Laparoscopic extended right hemicolectomy versus laparoscopic transverse colectomy for mid-transverse colon cancer: a multicenter retrospective study from Kanagawa Yokohama Colorectal Cancer (KYCC) study group.
The laparoscopic surgery approach for mid-transverse colon cancer (MTC) varies depending on tumor characteristics and the guidelines implemented by each surgeon; the optimal surgical procedure for MTC has not been established. This study aimed to compare the surgical outcomes of laparoscopic extended right hemicolectomy (Lap-ERHC) and laparoscopic transverse colectomy (Lap-TC) for MTC. This was a multicenter, retrospective study. We surveyed eight hospitals, by questionnaire, on MTC surgery policies and retrospectively compared the short- and long-term surgical outcomes for patients with MTC who underwent Lap-ERHC or Lap-TC between January 2008 and December 2019. A total of 129 patients were enrolled, of whom 35 underwent Lap-ERHC and 94 underwent Lap-TC. There were no significant differences in tumor progression between the two groups. Operation time was significantly longer (202 min vs. 185 min, p = 0.026). We observed a higher complication rate (≥ grade 3) in the Lap-ERHC group than in the Lap-TC group (11.4% vs. 3.2%, p = 0.086). Three patients (8.6%) who underwent Lap-ERHC developed anastomotic leakage; none of the patients who underwent Lap-TC had this complication (p = 0.018). The 3-year overall survival rates (stage I: 100% vs. 91.9%, p = 0.64; stage II: 100% vs. 95.5%, p = 0.46; stage III: 100% vs. 88.2%, p = 0.91, respectively) were similar between the two groups. Lap-ERHC for MTC has the same long-term outcomes as Lap-TC. However, Lap-ERHC for MTC has a higher complication rate. Therefore, Lap-TC may be recommended for patients with MTC. UMIN000042674.


Differential action of the albino mutation on two components of the rat's uncrossed retinofugal pathway.
The development of the uncrossed retinofugal pathways in normally pigmented and albino rats, aged from embryonic day (E) 14.5 to E18.5, was investigated. DiI was placed into one optic tract and the retinal origin of the uncrossed component, as well as its course in the optic stalk, was studied. The results show that, as in the mouse, the uncrossed retinal projection has two components. The first component is seen at E15.5 in normally pigmented animals. It develops exclusively in the central parts of the retina and is normal in albino littermates. The second component, which arises from the peripheral parts of the ventrotemporal retina, is seen two days later at E17.5 in all animals but is significantly smaller in albinos than in their pigmented littermates. Studies of axons in the optic stalk labelled retrogradely with DiI placed in the optic tract indicate that the uncrossed axons have no preference for any position in the stalk except when they approach the chiasm, where they tend to accumulate at the caudal region of the stalk. The uncrossed axons intermingle with the crossed axons along the entire length of the stalk. In albino embryos, no obvious difference in the prechiasmatic course of uncrossed axons was seen at any age examined. It is concluded that the albino mutation in rats affects the late ventrotemporal component of the uncrossed pathway selectively. It does not act on the early central component. Further, the intermingling of crossed and uncrossed axons in the stalk and the apparently unaffected prechiasmatic course of uncrossed axons in albinos indicate that the albino gene has its primary action in the retina.


Characterization of the Aspergillus niger prtT, a unique regulator of extracellular protease encoding genes.
Expression of several Aspergillus niger genes encoding major secreted, but not vacuolar, protease genes including the major acid protease gene pepA, was shown to be affected in the previously isolated A. niger protease mutant, AB1.13 [Mattern, I.E., van Noort, J.M., van den Berg, P., Archer, D.A., Roberts, I.N., Hondel, C.A.M.J.J., 1992. Isolation and characterization of mutants of Aspergillus niger deficient in extracellular proteases. Molecular & General Genetics 2, 332-336]. Complementation cloning of the putative protease-regulatory gene affected in this mutant was accomplished using a functional selection approach based on the use of the A. nidulans amdS selection marker driven by the A. niger pepA promoter. As expected the PpepA::amdS selection marker is not expressed in the mutant. Introduction of a self-replicating cosmid library into the mutant strain carrying the PpepA::amdS marker allowed selection of AmdS+ transformants functionally complementing the proposed regulatory mutation. Analysis of complementing cosmid clones revealed that the complementing sequences contained a gene encoding a member of the fungal-specific Zn2Cys6-binuclear cluster protein family. Sequence comparison of the encoded protein, PrtT, showed that it has homologues among different Aspergillus species. The A. oryzae homologue was shown to govern expression of the major alkaline protease AlpA and neutral protease Np1 in this species. In contrast to several other pathway specific regulators, such as AmyR and XlnR, no PrtT orthologues could be found in any other non-Aspergillus (or related) species and surprisingly, also not in Aspergillus nidulans. Interestingly, in all Aspergillus species carrying a prtT orthologue the gene is tightly clustered to a completely syntenous region carrying an amylolytic gene cluster including another Zn2Cys6-binuclear cluster protein, AmyR. Northern analysis of the A. niger prtT gene showed (constitutive) expression from two upstream promoters about 700 bp apart. The presence of several short upstream open reading frames downstream of both the distal and the proximal transcription start point of the prtT gene suggests regulation at the post-translational level. Also regulation at the level of differential splicing is suggested by the fact that several Aspergillus EST databases carry a considerable fraction of clones in which in frame intron sequences are retained.


Effects of liposoluble components of highland barley spent grains on physiological indexes, intestinal microorganisms, and the liver transcriptome in mice fed a high-fat diet.
The purpose of this study was to investigate the effects of the active ingredients of barley lees on the physiological indexes, intestinal flora, and liver transcriptome of mice fed a high-fat diet. Twenty-four male C57BL/6J mice were randomly divided into 4 groups and fed the experimental diets for 5 weeks. The results showed that the fat-soluble components of distillers' grains significantly reduced body weight, abdominal fat, perirenal fat, blood glucose, low-density lipoprotein cholesterol, triglycerides, and total cholesterol in the high-fat diet-fed mice (p < .05), significantly decreased alanine aminotransferase and malondialdehyde levels, and significantly increased total superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase levels (p < .05). At the phylum level, lipid-soluble components significantly increased the abundance of Bacteroidetes and decreased the Firmicutes/Bacteroidetes ratio. At the genus level, the relative abundances of Bacteroidetes and Clostridium were increased. Transcriptomic analysis showed that lipid-soluble components of spent grains reduced the mRNA expression of ANGPTL8, CD36, PLTP, and SOAT1 and increased the mRNA expression of CYP7A1 and ABCA1 in the cholesterol metabolism pathway, promoted the transport of cholesterol, and inhibited the absorption of cholesterol, which can decrease cholesterol levels by speeding up the conversion of cholesterol into bile acids.


Sequencing and analysis of four BAC clones containing innate immune genes from the Zhikong scallop (Chlamys farreri).
The sequencing of BAC clones (~100 kb) can reveal some characteristics of a genome that are challenging to obtain based on short sequences. Additionally, although the immune genes of the Zhikong scallop (Chlamys farreri) have been studied widely, few analyses have been conducted at the DNA level. In this study, four C. farreri BAC clones containing innate immune genes, including hsp70, l gbp (lipopolysaccharide and beta-1,3-glucan binding protein), serine protease and a gene with an immunoglobulin-like domain, were sequenced and analyzed both to explore the genomic characteristics of C. farreri based on long DNA sequences and to promote the study of C. farreri immune genes at the DNA level. The total length of the four BACs was 389.98 kb. A total of 34 genes were predicted in these sequences, and several features of protein-coding regions in the C. farreri genome were inferred based on this information. Two LGBP genes were located close together in a 22-kb region in one BAC clone, indicating the physical linkage of some immune genes in C. farreri. A cluster of membrane transport genes was also observed; these genes might play important roles in eliminating toxins in C. farreri, which lives as a filter feeder. Further analysis showed 15.43% of the BAC sequence was repetitive. Tandem repeats were the most abundant repeat type, followed by transposable elements. A total of 31 SSRs were predicted in the four BACs. An IS10 family transposon was identified, and a suspected regulatory non-coding RNA gene for this transposon (RNA-OUT) was observed to overlap with it complementarily. This work will promote future studies on the genomics, immune system and non-coding regions of C. farreri.


Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated with hypertriglyceridemia.
Hypertriglyceridemia is common in untreated diabetes mellitus. An abnormality in the interaction of lipoprotein lipase with endogenous circulating plasma lipoprotein triglyceride has been demonstrated in untreated diabetes. These diabetics have a decreased maximal removal capacity for plasma triglyceride (27.0 mg TG/kh/hr) and increased Km (390 mg/dl) for endogenous plasma triglyceride-lipoprotein lipase interaction compared to that found in nondiabetic hypertriglyceridemic subjects (Vmax, 32.0; km, 157). Diabetics treated for at least two months have a maximal removal capacity and Km similar to that of nondiabetic subjects (Vmax, 32.7; Km, 192). No evidence for an increase in triglyceride production due to diabetes per se was found. When diabetic subjects with triglyceride levels over 400 mg/dl were selected for study, most were found to have an independent familial form of hypertriglyceridemia.


Neonatal morbidity and growth in very low birth-weight infants after multiple courses of antenatal steroids.
To evaluate the neonatal morbidity and the growth in very low birth-weight (VLBW) infants after exposure to multiple courses of antenatal steroids. A total of 319 VLBW infants were placed in one of the two groups based on exposure to antenatal steroids: Group 1: less than two complete courses; Group 2: two complete courses or more. Anthropometric measurements at birth and discharge and neonatal morbidity were recorded. Composite morbidity was defined as presence of any of the following: death, chronic lung disease, major intraventricular hemorrhage and periventricular leukomalacia. The composite morbidity was not significantly different between the two groups (p=0.26). A significantly higher percentage of infants born after multiple courses of antenatal steroids had head circumference below 10th percentile at discharge (23 vs 9%, adjusted OR, 3.25, (95% CI, 1.4, 7.3); p=0.015). Multiple courses of antenatal steroids may predispose VLBW infants to impairment of postnatal somatic growth without providing any additional benefit for immediate neonatal outcome.


