Differential expression of novel genes by bone marrow-derived macrophage populations.
In the present study, we have constructed a subtraction cDNA library to identify novel genes induced by IFN-gamma in GM-CSF-derived bone marrow macrophage (m phi). M theta were treated with 50 U/ml IFN-gamma for 40, 70 and 140 min to induce expression of early genes regulated by IFN-gamma, and the M phi were pooled. Poly(A)+RNA was prepared from both unactivated and IFN-gamma-stimulated m theta, and cDNA libraries were constructed in lambda ZAP. Genes expressed in common by both m theta populations were removed by subtraction using biotin-avidin precipitation of hybrid complexes. Further selection was performed by differential screening using cDNA prepared from mRNA of unactivated m phi as a probe, followed by colony hybridization to remove sister clones. Of 17 clones from which sequence information was obtained, two appeared to be identical with the murine genes, C10 (clone GM2B1) and Mac-2 (clone GM2C4) and an additional two clones had high similarity to human cDNAs encoding proteins of unknown function. cDNAs containing sequences which did not match published sequences were used to probe Northern blots prepared from both unstimulated and IFN-gamma-activated GM-CSF- and CSF-1-derived m phi. Five clones (GM1A2, GM1B4, GM1F2, GM2A12 and GM2B8) showed enhanced transcript levels following IFN-gamma treatment of GM-CSF-derived m phi, but demonstrated high constitutive transcript levels in CSF-l-derived m phi. In addition, C10 transcripts were constitutively expressed by GM-CSF-derived m phi, but not by CSF-1-derived m phi, even after activation by IFN-gamma. These data suggest that much of the functional heterogeneity of GM-CSF- and CSF-1-derived m phi resides in the differential expression of early genes specifically induced by IFN-gamma.


The role of hyperglycemia in FAT/CD36 expression and function.
FAT/CD36 is a long-chain fatty acid transporter and scavenger receptor for oxidized LDL. Defects in FAT/CD36 have been linked to the hypertriglyceridemia and insulin resistance. Expression of FAT/CD36 was reported increase in type 1 diabetes; however, it remains unclear whether serum glucose or insulin plays an important role in this regulation. To elucidate the individual contribution of plasma glucose and insulin in the regulation of FAT/CD36 mRNA expression, we induced type 1 diabetes in male Sprague-Dawley rats using streptozotocin (STZ) and compared traditional insulin treatment with administration of the orally absorbed chemical agent vanadate, which reduces blood glucose levels via mechanisms that bypass insulin receptor action. STZ-exposed animals showed significant decreases in body weight (285.5 +/- 2.8 vs. 233.1 +/- 3.5 g, P < 0.001) and serum insulin levels (9.7 +/- 0.7 vs. 2.8 +/- 0.6 microU/ml, P < 0.05), accompanied by significant increases in blood glucose (71 +/- 3 vs. 433 +/- 11 mg/dl, P < 0.001), water intake (38.9 +/- 0.9 vs. 205.9 +/- 3.3 ml/day, P < 0.001) and food intake (22.0 +/- 0.4 vs. 36.9 +/- 1.0 g/day, P < 0.001). Diabetic animals demonstrated significant increases in FAT/CD36 mRNA levels in duodenum (2.2-fold), jejunum (1.8-fold), ileum (1.5-fold), adipose tissue (1.7-fold), and heart (2.5-fold) (P < 0.05). Insulin treatment reversed body weight loss and corrected hyperglycemia at diabetic rats as expected. Insulin treatment also corrected increased FAT/CD36 mRNA expression at diabetic rats. Vanadate significantly reduced serum glucose levels without increasing serum insulin or affecting body weight but reversed increased FAT/CD36 mRNA expression in diabetic rats. These data suggest that plasma glucose levels play more important role in the regulation of FAT/CD36 expression than concurrent changes in plasma insulin.


Changes in mismatch negativity across pre-hypnosis, hypnosis and post-hypnosis conditions distinguish high from low hypnotic susceptibility groups.
The role of alterations in mismatch negativity (MMN) in hypnosis was examined by recording MMN of the auditory ERP at frontal (F3, Fz, and F4) and mastoid (M1 and M2) placements. Frontal MMN is believed to reflect activity in right anterior cortical generators, whereas MMN at mastoid leads reflects generators located bilaterally in the temporal auditory cortex. MMN recordings were obtained in 11 low and 12 high hypnotically susceptible participants in three successive blocks; pre-hypnosis, hypnosis and post-hypnosis. Frontal (but not temporal) MMN showed a significant quadratic trend across testing conditions. It increased during hypnosis and then dropped post-hypnosis for both susceptibility groups. Linear trends for frontal and temporal MMN showed directly opposite patterns of change in the interaction between hypnotic susceptibility and testing blocks. Frontal MMN built up linearly over the test blocks in high relative to low susceptibility participants. Temporal MMN showed the reverse pattern and increased linearly across test conditions in those with low relative to high hypnotic susceptibility.


Ca2+-activated K+ channel blockers induce PKC modulated oscillatory contractions in guinea pig trachea.
Mechanisms underlying the Ca2+-activated K+ channel (K(Ca)) blockers-induced oscillatory contractions were investigated in guinea pig tracheal smooth muscle. The mean oscillatory frequencies induced by charybdotoxin (ChTX; 100 nM) and iberiotoxin (IbTX; 100 nM) were 9.8+/-0.8 (counts/h) and 8.0+/-1.3 (counts/h), respectively. Apamin (1 microM ), a blocker of SK(Ca), induced no contraction in guinea pig trachea and did not affect ChTX-induced oscillatory contractions. In Ca2+ free solution, no ChTX-induced contraction was observed. Nifedipine (100 nM), a blocker of voltage-dependent Ca2+ channels, and SK&F 96365 (10 microM), a blocker of capacitative Ca2+ entry, completely abolished ChTX-induced oscillatory contractions. Ryanodine (1 microM) decreased the amplitude, but increased the frequency of the oscillatory contractions. Thapsigargin (1 microM) changed contractions from the oscillatory type to the sustained type. Moreover, the protein kinase C (PKC) inhibitor, bisindolylamaleimide I (1 microM), decreased the amplitude and frequency, but PKC activator, phorbol 12-myristate 13-acetate (1 microM), increased the frequency of oscillatory contractions. These results suggest that K(Ca) inhibitors-induced oscillatory contractions are initiated by Ca2+ influx through L-type voltage-dependent Ca2+ channels. The ryanodine-sensitive calcium release channels in the sarcoplasmic reticulum may play an important role in maintaining the oscillatory contractions. Moreover, PKC activity modulates these oscillatory contractions.


Case report: a man with untreated rheumatoid arthritis, cryoglobulinemic vasculitis, membranous nephropathy and pulmonary sarcoidosis.
Glomerular involvement in rheumatoid arthritis has been known to be associated with treatment side effects from medications and secondary amyloidosis. However, limited basic science and clinical studies have been performed to address the potential disease specific immune-mediated mechanisms causing secondary glomerular pathology, its various types of presentation, and the potential treatments. A 41-year-old man with chronic active rheumatoid arthritis presented with nephrotic syndrome and was found to have membranous nephropathy with eosinophilic intracapillary thrombi on renal biopsy. Proteinuria persisted despite complete withdrawal from non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs). Throughout the disease course, he developed cryoglobulinemic vasculitis and pulmonary sarcoidosis, both of which achieved clinical resolution with glucocorticoids. However, only partial improvement was observed in proteinuria with treatment of steroids and Rituximab. Our case presented a unique and complicated clinical phenotype of active rheumatoid arthritis, with clinical features of cryoglobulinemic vasculitis, histopathologic features of membranous and cryoglobulinemic nephropathy in the absence of DMARDs use, as well as pulmonary sarcoidosis. We speculate that there is a wider spectrum of glomerular disease in patients with untreated rheumatoid arthritis. In addition, the potential association between rheumatoid arthritis and cryoglobulinemic vasculitis should probably be revisited and requires further studies to elucidate the underlying mechanisms and treatment options.


Acquisition and Transmission of Carbapenemase-Producing (blaKPC-2) Enterobacter cloacae in a Highly Frequented Outpatient Clinic.
The role of outpatient clinics as a potential transmission ground for multidrug-resistant organisms has not been adequately investigated. Here, we report a transmission cluster of blaKPC-2-positive Enterobacter cloacae among patients treated in a highly frequented outpatient department.


How to fast-track your meaningful use effort.
While there is no shortcut to meaningful use, getting the fundamentals right is essential to smoothing the way to qualifying for incentives.


[Flexion contracture of the interphalangeal joint in Dupuytren disease. Anatomic and clinical observations].
The cutaneous ligaments of the fingers which we detect seldom during routine operations, are demonstrated by anatomical preparation. Because they are involved in the tissue alterations of Dupuytren's disease the authors hope to clarify the different mechanisms of finger joint contracture.


The effect of human chorionic gonadotropin and estradiol-17beta on the maintenance of the human corpus luteum of early pregnancy.
The effect of exogenous human chorionic gonadotropin (HCG) and estradiol valerate (EV) on the maintenance of the corpus luteum of early pregnancy, assessed by serial estimations of serum progesterone and 17alpha-hydroxyprogesterone (17-OHP), was studied in 35 subjects following therapeutic termination of pregnancy by suction curettage before the tenth week of gestation. Continuous intravenous infusion of 50,000 International Units (I.U.) of HCG for 24 hours following termination of pregnancy delayed the decline of serum HCG levels, and 17-OHP levels were maintained at preoperative levels for the 24 hours of the infusion. Single intramuscular injections of 5,000 or 20,000 I.U. of HCG were ineffective. Administration of 25 mg. of EV intramuscularly immediately following therapeutic termination of pregnancy slightly retarded the decline of serum 17-OHP levels. The same treatment when administered in combination with the intravenous infusion of 50,000 I.U. of HCG completely prevented the ability of HCG to maintain serum levels of 17-OHP. These finding susggest an antagonism between estradiol and HCG in maintenance of the human corpus luteum during early pregnancy.


Gate length scaling effect on high-electron mobility transistors devices using AlGaN/GaN and AlInN/AlN/GaN heterostructures.
Compared to AlGaN/GaN HEMT with 0.15 μm T-gate length, the AlInN/AlN/GaN one exhibits much higher current density and transconductance of 1558 mA/mm at Vd = 2 V and 330 mS/mm, respectively. The high extrinsic ft and fmax of 82 GHz and 70 GHz are extracted from AlInN/AlN/GaN HEMT. Besides, we find that the transconductance roll-off is significant in AlGaN/GaN, but largely improved in AlInN/AlN/GaN HEMT, suggesting that the high carrier density and lattice-matched epitaxial heterostructure is important to reach both large RF output power and high operation frequency, especially for an aggressively gate length scaling.


