Phagocytic polymorphonuclear function in patients with progressive uremia and the effect of acute hemodialysis.
Susceptibility to infections is a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Polymorphonuclear leukocytes (PMNs) play a major role in the host defense against various infections. Although the phagocytic function of PMNs in uremic patients has been subjected to repeated evaluation, results have been inconsistent. Also, the effects of progressive uremia and acute hemodialysis (HD) on polymorphonuclear function have been scarcely evaluated. In this study, we assessed the phagocytic index (PI) of PMNs following their uptake of IgG-coated sheep erythrocytes in patients with varying severity of CKD and in healthy controls. In patients with advanced renal failure, the effects of acute HD on PI pre- and post-HD were also studied. A total of 30 patients with CKD and 15 healthy controls were studied. Patients with CKD were categorized into two groups: mild to moderate renal failure (S. Creatinine 2-6 mg/dL) and advanced renal failure (S. Creatinine >6 mg/dL) (n=15 for each). All three groups were age and sex matched. Patients with advanced renal failure had significantly impaired PI (4.03 +/- 1.15) as compared to patients with mild to moderate renal failure (7.17 +/- 2.62) and normal controls (8.13 +/- 3.31) (p < 0.001 for both). There was a statistically insignificant decline in the PI in patients with mild to moderate RF when compared to controls (7.17 +/- 2.62 versus 8.13 +/- 3.31). In patients with advanced renal failure, acute HD led to a significant improvement in PI (5.52 +/- 1.55 versus 4.03 +/- 1.15, p < 0.01). In patients with CKD, there is a progressive decline in the phagocytic index of the PMNs with increasing severity of uremia. Significant improvement in the phagocytic index following acute hemodialysis suggests the role of a circulating uremic toxin in this PMN dysfunction.


Increased systemic inflammatory interleukin-1ß and interleukin-6 during agitation as predictors of Alzheimer's disease.
Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study was to determine whether systemic inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD. We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1ß and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period. The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1ß or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1ß and IL-6 values at the agitation stage were significantly associated with AD, but not with VD. Our results indicate that systemic inflammatory IL-1ß and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.


Influence of location, fluid flow direction, and tissue maturity on the macroscopic permeability of vertebral end plates.
We implemented a pilot study in a growing animal model. The macroscopic permeability of the vertebral endplates was measured. The influence of location, tissue maturity, and fluid flow direction was quantified. We hypothesized that the macroscopic permeability of vertebral endplate may decrease with maturity of the vertebral segment. The alternation of loading induced by the diurnal cycle generates convective flux into the vertebral segment with the dominant flow path through the vertebral endplates. The alteration of mass transport at the disc-vertebrae interface may interrupt the mechanobiologic balance, and have an effect such as degenerative changes or scoliosis. A previously validated method for measuring permeability, based on the relaxation pressure caused by a transient-flow rate was used. Three specimens were extracted from each L1 to L5 endplate. Seventy-one specimens were frozen, and 64 were stored fresh in a standard culture media. A microscopic analysis completed the biomechanical analysis. At 2, 4, and 6 months, the mean permeability (10(-14) m/N x s, flow-in/flow-out) of the central zone was respectively: 1.23/1.66, 1.03/1.29, and 0.792/1.00. Laterally, it was 1.03/1.19, 1.094/1.001, and 0.765/0.863. For all groups, cartilage endplate and growth plate were both thinner in the center of the plate. Weak differences of the vascular network were detected, except for a small increase of vascular density in the central zone. The results from this animal study showed that the central zone of the vertebral endplate was more permeable than the periphery and the flow-out permeability was up to 35% greater than the flow-in permeability. Increase of permeability with decrease of cartilage thickness was noticed within the same age group. We also found a statistically significant decrease of the macroscopic permeability correlated with the tissue maturity.


Curcumin protects against the age-related hearing loss by attenuating apoptosis and senescence via activating Nrf2 signaling in cochlear hair cells.
Age-related hearing loss (ARHL) is a most widespread neurodegenerative disease affecting the elderly population, but effective pharmacological treatments remain limited. Curcumin is a bioactive compound of Curcuma longa with antioxidant properties. Herein, we looked into the effects of curcumin on the H2O2-induced oxidative stress in cochlear hair cells and hearing function in an ARHL animal model (C57BL/6J mice). We found that pretreatment of curcumin could attenuate H2O2-induced apoptosis and cell senescence in auditory hair cells and prevent mitochondrial function dysfunction. More specifically, Western blot and luciferase activity assay showed that curcumin activated the nuclear translocation of Nrf2, which in turn triggered the activation of its downstream target gene Heme Oxygenase1 (HO-1). The enhanced Nrf2 and HO-1 activity by curcumin was blocked by the AKT inhibitor LY294002, indicating the protective effect of curcumin was mainly achieved by activating Nrf2/HO-1 through the AKT pathway. Furthermore, the knockdown of Nrf2 with siRNA diminished the protective effects of Nrf2 against apoptosis and senescence, consolidating the pivotal role of Nrf2 in the protective effect of curcumin on auditory hair cells. More importantly, curcumin (10 mg/kg/d) could attenuate progressive hearing loss in C57BL/6J mice, as evident from the reduced threshold of auditory nerve brainstem response. Administration of curcumin also elevated the expression of Nrf2 and reduced the expression of cleaved-caspase-3, p21, and γ-H2AX in cochlear. This study is the first to demonstrate that curcumin can prevent oxidative stress-induced auditory hair cell degeneration through Nrf2 activation, highlighting its potential therapeutic value in preventing ARHL.


Direct evidence for mediation of an anticonflict effect of baclofen by GABAb receptors.
The present article reports an experiment on the effects of baclofen (0, 0.5, 1.0, and 2.0 mg/kg) on punished drinking in rats and the modification of these by delta-amino-n-valeric acid (DANVA) (0 and 10.0 mg/kg). Baclofen significantly enhanced punished drinking and this increase was abolished by DANVA, which had no intrinsic anxiogenic activity. It is concluded that GABAb receptors probably mediate this effect of baclofen and that such receptors may be a potential site of anxiolytic drug action.


Mouse organic solute transporter alpha deficiency alters FGF15 expression and bile acid metabolism.
Blocking intestinal bile acid (BA) absorption by inhibiting or inactivating the apical sodium-dependent BA transporter (Asbt) classically induces hepatic BA synthesis. In contrast, blocking intestinal BA absorption by inactivating the basolateral BA transporter, organic solute transporter alpha-beta (Ostα-Ostβ) is associated with an altered homeostatic response and decreased hepatic BA synthesis. The aim of this study was to determine the mechanisms underlying this phenotype, including the role of the farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15). BA and cholesterol metabolism, intestinal phenotype, expression of genes important for BA metabolism, and intestinal FGF15 expression were examined in wild type, Ostα(-/-), Fxr(-/-), and Ostα(-/-)Fxr(-/-) mice. Inactivation of Ostα was associated with decreases in hepatic cholesterol 7α-hydroxylase (Cyp7a1) expression, BA pool size, and intestinal cholesterol absorption. Ostα(-/-) mice exhibited significant small intestinal changes, including altered ileal villus morphology, and increases in intestinal length and mass. Total ileal FGF15 expression was elevated almost 20-fold in Ostα(-/-) mice as a result of increased villus epithelial cell number and ileocyte FGF15 protein expression. Ostα(-/-)Fxr(-/-) mice exhibited decreased ileal FGF15 expression, restoration of intestinal cholesterol absorption, and increases in hepatic Cyp7a1 expression, fecal BA excretion, and BA pool size. FXR deficiency did not reverse the intestinal morphological changes or compensatory decrease for ileal Asbt expression in Ostα(-/-) mice. These results indicate that signaling via FXR is required for the paradoxical repression of hepatic BA synthesis but not the complex intestinal adaptive changes in Ostα(-/-) mice.


[Telenavigation and expert consultation using a stereotaxic surgical videoserver].
The exponential increase of medical information creates a need for new methods in the visualization of medical imaging modalities for diagnosis and therapy. In this sense, visualization includes the display of medical image data and image-guided stereotaxic navigation as well as the advice of an expert. The Artma Virtual Patient System enables a remote expert to observe the surgical procedure via the Internet and interactively modify the interoperative visualization from the remote location. The expert in the remote location receives the planning data almost in real time over TCP/IP from a stereotaxic videoserver. In addition to live video streaming, stereotaxic navigation data are sent over the network as rigid body coordinates. The expert modifies the surgical simulation on the remote computer and the modified operating plan is sent back to the operating site. By teleconsulting, the composite images and overlapping graphics--instruments, target structures, landmarks, contour--can be seen in affiliated clinics with the possibility of interactive graphical assistance. With this image fusion technology the knowledge of a remote expert is included in virtual data structures and visualized by the overlay with live video data (augmented reality) in real time during surgery.


Identification and structural elucidation of ozonation transformation products of estrone.
Quantitative methods for the analysis of contaminants of emerging concern (CECs) are abundant in the scientific literature. However, there are few reports on systematic methods of identification and structural identification of transformation products. For this reason, a new method based on high-resolution mass spectrometry and differential analysis was developed in order to facilitate and accelerate the process of identification and structural elucidation of transformation products CECs. This method was applied to the study of ozonation transformation products (OTPs) of the natural hormone estrone (E1). A control compare trend experiment consisting in the comparison of a control sample to several samples having been exposed to decreasing concentrations of O3(aq) indicated that 593 peaks could be associated with OTPs. After applying various filters to remove background noise, sample contaminants and signal spikes, this data set was reduced to 16 candidate peaks. By inspection of the shape of these peaks, only two compounds OTP-276 (m/z 275.12930) and OTP-318 (m/z 317.14008) were considered as good candidates for further study. Multi-stage tandem mass spectrometry (MSn) experiments of SPE extracts of the ozonated samples of E1 and of a deuterium-labeled analogue (E1-d4) showed that OTP-276 and OTP-318 had carboxylic acid and hydroxyl functional groups, as previously reported for OTPs of other hormones. Structures for these two compounds were proposed based on their MSn spectra. These results indicate that the method proposed is a systematic and rapid approach to study transformation products of CECs.


