed by FEP (88-96%), without risk of excessive dosing. However, the intermittent and extended dosing regimens of piperacillin/tazobactam were unlikely to provide adequate exposure for empirical management of BSIs-Kae/Ecc (CFRs, 50-80%), regardless of renal function. Besides, the traditional intermittent piperacillin/tazobactam dosing regimens were highly likely to contribute to suboptimal therapeutic exposure when MIC was close to clinical breakpoints. Cefepime, not piperacillin/tazobactam, can be a reasonable carbapenem-sparing option in empirically treating BSIs-Kae/Ecc.


CAMAL: a new prognostic marker for remission in acute nonlymphoblastic leukemia.
A leukemia-associated antigen, CAMAL, shown to be present in bone marrow (BM) cells from patients with acute nonlymphoblastic leukemia (ANLL) even during remission, has been examined using indirect immunoperoxidase and a monoclonal antibody, CAMAL-1. We are ending the third year of an ongoing blind study designed to monitor the number of BM cells expressing the CAMAL protein (CAMAL BM value) in ANLL patients over the course of their disease. Results thus far have revealed that the CAMAL BM value in individual patients often changed significantly post-chemotherapy. This change appeared to be a useful prognostic marker in many instances. ANLL patients at initial presentation whose CAMAL BM values increased or stayed the same post-chemotherapy had significantly (p less than 0.025) shorter remission lengths (x = 6.8 months, n = 24) than those whose CAMAL BM values decreased (x = 19.2 months, n = 10). There are indications that increasing CAMAL BM values during remission occur prior to clinical relapse.


Cellular barcoding: From developmental tracing to anti-tumor drug discovery.
Clonal evolution has gained immense attention in explaining cancer cell status, history, and fate during cancer progression. Current single-cell or spatial transcriptome technologies have broadened our understanding of various mechanisms underlying cancer initiation, relapse, and drug resistance. However, technical challenges still hinder a better understanding of the dynamics of distinctive phenotypic states and abnormal trajectories from normal physiological transition to malignant stages. Cellular barcoding enabled lineage tracing on parallelly massive cells at single-cell resolution through different mechanisms lately, enabling new insights into exploring developmental trajectories, cancer progression, and targeted therapies. This review summarizes the latest noteworthy and robust strategies for different types of cellular barcodes. To introduce the major characteristics, advantages and limitations of these different strategies, this review will further guide in choosing or improving cellular barcoding technologies and their applications in cancer research.


Fetal thoracic circumference: a prospective cross-sectional study with real-time ultrasound.
We report a prospective cross-sectional study of ultrasound fetal chest growth during normal pregnancy. The fetal chest circumference was measured in 100 normal pregnancies from 13 to 41 weeks' gestation. Nomograms of chest circumference versus gestational age and femur length were constructed. Data from 18 cases at risk for pulmonary hypoplasia indicated that the fetal chest circumference measurement may be useful in the antenatal prediction of lethal or clinically severe pulmonary hypoplasia.


Association of an aminoacyl-tRNA synthetase complex and of phenylalanyl-tRNA synthetase with the cytoskeletal framework fraction from mammalian cells.
The intracellular distribution of several mammalian aminoacyl-tRNA synthetases was investigated by biochemical and immunocytological approaches. The fraction of amino-acyl-tRNA synthetases bound to the detergent-insoluble cytoskeletal framework obtained after extraction of NRK cells by 0.1% Triton X-100 was estimated, by activity measurements, to about 80% for phenylalanyl-tRNA synthetase and 40% for the high-molecular-weight (HMW) complex containing the seven aminoacyl-tRNA synthetases specific for glutamic acid, isoleucine, leucine, methionine, glutamine, lysine, and arginine. This association was shown to be salt-dependent. The subcellular localization of these enzymes was examined using an immunocytological approach. When cultured cells were fixed with paraformaldehyde and then permeabilized with Triton X-100, a fairly uniform cytoplasmic labelling was observed with antibodies directed to the aminoacyl-tRNA synthetase complex or to phenylalanyl-tRNA synthetase. By contrast, when cells were extracted with 0.1% Triton X-100 prior to fixation with paraformaldehyde, the staining patterns obtained with antibodies to aminoacyl-tRNA synthetases were very similar to that obtained with antibodies to rough endoplasmic reticulum, as assessed by single or double indirect immunofluorescence microscopy. These results suggest that free and bound forms of these aminoacyl-tRNA synthetases may coexist within the cell. In addition to cytoplasmic labelling, antibodies directed to phenylalanyl-tRNA synthetase stained the nucleus of rapidly growing cells. The possible significance of this finding is discussed.


