Metabolic reprogramming of tumor-associated macrophages by collagen turnover promotes fibrosis in pancreatic cancer.
A hallmark of pancreatic tumors is their highly desmoplastic stroma composed of fibroblasts, immune cells, and a dense network of collagen fibers. Tumor-associated macrophages are one of the most abundant immune cell populations in the pancreatic tumor stroma. Their protumorigenic function has been attributed predominantly to their capacity to promote immune evasion and metastasis. Tumor-assoc iated macrophages are also well known for their role in the remodeling of the stroma via collagen production and degradation, with the latter being mediated by mannose receptor (MRC1)-dependent endocytosis of collagen. Here we show that MRC1-mediated collagen internalization and subsequent lysosomal degradation by macrophages harboring a tumor-associated phenotype are accompanied by the accumulation of collagen-derived intracellular free amino acids and increased arginine biosynthesis. The resulting increase in intracellular arginine levels leads to the up-regulation of inducible nitric oxide synthase and the production of reactive nitrogen species. Furthermore, reactive nitrogen species derived from internalized and degraded collagen promotes a profibrotic phenotype in pancreatic stellate cells resulting in enhanced intratumoral collagen deposition. Overall, our findings identify a role for extracellular matrix remodeling in the functional modulation of tumor-associated macrophages via metabolic rewiring.


The bangladesh cyclone of 1991: why so many people died.
Living with natural disasters has become a way of life in Bangladesh. On the night of 29 April 1991 a severe cyclonic storm, accompanied by tidal surges up to 30 feet high, battered the coastal areas of Bangladesh for 3-4 hours. Thousands of people were killed and property worth billions of dollars was destroyed. After the cyclone, several studies, using epidemiological and anthropological methods, looked at the impact of the cyclone. It was estimated that over 67,000 people lost their lives. Women, children and the elderly were much more at risk and so were those from the socio-economically disadvantaged section of the population. Cyclone shelters were few in relation to need but proved very helpful in saving lives. At least 20 per cent more deaths would have occurred in the absence of these shelters. The article documents impressive improvements in Bangladesh's-ability to cope and makes recommendations for the future.


Tonic accommodation, tonic vergence and surround propinquity.
Previous studies have typically assessed tonic accommodation (TA) and tonic vergence (TV) by placing subjects in total darkness. However, a recent investigation demonstrated that even under such apparently stimulus-free conditions, subjects' awareness of the proximity of the adjacent surroundings and overall room topography (i.e. surround propinquity) may still influence the accommodative response. Accordingly, the aim of the present study was to measure TA and TV while subjects (n = 34) viewed an illuminated distant target (viewing distance = 6 m) to minimize this propinquity effect. TA was measured using an objective, open-field, infrared optometer under two conditions: first, while viewing the distant target monocularly through a 0.5 mm pinhole, and second in total darkness. Additionally, TV was assessed by determining the heterophoria subjectively while subjects viewed the distant target biocularly through 0.5 mm pinholes. The mean level of TA using the pinhole technique (mean = 0.28 D) was significantly lower than that observed in total darkness (mean = 0.60 D). Furthermore, a significant positive correlation (r = 0.86) was found when comparing the difference between the two TA measurements with the level obtained in total darkness. Those subjects having apparently high levels of TA in darkness exhibited the largest propinquity effect. Thus measurements of accommodation recorded in total darkness are likely to have overestimated both the magnitude and normal range of TA. The mean level of TV was 0.58 metre angle. No significant correlation was observed between TV and either of the two TA measurements.(ABSTRACT TRUNCATED AT 250 WORDS)