Reappraisal of criteria used to predict serious bacterial illness in febrile infants less than 8 weeks of age.
To re-evaluate the Philadelphia protocol and the Rochester criteria for identifying infants at low risk for serious bacterial illness (SBI) in a new population. The authors prospectively enrolled infants 56 days of age or younger with rectal temperatures greater than 100.6 degrees F. Physicians assigned an overall impression of sepsis and objectively scored each infant using the Infant Observation Score. Following a history and physical examination, a complete sepsis evaluation was performed. Infants were considered to have SBI if their blood, urine, cerebrospinal fluid, or stool cultures grew pathogenic bacteria. Infants were assigned to high- and low-risk groups for SBI according to the Philadelphia protocol and the Rochester criteria by a single investigator blinded to the final culture results. The test performance parameters of the Philadelphia protocol and the Rochester criteria in this population were compared with those reported from previous validation studies. One hundred eighty-one infants were assigned to risk groups using the Philadelphia protocol, and 259 infants using the Rochester criteria. In this population, the negative predictive value (NPV) of the Philadelphia protocol was 97.1% (95% confidence interval [95% CI] = 85.1% to 99.8%), compared with 99.7% in the original report, and the NPV of the Rochester criteria was 97.3% (95% CI = 90.5% to 99.2%), compared with a prior report of 98.9%. The Philadelphia protocol and the Rochester criteria maintained their previously reported NPVs when applied to a new population of febrile infants. These data illustrate the usefulness of retesting clinical decision rules in new populations prior to their universal acceptance.


Shear bond strength of the Tenure Solution dentin bonding system.
A liquid solution of an oxalate bonding system containing NTG-GMA and PMDM has become commercially available. The bond strength of this oxalate adhesive (Tenure Solution) to dentin was determined by bonding composite resin cylinders to extracted teeth. The bond strengths obtained in this study are compared to the bond strengths obtained in earlier studies with the first and second generation oxalate adhesives whose components were supplied as powders and required mixing. The oxalate solutions developed significantly higher bond strengths than the original powder type systems.


Purification and characterization of NADPH-cytochrome P-450 reductase from rat epidermis.
NADPH-cytochrome P-450 oxidoreductase (P-450 red) transfers reducing equivalents from NADPH to cytochrome P-450 (P-450) in the monooxygenase system. Detergent solubilized proteins from the membrane fraction of neonatal rat epidermis were purified by 2',5'-ADP-agarose affinity column chromatography. The purified protein showed an apparent homogeneity on sodium dodecylsulfate-polyacrylamide gel electrophoresis and molecular weight was estimated to be 78 kDa. NADPH-cytochrome c reductase activity increased by 95-fold in the purified enzyme. Epidermal P-450 red in vitro reconstituted benzo(a)pyrene hydroxylase activity in a dose dependent manner with P-450 purified from either rat liver or epidermis. Western blot analysis demonstrated that epidermal P-450 red immunologically cross reacts to liver P-450 red. Immunohistochemical staining showed that the enzyme was predominantly localized in the epidermis. The intensity of immunohistochemical staining of rat skin sections and tissue distribution did not change in the skin treated with beta-naphthoflavone, which results in a substantial increase in P-450 1A1 activity. Quantitative assessment of P-450 red in treated and untreated epidermis also showed no change. These findings indicate that constitutive P-450 red, fully capable of supporting P-450, exists in rat epidermis, and can function in metabolism of endogenous and exogenous compounds.


The molecular nature of cholecystokinin in human plasma.
Using a radioimmunoassay specific for the bioactive, tyrosine-sulfated sequence of cholecystokinin (CCK) we have studied the molecular nature of CCK in plasma from normal human subjects. CCK was extracted from postprandial plasma by Sep-Pak cartridges prior to Sephadex G-50 gel chromatography. Four CCK components eluting like CCK-58, CCK-33, CCK-22, and CCK-8, were identified in all samples. Of these, CCK-33- and CCK-8-like peptides predominated. The heterogeneity of circulating CCK emphasizes the importance of plasma assays that measure all bioactive forms of CCK.


Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis.
Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls. We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search. Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls. TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.


Musculoskeletal pain post-COVID-19 in patients undergoing physical therapy in Saudi Arabia: a cross-sectional study.
The COVID-19 (coronavirus disease 2019) pandemic has posed a challenge to the physical therapy service. In addition to pandemic-associated treatment interference, many recovered COVID-19 patients developed new or worsening musculoskeletal pain as a sequela of COVID-19, which has been shown to affect the musculoskeletal system. The objective of the study was to examine musculoskeletal pain post-COVID-19 in patients undergoing physical therapy in Saudi Arabia. The design of the study was a cross-sectional study. We approached patients attending physical therapy clinics who had COVID-19. Data were collected through an electronic survey consisting of multiple-choice questions related to sociodemographic data and pain. Pain severity was rated on a 10-point numerical rating scale. A total of 85 recovered COVID-19 patients participated in this study, 30 had musculoskeletal pain prior to getting COVID-19, while 55 acquired it after. The most affected sites for musculoskeletal pain were the lower back and shoulder. Mean pain levels reported increased from 4.48 ± 2.54 pre-COVID-19 to 6.92 ± 8.06 post-COVID-19 (mean difference, 1.61 ± 2.61; t = 5.68; p < 0.0001). Mean pain scores did not associate significantly with demographic or clinical factors. Patient responses skewed toward increased pain as well as decreased activity levels after being infected with COVID-19 versus pre-COVID-19 (all p < 0.0001). Recovered COVID-19 patients reported increased pain intensity and frequency, together with reduced activity levels, relative to pre-COVID-19 levels, without effects of sociodemographic or clinical characteristics.


Severe necrotizing pneumonia complicating influenza A (H1N1): the role of immunologic interaction.
This report describes the successful management of a documented necrotizing pneumonia due to Streptococcus pneumoniae in a child with pandemic influenza A (H1N1). The importance of early recognition of bacterial superinfection in patients with influenza and the immunologic interactive mechanisms between viruses and bacteria in determining respiratory diseases are highlighted. The role of modern molecular techniques in improving diagnostic microbiology sensitivity and informing consequent clinical care is emphasized.


Fluid structure interaction analysis reveals facial nerve palsy caused by vertebral-posterior inferior cerebellar artery aneurysm.
Cranial nerve palsy caused by aneurysmal compression has not been fully evaluated. The main causes of symptoms are considered to be direct mechanical compression and aneurysm pulsations. Recent studies indicate that nerve dysfunction is mainly induced by pulsation rather than by direct compression, and successful cases of endovascular surgery have been reported. We describe a patient with an unruptured vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysm compressing the facial nerve at the root exit zone (REZ). The patient presented with peripheral facial nerve palsy but not hemifacial spasm and was successfully treated by coil embolization. To investigate the mechanisms underlying peripheral facial nerve palsy, fluid structure interaction (FSI) analysis can approximate displacement and the magnitude of aneurysmal wall motion due to hemodynamic forces. In our case, maximum mesh displacement was observed at the aneurysmal wall attached to the facial nerve inside the pons rather than the REZ, which explains the clinical manifestation of facial nerve palsy in the absence of hemifacial spasm. This preliminary report demonstrates the utility of FSI analysis for investigating cranial nerve neuropathy.


[Common foundation of alexithymia and expressive suppression].
International studies could already prove a correlation between alexithymia and expressive suppression. This relationship has only been marginally considered in the German literature so far. The prioritized aim of the present study was to investigate a correlative and factorial relationship between alexithymia and expressive suppression. A total of 317 persons participated in an online survey. Data on alexithymia and expressive suppression were collected using the German versions of the Toronto alexithymia scale (TAS-26) and the emotion regulation questionnaire (ERQ). The results showed highly significant correlations between the TAS-26 subscale "difficulty in identifying feelings" and the ERQ scale "suppression" (r = 0.5; p < 0.001) and between the TAS-26 subscale "difficulty in describing feelings" and the ERQ scale "suppression" (r = 0.64; p < 0.001). The results of an exploratory factor analysis revealed a two-factor solution with common factor for the TAS-26 subscales "difficulty in identifying feelings" and "difficulty in describing feelings" and the ERQ scale "suppression" with a common variance of 38.2% (χ2 = 363.843, p < 0.001, Kaiser-Meyer-Olkin, KMO, value = 0.699). The results indicate that the TAS-26 scales in the components "difficulty in identifying feelings" and "difficulty in describing feelings" and the ERQ scale "suppression" in the component of "expressive suppression" have a common construct, which is referred to with the term speechlessness.


Surgical outcomes of the anterior versus posterior approach for advancement of the levator aponeurosis in Japanese patients.
To compare the surgical outcomes of the anterior and posterior approaches for advancement of the levator aponeurosis for aponeurotic blepharoptosis in relation to levator function (LF). This retrospective study included 223 eyelids from 125 patients with aponeurotic blepharoptosis. The anterior approach was used for 115 eyelids from 65 patients (anterior group), while the posterior approach was used in 108 eyelids from 60 patients (posterior group). Patients were subdivided into two groups in accordance with their LF (fair: 5-10 mm; good: > 10 mm). Functional success was defined as a margin reflex distance of 2-5 mm without serious complications at 3 months postoperatively. Cosmetic success was defined as the achievement of ≤ 1 mm laterality of the upper eyelid height, ≤ 2 mm laterality of the pretarsal show, and eyelid contour symmetry at 3 months postoperatively. The functional success rates of the anterior and posterior groups were comparable for patients with good LF (78.9% vs 87.7%, p = 0.228), whereas it was better in the posterior group (85.7%) than the anterior group (64.1%) in the total group (p = 0.022) and in patients with fair LF (p = 0.031). The posterior group achieved better cosmetic success than the anterior group regarding upper eyelid height symmetry (p = 0.042) and pretarsal show (p = 0.012). No serious complications occurred during follow-up. The posterior approach achieved better functional and cosmetic outcomes than the anterior approach, indicating that the posterior approach is more useful in patients with aponeurotic blepharoptosis, particularly for those with only fair LF.


