Predicting visual outcomes for macular disease using optical coherence tomography.
In recent years, the management of macular disease has undergone radical changes, in part because of new therapeutic approaches, but also due to the introduction of a new imaging modality - optical coherence tomography (OCT). The application of OCT imaging has clarified many aspects of chorioretinal disease pathophysiology and elucidated many hitherto unrecognized disease characteristics. From an early stage in its development, OCT has also been revolutionary in attempting to extract clinically useful measurements from image data in an automated fashion. As a result, OCT-derived measurements of retinal thickness have been rapidly embraced in clinical and research settings. However, as knowledge of OCT image analysis has developed, it has become increasingly clear that even accurate measurements of retinal thickness may fail to predict visual outcomes for many diseases. As a result, the focus of much current clinical imaging research is on the identification of other OCT-derived anatomic biomarkers predictive of visual outcomes - such biomarkers could serve as surrogate endpoints in clinical trials and provide prognostic information in clinical practice. In this review, we begin by highlighting the importance of accurate visual function assessment and describing the fundamentals of OCT image evaluation, before describing the current state-of-the-art with regard to predicting visual outcomes, for a variety of macular diseases, using OCT.


Legionella bozemanii pneumonia in an immunocompromised patient.
Legionella bozemanii, a rare cause of pneumonia, has a predilection for patients with impaired cellular immunity and underlying disease. We report the 12th culture-proven case of this infection, acquired in the community by a patient undergoing chemotherapy for chronic lymphocytic leukemia. The diagnosis was established when studies of bronchoalveolar lavage fluid produced a positive reaction with species-specific fluorescent antibody and growth on selective culture media. Although erythromycin was administered within 48 hours after the initial examination, the clinical condition did not improve substantially until rifampin was added to the antimicrobial regimen.


Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions.
To investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender. A pooled dataset from eight randomized, controlled trials of patients with major depressive disorder (MDD) was reanalyzed to compare remission rates following therapy with venlafaxine (n = 851), one of several selective serotonin reuptake inhibitors (SSRIs) (n = 748), or placebo (n = 446). Remission was defined as a final Hamilton Rating Scale for Depression (HAM-D) score < or =7. Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment, sex, and age (younger: <50; older: > or =50). Among older women, the impact of hormone replacement therapy (HRT) on remission rates also was examined. Remission rates on venlafaxine therapy were not affected by age, sex, or HRT use. Among women, but not men, there was a significant interaction reflecting poorer SSRI response in the older age group (Wald chi-square = 4.21, df = 1, p = 0.04); HRT appeared to eliminate this difference. Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women (6%-9%), the difference among older women not taking HRT was 23%. These findings provide further evidence that age, gender, and HRT moderate response to antidepressant medications.


Can dental registrants use the Index of Orthodontic Treatment Need accurately? Part 2. Factors influencing knowledge of IOTN among dental registrants.
Aim To understand the frequency of use and training of IOTN amongst dental registrants working in primary and secondary care. To ascertain which factors influence 'accuracy' of IOTN amongst dental registrants.Method Participants were asked to complete a short questionnaire at the same time as scoring the IOTN for 14 cases. The questionnaire was developed by the authors of this study to understand registrants' place of work, frequency of use of IOTN and training undertaken in IOTN. Multiple linear regression analysis was used to reveal which predictor factors best described a registrant's knowledge of IOTN.Results The mean kappa scores were the highest for participants working in secondary care (K = 0.68) when compared to those solely working in primary care. The SO and GDP groups were found to be the groups with the largest proportion of participants using IOTN on a daily basis. Only the participants that used the IOTN everyday achieved an acceptable mean DHC K >0.60. There is an increasing trend of mean DHC kappa scores evident with increasing frequency of use of IOTN. All participants had received training in the use of IOTN with the majority (n = 181/229) having their last episode of training within the last five years. The majority of the training received in IOTN was classified as being verifiable (n = 154/229) with the remainder classifying their training as non-verifiable. Two predictor variables were found to have a significant influence on the DHC kappa scores, which included registrant group and place of work. Only one of the predictor variables had a statistically significant influence on the AC kappa scores, which was the type of CPD, with participants who had received non-verifiable CPD having a lower kappa scores.Conclusion Place of work, frequency of use of IOTN and registrant group were the main factors which were found to influence accuracy of use of IOTN. This study has highlighted a need for greater support in terms of resources, training and tools to help dental registrants use the IOTN more accurately to an acceptable level.


Depletion of membrane skeleton in red blood cell vesicles.
A possible physical interpretation of the partial detachment of the membrane skeleton in the budding region of the cell membrane and consequent depletion of the membrane skeleton in red blood cell vesicles is given. The red blood cell membrane is considered to consist of the bilayer part and the membrane skeleton. The skeleton is, under normal conditions, bound to the bilayer over its whole area. It is shown that, when in such conditions it is in the expanded state, some cell shape changes can induce its partial detachment. The partial detachment of the skeleton from the bilayer is energetically favorable if the consequent decrease of the skeleton expansion energy is larger than the corresponding increase of the bilayer-skeleton binding energy. The effect of shape on the skeleton detachment is analyzed theoretically for a series of the pear class shapes, having decreasing neck diameter and ending with a parent-daughter pair of spheres. The partial detachment of the skeleton is promoted by narrowing of the cell neck, by increasing the lateral tension in the skeleton and its area expansivity modulus, and by diminishing the attraction forces between the skeleton and the bilayer. If the radius of the daughter vesicle is sufficiently small relative to the radius of the parent cell, the daughter vesicle can exist either completely underlaid with the skeleton or completely depleted of the skeleton.


Identification and validation of new quantitative trait loci for spike-related traits in two RIL populations.
Wheat (Triticum aestivum L.) is one of the most important cereal crops for ensuring food security worldwide. Identification of major quantitative trait loci (QTL) for spike-related traits is important for improvement of yield potential in wheat breeding. In this study, by using the wheat 55K single nucleotide polymorphism (SNP) array and diversity array technology (DArT), two recombinant inbred line populations derived from crosses avocet/chilero and avocet/huites were used to map QTL for kernel number per spike (KNS), total spikelet number per spike (TSS), fertile spikelet number per spike (FSS), and spike compactness (SC). Forty-two QTLs were identified on chromosomes 2A (4), 2B (3), 3A (2), 3B (7), 5A (11), 6A (4), 6B, and 7A (10), explaining 3.13-21.80% of the phenotypic variances. Twelve QTLs were detected in multi-environments on chromosomes 2A, 3B (2), 5A (4), 6A (3), 6B, and 7A, while four QTL clusters were detected on chromosomes 3A, 3B, 5A, and 7A. Two stable and new QTL clusters, QKns/Tss/Fss/SC.haust-5A and QKns/Tss/Fss.haust-7A, were detected in the physical intervals of 547.49-590.46 Mb and 511.54-516.15 Mb, accounting for 7.53-14.78% and 7.01-20.66% of the phenotypic variances, respectively. High-confidence annotated genes for QKns/Tss/Fss/SC.haust-5A and QKns/Tss/Fss.haust-7A were more highly expressed in spike development. The results provide new QTL and molecular markers for marker-assisted breeding in wheat. The online version contains supplementary material available at 10.1007/s11032-023-01401-4.


A Prospective Program to Reduce the Clinical Incidence of Clostridium difficile Colitis Infection after Cystectomy.
The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of C. difficile and assessed its impact on clinical C. difficile infection rates compared to historical matched controls. Prospective C. difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients who underwent cystectomy before the initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Patients who screened positive were placed in contact isolation and treated prophylactically with metronidazole. Multivariable models were built on an intent to screen basis and an effectiveness of screening basis to determine whether screening reduced the rate of symptomatic C. difficile infection postoperatively. With the implementation of the screening protocol the C. difficile infection rate declined from 9.4% to 5.5% (OR 0.52, p = 0.0268) in patients on the intent to screen protocol and from 9.2% to 4.9% in those on the effectiveness of screening protocol (OR 0.46, p = 0.0174). C. difficile screening prior to cystectomy is associated with a significant decrease in the rate of clinically symptomatic infection postoperatively. These results should be confirmed in a randomized controlled trial.


Drinking through rosé-coloured glasses: Influence of wine colour on the perception of aroma and flavour in wine experts and novices.
Wine colour carries a myriad of meanings regarding the provenance and expected sensory qualities of a wine. That meaning is presumably learnt through association, and part of a wine taster's skill comes from being able to decode information that can be discerned in subtle variations in the colour of the wine that they drink/evaluate. However, reliance on colour means that wine tasters, especially experts, often exhibit colour-induced olfactory biases. The present study assesses how wine colour - specifically the pink hue of rosé wines - can influence both the perceived aroma and flavour in a large sample of wine novices and experts. Participants (N = 168) tasted three wines - a white wine (W), a rosé wine (R), and the white wine dyed to match the rosé (Ŕ) - and freely selected three aroma and three flavour descriptors from a list. They also rated wine liking, flavour intensity, and description difficulty for each wine. Linguistic analysis demonstrated that those with wine tasting experience judged Ŕ to be much more similar to R than to W, even though Ŕ and W were the same. Moreover, red fruit descriptors were attributed to both R and Ŕ, especially in terms of flavour. Quantitative ratings revealed that Ŕ was liked less than W or R, and participants found it more difficult to describe Ŕ than R. These results demonstrate that while participants found the dyed rosé somehow different from the undyed wines, they nevertheless used the red fruit terms to describe its aroma and flavour. The implications of such results in terms of cognitive representations of wine and the role of sensory expectations are discussed.


Hypopharyngeal lipomatous hamartoma in piriform fossa: A case report and review of literature.
Most hypopharyngeal disease presentations involve tumours or growths of various cellular origin. These lesions may include choristomas, hamartomas, hyperplasia, and harmless or dangerous neoplasms. A hamartoma is a benign focal malformation of tissue at the site of origin that lacks specific distinguishing features and is often designated as a neoplasm without consideration of pathology or biological behaviour. Here, we discuss the case of a 56-year-old man who presented with gradual dysphagia for 4 months along with sleep apnoea and voice changes. No palpable neck masses or abnormal lymphadenopathy was found. A left-sided homogeneous cyst-like mass was seen in the piriform fossa on laryngoscopy. The vocal cords were visualized and mobile. A contrast-enhanced computed tomography scan showed the obliteration of the piriform sinus on the left side by a faintly enhanced heterogeneous soft tissue lesion. The lesion originated from the left aryepiglottic fold, and was approached via micro-laryngoscopy and excised. Histopathological analysis led to a diagnosis of lipomatous hamartoma.