Hyponatremia after transsphenoidal surgery for pituitary tumors.
We studied the incidence of postoperative hyponatremia in 91 consecutive patients (44 males and 47 females; age, 45 yr; range, 12-76) operated on transsphenoidally for pituitary tumors. A postoperative serum sodium concentration less than 135 mmol/L (the lowest, 109 mmol/L) was observed in 32 (35%) patients. Hyponatremia occurred most commonly in patients operated on for Cushing's disease (11 of 18 patients; 61%). Hyponatremia was symptomatic in 18 (56%) of the patients. Neither the size nor the operability of the tumor or transient postoperative polyuria predicted the development of hyponatremia. Hyponatremia was first observed on the sixth or seventh postoperative day. The patients were treated with water restriction and by increasing the hydrocortisone replacement dose in the case of ACTH deficiency, and recovery took place, on the average, within 5 days. High urinary osmolality and plasma arginine vasopressin concentration during hyponatremia in a subgroup of study patients with these measurements indicated that inappropriate vasopressin secretion was involved in the pathogenesis of hyponatremia. In conclusion, postoperative hyponatremia after transsphenoidal surgery is common and may put the patients at increased risk of severe hyponatremic symptoms. Therefore, all patients should be screened for serum electrolytes for 1 week after transsphenoidal surgery.


An Embedded Sensory System for Worker Safety: Prototype Development and Evaluation.
At a construction site, workers mainly rely on two senses, which are sight and sound, in order to perceive their physical surroundings. However, they are often hindered by the nature of most construction sites, which are usually dynamic, loud, and complicated. To overcome these challenges, this research explored a method using an embedded sensory system that might offer construction workers an artificial sensing ability to better perceive their surroundings. This study identified three parameters (i.e., intensity, signal length, and delay between consecutive pulses) needed for tactile-based signals for the construction workers to communicate quickly. We developed a prototype system based on these parameters, conducted experimental studies to quantify and validate the sensitivity of the parameters for quick communication, and analyzed test data to reveal what was added by this method in order to perceive information from the tactile signals. The findings disclosed that the parameters of tactile-based signals and their distinguishable ranges could be perceived in a short amount of time (i.e., a fraction of a second). Further experimentation demonstrated the capability of the identified unit signals combined with a signal mapping technique to effectively deliver simple information to individuals and offer an additional sense of awareness to the surroundings. The findings of this study could serve as a basis for future research in exploring advanced tactile-based messages to overcome challenges in environments for which communication is a struggle.


A detailed examination of the in vivo and in vitro effects of ACTH on gonadotropin secretion in the adult rat.
These studies were designed to: (1) determine the effects of continuous infusion of synthetic ACTH(1-24) on postcastration changes in serum and pituitary LH, FSH and prolactin in the male rat; (2) assess the effects of adrenalectomy on the gonadotropin and prolactin response to ACTH, and (3) test the hypothesis that ACTH may directly (not via adrenal factors) alter gonadotropin secretion at the brain and/or pituitary level. Adult male rats were either orchidectomized (ORX) or orchidectomized-adrenalectomized (ORX-ADX), and were treated continuously for 6 days with ACTH(1-24) (10 micrograms/day) or saline using an osmotic minipump. Animals were killed on day 6 following castration. ACTH treatment reduced serum LH and prolactin levels in ORX rats to mean values +/- SE of 204 +/- 25 and 37 +/- 3 ng/ml respectively, compared to 366 +/- 72 and 62 +/- 7 ng/ml in saline-treated ORX animals. Serum FSH concentrations were not altered by ACTH administration. Pituitary concentrations of LH and FSH, but not prolactin were enhanced by ACTH treatment. Adrenalectomy had no effect on serum and pituitary gonadotropin and prolactin levels, but abolished the effects of ACTH on these parameters. Central (intracerebroventricular) infusion of ACTH(1-24) (6 micrograms/day X 4 days) failed to alter the rise in serum LH in male rats following orchidectomy. Acute treatment with large doses of ACTH of perifused anterior pituitary glands from male rats and chronic treatment with ACTH of enzymatically dispersed anterior pituitary cells from female rats did not influence basal or GnRH-stimulated LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)