Hexamethylene bisacetamide inhibits malignant phenotype in T-ALL cell lines.
T acute lymphoblastic leukemia cell lines treated with hexamethylene bisacetamide (HMBA) undergo a delay in cell cycle progression and increase susceptibility to apoptosis, although they never overcome the differentiation block. In accordance with changes in cell cycle and apoptosis, transitory p53 pathway activation commonly occurs. Bcl-2 inhibition further favours the pro-apoptotic effect of HMBA. Notch1 expression is down regulated by reduction of its transcription level. Accordingly, Notch1 protein and transcriptional activity were affected. Even if HMBA generally reduces Notch1 level in T acute lymphoblastic leukemia (T-ALL) cell lines, this does not commonly influence the biological response; in fact all the analysed cell lines, except CEM cells, display no biological effect following DAPT-induced Notch inhibition.


Interleukin-4 and interleukin-5 are rarely co-expressed by human T cells.
Interleukin (IL)-4 and IL-5 are two cytokines which synergize in the induction of several biological effector functions. They are produced by mouse and human T helper 2 (Th2) and T helper 0 (Th0) cells. Little is known about the regulation of the two cytokines at the single-cell level. Here we show, using a flow cytometric intracellular staining technique, that IL-4 and IL-5 are predominantly produced by different human peripheral CD4+ and CD8+ T cells, whereas interferon (IFN)-gamma and IL-2 are produced by the same cells. In contrast, cloned human Th0 and Th2 cells were able to produce IL-4 and IL-5 simultaneously. The segregation of IL-4 and IL-5 in activated peripheral T cells was found within 72 h of activation upon anti-CD3 or phorbol ester + ionomycin stimulation. The kinetics of IL-4 and IL-5 production were different at the mRNA and the intra- and extracellular protein level, indicating that the cytokines are regulated differently. T cells from three patients with hyper-IgE syndrome did not display a substantial proportion of IL-4/IL-5 double-positive cells. However, simultaneous production could be induced in normal human T cells after prolonged stimulation with a minimum of two restimulation cycles. We conclude that the simultaneous production of IL-4 and IL-5 is a feature of repetitively activated human T cells.


An iterative phase correction program for nuclear magnetic resonance (NMR) spectra.
An iterative algorithm is given to correct for the zeroth and first order phase errors in NMR spectroscopy. A FORTRAN computer program is listed and two sample runs exemplified. No a priori knowledge of the existing phase errors is required. The parameters are optimised iteratively under the assumption that when the spectrum is correctly phased the ratio of the area above the spectrum to that below it is a maximum.


Endogenous bacterial endophthalmitis masquerading as an intraocular tumor.
A 40-year-old female patient referred for a possible intraocular tumor was found to have an endogenous bacterial endophthalmitis in her right eye. Fundus examination revealed an amelanotic dome shaped choroidal mass and an exudative retinal detachment. Enhanced Depth Imaging-Optical Coherence Tomography (EDI-OCT), fundus autofluorescence (FAF) and ultrasounds were suggestive of a possible choroidal melanoma. A multimodal imaging approach and a thorough anamnesis were instrumental in establishing the correct diagnosis.


Pd-catalyzed oxidative annulation of hydrazides with isocyanides: synthesis of 2-amino-1,3,4-oxadiazoles.
An efficient palladium-catalyzed oxidative annulation reaction was developed through sequential isocyanide insertions into N-H and O-H bonds of hydrazides, which provides an efficient access to valuable 2-amino-1,3,4-oxadiazoles and their derivatives.


Effects of corn grain processing and protein source on calf performance, rumen fermentation, and blood metabolites.
The objective of this study was to investigate the effects of the interaction between corn grain processing and protein source on feed intake, growth performance, rumen fermentation, and blood metabolites of dairy calves. Seventy-two 3-day-old Holstein calves with an initial weight of 39.1 ± 3.24 kg were randomly assigned (n = 12 calves (6 male and 6 female) per treatment) to a 2 × 3 factorial arrangement of treatments with the factors of physical form of the corn grain [coarsely ground (CG) and steam-flaked (SF)] and protein type [canola meal (CAN), canola meal + soybean meal (CASY), and soybean meal (SOY)] were assigned. The study showed a significant correlation between corn grain processing method and protein source on calf performance, including starter feed intake, total dry matter intake (DMI), body weight, average daily gain (ADG), and feed efficiency (FE). The CG-CAN and SF-SOY treatments resulted in the highest feed intake and DMI in the post-weaning and total period, respectively. Interestingly, corn processing did not affect feed intake, ADG, and FE, but the highest ADG was observed at SF-SOY and CG-CAN. In addition, the interaction between corn processing method and protein source improved FE in calves fed CG-CAN and SF-SOY during the preweaning period and throughout the period. Although skeletal growth parameters were unchanged, calves fed SOY and CASY had greater body length and withers height than calves fed CAN during the preweaning period. Rumen fermentation parameters were also not affected by the treatments, except that calves fed CAN had a higher molar proportion of acetate than calves fed SOY and CASY. Corn grain processing and protein source did not affect glucose, blood urea nitrogen (BUN), or β-hydroxybutyrate (BHB) concentrations, except for the highest blood glucose level observed in the CAN treatment and the highest BUN level observed in the preweaned calves fed SOY. However, a two-way interaction was observed for BHB concentration, suggesting that ground corn grain resulted in higher BHB concentration during the preweaning and postweaning periods than steam-flaked corn. In summary, it is recommended to incorporate canola meal with ground corn or soybean meal with steam-flaked corn in calf starters to enhance calf growth.


Diagnosis of pulmonary tuberculosis via identification of core genes and pathways utilizing blood transcriptional signatures: a multicohort analysis.
Blood transcriptomics can be used for confirmation of tuberculosis diagnosis or sputumless triage, and a comparison of their practical diagnostic accuracy is needed to assess their usefulness. In this study, we investigated potential biomarkers to improve our understanding of the pathogenesis of active pulmonary tuberculosis (PTB) using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed between PTB and healthy controls (HCs) based on two microarray datasets. Pathways and functional annotation of DEGs were identified and ten hub genes were selected. They were further analyzed and selected, then verified with an independent sample set. Finally, their diagnostic power was further evaluated between PTB and HCs or other diseases. 62 DEGs mostly related to type I IFN pathway, IFN-γ-mediated pathway, etc. in GO term and immune process, and especially RIG-I-like receptor pathway were acquired. Among them, OAS1, IFIT1 and IFIT3 were upregulated and were the main risk factors for predicting PTB, with adjusted risk ratios of 1.36, 3.10, and 1.32, respectively. These results further verified that peripheral blood mRNA expression levels of OAS1, IFIT1 and IFIT3 were significantly higher in PTB patients than HCs (all P < 0.01). The performance of a combination of these three genes (three-gene set) had exceeded that of all pairwise combinations of them in discriminating TB from HCs, with mean AUC reaching as high as 0.975 with a sensitivity of 94.4% and a specificity of 100%. The good discernibility capacity was evaluated d via 7 independent datasets with an AUC of 0.902, as well as mean sensitivity of 87.9% and mean specificity of 90.2%. In regards to discriminating PTB from other diseases (i.e., initially considered to be possible TB, but rejected in differential diagnosis), the three-gene set equally exhibited an overall strong ability to separate PTB from other diseases with an AUC of 0.999 (sensitivity: 99.0%; specificity: 100%) in the training set, and 0.974 with a sensitivity of 96.4% and a specificity of 98.6% in the test set. The described commonalities and unique signatures in the blood profiles of PTB and the other control samples have considerable implications for PTB biosignature design and future diagnosis, and provide insights into the biological processes underlying PTB.


Establishment of immortalized Schwann cells from Fabry mice and their low uptake of recombinant alpha-galactosidase.
Peripheral neuropathy is one of the important manifestations of Fabry disease. Enzyme replacement therapy with presently available recombinant alpha-galactosidases does not always improve the Fabry neuropathy. But the reason has not been determined yet. We established a Schwann cell line from Fabry mice, characterized it, and then examined the uptake of alpha-galactosidase by cells and its effect on the degradation of accumulated substrate. The cells exhibited a distinct Schwann cell morphology and biochemical phenotype (alpha-Galactosidase activity was deficient, and numerous cytoplasmic inclusion bodies were present in the cells). A recombinant alpha-galactosidase added to the culture medium was incorporated into the cultured Fabry Schwann cells dose dependently. But the increase in cell-associated enzyme activity was less than that in the cases of human and mouse Fabry fibroblasts. The administration of a high dose of the enzyme improved the pathological changes in cells, although a low dose of it did not. Cellular uptake of the enzyme was strongly inhibited in the presence of mannose 6-phosphate. This suggests that the enzyme is incorporated via cation-independent mannose 6-phosphate receptors in Schwann cells. The low expression of cation-independent mannose 6-phosphate receptors in Schwann cells must be one of the reasons their uptake of the present enzymes was low. The administration of a high dose of the enzyme or the development of an enzyme containing many mannose 6-phosphate residues is required to improve Fabry neuropathy.


Major mental illness and childbearing. A role for the consultation-liaison psychiatrist in obstetrics.
Considerable attention has been paid to psychiatric disorders arising in the postpartum period. However, there has been very little systematic study of mental illness during pregnancy. Although quantitatively not a major problem, it can pose several difficulties for mother and fetus. This article reviews the existing literature and along with illustrative cases discusses the management of mental illness related to pregnancy. The relationship between the consultation-liaison psychiatrist and the obstetrician-gynecologist in caring for such problems is emphasized.


A Retrospective Dosimetric Study of Radiotherapy Patients with Left-Sided Breast Cancer; Patient Selection Criteria for Deep Inspiration Breath Hold Technique.
Several studies have investigated cardiac dose reduction when utilizing the deep inspiration breath hold (DIBH) technique in patients undergoing radiotherapy for left-sided breast cancer. This paper aims to recommend potential selection criteria based on a retrospective single institute study of free breathing (FB) and DIBH computed tomography (CT) simulation planning scans. Dosimetric comparisons were performed retrospectively for 20 patients correlating the dose reduction and patient anatomical factors (anatomical variation of chest shape, chest wall separation, total lung volume (TLV) and others). Paired t-tests demonstrated significant cardiac dose reduction for most patients but not all. Minimal cardiac dose reduction was observed for three patients using their DIBH plan, with one patient receiving a higher dose. Linear regression analysis identified a positive correlation between the patient's TLV (on the FB CT simulation scan) and the magnitude of dosimetric benefit received (0.4045 R²). The TLV measured on a FB plan could potentially be utilised to predict cardiac exposure and assist with patient selection for DIBH. This is important in resource allocation, as DIBH may be unnecessarily recommended for some patients with little dosimetric benefit.