Examination of geniculate ganglion cells contributing sensory fibers to the rat facial 'motor' nerve.
Using a method to visualize HRP-containing cells in the geniculate ganglion (GG) in situ after decalcifying surrounding bone, we found that about 30% of the total (about 1000) GG cells contributed sensory fibers to the posterior auricular branch of the facial motor nerve. These cells are relatively large for GG cells in general. The remaining facial motor nerve branches, including those involved in vibrissal movement, contained few sensory afferent fibers originating from GG cells.


Intrathecal Administration of Nusinersen Using the Ommaya Reservoir in an Adult with 5q-Related Spinal Muscular Atrophy Type 1 and Severe Spinal Deformity.
Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, typically caused by survival motor neuron 1 (SMN1) gene deletion in chromosome 5q resulting in loss of SMN protein. SMA type 1 progresses rapidly leading to increased mortality usually before the age of 2 years. Nusinersen, the first approved disease-modifying treatment for all 5q-SMA types and ages, is an antisense oligonucleotide administered intrathecally via repeated lumbar punctures. However, adult SMA patients typically present with severe scoliosis and spinal deformity. We present a 28-year-old patient with SMA type 1 and severe spinal deformity, who received nusinersen via a subcutaneously implanted Ommaya reservoir connected with an intrathecal catheter at the thoracic level. The repetitive administrations were completed uneventfully, obviating the need for repeated laborious lumbar punctures and eliminating radiation exposure. In adult SMA patients, performing recurrent lumbar punctures can be technically challenging raising the need for an alternative route of administration. The use of Ommaya reservoirs is a viable, practical for repeated infusions, and safe option for the intrathecal delivery of nusinersen for select cases such as an adult SMA type 1 survivor with severe spinal deformity.


TMP778, a selective inhibitor of RORγt, suppresses experimental autoimmune uveitis development, but affects both Th17 and Th1 cell populations.
Experimental autoimmune uveitis (EAU), an animal model for severe intraocular inflammatory eye diseases, is mediated by both Th1 and Th17 cells. Here, we examined the capacity of TMP778, a selective inhibitor of RORγt, to inhibit the development of EAU, as well as the related immune responses. EAU was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). Treatment with TMP778 significantly inhibited the development of EAU, determined by histological examination. In addition, the treatment suppressed the cellular immune response to IRBP, determined by reduced production of IL-17 and IFN-γ, as well as lower percentages of lymphocytes expressing these cytokines, as compared to vehicle-treated controls. The inhibition of IFN-γ expression by TMP778 is unexpected in view of this compound being a selective inhibitor of RORγt. The observation was further confirmed by the finding of reduced expression of the T-bet (Tbx21) gene, the transcription factor for IFN-γ, by cells of TMP778-treated mice. Thus, these data demonstrate the capacity of TMP778 to inhibit pathogenic autoimmunity in the eye and shed new light on its mode of action in vivo.


Intramural esophageal dissection with eosinophilic esophagitis.
Intramural esophageal dissection (IED), like esophageal perforation, is a rare complication of eosinophilic esophagitis (EoE). A 44-year-old woman who had experienced EoE for 8 years complained of food impaction, severe neck pain, and odynophagia as well as consulted the emergency unit. She was diagnosed with IED with mediastinal emphysema by enhanced computed tomography. After admission, she was treated conservatively with noninvasive treatment, including fasting, intravenous feeding, and antibiotics. Only nine cases of IED with EoE have been previously reported. All were male, and our patient was the first female patient from Asia. Urgent endoscopy was conducted in eight cases, of which three were worse after endoscopy, and in one case, total esophagectomy was conducted due to subsequent esophageal perforation. We did not perform urgent endoscopy on our patient because of a potentially increased risk of esophageal perforation through the procedure. When patients with EoE complain of severe retrosternal pain, odynophagia, or dysphagia, IED should be considered in addition to food impaction.


Structure and function of chicken interleukin-1 beta mutants: uncoupling of receptor binding and in vivo biological activity.
Receptor-binding and subsequent signal-activation of interleukin-1 beta (IL-1β) are essential to immune and proinflammatory responses. We mutated 12 residues to identify sites important for biological activity and/or receptor binding. Four of these mutants with mutations in loop 9 (T117A, E118K, E118A, E118R) displayed significantly reduced biological activity. Neither T117A nor E118K mutants substantially affected receptor binding, whereas both mutants lack the IL-1β signaling in vitro but can antagonize wild-type (WT) IL-1β. Crystal structures of T117A, E118A, and E118K revealed that the secondary structure or surface charge of loop 9 is dramatically altered compared with that of wild-type chicken IL-1β. Molecular dynamics simulations of IL-1β bound to its receptor (IL-1RI) and receptor accessory protein (IL-1RAcP) revealed that loop 9 lies in a pocket that is formed at the IL-1RI/IL-1RAcP interface. This pocket is also observed in the human ternary structure. The conformations of above mutants in loop 9 may disrupt structural packing and therefore the stability in a chicken IL-1β/IL-1RI/IL-1RAcP signaling complex. We identify the hot spots in IL-1β that are essential to immune responses and elucidate a mechanism by which IL-1β activity can be inhibited. These findings should aid in the development of new therapeutics that neutralize IL-1 activity.


Ischemic or Coronary Evaluations in Patients With Monomorphic VT Electrical Storm Undergoing VT Ablation.
Monomorphic ventricular tachycardia (VT) electrical storm (ES) in patients with coronary artery disease is dependent on scarred myocardium. The role of routine ischemic or coronary evaluations before ablation in patients presenting with monomorphic VT storm, without acute coronary syndrome (ACS), remains unknown. This study sought to assess the impact of ischemic or coronary evaluations on procedural outcomes and post-ablation mortality in monomorphic VT storm patients. All patients undergoing VT ablation at the Cleveland Clinic from 2014 to 2020 after presenting with monomorphic VT storm were enrolled in a prospectively maintained registry. The associations among ischemic or coronary evaluations and short-term procedural efficacy, acute outcomes, and mortality during follow-up were assessed. A total of 97 consecutive patients with monomorphic VT storm in the absence of ACS underwent VT ablations. This cohort was characterized by severe LV systolic dysfunction (mean left ventricular ejection fraction 30.3%, 67% with known ischemic cardiomyopathy) with moderately severe heart failure (median NYHA functional class II); 45% of patients underwent ischemic or coronary evaluations via coronary angiography (10%), noninvasive myocardial perfusion (26%), or both (9%). The yield of these evaluations was low: No acute coronary occlusions were identified. There was no association between ischemic evaluation and acute ablation outcomes or mortality during follow-up. Similarly, in a secondary analysis, the yield of ischemic or coronary evaluations in patients with monomorphic VT storm and known coronary disease (regardless of ablation status) was found to be low. Ischemic evaluations in patients with monomorphic VT storm without ACS may not improve procedural outcomes or mortality after ablation.


Intraoperative monitoring for spinal radiculomedullary artery aneurysm occlusion treatment: What, when, and how long?
Spinal radiculomedullary artery aneurysms are extremely rare. Treatment should be tailored to clinical presentation, distal aneurysm flow, and lesion anatomical features. When a surgical occlusion is planned, it is necessary to evaluate whether intraoperative monitoring (IOM) should be considered as an indispensable tool to prevent potential spinal cord ischemia. We present a patient with symptoms and signs of spinal subarachnoid hemorrhage resulting from the rupture of a T4 anterior radiculomedullary aneurysm who underwent open surgical treatment under motor evoked potential (MEP) monitoring. Due to the aneurysmal fusiform shape and preserved distal flow, the afferent left anterior radiculomedullary artery was temporarily clipped; 2 minutes after the clamping, the threshold stimulation level rose higher than 100 V, and at minute 3, MEPs amplitude became attenuated over 50%. This was considered as a warning criteria to leave the vessel occlusion. The radiculomedullary aneurysm walls were reinforced and wrapped with muscle and fibrin glue to prevent re-bleeding. The patient awoke from general anesthesia without focal neurologic deficit and made an uneventful recovery with complete resolution of her symptoms and signs. This paper attempts to build awareness of the possibility to cause or worsen a neurological deficit if a radiculomedullary aneurysm with preserved distal flow is clipped or embolized without an optimal IOM control. We report in detail MEP monitoring during the occlusion of a unilateral T4 segmental artery that supplies an anterior radiculomedullary artery aneurysm.


[Place of bilateral pulpectomy as a method of androgen suppression therapy in prostate cancer].
To report the oncologic results and morbidity of bilateral pulpectomy and to identify factors that make this method of androgen suppression therapy the most used in our country. We conducted a prospective study in the urology department of Aristide Le-Dantec hospital (Dakar) between January 2008 and June 2010 (30 months). It included 84 cases of prostate cancer treated by bilateral pulpectomy under local anesthesia. The mean age of patients was 72.17±12.48 years (53-91). The median PSA level was 101 ng/mL (12.18-9990). Metastasis have been detected in 75% of cases. The Gleason score was higher than 7 in 40 patients (47.6%). Three months after pulpectomy, an improvement of performance status was seen in 76 patients (90.4%). The back pain significantly decreased in intensity or disappeared in 65.3% (32/49) of cases. A complete recovery of lower limbs motor deficit was observed in 50% of cases (7/14). The PSA levels decreased in 57 of the 76 patients alive and the mean PSA level was then 72±11.7 ng/mL (3.8-2433). At six months, of the 53 patients in urinary retention, 18 had recovered spontaneous and complete urination. The PSA level was below 4 ng/mL in 33.8% (22/65) of cases and between 4 and 10 ng/mL in 52.3% (34/65) of cases. At 12 months, the median PSA nadir was 0.76 ng/mL (0,002-8,17) and 57.4% of the 54 patients alive had a PSA nadir less than 2 ng/mL. The mean follow-up was 11.08±10.34 months (1-30). A rising PSA occurred in 17 patients (20.2%) after an mean progression-free survival of 10.5 months (6-25). The overall survival at 6, 12 and 24 months were respectively 77.3, 64.3 and 52.3%. The overall cost of pulpectomy was 50 000 FCFA (76€). The specific morbidity of pulpectomy was two cases (2.4%) of infection of the operative site. The bilateral pulpectomy was a method of androgen suppression immediately effective, efficacious with a low morbidity. Its very low cost is the main reason why it is still the most used method in our country.