[Intrahospital infections and antimicrobial resistance at University Clinical Center Tuzla].
The aim of presented research was to determine microorganisms which cause intrahospital infections (IHI) with specific anatomical localization and to determine the antimicrobial resistance of these organisms in a group of 5106 patients hospitalized at Surgery Department of the University Clinical Center Tuzla in the period between 1 January to 31 December 2004. The research was conducted in accordance with the National Nosocomial Infections Surveillance (NNIS) methodology. The results show that in 73.82% of cases the gram-negative organisms (p < 0.001) have been isolated and identified as the IHI pathogens, while the gram-positive organisms (p < 0.05) have been isolated and identified as the IHI pathogens in remaining 26.18% of cases. Urinary tract infections, surgical site infections, respiratory tract infections and bloodstream infections have been mostly caused by gram-negative organisms, while the other infections have been more often caused by gram-positive organisms. Gram-positive organisms were found to be resistant to beta-lactam antibiotics and sensitive to the vancomycin. Gram-negative organisms have shown resistance to beta-lactams, aminoglycoside and cephalosporins of third generation. They were well sensitive to cinolones and carbapenems.


The scaffold protein PDZK1 governs diurnal localization of CNT2 on the plasma membrane in mouse intestinal epithelial cells.
Diurnal oscillations in the expression of several types of cell surface transporters have been demonstrated in the intestinal epithelial cells, which are mainly generated at transcriptional or degradation processes. Concentrative nucleoside transporter-2 (CNT2) is expressed at the apical site of intestinal epithelial cells and contributes to the uptake of nucleosides and their analogs from the intestinal lumen into the epithelial cells. In this study, we demonstrated that the localization of CNT2 protein in the plasma membrane of mouse intestinal epithelial cells exhibited a diurnal oscillation without changing its protein level in the whole cell. The scaffold protein PDZK1 interacted with CNT2 and stabilized its plasmalemmal localization. The expression of PDZK1 was under the control of molecular components of the circadian clock. Temporal accumulation of PDZK1 protein in intestinal epithelial cells enhanced the plasmalemmal localization of CNT2 at certain times of the day. The temporal increase in CNT2 protein levels at the plasma membrane also facilitated the uptake of adenosine into the intestinal epithelial cells. These results suggest a novel molecular mechanism for the diurnal localization of cell surface transporters and extend our understanding of the biological clock system that generates apparent physiological rhythms.


Noninvasive Monitoring of Bleomycin-induced Lung Injury in Rats Using Pulmonary Function Test.
The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume (VT), minute volume (VM), and respiratory frequency (FR) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of FR, VT, and VM.


Investigating Antimicrobial Resistance and ESBL Producing Gene in Klebsiella Isolates among Neonates and Adolescents in Southern Bangladesh.
Multidrug-resistant (MDR) clones of Klebsiella pneumoniae (Kpn) have been increasingly documented in community-acquired and nosocomial infections all around the globe. Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamase enzymes derived from SHV genes by mutations. This research work aimed to investigate and analyze the widespread prevalence of Kpn antibiotic resistance in different areas of the southern part of Bangladesh. This particular study was executed and implemented by using 501 clinical samples or isolates from two different hospitals in Chattogram. The disk diffusion method was used to detect Kpn's sensitivity to 16 antibiotics in a drug susceptibility test. By using the PCR technique, the widespread prevalence of antibiotic-resistant gene blaSHV-11 was studied. Sequencing along with phylogenetic analysis was utilized to verify isolates with the blaSHV-11 gene. Almost all of the Kpn isolates were spotted to be antibiotic-resistant. These Kpn isolates were resistant to β-lactams, aminoglycosides, and quinolones at high levels. The spatial analysis displayed that infections involving Kpn were more common in the urban areas (70%) than in the rural areas (30%). Neonates had substantially higher levels (p < 0.001) of resistance to multidrug than other age groups. Cefepime was identified as the most frequent antibiotic-resistant to all age groups (56.68%). The highest numbers of resistant isolates (36.92%) were found in urine samples. The ESBL gene blaSHV-11 was found in 38% isolates. The significant frequency of MDR Kpn harboring β-lactamases and AMR genes strongly suggests the requirement to develop effective antimicrobial resistance control and prevention measures in Bangladesh.