Correction: Four new species of Pristimantis Jiménez de la Espada, 1870 (Anura: Craugastoridae) in the eastern Amazon.
[This corrects the article DOI: 10.1371/journal.pone.0229971.].


[Solubilization Specificities Interferon beta-1b from Inclusion Bodies].
A new solubilization method of recombinant interferon beta-1b (IFNβ-1b) from the inclusion bodies was developed. This method allows to extract the target protein selectively in the solutions of different alcohols, such as ethanol, propanol and isopropanol. It was shown that the more effective IFNβ-1b solubilization was achieved in the 55% propanol solution. This method allowed to extract the target protein from inclusion bodies around 85-90%, and significantly reduced Escherichia coli content in the solubilizate, in comparison with standard methods.


Single and mixed effects of prenatal exposure to multiple bisphenols on hemoglobin levels and the risk of anemia in pregnant women.
Bisphenols have endocrine-disrupting effects, which may disrupt hemoglobin (Hb) homeostasis and lead to anemia. However, the effects of bisphenols on anemia remain unknown. Therefore, we assessed the effects of single- and multiple-exposure to bisphenols on Hb levels and anemia of pregnant women. The study involved 2035 pregnant women from Guangxi Zhuang Birth Cohort in China. Generalized linear regression, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were performed to examine the effects of serum bisphenols on Hb levels and the risk of anemia. After adjustment, elevated bisphenol A (BPA) levels were correlated with decreased Hb concentrations (β = -0.51; 95%CI: -0.92, -0.10) in the first trimester, and these correlations were more sensitive in mothers of males. Compared with the low-exposure group, bisphenol B (BPB) levels in the high-exposure group led to a 1.52 g/L (95%CI: -3.01, -0.03) decrease in Hb levels in the second trimester; tetrabromobisphenol A (TBBPA) levels in the high-exposure group led to a higher the risk of anemia in the third trimester (OR = 1.46; 95%CI: 1.07, 1.99); bisphenol F (BPF) in the high-exposure group led to lower Hb levels (β = -2.42; 95%CI:-4.69, -0.14) in mothers of male fetuses in the third trimester. Qgcomp showed that elevated levels of bisphenol mixture was correlated with (β = -1.42; 95%CI: -2.61, -0.24) decrease in Hb levels in the second trimester. PCA revealed a negative association between PC2 and Hb levels in the first trimester (β = -0.89; 95%CI: -1.61, -0.17). Similarly, a negative relationship was observed between PC1 and Hb levels in the third trimester among mothers with male fetuses (β = -1.00; 95%CI: -1.94, -0.06). Prenatal exposure to single and mixed bisphenols may decrease Hb levels and increase the risk of anemia during pregnancy, the associations may be greater in mothers with male fetuses than those with female fetuses.


Immunogenicity, reactogenicity and consistency of a new, inactivated hepatitis A vaccine--a randomized multicentre study with three consecutive vaccine lots.
We investigated immunogenicity, reactogenicity and consistency of three consecutive lots of an inactivated hepatitis A vaccine in 204 seronegative volunteers. Each volunteer received a total of three doses of vaccine (720 EIU) according to a 0, 1 month primary vaccination schedule with a booster dose given at month 6. Mild, moderate and mostly local side effects were reported in 49.7% after the first and in less than 30% after the third injection. Seroconversion rate after one vaccine dose was as high as 91%. All subjects but one had already seroconverted by 1 month after the second injection, corresponding to a seroconversion rate of 99%. The geometric mean titres (GMT) increased with each dose of vaccine administered. Our results show that this inactivated hepatitis A vaccine is highly immunogenic, safe and well tolerated. Furthermore, there were no significant differences between the three vaccine lots in respect to seroconversion rate, size of antibody titre or reactogenicity.


Interleukin-1 in the pathogenesis of and protection from inflammatory bowel disease.
Inflammatory bowel disease affects millions of people, some with fatal consequences. Little is known about the factors which contribute to its pathogenesis particularly regarding cytokine production and action. In this paper we summarize our recent findings using the rabbit model for immune complex-generated experimental colitis, a model which is similar to ulcerative colitis in humans. Recombinant human IL-1 was perfused through rabbit colons and we observed elevated levels of PGE2, TxB2 and 6-keto-PGF1 alpha, the stable metabolite of PGI2. Using radioimmunoassays specific for rabbit IL-1 alpha and IL-1 beta, we induced immune complex colitis and measured the generation of these IL-1's in various tissues. Markedly elevated levels of IL-1 were detected only in inflamed tissues. The levels of IL-1 correlated with the degree of inflammation as judged by a blinded assessment of pathological changes. Similar to other disease models in which small doses of the agonist can afford protection or result in a state of "desensitization" when administered prior to the onset of the disease, we accordingly injected rabbits with a single, small (300 ng/kg) dose of IL-1 and observed a significant reduction in the inflammatory index and necrosis of immune complex colitis. However, unlike other models of IL-1-induced protection, in this model cyclooxygenase products were required since we prevented the IL-1-induced protection with a single dose of ibuprofen given at the same time as the IL-1. This correlated with the reduction in IL-1-induced PGE2. These results demonstrate that IL-1 plays a key role in the pathogenesis of inflammatory bowel disease in the rabbit and that the protection afforded by a low dose of IL-1 24 hours before the onset of the colitis requires IL-1-induced cyclooxygenase products.


Radioprotective effect of a protein free parathyroid extract on the mitotic index of rat bone marrow cells.
The protective efficacy of an orally administered bovine protein-free parathyroid extract (PF-PTE) was studied on rat bone marrow cells in vivo with the mitotic index after 850 R irradiation. A remarkable decrease was found in the mitotic activity of bone marrow cells after irradiation in the non-protected animals. However, in the animals treated with PF-PTE after irradiation, a significantly smaller decrease and a faster recovery were found in the mitotic activity of the bone marrow cells.


Evaluating the impact of faculty development programme initiative: Are we really improving skills in MCQ writing?
A series of seven workshops were conducted in 2018, at the National University of Medical Sciences and its affiliated institutes, to evaluate the effectiveness of a three-hour workshop in improving faculty competence in developing high quality test items. Participants' satisfaction was evaluated with a post-workshop feedback questionnaire. A self-made structured questionnaire was required to be filled as a pre-test and post-test assessment. Paired t-test was applied and difference in mean scores of responses was evaluated. A total of 141 faculty members were trained. The training session led to high satisfaction in all elements of workshop, significant improvements in boosting confidence in item writing skills (p=0.001), recognising parts of MCQs (p=0.001), identifying item writing flaws (p=0.001), and levels of Millers pyramid and blooms taxonomy (p=0.001). Training sessions of short duration are effective in improving faculty competence in writing high quality test items, if hands-on experience is built-in and effective feedback is provided.


Loss of red cell alloantibodies over time.
The loss of red cell alloantibodies over time was analyzed in 160 patients with 209 antibodies retested 1 to 60 months after initial identification. The mean follow-up consisted of 3.6 specimens taken over 18 months. Twenty-nine percent of clinically significant and 72 percent of clinically insignificant antibodies were not detected on at least one follow-up screening. Anti-Jka and anti-C were lost in 59 and 45 percent of cases, respectively. No significant differences in overall antibody loss were found according to sex, diagnosis, or the presence of multiple antibodies. Patients under 20 years of age may be more likely to lose significant antibodies. Pretransfusion review of previous records is vital for the prevention of delayed hemolytic transfusion reactions, because of the high number of clinically significant antibodies that are undetected in subsequent routine screening.


Ecological factors affecting first-time mothers' satisfaction with Sanhujoriwons (postpartum care centres) from South Korea: a cross-sectional and correlational study.
In South Korea, commercial postpartum care centres, known as Sanhujoriwons, have emerged as important institutions aiding mothers' physical recovery after childbirth. Although previous studies have measured mothers' satisfaction level with Sanhujoriwons, this study applies Bronfenbrenner's ecological model to identify the factors influencing first-time mothers' satisfaction with Sanhujoriwons. This descriptive correlational study involved 212 first-time mothers admitted to Sanhujoriwons for two weeks with their new-borns (healthy babies weighing at least 2.5 kg) after giving birth after 37 weeks of pregnancy. Data were collected using a self-report questionnaire at five postpartum care centres in the metropolitan area of South Korea from October to December 2021, on the day of the mothers' discharge. This study considered ecological factors such as perceived health status, postpartum depression, childcare stress, maternal identity at the individual level; partnership with Sanhujoriwon staff at the microsystem level; and the Sanhujoriwons' education support system at the exo-system level. The data were analysed using descriptive statistics, t-test, one-way ANOVA, correlation analysis, and hierarchical regression analysis using the SPSS 25.0 Win program. The mean score of satisfaction with Sanhujoriwons was 59.67 ± 10.14 out of 70, indicating a high level of satisfaction. The hierarchical regression analysis showed that satisfaction with Sanhujoriwons was significantly affected by the perceived health status (β = 0.19, p < 0.001), partnership between mothers and the caregivers (β = 0.26, p < 0.001), and education support system of the Sanhujoriwons (β = 0.47, p < 0.001). The explanatory power of the model for these variables was 62.3%. Our results indicate that not only the mother's health status but also the educational support system of postpartum care centres and partnerships are important for improving first-time mothers' satisfaction with postpartum care centres. Thus, when developing an intervention program for postpartum care centres, practitioners should focus on developing various kinds of support and strategies to improve the physical health condition of mothers, build partnerships between mothers and care staff, and improve the quality of the educational support offered to mothers. Further studies to develop and test the effectiveness of such intervention programs are strongly suggested.