Tracking movements of lipids and Thy1 molecules in the plasmalemma of living fibroblasts by fluorescence video microscopy with nanometer scale precision.
The lateral diffusion of 100 nm fluorescent latex microspheres (FS) bound to either N-biotinyl-phosphatidyl-ethanolamine or the glycosylphosphatidylinositol-linked protein Thy1 were monitored in the plasmalemma of primary rat fibroblasts by single particle tracking of FS centroids from digital fluorescence micrographs. A silicon intensified target camera was found to be superior to slow scan cooled CCD and intensified interline transfer CCD cameras for monitoring lateral diffusion of rapidly moving FS with nanometer level precision. To estimate the maximum tracking precision, a 4 sec-sequence comprising 120 images of FS fixed to a cover glass was obtained. The mean distance of the centroids from the origin was 7.5 +/- 0.4 nm, and no centroids were beyond 16 nm from the origin. The SIT camera was then used to track FS attached to lipids and Thy1 molecules on the surface of fibroblasts. The lateral diffusion of lipid-bound FS was unconstrained, and the ensemble averaged diffusion coefficient was 0.80 x 10(-9) cm2/sec. Thy1-bound FS existed in two mobility populations, both of which demonstrated constrained mobility. The rapidly moving population, comprising 61% of the total, had an ensemble diffusion coefficient of 6.1 x 10(-10) cm2/sec, and appeared to be restricted to domains with a mean length of about 700 nm. The slowly moving population, comprising about 39% of the total, had a diffusion coefficient of 5.7 x 10(-12) cm2/sec. These results demonstrate that nanovid can be extended to the realm of fluorescence microscopy and support previous studies indicating that while the lateral mobilities of at least some lipids are not constrained to small domains by barriers to lateral diffusion in the fibroblast plasmalemma, a peripheral membrane protein which is bound only by a lipid anchor can be prevented from diffusing freely.


Anti-interleukin-2 receptor monoclonal antibody therapy induces anti-idiotypic antibodies in mice that block both in vitro and in vivo activity.
Monoclonal antibodies (Mab) targeting certain T cell-surface proteins including the interleukin-2 (IL2) receptor molecule exert powerful immunosuppressive effects. A potential limiting factor to Mab therapy is the formation of neutralizing anti-idiotypic antibodies (Anti-Id). In this study, we demonstrate that an anti-IL2 receptor Mab, M7/20, when administered at doses which are immunosuppressive in vivo rapidly elicits an anti-idiotypic (anti-Id) antibody response. The induced antibodies are capable of blocking M7/20 binding to its target, the IL2 receptor, in vitro. Such anti-Id when given in concert with M7/20 block the expected in vivo inhibitory effects in delayed type hypersensitivity. Thus, mice respond to therapeutic doses of Mab therapy with the formation of neutralizing anti-Id. As this response is similar to that observed in humans given xenogeneic Mab, this model may be useful to further our understanding of this form of therapy.


Interhemispheric nigrostriatal projections in the rat: bifurcating nigral projections and loci of crossing in the diencephalon.
The organization of interhemispheric nigrostriatal projections in the rat was studied with (1) a double labeling technique combined with a histofluorescence method for monoamines and with (2) horseradish-peroxidase (HRP) as a tracer. Each animal received an injection of Fast Blue (FB) into the caudate nucleus (NC) of one hemisphere and an injection of Nuclear Yellow (NY) into the NC of the other hemisphere. Brains were processed according to the sucrose-potassium phosphate-glyoxylic acid (SPG) method in order to identify monoaminergic neurons. About 5% of the neurons which were labeled by either of the tracers in the substantia nigra (SN) ipsilateral to the injection site were also labeled in the contralateral SN. Most of these interhemispherically projecting SN-neurons were monoaminergic. A small number of neurons in either SN was labeled with both fluorescent tracers. This suggests that bifurcating, monoaminergic neurons in the SN project to both NC. In the second experiment, rats received a unilateral injection of HRP into NC. After a survival time of several hours the animals were perfused and the brains were processed using benzidine-dihydrochloride. Fibers crossing the hemisphere were found within the massa intermedia of the thalamus and within the inferior thalamic peduncle. The results are discussed with respect to a possible functional role of interhemispheric nigrostriatal connections.


Selective visual attention in Alzheimer's and Parkinson's patients: memory- and data-driven control.
An automated visual search experiment was carried out on patients with incipient Alzheimer's disease, non-demented Parkinsonians and healthy controls to test for selective attention control within the framework of the Norman and Bobrow (1975) model. The performances of the Parkinsonians and healthy controls were consistent with the predictions of this model but those of the Alzheimer patients were not. These patients appeared to be no longer sensitive to the facilitation supplied by the stimulus context and to spend most of their residual resources on achieving accuracy. The reduction of their attentional resources possibly interferes with the control of the speed-accuracy trade-off.


Raw versus relative scores in the assessment of coping strategies.
Raw scores (frequency of efforts) versus relative scores (percentage of efforts) were compared on the five scales of the revised Ways of Coping Checklist. It was hypothesized that, conditional on the source of and appraisal of a stressor, problem-focused coping should be inversely related and Wishful Thinking should be positively related to depression when relative scores were used but that raw problem-focused scores would be less clearly related to depression in such a way. It was further hypothesized that these relationships would hold for very diverse samples: psychiatric outpatients (n = 145), spouses of patients with Alzheimer's disease (n = 66), and medical students (n = 185). Given the maladaptive status of the psychiatric outpatients, it was hypothesized that they would report more emotion-focused strategies and less problem-focused coping than the nonclinical samples and that these differences would be better observed using relative rather than raw scores. The hypotheses were generally supported.


Role of retrograde flow in the shear stimulus associated with exercise blood flow.
To test the hypothesis that retrograde flow influences the shear stimulus of exercise blood flow, eight healthy men [25.6+/-3.1 years (SD)] performed 20 min of single-leg knee-extension exercise at two contraction velocities: fast (FR, 1.5 m s(-1)) and slow (SR, 0.4 m s(-1)). Contraction frequency (30 cpm) and workload (5 kg) were kept constant resulting in a work rate of 15.25 W for both contraction velocities. Common femoral artery diameter and blood velocity were measured at rest and during exercise using ultrasound Doppler. Mean blood flow was not different between contraction velocities while antegrade (2012.4+/-379.9 versus 1745.6+/-601.5 ml min(-1); P=0.05) and retrograde (121.7+/-43.0 versus 11.2+/-6.6 ml min(-1); P<0.001) flows were higher during FR than SR contractions, respectively. Despite the similar mean blood flow response, vascular resistance was lower during FR than SR contractions (0.06+/-0.01 versus 0.08+/-0.03 units; P=0.03) and was closely related to shear rate (pooled data: r=-0.77, P<0.01). Retrograde flow was associated with a lower vascular resistance during exercise (pooled data: r=-0.48, P<or=0.05). In addition, calculated oscillatory flow indices were higher during FR than SR contractions and were significantly correlated to retrograde flow, shear rate and vascular resistance. These results indicate that retrograde blood flow influences the shear stimulus of exercise blood flow by enhancing the oscillatory behaviour of flow.


Partial amino acid sequence of an amyloid fibril protein from nodular primary cutaneous amyloidosis showing homology to lambda immunoglobulin light chain of variable subgroup III (a lambda III).
An amyloid fibril protein (MA) was purified as a 17,000-dalton protein from a case of nodular primary cutaneous amyloidosis, and its partial amino acid sequence (22 residues from N-terminal) was determined. A sequence closely homologous to that of the lambda III subgroup of the immunoglobulin light chain was detected. This is the third case of nodular primary cutaneous amyloidosis which has been studied at the level of sequence analysis of purified amyloid fibril proteins, and the first case of nodular primary cutaneous amyloidosis in which a lambda III amyloid protein has been shown to be present by sequence analysis.


Misplacement of a jugular line in a facial vein.
We report an exceptional misplacement of a central venous catheter, from the right jugular vein where it was introduced, into the right thyro-lingual-facial trunk. A brief description of the clinical course and a literature review on catheter misplacement is presented. This case illustrates the importance of routine use of a chest X-ray, and when necessary contrast medium, to verify the correct location of the catheter tip.


Dense-cored vesicles, smooth endoplasmic reticulum, and mitochondria are closely associated with non-specialized parts of plasma membrane of nerve terminals: implications for exocytosis and calcium buffering by intraterminal organelles.
To determine whether there are anatomical correlates for intraterminal Ca2+ stores to regulate exocytosis of dense-cored vesicles (DCVs) and whether these stores can modulate exocytosis of synaptic vesicles, we studied the spatial distributions of DCVs, smooth endoplasmic reticulum (SER), and mitochondria in 19 serially reconstructed nerve terminals in bullfrog sympathetic ganglia. On average, each bouton had three active zones, 214 DCVs, 26 SER fragments (SERFs), and eight mitochondria. DCVs, SERFs and mitochondria were located, on average, 690, 624, and 526 nm, respectively, away from active zones. Virtually no DCVs were within "docking" (i.e., < or = 50 nm) distances of the active zones. Thus, it is unlikely that DCV exocytosis occurs at active zones via mechanisms similar to those for exocytosis of synaptic vesicles. Because there were virtually no SERFs or mitochondria within 50 nm of any active zone, Ca2+ modulation by these organelles is unlikely to affect ACh release evoked by a single action potential. In contrast, 30% of DCVs and 40% of SERFs were located within 50 nm of the nonspecialized regions of the plasma membrane. Because each bouton had at least one SERF within 50 nm of the plasma membrane and most of these SERFs had DCVs, but not mitochondria, near them, it is possible for Ca2+ release from the SER to provide the Ca2+ necessary for DCV exocytosis. The fact that 60% of the mitochondria had some part within 50 nm of the plasma membrane means that it is possible for mitochondrial Ca2+ buffering to affect DCV exocytosis.


Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria.
Direct cDNA sequencing was performed on asymmetrically amplified transcripts from the porphobilinogen deaminase (PBG-D) gene of thirteen unrelated individuals with acute intermittent porphyria. Four different mutations and a polymorphic site were detected in exon 12 of the gene, four being the result of single base substitutions and one being caused by dinucleotide deletion. All of these mutations are located in domain 3 of the PBG-D molecule, with the single base substitutions affecting the hydrophobic interfaces between domains 1 and 3. The dinucleotide deletion results in a frame-shift producing a premature stop codon.


Mechanism of G1-like arrest by low concentrations of paclitaxel: next cell cycle p53-dependent arrest with sub G1 DNA content mediated by prolonged mitosis.
Paclitaxel (PTX) and other microtubule inhibitors cause mitotic arrest. However, low concentrations of PTX (low PTX) paradoxically cause G1 arrest (without mitotic arrest). Here, we demonstrated that unexpectedly, low PTX did not cause G1 arrest in the first cell cycle and did not prevent cells from passing through S phase and entering mitosis. Mitosis was prolonged but cells still divided, producing either two or three cells (tripolar mitosis), thus explaining a sub G1 peak caused by low PTX. Importantly, sub G1 cells were viable and non-apoptotic. Some cells fused back and then progressed to mitosis, frequently producing three cells again before becoming arrested in the next cell-cycle interphase. Thus, low PTX caused postmitotic arrest in second and even the third cell cycles. By increasing concentration of PTX, tripolar mitosis was transformed to mitotic slippage, thus eliminating a sub G1 peak. Time-lapse microscopy revealed that prolonged mitosis ensured a p53-dependent postmitotic arrest. We conclude that PTX directly affects cells only in mitosis and the duration of mitosis determines cell fate, including p53-dependent G1-like arrest.


Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells.
The effects of synthetic rat adrenomedullin (rAM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, on receptor binding and cAMP generation were studied in cultured rat vascular smooth muscle cells (VSMC). A binding study using [125I]rAM revealed the presence of a single class of high-affinity (Kd 1.3 x 10(-8) M) binding sites for rAM in VSMC. The apparent Ki of rat calcitonin gene-related peptide (rCGRP) was 3 x 10(-7) M. Affinity labeling of VSMC membranes with [125I]rAM revealed two distinct labeled bands with apparent molecular weights of 120 and 70 kDa, both of which were abolished by excess unlabeled rAM or rCGRP, rAM stimulated cAMP formation with an approximate EC50 of 10(-8) M, the effect of which was additive with isoproterenol, but not with rCGRP. The rAM-induced cAMP response was unaffected by propranolol, indomethacin, or quinacrine, but inhibited by a CGRP receptor antagonist, human CGRP[8-37]. These data suggest that VSMC possesses specific AM receptors functionally coupled to adenylate cyclase with which CGRP interacts.


Segmentation of subcortical brain structures using fuzzy templates.
We propose a novel method to automatically segment subcortical structures of human brain in magnetic resonance images by using fuzzy templates. A set of fuzzy templates of the structures based on features such as intensity, spatial location, and relative spatial relationship among structures are first created from a set of training images by defining the fuzzy membership functions and by fusing the information of features. Segmentation is performed by registering the fuzzy templates of the structures on the test image and then by fusing them with the tissue maps of the test image. The final decision is taken in order to optimize the certainty in the intensity, location, relative position, and tissue content of the structure. Our method does not require specific expert definition of each structure or manual interactions during segmentation process. The technique is demonstrated with the segmentation of five structures: thalamus, putamen, caudate, hippocampus, and amygdala; the performance of the present method is comparable with previous techniques.


Management of Erythrocytosis in Men Receiving Testosterone Therapy: Clinical Consultation Guide.
The most common side effect of testosterone therapy (TT) is erythrocytosis. Patient-specific factors therefore should be considered when choosing an appropriate TT dosage and modality. Providers should decrease or discontinue therapy if the patient's hematocrit exceeds 54% until the hematocrit normalizes.


Eggshell membrane derived nitrogen rich porous carbon for selective electrosorption of nitrate from water.
Nitrate (NO3-) is a ubiquitous contaminant in water and wastewater. Conventional treatment processes such as adsorption and membrane separation suffer from low selectivity for NO3- removal, causing high energy consumption and adsorbents usage. In this study, we demonstrate selective removal of NO3- in an electrosorption process by a thin, porous carbonized eggshell membrane (CESM) derived from eggshell bio-waste. The CESM possesses an interconnected hierarchical pore structure with pore size ranging from a few nanometers to tens of micrometers. When utilized as the anode in an electrosorption process, the CESM exhibited strong selectivity for NO3- over Cl-, SO42-, and H2PO4-. Adsorption of NO3- by the CESM reached 2.4 × 10-3 mmol/m2, almost two orders of magnitude higher than that by activated carbon (AC). More importantly, the CESM achieved NO3-/Cl- selectivity of 7.79 at an applied voltage of 1.2 V, the highest NO3-/Cl- selectivity reported to date. The high selectivity led to a five-fold reduction in energy consumption for NO3- removal compared to electrosorption using conventional AC electrodes. Density function theory calculation suggests that the high NO3- selectivity of CESM is attributed to its rich nitrogen-containing functional groups, which possess higher binding energy with NO3- compared to Cl-, SO42-, and H2PO4-. These results suggest that nitrogen-rich biomaterials are good precursors for NO3- selective electrodes; similar chemistry can also be used in other materials to achieve NO3- selectivity.


Cardiac amyloidosis: pathology, nomenclature, and typing.
Amyloidosis is an increasingly recognized cause of heart disease, caused by the deposition of misfolded protein within the heart. These proteins may deposit systemically and include the heart or deposit only within the heart muscle itself. In either case, cardiac symptoms may be the primary manifestation. The diagnosis is usually made by the pathologist identifying amyloid within a tissue sample. The diagnosis, however, does not end with such visual recognition of the presence of amyloid. Newer generation pharmacotherapeutic agents that are protein specific necessitate a closer evaluation to determine the type of protein being deposited and accurately conveying this to the treating clinician. Herein, the gross and histopathologic features of cardiac amyloidosis are reviewed along with a review of amyloid typing strategies (both direct and indirect) that may be employed in the diagnostic workup as well as the nomenclature standards for reporting.


Two intrinsic timing mechanisms set start and end times for dendritic arborization of a nociceptive neuron.
Choreographic dendritic arborization takes place within a defined time frame, but the timing mechanism is currently not known. Here, we report that the precisely timed lin-4-lin-14 regulatory circuit triggers an initial dendritic growth activity, whereas the precisely timed lin-28-let-7-lin-41 regulatory circuit signals a subsequent developmental decline in dendritic growth ability, hence restricting dendritic arborization within a set time frame. Loss-of-function mutations in the lin-4 microRNA gene cause limited dendritic outgrowth, whereas loss-of-function mutations in its direct target, the lin-14 transcription factor gene, cause precocious and excessive outgrowth. In contrast, loss-of-function mutations in the let-7 microRNA gene prevent a developmental decline in dendritic growth ability, whereas loss-of-function mutations in its direct target, the lin-41 tripartite motif protein gene, cause further decline. lin-4 and let-7 regulatory circuits are expressed in the right place at the right time to set start and end times for dendritic arborization. Replacing the lin-4 upstream cis-regulatory sequence at the lin-4 locus with a late-onset let-7 upstream cis-regulatory sequence delays dendrite arborization, whereas replacing the let-7 upstream cis-regulatory sequence at the let-7 locus with an early-onset lin-4 upstream cis-regulatory sequence causes a precocious decline in dendritic growth ability. Our results indicate that the lin-4-lin-14 and the lin-28-let-7-lin-41 regulatory circuits control the timing of dendrite arborization through antagonistic regulation of the DMA-1 receptor level on dendrites. The LIN-14 transcription factor likely directly represses dma-1 gene expression through a transcriptional means, whereas the LIN-41 tripartite motif protein likely indirectly promotes dma-1 gene expression through a posttranscriptional means.


Relationship between diabetic macular edema and peripheral Th1/Th2 balance.
To determine whether inflammatory reactions are involved in the pathogenesis of diabetic macular edema, we examined the relationship between diabetic macular edema and the ratio of T helper 1 (Th1) to T helper 2 (Th2) cells. Thirty-nine diabetic patients with diabetic retinopathy were evaluated at our hospital between February 2004 and February 2005. Blood samples were collected from each patient, and the ratio of CD4+ Th1 to Th2 cells (Th1/Th2) was determined by flow cytometry after fluorescent antibody staining for intracellular cytokines. Logistic regression analysis was used to determine the association of macular edema with age, gender, HbA(1c) level, interval after retinal photocoagulation and Th1/Th2 ratios. Differences in these parameters were also compared between patients with and without macular edema. Logistic regression analysis showed that the Th1/Th2 ratios were significantly associated with macular edema (odds ratio = 0.838; p = 0.02), while other variables were not. The Th1/Th2 ratio was significantly lower in the patients with diabetic macular edema than in those without (p = 0.02; t test). Higher Th1/Th2 ratios tended to be associated with better visual acuity. Shifts in the balance of Th1/Th2 towards a predominance of Th2 may represent an exacerbating factor for diabetic macular edema, although a causal relationship has still not been definitively determined.