Aminopeptidase activity in the brains of mice with chronic Toxoplasma gondii infections.
Aminopeptidase activity on beta-naphthylamide (NA) substrates was assayed in brain extracts from normal and Toxoplasma gondii-infected mice at 4 months postinfection. Correlations of levels of aminopeptidase activity, Toxoplasma-specific antibody production, and the number of brain cysts were studied in normal and Toxoplasma-infected mice. The Toxoplasma-specific antibody and the formation of cysts were markedly enhanced in the parasite-infected mice. The highest levels of activity for the NA substrates tested were observed in normal mice. In contrast, the activity levels were significantly lower in T. gondii-infected mice than in the corresponding normal mice. These results suggest an association between chronic toxoplasmosis and aminopeptidase activity in the parasite-infected host brain.


The effect of lamotrigine on the EEGs of children and adolescents with epilepsy.
Lamotrigine (LTG) is one of the newer-generation antiepileptic drugs (AEDs) with broad-spectrum efficacy against a variety of seizures and epileptic syndromes. We retrospectively evaluated the effects of LTG as add-on therapy on EEGs of children and adolescents. The EEGs of 53 patients (mean age: 12.5 years) with primarily pharmacoresistant epilepsy were reviewed prior to and after LTG add-on therapy. Multiple seizure types were seen in 25, generalized seizures in 15, and complex partial seizures in 13 of the patients. Preceding LTG therapy, the baseline EEG was abnormal because of slow background in 60.3% and localized spikes in 35.8%, generalized spikes in 28.3%, or both in 24.5%. The EEG analysis during the 2-year follow-up period showed improvement in the background in 21.9%, interictal activity in 37.8%, and ictal pattern in 41.1% of the EEG recordings. Overall, LTG resulted in improvement in electrographic features which paralleled the clinical improvement.


Calcium signaling in cancer and vitamin D.
Calcium signals induced by the Ca(2+) regulatory hormone 1,25(OH)(2)D(3) may determine the fate of the cancer cell. We have shown that, in breast cancer cell lines, 1,25(OH)(2)D(3) induces a sustained increase in concentration of intracellular Ca(2+) ([Ca(2+)](i)) by depleting the endoplasmic reticulum (ER) Ca(2+) stores via inositol 1,4,5-trisphosphate receptor/Ca(2+) release channel and activating Ca(2+) entry from the extracellular space via voltage-insensitive Ca(2+) channels. In normal cells, 1,25(OH)(2)D(3) triggered a transient Ca(2+) response via activation of voltage-dependent Ca(2+) channels, which were absent in breast cancer cells. The normal cells, but not breast cancer cells, expressed the Ca(2+) binding/buffering protein calbindin-D(28k) and were capable of buffering [Ca(2+)](i) increases induced by a mobilizer of the ER Ca(2+) stores, thapsigargin, or a Ca(2+) ionophore, ionomycin. The 1,25(OH)(2)D(3)-induced sustained increase in [Ca(2+)](i) in breast cancer cells was associated with induction of apoptotic cell death, whereas the transient [Ca(2+)](i) increase in normal cells was not. The forced expression of calbindin-D(28k) in cytosol or increase in the cytosolic Ca(2+) buffering capacity with the cell-permeant Ca(2+) buffer BAPTA prevented induction of apoptosis with 1,25(OH)(2)D(3) in cancer cells. The sustained increase in [Ca(2+)](i) in breast cancer cells was associated with activation of the Ca(2+)-dependent apoptotic proteases, mu-calpain and caspase-12, as evaluated with antibodies to active (cleaved) forms of the enzymes and the fluorogenic peptide substrates. Selective inhibition of the Ca(2+) binding sites of mu-calpain decreased apoptotic indices in the cancer cells treated with 1,25(OH)(2)D(3), thapsigargin, or ionomycin. The mu-calpain activation preceded expression/activation of caspase-12, and calpain was required for activation/cleavage of caspase-12. Certain non-calcemic vitamin D analogs (e.g., EB 1089) triggered a sustained [Ca(2+)](i) increase, activated Ca(2+)-dependent apoptotic proteases, and induced apoptosis in breast cancer cells in a fashion similar to that of 1,25(OH)(2)D(3). The 1,25(OH)(2)D(3)-induced transient Ca(2+) response in normal mammary epithelial cells was not accompanied by activation of mu-calpain and caspase-12. In conclusion, we have identified the novel apoptotic pathway in breast carcinoma cells treated with 1,25(OH)(2)D(3): increase in [Ca(2+)](i)-->mu-calpain activation-->caspase-12 activation-->apoptosis. Our results support the hypothesis that 1,25(OH)(2)D(3) directly activates this apoptotic pathway by inducing a sustained increase in [Ca(2+)](i). Differences of Ca(2+) regulatory mechanisms in cancer versus normal cells seem to allow 1,25(OH)(2)D(3) and vitamin D analogs to induce Ca(2+)-mediated apoptosis selectively in breast cancer cells. Thus, deltanoids may prove to be useful in the treatment of tumors susceptible to induction of Ca(2+)-mediated apoptosis.


Early Assessment of Treatment Response in Takayasu Arteritis: An 18FDG PET Procedure.
To describe a procedure allowing early assessment of treatment response in Takayasu arteritis (TA) patients by averaging the standard uptake value obtained from N hottest voxels irrespective of their location within the F-FDG-positive vessel walls (SUVmax-N). The procedure is illustrated in a score-V TA patient before and after 1 and 3 months of glucocorticoid treatment (scans 0-1-3, respectively). Comparison between scans was made by using SUVmax-N repeatability percentages with 95-99-99.9% reliability. No significant difference in SUVmax (ie, N = 1) was found between scan 0 and 1, and between scan 1 and 3, with 95% reliability. A significant difference in SUVmax-N was found with 99.9% reliability for each scan pair by averaging N = 4100-515 hottest voxels (total hottest volume of 100.0-12.6 mL), respectively. The proposed SUVmax-N procedure may be an efficient tool to early assess treatment response in TA patients. Further studies involving series of patients with large vessel vasculitis are warranted to investigate its usefulness in their management.


Properties of the tungsten-substituted molybdenum formylmethanofuran dehydrogenase from Methanobacterium wolfei.
In Methanobacterium wolfei two formylmethanofuran dehydrogenases are present, one of which is a molybdenum- and the other a tungsten enzyme. We report here that also the 'molybdenum' enzyme contained tungsten when the archaeon was grown on molybdenum-deprived medium supplemented with tungstate (1 microM). Unexpectedly the tungsten-substituted molybdenum enzyme was catalytically active and displayed a rhombic EPR signal which was attributed to tungsten by the characteristic 183W splitting.


Synthesis and characterization of unsymmetrical oxidovanadium complexes: DNA-binding, cleavage studies and antitumor activities.
Four oxidovanadium(IV) complexes, [VO(hntdtsc)(phen)] (1), [VO(hntdtsc)(bpy)] (2) (hntdtsc=2-hydroxy-1-naphthaldehyde thiosemicarbazone, phen=1,10-phenanthroline), [VO(satsc)(phen)] (3) and [VO(satsc)(bpy)] (4) (satsc=salicylaldehyde thiosemicarbazone, bpy=2,2'-bipyridine) have been synthesized and characterized. The results show that complexes 1, 2, 3 and 4 interact with DNA through intercalative mode and can efficiently cleave the plasmid pBR 322 DNA. It is interesting to note that these four complexes present highly cytotoxic activities against Myeloma cell (Ag8.653) and Gliomas cell (U251) lines. Complex 1 was found to be the most potent antitumor agent among the four complexes.


The evaluation of bone marrow edema in sacroiliac joint in patients with ankylosing spondylitis using magnetic resonance imaging Dixon sequence.
Bone marrow edema of the sacroiliac joint is the early imaging manifestation, an indicator of inflammatory activity of ankylosing spondylitis (AS) (Yang R, et. al. Medicine (Baltimore) 98:e14620, 2019). The aim of the study was to investigate the value of magnetic resonance imaging (MRI) Dixon sequence in the diagnosis of marrow edema of the sacroiliac joint in patients with AS. Forty-five patients with AS admitted in our hospital between November 2016 and February 2019 were selected retrospectively as the case group. Forty-five healthy subjects recruited between November 2016 and February 2019 served as the control group. Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded after admission to the hospital. The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were compared with indicators above in order to find the correlation. The water-fat ratio under the bilateral sacroiliac joints on Dixon sequence images in the case group was significantly higher than that in the healthy control group (P<0.05). The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were positively correlated with spinal arthritis research (SPARCC), BASFI and BASDAI score (all P < 0.05), but did not correlate with ESR and CRP. The water-fat ratio of magnetic resonance Dixon sequence can be used as a reference index to evaluate the degree of bone marrow edema in active stage of sacroiliac arthritis.


Modeling risks in marine protected areas: Mapping of habitats, biodiversity, and cultural ecosystem services in the southernmost atlantic coral reef.
Marine Protected Area (MPA) is a fundamental strategy for the maintenance of ocean ecological processes worldwide and, consequently, their associated ecosystem services. Nevertheless, the quality of the services provided by MPAs, including cultural services such as recreational activities, depends on the effective management of marine habitats and biodiversity. Here, we performed an ecosystemic assessment in reef environments within a subtropical MPA, modeling the potential risks for their habitats and their recreational activities. The Queimada Grande Island (QGI), southeastern Brazil, was used as the model area since this island encompasses a unique and irreplaceable marine habitat, the Southernmost Atlantic coral reef. We firstly assessed and mapped the habitats, the biodiversity, and the recreational activities associated with QGI reefs. Next, we considered different scenarios of management for the modeling risks across the study area. We found that the coral reef and its adjacent habitats, such as the rhodolith bed, make the sheltered face of the island an important area for the provision of the cultural ecosystem services and overlapping uses such as onboard recreational fishing, spearfishing, and recreational diving. This area was also evaluated as the one under the highest risk of impact, considering the current scenario of management. The most successful scenario modeling to reduce these risks was the hypothetical implementation of a 66% reduction of all activities over all QGI habitats. Despite that, the scenario simulating the application of the regulations present in the MPA management plan was enough to reduce almost half the maximum risk value. Therefore, we concluded that to provide a balance among conservation, uses, and the local economy, the application of these regulations is the better management scenario modeled for the study area. Such results provided useful information and tools for local management and decision-making in this singular marine environment, also being an example for mapping ecosystem services and modeling risks in MPAs worldwide.