Conservative Treatment Using Chiropractic Care and Orofacial Myofunctional Therapy for Obstructive Sleep Apnea: A Case Report.
The purpose of this case study was to describe the use of chiropractic care in the treatment of obstructive sleep apnea (OSA). A 42-year-old man with obesity presented for chiropractic care. He had OSA and was seeking a way to reduce snoring. The patient had a previous diagnosis of OSA and had been using a continuous positive airway pressure machine for over 5 years. The patient was a mouth breather, exhibiting poor oral and spinal posture. The patient was treated for 90 days, which included chiropractic manipulation, orofacial myofunctional therapy exercises, nutritional modification, postural/ergonomic correction, and regular exercise. After a course of care, there was a drop in his apnea-hypopnea index from 55.4 events per hour to 3.4 events per hour. The patient lost 40 pounds, with an 8% reduction in body fat and an 8-point drop in his body mass index. This patient's sleep apnea and other health outcomes improved under a course of a combination of chiropractic adjustments, orofacial myofunctional therapy, nutritional modification, postural/ergonomic correction, and exercise.


Histone gene transcripts in the cleavage and mesenchyme blastula embryo of the sea urchin, S. purpuratus.
Two distinct populations of histone gene transcripts have been identified in the sea urchin embryo. Both late cleavage and mesenchyme blastula stages contain histone transcripts which hybridize to a full-length histone repeat recombinant DNA, pCO1. The histone RNAs of the two stages, however, are dissimilar in sequence. While the transcripts of the cleavage embryo form well matched hybrids with the plasmid DNA which are relatively resistant to RNAase, the hybrids containing the mesenchyme blastula transcripts melt some 10 degrees C lower and are twice as sensitive to RNAase. Hybridization of the two RNA samples to the Hha I fragments of the histone DNA, or to segments of the histone repeat subcloned in other plasmids, shows that many regions scattered along the repeat are complementary to widely diverged transcripts in the mesenchyme blastula RNA. The two RNA populations consist predominantly of polysomal RNA sequences and are most probably mRNAs for the five histones. The mesenchyme blastula RNA sequences in both S. purpuratus and L. pictus form hybrids with pCO1 DNA that are less stable than those containing L. pictus cleavage RNA, indicating the wide divergence of the two histone RNA populations. The bulk of the histone genes in S. purpuratus appear to be of the type coding for the early mRNAs. Only a small percentage of the several hundred gene copies are candidates for the type coding for the late mRNAs. The melting characteristics of the hybrids and the sensitivity of RNAase provide an assay for the late embryonic histone genes. Of the total RNA labeled during a 10 min pulse in the cleavage embryo, histone transcripts represent approximately 9.7 and 6.5% of the radioactivity in S. purpuratus and L. pictus, respectively. These values fall to 0.57 and 1.4%, respectively, at the mesenchyme blastula stage. Although histone genes are transcribed during these two periods, the type of gene which is active is switched at some point prior to the mesenchyme blastula stage.


Cigarette smoking, by accelerating the cell cycle, promotes the progression of non-small cell lung cancer through an HIF-1α-METTL3-m6A/CDK2AP2 axis.
Cigarette smoking killed about 8 million people every year and promoted non-small cell lung cancer (NSCLC). We investigated the molecular mechanism of smoking-promoted NSCLC progression. Relative to non-smokers, NSCLC patients who were smokers had a higher tumor malignancy. For NSCLC cells, cigarette smoke extract (CSE) increased levels of HIF-1α, METTL3, Cyclin E1, and CDK2 and promoted the G1/S transition, which promoted cell proliferation. Down-regulation HIF-1α or METTL3 reversed these effects. meRIP-seq and RNA-seq revealed the m6A modification in Cyclin Dependent Kinase 2 Associated Protein 2 (CDK2AP2) mRNA as the key downstream target. Further, for NSCLC cells exposed to CSE, HIF-1α activated METTL3 transcription. Xenografts in nude mice demonstrated that HIF-1α via METTL3 participated in tumor growth. In NSCLC tissues of smokers, protein levels of HIF-1α and METTL3 were higher, and levels of CDK2AP2 were lower. In conclusion, HIF-1α via METTL3 regulation of the m6A modification of CDK2AP2 mRNA drives smoking-induced progression of NSCLC through promoting cell proliferation. This is a previously unknown molecular mechanism for smoking-induced NSCLC progression. The results have potential value for treatment of NSCLC, especially for patients who smoke.


Base-Promoted Synthesis of N-Substituted 1,2,3-Triazoles via Enaminone-Azide Cycloaddition Involving Regitz Diazo Transfer.
The domino reactions between NH-based secondary enaminones and tosyl azide have been developed for the synthesis of various N-substituted 1,2,3-triazoles by employing t-BuONa as the base promoter. Through a key Regitz diazo-transfer process with tosyl azide, the reactions proceed efficiently at room temperature with good substrate tolerance.


Indications for the presence of two populations of serotonin-containing pinealocytes in the pineal complex of the golden hamster (Mesocricetus auratus). An immunohistochemical study.
Serotonin-like immunoreactivity was investigated in the pineal complex of the golden hamster by use of the indirect immunohistochemical technique. The superficial and deep portions of the pineal gland, and also the pineal stalk exhibited an intense cellular immunoreaction for serotonin. In addition, perivascular serotonin-immunoreactive nerve fibers were observed. Some serotonin-immunoreactive processes of the pinealocytes terminated on the surface of the ventricular lumen in the pineal and suprapineal recesses, indicating a receptive or secretory function of these cells. Several serotonin-immunoreactive processes connected the deep pineal with the habenular area. One week after bilateral removal of both superior cervical ganglia the serotonin immunoreaction of the entire pineal complex was greatly decreased. However, some cells in the pineal complex, of which several exhibited a neuron-like morphology, remained intensively stained after ganglionectomy. This indicates that the indoleamine content of some cells in the pineal complex of the golden hamster is independent of the sympathetic innervation.


A novel peptide specifically targeting the vasculature of orthotopic colorectal cancer for imaging detection and drug delivery.
Colorectal cancer (CRC) is the third most common malignancy and the fourth most frequent cause of cancer deaths worldwide. Ligand-mediated diagnosis and targeted therapy would have vital clinical applications in cancer treatment. In this study, an orthotopic model of colorectal cancer was established in mice. In vivo phage library selection was then utilized to isolate peptides specifically recognizing the vasculature of colorectal cancer tissues. A phage (termed TCP-1 phage) was isolated by this manner and it homed to the colorectal cancer tissues by 11- to 94-fold more than other organs. Chemical synthetic peptide (CTPSPFSHC, termed TCP-1) displayed by TCP-1 phage inhibited the homing ability of the phage to the tumor mass when co-injected intravenously with the TCP-1 phage into mice with colon cancer. Meanwhile, immunostaining analysis indicated that TCP-1 phage and peptide localized in the vasculature of the colorectal cancer tissue, but not of normal tissues. Moreover, TCP-1 peptide bound to blood vessels of surgical tissue samples of human colorectal cancer. After intravenous injection of FITC-labeled TCP-1 into the tumor-bearing mice for 20h, there was a strong fluorescent signal in the tumors but not other tissues when observed under blue light. In addition, TCP-1 conjugated with a pro-apoptotic peptide specifically induced apoptosis of tumor-associated blood vessels in vivo. The data define a novel peptide TCP-1 as an effective agent for imaging detection and drug delivery for colorectal cancer.


Effectiveness and Tolerability of Trimetazidine 80 Mg Once Daily in Patients with Stable Angina Uncontrolled with Bisoprolol-Based Therapy: The Modus Vivendi Observational Study.
Modus Vivendi was conducted in routine clinical practice to evaluate the effect of adding trimetazidine 80 mg once daily (TMZ 80 OD) to treat patients with persistent symptoms despite treatment with background antianginal therapies including maximally tolerated bisoprolol. This multicenter, prospective, observational, open-label, uncontrolled study recruited adult outpatients with a confirmed diagnosis of stable angina to whom physicians had decided to prescribe TMZ 80 OD. All patients were symptomatic despite treatment, including maximally tolerated doses of bisoprolol. Data on number of angina attacks, use of short-acting nitrates, and quality of life (QoL) were collected at baseline (V1) and at 1-month (V2) and 3-month (V2) follow-up visits. Two sub-analyses assessed efficacy in patients who remained on a stable bisoprolol dose throughout the study, and in patients in whom background antianginal therapy was known. A total of 1939 patients were recruited (57.2% women). The mean age was 65.6 ± 8.8 years; 73.8% had class II and 26.2% class III angina. At V1, the mean number of angina attacks per week was 6.2 ± 6.5 despite antianginal therapy including maximally tolerated bisoprolol dosage. Following the addition of TMZ 80 OD, this decreased to 3.4 ± 4.2 attacks per week at V2, and 1.6 ± 2.6 at V3 (P < 0.05 at V2 and V3), with concomitant reductions in short-acting nitrate use (P < 0.05). Significant improvements in QoL were observed throughout the study. Subgroup analyses showed that the addition of TMZ 80 OD to guideline-recommended antianginal therapy was associated with significant reductions in the mean number of weekly angina attacks and consumption of short-acting nitrates and improvements in QoL whether patients were treated with maximally tolerated bisoprolol and TMZ 80 OD alone, or maximally tolerated bisoprolol and TMZ 80 OD on top of other antianginal therapies. Treatment was well tolerated. The study findings support the addition of TMZ 80 OD to bisoprolol with or without other antianginal therapies for patients with persistent angina. This study was retrospectively registered under the number ISRCTN29992579.


Differences in possible TCA cycle replenishing pathways in purple non-sulfur bacteria possessing glyoxylate pathway.
Pathways replenishing tricarboxylic acid cycle were divided into four major groups based on metabolite serving as source for oxaloacetic acid or other tricarboxylic acid cycle component synthesis. Using this metabolic map, the analysis of genetic potential for functioning of tricarboxylic acid cycle replenishment pathways was carried out for seven strains of purple non-sulfur bacterium Rhodopseudomonas palustris. The results varied from strain to strain. Published microarray data for phototrophic acetate cultures of Rps. palustris CGA009 were analyzed to validate activity of the putative pathways. All the results were compared with the results for another purple non-sulfur bacterium, Rhodobacter capsulatus SB1003 and species-specific differences were clarified.