Production, purification, characterization and application of a new halotolerant and thermostable endoglucanase of Botrytis ricini URM 5627.
A halotolerant endoglucanase with a molecular mass of 39 kDa was obtained from the solid fermentation of sugarcane bagasse by the fungus Botrytis ricini URM 5627 and isolated using only two purification processes: fractionation with ammonium sulphate and size-exclusion chromatography resulting in an activity of 1289.83 U/mL. After the isolation, biochemical characterizations were performed, giving a temperature of 50 °C and optimum pH of 5. The enzyme was stable at 39-60 °C for 60 min and at a pH of 4-6. The enzymatic activity increased in the presence of Na+, Mn2+, Mg2+ and Zn2+ and decreased in the presence of Ca2+, Cu2+, and Fe2+. The endoglucanase revealed a halotolerant profile since its activity increased proportionally to an increase in NaCl concentration. The maximum activity was reached at 2 M NaCl with a 75% increase in activity. The enzyme had a Km of 0.1299 ± 0.0096 mg/mL and a Vmax of 0.097 ± 0.00121 mol/min/mL. During application in saccharification tests, the enzyme was able to hydrolyse sugarcane bagasse, rice husk, and wheat bran, with the highest production of reducers/fermentable sugars within 24 h of saccharification for wheat bran (137.21 mg/g). Therefore, these properties combined make this isolated enzyme a potential candidate for biotechnological and industrial applications.


Relation between functional deficit and intraneural local anesthetic during peripheral nerve block. A study in the rat sciatic nerve.
During peripheral nerve block, local anesthetic (LA) penetrates within and along the nerve to produce the observed functional deficits. Although much is known about the kinetics and steady-state relation for LA inhibition of impulse activity in vitro in isolated nerve, little is known about the relation between functional loss and intraneural LA content in vivo. This study was undertaken to investigate the relation of functional change to intraneural LA. A sciatic nerve block was performed in rats with 0.1 ml 1% lidocaine radiolabeled with 14C. The total intraneural uptake of LA was determined at different times after injection, and the distribution of lidocaine along the nerve was assayed at different stages of functional block. Drug content was also compared with equilibrium lidocaine uptake in the isolated rat sciatic nerve. Total intraneural lidocaine in vivo increased to near steady-state in about 3 min, stabilizing at approximately 14.3 nmol/mg wet tissue for about 12 min before decreasing to zero at 70 min after injection. Although intraneural lidocaine was 1.6% of the injected dose during full block, only 0.3% was left when deep pain sensation returned and 0.065% was still detected when functions fully recovered. Despite these large differences in total lidocaine content, the longitudinal distribution remained constant. Intraneural lidocaine concentrations obtained at full block and partial recovery could be achieved in vitro by equilibration in 0.7-0.9 and 0.2-0.3 mM lidocaine, respectively. During peripheral nerve block only a small amount of injected LA penetrates into the nerve. The intraneural content of LA correlates with the depth of functional block.


Benefits of using culturally unfamiliar stimuli in ambiguous emotion identification: A cross-cultural study.
A novel emotion recognition task that employs photos of a Japanese mask representing a highly ambiguous stimulus was evaluated. As non-Asians perceive and/or label emotions differently from Asians, we aimed to identify patterns of task-performance in non-Asian healthy volunteers with a view to future patient studies. The Noh mask test was presented to 42 adult German participants. Reaction times and emotion attribution patterns were recorded. To control for emotion identification abilities, a standard emotion recognition task was used among others. Questionnaires assessed personality traits. Finally, results were compared to age- and gender-matched Japanese volunteers. Compared to other tasks, German participants displayed slowest reaction times on the Noh mask test, indicating higher demands of ambiguous emotion recognition. They assigned more positive emotions to the mask than Japanese volunteers, demonstrating culture-dependent emotion identification patterns. As alexithymic and anxious traits were associated with slower reaction times, personality dimensions impacted on performance, as well. We showed an advantage of ambiguous over conventional emotion recognition tasks. Moreover, we determined emotion identification patterns in Western individuals impacted by personality dimensions, suggesting performance differences in clinical samples. Due to its properties, the Noh mask test represents a promising tool in the differential diagnosis of psychiatric disorders, e.g. schizophrenia.


An ultrastructural study of mast cells in the alveolar wall of normal and asthmatic lung.
Specimens of normal and asthmatic lungs were studied at the electron microscopic level and the frequency and ultrastructural features of mast cells and their granules within the alveolar wall were assessed with morphometric techniques. The numerical density of mast cells per square millimetre of alveolar wall was 299 (SD = 258) in normal and 366 (SD = 260) in asthmatic lung. The mean area of the mast cell nucleated profile was 25.7 microns2 (SD = 6.3) in normal lung and 29.8 (SD = 6.2) in asthmatic. The average number of secretory granules per single mast cell nucleated profile was 55 (SD = 13) in normal lung and 60 (SD = 12) in asthmatic lung. The diameter of the individual secretory granule was 338.9 nm (SD = 42.6) in normal and 345.6 (SD = 47.7) in asthmatic lung. The volume density of secretory granules in normal and asthmatic lung was 6.31 microns3 and 5.81 microns3, respectively. The mean diameter of the individual subunit ('scroll') inside the secretory granule was 88.8 nm for both normal and asthmatic lung. In normal lung 64.2% of granules were of 'scroll' and 'combined' type, and 35.8% of granules were 'particulate' or 'empty'. In specimens from asthmatic patients 40.3% of granules had 'scroll' or 'combined' structures and 59.7% were 'particulate' or 'empty'. Our data suggest that there is no difference between the number of mast cells in normal and asthmatic lung. However, in pulmonary mast cells from asthmatic lung, degranulation is more common than in normal lung.


CO(2) in large-scale and high-density CHO cell perfusion culture.
Productivity in a CHO perfusion culture reactor was maximized when pCO(2) was maintained in the range of 30-76 mm Hg. Higher levels of pCO(2) (> 150 mm Hg) resulted in CHO cell growth inhibition and dramatic reduction in productivity. We measured the oxygen utilization and CO(2) production rates for CHO cells in perfusion culture at 5.55×10(-17) mol cell(-1) sec(-1) and 5.36×10(-17) mol cell(-1) sec(-1) respectively. A simple method to directly measure the mass transfer coefficients for oxygen and carbon dioxide was also developed. For a 500 L bioreactor using pure oxygen sparge at 0.002 VVM from a microporous frit sparger, the overall apparent transfer rates (k(L)a+k(A)A) for oxygen and carbon dioxide were 0.07264 min(-1) and 0.002962 min(-1) respectively. Thus, while a very low flow rate of pure oxygen microbubbles would be adequate to meet oxygen supply requirements for up to 2.1×10(7) cells/mL, the low CO(2) removal efficiency would limit culture density to only 2.4×10(6) cells/mL. An additional model was developed to predict the effect of bubble size on oxygen and CO(2) transfer rates. If pure oxygen is used in both the headspace and sparge, then the sparging rate can be minimized by the use of bubbles in the size range of 2-3 mm. For bubbles in this size range, the ratio of oxygen supply to carbon dioxide removal rates is matched to the ratio of metabolic oxygen utilization and carbon dioxide generation rates. Using this strategy in the 500 L reactor, we predict that dissolved oxygen and CO(2) levels can be maintained in the range to support maximum productivity (40% DO, 76 mm Hg pCO(2)) for a culture at 10(7) cells/mL, and with a minimum sparge rate of 0.006 vessel volumes per minute.A = volumetric agitated gas-liquid interfacial area at the top of the liquid, 1/mB = cell broth bleeding rate from the vessel, L/minCER = carbon dioxide evolution rate in the bioreactor, mol/min[CO(2)] = dissolved CO(2) concentration in liquid, M[CO(2)](*) = CO(2) concentration in equilibrium with sparger gas, M[CO(2)](**) = CO(2) concentration in equilibrium with headspace gas, MCO(2)(1) = dissolved carbon dioxide molecule in water[C(T)] = total carbonic species concentration in bioreactor medium, M[C(T)](F) = total carbonic species concentration in feed medium, MD = bioreactor diameter, mD(I) = impeller diameter, mD(b) = the initial delivered bubble diameter, mF = fresh medium feeding rate, L/minH(L) = liquid height in the vessel, mk(A) = carbon dioxide transfer coefficient at liquid surface, m/mink (infA) (supO) = oxygen transfer coefficient at liquid surface, m/min.


[Pacemaker dependant and/or repetitive ICD therapies. How to solve the dilemma of lead extraction?].
Bridging pacemaker-dependent patients or patients with repetitive ICD therapies after device and lead extraction is often challenging. Temporary pacing by means of an active fixation lead connected to an external reusable permanent pacemaker, or of a subxiphoidally implanted pacemaker with an epicardial lead is a safe option for bridging pacemaker-dependent patients after device and lead explantation. The wearable cardioverter defibrillator (WCD; LifeVest(®)) is a safe and effective tool for patients who need a continuous monitoring and ICD backup after device explantation.


The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production.
Studies have suggested that endogenous glutamate and N-methyl-d-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines. Although the expressions of NMDARs were different between MRC-5 and HFL-1, 1mM NMDA elicited the same trend in the downregulation of NR2A expression, the upregulation of NR2D, and the increase of cells proliferation and collagen production. Glutamate stimulation after 24-h of NMDA exposure resulted in weaker and more delayed but more prolonged iCa2+ elevation in HFL-1 than no NMDA exposed cells. NMDA increased the level of pERK1/2, cells proliferation and collagen production, whereas nonspecific NMDAR antagonist MK-801, NR2D-preferring receptor antagonist UBP141 and ERK1/2 phosphorylation inhibitor U0126 suppressed it, respectively. In conclusion, we found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism.


[Integral tests of the hemostasis system in assessing the efficiency of acetylsalicylic acid in patients with ischemic heart disease].
Despite the fact that acetylsalicylic acid (ASA) is the "gold" standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed in platelet-rich plasma (PRP) using integral tests of the hemostasis study: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT). The study involved 34 patients with stable CAD (11 women, 23 men) and people (15 women, 18 men) in the control group. As a result of assessing the activity of thrombus formation using the T-TAS system, a significant decrease in the area under the curve (AUC10) was found in the group with CAD patients compared with the control (135.6 [88.0-222.3] and 260.5 [217.3-301.9], respectively, p.