The application of network agenda setting model during the COVID-19 pandemic based on latent dirichlet allocation topic modeling.
Based on Network Agenda Setting Model, this study collected 42,516 media reports from Party Media, commercial media, and We Media of China during the COVID-19 pandemic. We trained LDA models for topic clustering through unsupervised machine learning. Questionnaires (N = 470) and social network analysis methods were then applied to examine the correlation between media network agendas and public network agendas in terms of explicit and implicit topics. The study found that the media reports could be classified into 14 topics by the LDA topic modeling, and the three types of media presented homogeneity in the topics of their reports, yet had their own characteristics; there was a significant correlation between the media network agenda and the public network agenda, and the We Media reports had the most prominent effect on the public network agenda; the correlation between the media agenda and the implicit public agenda was higher than that of the explicit public agenda. Overall, findings showed a significant correlation between network agendas among different media.


[Ganglioneuroma of the appendix. A case report.].
Ganglioneuroma of the appendix are among the most uncommon benign appendiceal tumours. They sometimes obstruct the lumen of the appendix and cause abdominal pain or appendicitis but some are diagnosed incidentally at autopsy or abdominal operations. The first known case in Iceland is represented and the literature reviewed.


Modifying the surface charge of single track-etched conical nanopores in polyimide.
Chemical modification of nanopore surfaces is of great interest as it means that the surface composition is no longer fixed by the choice of substrate material, even to the point where large biomolecules can be attached to the pore walls. Controlling nanopore transport characteristics is one important application of surface modification which is very relevant given the significant interest in sensors based on the transport of ions and molecules through nanopores. Reported here is a method to change the surface charge polarity of single track-etched conical nanopores in polyimide, which also has the potential to attach more complex molecules to the carboxyl groups on the nanopore walls. These carboxyl groups were converted into terminal amino groups, first by activation with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) followed by the covalent coupling of ethylenediamine. This results in a changed surface charge polarity. Regeneration of a carboxyl-terminated surface was also possible, by reaction of the amino groups with succinic anhydride. The success of these reactions was confirmed by measurements of the pore's pH sensitive current-voltage (I-V) characteristics before and after the chemical modification, which depend on surface charge. The permselectivity of the pores also changed accordingly with the modification.


Effect of Grandmaternal Smoking on Body Size and Proportions at Birth.
Many long-term adverse effects of smoking during pregnancy are known. Increasingly, adverse effects in the grandchild after grandmaternal smoking during pregnancy are reported. We explored this in a birth cohort of 24,000 grandmother-mother-child triads identified from the Finnish Medical Birth Register in 1991-2016. Multiple logistic regression was used to analyze the association between any smoking during pregnancy by both grandmother and mother, or only grandmother or mother on adverse birth outcomes. No smoking by neither grandmother nor mother was used as the reference. As endpoints, preterm birth, low birth weight, small for gestational age (birth weight, birth length, head circumference), and body proportionality (low ponderal index, high brain-to-body ratio, high head-to-length ratio) were included. Smoking by both grandmother and mother was consistently associated with higher risks than smoking only by the mother. Birth length and weight were especially sensitive to (grand)maternal smoking. In conclusion, the combined effect of grandmaternal and maternal smoking is associated with higher risks than only maternal smoking.


Pergolide mesylate: a potent day-long inhibitor of prolactin in rhesus monkeys and patients with Parkinson's disease.
The effect of a new synthetic ergot alkaloid, pergolide mesylate, on the inhibition of PRL during 24-h periods was evaluated in four rhesus monkeys and three patients with Parkinson's disease. In the monkeys, the mean PRL level during the 24-h period fell to 24% of control in response to 50 micrograms. With 1000 micrograms pergolide daily and to 6.6% of control with 200 micrograms pergolide daily, PRL was unmeasurable in the great majority of samples over 24 h. In addition, the marked episodic fluctuation in PRL occurring in controls was not observed in treated animals. In three patients with Parkinson's disease, treatment with pergolide also resulted in uniform 24-h suppression of PRL. In one patient on pergolide (100 micrograms/day), the mean 24-h PRL level fell to 18% of control, and in two other patients on 200 and 600 micrograms pergolide, respectively, whose mean PRL levels were 4.1 and 7.4 ng/ml, respectively, before treatment, no PRL was detected in any of the blood samples obtained during the 24-h periods. These data provide evidence that pergolide is a potent inhibitor of PRL in rhesus monkeys and in patients with Parkinson's disease; the effect is iniform over 24-h periods.


Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure.
Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters--some of which may be subject to considerable uncertainty--that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg(-1).


[Influence of five-in-one management mode on disease prevention and control of school children with asthma].
Objective: To investigate the influence of five-in-one management mode(standardized asthma treatment, asthma diary, peak expiratory flow (PEF) monitoring, reasonable diet and physical exercise) on disease prevention and control of school children with asthma. Methods: From April to October 2018, 70 children with asthma in clinical remission were selected from Affiliated Hospital of Qingdao University using randomized controlled study design. These children were randomly divided into study group and control group, with 35 cases in each group. In the study group, 5 cases were lost to follow-up, and 30 cases were actually enrolled. In the control group, 6 cases were lost to follow-up, and 29 cases were actually enrolled. Children in the control group received routine medication and regular outpatient consultation, and children in the study group received the five-in-one asthma management model. In the first time of seeing a doctor, after 3 months and 6 months of follow-up, asthma control test score, medication compliance index score and lung function index (forced expiratory volume in 1 second (FEV1), PEF were evaluated respectively.Parental satisfaction, asthma acute episodes, weight, height and biochemical index were recorded during the 6 months of follow-up. Pulmonary function index, asthma control score and body mass index of overweight children with asthma were compared with t-test, medication compliance was compared with chi-square test, and the rank sum test was used for the comparison of the number of emergency visits of asthma attacks and parents' satisfaction. Results: A total of 59 children with asthma were included, among them 30 were in the study group (8.1±1.5) years old and 29 in the control group (9.2±1.1) years old. After 3 months of follow-up, FEV1, PEF, asthma control score in the study group were (86.3±1.5)%, (83.3±2.4)%, (24.7±2.6) points respectively; and in the control group, FEV1, PEF, asthma control score were (84.4±2.5)%, (82.2±1.9)%, (21.1±1.3) points respectively. The indicators in the study group were higher than those in the control group (t=3.62, 1.97, 6.64, P<0.05). After 6 months of follow-up, FEV1, PEF, asthma control score in the study group were (88.4±2.3)%, (85.4±2.2)%, (26.8±1.8) points respectively; and in the control group, FEV1, PEF, asthma control score were (85.5±1.9)%, (83.2±1.7)%, (22.5±1.4) points respectively. The indicators in the study group were significantly higher than those in the control group (t=5.34, 4.24, 10.41, P<0.05). During the 6-month follow up, the number of emergency visits of asthma attacks in the study group and in the control group were 0.42(0.36, 0.51) and 0.92(0.72, 1.27) respectively. The indicator in the study group was significantly lower than that in the control group (Z=3.21, P<0.05). After 3 months of follow-up, the proportions of children with good compliance in the study group and control group were 67% (20/30) and 62% (18/29), the proportions of poor compliance were 27% (8/30) and 34% (10/29), the proportions of non-compliance were 7% (2/30) and 7% (2/29). There were no statistically significant differences (χ(2)=0.14, 0.43, 0.00, P=0.71, 0.51, 0.97). After 6 months of follow-up, the proportions of children with good compliance in the study group and control group were 87% (26/30) and 69% (20/29), the proportion of poor compliance were 10% (3/30) and 28% (8/29), the proportion of non-compliance were 3% (1/30) and 7% (2/29), There were no statistically significant differences (χ(2)=2.70, 3.00, 0.39, P=0.10, 0.08, 0.53). After 6 months of follow-up, the number of great satisfaction, satisfaction and dissatisfaction in the study group were 20, 10 and 0 respectively, the satisfaction rate was 100%, meanwhile those indicators in the control group were 4, 15 and 10 respectively, the satisfaction rate was 66%, The indicator in the study group was significantly higher than that in the control group (Z=4.60, P<0.05). Conclusions: The application of "five-in-one" asthma management model (standardized asthma treatment, asthma diary, PEF monitoring, reasonable diet and physical exercise) for school-age children with asthma can significantly improve lung function, as well as reduce the number of acute asthma attacks. It has a high parent satisfaction, therefore it should be recommended for clinical implementation.