DEAD-box proteins unwind duplexes by local strand separation.
DEAD-box proteins catalyze ATP-driven, local structural changes in RNA or RNA-protein complexes (RNP) during which only few RNA base pairs are separated. It is unclear how duplex unwinding by DEAD-box proteins differs from unwinding by canonical helicases, which can separate many base pairs by directional and processive translocation on the nucleic acid, starting from a helical end. Here, we show that two different DEAD-box proteins, Ded1p and Mss116p, can unwind RNA duplexes from internal as well as terminal helical regions and act on RNA segments as small as two nucleotides flanked by DNA. The data indicate that duplex unwinding by DEAD-box proteins is based on local destabilization of RNA helical regions. No directional movement of the enzymes through the duplex is involved. We propose a three-step mechanism in which DEAD-box proteins unwind duplexes as "local strand separators." This unwinding mode is well-suited for local structural changes in complex RNA or RNP assemblies.


Highly Efficient Additive-Free Dehydrogenation of Neat Formic Acid.
Formic acid (FA) is a promising hydrogen carrier which can play an instrumental role in the overall implementation of a hydrogen economy. In this regard, it is important to generate H2 gas from neat FA without any solvent/additive, for which existing systems are scarce. Here we report the remarkable catalytic activity of a ruthenium 9H-acridine pincer complex for this process. The catalyst is unusually stable and robust in FA even at high temperatures and can catalyse neat FA dehydrogenation for over a month, with a total turnover number of 1,701,150, while also generating high H2/CO2 gas pressures (tested up to 100 bars). Mechanistic investigations and DFT studies are conducted to fully understand the molecular mechanism to the process. Overall, the high activity, stability, selectivity, simplicity and versatility of the system to generate a CO-free H2/CO2 gas stream and high pressure from neat FA makes it promising for large-scale implementation.


Tissue distribution of and species differences in deacetylation of N-acetyl-L-cysteine and immunohistochemical localization of acylase I in the primate kidney.
Species differences in the biotransformation of N-acetyl-L-cysteine (NAC) have been investigated to evaluate the usefulness of NAC as a constituent in parenteral nutrition solutions in place of cysteine. The activity of NAC-deacetylating enzyme (acylase) was measured in various tissues of different species (rat, rabbit, dog, monkey, and man). Acylase activity was highest in the kidney in all species studied. Enzyme activity in the liver was 10 %-22 % of that in the kidney in the rat, rabbit, monkey, and man, but almost no hepatic activity was seen in the dog. NAC-deacetylating activity was very low in other organs. The tissue distribution of acylase I was determined by Western blotting and an immunohistochemical method employing specific antibody against porcine acylase I (EC 184.108.40.206). The immunoblotting study showed a 46-kDa protein band corresponding to porcine acylase I in the kidney of all species. In liver cytosol, 46 kDa and/or 29 kDa bands were observed in the rat, rabbit, monkey, and man, but not in the dog. In the immunohistochemical study, positive staining with anti-acylase I antibody was observed clearly in the renal proximal tubules in the monkey and man. These results suggested that the kidney and liver were the main organs responsible for the biotransformation of NAC to cysteine in mammals other than the dog.


Current Status of Social Problems during Pregnancy at a Perinatal Center in Japan.
To support pregnant women with serious social problems, we retrospectively examined the current status of social problems during pregnancy in Japan. We examined the frequency, associated factors, and outcomes of the pregnant women with social problems at our institute for each year from 2016 to 2019. The frequency of pregnant women with social problems significantly increased year by year (p < 0.01). The breakdown of high-risk factors associated with the social problems has remained almost unchanged; however, the frequency of unmarried pregnant women, unplanned pregnancy, foreigners who cannot speak either Japanese or English, and pregnant women who are somehow anxious significantly increased (p < 0.05). We will endeavor to solve the various social problems of pregnant women through multidisciplinary collaboration.


Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence.
Although many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI. VA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200 mg twice daily for 10 days and vancomycin (VAN) 125 mg four times daily for 10 days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125 mg four times daily for 10 days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59. CSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic. This study is registered with clinicaltrials.gov (Identifier: NCT02667418).


Microdebrider bronchoscopy: a new tool for the interventional bronchoscopist.
We report our experience with a new airway tool, the microdebrider, in treating central airway obstruction. From April 2002 to April 2004, 23 patients undergoing treatment of central airway obstruction were managed with the microdebrider. All procedures were done under general anesthesia with either a rigid bronchoscope (19 patients) or a suspension laryngoscope (4 patients). The microdebrider was used in an oscillating mode with rotation speeds of 1,000 to 3,000 rpm to resect obstructing tissue. Fourteen patients (61%) had tracheal granulation tissue from prior intubation or tracheostomy, 6 (26%) had idiopathic subglottic stenosis, and 3 (26%) had malignant disease. Obstructing lesions were rapidly removed in all patients with interventions lasting between 2 and 15 minutes. There were no procedure-related complications. No patients required reoperation for airway obstruction in follow-up ranging from 1 to 24 months. Microdebrider bronchoscopy is a new technique that allows for precise, rapid, and safe removal of lesions obstructing the central airways. Complications of thermal modalities such as airway injury, tracheoesophageal fistulas, and airway fires can be avoided.


Plasticity of human stem cells in the fetal sheep model of human stem cell transplantation.
Experimental models that allow the evaluation of the full potential of stem cells under normal physiological conditions and in the absence of genetic or injury-induced dysfunction would serve as valuable tools for the study of the mechanisms underlying stem cell differentiation. Ideally, such a model would also permit the robust formation of donor-derived tissue-specific cells. Because studies have shown that the differentiation of stem cells into cells of a different germinal layer is highly inefficient in the absence of selective pressure, it is very unlikely that a healthy adult animal can fulfill these requirements. In this review, we describe the advantages of the permissive aspects of the developing preimmune fetus in the early gestational age that led us to develop the sheep as a large-animal model of human stem cell plasticity.


Episodic-like memory in pigeons.
It has been proposed that memory for personal experiences (episodic memory, rather than semantic memory) relies on the conscious review of past experience and thus is unique to humans. In an attempt to demonstrate episodic-like memory in animals, we first trained pigeons to respond to the (nonverbal) question "Did you just peck or did you just refrain from pecking?" by training them on a symbolic matching task with differential responding required to the two line-orientation samples and reinforcing the choice of a red comparison if they had pecked and the choice of a green comparison if they had not pecked. Then, in Experiment 1, after providing the conditions for (but not requiring) the pigeons to peck at one new stimulus (a yellow hue) but not at another (a blue hue), we tested them with the new hue stimuli and the red and green comparisons. In Experiment 2, we tested the pigeons with novel stimuli (a circle, which they spontaneously pecked, and a dark response key, which they did not peck) and the red and green comparisons. In both experiments, pigeons chose the comparison appropriate to the response made to the test stimulus. Thus, the pigeons demonstrated that they could remember specific details about their past experiences, a result consistent with the notion that they have the capacity for forming episodic-like memories.


Conservation of migratory species.
Were you to find yourself somehow transported to the American Midwest in the 18th century, one feature that might strike you would be a curiously shifting cloud approaching from the northeast. As it drew closer, you might begin to discern some sound, "[like] an army of horses laden with sleigh bells" in the words of a Potawatomi Native American. However, not until it was nearly upon you would it become apparent that this cloud was made up of billions of individual birds. This was the autumn migration of the passenger pigeon (Ectopistes migratorius), the most abundant bird to ever be found in North America and perhaps in the world (Figure 1). By some estimates, the number of passenger pigeons in North America at the time of European colonization was greater than the combined number of all birds of all species found on the continent today. Yet, by the beginning of the 20th century, passenger pigeons had effectively been eradicated, in large part due to the extraordinary keenness with which they were hunted. By 1914, 5 billion birds were gone and the last passenger pigeon, Martha, died in the Cincinnati Zoo. Passenger pigeons represented an extraordinary example of one of Earth's great natural phenomena: the annual migration of organisms. They also highlight the potential vulnerability of migratory species. These seasonal movements are not only awe-inspiring; they are also critical for the health of countless species and ecosystems.


Population data of 13 nonCODIS STR markers located inside the 6 nonsyndromic oculocutaneous albinism genes.
Allele frequencies and forensic statistics of 13 autosomal short tandem repeat loci were estimated in 56 unrelated Iranian individuals. Except for two loci which were monomorph, a total of 5-11 alleles at each locus were observed and altogether 94 alleles for all selected loci were found. Our results show that 11 out of 13 nonCODIS STR loci are polymorphic and can be useful for human identification and kinship analysis and relationship investigations in Iran.


Studies on Ca2+-stimulated adenosine triphosphatase in rat submandibular glands: its distribution and properties.
Intracellular distribution and some characteristics of a Ca2+-stimulated adenosine triphosphatase (ATPase) in rat submandibular glands were investigated. This enzyme was activated by calcium alone, and magnesium was not necessary for its activation. Mg2+-stimulated ATPase also was investigated in the same enzyme preparations.