Fabrication, optimization, and characterization of ultra-small superparamagnetic Fe3O4 and biocompatible Fe3O4@ZnS core/shell magnetic nanoparticles: Ready for biomedicine applications.
Magnetic nanoparticles that preferred for biomedical applications are required to be biocompatible, nanosized and superparamagnetic. In this research, ultra-small superparamagnetic Fe3O4 nanoparticles and novel superparamagnetic Fe3O4@ZnS core/shell nanocomposites were fabricated using biocompatible ethylenediaminetetraacetic acid (EDTA) as a capping agent by a facile refluxing assisted co-precipitation method at optimum condition. The Fe3O4 and Fe3O4@ZnS nanoparticles were investigated using X-ray diffraction (XRD), scanning and transmission electron microscopy (SEM and TEM), UV-Vis spectroscopy, vibrating sample magnetometer (VSM) and Dynamic Light Scattering (DLS). The VSM results indicated that all of the samples have superparamagnetic behavior. The particle size of the Fe3O4 and Fe3O4@ZnS nanoparticles were obtained at about 10 and 22 nm, respectively.


Barriers to access to antiretroviral treatment in developing countries: a review.
To present a review of barriers impeding people living with HIV/AIDS in developing countries from accessing treatment, and to make recommendations for further studies. Electronic databases, websites of main global agencies and international AIDS conferences were searched for relevant articles published between 1996 and 2007. Articles were reviewed using the Andersen and May framework of access to health services and barriers were categorized as either population-level or health system-level barriers. A total of 19 studies (7 articles and 12 abstracts) in English were reviewed. The barriers most frequently cited at the population level were lack of information about antiretroviral therapy (ART), perceived high costs for ART and stigma. Barriers most frequently cited at the health system level were long distance from home to the health facility, lack of co-ordination across services and limited involvement of the community in the programme planning process. Dissemination of information about HIV/AIDS and alternative related care, and alternative health financing policies seem to be the most relevant policy measures to remove barriers. In view of the paucity of evidence on barriers to access to ART, research should address the relative importance of barriers, include a mix of qualitative and quantitative research methods and evaluate barriers in different settings.


A histologic study of laser-induced transmyocardial channels.
Carbon dioxide lasers are reported to provide ischemic myocardium direct access to blood within the ventricular cavity by inducing transmyocardial channels which maintain patency in long-term experiments. We have histologically examined the natural history of channels produced with this technique and compared them with transmyocardial channels created by needle puncture. Immediately after application of the laser, four concentric zones vaporization, carbonization, fixation, and transition could be distinguished along the transmyocardial path. Needle puncture channels were fully occluded within 48 hr, whereas laser-induced channels maintained partial patency for a 2-week period, after which they also became occluded. It appears likely that the instantaneous vaporization produced by the laser may delay the release of factors which mediate the healing process, but occlusion of channels was universal in this study. It remains to be determined whether or not variables such as wattage, beam diameter, or tissue temperature influence long-term channel patency.


Phloretin Ameliorates Acetic Acid Induced Colitis Through Modulation of Immune and Inflammatory Reactions in Rats.
Adverse effects associated with current therapy for Ulcerative colitis (UC) over prolonged treatment periods and the high relapse rate limit their use. Incorporating fruits as regular diet has beneficial role in the management of UC. Phloretin, a dihydrochalcone of apple is reported for its anti-oxidant and anti-inflammatory effects. Our study aims to evaluate the effectiveness of phloretin on experimentally induced ulcerative colitis in rats. In vitro study was performed using Raw 264.7 cells stimulated with LPS (1μg/mL) and in in-vivo study, colitis was induced by intra rectal administration of 4% Acetic acid. Phloretin (50 mg/kg) was given orally for 3 days to Wistar rats after induction for the post-treatment group and 1 day before induction to the pre-treatment group. Macroscopical, biochemical and histopathological evaluations were performed to assess the effectiveness. A concentration dependent inhibition of MPO and iNOS activity was obtained in LPS stimulated neutrophil cells. Phloretin exerted ameliorative effect in both pre and post-treatment groups by restoring plasma ALP and LDH level and reduce inflammatory markers like myeloperoxidase, nitric oxide and eosinophil peroxidase level as well as downregulates colon ICAM-1 gene in acetic acid induced ulcerative colitis in rats. Antioxidative potency was confirmed by restoring tissue GSH level. Phloretin prevents mucosal damage and it was confirmed by histopathological analysis. Collectively, our findings provide evidence that phloretin might be useful as a natural therapeutic agent in the management of UC as well as may pose a promising outcome for future clinical usage.


Prediction of patients with idiopathic generalized epilepsy from healthy controls using machine learning from scalp EEG recordings.
Epilepsy detection is essential for patients with epilepsy and their families, as well as for researchers and medical staff. The use of electroencephalogram (EEG) as a tool to support the diagnosis of patients with epilepsy is fundamental. Today, machine learning (ML) techniques are widely applied in neuroscience. The main objective of our study is to differentiate patients with idiopathic generalized epilepsy from healthy controls by applying machine learning techniques on interictal electroencephalographic recordings. Our research predicts which patients have idiopathic generalized epilepsy from a scalp EEG study. In addition, this study focuses on using the extreme gradient boosting (XGB) method applied to scalp EEG. XGB is one of the variants of gradient boosting and is a supervised learning algorithm. This type of system is developed to increase performance and processing speed. Through this proposed method, an attempt is made to recognize patterns from scalp EEG recordings that would allow the detection of IGE with high accuracy and differentiate IGE patients from healthy controls, creating an additional tool to support clinicians in their decision-making. Among the ML methods applied, the proposed XGB method achieves a better prediction of the distinct features in EEG signals from patients with IGE. XGB was 6.26% more accurate than the k-Nearest Neighbours method and was more accurate than the support vector machine (10.61%), decision tree (9.71%) and Gaussian Naïve Bayes (11.83%). Besides, the proposed XGB method showed the highest area under the curve (AUC 98%) and balanced accuracy (98.13%) of all methods tested. Application of ML technique in EEG of patients with epilepsy is very recent and is emerging with promising results. In this research work, we showed the usefulness of ML techniques to identify and predict generalized epilepsy from healthy controls in scalp EEG studies. These findings could help develop automated tools that integrate these ML techniques to assist clinicians in differentiating between patients with IGE from healthy controls in daily practice.


The roles of the simian virus 40 tumor antigens in transformation of Chinese hamster lung cells.
Simian virus 40 mutants and deletions between 0.54 and 0.59 map units direct the synthesis of defective 20K t antigens (Crawford et al., 1978). These deletion mutants transformed actively growing CHL cells nearly as efficently as did wild-type virus, in either the focus formation assay or the growth in soft agar assay. In contrast, when CHL cells were in a resting state during infection, the transformation frequency of the mutants relative to wild-type dropped approximately 50 fold. The presence of the phorbol ester, TPA, diminished this difference. CHL cell lines transformed by the deletion mutants and selected by the focus assay grew almost as efficiently in soft agar as lines transformed by wild-type SV40. Both produced tumors in nude mice. The function of the 20K t antigen is discussed.


Identification of lysine 134 in the steroid-binding site of the sex steroid-binding protein of human plasma.
The sex steroid-binding protein of human plasma SBP (or sex hormone-binding globulin, SHBG) was specifically inhibited with the alkylating affinity label, 17 beta-[[( 2-14C]bromoacetyl)oxy]-5 alpha-androstan-3-one. The natural ligand, 5 alpha-dihydrotestosterone, was shown to protect against inactivation and labeling. The steroid-binding activity of the protein was abolished when approximately 1 mol of label was incorporated into 1 mol of dimeric SBP. In order to identify and locate the labeled amino acid in the steroid-binding site, the steroidal portion of the bound label was first removed and the protein was digested with Achromobacter protease and subdigested with trypsin. Seven radioactive peptides were isolated, sequenced, and found to contain the common sequence QVSGPLTSXR. Residue X was identified as lysine-134 from the SBP amino acid sequence (Walsh, K. A., Titani, K., Kumar, S., Hayes, R., and Petra, P. H. (1986) Biochemistry 25, 7584-7590). The results indicate that only 1 of the 2 lysine-134 residues in the homodimer was labeled. This suggests that the steroid-binding site is constructed from an association of the two subunits in an AB to BA "sandwich" configuration with lysine-134 residue of one subunit on one surface near the D-ring and the lysine-134 of the other subunit at the opposite end of the steroid, or well away from the steroid-binding site. Although the nature of the data does not allow description of a specific role for lysine-134, its proximity to the 17 beta-OH of the steroid nucleus suggests participation in the binding process through direct or indirect hydrogen bonding.


Glare disability in patients with hydrophilic and hydrophobic acrylic intraocular lens implants.
To compare glare disability test results in patients with hydrophilic and hydrophobic acrylic intraocular lenses (IOL). Sixty eyes of 60 patients were studied in three groups of 20. Each eye in Group 1 had a single-piece hydrophilic acrylic (Bioacryl, Biotech, France) IOL implant, and each eye in Group 2 had a three-piece hydrophobic acrylic (AcrySof, Alcon, USA) IOL implant. Group 3 was the control group, and consisted of eyes without cataracts. Glare disability was tested using the Ophthimus glare sensitivity test (Ophthimus, Sweden). For each eye, we determined log contrast sensitivity values without exposure to glare source and with exposure to glare source. The difference between these values was recorded as the threshold contrast increase. An infrared camera was used to measure pupil diameter during glare disability testing, and pupil diameter greater than 4 mm was used as an exclusion criterion to eliminate edge design as a potential contributor to glare disability. The respective mean log contrast sensitivity scores for Groups 1, 2, and 3 in the absence of the glare source were 0.80 +/- 0.03, 0.81 +/- 0.04, and 0.79 +/- 0.08. The corresponding findings with glare source were 0.84 +/- 0.07, 0.89 +/- 0.07, and 0.84 +/- 0.03. The threshold contrast increase in Group 2 (0.070 +/- 0.035) was significantly higher than that in both Group 1 (0.043 +/- 0.040) and the control group (0.045 +/- 0.026) (p < 0.05 for both comparisons). There were no significant differences between Group 1 and the control group regarding log contrast sensitivity values with glare source and threshold contrast increase (p > 0.05 for both comparisons). The eyes with hydrophilic acrylic IOL showed better glare disability results than those with hydrophobic acrylic IOL. The superior performance of the hydrophilic acrylic IOL could be related to their lower refractive index and equi-convex design.