Incidence of cancer and related deaths in hemoglobinopathies: A follow-up of 4631 patients between 1970 and 2021.
The correlation between thalassemia and malignancies other than hepatocellular carcinoma (HCC) and the possible relationship between other hemoglobinopathies and tumor risk have been poorly evaluated. Eight Italian specialized centers evaluated the incidence of malignant neoplasms in hemoglobinopathies as well as their sites and features. The study cohort included 4631 patients followed between 1970 and 2021 (transfusion-dependent β-thalassemia, 55.6%; non-transfusion-dependent thalassemia, 17.7%; sickle cell disease, 17.6%; hemoglobin H disease, 8.3%). A total of 197 diagnoses of cancer were reported (incidence rate, 442 cases per 100,000 person-years). The liver was the most frequent site of tumors in both sexes, with a higher incidence (190 cases per 100,000 person-years) in comparison with the general population found in all types of hemoglobinopathies (except hemoglobin H disease). In recent years, tumors have become the second cause of death in patients with transfusion-dependent thalassemia. A lower risk of breast and prostate cancer was observed in the whole group of patients with hemoglobinopathies. The first cancer diagnoses dated back to the 1980s, and the incidence rate sharply increased after the 2000s. However, although the incidence rate of cancers of all sites but the liver continued to show an increasing trend, the incidence of HCC showed stability. These findings provide novel insights into the relationship between cancer and hemoglobinopathies and suggest that the overall risk is not increased in these patients. HCC has been confirmed as the most frequent tumor, but advances in chelation and the drugs that have led to the eradication of hepatitis C may explain the recent steadiness in the number of diagnoses that is reported here.


Noninvasive evaluation of vascular endothelial growth factor-A (VEGF-A) protein concentrations in the stratum corneum and serum of healthy and atopic dogs.
Vascular endothelial growth factor (VEGF) is a cytokine involved primarily in angiogenesis. In human atopic dermatitis (AD), VEGF has been detected in the stratum corneum and blood. To evaluate VEGF-A expression in the serum and stratum corneum of healthy and atopic dogs, and its possible correlation with disease severity in atopic dogs. Fifteen atopic and 15 healthy, privately owned dogs. The severity of clinical signs associated with AD was evaluated with the Canine Atopic Dermatitis Extent and Severity Index (CADESI-04). For all dogs, a single blood sample was performed and serum collected. Tape stripping (15 times) was performed on the left periocular area (lesional skin). A commercially available canine-specific VEGF-A enzyme-linked immunosorbent assay was performed with all samples. Vascular endothelial growth factor-A was undetectable in the serum. In the stratum corneum, there was no significant difference in VEGF-A concentrations between healthy (mean 89.4 ± 59.5 pg/ml) and atopic dogs (mean 100.3 ± 77.1pg/ml) (P = 0.71). There was no correlation between stratum corneum VEGF-A concentrations and CADESI-04 scores. The role of VEGF in canine AD is unclear. Because of many variants, VEGF-C and VEGF-D or VEGF-A isotopes should be explored in the skin to better evaluate the role of VEGF in canine atopy. Full-thickness skin biopsy, molecular biology and histopathological investigation may be necessary to further assess cutaneous VEGF expression.


Loss of Stromal Antigen 2 (STAG2) Expression in Upper Urinary Tract Carcinoma: Differential Prognostic Effect According to the Ki-67 Proliferating Index.
Inactivating mutation and consequent expression loss of stromal antigen 2 (STAG2, also known as SA2), a component of the cohesion complex, is one of the most common genetic aberrations in urothelial carcinoma. However, the clinicopathologic or prognostic significance of STAG2 alterations in upper tract urothelial carcinoma (UTUC) is largely unknown. This study immunohistochemically examined the expression of STAG2 in 171 patients with UTUC. The correlations of STAG2 loss with clinicopathologic features and patients' prognoses were examined. Loss of STAG2 expression was observed in 28 cases (16%). Loss of STAG2 was significantly correlated with histological low grade, papillary architecture, noninvasive tumors, absence of concomitant carcinoma in situ, and lower Ki-67 expression. Loss of STAG2 alone was not significantly associated with patients' prognoses in either the uni- or multivariate analysis. However, STAG2 loss was significantly associated with worse clinical outcome in UTUC with high Ki-67 proliferation indexes, but not in UTUC with low Ki-67 expression. Loss of STAG2 was generally associated with less aggressive features in UTUC. However, the STAG2 loss was an ominous sign in the subpopulation with higher Ki-67 proliferation indexes. Examining both STAG2 and Ki-67 status may be useful for identifying aggressive clinical behavior of UTUC.


Invited commentary 'Comparison of three different bone graft methods for single segment lumbar tuberculosis: A retrospective single-center cohort study.
The study is designed to contrast the clinical efficacy of one stage posterior debridement with iliac bone graft, titanium mesh bone graft or granular bone graft in the surgical treatment of single segment lumbar tuberculosis [1].