"The contemporary, irreverent brand of youth with an independent streak": BAT's youth promotions in Myanmar.
"British American Tobacco strongly believes children should not smoke, and smoking should only be for adults who understand the risks associated with it. Our Group companies support and run programmes worldwide tackling underage smoking, and we are committed to pooling our resources and experience globally with others in the tobacco industry--and with governments and NGOs--to help prevent youth smoking. Along with the other two largest international tobacco groups--Philip Morris International and Japan Tobacco International--our Group companies have funded and supported more than 130 Youth Smoking Prevention (YSP) programmes in more than 70 countries. We fully support laws and regulations on a minimum age for buying tobacco products, and penalties for retailers who break the law. Our company policy worldwide is not to market to anyone under 18 years old, or more if the law in a particular country sets the age higher."--BAT website November 2003.


Troponin T measurement after myocardial infarction can identify left ventricular ejection of less than 40%.
To determine whether measurement of serum troponin T concentration after first acute myocardial infarction can be used to identify patients with a left ventricular ejection fraction of < 40%, who have an adverse prognosis. Troponin T concentration was measured, and coronary and left ventriculography performed in 50 consecutive patients with acute myocardial infarction. Angiographic left ventricular ejection fraction was compared with serum troponin T concentration. Patients with previous myocardial infarction were excluded. There was a strong negative correlation between left ventricular ejection fraction and troponin T concentration. Spearman's rank correlation coefficient (corrected for ties) was -0.72 (95% confidence intervals (CI) -0.55 to -0.83; p < 0.0001). Analysis by receiver operator characteristic curve produced an area under the curve of 0.9773 (95% CI 0.9409 to 1.0136). A troponin T concentration of > 2.8 micrograms/l predicted a left ventricular ejection fraction of < 40% with a sensitivity of 100% (CI 84.6 to 100.0) and specificity of 92.9% (CI 76.5 to 99.1). Exclusion of patients who did not receive thrombolytic treatment did not significantly affect the results. Serum troponin T concentration measured 12-48 hours after admission for first myocardial infarction is a reliable, simple, quick, inexpensive, non-invasive method for identifying patients with a left ventricular ejection fraction of < 40% for whom there is a poor prognosis.


Giant pulmonary bulla causing respiratory compromise in a very low-birthweight infant.
Acquired cystic lung disease in premature infants is a serious respiratory complication, and pulmonary interstitial emphysema (PIE) has been widely reported. We report a rare case of giant pulmonary bulla in an infant treated with bullectomy where chest computed tomography was useful in directing treatment.


Use of self-inflating bags for neonatal resuscitation.
Lung inflation is the most important, and most difficult step in newborn resuscitation. A wide variety of devices are used to achieve lung inflation, but there are relatively few data to guide clinicians in their choice of device. We tested the ability of instructors and trained candidates on a newborn life support course to deliver initial inflation breaths to a test lung, using a pressure limited blow-off valve, a 240-ml self-inflating bag and a 500-ml self-inflating bag in sequence. Use of a 240-ml self-inflating bag was associated with shorter initial inflations of 1.8 s mean (95% CI 1.60-1.99 s), compared with 2.42 s (2.24-2.61 s), 2.40 s (2.08-2.71 s) for 500-ml self-inflating bags and "Tom Thumb" T piece, respectively. Delivery of breaths within a target pressure range of 30+/-5 cm H2O was significantly better using a T piece than either self-inflating bag (proportion within target range 0.05 (95% CI 0-0.11), 0.17 (95% CI 0.12-0.23), 0.89 (95% CI 0.83-0.94) for 240-ml and 500-ml self-inflating bags and "Tom Thumb" T piece, respectively. Excessive pressure delivery with both sizes of self-inflating bag was frequent. These data do not support use of 240-ml or 500-ml self-inflating bags for resuscitation of newborn term infants. A variable pressure T piece blow-off system may be the easiest device to use for newborn resuscitation and the most reliable at delivering desired pressures for set times.


[Characteristics of the blood system of inbred and mongrel mice].
Peripheral blood and bone marrow indices were studied in inbred (101/H, CC57W, A2G, CBA/Lac, B6WV, C57BL/6, ACR) and mongrel mice. Normal values of the morphological composition of the blood and bone marrow were established. Comparative analysis demonstrated the existence of differences in the mentioned indices not only between the inbred and mongrel mice, but also within the individual animal strains.


Unrelated cord blood transplantation after myeloablative conditioning in adults with ALL.
We analyzed the disease-specific outcomes of adult ALL treated with cord blood transplantation (CBT) after myeloablative conditioning. Between October 2000 and November 2007, 27 adult patients with ALL were treated with unrelated CBT. All patients received four fractionated 12 Gy TBI and chemotherapy as myeloablative conditioning. The median age was 36 years, the median weight was 57 kg and the median number of nucleated cells was 2.47 x 10(7)/kg. All patients received a single and HLA-mismatched cord blood unit. The cumulative incidence of neutrophil recovery at day 30 and platelet recovery at day 200 was 92.6 and 92.3%, respectively. With a median follow-up of 47 months, the probability of EFS at 5 years was 57.2%. The 5-year cumulative incidence of TRM and relapse was 3.7 and 27.4%, respectively. These results suggest that unrelated CBT after myeloablative conditioning could be safely and effectively used for adult patients with ALL.


DeDoc2 Identifies and Characterizes the Hierarchy and Dynamics of Chromatin TAD-Like Domains in the Single Cells.
Topologically associating domains (TADs) are functional chromatin units with hierarchical structure. However, the existence, prevalence, and dynamics of such hierarchy in single cells remain unexplored. Here, a new generation TAD-like domain (TLD) detection algorithm, named deDoc2, to decode the hierarchy of TLDs in single cells, is reported. With dynamic programming, deDoc2 seeks genome partitions with global minimal structure entropy for both whole and local contact matrix. Notably, deDoc2 outperforms state-of-the-art tools and is one of only two tools able to identify the hierarchy of TLDs in single cells. By applying deDoc2, it is showed that the hierarchy of TLDs in single cells is highly dynamic during cell cycle, as well as among human brain cortex cells, and that it is associated with cellular identity and functions. Thus, the results demonstrate the abundance of information potentially encoded by TLD hierarchy for functional regulation. The deDoc2 can be freely accessed at https://github.com/zengguangjie/deDoc2.


Remote MEG dipoles in focal cortical dysplasia at bottom of sulcus.
To investigate whether the magnetoencephalography (MEG) single moving dipole (SMD) method could delineate the epileptic zone of focal cortical dysplasia (FCD) at the bottom of sulcus (FCDB). We retrospectively analyzed 17 children (11 male; mean age 8.8 years, range 3-17 years) with FCD type II who underwent epilepsy surgery. We compared spatial congruence between the following: (1) MEG cluster and FCDB and (2) MEG cluster and FCD at the brain surface (FCDS). We measured the volume and depth of magnetic resonance imaging (MRI)-visible lesions to investigate whether they affect spatial congruence between MEG cluster and MRI-visible lesion. Eight children had FCDB and the other nine children had FCDS. The volume of MRI-visible lesions for FCDB ranged from 1,632 to 4,707 mm(3) (mean ± standard deviation [SD] 3,095 ± 1,211 mm(3) ). The depth of FCDB ranged from 19 to 33 mm (mean ± SD 26 ± 4 mm). The volume of MRI-visible lesion for FCDS ranged from 2,375 to 57,331 mm(3) (15,470 ± 18,455 mm(3) ). There was a tendency for a smaller volume of MRI-visible lesion for FCDB, relative to FCDS(p = 0.079). In FCDB, six children showed clusters of MEG dipoles and two children showed scattered MEG dipoles for interictal spikes. The spatial congruence between the MEG result and FCDB was partially overlapping in four children and discordant in another four children. In FCDS, eight children had MEG cluster and one child had MEG scatter alone. The spatial congruence between MEG result and FCDS was overlapping in eight of nine children (fully two; partially six) and discordant in one of nine children. Fifteen children (88%; FCDB eight; FCDS seven) became seizure-free after resective surgery. MEG spike dipole resection ratio in the cluster ranged from 4-100% (mean 67%) in 6 FCDB and 23-99% (mean 77%) in 8 FCDS. The SMD method may drift MEG spike dipoles for FCDB. Lesionectomy can control seizures for four of eight patients in FCDB despite the remote MEG dipoles. The FCDB or FCDS partially overlapped with MEG cluster may have an extending/invisible epileptogenic zone consecutive to the MRI-visible lesion.


Evidence for suppression of serum LH without elevation in serum estradiol or prolactin with a brain-enhanced redox delivery system for estradiol.
We developed a redox system for brain-enhanced delivery of estradiol based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Estradiol (E2), when combined with the lipoidal carrier, readily crosses the blood-brain barrier. The carrier, when oxidized, reduces the rate of exit of the estradiol-carrier complex from the brain. Subsequent hydrolysis of the carrier provides sustained production of estradiol in the brain. The aim of the study was to evaluate the effects of single vs. multiple injections of the estradiol-chemical delivery system (E2-CDS) on both central and peripheral estrogen-responsive tissues. Ovariectomized Sprague-Dawley rats received an intravenous injection of E2-CDS at 10, 33, 100 or 333 micrograms/kg BW or the drug vehicle, dimethyl sulfoxide (DMSO; 0.5 ml/kg) every 2 days for 7 injections (2 weeks) or a single injection only at 2 days before sacrifice. With a single injection, E2-CDS did not affect serum luteinizing hormone (LH) levels at the 10 micrograms/kg dose but caused a dose-dependent reduction in serum LH of 39-52% at the dose range of 33 to 333 micrograms/kg. By contrast, multiple injections of E2-CDS caused a 32 to 76% reduction in serum LH levels at doses ranging from 10 micrograms/kg to 333 micrograms/kg. Additionally, multiple doses of E2-CDs caused a dose-dependent reduction in body weight at the 10 and 33 micrograms/kg doses with the higher doses causing no further weight reduction. For both single and multiple dosage groups, serum E2 levels remained unchanged after doses of E2-CDS of 10 and 33 micrograms/kg, then increased to 21 pg/ml for the single dosage group and to 23 pg/ml for the multiple dosage group at the 100 micrograms/kg dose, and to 59 pg/ml for singly-injected rats and 60 pg/ml for multiply-injected rats at the 333 micrograms/kg dose. Serum prolactin concentrations were closely correlated with serum E2 levels for both the single and multiple dose groups. These data reveal that a single or multiple doses of E2-CDS can reduce serum LH levels without elevating serum E2 or prolactin concentrations, supporting the concept of brain-enhanced delivery of estradiol with an estradiol chemical delivery system.