[Semiquantitative display of regional cerebral blood flow and neuronal function using N-isopropyl-(123I)-p-iodoamphetamine (IMP) and emission tomography].
Between June 1983 and March 1985 197 patients were examined with 123I-IMP brain scintigraphy and ECT. They had various neurological diseases, the majority suffered from cerebrovascular affections. The reference for pathological findings was a group of 14 healthy volunteers. A visual interpretation of the ECT-slices alone is not reliable enough. A semiquantitative assessment of perfusion abnormalities seems to be very important, especially in diffuse or bilateral alterations. The proposed semiquantitative evaluation makes use of the total cerebral accumulation in the control group (35.6 +/- 4.3 cts/pixel/mCi/min) and right-left ratios of 14 paired and fixed regions of interest (ROI) in three ECT slices. The ROIs are related to the anatomical flow supply areas in the brain. The right-left ratios are around 1.0 with a physiological asymmetry of +/- less than 2% (standard deviation). The asymmetry is an important parameter in assessing presence and severity of disease. If pathological findings are diffuse or symmetric, the visual interpretation of scintigrams or the calculation of right-left ratios are often unsuccessful. Thus, the same ROI-data were separated for the right and left hemisphere and drawn as cts/ROI/pixel/mCi in diagrams as profile. The diagram demonstrates perfusion abnormalities semiquantitatively without using calculation of asymmetry, since asymmetry alone cannot differentiate between hypoperfusion of one and hyperperfusion of the contralateral side.


MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer.
MicroRNAs (miRNAs) regulate the function of several immune cells, but their role in promoting CD8(+) T cell immunity remains unknown. Here we report that miRNA-155 is required for CD8(+) T cell responses to both virus and cancer. In the absence of miRNA-155, accumulation of effector CD8(+) T cells was severely reduced during acute and chronic viral infections and control of virus replication was impaired. Similarly, Mir155(-/-) CD8(+) T cells were ineffective at controlling tumor growth, whereas miRNA-155 overexpression enhanced the antitumor response. miRNA-155 deficiency resulted in accumulation of suppressor of cytokine signaling-1 (SOCS-1) causing defective cytokine signaling through STAT5. Consistently, enforced expression of SOCS-1 in CD8(+) T cells phenocopied the miRNA-155 deficiency, whereas SOCS-1 silencing augmented tumor destruction. These findings identify miRNA-155 and its target SOCS-1 as key regulators of effector CD8(+) T cells that can be modulated to potentiate immunotherapies for infectious diseases and cancer.


The DOTA macrocyclic cavity in metallic radiopharmaceuticals: Mythology or reality?
The hypothetical concept of 'macrocyclic cavity' is largely employed as useful model to interpret the affinity of metal ions for the macrocyclic chelating ligand 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (H4DOTA). It Is hypothesized that a close matching between the size of the macrocyclic cavity and that of the metallic ion is a key parameter to ensure the high-yield formation of stable coordination metal-DOTA complex. This approach has become popular in the design of radiopharmaceuticals containing radiometals and H4DOTA as chelating group. Based on X-ray structural data of metallic complexes formed by the ligand H4DOTA upon coordination with a variety of metals, an elementary argument based on Euclidean geometry is presented here that questions the existence of the hypothetical 'macrocyclic cavity' within the chelator macrocycle. The geometrical analysis was applied to the complex formed by a Ga3+ ion coordinated to H4DOTA as model compound. Application of Euclidean geometry to calculate bond angles in the coordination complex of the ligand H4DOTA with the Ga+3 ion, supposed to incorporate a hypothetical 'macrocyclic cavity', revealed that this conceptual entity has no physical reality and, therefore, cannot be considered a meaningful description of a stable structural arrangement for metallic radiopharmaceuticals.


Treatment of class II malocclusion with open bite and absence of central maxillary incisor lost by trauma aided by use of orthodontic mini-implants.
The aim of this article is to report the clinical case of non-surgical treatment of a Class II malocclusion with anterior open bite, associated with absence of a maxillary central incisor avulsed due to trauma. Treatment proceeded with the use of orthodontic mini-implants as an anchorage device for intrusion of the maxillary molars and for mesial movement of the lateral incisor to replace the central incisor. Treatment resulted in good occlusion, with anterior and lateral guides, enhancement of the facial profile, and good dental esthetic appearance without the need for prosthetic treatment. The treatment outcome was satisfactory but needs long-term or permanent retention.


Knockdown of MTHFD2 inhibits proliferation and migration of nasopharyngeal carcinoma cells through the ERK signaling pathway.
Folate-mediated one-carbon metabolism (FOCM) plays a vital role in supporting cancer cells hyperproliferation. Malignant cells, including nasopharyngeal carcinoma (NPC) cells, are characterized by rapid proliferation and thus need large numbers of nucleotides and nutrients generated from FOCM. However, the mechanism and key genes involved in FOCM playing a vital role in NPC progression are still unclear. This study aimed to find out the key gene, and its functions in NPC and explore the potential mechanism. Bioinformatics analysis based on TCGA and GSEA database were performed to screen the key FOCM related gene in HNSCC. The effects of MTHFD2 on cell proliferation, apoptosis and migration were conducted through MTHFD2 knockdown cell lines in vitro experiments. Cell proliferation was explored by CCK8 assay and colony formation assay. Cell apoptosis was tested through flow cytometry. Transwell migration assay was performed to study the cell migration. The potential pathway was explored by RNA-seq and the ERK inhibitor SCH772984 and the ERK activator tBHQ were applied to verify the effect of MTHFD2 in NPC via the ERK pathway. Finally, xenograft tumor model was used to explore the tumorigenicity of NPC cells in vivo and IHC was performed to study the expression of related proteins. MTHFD2 was highly expressed in NPC and associated with a poor prognosis. MTHFD2 knockdown inhibited the proliferation, migration and induced apoptosis of NPC cells in vitro. In consistent with cellular results, knockdown of MTHFD2 suppressed the tumorigenicity of NPC cells in vivo. MAPK pathway was enriched among DEGs between MTHFD2 knockdown cells and control cells. And the level of p-ERK1/2 and p-p38 MAPK was decreased in MTHFD2 knockdown cells and xenograft tumors of MTHFD2 knockdown cells. Furthermore, the application of the selective ERK inhibitor SCH772984 and the ERK activator tBHQ confirmed that MTHFD2-knockdown inhibited the proliferation and migration of NPC cells via the ERK signaling pathway. MTHFD2 was up-regulated in NPC tissues and its high expression was linked to a poor prognosis. Knockdown of MTHFD2 inhibited proliferation and migration of NPC cells through the ERK signaling pathway, which may provide new clues and targets for the treatment of NPC.


[Quantitative evaluation of thermosensitivity in patients with mandibular fractures].
The temperature and pain thresholds of 30 patients with mandibular fractures were evaluated with a specially developed measuring device in a prospective study to examine neurosensory disturbances of the inferior alveolar nerve (IAN). Measurements in 30 patients with 45 mandibular fractures were done before, immediately after, and over the course of half a year after operation. Outcomes of the thermosensitivity measurement (TSM) were compared to the results of the two point discrimination (2-PD) test, sharp/blunt test (SBT), and questioning the patients about their subjective feelings (SF). Post-traumatically, neurosensory testing revealed up to 2.8 degrees C (mean) increased thresholds as compared with the intact side. By contrast, post operative diagnostics clearly revealed up to 8.1 degrees C (mean) increased thresholds. Compared with the clinical sensory tests, the post-therapeutic (3-6 months postoperative) measurements with the TSM device proved a resensitization and threshold decrease by up to 3 degrees C. We found more exact and reproducible results of the TSM in comparison to those of the 2-PD and SBT for the evaluation of sensory disturbances of the IAN. Close agreements between the results of the TSM and the SF could be detected. Because of its sensitivity and accuracy in the quantitative detection of temperature and pain thresholds, the TSM is particularly suitable for evaluating neurosensory deficits and monitoring their progression.


The evolution of Trypanosoma cruzi: the 'bat seeding' hypothesis.
Recent discussions on the evolution of Trypanosoma cruzi have been dominated by the southern super-continent hypothesis, whereby T. cruzi and related parasites evolved in isolation in the mammals of South America, Antarctica and Australia. Here, we consider recent molecular evidence suggesting that T. cruzi evolved from within a broader clade of bat trypanosomes, and that bat trypanosomes have successfully made the switch into other mammalian hosts in both the New and Old Worlds. Accordingly, we propose an alternative hypothesis--the bat seeding hypothesis--whereby lineages of bat trypanosomes have switched into terrestrial mammals, thereby seeding the terrestrial lineages within the clade. One key implication of this finding is that T. cruzi may have evolved considerably more recently than previously envisaged.


Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients.
The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients. Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited. A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female subjects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 ± 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia-treated incidence and death during the follow-up period, with a particular focus on primary prevention patients. Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p = 0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p < 0.001). Female sex was an independent predictor of ventricular arrhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p = 0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p = 0.25). Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects.


Patients' knowledge and beta blocker treatment improve prognosis of patients from a heart failure clinic.
Several studies have shown improvement of prognosis in patients managed in heart failure (HF) clinics. However, the value of the individual management components is not well established. To assess the prognostic value of pharmacological treatment and patient's knowledge in patients receiving care in a HF clinic. In our prospective cohort study we followed 115 patients (50 from an HF clinic and 65 receiving usual care) for at least 12 months. Knowledge was assessed using a Patient Knowledge Questionnaire (PKQ). During a median follow-up of 561 days, fewer patients from the HF clinic died or were rehospitalized due to HF than those receiving usual care (42% vs. 65%, p = 0.016). The prescription rates of ACE inhibitors (94% to 98%) and beta blockers (40% to 94%) increased in the patients from the HF clinic. In these patients the PKQ score also increased from 4.8 (1.5) to 7.9 (1.3), p<0.001. In the Cox proportional hazard model, treatment with beta blockers at > or = 50% of the target daily dose (Hazard Ratio [HR] 0.3, 95% Confidence Interval [CI] 0.10-0.95) and a PKQ score <7 (HR 3.92, 95% CI 1.39-11.03) predicted prognosis in the patients from the HF clinic. Patient management in the HF clinic reduced the incidence of death or of HF rehospitalization. Poor prognosis of patients receiving care in the HF clinic was predicted by poor patient knowledge and underdosing with beta blockers.