Mother's dietary diversity and association with stunting among children <2 years old in a low socio-economic environment: A case-control study in an urban care setting in Dhaka, Bangladesh.
Mothers are often responsible for preparing nutritious foods in their households. However, the quality of mother's diets is often neglected, which may affect both mother's and child's nutrition. Because no single food contains all necessary nutrients, diversity in dietary sources is needed to ensure a quality diet. We aimed to study the association between mother's dietary diversity and stunting in children <2 years attending Dhaka Hospital of icddr,b, a diarrhoeal disease hospital in Dhaka, Bangladesh. A case-control study (n = 296) was conducted from November 2016 to February 2017. Data were collected from mothers of stunted children <2 years (length-for-age z score [LAZ] < -2) as "cases" and nonstunted (LAZ ≥ -1) children <2 years as "controls." Mothers were asked to recall consumption of 10 defined food groups 24 hr prior to the interview as per Guidelines for Minimum Dietary Diversity for Women. Among the mothers of cases, 58% consumed <5 food groups during the last 24 hr, compared with 45% in control mothers (P = 0.03). Children whose mothers consumed <5 food groups were 1.7 times more likely to be stunted than children whose mothers consumed ≥5 food groups (P = 0.04). Intake of food groups such as pulses, dairy, eggs, and vitamin A rich fruit was higher in control mothers. Proportion of mother's illiteracy, short stature, monthly family income <BDT 11,480, absence of bank account, and poor sanitation was also found to be higher in stunted group. Further study particularly intervention or longitudinal study to see the causality of mother's dietary diversity with child stunting is recommended.


Aortic valve repair for congenital abnormalities of the aortic valve.
Due to shortcomings of any valve replacement, repairing and retaining the native valve may be beneficial for congenital aortic valve disease. Retrospective review of data and follow-up of aortic valve repair from a single institution. From 1993 to 2001, 56 patients underwent aortic valve repair [median age 13.4 years (range 1 day to 45 years)]. The predominant aortic valve lesion was mixed aortic stenosis/aortic insufficiency 25 (45%), aortic insufficiency 24 (43%) and aortic stenosis 7 (13%). Repair techniques included sub-commissural plication 36 (64%), commissurotomy 24 (43%), cusp plication 15 (27%), pericardial patch cusp extension 8 (14%) and resuspension of commissures 4 (7%). Most patients (88%) required a combination of techniques; 61% required additional procedures. Hospital survival was 55/56 [98%; (95% CI 91-100%)] no patient was discharged on anticoagulation for aortic valve pathology. Fifty-three patients [95%; (95% CI 85-98%)] remain alive after a median follow-up of 37 months; four survivors required aortic valve replacement and two required repeat aortic valve repair [84%; (95% CI 72-91%) reintervention-free survival]. (1) In this study, aortic valve repair for congenital abnormalities avoided reoperation in the majority of patients, avoided anticoagulation and retained growth potential of the valve. (2) Repeat aortic valve repair or replacement was used to treat subsequent valve deterioration.


Immunological Differences Between Immune-Rich Estrogen Receptor-Positive and Immune-Rich Triple-Negative Breast Cancers.
A subset of estrogen receptor-positive (ER-positive) breast cancer (BC) contains high levels of tumor-infiltrating lymphocytes (TILs), similar to triple-negative BC (TNBC). The majority of immuno-oncology trials target TNBCs because of the greater proportion of TIL-rich TNBCs. The extent to which the immune microenvironments of immune-rich ER-positive BC and TNBC differ is unknown. RNA sequencing data from The Cancer Genome Atlas (TCGA; n = 697 ER-positive BCs; n = 191 TNBCs) were used for discovery; microarray expression data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1,186 ER-positive BCs; n = 297 TNBCs) was used for validation. Patients in the top 25th percentile of a previously published total TIL metagene score distribution were considered immune rich. We compared expression of immune cell markers, immune function metagenes, and immuno-oncology therapeutic targets among immune-rich subtypes. Relative fractions of resting mast cells (TCGA P adj = .009; METABRIC P adj = 4.09E-15), CD8+ T cells (TCGA P adj = .015; METABRIC P adj = 0.390), and M2-like macrophages (TCGA P adj= 4.68E-05; METABRIC P adj = .435) were higher in immune-rich ER-positive BCs, but M0-like macrophages (TCGA P adj = 0.015; METABRIC P adj = .004) and M1-like macrophages (TCGA P adj = 9.39E-08; METABRIC P adj = 6.24E-11) were higher in immune-rich TNBCs. Ninety-one immune-related genes (eg, CXCL14, CSF3R, TGF-B3, LRRC32/GARP, TGFB-R2) and a transforming growth factor β (TGF-β) response metagene were significantly overexpressed in immune-rich ER-positive BCs, whereas 41 immune-related genes (eg, IFNG, PD-L1, CTLA4, MAGEA4) were overexpressed in immune-rich TNBCs in both discovery and validation data sets. TGF-β pathway member genes correlated negatively with expression of immune activation markers (IFNG, granzyme-B, perforin) and positively with M2-like macrophages (IL4, IL10, and MMP9) and regulatory T-cell (FOXP3) markers in both subtypes. Different immunotherapy strategies may be optimal in immune-rich ER-positive BC and TNBC. Drugs targeting the TGF-β pathway and M2-like macrophages are promising strategies in immune-rich ER-positive BCs to augment antitumor immunity.


Supramolecular aggregates formed by sulfadiazine and sulfisomidine inclusion complexes with α- and β-cyclodextrins.
Sulfadiazine (SDA) and sulfisomidine (SFM) inclusion complexes with two cyclodextrins (α-CD and β-CD) are studied in aqueous as well as in solid state. The inclusion complexes are characterized by UV-visible, fluorescence, time correlated single photon counting, FTIR, DSC, PXRD and (1)H NMR techniques. The self assembled SDA/CD and SFM/CD inclusion complexes form different types of nano and microstructures. The self assembled nanoparticle morphologies are studied using SEM and TEM techniques. SDA/α-CD complex is formed hierarchal morphology, SDA/β-CD and SFM/β-CD complexes form the nanosheet self assembly. However, SFM/α-CD complex forms nanoporous sheet self assembly. van der Waals, hydrophobic and hydrogen bonding interaction play a vital role in the self assembling process.


System design of a text messaging program to support the mental health needs of non-treatment seeking young adults.
Young adults (ages 18-25) experience the highest levels of mental health problems of any adult age group, but have the lowest mental health treatment rates. Text messages are the most used feature on the mobile phone and provide an opportunity to reach non-treatment engaged users throughout the day in a conversational manner. We present the design of an automated text message-based intervention for symptom self-management. The intervention comprises: (1) psychological strategies (i.e., types of evidence-based techniques leveraged to achieve symptom reduction) and (2) interaction types or the form that intervention content takes as it is delivered to and elicited from users.


Enhancement and inhibition of DNA transcriptional activity by spermine: a marked difference between linear and circular templates.
We compared the transcriptional activities of the circular and linear forms of short (4kbp) and giant (106kbp) DNA molecules in the presence of a polyamine, spermine (4+). With an increase in the spermine concentration, transcriptional activity was enhanced, followed by an inhibitory effect, and complete inhibition was observed in the sole case of long, linear templates. A difference between the transcriptional properties of circular and linear conformations is found for giant DNA molecules. These results are discussed in relation to DNA conformational transitions.


Identification of a novel therapeutic target for lung cancer: Mitochondrial ribosome protein L9.
Lung cancer has a high fatality rate and incidence rate. At present, the initial and progress mechanism of lung cancer has not been completely elucidated and new therapeutic targets still need to be developed. In this study, the screening process was based on lung cancer expression profile data and survival analysis. Mitochondrial ribosome protein L9 (MRPL9) was upregulated in lung cancer tissues and related to the poor overall survival rate and recurrence-free survival rate of lung cancer patients. Knockdown of MRPL9 inhibited the proliferation, sphere-formation, and migration ability of lung cancer cells. MRPL9 was associated with the c-MYC signaling pathway, and lung cancer patients with high expression of both MRPL9 and MYC had a poor prognosis. Furthermore, c-MYC was associated with the epithelial-mesenchymal transition (EMT) regulatory protein zinc finger E-box binding homeobox 1 (ZEB1) by bioinformatics analysis. The relationship between ZEB1 and c-MYC was further confirmed by interfering with c-MYC expression. MRPL9 is a potential therapeutic target for lung cancer and exerts its biological functions by affecting the transcription factor c-MYC thereby regulating the EMT regulator ZEB1.


Ethnobotanical study on medicinal plants used by Maonan people in China.
This paper is based on an ethnobotanical investigation that focused on the traditional medicinal plants used by local Maonan people to treat human diseases in Maonan concentration regions. The Maonan people have relied on traditional medicine since ancient times, especially medicinal plants. The aim of this study is to document medicinal plants used by the Maonans and to report the status of medicinal plants and associated traditional knowledge. Ethnobotanical data were collected from June 2012 to September 2014 in Huanjiang Maonan Autonomous County, northern Guangxi, southwest China. In total, 118 knowledgeable informants were interviewed. Following statistically sampling method, eighteen villages from 5 townships were selected to conduct field investigations. Information was collected through the approache of participatory observation, semi-structured interviews, ranking exercises, key informant interviews, focus group discussions, and participatory rural appraisals. A total of 368 medicinal plant species were investigated and documented together with their medicinal uses by the Maonans, most of which were obtained from the wild ecosystems. The plants were used to treat 95 human diseases. Grinding was a widely used method to prepare traditional herbal medicines. There were significant relationships between gender and age, and between gender and informants' knowledge of medicinal plant use. Deforestation for agricultural purposes was identified as the most destructive factor of medicinal plants, followed by drought and over-harvest. The species diversity of medicinal plants used by the Maonans in the study area was very rich. Medicinal plants played a significant role in healing various human disorders in the Maonan communities. However, the conflicts between traditional inheriting system and recent socio-economic changes (and other factors) resulted in the reduction or loss of both medicinal plants and associated indigenous knowledge. Thus, conservation efforts and policies, and innovation of inheriting system are necessary for protecting the medicinal plants and associated indigenous knowledge. Awareness is also needed to be raised among local Maonans focusing on sustainable utilization and management of both medicinal plants and traditional knowledge.