Alternative conformations of human replication protein A are detected by crosslinks with primers carrying a photoreactive group at the 3'-end.
To analyze the influence of single-stranded template extension of DNA duplex on the conformation of human replication protein A (RPA) bound to DNA we have designed two template-primer systems differing by the size of the single-stranded template tail (9 and 19 nucleotides (nt)). Base-substituted photoreactive dUTP analogs were used as substrates for elongation of radiolabeled template-primer by DNA polymerase beta in the absence or in the presence of RPA. Following UV-crosslinking it was demonstrated that the pattern of RPA subunit labeling and consequently RPA arrangement near the 3'-end of the primer is strongly dependent upon the length of the template extension.


Content and style of speech from mothers with schizophrenia towards their infants.
Schizophrenia can affect verbal communication and relational processes, but how it might disrupt maternal infant-directed (ID) speech is unknown. Maternal speech characteristics were coded, blind to clinical information, from brief videotaped mother-infant interactions of 14 mothers with schizophrenia and 36 mothers with similar hospitalisation but with other clinical diagnoses. Compared with the non-schizophrenia group, the speech of mothers with schizophrenia was less infant-focused. Infant-focused content was also predicted by maternal age, but not by duration of hospitalisation or infant gender. Mothers with schizophrenia also used significantly fewer songs or rhymes than the comparison group, and showed a trend towards fewer negative comments. Speech prosody/content deviations were rarely observed in either group, and no differences were found in speech rate or structure. The marked lack of ID speech content of mothers with schizophrenia reflects low maternal sensitivity, perhaps due to 'theory of mind' impairment and blunted affect, and may contribute to the early developmental vulnerability of their children.


Effects of cholinergic receptor agonists and antagonists on miniature stimulatory postsynaptic ionic currents in somatic muscle cells of lumbricus terrestris.
Miniature stimulating postsynaptic currents of Lumbricus terrestris somatic muscle cells were recorded. Atropine, d-tubocurarin, alpha-bungarotoxin, carbacholine, and proserin did not modify the amplitude and temporal parameters of miniature stimulatory postsynaptic currents, while carbacholine and nicotine depolarized the muscle membrane. Presumably, Lumbricus terrestris muscle cells contain acetylcholine-sensitive channel-receptor complexes not belonging to classical nicotinic or muscarinic acetylcholine receptors.


Inhibitory effect of hena (Lawsonia inermis leaves) and carrot root on aflatoxin production byAspergillus parasiticus.
Experiments were undertaken to evaluate the effect of some natural products (hena, and carrot root) on growth and aflatoxins production byAspergillus parasiticus FRR 2752. Powdered hena (0.5 and 5%) inhibited mycelial growth and delayed 1 sporulation ofA parasiticus during 7 days.The inhibition of growth was increased with increasing the added amount. Aflatoxins production byA parasiticus was reduced with 40-100% in the presence of hena (Lawsonia inermis leaves). Carrot root extract stimulated the fungal growth and aflatoxin production, whereas carrot root fibers slightly enriched fungal growth, inhibited aflatoxins production (B1, G1, and G2), but there was no inhibition of aflatoxin B2 production byA parasiticus.


Characterization of the distribution of the sintering activator boron in powder metallurgical steels with SIMS.
Powder metallurgy is a well-established method for manufacturing ferrous precision parts. A very important step is sintering, which can be strongly enhanced by the formation of a liquid phase during the sintering process. Boron activates this process by forming such a liquid phase at about 1200 degrees C. In this work, the sintering of Fe-B was performed under the protective atmospheres of hydrogen, argon or nitrogen. Using different grain sizes of the added ferroboron leads to different formations of pores and to the formation of secondary pores. The effect of boron was investigated by means of Secondary Ion Mass Spectrometry (SIMS) supported by Scanning Electron Microscopy (SEM) and Light Microscopy (LM). To verify the influence of the process parameters on the mechanical properties, the microstructure (pore shape) was examined and impact energy measurements were performed. The concentrations of B in different samples were varied from 0.03-0.6 weight percent (wt%). Higher boron concentrations are detectable by EPMA, whereas the distributions of boron in the samples with interesting overall concentration in the low wt% range are only detectable by means of SIMS. This work shows that the distribution of boron strongly depends on its concentration and the sintering atmosphere used. At low concentration (up to 0.1 wt%) there are boride precipitations; at higher concentration there is a eutectic iron-boron grain boundary network. There is a decrease of the impact energy observed that correlates with the amount of eutectic phase.


Recent progress of 3D-printed microneedles for transdermal drug delivery.
Microneedles as novel transdermal drug delivery systems have lately attracted extensive attention due to their distinguished properties, including improved patient compliance and self-administration, compared to traditional parenteral administrations such as intravenous injection, intramuscular injection and subcutaneous injection. However, the great difficulties of precisely manufacturing those microneedles and patches within micro scale have strongly retarded their commercialization and clinical applications, particularly for the personalized medicine. Recently, numerous researches of utilizing 3D-priting process to fabricate transdermal drug delivery systems have been reported, not only adopting versatile printing methodologies, but also utilizing with different formulation strategies, to fabricate both artificial cargo delivery systems and sophisticated bio-inspired microneedles. This review aims to summarize those lately reported studies and to elaborate their advantages and limitations, discussing promising potential applications as novel drug delivery systems.


Altered erythrocyte pyrimidine activity in vitamin B12 or folate deficiency.
The net activity of orotidylic pyrophosphorylase and decarboxylase, sequential enzymes which catalyse the formation of uridine monophosphate from orotic acid in de novo pyrimidine biosynthesis, has been evaluated in erythrocytes of patients with folate or cobalamin deficiency. In patients with normoblastic haemopoiesis and normal cobalamin and folate status a direct relationship exists between the maturity of the peripheral blood erythrocyte population, as indicated by G6PD activity, and net orotidylic activity. In contrast in cobalamin or folate deficiency this co-ordinate relationship is not observed and net orotidylic activity is relatively reduced. Fractionation of erythrocytes by centrifugation demonstrates that this inordinately low orotidylic activity consistently occurs in the young erythrocyte population and is reversed by specific replacement therapy. In vitamin B12 or folate deficiency an impressive array of evidence now exists to implicate altered folate metabolism for the observed alterations in purine and pyrimidine metabolism (Das & Herbert, 1976). Of these changes the cornerstone defect resulting in megaloblastic maturation is impaired methylation of deoxyuridine monophosphate to thymidine monophosphate (Hoffbrand et al, 1976). In this context the reduced serum uridine plus uracil levels in patients with vitamin B12 deficiency (Parry & Blackmore, 1976) and the haematological response of these patients to orotic acid therapy (Rundles & Brewer, 1958) are not readily explicable. Since the conversion of orotic acid to uridine monophosphate depends on the integrity of the coupled activities of orotidylic pyrophosphorylase and decarboxylase, this study has quantitated this capacity in peripheral blood erythrocytes in patients with vitamin B12 or folate deficiency.


Cholinoceptor-mediated mechanical and electrical responses of rat oesophageal striated musculature. A comparison of two in vitro methods.
1. Both muscarinic and nicotinic cholinoceptor agonists produce a contractile response of the rat oesophageal tunica muscularis externa (TME) in vitro. 2. The muscarinic receptor-mediated responses were confined to the distal 0.5 cm of the TME, which contains an admixture of smooth muscle. 3. Nicotinic receptor-mediated responses were obtained throughout the length of the TME striated musculature and consisted of a fast and slow component, representing TTX-sensitive contractions, associated with muscle action potentials, and electrically silent contractures, respectively. 4. Contractions were observed only in superfused preparations. 5. Contractures were resistant to changes in extracellular cation concentrations designed to eliminate generation of nerve and muscle action potentials or release of neurotransmitters.


Performance of rapid antigen tests in identifying Omicron BA.4 and BA.5 infections in South Africa.
Concerns around accuracy and performance of rapid antigen tests continue to be raised with the emergence of new SARS-CoV-2 variants. To evaluate the performance of two widely used SARS-CoV-2 rapid antigen tests during BA.4/BA.5 SARS-CoV-2 wave in South Africa (May - June 2022). A prospective field evaluation compared the SARS-CoV-2 Antigen Rapid test from Hangzhou AllTest Biotech (nasal swab) and the Standard Q COVID-19 Rapid Antigen test from SD Biosensor (nasopharyngeal swab) to the Abbott RealTime SARS-CoV-2 assay (nasopharyngeal swab) on samples collected from 540 study participants. Overall 28.52% (154/540) were SARS-CoV-2 RT-PCR positive with median cycle number value of 12.30 (IQR 9.30-19.40). Out of the 99 successfully sequenced SARS-CoV-2 positive samples, 18 were classified as BA.4 and 56 were classified as BA.5. The overall sensitivities of the AllTest SARS-CoV-2 Ag test and Standard Q COVID-19 Ag test were 73.38% (95% CI 65.89-79.73) and 74.03% (95% CI 66.58-80.31) and their specificities were 97.41% (95% CI 95.30-98.59) and 99.22% (95% CI 97.74-99.74) respectively. Sensitivity was >90% when the cycle number value was <20. The sensitivity of both rapid tests was >90% in samples infected with Omicron sub-lineage BA.4 and BA.5. Accuracy of tested rapid antigen tests that target the nucleocapsid SARS-CoV-2 protein, were not adversely affected by BA.4 and BA.5 Omicron sub-variants.