Genomic African and Native American Ancestry and 15-Year Cognitive Trajectory: Bambui Study, Brazil.
To investigate the association between African and Native American genomic ancestry and long-term cognitive trajectories in admixed Brazilians. Population-based longitudinal study. Bambui-Epigen (Brazil) cohort study. Adults aged 60 and older (N=1,215) MEASUREMENTS: Participants were followed from January 1997 to December 2011. Cognitive function was assessed annually using the Mini-Mental State Examination (MMSE), totaling 12,208 measurements. We used linear mixed-effects pattern models to assess MMSE score trajectories. Ancestry was assessed using a genome-wide approach. After adjustments for covariates, the highest quintile of African ancestry was associated with poorer baseline cognitive performance (β=-0.73, 95% confidence interval (CI)=-1.36 to -0.11) but not with cognitive trajectory. Educational level modified the baseline association between highest African ancestry and cognitive performance in that the association was observed only in those with very low (<4 years) education (β=-1.13, 95% CI=-2.02 to -0.23). No association was found between Native American ancestry and baseline cognitive function or its trajectory. Genomic African and Native American ancestry levels had no prognostic value for age-related cognitive decline in this admixed population.


Cephalometric evaluation of the anterior open bite treatment.
The present study was aimed at evaluating the treatment changes of anterior open bite malocclusion cases treated by means of the Multiloop Edgewise Arch Wire technique, which is considered one of the more effective treatment modalities for anterior open bite malocclusions. The open bite sample was composed of 16 young adults, 4 males and 12 females. The normal occlusion sample, as a controlled sample was composed of 58 young adults who had pleasing facial profiles and normal occlusions with no experience of orthodontic or prosthodontic treatment. The normal sample was subdivided by the cephalometric vertical facial relationships. Forty adults with cephalometric vertical facial relationships within the normal range of Korean standards were classified as Normal Occlusion Group 1. Eighteen adults with an increased vertical facial relationship but with normal occlusion, were classified as Normal Occlusion Group 2. Thirty-nine reference points were digitized on each film, and the computerized cephalometric analysis was obtained with 8 skeletal, 10 dentoalveolar, 17 teeth angulations, and 4 occlusal plane measurements. Treatment changes were determined by the paired t test, and the structural differences between the four groups were tabulated by the Student's t test. The treatment changes were observed mainly in the dentoalveolar region in the upper and the lower occlusal planes, accompanied by the uprighting of the posterior teeth to the occlusal plane through the distal tipping movement of the entire dentition. After the treatment, there was a tendency for the structural feature of the open bite group to approximate those of the normal occlusion group 2. This ascertains that the treatment changes of open bite malocclusion produced by means of the multiloop edgewise arch wire technique are similar to those found in the natural dentoalveolar compensatory mechanism.


Adult mental health consequences of peer bullying and maltreatment in childhood: two cohorts in two countries.
The adult mental health consequences of childhood maltreatment are well documented. Maltreatment by peers (ie, bullying) has also been shown to have long-term adverse effects. We aimed to determine whether these effects are just due to being exposed to both maltreatment and bullying or whether bullying has a unique effect. We used data from the Avon Longitudinal Study of Parents and Children in the UK (ALSPAC) and the Great Smoky Mountains Study in the USA (GSMS) longitudinal studies. In ALSPAC, maltreatment was assessed as physical, emotional, or sexual abuse, or severe maladaptive parenting (or both) between ages 8 weeks and 8·6 years, as reported by the mother in questionnaires, and being bullied was assessed with child reports at 8, 10, and 13 years using the previously validated Bullying and Friendship Interview Schedule. In GSMS, both maltreatment and bullying were repeatedly assessed with annual parent and child interviews between ages 9 and 16 years. To identify the association between maltreatment, being bullied, and mental health problems, binary logistic regression analyses were run. The primary outcome variable was overall mental health problem (any anxiety, depression, or self-harm or suicidality). 4026 children from the ALSPAC cohort and 1420 children from the GSMS cohort provided information about bullying victimisation, maltreatment, and overall mental health problems. The ALSPAC study started in 1991 and the GSMS cohort enrolled participants from 1993. Compared with children who were not maltreated or bullied, children who were only maltreated were at increased risk for depression in young adulthood in models adjusted for sex and family hardships according to the GSMS cohort (odds ratio [OR] 4·1, 95% CI 1·5-11·7). According to the ALSPAC cohort, those who were only being maltreated were not at increased risk for any mental health problem compared with children who were not maltreated or bullied. By contrast, those who were both maltreated and bullied were at increased risk for overall mental health problems, anxiety, and depression according to both cohorts and self-harm according to the ALSPAC cohort compared with neutral children. Children who were bullied by peers only were more likely than children who were maltreated only to have mental health problems in both cohorts (ALSPAC OR 1·6, 95% CI 1·1-2·2; p=0·005; GSMS 3·8, 1·8-7·9, p<0·0001), with differences in anxiety (GSMS OR 4·9; 95% CI 2·0-12·0), depression (ALSPAC 1·7, 1·1-2·7), and self-harm (ALSPAC 1·7, 1·1-2·6) between the two cohorts. Being bullied by peers in childhood had generally worse long-term adverse effects on young adults' mental health. These effects were not explained by poly-victimisation. The findings have important implications for public health planning and service development for dealing with peer bullying. Wellcome Trust, Medical Research Council, Economic and Social Research Council, National Institute of Mental Health, the National Institute on Drug Abuse, NARSAD (Early Career Award), and the William T Grant Foundation.


Grain-sized moxibustion at Zusanli (ST36) promotes hepatic autophagy in rats with hyperlipidemia by regulating the ULK1 and TFEB expression through the AMPK/mTOR signaling pathway.
Grain-sized moxibustion is an effective treatment for hyperlipidemia, but how it regulates dyslipidemia and liver lipid deposits still needs to be fully understood. This study explored the molecular biological mechanism of grain-sized moxibustion to regulate hepatic autophagy in hyperlipidemic rats by affecting ULK1 and TFEB through the AMPK/mTOR signaling pathway. Thirty male Sprague-Dawley (SD) rats were fed a high-fat diet for eight weeks to induce hyperlipidemia. Hyperlipidemic rats were divided into the HFD group, HFD + Statin group, HFD + CC + Moxi group, and grain-sized moxibustion intervention group (HFD + Moxi group). The control (Blank) group consisted of normal rats without any intervention. Grain-sized moxibustion and drug interventions were initiated eight weeks after high-fat diet induction and continued for ten weeks. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), as well as hepatic triglyceride (TG), were measured after treatment. Hepatic steatosis and the expression of LC3I, LC3II, p62, p-AMPK, AMPK, p-mTOR, mTOR, ULK1, p-ULK1, and TFEB in the liver were analyzed. Compared with the HFD group, grain-sized moxibustion improved hyperlipidemia and hepatocyte steatosis, increased the LC3, p-AMPK, p-ULK1, and nuclear TFEB expression in the liver, but decreased the p62 and p-mTOR expression. Grain-sized moxibustion at ST36 acupoints could regulate the blood lipid level of SD rats with hyperlipidemia, increase the expression level of ULK1 and TFEB by activating the AMPK/mTOR signaling pathway in liver tissues, and initiate the transcription of autophagy genes such as LC3.


Metabolomic profiling of Burkholderia cenocepacia in synthetic cystic fibrosis sputum medium reveals nutrient environment-specific production of virulence factors.
Infections by Burkholderia cenocepacia lead to life-threatening disease in immunocompromised individuals, including those living with cystic fibrosis (CF). While genetic variation in various B. cenocepacia strains has been reported, it remains unclear how the chemical environment of CF lung influences the production of small molecule virulence factors by these strains. Here we compare metabolomes of three clinical B. cenocepacia strains in synthetic CF sputum medium (SCFM2) and in a routine laboratory medium (LB), in the presence and absence of the antibiotic trimethoprim. Using a mass spectrometry-based untargeted metabolomics approach, we identify several compound classes which are differentially produced in SCFM2 compared to LB media, including siderophores, antimicrobials, quorum sensing signals, and various lipids. Furthermore, we describe that specific metabolites are induced in the presence of the antibiotic trimethoprim only in SCFM2 when compared to LB. Herein, C13-acyl-homoserine lactone, a quorum sensing signal previously not known to be produced by B. cenocepacia as well as pyochelin-type siderophores were exclusively detected during growth in SCFM2 in the presence of trimethoprim. The comparative metabolomics approach described in this study provides insight into environment-dependent production of secondary metabolites by B. cenocepacia strains and suggests future work which could identify personalized strain-specific regulatory mechanisms involved in production of secondary metabolites. Investigations into whether antibiotics with different mechanisms of action induce similar metabolic alterations will inform development of combination treatments aimed at effective clearance of Burkholderia spp. pathogens.


Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure.
Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/- 0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm, NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/- 9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8 ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our patient group. We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.


Plug-In Safe-by-Design Nanoinorganic Antibacterials.
Due to antimicrobial resistance and the adverse health effects that follow broad and inappropriate use of antibacterial agents, new classes of antibacterials with broad and strong bactericidal activity and safety for human use are urgently required globally, increasingly so with the onset of climate change. However, R&D in this field is known to be rarely profitable, unless a cost-effective, flexible, and convenient platform that ensures the production of workable candidate antibacterials can be developed. To address this issue, inorganic nanomaterials have been considered for their bactericidal activities, yet further investigations of composition crystalline modifications and/or surface biomaterial coatings are still required to provide effective and safe antibacterial nanoparticles. In this study, we developed a plug-in system comprising a spark plasma reactor and a flow heater under nitrogen gas flow to supply precursor inorganic nanoparticles (Cu-Te configuration) that can be modulated in-flight at different temperatures. From antibacterial and toxicological assays in both in vitro and in vivo models, bactericidal and toxicological profiles showed that the plug-in system-based platform can be used to identify key parameters for producing safe-by-design agents with antibacterial activity [>88% (in vitro) and >80% (in vivo) in antibacterial efficiency] and safety (>65% in in vitro viability and >60% in in vivo survival rate).