Effect of thrombin inhibitors on thrombin-induced platelet release and aggregation.
Thrombin-induced platelet activation was interrupted with hirudin or Dansylarginine N-(3-ethyl-1-5-pentanediyl) amide (DAPA) to study the time requirement for receptor occupancy by thrombin in promoting platelet responses at low (0.25 U/ml), intermediate (0.5 U/ml) and high (1 U/ml) thrombin concentrations. Each of these thrombin inhibitors suppressed adenosine triphosphate (ATP) release and aggregation by thrombin when added either before or simultaneously with thrombin or within seconds of the initiation of these responses by thrombin. If the inhibitors were added later, yet before aggregation or release was complete, no effect was present. The period of time for which active thrombin was required in order to promote these reactions had the following characteristics: (i) it is thrombin concentration dependent for a given response; (ii) it is longer for aggregation than for ATP secretion at each thrombin concentration; (iii) it is increased in platelets modified by chymotrypsin or platelets partially inhibited by antimycin A and 2-deoxy-D-glucose, which have prolonged aggregation and ATP release responses. In direct comparison studies, the inhibitory effects of hirudin and DAPA were identical on aggregation and ATP release. Thrombin binding, under similar experimental conditions identical to those used to measure platelet activation, was prevented by hirudin, but not by DAPA. Therefore, the effect of DAPA on thrombin must be at the proteolytic site region and not at the hirudin-inhibitable platelet binding region. It is concluded from these studies that the tight coupling requirements for thrombin to induce platelet dense granule release and aggregation are directly dependent upon both the thrombin concentration and the rate of the individual platelet responses. Catalytic site integrity is required for the duration of this period of receptor occupancy.


Intergenerational transmission of somatization behaviour: 2. Observations of joint attention and bids for attention.
Somatoform disorders may have their roots in childhood through processes that involve an enhanced parental focus on health. The aim of this study was to test the hypothesis that somatizing mothers will show less joint involvement than other mothers during play but greater responsiveness when this play involves a 'medical' theme. Cross-sectional observational study of 42 chronic somatizers, 44 organically ill and 50 healthy mothers and their 4-8 year-old children during structured play and a meal. Tasks comprised boxes containing tea-set items, 'medical' items and a light snack. Somatizing mothers were emotionally flatter and showed lower rates of joint attention than other mothers during both play tasks. While the three groups had similar rate of bids for attention, somatizing mothers were more responsive to their child's bids during play with the medical box than at other times. In contrast, the children of somatizing mothers ignored a greater proportion of their mother's bids during play with the medical box than did children of other mothers or during play with a non-medical theme. The study has demonstrated tentative evidence in support of the hypothesis.


A new, fluorescence-based method for visualizing the pseudopupil and assessing optical acuity in the dark compound eyes of honeybees and other insects.
Recent interest in applying novel imaging techniques to infer optical resolution in compound eyes underscores the difficulty of obtaining direct measures of acuity. A widely used technique exploits the principal pseudopupil, a dark spot on the eye surface representing the ommatidial gaze direction and the number of detector units (ommatidia) viewing that gaze direction. However, dark-pigmented eyes, like those of honeybees, lack a visible pseudopupil. Attempts over almost a century to estimate optical acuity in this species are still debated. Here, we developed a method to visualize a stable, reliable pseudopupil by staining the photoreceptors with fluorescent dyes. We validated this method in several species and found it to outperform the dark pseudopupil for this purpose, even in pale eyes, allowing more precise location of the gaze centre. We then applied this method to estimate the sampling resolution in the frontal part of the eye of the honeybee forager. We found a broad frontal acute zone with interommatidial angles below 2° and a minimum interommatidial angle of 1.3°, a broader, sharper frontal acute zone than previously reported. Our study provides a new method to directly measure the sampling resolution in most compound eyes of living animals.


Antihepatotoxic efficacy of Mangifera indica L. polysaccharides against cyclophosphamide in rats.
The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS) and/or silymarine against cyclophosphamide (CP) toxicity in male albino rats. The MPS and/or silymarin significantly decreased the activities of serum ASAT and ALAT. However, MPS (1000 mg/kg) normalized their activities towards the normal levels recording 28.75 and 78.75 U/ml respectively. The recorded data also showed the antioxidant effect of MPS by decreasing the level of malondialdehyde (MDA) and increasing the level of reduced glutathione (GSH) as well as normalized the activities of the antioxidant enzyme GST and SOD. Histopathological examinations also confirmed the protective efficacy of MPS against liver toxicity of CP. In conclusion, the recorded results of the present study support the protective role of MPS and/or silymarin against CP-induced hepatic damage.


Corrigendum to "Does the CFO serving as the secretary of the board affect the financial statement comparability?--Evidence from China" [Heliyon 9(3) (February 2023) e13609].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e13609.].


Facile synthesis and potential bioimaging applications of hybrid upconverting and plasmonic NaGdF4: Yb3+, Er3+/silica/gold nanoparticles.
We present a simple method for preparing water dispersible NaGdF4: Yb3+, Er3+/silica/gold nanoparticles. The emission intensity and color of the upconverting cores are modulated by the plasmonic absorbance and field enhancement from the gold nanoparticles. The applicability of hybrid NPs for multi-modal bioimaging probes is illustrated by in vitro confocal microscopy of living cancer cells.


Detection of antigens in immune complexes by a dot blot assay.
A simple assay is described for detection of antigens as a part of immune complexes. The complexes together with free IgG molecules are absorbed on protein A (or G)-Sepharose. The Sepharose beads are transferred to nitrocellulose membrane where all IgG including their complexes with antigens are eluted by acidic buffer directly on the surface of the membrane. The antigens immobilized on the membrane after elution are detected by corresponding labeled antibodies. The validity of the procedure was assessed by experiments with complexes of avidin and rabbit antibodies. The assay was used also for detection of DNA in immune complexes in mice with experimental systemic lupus erythematosus (SLE).


Inter and intra-specific hybridization in tuco-tucos (Ctenomys) from Brazilian coastal plains (Rodentia: Ctenomyidae).
The present work describes chromosomal polymorphisms in zones of contact between divergent populations of Ctenomys minutus parapatrically distributed in the coastal plain of southern Brazil, and inter-specific hybridization with C. lami a closely related species. A sample of 171 specimens from 32 sample sites distributed along 161 km of the coastal plain was cytogenetically analyzed. Nine polymorphic populations were found: four with specimens with 2n = 46-48 (autosomal arm number (AN) = 76); three only have specimens with 2n = 47 and 48; one population sampled presented specimens with 2n = 43-46 (AN = 74-76) and one population with 2n = 50-52 (AN = 76-80). The remainder populations were fixed for 2n = 42, 46 or 48. The variation is the result of Robertsonian mechanisms of chromosomal evolution and a fusion in tandem rearrangement. The polymorphisms have been considered the result of secondary contact of populations after divergence in allopatry. The geomorphological evolution of the coastal plain provides clues to the possible existence of past geographic barriers acting over populations of Ctenomys, during the Holocene.


Myelin growth and initial dynamics.
During the dissolution of solid surfactants in water, various types of nonequilibrium microstructures have been observed. The most important one is the myelin growth which can be observed when some poorly water soluble surfactants such as phosphatidylcholine (PC), Aerosol-OT (AOT), etc. are contacted with water. In this study initial myelin growth for a period of 2-4 s is studied both qualitatively as well as quantitatively in all the directions with respect to water flow in a PC system using digital video microscopy. Further, overall myelin growth is studied by means of optical microscopy to understand the effect of distance between cover slip and glass slide on myelin growth. Experiments are also performed to study effect of additives (silica) to lamellar phase on diffusion coefficients. It has been observed that the presence of silica particles causes extensive coiling of myelin structures. The mechanism of water transport into the lamellar phase during myelin growth is investigated by using silica in a colloidal range as dopant material.


Detection the eDNA of Batrachuperus taibaiensis from the Zhouzhi Heihe River Using a Nested PCR Method and DNA Barcoding.
The Taibai stream salamander (Batrachuperus taibaiensis) is a recently described species of the genus Batrachuperus that occurs in the Zhouzhi Heihe River and is endangered in its native range. Here, we have established a method for water environmental DNA (eDNA) analysis of Batrachuperus using a series of optimizations. We have designed a specific set of primers for the genus Batrachuperus to amplify a 160 bp fragment of Cytb. The sequences were obtained from nested PCR on eDNA extracted from water samples, after which DNA barcoding was performed according to sequence analysis to determine the presence of the target species in the water. The method was validated using water from the Zhouzhi Heihe River with known B. taibaiensis populations and found that B. taibaiensis eDNA can move at least 150 m downstream from its point of origin. This study is the first to establish an optimal method for obtaining the eDNA of Batrachuperus from water samples, which provides a theoretical basis for resource investigation and the protection of B. taibaiensis in future research. It is also an example of the eDNA extraction of other species that live in similar waters and are less genetically diverse between species.


Very Long-term Outcome of Minimally Invasive Direct Coronary Artery Bypass.
Minimally invasive direct coronary artery bypass (MIDCAB) is a well-established, low-impact surgical procedure for revascularization of the left descending coronary artery with the left internal mammary artery. This study aimed to evaluate safety, overall survival, and freedom from major adverse cardiocerebral-related events (MACCE) after 20 years of MIDCAB. This study retrospectively collected a series of 141 patients who underwent MIDCAB between 1997 and 2017, to assess long-term outcome. A total of 133 patients who underwent revascularization of the left descending coronary artery with the left mammary artery through a full median sternotomy were analyzed. Actuarial survival rates on a Kaplan-Meier curve were 100%, 95%, 90%, 83%, and 70% at 1, 5, 10, 15, and 20 years, respectively. Freedom from MACCE, defined as myocardial infarction, stroke, and cardiac death, was 97%, 90%, 79%, 75%, and 61% at 1,5,10,15, and 20 years, respectively. At Cox multivariable analysis, age, cancer, and chronic renal insufficiency were found to be independent predictors affecting long-term survival, with a hazard ratio of 1.12 (P = .007), 17.63 (P < .001), and 5.16 (P = .03), respectively. The MIDCAB group showed a significantly shorter hospital length of stay and significantly lower rates of blood transfusions, cardiac-related events, and all-cause events compared with the full sternotomy group (P = .02 and P = .001, respectively). The very long-term clinical outcome of MIDCAB is satisfactory in terms of survival and freedom from MACCE. MIDCAB significantly reduces hospital length of stay and blood transfusions when compared with full sternotomy bypass surgery on the left descending coronary artery and appears to improve prognosis in terms of cardiac-related events and all-cause events effectively.


Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.
The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.


Spectrographic determination of zinc in the tissues of adenoma and carcinoma of the prostate.
The authors describe a spectrographic method for the determination of zinc in solid matter. This method may be used to determine semiquantitatively the zinc-content of prostatic tissue. It has been found by this method that the ash from neoplastic prostatic tissue contained less zinc than that from adenomatous prostatic tissue.


Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines.
Cell lines of non-small cell lung cancer (non-SCLC) have been shown to contain activating mutation of the K-ras oncogene in about 30% of cases, whereas no small cell lung cancer (SCLC) cell lines displayed these mutations. Biochemically, these mutations result in the ras gene product (p21) being constitutively activated in its GTP-bound form and insensitive to the hydrolytic action of the ras-specific GTPase-activating protein (ras GAP). We hypothesized that, if tumor development is related to the p21 ras being in the active GTP-bound state, then a similar malignant phenotype may result from an inactivating mutation in the ras GAP gene in the region that interacts with ras p21 (so-called catalytic domain). To test this hypothesis, we screened a panel of SCLC and non-SCLC cell lines for major genetic alterations in the catalytic domain of the GAP gene with the Southern blot technique, and for minor genetic abnormalities (e.g., point mutations) with denaturing gradient gel electrophoresis and single-strand conformation polymorphism. Mutations in the catalytic domain of the GAP gene could not be demonstrated by any technique in any cell line examined. We conclude that mutational inactivation of the catalytic domain of the GAP gene probably does not contribute to the development of lung cancer.


Enhanced antiglobulin-mediated neutralization of herpes simplex virus-IgG complexes by complement and heterologous anti-immunoglobulin.
The ability of IgG anti-Fc and anti-Fab to neutralize infectious herpes simplex virus-IgG (HSV-IgG) complexes was determined. When limiting amounts of antiglobulin were used, antibody directed against the Fab portion of human IgG was significantly more effective than anti-Fc antibodies in neutralizing the HSV-IgG complexes. The detection of viral bound antibody was enhanced by the incorporation of heterologous antiglobulin or complement in the antiglobulin neutralization test. Specifically, HSV-IgG which had been incubated with rabbit antihuman globulin was further neutralized by goat antirabbit IgG or guinea pig serum complement. This augmented neutralization test could prove useful in detecting small amounts of antibody bound to virus in infectious isolates from patients or experimental animals with viral diseases.


Amphimela raydahensis sp. nov. from the Kingdom of Saudi Arabia (Coleoptera: Chrysomelidae: Galerucinae: Alticini).
Amphimela raydahensis sp. nov. is described from Garf Raydah Nature Reserve (Abha, Asir Province), southwestern Kingdom of Saudi Arabia. This species was collected using black light traps at different elevations dominated by cacti and wild olive trees. This is the first confirmed species of Amphimela known from the Arabian Peninsula.


Echocardiographic assessment of the adequacy of pulmonary arterial banding.
Thirty-one echocardiograms of 21 patients who had pumonary arterial banding were analyzed to assess the aequacy of surgery. In 5 patients the echocardiograms were obtained before and after banding and in 16 patients only after surgery. Right and left ventricular systolic time intervals were measured echographically. The ratios of the right ventricular preejection period to right ventricular ejection time (RPEP/RVET) were correlated with both diastolic (r = 0.94) and systolic (r = 0.86) pulmonary arterial pressures distal to the band. The analysis of right ventriclar systolic time intervals, especially the RPEP/RVET ratio, clearly differentiated patients with an adequate band (distal pulmonary arterial diastolic pressure less than 15 mm Hg) from patients with an inadequate band (distal pulmonary arterial diastolic pressure equal to or greater than 30 mm Hg). The results indicate that echocardiography is a useful noninvasive tool in evaluating the adequacy of the pulmonary arterial band and facilitates the follow-up of patients after banding.


Expression-targeted gene therapy for the treatment of transitional cell carcinoma.
Targeted gene delivery for induced apoptosis of transitional cell carcinomas was carried out in vivo in mice via utilization of the murine cyclooxygenase type 2 (Cox-2) promoter (Tis10). MB49 cells, which constitutively overexpress Cox-2 like numerous other carcinomas, selectively expressed delivered genes that utilized this transcriptional control element. The products of the delivered genes were artificially inducible forms of caspases 3 and 9, which remained inactive until a chemical inducer of dimerization was later injected intraperitoneally. The genes were delivered intravesically as plasmids complexed with poly(ethylenimine). Significant improvements, in the form of reduced bladder mass, reduced tumor volume, anti-angiogenesis and inhibition of tumor growth were seen versus untreated or unactivated controls. In some instances, tumors were seen to go into complete remission. There were no apparent bystander effects associated with the treatments. This targeted gene therapy regimen could have wide applicability to numerous cancers due to constitutive overexpression of Cox-2.


Tumour necrosis factor-α-857T allele reduces the risk of hepatitis B virus infection in an Asian population.
Tumour necrosis factor-α (TNF-α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF-α-857 polymorphism and chronic HBV infection have reported conflicting results. So a meta-analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966-March, 2011) and the China Biological Medicine Database (January, 1978-March, 2011) were searched using the keywords TNF-α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta-analysis. All fourteen studies focussed on an Asian population. The overall meta-analysis suggested that TNF-α-857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71-0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy-Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68-0.98, P = 0.043; OR = 0.77, 95% CI: 0.68-0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70-0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF-α-857T allele reduces the risk of chronic HBV infection in this Asian population.


Cellular responses to bacterial lipopolysaccharide: T cells recognize LPS determinants.
An in vitro proliferative system was used to assess the capacity of lipopolysaccharide (LPS) to induce a specific T-cell response in mice. Sensitized T cells were generated in vivo by subcutaneous inoculation with LPS. These T cells, which were purified on nylon wool columns, were stimulated to proliferate in vitro by LPS. Results of several lines of experimentation confirmed that the responding cells were T cells. Additional experiments indicated that sensitized T cells could distinguish between LPS and ovalbumin. Finally, it was found that genetic responsiveness to the biological effects of lipid A was required for full elicitation of LPS-induced T-cell proliferation. The data were interpreted to indicate that LPS interacted with, and stimulated, antigen-specific murine T cells.


Deep brain stimulation for obsessive-compulsive disorder is associated with cortisol changes.
Deep brain stimulation (DBS) is an effective treatment for obsessive-compulsive disorder (OCD), but its mechanism of action is largely unknown. Since DBS may induce rapid symptomatic changes and the pathophysiology of OCD has been linked to the hypothalamic-pituitary-adrenal (HPA) axis, we set out to study whether DBS affects the HPA axis in OCD patients. We compared a stimulation ON and OFF condition with a one-week interval in 16 therapy-refractory OCD patients, treated with DBS for at least one year, targeted at the nucleus accumbens (NAc). We measured changes in 24-h urinary excretion of free cortisol (UFC), adrenaline and noradrenaline and changes in obsessive-compulsive (Y-BOCS), depressive (HAM-D) and anxiety (HAM-A) symptom scores. Median UFC levels increased with 53% in the OFF condition (from 93 to 143nmol/24h, p=0.12). There were no changes in urinary adrenaline or noradrenaline excretion. The increase in Y-BOCS (39%), and HAM-D (78%) scores correlated strongly with increased UFC levels in the OFF condition. Our findings indicate that symptom changes following DBS for OCD patients are associated with changes in UFC levels.


Paediatric orbital ultrasound: Tips and tricks.
The orbital structures are ideally suited for ultrasound examination due to their superficial location and cystic composition of the eye. However, orbital ultrasound remains an underutilised modality due to preference for other cross-sectional modalities in general practice. In this article, we review the basic principles, clinical uses and technique of orbital ultrasound in peadiatric patients. The clinical utility of orbital ultrasound in peadiatric patients is demonstrated using selected cases. Ultrasound is useful in the diagnosis of various posterior segment pathologies, especially in conditions causing opacification of light-conducting media of the eye. It is also beneficial in diagnosing various orbital pathologies, particularly in differentiating solid from cystic lesions. The added advantages of its use in children include lack of ionising radiation and reduced requirement of sedation or general anesthesia. Ultrasound is the most practical initial investigation in cases where ophthalmoscopy is limited by opacification of ocular media. The addition of color Doppler on ultrasound can give additional information about the vascularity of the lesion. Use of ultrasound can be streamlined into the workup of various orbital and ocular pathologies either as an initial investigation or as a problem-solving tool in cases with a diagnostic dilemma on other modalities.


Left ventricular pump failure associated with diffuse coagulation in experimental intraoperative autotransfusion.
Autotransfusion of blood from the peritoneal cavity of pigs under a regimen of acid citrate dextrose solution 1:10 v/v for reservoir anticoagulation or systemic heparinization with 300 Iu/kg did not affect cardiac performance. Rapid deterioration of left ventricular pump performance was observed when low dose systemic heparin 100 Iu/kg was used. Evidence suggests that this is related to diffuse coagulation.


[A case of osteomyelitis caused by salmonella in a subject with thalassemia-drepanocytosis].
The authors show a case of osteomyelitis due to salmonella, they had the opportunity to observe in a patient suffering from thalassemia and sickle-cells disease in heterozygote from. They describe all the clinical and instrumental ascertainments performed and the surgical treatment effected at level of the osteomyelitic focus with subsequent recovery.