Virtual screening and drug repurposing experiments to identify potential novel selective MAO-B inhibitors for Parkinson's disease treatment.
The main study's purpose is to detect novel natural products (NPs) that are potentially selective MAO-B inhibitors and, additionally, to computationally reposition the marketed drugs with a new therapeutic role for Parkinson's disease. To reach the goals, 3D similarity search, docking, ADMETox, and drug repurposing approaches were employed. Thus, an unbiased benchmarking dataset was built including selective and nonselective inhibitors for MAO-B compliant with both ligand- and structure-based virtual screening approaches. A retrospective and prospective mining scenario was applied to SPECS NP and DrugBank databases to detect novel scaffolds with potential benefits for Parkinson's disease patients. Out of the three best selected natural products, cardamomin showed excellently predicted drug-like properties, superior pharmacological profile, and specific interactions with MAO-B active site, indicating a potential selectivity over MAO-B. Two marketed drugs, fenamisal and monobenzone, were proposed as promising candidates repurposed for Parkinson's disease. The application of shape, physicochemical, and electrostatic similarity searches protocol emerged as a plausible solution to explore MAO-B inhibitors selectivity. This protocol might serve as a rewarding tool in early drug discovery and can be extended to other protein targets.


{N'-[(E)-1-(5-Chloro-2-oxidophen-yl)ethyl-idene]-4-meth-oxy-benzohydrazidato-κ3 O,N',O'}(1H-imidazole-κN 3)nickel(II).
In the title complex, [Ni(C16H13ClN2O3)(C3H4N2)], the NiII ion is coordinated by two O atoms and one N atom derived from the dianionic N'-[(1E)-1-(5-chloro-2-hy-droxy-phen-yl)ethyl-idene]-4-meth-oxy-benzohydrazide ligand and one N atom from the imidazole mol-ecule. The N2O2 donor set defines an approximate square-planar geometry. The dihedral angles between the imidazole ring and the fused six-membered and meth-oxy-benzene rings are 17.78 (14) and 13.23 (16)°, respectively; the dihedral angle between the C6 rings is 6.63 (12)°. The most prominent feature of the mol-ecular packing is the formation of 41-helical chains (along the c axis) mediated by imidazole-N-H⋯O(phenoxide) hydrogen bonding; these are linked by methyl-C-H⋯Cl inter-actions.


Tyrosine hydroxylase expression in CD4(+) T cells is associated with joint inflammatory alleviation in collagen type II-induced arthritis.
We have recently reported that CD4(+) T cells synthesize and secrete catecholamines that facilitate a shift of T helper 1 (Th1)/Th2 balance toward Th2 polarization. In this study, we used an animal model of human rheumatoid arthritis, collagen type II-induced arthritis (CIA), to explore relationship between catecholamine production in CD4(+) T cells and Th1-/Th2-mediated joint inflammation. Histopathological observation of ankle joints of CIA mice displayed an evident inflammatory change on day 35 and a major damage to bones on day 55 post-immunization. Expression of Th1-specific transcription factor, T-bet, and cytokines, IL-2 and IFN-γ, and Th2-specific transcription factor, GATA-3, and cytokines, IL-4 and IL-10, was all upregulated on days 35 and 55 post-immunization, but the elevated Th1 response tended to decrease and the enhanced Th2 response tended to increase with the CIA progression. Expression of tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of catecholamines, dramatically increased in ankle joints of CIA mice, although this increase was reduced on day 55 relative to that on day 35 post-immunization. In synovial tissue of CIA ankle joints but not normal joints, CD4-, T-bet-, GATA-3-, and TH-immunoreactive cells were found. Importantly, co-expressed cells with CD4 and TH, T-bet and TH, and GATA-3 and TH were observed in synovial tissue of CIA ankle joints. These results suggest that an increase in catecholamine production occurs in inflamed joints of CIA. The catecholamines are, at least in part, from Th1 and Th2 cells, and they may be related to joint inflammatory alleviation in CIA progression.


Neurology of the cryopyrin-associated periodic fever syndrome.
The cryopyrin-associated periodic fever syndrome (CAPS) is an autosomal dominant autoinflammatory disorder caused by mutations in the NLRP3 gene and is typified by recurrent episodes of systemic inflammation resulting in fever, urticarial rash and arthralgia. In addition to these systemic aspects, CAPS has multiple neurological manifestations. The largest case series to date is presented focusing on the neurological features of this disorder. The case histories of a cohort of 38 UK patients with genetically proven CAPS who were treated with interleukin 1β (IL-1β) inhibition as part of a national treatment programme and underwent detailed neurological assessment were reviewed. Across the entire disease course neurological manifestations were present in 95% of patients; 84% had some form of headache; 66% sensorineural hearing loss; 60% myalgia; 34% papilloedema and 26% optic atrophy. Patients with the T348M mutation tended to have a more severe neurological phenotype with an earlier age of onset. Four patients had cerebrospinal fluid examination, three of whom had evidence of aseptic meningitis. There was a marked response to IL-1β inhibition, which has revolutionized management of these patients (29/32 patients with headache responding). Neurological symptoms are extremely common in CAPS and these results highlight the importance of increasing awareness amongst neurologists, particularly as highly effective therapies are available.


O-antigenic corss-reactivity in Fusobacterium nucleatum: chemotype V lipopolysaccharides.
nucleatum lipopolysaccharides (LPS) of chemotype V were examined for cross-reactivity by indirect haemagglutination in non-absorbed and absorbed antisera. At least three O-antigenic specificities were detected in LPS of five strains. There was a slight cross-reactivity between the LPS of chemotype V and those of chemotype II.


A functional polymorphism in the promoter region of the IL1B gene is associated with risk of multiple myeloma.
The cytokine interleukin-1β (IL1B) is important for anti-tumour immune response. Genetic variation may modify the expression of IL1B and thereby influence the risk of disease. We investigated genetic variations with functional importance in the IL1B and NFKB1 genes in 348 population-based samples of multiple myeloma (MM) and a random sample of 1700 individuals. Carriers of the variant T-allele IL1B C-3737T and carriers of the TGT haplotype were at lower risk of MM [relative risk (RR) 0·58 (95% confidence interval (CI) = 0·41-0·84) and RR 0·59 (95%CI 0·40-0·85), respectively]. No association with risk of MM was found for the NFKB1- 94 ins/del polymorphism.


Mean 14-year Outcomes of Hybrid Total Hip Arthroplasty Using Bulk Femoral Head Autografts for Acetabular Reconstruction.
We aimed to evaluate the mean 14-year outcomes of hybrid total hip arthroplasty (THA) with cementless acetabular cups using bulk femoral head autografts in acetabular reconstruction and specify the radiological characteristics of cementless acetabular cups using this technique. This retrospective study included 98 patients (123 hips) who underwent hybrid THA with a cementless acetabular cup using bulk femoral head autografts for bone deficiency in acetabular dysplasia and who were followed-up for a mean of 14 years (range, 10 to 19.6). The percentage of bone coverage index (BCI) and cup center-edge (CE) angles were evaluation radiologically of acetabular host bone coverage. The survival rate of the cementless acetabular cup and autograft bone ingrowth were assessed. The survival rate with all revisions of cementless acetabular cups was 97.1% (95% confidence interval: 91.2 to 99.1). The autograft bone was remodeled or reoriented in all cases except in 2 hips where the bulk femoral head autograft collapsed. Radiological evaluation revealed a mean cup CE angle of -17.8° (range, -52 to -7°) and a BCI of 44.4% (range, 10 to 75.4%). Cementless acetabular cups using bulk femoral head autografts for bone deficiency of the acetabular roof remained stable even if the average BCI was 44.4% and the average cup CE angle was -17.8°. Cementless acetabular cups using these techniques showed good 10-year to 19.6-year outcomes and viabilities of graft bones.


Allergy Safety Events in Health Care: Development and Application of a Classification Schema Based on Retrospective Review.
Allergy safety requires understanding the operational processes that expose patients to their known allergens, including how and when such processes fail. To improve health care safety for patients with allergies, we developed and assessed an allergy safety event classification schema to describe failures resulting in allergy-related safety events. Using keyword searches followed by expert manual review of 299,031 voluntarily-filed safety event reports at 2 large academic medical centers, we identified and classified allergy-related safety events from 5 years of safety reports. We used driver diagrams to elucidate root causes for commonly observed allergy safety events in health care settings. From 299,031 safety reports, 1922 (0.6%) were extracted with keywords and 744 (0.2%) were manually confirmed as allergy-related safety events. Safety failures were due to incomplete/inaccurate electronic health record documentation (n = 375, 50.4%), human factors (n = 175, 23.5%), allergy alert limitation and/or malfunction (n = 127, 17.1%), data exchange and interoperability failures (n = 92, 12.4%), and electronic health record system default options (n = 30, 4.0%). Safety failures resulted in known allergen exposures to drugs (n = 537), including heparin (n = 27) and topical anesthetics such as lidocaine (n = 8); latex (n = 114); food allergens (n = 73); and adhesive (n = 23). We identified 744 allergy-related safety events to inform a novel safety failure classification schema as an important step toward a safer health care environment for patients with allergies. Improved systems are required to address safety issues with certain food and drug allergens.


Measurement of blood pressure in unrestrained rats.
A method that allows continuous recroding of blood pressure in rats and other small animals is described. Surgical, recording, calibration, and catheter construction techniques are explained. The techniques allow blood pressure recording from free-roving rats for relatively long periods of time but do not require complicated maintenance procedures to insure catheter patency.


Comparison of crenarchaeal consortia inhabiting the rhizosphere of diverse terrestrial plants with those in bulk soil in native environments.
To explore whether the crenarchaeal consortium found in the rhizosphere is distinct from the assemblage of crenarchaeotes inhabiting bulk soil, PCR-single-stranded-conformation polymorphism (PCR-SSCP) profiles were generated for 76 plant samples collected from native environments. Divergent terrestrial plant groups including bryophytes (mosses), lycopods (club mosses), pteridophytes (ferns), gymnosperms (conifers), and angiosperms (seed plants) were collected for this study. Statistical analysis revealed significant differences between rhizosphere and bulk soil PCR-SSCP profiles (Hotelling paired T(2) test, P < 0.0001), suggesting that a distinct crenarchaeal consortium is associated with plants. In general, phylotype richness increased in the rhizosphere compared to the corresponding bulk soil, although the range of this increase was variable. Examples of a major change in rhizosphere (versus bulk soil) PCR-SSCP profiles were detected for all plant groups, suggesting that crenarchaeotes form associations with phylogenetically diverse plants in native environments. In addition, examples of minor to no detectable difference were found for all terrestrial plant groups, suggesting that crenarchaeal associations with plants are mediated by environmental conditions.