Thallium-201 imaging in anomalous left coronary artery originating from pulmonary trunk.
A 3-month-old infant with anomalous origin of the left main coronary artery (LMCA) from the pulmonary trunk was evaluated using resting thallium imaging. The imaging findings were consistent with myocardial scar and ischemia of the anterolateral and posterolateral walls in the distribution of the LMCA.


A randomised trial to compare Truview PCD®, C-MAC® and Macintosh laryngoscopes in paediatric airway management.
To evaluate and compare the Truview PCD and C-MAC laryngoscopes to the standard Macintosh laryngoscope in paediatric patients. One hundred and fifty ASA I-II patients in the age group of 1-6 years (10-20 kg) scheduled for elective surgery were randomised into three equal groups for laryngoscopy and intubation with either Truview PCD (Group T), C-MAC (Group C) or Macintosh (Group M) laryngoscopes under general anaesthesia. Percentage of glottic opening (POGO) score, application of external laryngeal manoeuvre, time to intubation, number of attempts at intubation, failed intubations, episodes of desaturation and trauma caused were recorded and statistically analysed. A p value of <0.05 was taken as significant. POGO scores were significantly better with Truview PCD as compared with C-MAC and Macintosh laryngoscopes (94.7 ± 12.9/82 ± 25.0/85.1 ± 17.1; p < 0.01). There were no failed attempts, episodes of desaturation or trauma in any of the patients. The mean intubation time taken was 19.2 s in group T, 12.3 s in group C and 10.7 s in group M, respectively. There is a statistically significant difference among groups (p < 0.01). Eight patients in group T, 21 out of 50 patients in group C and 19 out of 50 patients in group M needed OELM, respectively. There is significant difference among the groups (p < 0.01) CONCLUSION: Using Truview PCD to assist intubation offers excellent view field of glottic opening after OLEM and the mean time taken is less than 20 s. The Truview PCD tool is suitable for paediatric patients.


Motor innervation of striated oesophageal muscle. Part 2. Characteristics of the oesophagomotor fibres in the rat studied by implanting the vagus nerve into a skeletal muscle.
In 12 rats the right vagus nerve distal to its recurrent laryngeal branch was implanted into the inferior segment of the denervated sternohyoid muscle. One month after implantation the first signs of neuromuscular transmission at the vagal motor endings could be recorded. Two months after implantation the reinnervated muscles showed vigorous contractions on electrical stimulation of the vagus nerve. During the performance of propulsive waves of the oesophagus the implanted vagus nerve caused clonic to tetanic contractions of the sternohyoid muscle, thus proving the oesophagomotor genesis of the reinnervating nerve fibres. In addition, the vagus-innervated motor end-plates were shown to exhibit the same ultrastructural peculiarities as the original neuromuscular junctions of the oesophagus. In sections stained for cholinesterase it could be demonstrated that the oesophagomotor fibres had preferentially reinnervated the denervated motor end-plates. In many instances the subneural apparatus was not completely covered by the vagal axon terminals. Newly formed, ectopic vagal motor endings were few in number and confined to muscle fibres immediately adjacent to the site of nerve-implantation. Six months after implantation some of the vagal motor endings showed signs of degeneration. As in the oesophagus, the reinnervating oesophagomotor fibres proved to be unmyelinated, sometimes forming a plexus-like intramuscular network before terminating at motor end-plates. Myelinated vagal nerve fibres were also observed running between the skeletal muscle fibres, but they did not establish any demonstrable form of neuromuscular contacts. It was concluded that, in the rat, the myelinated fibres of the oesophageal nerves are afferent, whereas the oesophagomotor fibres, although supplying striated muscle, are unmyelinated.


Stability and emetic activity of enterotoxin like X (SElX) with high carrier rate of food poisoning Staphylococcus aureus.
In order to analyze and clarify the thermal stability of food poisoning Staphylococcus aureus (S. aureus) enterotoxin-like X (SElX) and the biological characteristics of digestive enzymes, and to evaluate the risk of S. aureus carrying selx gene in food poisoning, the selx gene carrying rates of 165 strains isolated from 95 food poisoning events from 2006 to 2019 were first statistically analyzed. Subsequently, the purified recombinant SElX protein was digested and heated, and the superantigen activity was verified with mouse spleen cells and peripheral blood mononuclear cells of kittens. At the same time, the emetic activity and toxicity of SElX were evaluated using the kitten vomiting animal model, mice toxin model and in vitro cell models. The results showed the selx gene carrying rate of 165 food poisoning S. aureus strains was 90.30 %. SElX had significant resistance to heat treatment and pepsin digestion (pH = 4.0 and pH = 4.5), and had good superantigen activity and emetic activity. However, there is no significant lethal effect on mice and no significant toxicity to cells. Importantly, we found that SElX had an inhibitory effect on acidic mucus of goblet cells in various segments of the small intestine. The present study investigated the stability of SElX, and confirmed the emetic activity of SElX by establishing a kitten vomiting model for the first time, suggesting that SElX is a high risk toxin of food poisoning, which will provide new ideas for the prevention and control of S. aureus food poisoning.


Cryo-FIB-lift-out: practically impossible to practical reality.
In this paper, we explore the development of the Cryo-Lift-Out (cryo-LO) technique as preparation tool for cryogenic transmission electron microscopy (cryo-TEM). What started in early work defying what was considered 'practically impossible' has developed into state-of-the-art practical reality. This paper presents the key hardware, basic principles and key considerations for the practical usage of cryogenic Lift-Out for those new to the field. Detailed protocols and in-depth description of considerations and points for further development are presented. The authors have attempted to formalise everything known about the technique gathered together from their expertise gained in the development of this approach. LAY DESCRIPTION: A major challenge in electron microscopy is the production of suitable samples from hydrated biological and soft-matter materials for subnanometre resolution imaging in a cryo-Transmission Electron Microscope (TEM). A well-known solution for room temperature materials is called (in situ) Lift-Out. It uses a fine needle that picks up a tiny section called a lamella. Lamellae are made by a Focused Ion Beam (FIB). In this paper, we seek to set out the beginnings of Lift-Out sample preparation conducted under cryogenic conditions and the development of this approach as applied to frozen, hydrated biological and soft-matter samples. We discuss the required basic hardware and provide a thorough description of developed protocols. We aim at those new to the field of cryo-Lift-Out to fully educate them in the finer points of hardware setup and practical considerations when attempting to perform cryo-Lift-Out and to demonstrate what has been achieved thus far. We also discuss areas of further improvement and talking points for the future direction of this promising sample preparation technique.


Study of cultured skin fibroblasts from patients with and without ischemic heart disease. Metabolism of low density lipoprotein and cholesterol ester, synthesis of cellular lipids and effect of chloroquine on accumulation of cholesterol ester.
The aim of the present study was to determine whether skin fibroblasts derived from patients with ischemic heart disease (IHD), which could not be related to accepted risk factors, would show a metabolic abnormality with respect to lipid or lipoprotein metabolism. Male patients 30-52 years old suffering from IHD were subdivided into two groups: those in whom IHD was not associated with risk factors such as hypertension, hyperlipoproteinemia, diabetes or smoking (group I); and those in whom heavy smoking was the only major risk factor recognized (group II). The controls were patients with angiographically normal coronary arteries (group III). Skin fibroblasts obtained from these patients were cultured and investigated with respect to metabolism of low density lipoprotein (LDL), synthesis of cellular lipids and induction of cholesterol ester accumulation in the presence of chloroquine, an inhibitor of lysosomal hydrolases. After 24 h incubation, the uptake and degradation of LDL protein in cells from patients of group II was significantly higher than in the controls, group III, but not different from those of group I. Hydrolysis of [3H] cholesterol linoleate, and incorporation of [3H] oleic acid into total lipids and into cholesterol esters was similar in cell cultures of the 3 groups studied. After exposure to chloroquine and LDL, the cells from the different donors accumulated cholesterol ester to a similar extent. Thus, whereas no significant difference was encountered in the lipid and lipoprotein metabolism in cells of patients with IHD without risk factors and controls, some increase in LDL metabolism was seen in cells from patients with IHD and with a history of smoking. It remains to be determined whether this increase was causally related to smoking.


Trabecular bone does not have a fractal structure on light microscopic examination.
The fractal dimension of the boundary of trabecular bone in 62 biopsies was measured on histological sections using a box-counting method implemented on a microcomputer image analysis system. The calculated fractal dimension had a mean value of 0.99 with a normal distribution. Since this value is not greater than the topological dimension, trabecular bone, when examined by light microscopy, does not have a fractal structure. Conventional Euclidean dimensions will continue to be the most useful measurements in bone histomorphometry.


Effect of mefenamic acid on bowel transit time in healthy adult volunteers.
The effect of mefenamic acid on bowel transit time was investigated. Seven healthy adult male subjects of age 39 +/- 2.4 years (mean +/- S.E.M.) received placebo or mefenamic acid (500 mg t.d.s) orally in randomized order for five days, with a 7-day washout between studies. On the third morning after starting the drug they had a meal containing Redi-Brek and baked beans with radio-opaque markers. Small bowel transit time was measured using breath hydrogen, and whole gut transit time was measured using radio-opaque markers. The small bowel transit times were 160 min (median) with placebo and 50 min with mefenamic acid (P less than 0.05). The percentages of appearance of marker in stool within 24 h were 24.9 +/- 11.8 (mean +/- S.E.M.) with placebo and 48.9 +/- 11.7 with mefenamic acid (P less than 0.05). The times of appearance of twenty-fifth marker in stool were 41.0 +/- 4.4 h with placebo and 26.9 +/- 3.2 h with mefenamic acid (P less than 0.05). The total weights of faeces in 72 h were 500.9 +/- 96.2 g with placebo and 657.1 +/- 118.8 g with mefenamic acid (P less than 0.05). Mefenamic acid in therapeutic doses (500 mg t.d.s.) accelerated bowel transit time in healthy subjects.