Severity of coronary atherosclerosis in patients with COPD.
Chronic obstructive pulmonary disease (COPD) has many comorbidities such as coronary artery disease (CAD) and stroke. Chronic low-grade systemic inflammation and oxidative stress play a significant role in CAD and COPD. We analysed that impact of COPD on intensity and severity of coronary artery lesions on the angiogram in the groups of patients with COPD according to the Global Initiative for Obstructive Lung Disease (GOLD) grades updated in 2015. The study included 102 COPD patients and 80 randomly selected subjects without any pulmonary disease who underwent coronary angiography. According to the GOLD grade for COPD, patients were divided into four groups: A, B, C and D. The severity and extent of CAD were determined using the Gensini score. There were no significant between-group differences in age, body mass index, smoking history, plasma lipids levels, frequency of hypertension, diabetes and CAD. The mean Gensini score in patients with COPD was significantly higher than those without (respectively, 25.7 ± 32.9 vs 17.5 ± 24.8, P = 0.01). While Gensini score was the highest level in the patient group D (64.9 ± 34.9), it was the lowest level in the patient group A (10.2 ± 19.4, P = 0.0001). The Gensini scores increased in accordance with increases in the GOLD grades. We observed that COPD was independently predictive for Gensini score after a multi-variate logistic regression analysis (odds ratio 1.374; 95% confidence interval 1.672-9.232; P = 0.001). Severity and intensity of coronary atherosclerosis increases in accordance with increases in the GOLD grades for COPD.


Comparative validation of a bilingual interactive multimedia dietary assessment tool.
To perform comparative validity testing for a bilingual interactive multimedia (IMM) dietary assessment tool that mimics a dietary recall against an interview-administered dietary recall. This was a two-period crossover design study. First, participants were randomly assigned to complete an IMM recall or interview-administered 24-hour recall. The IMM recall generated a nutrient profile that included 20 dietary constituents. The interview-administered recall was analyzed using the Food Intake Analysis System (FIAS) and the Expanded Food and Nutrition Education Program (EFNEP) Evaluating/Reporting System. The effect of substituting standardized portion sizes for reported portion sizes was examined. Of 80 adult participants, 71 (91%) were female, 45 (56%) had 12th grade or less education, 65 (81%) had an annual income of dollar 15,000 or less, and 21 (26%) completed the IMM recall in Spanish. Analysis of variance and unadjusted and energy-adjusted correlations were used. No significant group differences were found for order of administration or demographic characteristics. There was only one significant (P=.025) method effect, whereby vitamin C intake was higher in the IMM recall than the FIAS. The unadjusted correlations between the IMM recalls and interview-administered recalls analyzed using both FIAS and EFNEP Evaluating/Reporting System were generally approximately 0.6. Energy-adjusted correlations were consistently lower. Substituting standardized portion sizes resulted in significant differences for six nutrients and caused all correlations to decrease. The IMM dietary recall is a valid method for assessing dietary intake within the tested group. The results of comparative validity testing and positive reactions received from participants and nutrition educators indicate that diet assessment using IMM has tremendous potential.


Transcatheter embolization of the esophagomediastinal fistula with N-butyl cyanoacrylate glue: A case report.
Acute mediastinitis with esophageal perforation is a very fatal condition and must be treated promptly. Esophagomediastinal fistula is a rare complication of acute mediastinitis with esophageal perforation. There are many treatment options such as surgery or endoscopic treatment, but it is most important to start treatment immediately. A 69-year-old female presented with chest pain and fever. Contrast enhanced chest computed tomography was compatible with acute mediastinitis and esophageal perforation. Esophagography revealed esophagomediastinal fistula in the upper esophagus. Endoscopic clipping with fibrin was failed and endoscopic vacuum therapy (EVT) was not effective for esophagomediastinal fistula. We performed the successful transcatheter embolization of the esophagomediastinal fistula with N-butyl cyanoacrylate (NBCA) glue. There are many considerations in the treatment of acute mediastinitis with esophageal perforation, but surgery is the mainstay of treatment. Recently non operative management is appropriate in certain well-defined situations. Like our case patients, non-operative management may be considered if the diagnosis is delayed and the surgical treatment period is missed. Currently, endoscopic treatment such as covered stenting, clipping and application of fibrin glue are useful and a less invasive rather than surgical treatment. However, if endoscopic or surgical procedure are not possible, we considered transcatheter NBCA glue embolization. Transcatheter embolization with NBCA glue was proven to its effectiveness as an alternative therapeutic option in the treatment of esophagomediastinal fistula which endoscopic or surgical treatment are impossible or fails.


Selection of herbal therapeutics against deltatoxin mediated Clostridial infections.
Clostridium perfringens (a versatile pathogenic bacterium) secretes enterotoxins (the deltatoxin, virulent factor) and causes food borne gastroenteritis and gasgangrene. The organism was isolated and characterized from improperly cooked meat and poultry samples. The isolated organism showed multiple drug resistance indicating that the treatment is challenging. Hence, there is need for improved therapeutic agents. The rational design of improved therapeutics requires the crystal structure for the toxin. However, the structure for the toxin is not yet available in its native form. Thus, we modeled the toxin structure using α- hemolysin of Staphylococcus aureus (PDB: 3M4D chain A) as template. The docking of the toxin with the herbal extract curcumin (1,7-bis(4-hydroxy-3- methoxyphenyl)hepta-1,6-diene-3,5-dione) showed a binding energy of -8.6 Kcal/mol, in comparison to the known antibiotic Linezolid with binding energy of -6.1 Kcal/mol. This data finds application in the design and development of novel compounds against the deltatoxin from Clostridium perfringens.


Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes.
SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species-one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters-following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10-28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.


Lifestyle factors associated with serum N-3 fatty acid levels in breast cancer patients.
Long chain n3 fatty acids appear to have beneficial effects in several domains of health relevant to breast cancer survivors. This study evaluated inter-individual differences in serum levels of n3 fatty acids in 40 breast cancer patients who were participating in a pilot study for prevention of weight gain. Significant predictors of baseline n3 fatty acid levels in serum were dietary intakes of n3 fatty acids, BMI, serum levels of carotenoids and TV hours watched/day, accounting for 43% of the variance. Counseling for prevention of weight gain also tended to increase n3 fatty acid blood levels over time during chemotherapy.


Secondary carnitine deficiency in hyperammonemic attacks of ornithine transcarbamylase deficiency.
Carnitine status was evaluated in 12 patients with hyperammonemic attacks caused by a deficiency in ornithine transcarbamylase. We found decreased free carnitine and increased acylcarnitine levels in the serum, a decreased free carnitine content and an elevated acyl/free carnitine ratio in the liver, and increased excretion of free and acylcarnitine in the urine. Analyses of urinary acylcarnitine using the secondary ion mass spectrometry technique revealed increased amounts of acetylcarnitine and dicarboxylic acid derivatives. These data suggest that the patients had a secondary carnitine deficiency, possibly an aggravating factor in urea cycle dysfunction. After oral administration of L-carnitine (50 to 100 mg/kg/d) in two patients, hyperammonemic episodes were less frequent. Blood ammonia levels decreased significantly, accompanied by an increase in serum free carnitine levels.


FOXD3 suppresses the Proliferation of CRC Bone Metastatic Cells via the Ras/Raf/MEK/ERK Signaling Pathway.
The improvements in the treatment of colorectal cancer (CRC) and prolongation of survival time have improved the incidence of bone metastasis. Forkhead box D3 (FOXD3) is involved in the development of CRC. However, the role and mechanism of FOXD3 in CRC bone metastases development are unknown. Using the combined bioinformatics and cytology experimental analyses, this study aimed to explore the mechanistic role of FOXD3 in the bone metastasis of colon cancer, thereby aiding in the treatment of colon cancer bone metastasis and identification of drug-targeting markers. First, the changes in the expression levels of the FOXD3 gene and differentially expressed genes (DEGs) between the colon cancer samples and colon cancer metastases were obtained from The Cancer Genome Atlas (TCGA) database. Then, the correlations of the FOXD3 gene with the DEGs were identified. Next, the effects of the FOXD3 on the proliferation and invasion abilities of colon cancer bone metastatic cells were identified using Cell Counting Kit-8 (CCK8) and Transwell cell migration assays, respectively. In addition, Western blot analysis was used to identify the expression levels of the proteins related to the EGFR/Ras/Raf/MEK/ERK(EGFR/ERK) signaling pathway and epithelial-to-mesenchymal transition (EMT). FOXD3 was downregulated in colon cancer and could interact with multiple DEGs in colon cancer bone metastases. FOXD3 gene knockdown could increase the proliferation of human colon cancer bone metastatic cells and their invasive ability. FOXD3 gene knockdown could activate the expression of EGFR/ERK signaling pathway-related proteins and inhibit/promote the expression of EMT-related proteins, which in turn promoted the proliferation and metastasis of LoVo cells from colon cancer bone metastases. Overall, this study demonstrated that the downregulation of the FOXD3 gene might promote the proliferation of colon cancer bone metastatic cell lines through the EGFR/ERK pathway and promote their migration through EMT, thereby serving as a promising therapeutic target.


A subgroup analysis of the Scripps Coronary Radiation to Inhibit Proliferation Poststenting Trial.
In the Scripps Coronary Radiation to Inhibit Proliferation Poststenting (SCRIPPS) Trial, 192Ir significantly reduced angiographic, ultrasonographic, and clinical endpoints of restenosis. The objective of this analysis was to quantitate the impact of patient, lesion and technical characteristics on late angiographic outcome. Patients with restenotic, stented coronary lesions were randomized to receive either 192Ir or placebo sources. Late luminal loss and loss index were calculated for several patient subgroups, including patients with diabetes, in-stent restenosis, multiple previous percutaneous transluminal coronary angioplasty (PTCA) procedures, longer lesion lengths, saphenous vein grafts, small vessel diameters, and minimum dose exposures < 8.00 Gy. Two-factor analysis of variance was used to test for an interaction between patient characteristics and treatment effect. In the treated group, late loss was particularly low in patients with diabetes (0.19 mm), in-stent restenosis (0.17 mm), reference vessel diameters < 3.0 mm (0.07 mm), and patients who received a minimum radiation dose to the entire adventitial border of at least 8.00 Gy. The loss index in each of these subgroups was similarly low at -0.02, 0.03, -0.02, and 0.03, respectively. By 2-factor analysis of variance, a significant interaction between subgroup characteristic and treatment effect (late loss) was found in patients with in-stent restenosis (p = 0.035), and patients receiving a minimum dose of 8.00 Gy to the adventitial border (p = 0.009). In this pilot study, patient characteristics associated with a more aggressive proliferative response to injury appeared to confer an enhanced response to radiotherapy. Furthermore, a dose threshold response to 192Ir was found with an enhanced response occurring when the entire circumference of the adventitial border was exposed to at least 8.00 Gy.