Dimension reduction by balanced truncation: application to light-induced control of open quantum systems.
In linear control, balanced truncation is known as a powerful technique to reduce the state-space dimension of a system. Its basic principle is to identify a subspace of jointly easily controllable and observable states and then to restrict the dynamics to this subspace without changing the overall response of the system. This work deals with a first application of balanced truncation to the control of open quantum systems which are modeled by the Liouville-von Neumann equation within the Lindblad formalism. Generalization of the linear theory has been proposed to cope with the bilinear terms arising from the coupling between the control field and the quantum system. As an example we choose the dissipative quantum dynamics of a particle in an asymmetric double well potential driven by an external control field, monitoring population transfer between the potential wells as a control target. The accuracy of dimension reduction is investigated by comparing the populations obtained for the truncated system versus those for the original system. The dimension of the model system can be reduced very efficiently where the degree of reduction depends on temperature and relaxation rate.


Updates to the management of chronic lymphocytic leukemia.
The decision of when to start treatment for patients with chronic lymphocytic leukemia (CLL) has not markedly changed; it is triggered by parameters of active disease, such as progressive symptoms or progressive cytopenias related to bone marrow compromise from disease. How to treat patients with CLL has become less complicated, given the growing list of options for CLL, and generally depends on the patient's age, presence of comorbidities, and risk factors (such as chromosome 17 or 11 deletion). During his presentation at the NCCN 20th Annual Conference, Dr. William Wierda focused attention on many of the new kids on the therapeutic block for CLL--the CD20 monoclonal antibodies obinutuzumab and ofatumumab, the BTK inhibitor ibrutinib, the PI3K inhibitor idelalisib, and the BCL-2 inhibitor venetoclax--and reviewed some of the clinical data supporting the use of these agents in different patient populations with CLL.


The Role of Beta-Adrenergic Receptors in Depression and Resilience.
Norepinephrine is a catecholamine neurotransmitter that has been extensively implicated in the neurobiology of major depressive disorder (MDD). An accumulating body of evidence indicates that investigations into the action of norepinephrine at the synaptic/receptor level hold high potential for a better understanding of MDD neuropathology and introduce possibilities for developing novel treatments for depression. In this review article, we discuss recent advances in depression neuropathology and the effects of antidepressant medications based on preclinical and clinical studies related to beta-adrenergic receptor subtypes. We also highlight a beta-3 adrenergic receptor-involved mechanism that promotes stress resilience, through which antidepressant efficacy is achieved in both rodent models for depression and patients with major depression-an alternative therapeutic strategy that is conceptually different from the typical therapeutic approach in which treatment efficacy is achieved by reversing pathological alterations rather than by enhancing a good mechanism such as natural resilience. Altogether, in this review, we systematically describe the role of beta-adrenergic receptors in depression and stress resilience and provide a new avenue for developing a conceptually innovative treatment for depression.