Acerola (Malpighia glabra L.) and guava (Psidium guayaba L.) industrial processing by-products stimulate probiotic Lactobacillus and Bifidobacterium growth and induce beneficial changes in colonic microbiota.
This study evaluated whether by-products from industrial processing of acerola (Malpighia glabra L.; AB) and guava (Psidium guajava L.; GB) fruit may stimulate the growth and metabolism of probiotic Lactobacillus and Bifidobacterium and induce changes in human colonic microbiota. The ability of non-digested and digested AB or GB to stimulate the growth ad metabolism of Lactobacillus acidophilus LA-05, Lactobacillus casei L-26 and Bifidobacterium animalis subsp. lactis BB-12 was evaluated. Changes in populations of distinct bacterial groups of human colonic microbiota induced by digested AB and GB were evaluated using an in vitro colonic fermentation system. Non-digested and digested AB and GB favoured probiotic growth. No difference among counts of probiotics in media with glucose, fructooligosaccharides and non-digested and digested AB and GB was found during a 48-h cultivation. Cultivation of probiotics in media with non-digested and digested AB and GB resulted in decreased pH, increased organic acid production and sugar consumption over time. Digested AB and GB caused overall beneficial changes in abundance of Bifidobacterium spp., Lactobacillus-Enterococcus, Eubacterium rectall-Clostridium coccoides and Bacteroides-Provotella populations, besides to decrease the pH and increase the short-chain fatty acid production during a 24-h in vitro colonic fermentation. AB and GB could be novel prebiotic ingredients because they can stimulate the growth and metabolism of probiotics and induce overall beneficial changes in human colonic microbiota. AB and GB stimulated the growth and metabolism of probiotics, in addition to induce beneficial alterations in human colonic microbiota composition and increase short-chain fatty acid production. These results characterize AB and GB as potential prebiotic ingredients and fruit processing by-products as sources of added-value compounds.


National reporting of deaths after enhanced Ebola surveillance in Sierra Leone.
Sierra Leone experienced the largest documented epidemic of Ebola Virus Disease in 2014-2015. The government implemented a national tollfree telephone line (1-1-7) for public reporting of illness and deaths to improve the detection of Ebola cases. Reporting of deaths declined substantially after the epidemic ended. To inform routine mortality surveillance, we aimed to describe the trends in deaths reported to the 1-1-7 system and to quantify people's motivations to continue reporting deaths after the epidemic. First, we described the monthly trends in the number of deaths reported to the 1-1-7 system between September 2014 and September 2019. Second, we conducted a telephone survey in April 2017 with a national sample of individuals who reported a death to the 1-1-7 system between December 2016 and April 2017. We described the reported deaths and used ordered logistic regression modeling to examine the potential drivers of reporting motivations. Analysis of the number of deaths reported to the 1-1-7 system showed that 12% of the expected deaths were captured in 2017 compared to approximately 34% in 2016 and over 100% in 2015. We interviewed 1,291 death reporters in the survey. Family members reported 56% of the deaths. Nearly every respondent (94%) expressed that they wanted the 1-1-7 system to continue. The most common motivation to report was to obey the government's mandate (82%). Respondents felt more motivated to report if the decedent exhibited Ebola-like symptoms (adjusted odds ratio 2.3; 95% confidence interval 1.8-2.9). Motivation to report deaths that resembled Ebola in the post-outbreak setting may have been influenced by knowledge and experiences from the prolonged epidemic. Transitioning the system to a routine mortality surveillance tool may require a robust social mobilization component to match the high reporting levels during the epidemic, which exceeded more than 100% of expected deaths in 2015.


An autopsy case of poisoning by massive absorption of cresol a short time before death.
A 65-year-old male patient who was hospitalized with schizophrenia died about 15 min later after ingestion of a large volume of saponated cresol solution in a mental hospital. Fatal levels of free p- and m-cresol in the heart blood were detected at 458.8 and 957.3 microg/ml, respectively, which far exceeded the fatal levels determined previously. The levels in the heart muscle, liver and spleen tissues were also extremely high, and there was 250 ml of cresol-odor-emitting fluid in the stomach. The levels of glucuronic-acid-conjugated p- and m-cresols in the heart blood were 38.2 and 85.6 microg/ml, respectively. Although the high levels of cresols in the heart blood may be due to diffusion from the stomach contents, it is surmised that the essential levels of free and conjugated forms in blood were at least 99 and 240 microg/ml, respectively, considering the results of postmortem examinations and some case reports. It was concluded that about 340 microg/ml of the total cresols was absorbed in a very short period following oral ingestion of saponated cresol solution in this case.


National trends in oropharyngeal cancer surgery and the effect of surgeon and hospital volume on short-term outcomes and cost of care.
The past 2 decades have witnessed an increase in the use of chemoradiation in the treatment of oropharyngeal cancer. We sought to characterize contemporary patterns of oropharyngeal cancer surgical care and the effect of volume on surgical care and short-term outcomes. Retrospective cross-sectional study. Using the Nationwide Inpatient Sample database, temporal trends in oropharyngeal cancer surgical care were evaluated in 75,828 cases performed from 1993 through 2008, and relationships between volume and mortality, complications, length of stay, and costs were evaluated in 29,030 cases performed from 2003 through 2008 using regression analysis, adjusting for patient and provider characteristics. Oropharyngeal cancer surgery from 2001 through 2008 was associated with increased use of high-volume hospitals (odds ratio [OR], 2.2; P = .016); an increase in tonsil (OR, 1.4; P < .001) and tongue base (OR, 1.3; P = .001) tumors; an increase in patients aged 40 to 64 years (OR, 1.5; P < .001); a decrease in partial glossectomy (OR, 0.8; P < .001), pharyngectomy (OR, 0.8; P = .003), mandibulectomy (OR, 0.6; P < .001) and laryngectomy procedures (OR, 0.6; P < .001); and an increase in prior radiation (OR, 1.7; P = .026), advanced comorbidity (OR, 1.4; P = .007), and wound complications (OR, 1.5; P = .029), compared to 1993 through 2000. High-volume hospitals were significantly associated with pharyngectomy (OR, 2.6; P = .001), while high-volume surgeons were associated with flap reconstruction (OR, 1.6; P = .005) and prior radiation (OR, 2.6; P = .013). After controlling for all other variables, a statistically significant interaction was observed between high-volume surgeons and high-volume hospitals, with reduced hospital-related costs for surgery performed by high-volume surgeons at high-volume hospitals. These data reflect changing trends in the epidemiology and primary management of oropharyngeal cancer, with meaningful differences in the type of surgical care provided by high-volume providers.


Goniometer not better than unaided visual inspection at estimating ventral penile curvature on plastic models.
The assessment of penile curvature is a key component of hypospadias surgery, as it often determines if a one- or two-stage procedure should be performed. The objective of this study was to compare unaided visual inspection (UVI) against goniometry estimations of ventral penile curvature (VC) among pediatric urologists. A total of nine different penile models (1.5 cm wide and 5-6 cm long) representing each decile of curvature from 10° to 90° were created. The nine models were divided in two groups: one with five models (group 1: 10°, 30°, 50°, 70°, and 90°) and the other with four models (group 2: 20°, 40°, 60°, and 80°). Each subject measured the VC of each model in group 1 using one method (i.e. UVI) and the curvature of each model in group 2 using the other method (i.e. goniometry). The next subject then used the opposite method for group 1 (goniometry) and group 2 (UVI), and so on, alternating the methods used to measure each group in between the subjects (Figure). The mean error (difference in between the true curvature and the subject estimation) was compared in between the two measurement methods (UVI and goniometry). A statistician calculated that 20-30 subjects would be needed to detect more than 10° difference in between the methods. A total of 25 subjects were recruited for the study (24 pediatric urologists and 1 adult urologist). Mean errors for all degrees of penile curvature and methods ranged from 3.5° (90° model) to 13.6° (30° model). The mean error was not statistically different in between UVI and goniometry methods for any degree of curvature. A subgroup analysis of only goniometry estimations comparing subjects with and without prior experience with goniometry showed a statistically significant difference only for the 60° model. If choosing the correct surgery depended on determining if the curvature was ≤30° or >30°, all subjects would have chosen the right surgery for all except the 20°, 30°, and 40° models, where wrong surgery was chosen in 6/25, 15/25, and 7/25, respectively. In this preliminary study, goniometry was not superior to UVI at estimating VC. There is pressing need in the field of hypospadias surgery to develop a tool that can measure VC in a reproducible and reliable fashion.


Determination of benzoylecgonine and cocaine in biologic fluids by automated gas chromatography.
A method is described for extraction of the cocaine metabolite benzoylecgonine, conversion to the butyl ester derivative and gas chromatographic analysis using packed or capillary columns. Using a capillary column, cocaine and benzoylecgonine may be determined simultaneously. The extraction scheme has been designed to facilitate processing of large numbers of samples generated in pharmacokinetic studies. Structural analogues, m-toluylecgonine and m-toluylecgonine methyl ester, are used as internal standards. Concentrations as low as 10 ng/ml in 1-ml samples of plasma or urine are readily determined. Between-run coefficients of variation were 1.01% for cocaine and 4.18% for benzoylecgonine for concentrations of 75 and 350 ng/ml, respectively.


Viroid trafficking: a small RNA makes a big move.
RNA trafficking has broad implications in the systemic spread of infectious agents, plant defense, and the systemic regulation of gene expression. The mechanisms that regulate trafficking remain poorly understood. The non-coding, infectious viroid RNAs are emerging as highly tractable model systems for the investigation of the basic mechanisms of RNA trafficking. Recent studies on viroids have led to new insights into the direct role of RNAs in intracellular and systemic trafficking, and to the identification of cellular proteins that might play a role in RNA trafficking. Here, we discuss these areas of progress, emphasizing on the unifying principles that control the trafficking of viroid, viral and endogenous RNAs.


Gremlin1 expression associates with serrated pathway and favourable prognosis in colorectal cancer.
Gremlin1 is a bone morphogenetic protein (BMP) antagonist with a suggested role in colorectal cancer (CRC) progression. We have analysed Gremlin1 protein expression in CRC and assessed its correlation with clinicopathological characteristics, including developmental pathway and prognosis. Material included a non-selected series of 148 surgically treated CRC cases. The tumour-node-metastasis (TNM) stage, histological grade and inflammatory infiltrate at the invasive margin were assessed, and tumours were classified to serrated or non-serrated types. Immunohistochemistry was conducted to evaluate Gremlin1 expression. Prognosis (60-month follow-up) was analysed by Kaplan-Meier methods and Cox regression analysis. Gremlin1 expression was detected in epithelial cells both in normal mucosa and in carcinomas. Abundant expression in carcinomas associated with low TNM stage (P = 0.044), low histological grade (P = 0.044), serrated histology (P = 0.033 or P = 0.053 depending on the classification cut-off) and intensive inflammatory infiltrate at the invasive margin (P = 0.044), and was a stage independent indicator of extended survival (P = 0.029). Gremlin1 protein expression in CRC associates with low tumour stage and extended survival independently of tumour stage, suggesting that it represents a relevant prognostic indicator in CRC. High expression in carcinomas with serrated histology suggests a potential role for Gremlin1 in the serrated pathway of CRC.