Amniotic membrane-derived cells inhibit proliferation of cancer cell lines by inducing cell cycle arrest.
Cells derived from the amniotic foetal membrane of human term placenta have drawn particular attention mainly for their plasticity and immunological properties, which render them interesting for stem-cell research and cell-based therapeutic applications. In particular, we have previously demonstrated that amniotic mesenchymal tissue cells (AMTC) inhibit lymphocyte proliferation in vitro and suppress the generation and maturation of monocyte-derived dendritic cells. Here, we show that AMTC also significantly reduce the proliferation of cancer cell lines of haematopoietic and non-haematopoietic origin, in both cell-cell contact and transwell co-cultures, therefore suggesting the involvement of yet-unknown inhibitory soluble factor(s) in this 'cell growth restraint'. Importantly, we provide evidence that the anti-proliferative effect of AMTC is associated with induction of cell cycle arrest in G0/G1 phase. Gene expression analyses demonstrate that AMTC can down-regulate cancer cells' mRNA expression of genes associated with cell cycle progression, such as cyclins (cyclin D2, cyclin E1, cyclin H) and cyclin-dependent kinase (CDK4, CDK6 and CDK2), whilst they up-regulate cell cycle negative regulator such as p15 and p21, consistent with a block in G0/G1 phase with no progression to S phase. Taken together, these findings warrant further studies to investigate the applicability of these cells for controlling cancer cell proliferation in vivo.


Characterization of human umbilical cord blood-derived mast cells using high-throughput expression profiling and next-generation knowledge discovery platforms.
Mast cells (MCs) are tissue-resident innate immune cells that express the high-affinity receptor for immunoglobulin E and are responsible for host defense and an array of diseases related to immune system. We aimed in this study to characterize the pathways and gene signatures of human cord blood-derived MCs (hCBMCs) in comparison to cells originating from CD34- progenitors using next-generation knowledge discovery methods. CD34+ cells were isolated from human umbilical cord blood using magnetic activated cell sorting and differentiated into MCs with rhIL-6 and rhSCF supplementation for 6-8 weeks. The purity of hCBMCs was analyzed by flow cytometry exhibiting the surface markers CD117+CD34-CD45-CD23-FcεR1αdim. Total RNA from hCBMCs and CD34- cells were isolated and hybridized using microarray. Differentially expressed genes were analyzed using iPathway Guide and Pre-Ranked Gene Set Enrichment Analysis. Next-generation knowledge discovery platforms revealed MC-specific gene signatures and molecular pathways enriched in hCBMCs and pertain the immunological response repertoire.


Background-free 3D chemical imaging based on polarization coherent Raman holography.
We report on a holographic coherent anti-Stokes Raman scattering imaging by using polarization discrimination for nonresonant background suppression. With reduced polarization scrambling effect under weakly focused excitation, nonresonant background-free coherent Raman imaging is demonstrated. A fast chemically selective imaging is achieved in a three-dimensional volume of 70 μm ×70 μm ×100 μm in 2 s.


Productivity, Nutrient Digestibility, Nitrogen Retention, and Meat Quality in Rabbits Fed Diets Supplemented with Sida hermaphrodita.
Alfalfa (Medicago sativa) is an important forage crop in rabbit nutrition. Despite the numerous advantages of alfalfa, efforts have been made to find its potential substitutes. The aim of this study was to evaluate the efficacy of Sida hermaphrodita meal as a substitute for alfalfa meal in rabbit diets. The experiment was performed on 90 New Zealand White rabbits divided into three groups. DA group was fed a diet containing 20% dehydrated alfalfa. In the DA/DS group, rabbits received a diet containing 10% dehydrated alfalfa and 10% dehydrated Sida. The diet administered to the DS group contained 20% dehydrated Sida. The results of this study indicate that the dietary supplementation with Sida contributed to an increase in the final body weight of rabbits and improved the feed-conversion ratio. Experimental diets had no influence on nutrient digestibility, nitrogen retention, and selected carcass characteristics of rabbits, except for the proportion of the hind part. The content of dry matter, total protein, and monounsaturated fatty acids in the hind leg muscles of rabbits was higher in the DA group than in the experimental groups. The concentrations of saturated fatty acids were higher in the tissues of animals fed diets supplemented with Sida.


CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes.
To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage. The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively. Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA). A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of cellular MDA level, LDH, and AST activities in supernatants. Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes. A positive relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage.


Mutants of Escherichia coli defective in membrane phospholipid synthesis. Phenotypic suppression of sn-glycerol-3-phosphate acyltransferase Km mutants by loss of feedback inhibition of the biosynthetic sn-glycerol-3-phosphate dehydrogenase.
Revertants of Escherichia coli mutants defective in the first enzyme of membrane phospholipid synthesis, sn-glycerol-3-phosphate (glycerol-P) acyltransferase, were investigated. These glycerol-P acyltransferase mutants, selected as glycerol-P auxotrophs, contained membranous glycerol-P acyltransferase activity with an apparent Km for glycerol-P 10 times higher than the parental activity. The glycerol-P acyltransferase activity was also more thermolabile in vitro than the parental activity. Most revertants no longer requiring glycerol-P for growth regained glycerol-P acyltransferase activity of normal thermolability and apparent Km for glycerol-P. However, two novel revertants were isolated which retained an abnormal glycerol-P acyltransferase activity. The glycerol-P dehydrogenase activities of these novel revertants were about 20-fold less sensitive to feedback inhibition by glycerol-P. The feedback-resistant glycerol-P dehydrogenase co-transduced with gpsA, the structural gene for the glycerol-P dehydrogenase. Further transduction experiments demonstrated that the feedback resistant glycerol-P dehydrogenase phenotypically suppressed the glycerol-P acyltransferase Km lesion. The existence of the class of glycerol-P auxotrophs which owe their phenotype to the glycerol-P acyltransferase Km lesion therefore depends on the feedback regulation of glycerol-P synthesis in E. coli.


Variables affecting efficiency of molasses fermentation wastewater ozonation.
The main operating variables affecting ozonation efficiencies of wastewater from beet molasses alcoholic fermentation have been studied. Semibatch experiments have been performed in order to analyze the influence of pH, bicarbonate ion, temperature and stirring rate on color and organic matter removals. The efficiencies were similar regardless of the pH, which indicates that direct reactions of ozone with wastewater organics were predominant to radical reactions. Gel permeation chromatography confirmed the reduction in the concentration of organics absorbing light at 475 nm after ozonation. The elimination of bicarbonate ion, strong inhibitor of hydroxyl radical reactions, yielded an improvement in both color and COD reduction efficiencies. Acidification for removing bicarbonate ions produced a shift of colored compounds to smaller molecular weights. The highest efficiencies were achieved at 40 degrees C. Color and COD reductions at 40 degrees C were about 90% and 37%, respectively. In no case, the percentage of TOC removed was higher than 10-15%. Stirring rate had a slightly positive effect during the first stage of the ozonation showing that mass transfer played a role only during the initial reaction phase when direct attack of ozone molecules to aromatic/olefinic structures of colored substances was the predominant pathway.


Lacosamide tolerability in adult patients with partial-onset seizures: Impact of planned reduction and mechanism of action of concomitant antiepileptic drugs.
We evaluated the impact of planned dose reduction and mechanism of action of concomitant AEDs on tolerability in adults with partial-onset seizures undergoing lacosamide (LCM) titration. Data were collected at baseline and 3-6 and 12-24 months post-LCM initiation. Subjects were categorized as having planned reduction of concomitant AEDs or not; AEDs were categorized as traditional sodium channel blockers (TSCB) or non-TSCB (NTSCB). Groups with/without planned reduction were compared on the presence and number of treatment-emergent adverse events (TEAEs) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods controlling for standardized (STD) AED dose, a measure of concomitant AED load. Similar analyses were performed comparing subjects taking TSCB and NTSCB agents and used to identify relationships with ≥50% decreases in seizure frequency. One hundred six adults (mean age 41.4 ± 13.4; 50% male) underwent LCM titration from June 2009-2011 with complete data. Reduction of concomitant AEDs was planned at the time of LCM initiation in 59 (55.7%) subjects. Fewer subjects with planned reduction had TEAEs (49.2% vs. 68.1%; p=0.05), and these subjects had a lower risk of TEAEs (OR 0.36; p=0.019) after adjusting for STD AED dose. The hazard ratio (95% CI) for LCM discontinuation was 0.46 (0.23, 0.94) in subjects with planned reduction of concomitant AEDs vs. others (p=0.033) and 3.29 (1.01, 10.70) in subjects taking TSCB vs. NTSCB agents (p=0.048). Among all cases, those who ever had TEAEs had significantly higher STD dose at both follow-up visits (p=0.033 and p=0.023, respectively). Seizure outcomes were not significantly different between groups at the last follow-up assessment. Planned reduction of concomitant AEDs during LCM initiation and the use of NTSCB agents only are associated with a reduced risk of TEAEs and LCM discontinuation in adults with partial-onset seizures. This study extends prior observations by considering total AED load in the assessment of tolerability and supports the benefits of early reduction of concomitant AEDs during LCM initiation.


Platelet aggregation is not altered among men with diabetes mellitus.
Platelets are pivotal in arterial thrombosis, and platelet hyperresponsiveness may contribute to the increased incidence of cardiovascular events in diabetes mellitus. Consequently, we hypothesized that increased in vitro platelet aggregation responses exist in men with diabetes mellitus. The Danish Cardiovascular Screening Trial (DANCAVAS) is a community-based cardiovascular screening trial including men aged 65-74 years. Platelet aggregation was tested using 96-well light transmission aggregometry with thrombin receptor-activating peptide (TRAP), adenosine diphosphate, collagen type 1, arachidonic acid and protease-activated receptor-4 in three concentrations. Further, cardiovascular risk factors and coronary artery calcification (CAC), estimated by CT scans and ankle-brachial index, were obtained. Included were 720 men aged 65-74 years, 110 with diabetes mellitus. Overall, there was no difference in platelet aggregation among men with versus without diabetes mellitus when adjusting for or excluding platelet inhibitor treatment and men with established cardiovascular disease (CVD). This was true for all agonists, e.g., 10 µM TRAP-induced platelet aggregation of median 69% (IQR 53-75) versus 70% (IQR 60-76) in men with versus without diabetes mellitus. Platelet aggregation did not correlate with HbA1c or CAC. Men with diabetes mellitus displayed higher CAC, median 257 Agatston units (IQR 74-1141) versus median 111 Agatston units (IQR 6-420) in the remaining individuals, p < 0.0001. Among outpatients with diabetes mellitus, but no CVD and no platelet inhibitor treatment, neither are platelets hyperresponsive in diabetes mellitus, nor is platelet aggregation associated with glycemic status or with the degree of coronary atherosclerosis. ISRCTN12157806.