Prevalence and Prognostic Implications of Increased Apical-to-Basal Strain Ratio in Patients with Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.
The aim of this study was to investigate the preoperative prevalence, relation to symptoms, and prognostic implications of elevated left ventricular (LV) apical-to-basal strain ratio (ABr) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement. A total of 499 contemporary consecutive patients with AS treated with transcatheter aortic valve replacement were retrospectively included. Patients were included if they underwent preoperative echocardiography with adequate image quality for assessment of LV global longitudinal strain. Baseline clinical and echocardiographic data were collected and analyzed in ABr subgroups. From two-dimensional echocardiographic apical images, ABr was calculated as mean longitudinal strain of the five LV apical segments divided by the mean of the six basal segments. Median follow-up time was 743 days. Mean age was 79.8 ± 7 years. The prevalence of severely increased ABr ≥4 was 16% (n = 78). Patients with ABr ≥4 had higher preoperative New York Heart Association functional class; 77% of those with ABr ≥4 were in New York Heart Association functional class III or IV compared with 59% of those with ABr of 0 to 1.9 (P < .01). Median preoperative N-terminal pro-brain natriuretic peptide level in patients with ABr ≥4 was 1,781 pmol/L, compared with 876 pmol/L in those with ABr of 0 to 1.9 (P = .003). N-terminal pro-brain natriuretic peptide levels at 3-month follow-up remained considerably elevated in patients with ABr ≥4 (the median in patients with ABr ≥4 was 1,262 pmol/L vs 645 pmol/L in those with ABr of 0 to 1.9, P < .01). AS severity was comparable across ABr subgroup levels. Overall, increased ABr ≥4 was associated with poor survival, as overall 3-year survival was 67% among patients with ABr ≥4 compared with 83% in those with ABr of 2 to 3.9 and 86% in those with ABr of 0 to 1.9 (P = .04). Among patients with increased ABr ≥4, pre- and postoperative New York Heart Association functional class, serum N-terminal pro-brain natriuretic peptide level, and mortality were significantly increased, and ABr may thus serve as a new echocardiographic marker of high mortality risk among patients with AS treated with transcatheter aortic valve replacement.


Corrosive esophageal injuries. II. An investigation of treatment methods and histochemical analysis of esophageal strictures in a new animal model.
The unique clinical experience of having to treat simultaneously nine young adults who had ingested the same corrosive substance prompted this investigation in rabbits of the pathophysiology of corrosive esophageal injury and of drugs that might prevent formation of stricture. Treatment of experimental corrosive esophageal injury in these animals consisted of antegrade dilatation and administration of two lathyrogenic drugs, colchicine and penicillamine, in various combinations. This study demonstrated that the rabbit can serve as a suitable animal model for study of corrosive injury of the esophagus, that penicillamine given alone affected wound healing with less severe stricture after such an injury, and that colchicine was associated with delayed wound healing and severe stricture.


Critically-ill patients receiving total parenteral nutrition show altered amikacin pharmacokinetics.
The purpose of this clinical study was to characterise the kinetic behavior of amikacin in the parenterally-fed critically-ill adult patient. 22 critically-ill adult patients treated with amikacin (15.5 +/- 7.9 mg/kg/day) for severe gram-negative infections were enrolled into a non-randomised control trial. Malnourished patients were administered total parenteral nutrition (TPN, n = 11), while well-nourished patients received fluid therapy (FT, n = 11). Amikacin pharmacokinetic parameters were estimated by non-linear regression analysis, assuming a one-compartment model and central first-order elimination. Patients receiving TPN showed an expanded amikacin distribution volume (0.403 +/- 0.0961/kg vs. FT 0.298 +/- 0.083 l/kg, p < 0.05), and a tendency towards increased total body clearance (0.089 +/- 0.029 l/kg/h vs. FT 0.069 +/- 0.0201/kg/h, p = 0.09). TPN produced lower peak concentrations (19.3 +/- 3.1 mcg/ml vs. 23.1 +/- 3.5 mcg/ml, p < 0.05), but had no significant influence on trough concentrations (p = 0.56). Patients on TPN also showed increased body temperature (p < 0.05) and fluid intake (p < 0.05), and decreased hematocrit (p < 0.05). Stress, malnutrition, parenteral nutrition itself, fluid and osmotic overload, and fever often occur concurrently in parenterally-fed patients and appear to produce lower amikacin serum levels. Consequently, critically-ill patients receiving TPN need higher amikacin doses and individualised treatment by monitoring serum concentrations, to ensure optimal therapeutic response.


Microanatomy and behaviour of the date mussel's adductor and foot muscles after chronic exposure to bisphenol A, with inhibition of ATPase enzyme activities and DNA damage.
Environmental contaminants with estrogenic activity have recently received attention due to the potential harm they could cause to humans and wildlife. To assess the toxic effects of bisphenol A (BPA) on marine mussels, Lithophaga lithophaga were exposed for 4 weeks to 0, 0.25, 1, 2, and 5 μg/L BPA. Aside from DNA damage, a behavioural study including valve closure duration (VCD), valve opening duration (VOD), levels of malondialdehyde (MDA), and total glutathione, as well as superoxide dismutase (SOD) and ATPase activities in adductor muscle extracts, and histopathological examination of the adductor muscle and foot were performed. The behavioural response was marked by an increase in the percentage of VCD and a decrease in the percentage of VOD during 8 h. Furthermore, BPA treatments resulted in a significant concentration-dependent increase in muscle MDA and total glutathione levels. However, when compared to controls, SOD and ATPase activity was significantly reduced in the adductor muscles of BPA treatments. Histological examination of the adductor and foot muscles revealed qualitatively distinct abnormalities. DNA damage was strongly induced in a concentration-dependent manner. Our findings suggested that BPA exposure altered detoxification, antioxidation, ATPase activity, histopathological characteristics, and DNA damage, which resulted in behavioural changes. The multi-biomarker approach used suggests that clear relationships exist between genotoxic and higher-level effects in some cases, which could be used as an integrated tool to evaluate various long-term toxic effects of BPA.


The dinoflagellate Noctiluca scintillans in China: A review of its distribution and role in harmful algal blooms.
The dinoflagellate Noctiluca scintillans is often reported as a worldwide HAB species and caused severe financial losses to local aquaculture. In this review, we summarized the temporal and geographical distribution of its HABs in China, as well as its position in the plankton structure. Increasing N. scintillans HABs, both frequency and coverage, have broken out in almost all Chinese coastal regions mainly from April to June, with short-term and small coverage blooms as the primary type. The HAB period seems to shift with age and latitude. Recently, increasing abundance and dominance of N. scintillans were also reported in plankton communities in Chinese coastal waters, with multiple environmental factors related. In particular, trophic relationships may play an important role in its dominance and outbreaks of HABs. However, how N. scintillans became a dominant species in China and the mechanisms responsible for its HABs require further study.


Cytogenetic and DNA-flow cytometric studies of separated blasts.
With Percoll density gradients, blasts from peripheral blood and bone marrow could be separated with a significant enrichment, and very often with a high degree of purity. This allowed a study of selected cases, where the separated sample exhibited chromosome abnormalities and/or an abnormal DNA content distribution (as measured by DNA-flow cytometry). The anomalies were shown to be associated with the separated blast fraction.


Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats.
Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.).


Palliative cancer patients and their families on the Internet: motivation and impact.
Increasingly, palliative patients and their families are going online. A series of cases are presented to explore the reasons they go online and the effects of their online activity, both harmful and beneficial. This paper highlights the need to take this growing phenomenon and its effects on patient care seriously, and identifies key areas that need to be explored further.


White matter brain structure predicts language performance and learning success.
Individual differences in the ability to process language have long been discussed. Much of the neural basis of these, however, is yet unknown. Here we investigated the relationship between long-range white matter connectivity of the brain, as revealed by diffusion tractography, and the ability to process syntactically complex sentences in the participants' native language as well as the improvement thereof by multiday training. We identified specific network motifs by singular value decomposition that indeed related white matter structural connectivity to individual language processing performance. First, for two such motifs, one in the left and one in the right hemisphere, their individual prevalence significantly predicted the individual language performance, suggesting an anatomical predisposition for the individual ability to process syntactically complex sentences. Both motifs comprise a number of cortical regions, but seem to be dominated by areas known for the involvement in working memory rather than the classical language network itself. Second, we identified another left hemispheric network motif, whose change of prevalence over the training period significantly correlated with the individual change in performance, thus reflecting training induced white matter plasticity. This motif comprises diverse cortical areas including regions known for their involvement in language processing, working memory and motor functions. The present findings suggest that individual differences in language processing and learning can be explained, in part, by individual differences in the brain's white matter structure. Brain structure may be a crucial factor to be considered when discussing variations in human cognitive performance, more generally.


Corrigendum to 'Cave Diving for a Diagnosis: Disseminated Histoplasmosis in the Immunocompromised' [IDCases 12 (2018) 92-94].
[This corrects the article DOI: 10.1016/j.idcr.2018.03.020.].


Bronchovascular fistula formation: a rare airway complication after lung transplantation.
Although most late complications after lung transplantation are related to chronic rejection, airway anastomotic disease cannot be overlooked as a substantial contributor to morbidity and mortality. A rare, but nearly universally fatal example of anastomotic disease is fistula formation with the vascular system. Reports of fistula formation between the respiratory tree and the vascular system are not uncommon, but in the lung transplant population, specifically, only scattered case reports exist. Here we describe 3 cases of bronchovascular fistula formation after lung transplantation, with a review of the literature and exploration of possible risk factors, diagnostic techniques, and treatment modalities.