Searching for excystment-regulated genes in Sterkiella histriomuscorum (Ciliophora, Oxytrichidae): a mRNA differential display analysis of gene expression in excysting cells.
In the absence of food, the oxytrichid Sterkiella histriomuscorum transforms like many ciliates into resting cysts. When transferred back into feeding medium, the cyst re-transforms into a vegetative cell. The entry into and exit from the dormant cyst stage are complex developmental processes still poorly investigated at the molecular level. Assuming that these changes in state could involve changes in gene expression, we have used the technique of mRNA differential display to detect differentially expressed genes in cysts and two different stages of excysting cell. Variation in the temporal expression pattern of transcripts could be detected and, in using an inverse-PCR strategy on circularized macronuclear DNA, we have sequenced the macronuclear genes of three of the isolated cDNAs. which correspond to 1) a nucleotide-binding domain-encoding gene, 2) a DHHC-domain-carrying gene, and 3) a phosphatase type 2C-encoding gene. For the first two genes, Northern blot analyses supported an excystment-associated regulated gene expression. We discuss their possible role during excystment and we show that the combination of differential display and inverse PCR constitutes a powerful approach to isolate excystment-regulated genes in hypotrichs.


MspA-Mycobacterium tuberculosis-transformant with reduced virulence: the "unbirthday paradigm".
Expressing mspA porin gene from Mycobacterium smegmatis in Mycobacterium tuberculosis attenuated this pathogen. Intracellular growth of the transformants into free-living amoeba and murine and human macrophages decreased. Furthermore, transformants decreased the microbicidal program of human monocyte-derived macrophages. BALB/c mice inoculated with transformants exhibited higher weights, lower histological lesions and lower M. tuberculosis inoculum in the liver, spleen and lungs than control mice challenged with wild-type M. tuberculosis. Preliminary evaluation indicated that mice inoculated with this transformant showed higher weights and lower numbers of lung nodules and tissular mycobacteria than control mice when challenged with wild-type M. tuberculosis. Similar to the paradoxical "unbirthday" gift coined by Lewis Carroll in Alice's Adventures in Wonderland, adding mspA gene reduced the virulence of M. tuberculosis and yielded a protective effect. Lost of non-virulence genes is a mechanism for virulence in mycobacteria. Engineering non-virulence genes in M. tuberculosis may yield strains with decreased virulence and increased immunogenicity.


Clinical utility of sperm DNA damage in male infertility.
Sperm DNA fragmentation (SDF) is an advanced test of sperm function that is utilized during male fertility evaluation. Recently, a guideline was published highlighting the detrimental impact of SDF on sperm function identifying practice-based clinical indications for SDF testing. This review illustrates the commonly utilized SDF measurement techniques and explores the current evidence behind their utility in clinical practice. Patients diagnosed with varicocele, unexplained infertility, recurrent pregnancy loss, recurrent failure of assisted reproductive techniques (ART) and those at risk of lifestyle/environmental exposures are recognized candidates for SDF testing. On a therapeutic level, SDF can help in selecting patients for varicocelectomy, choosing the ART modality and intervention associated with highest pregnancy and live birth outcomes and monitoring treatment response in patients with lifestyle risk factors.


Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: a meta-analysis of randomized controlled trials.
Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified 11 RCTs including 1,772 patients, who met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients [relative risk (RR)=0.39; 95% confidence interval (CI)=0.26-0.59; p=0.000], subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR=0.44; 95% CI=0.28-0.68; p=0.000); but HCC incidence in nonresponders to initial antiviral therapy did not reduce by maintenance IFN therapy (RR=0.96; 95% CI=0.59-1.56; p=0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR=0.23; 95% CI=0.05-1.04; p=0.056). Besides, IFN did not improve one-year overall survival of advanced HCC patients significantly (RR=1.61; 95% CI=0.96-2.69; p=0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising, but its administration in other subpopulations still requires further exploration.