Troponin elevation after noncardiac surgery: Significance and management.
How to interpret and manage troponin elevations after noncardiac surgery is a common clinical question for cardiologists and internists. An estimated 5% to 25% of patients who undergo noncardiac surgery have an elevated postoperative troponin level. Patients with troponin elevation are at higher short-term and long-term risk of morbidity and mortality. Current guidelines provide few recommendations on how to manage these patients. The authors review the evidence and guidelines and propose treatment strategies.


Benefits and Harms of Exercise Therapy for Patients With Diabetic Foot Ulcers: A Systematic Review.
Exercise therapy is a core element in the treatment of diabetes, but the benefits and harms for patients with a diabetic foot ulcer (DFU) are unknown. We therefore aimed to systematically review the benefits on health-related quality of life (HRQoL) and harms of exercise therapy for patients with DFU. We searched 6 major databases. We performed citation and reference searches of included studies and contacted authors of ongoing trials. We included randomized controlled trials (RCTs) to assess potential benefits on HRQoL and harms of exercise therapy. Observational studies were included to identify potential harms of exercise therapy. We included 10 published publications of 9 trials and results from 2 unpublished trials including a total of 281 individuals with DFUs receiving various forms of exercise therapy. Due to lack of HRQoL measurements and high heterogeneity, it was not possible to perform meta-analyses. Results on HRQoL was present in one unpublished study. Harms reported ranged from musculoskeletal problems, increased wound size, to amputation; however, no safe conclusions could be drawn from the available data due to high heterogeneity and risk of bias in the trials. Protective strategies are often preferred over therapeutic exercise that might have unforeseen consequences for patients over time. Based on the current literature, no evidence-based recommendations can be provided on the benefits and harms of exercise therapy for patients with DFUs. Well-conducted RCTs are needed to guide rehabilitation including detailed description of adverse events and an exercise program in a semisupervised or fully supervised setting.


The validity of self-reported hypertension and correlates of hypertension awareness among blacks and whites within the stroke belt.
Hypertension surveillance activities increasingly are relying on information obtained by self-report. However, limited information is available concerning the validity of such data, especially among populations residing within the stroke belt. We used interview information and blood pressure measurements from the South Carolina Cardiovascular Disease Prevention Project to determine the validity of self-reported hypertension and the correlates of hypertension awareness among 2,210 whites and 704 blacks who participated in the program in 1987. The sensitivity, specificity, positive predictive value, and negative predictive value of self-reported hypertension were 79%, 91%, 76%, and 93% among white women; 82%, 88%, 79%, and 89% among black women; 62%, 91%, 75%, and 85% among white men; and 72%, 89%, 78%, and 85% among black men, respectively. Groups with highest sensitivity included women, persons older than age 39 years, and those who had seen a physician for preventive care within the last year. Correlates of hypertension awareness included an older age, visit to a physician for preventive care, and a family history of high blood pressure. Among hypertensive blacks, overweight persons were substantially more likely than nonoverweight persons to be aware of their hypertension (odds ratio [OR] = 4.6, 95% confidence intervals [CI] = 1.9, 10.7 in black women and OR = 4.4, 95% CI = 1.0, 17.9 in black men). The validity of self-reported hypertension was relatively high in all race-sex groups. There is a need to increase hypertension awareness among hypertensive blacks who are not overweight.


Assessment of cerebral blood flow velocities, brain midline shift and optic nerve sheath diameter by ultrasound in patients undergoing elective craniotomy: A prospective observational feasibility study.
Brain ultrasound allows measuring the cerebral flow velocity, brain midline shift and optic nerve sheath diameter. Literature is scarce in determining the feasibility to perioperatively perform these measurements altogether and the cerebrovascular behavior in patients scheduled for elective craniotomy. We assessed bilateral cerebral flow velocities, composite index, brain midline shift and optic nerve sheath diameter by cerebral ultrasound in patients scheduled for elective craniotomy before anesthetic induction, at extubation, and at 6 and 24 h after. The aim was to assess the feasibility of brain ultrasound in patients for elective craniotomy and to describe the changes in cerebral flow velocities, brain midline shift and optic nerve sheath diameter from baseline values at different times in the postoperative period. Sixteen patients were included, of these two were excluded from analysis due to an inadequate sonographic window. There were no changes throughout the study regarding cerebral flow velocity, brain midline shift nor optic nerve sheath diameter assessments. All parameters were maintained in the physiological range without significant variations during the procedure. No perioperative complications were detected. The results of our study show the feasibility to perform a perioperative assessment of cerebral flow velocity, brain midline shift or optic nerve sheath diameter jointly and successfully to obtain additional information of baseline cerebral hemodynamics in patients scheduled for elective craniotomy and their postoperative changes during the first 24 h. Future studies with lager samples are needed to address the efficacy of cerebral ultrasound as a monitoring tool.


Dosage compensation in mammals: why does a gene on the inactive X yield less product than one on the active X?
An expressed gene on the inactive mammalian X chromosome yields less product than the same gene on the active X. Characteristics of the inactive X which might be responsible for this are late replication, chromatin clumping, and altered patterns of DNA methylation. If an expressed gene on the inactive X is not replicated until late in S, it will be present in two copies for a shorter fraction of the cell cycle than its early replicating homologue and therefore yield less product. Alternatively, transcription may be slowed by a microenvironment of highly condensed chromatin or by an abnormal pattern of methylation of the DNA template. Experiments are proposed by which to test these and related hypotheses.


Acute Colonic Pseudo-Obstruction (Ogilvie's Syndrome).
Acute colonic pseudo-obstruction is a complication that occurs in hospitalized patients with serious underlying medical or surgical conditions; it is characterized by acute colonic dilatation in the absence of mechanical obstruction. The pathogenesis is incompletely elucidated, but changes in autonomic nervous system function are likely to contribute, as are metabolic and pharmacologic factors. Early diagnosis and appropriate intervention are critical in this disorder, which carries with it considerable morbidity and mortality. Treatment options, consecutively applied, include conservative measures, pharmacologic treatment with neostigmine, and endoscopic decompression. Surgical decompression or resection is necessary in case of refractoriness or perforation, respectively.


Determining the effect of stair nosing shape on foot trajectory during stair ambulation in healthy and post-stroke individuals.
Stair design can influence the risk of stair falls. Stair nosings are intended to provide greater foot accommodation, although to date little is known about how the nosing shape can affect foot trajectory during stair ambulation. This study investigates the impact of different nosing shapes (round, square, tapered, and no nosing) on foot clearance and overhang measures during stair ascent and descent among healthy and post-stroke older adults. Slower cadence in ascent and descent, and greater foot overhang during descent highlighted the increased risk of stair falls for persons with chronic stroke. For both healthy and post-stroke participants, the tapered and round nosing shapes resulted in the largest horizontal foot clearance, and smallest foot overhang, respectively. However, given the greater step-to-step variability detected with round nosings, the tapered nosing presents as the safest choice among all evaluated designs. The results of this work can be used to inform architectural and accessible design standards for a safer built environment.


Immediate balloon deflation for prevention of persistent phrenic nerve palsy during pulmonary vein isolation by balloon cryoablation.
Persistent phrenic nerve palsy is the most frequent complication of cryoballoon ablation for atrial fibrillation and can be disabling. To describe a technique-immediate balloon deflation (IBD)-for the prevention of persistent phrenic nerve palsy, provide data for its use, and describe in vitro simulations performed to investigate the effect of IBD on the atrium and pulmonary vein. Cryoballoon procedures for atrial fibrillation were analyzed retrospectively (n = 130). IBD was performed in patients developing phrenic nerve dysfunction (n = 22). In vitro simulations were performed by using phantoms. No adverse events occurred, and all patients recovered normal phrenic nerve function before leaving the procedure room. No patient developed persistent phrenic nerve palsy. The mean cryoablation time to onset of phrenic nerve dysfunction was 144 ± 64 seconds. Transient phrenic nerve dysfunction was seen more frequently with the 23-mm balloon than with the 28-mm balloon (11 of 39 cases vs 11 of 81 cases; P = .036). Balloon rewarming was faster following IBD. The time to return to 0 and 20° C was shorter in the IBD group (6.7 vs 8.9 seconds; P = .007 and 16.7 vs 37.6 seconds; P<.0001). In vitro simulations confirmed that IBD caused more rapid tissue warming (time to 0°C, 14.0 ± 3.4 seconds vs 46.0 ± 8.1; P = .0001) and is unlikely to damage the atrium or pulmonary vein. IBD results in more rapid tissue rewarming, causes no adverse events, and appears to prevent persistent phrenic nerve palsy. Simulations suggest that IBD is unlikely to damage the atrium or pulmonary vein.


Diagnostic Methods in Primary Ciliary Dyskinesia.
Diagnosing primary ciliary dyskinesia is difficult. With no reference standard, a combination of tests is needed; most tests require expensive equipment and specialist scientists. We review the advances in diagnostic testing over the past hundred years, with emphasis on recent advances. We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing. We discuss the international efforts that are in place to advance the evidence base for diagnostic tests.


Protective effect of intraoperative nerve monitoring against recurrent laryngeal nerve injury during re-exploration of the thyroid.
Previous thyroid or parathyroid surgery induces scarring or distorts anatomy, and increases the risk of recurrent laryngeal nerve (RLN) injury for a reoperation. The benefit of intraoperative nerve monitoring (IONM) for re-exploration (a second nerve exploration) and reoperation has not been established. Two hundred and ten patients were given a thyroid or parathyroid reoperation at our hospital between 2001 and 2010. Using IONM, we re-explored 56 patients who had been operated on before June 2007. The injury rate in these patients was compared with that of the 15 patients re-explored without IONM between 2001 and 2006. Of the 70 nerves that were re-explored using IONM, only one was incidentally injured, significantly fewer than the three injured in the 15 nerves re-explored without using IONM (1.43% vs. 20%, P = 0.0164). IONM helped prevent RLN damage when re-exploring nerves during thyroid and parathyroid surgery. We recommend the routine use of IONM in thyroid and parathyroid reoperations.


Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice.
Analogs of A-98593 (1) and its enantiomer ABT-594 (2) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as 1 and 2. Analogs of 2 with one or two methyl substituents at the 3-position of the azetidine ring also were prepared and found to be substantially less active in both assays.


A case report of hypocomplementemic urticarial vasculitis presenting with membranoproliferative glomerulonephritis.
Hypocomplementemic urticarial vasculitis syndrome is an infrequent condition characterized by ocular, renal, gastrointestinal and pulmonary involvement with low serum complement levels and autoantibodies. Renal manifestations vary from microscopic hematuria to nephrotic syndrome and acute kidney injury. Accordingly differing histologic patterns have been reported. We present the case of a 65 years old woman with a history of chronic uveitis who presented with arthralgias, urticarial rush, nephrotic syndrome, glomerular hematuria and low serum complement. Kidney biopsy revealed an immune-complex membranoproliferative glomerulonephritis. The patient received induction therapy with steroids, cyclophosphamide and hydroxychloroquine followed by rapid clinical improvement and remission of proteinuria. Maintenance treatment consisted of rituximab pulses. The majority of hypocomplementemic urticarial vasculitis syndrome cases is idiopathic, although an association to drugs, infections or other autoimmune disorders has been recorded. Given the rarity and heterogeneity of the disease, no standard treatment is established.


Partial reversal of the acetaldehyde and butyraldehyde oxidation reactions catalysed by aldehyde dehydrogenases from sheep liver.
In the presence of acetic anhydride or butyric anhydride, liver aldehyde dehydrogenases catalyse the oxidation of NADH at pH 7.0 and 25 degrees C. The maximum velocities and Michaelis constants for NADH at saturating anhydride concentrations are independent of which anhydride is used, the values being V'max. = 12 min-1 and Km for NADH = 9 micrometer for the mitochondrial enzyme and V'max = 25 min-1 and Km for NADH = 20 micrometer for the cytoplasmic enzyme. Substitution of [4A-2H]NADH for NADH resulted in 2-fold and 4-fold decreases in rate for the mitochondrial and cytoplasmic enzymes respectively.


Decompressive craniectomy with clot evacuation in large hemispheric hypertensive intracerebral hemorrhage.
Decompressive hemicraniectomy in large hemispheric infarctions has been reported to lower mortality and improve the unfavorable outcomes. Hematoma volume is a powerful predictor of 30-day mortality in patients with intracerebral hemorrhage (ICH). Hematoma volume adds to intracranial volume and may lead to life-threatening elevation of intracranial pressure. Records of 12 consecutive patients with hypertensive ICH treated with decompressive hemicraniectomy were reviewed. The data collected included Glasgow Coma Scale (GCS) score at admission and before surgery, ICH volume, ICH score, and a clinical grading scale for ICH that accurately risk-stratifies patients regarding 30-day mortality. Outcome was assessed as immediate mortality and modified Rankin Score (mRS) at the last follow-up. Of the 12 patients with decompressive hemicraniectomy, 11 (92%) survived to discharge; of those 11, 6 (54.5%) had good functional outcome, defined as a mRS of 0 to 3 (mean follow-up: 17.13 months; range: 2-39 months). The mean age was 49.8 years (range: 19-76 years). Three of the 7 patients with pupillary abnormalities made a good recovery; of the 11 patients with intraventricular extensions (IVEs), 7 made a good recovery. The clinical finding (which was present in all 3 patients with mRS equal to 5 and which was not present in patients with mRS less than 5) was abnormal occulocephalic reflex. Of the 10 patients with an ICH score of 3, 9 (90%) survived to discharge, 4 (44%) had good functional outcome (mRS: 1-3). Hematoma volume was 60 cm3 or greater in eight patients, four (50%) of whom had good functional outcome (mRS: 0-3). Decompressive hemicraniectomy with hematoma evacuation is life-saving and improves unfavorable outcomes in a select group of young patients with large right hemispherical ICH.


Structure-guided discovery of antioxidant peptides bounded to the Keap1 receptor as hunter for potential dietary antioxidants.
Human health can be damaged by free radicals, and antioxidant peptides are excellent radical scavengers. Antioxidant tripeptides data set based on 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulofnic acid) (ABTS) assay was created, 9 types of descriptors were integrated and 4 quantitative structure-activity relationship (QSAR) models were constructed in this study. Several structural factors influencing the activity of antioxidant tripeptides and the dominant amino acids at each position of tripeptides were revealed by the optimal model. Ten food-derived tripeptides with higher activity were selected for synthesis and activity determination. Molecular docking results demonstrated that these tripeptides were stably bound to the Keap1 receptor, further elucidating the antioxidant mechanism. It was known from the simulation of gastrointestinal digestion experiments that the model results possessed a guiding effect on the selection of proteins with high antioxidant activity. The performance of the model was proved to be robust after validation.


Chlorpyrifos-induced DNA damage in rat liver and brain.
Chlorpyrifos (O,O'-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF) is a broad spectrum organophosphate pesticide used to control a variety of pests. The present study was undertaken to test the in vivo genotoxic potential of CPF in rats, using the single cell gel electrophoresis (or comet) assay. The rats were administered 50 mg and 100 mg CPF/kg body weight daily for 1, 2, and 3 days as well as 1.12 mg and 2.24 mg CPF/kg body weight for 90 days. The level of DNA damage was estimated by scoring 100 cells per animal, dividing into five types: types 0, I, II, III, and IV. The results clearly indicate that exposure to CPF, acutely or chronically, caused a dose-dependent increase in DNA damage in the liver and brain of rats. From the present study, it can be concluded that CPF exhibits genotoxic potential in vivo.


Salivary dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus.
Mothers giving birth to children with manifestations of neonatal lupus (NL) represent a unique population at risk for the development of clinically evident pathologic autoimmunity since many are asymptomatic and only become aware of anti-SSA/Ro positivity (anti-Ro+) based on heart block in their fetus. Accordingly, we hypothesized that the microbiome in saliva is associated with the development of autoreactivity and in some cases the progression in health status from benign to overt clinical disease including Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The study comprised a clinical spectrum of anti-Ro+ mothers, all of whom gave birth to a child with NL: 9 were asymptomatic or had an undifferentiated autoimmune disease (Asym/UAS) and 16 fulfilled criteria for SS and/or SLE. Microbial diversity was reduced across all levels from kingdom to species for the anti-Ro+ mothers vs healthy controls; however, there were no significant differences between Asym/UAS and SS/SLE mothers. Relative abundance of Proteobacteria and more specifically class Betaproteobacteria decreased with clinical severity (healthy controls < Asym/UAS < SS/SLE). These ordered differences were maintained through the taxonomic hierarchy to three genera (Lautropia, Comamonas, and Neisseria) and species within these genera (L. mirabilis, N. flavescens and N. oralis). Biometric analysis comparing von Willebrand Factor domains present in human Ro60 with L. mirabilis proteins support the hypothesis of molecular mimicry. These data position the microbiome in the development of anti-Ro reactivity and subsequent clinical spectrum of disease.


Spiro-Structure: A Good Approach to Achieve Mechanoluminescence Property.
Following the development of organic mechanoluminescence (ML) materials, molecular packing was proved as the key point to the emission process under an external force. In this text, with the introduction of spiro-(fluorene-9-9'-xanthene) (SFX) unit as the building block, the molecular packing of the resultant compound (BSFXA) was optimized with the interlaced mode, directly leading to the efficient ML effect. The key role of SFX with a spiro-structure can be further confirmed by the ML inactivity of reference compound BFA with the replacement of SFX unit by dimethyl fluorene (MeF), which provided a novel strategy to construct organic ML luminogens.


Clonal variation of adenylyl cyclase activity in a rat tumor cell line caused by change in G protein-catalytic unit interaction.
Two subclones of the rat XC cell line characterized by different morphology exhibited quite different adenylyl cyclase responses upon various stimulations. Upon treatment with cholera toxin, clone RK1 accumulated a high level of intracellular cAMP thereby changing its polygonal morphology to an elongated morphology, while the other clone, LK1, with a fibroblastic morphology, failed to increase the intracellular cAMP and remained morphologically unchanged. When membrane fractions derived from these two clones were stimulated with 10 microM forskolin, 10 microM GTP gamma S, or 10 mM NaF, five- to 20-fold more cAMP was accumulated in RK1-derived membranes than in LK1-derived membranes. With the same membrane fractions, upon treatment with Mn(+)+, which directly stimulates the catalytic unit, a high level of cAMP was accumulated both in RK1 and LK1, indicating that the catalytic function inducible by Mn(+)+ was similar in both clones. There was no significant difference in the level of expression of G protein alpha 2, alpha i (at least alpha i1 and alpha i2), and beta subunits between LK1 and RK1. Cholate extracts of the membrane proteins of LK1 and RK1 reconstituted the adenylyl cyclase activity of the cyc- variant of S49 lymphoma cells to the same level. Therefore, it is inferred that the defect in LK1 resides in the interaction of stimulatory G proteins and the actual catalyst.


Opioid-free anesthesia-caution for a one-size-fits-all approach.
Post-operative pain management should ideally be optimized to ensure patient's mobilization and ability to partake in effective pulmonary exercises for patient's early recovery. Opioids have traditionally been the main mode for analgesia strategy in the perioperative period. However, the recent focus on opioid crisis in the USA has generated a robust discussion on rational use of opioids in the perioperative period and also raised the concept of "opioid-free anesthesia" in certain circles. Opioid-related adverse drug events (ORADE) and questionable role of opioids in cancer progression have further deterred some anesthesiologists from the routine perioperative use of opioids including their use for breakthrough pain. However, judicious use of opioid in conjunction with the use of non-opioid analgesics and regional anesthetic techniques may allow for optimal analgesia while reducing the risks associated with the use of opioids. Importantly, the opioid epidemic and opioid-related deaths seem more related to the prescription practices of physicians and post-discharge misuse of opioids. Focus on patient and clinician education, identification of high-risk patients, and instituting effective drug disposal and take-back policies may prove useful in reducing opioid misuse.