Differential radiation sensitization of human cervical cancer cell lines by the proteasome inhibitor velcade (bortezomib, PS-341).
Cervical cancer is one of the deadliest cancers in women with a death toll of 230,000 worldwide each year, nearly 80% in developing countries. Radiotherapy (RT) is a major treatment modality for advanced cervical cancer but the local relapse rate is 30-44% in patients treated with RT alone and 19-25% in patients treated with concurrent chemoradiotherapy. Previous studies have shown that the transcription factor NF-kappaB is constitutively expressed in human cervical squamous cell carcinomas. NF-kappaB activation also contributes to the resistance of cervical cancer cells to apoptosis induced by chemotherapeutic agents and radiation. Therefore, inhibition of NF-kappaB in tumor cells may render them more sensitive to chemo/radiation therapies. The objective of this study is to investigate the potential of radiosensitization of NF-kappaB inhibition by Velcade in human cervical cancer cell lines. We used the human cervical cancer cell lines HeLa and SiHa. Both are highly radioresistant and chemoresistant as compared to other cervical cancer cell lines. These cells had been treated with Velcade before they were irradiated with different doses of ionizing radiation. MTT metabolic assays and clonogenic cell survival assays were performed to evaluate the effects of Velcade on radiation resistance. Inhibition of NF-kappaB by Velcade alone decreased metabolic potential (MTT) and clonogenic survival in SiHa, but not in HeLa cells. Furthermore, pre-treatment of SiHa, but not HeLa cells with Velcade enhanced radiation sensitivity. Inhibition of NF-kappaB by the proteasome inhibitor Velcade enhances radiosensitivity of certain human cervical carcinoma cancer cells in vitro. These results raise the possibility that inhibition of NF-kappaB will result in radiosensitization only in those tumor cells which are more dependent on NF-kappaB for their metabolism and survival, however, the radiosensitivity of "NF-kappaB independent" cells are not likely influenced by it.


Stable and High-Power Calcium-Ion Batteries Enabled by Calcium Intercalation into Graphite.
Calcium-ion batteries (CIBs) are considered to be promising next-generation energy storage systems because of the natural abundance of calcium and the multivalent calcium ions with low redox potential close to that of lithium. However, the practical realization of high-energy and high-power CIBs is elusive owing to the lack of suitable electrodes and the sluggish diffusion of calcium ions in most intercalation hosts. Herein, it is demonstrated that calcium-ion intercalation can be remarkably fast and reversible in natural graphite, constituting the first step toward the realization of high-power calcium electrodes. It is shown that a graphite electrode exhibits an exceptionally high rate capability up to 2 A g-1 , delivering ≈75% of the specific capacity at 50 mA g-1 with full calcium intercalation in graphite corresponding to ≈97 mAh g-1 . Moreover, the capacity stably maintains over 200 cycles without notable cycle degradation. It is found that the calcium ions are intercalated into graphite galleries with a staging process. The intercalation mechanisms of the "calciated" graphite are elucidated using a suite of techniques including synchrotron in situ X-ray diffraction, nuclear magnetic resonance, and first-principles calculations. The versatile intercalation chemistry of graphite observed here is expected to spur the development of high-power CIBs.


Impact of electrical cardioversion on quality of life for patients with symptomatic persistent atrial fibrillation: Is there a treatment expectation effect?
It is assumed that electrical cardioversion (ECV) improves the quality of life (QoL) of patients with atrial fibrillation (AF) by restoring sinus rhythm (SR). We examined the effect of ECV and rhythm status on QoL of patients with symptomatic persistent AF in a randomized controlled trial. The elective cardioversion for prevention of symptomatic atrial fibrillation trial examined the efficacy of dronedarone around the time of ECV in maintaining SR. Quality of life was measured with the University of Toronto Atrial Fibrillation Severity Scale. The primary outcome was the change in AF symptom severity (∆AFSS) score over 6 months (0-35 points, with higher scores reflecting worse QoL and a minimal clinically important difference defined as ∆AFSS ≥3 points). Multivariable linear regression was performed to identify factors associated with changes in QoL. We included 148 patients with complete AFSS scores at baseline and 6 months. Over 6 months, QoL improved irrespective of rhythm status (ΔAFSS scores for patients who (i) maintained SR; (ii) had AF relapse after successful ECV; and (iii) had unsuccessful ECV were -6.8 ± 6.4 points, -4.1 ± 6.2 points, and -4.0 ± 5.8 points respectively, P < .01 for all subgroups). After adjustment of baseline covariates, maintenance of SR was associated with QoL improvement (ΔAFSS: -3.8 points, 95% CI: -6.0 to -1.6 points, P < .01). Maintenance of SR was associated with clinically relevant improvement in patients' QoL at 6 months. Patients with AF recurrence had a small but still relevant improvement in their QoL, potentially due to factors other than sinus rhythm.


Prediction of MHC class II binders using the ant colony search strategy.
Predictions of the binding ability of antigen peptides to major histocompatibility complex (MHC) class II molecules are important in vaccine development. The variable length of each binding peptide complicates this prediction. Motivated by the search properties of the ant colony system (ACS), a method for the identification of an alignment for a given set of short protein peptides has been developed. This alignment is further used for the derivation of a position specific scoring matrix. The distinguishing feature of this method is the use of the collective optimized search strategy of ants for the selection of the alignment. The performance of the new model has been evaluated with several benchmark datasets. It achieves better or comparable results as compared to the performance of existing methods. The experiments demonstrate that the predictive performance of the scoring matrix embodies several promising characteristics.


An evaluation of feeding practices and determination of barriers to providing nutritional support in a multidisciplinary South African intensive care unit.
Adequate nutritional support is crucial to optimising intensive care unit (ICU) outcomes. To assess adherence to current nutritional guidelines in critically ill patients in South Africa (SA). To identify risk factors for non-adherence to guideline. Retrospective observational chart review of nutritional practices, from 1 December 2017 to 31 May 2018, during the first week of ICU admission in adult patients admitted to a tertiary, multidisciplinary ICU in Durban, SA, for >48 hours. The study cohort (N=150) had a median age of 39 years and an ICU mortality of 28%. Surgical patients accounted for 50.7% of admissions. Ninety-eight percent of patients received mechanical ventilation, 75% required inotropic support, and 56% had acute kidney injury. The median time to initiation of enteral nutrition (EN) was 3 days, with EN being initiated within 48 hours in 39% of patients, and by day 7 80% of patients had received EN. Goal feeds were reached in 23% of patients by discharge, death or day 7. Parenteral nutrition was initiated in 16.7% of patients. There was an association between shock, acute kidney injury, increasing sequential organ failure assessment score and inotrope dose, and failure to initiate EN. Failure to initiate EN was predominantly due to unavoidable factors, but a number of clinical and administrative areas were identified to improve EN delivery. Adequate nutrition is associated with reduced morbidity, ICU length of stay, mortality and improved functional outcomes. More attention to avoiding barriers to adequate ICU nutrition and enhanced adherence to feeding protocols should be encouraged. This study significantly adds to the limited data available from sub- Saharan Africa on nutritional practices in critical care, and in particular barriers to provision of EN. It is further anticipated that the findings of the study will contribute in making recommendations in an attempt to improve the outcomes.


Local application of IGFBP5 protein enhanced periodontal tissue regeneration via increasing the migration, cell proliferation and osteo/dentinogenic differentiation of mesenchymal stem cells in an inflammatory niche.
Periodontitis is a widespread infectious disease ultimately resulting in tooth loss. The number of mesenchymal stem cells (MSCs) in patients with periodontitis is decreased, and MSC functions are impaired. Rescuing the impaired function of MSCs in periodontitis is the key for treatment, especially in a manner independent of exogenous MSCs. Our previous study found that overexpressed insulin-like growth factor binding protein 5 (IGFBP5) could promote exogenous MSC-mediated periodontal tissue regeneration. Here, we investigate the role of IGFBP5 protein in MSCs and periodontal tissue regeneration independent of exogenous MSCs in an inflammatory niche. TNFα was used to mimic the inflammatory niche. Lentiviral IGFBP5 shRNA was used to silence IGFBP5 and recombinant human IGFBP5 protein (rhIGFBP5) was used to stimulate the periodontal ligament stem cells (PDLSCs) and bone marrow stem cells (BMSCs). The effects of IGFBP5 on PDLSCs were evaluated using the scratch-simulated wound migration, Transwell chemotaxis, alkaline phosphatase (ALP) activity, Alizarin red staining, Cell Counting Kit-8, Western blot, Real-time PCR, Co-IP and ChIP assays. The swine model of periodontitis was used to investigate the functions of IGFBP5 for periodontal regeneration and its anti-inflammation effect. We discovered that 0.5 ng/ml rhIGFBP5 protein enhanced the migration, chemotaxis, osteo/dentinogenic differentiation and cell proliferation of MSCs under the inflammatory condition. Moreover, 0.5 ng/ml rhIGFBP5 application could rescue the impaired functions of IGFBP5-silenced-MSCs in the inflammatory niche. Furthermore, local injection of rhIGFBP5 could promote periodontal tissue regeneration and relieve the local inflammation in a minipig model of periodontitis. Mechanistically, we found that BCOR negatively regulated the expression of IGFBP5 in MSCs. BCOR formed a protein complex with histone demethylase KDM6B and raised histone K27 methylation in the IGFBP5 promoter. This study revealed that rhIGFBP5 could activate the functions of MSCs in an inflammatory niche, provided insight into the mechanism underlying the activated capacities of MSCs, and identified IGFBP5 as a potential cytokine for improving tissue regeneration and periodontitis treatment independent of exogenous MSCs and its potential application in dental clinic.