The association between depression, anxiety, and cognitive function in the elderly general population--the Hordaland Health Study.
To examine the association between depression and/or anxiety and cognitive function in the elderly general population. Non-demented participants from the general population (n = 1,930) aged 72-74 years. Symptoms and caseness of depression and anxiety disorder were assessed using the Hospital Anxiety and Depression Scale (HADS). Cognitive function was assessed by the Digit Symbol Test (modified version), the Kendrick Object Learning Test, and the 'S'-task from the Controlled Oral Word Association Test. There was a significant association between depression and reduced cognitive function. The inverse association between anxiety and reduced cognitive performance was explained by adjustment for co-morbid depression. The inverse association between depressive symptoms and cognitive function was found to be close to linear, and was also present in the sub-clinical symptom range. Males were more affected cognitively by depressive symptoms than females. The inverse association between depression and cognitive function is not only a finding restricted to severely ill patient samples, but it can also be found in the elderly general population.


Remote monitoring of total dissolved phosphorus in eutrophic Lake Taihu based on a novel algorithm: Implications for contributing factors and lake management.
Understanding the spatiotemporal dynamics of total dissolved phosphorus concentration (CTDP) and its regulatory factors is essential to improving our understanding of its impact on inland water eutrophication, but few studies have assessed this in eutrophic inland lakes due to a lack of suitable bio-optical algorithms allowing the use of remote sensing data. We developed a novel semi-analytical algorithm for this purpose and tested it in the eutrophic Lake Taihu, China. Our algorithm produced robust results with a mean absolute square percentage error of 29.65% and root mean square error of 9.54 μg/L. Meanwhile, the new algorithm demonstrates good portability to other waters with different optical properties and could be applied to various image data, including Moderate Resolution Imaging Spectroradiometer (MODIS), Medium Resolution Imaging Spectrometer (MERIS), and Ocean and Land Color Instrument (OLCI). Further analysis based on Geostationary Ocean Color Imager observations from 2011 to 2020 revealed a significant spatiotemporal heterogeneity of CTDP in Lake Taihu. Correlation analysis of the long-term trend between CTDP and driving factors demonstrated that air temperature is the dominant regulating factor in variations of CTDP. This study provides a novel algorithm allowing remote-sensing monitoring of CTDP in eutrophic lakes and can lead to new insights into the role of dissolved phosphorus in water eutrophication.


Social inequality in patients' physical and psychological state and participation in rehabilitation after myocardial infarction in Germany.
Several Anglo-American studies found that vertical social characteristics made a difference in the utilization of cardiac rehabilitation programmes. A social gradient was also demonstrated for prevalence of risk factors, psychological strain and psychosocial resources. This study investigated social differences for these factors in a group of 536 patients who had suffered from a myocardial infarction. In contrast to findings in other industrialized countries, German patients of higher status groups made less use of cardiac rehabilitative services than patients with a lower and middle class status. However, similar to Anglo-American findings, patients with a lower socio-economic status were more likely to be smokers and more likely to be obese than other patients. Also they had higher levels of comorbidity and depression and lower self-efficacy expectations. Thus while there were no social disadvantages in terms of participation in cardiac rehabilitation programmes, which seems to be largely due to the specific characteristics of the German health care system, patients of lower socio-economic status seem to have worse baseline conditions and as a result of this a specific need for rehabilitative support.


A straightforward LC approach using an amine column and single quad mass detector to determine choline chloride in feed additives and feeds.
Considering choline (ChCl) as an essential ingredient for animals and that it is administered through feed, we developed an easy, accurate, and sensitive method for its analysis. The method is straightforward, derivatization-free and has no secondary chromatographic interactions. •We demonstrated that the method can be used for quality control for feeds and feed additives containing choline chloride•We report a simple chromatographic method which takes advantage of the hydroxyl moiety present in ChCl and a MS detector.•We demonstrated that a single quadrupole detector is an effective option for the quantification of ChCl in feeds as an alternative for the more expensive tandem MS system.


Prognostic Implications of Biventricular Global Longitudinal Strain in Patients With Severe Isolated Tricuspid Regurgitation.
Isolated TV surgery can be performed in patients with symptoms caused by severe isolated tricuspid regurgitation (TR), preferably before the onset of significant right ventricular (RV) dysfunction. In patients with severe TR, intrinsic RV dysfunction tends to be masked and promotes left ventricular (LV) mechanical dysfunction. This study investigated the prognostic implications of biventricular global longitudinal strain (GLS) in patients receiving isolated tricuspid valve (TV) surgery. Among 1,670 patients who underwent TV surgery between January 2000 and December 2020, 111 patients with severe isolated TR who underwent echocardiography before and after TV surgery were analyzed. We assessed LV, RV, and biventricular GLS using speckle tracking echocardiography. Biventricular GLS was defined as the sum of LV-GLS and RV free-wall strain. The primary outcomes were cardiovascular death, heart failure hospitalization, re-done TV surgery, and heart transplantation. During 3.9 ± 3.8 years of follow-up after the postoperative echocardiography, 24 (21.6%) patients experienced a primary outcome. Those patients had more comorbidities and more impaired preoperative RV-GLS and biventricular GLS than those who did not experience a primary outcome, although the two groups did not differ in preoperative LV-GLS. Patients with a primary outcome also showed significantly impaired postoperative RV-GLS, biventricular GLS, and LV-GLS compared those without a primary outcome. In multivariate analyses, both pre- and postoperatively assessed RV-GLS [preoperative; hazard ratio (HR) 0.86, confidence interval (CI) 0.79-0.93, p < 0.001, postoperative; HR 0.89, CI 0.82-0.96, p = 0.004] and biventricular GLS [preoperative; HR 0.96, CI 0.91-1.00, p = 0.048, postoperative; HR 0.94, CI 0.89-0.99, p = 0.023] were independently associated with the primary outcomes. In patients with severe isolated TR undergoing TV surgery, the absolute value of RV-GLS under 17.2% is closely associated with a poor prognosis, and that of biventricular GLS under 34.0%, mainly depending on the RV-GLS, is related to the poor prognosis. Further prospective multicenter studies are warranted to establish the risk stratification of isolated TV surgery.


The diurnal course of plant water potential, stomatal conductance and transpiration in a papyrus (Cyperus papyrus L.) canopy.
The diurnal course of water potential, stomatal conductance and transpiration was measured on mature umbels (the major evaporating surface) of papyrus (Cyperus papyrus L.) growing in a fringing swamp on Lake Naivasha, Kenya.Umbel water potential declined only slightly during the morning but fell rapidly after midday to a minimum value of-1.5 M Pa in early afternoon. The two main structures forming the umbels, the bracteoles and rays, showed similar patterns of change of stomatal conductance throughout the day. The values of conductance indicate major stomatal opening during the morning, partial midday closure and some recovery of opening during the afternoon.It appears that the increase in water vapour pressure deficit of the air is the major cause of the midday closure of the stomata and that plant water potential has little effect. The reason why transpiration is reduced at high vapour pressure deficits when water is freely available to the roots is not clear. However, it is speculated that the restricted water movement into the plant from the anaerobic root environment has the effect of reducing the uptake of toxic ferrous iron.The daily total of canopy transpiration is estimated to be 12.5 mm, twice the value previously reported for papyrus but similar to daily valus determined for other wetland communities.


Activated STAT1 transcription factors conduct distinct saltatory movements in the cell nucleus.
The activation of STAT transcription factors is a critical determinant of their subcellular distribution and their ability to regulate gene expression. Yet, it is not known how activation affects the behavior of individual STAT molecules in the cytoplasm and nucleus. To investigate this issue, we injected fluorescently labeled STAT1 in living HeLa cells and traced them by single-molecule microscopy. We determined that STAT1 moved stochastically in the cytoplasm and nucleus with very short residence times (<0.03 s) before activation. Upon activation, STAT1 mobility in the cytoplasm decreased ∼2.5-fold, indicating reduced movement of STAT1/importinα/β complexes to the nucleus. In the nucleus, activated STAT1 displayed a distinct saltatory mobility, with residence times of up to 5 s and intermittent diffusive motion. In this manner, activated STAT1 factors can occupy their putative chromatin target sites within ∼2 s. These results provide a better understanding of the timescales on which cellular signaling and regulated gene transcription operate at the single-molecule level.


Porous material-immobilized iodo-Bodipy as an efficient photocatalyst for photoredox catalytic organic reaction to prepare pyrrolo[2,1-a]isoquinoline.
Iodo-Bodipy immobilized on porous silica was used as an efficient recyclable photocatalyst for photoredox catalytic tandem oxidation-[3+2] cycloaddition reactions of tetrahydroisoquinoline with N-phenylmaleimides to prepare pyrrolo[2,1-a]isoquinoline.


Annual reports from departments of clinical chemistry: a NORDKEM project.
The purpose of this report is to describe briefly the structure and purpose of NORDKEM, to illustrate how projects are developed within NORDKEM, and to discuss the results obtained in the project chosen for this presentation.


[Multicenter reticulohistiocytosis. A contribution to clinical aspects and therapy].
It is reported on a 48-year-old woman suffering from a multicentric reticulohistiocytosis. Most trouble in this case is caused by severe arthritis, which could not be stopped by various therapy schedules. The actual treatment is the combination of Prednisolone, Chloroquine, Ibuprofen and roentgenotherapy of the hands.


The interaction of arsenite with the molybdenum center of chicken liver xanthine dehydrogenase.
Inactivation of chicken liver xanthine dehydrogenase by arsenite is reflected in the molybdenum electron paramagnetic resonance signal at g = 1.97. The arsenite spectrum shows additional splittings and considerable broadening yet remains comparable to the native in total intensity. Further subtle alterations of the molybdenum signal of arsenite-treated enzyme are seen in the presence of purine-type substrates or inhibitors.


[Familial occurrence of multiple basalomas associated with hyperostotic spondylosis].
We report on brother and sister suffering from hyperostotic spondylosis and multiple basal cell carcinomas. Localisation and multiplicity of the tumors are remarkable. On account of the family tree, we assume recessive inheritance.


Localization of allodeterminants on H-2Kb antigens determined with monoclonal antibodies and H-2 mutant mice.
The topographic arrangement of antigenic determinants on the H-2Kb molecule was investigated by antibody competition studies with a series of monoclonal anti-Kb antibodies. For identification of amino acid residues participating in formation of allodeterminants H-2Kb mutant mice with defined amino acid substitutions were analyzed. The determinants were found to be located in at least two spatially separate clusters on the H-2Kb molecule. Determinants of one cluster are affected by mutations at amino acid positions 155 and 156, whereas determinants of a second cluster are modified by amino acid substitutions at positions 77 and 89. For a third cluster of determinants no relevant amino acid positions could be identified, but competition data indicate that this cluster is adjacent to the second one. The data suggest that the first two domains of H-2 antigens carry most allodeterminants.