Prediction of Mechanical Properties of Highly Functional Lightweight Fiber-Reinforced Concrete Based on Deep Neural Network and Ensemble Regression Trees Methods.
Currently, one of the topical areas of application of artificial intelligence methods in industrial production is neural networks, which allow for predicting the performance properties of products and structures that depend on the characteristics of the initial components and process parameters. The purpose of the study was to develop and train a neural network and an ensemble model to predict the mechanical properties of lightweight fiber-reinforced concrete using the accumulated empirical database and data from construction industry enterprises, and to improve production processes in the construction industry. The study applied deep learning and an ensemble of regression trees. The empirical base is the result of testing a series of experimental compositions of fiber-reinforced concrete. The predicted properties are cubic compressive strength, prismatic compressive strength, flexural tensile strength, and axial tensile strength. The quantitative picture of the accuracy of the applied methods for strength characteristics varies for the deep neural network method from 0.15 to 0.73 (MAE), from 0.17 to 0.89 (RMSE), and from 0.98% to 6.62% (MAPE), and for the ensemble of regression trees, from 0.11 to 0.62 (MAE), from 0.15 to 0.80 (RMSE), and from 1.30% to 3.4% (MAPE). Both methods have shown high efficiency in relation to such a hard-to-predict material as concrete, which is so heterogeneous in structure and depends on many factors. The value of the developed models lies in the possibility of obtaining additional useful information in the process of preparing highly functional lightweight fiber-reinforced concrete without additional experiments.


Lessons learned from advanced intracoronary imaging in patients with acute myocardial infarction.
The use of percutaneous coronary intervention (PCI) as a primary treatment for acute myocardial infarction (AMI) has contributed to save lives. But, in addition to this, it has generated new opportunities to study the culprit and non-culprit arteries with intracoronary imaging during and after reperfusion treatments, and thus to get a richer view of this syndrome. From this perspective, intracoronary imaging has contributed to our knowledge of AMI in a number of ways: it has complemented the available information on the substrate of AMI with in-vivo observations, reinforcing the current pathophysiological paradigm on this entity; it has allowed longitudinal documentation on the reparative vascular processes at the culprit lesion over the months and years following the acute event; it has generated valuable observations on the vascular responses to interventions performed during primary PCI, such as implantation of drug eluting stents (DES); it has been used to guide or monitor specific interventions, either pharmacological agents like antithrombotics or devices like thrombectomy catheters or stents, at the culprit stenosis of AMI; and it has revealed the characteristics of concomitant atheromatosis in non-culprit vessels. In this article, we review the available literature on these different aspects.


The Use of Comparative Genomic Analysis for the Development of Subspecies-Specific PCR Assays for Mycobacterium abscessus.
Mycobacterium abscessus complex (MABC) is an important pathogen of immunocompromised patients. Accurate and rapid determination of MABC at the subspecies level is vital for optimal antibiotic therapy. Here we have used comparative genomics to design MABC subspecies-specific PCR assays. Analysis of single nucleotide polymorphisms and core genome multilocus sequence typing showed clustering of genomes into three distinct clusters representing the MABC subspecies M. abscessus, M. bolletii and M. massiliense. Pangenome analysis of 318 MABC genomes from the three subspecies allowed for the identification of 15 MABC subspecies-specific genes. In silico testing of primer sets against 1,663 publicly available MABC genomes and 66 other closely related Mycobacterium genomes showed that all assays had >97% sensitivity and >98% specificity. Subsequent experimental validation of two subspecies-specific genes each showed the PCR assays worked well in individual and multiplex format with no false-positivity with 5 other mycobacteria of clinical importance. In conclusion, we have developed a rapid, accurate, multiplex PCR-assay for discriminating MABC subspecies that could improve their detection, diagnosis and inform correct treatment choice.


Pressure Dependence of Superconductivity in a Charge-Density-Wave Superconductor Bi2Rh3Se2.
The structural and superconducting properties of a Bi-based compound, Bi2Rh3Se2, are investigated over a wide pressure range. Bi2Rh3Se2 is a superconductor with a superconducting transition temperature, Tc, of 0.7 K. This compound is in a charge-density-wave (CDW) state below 240 K, which implies the coexistence of superconducting and CDW states at low temperatures. Here, the superconducting properties of Bi2Rh3Se2 are studied from the perspective of the temperature dependence of electrical resistance (R) at high pressures (p's). The pressure dependence of Tc of Bi2Rh3Se2 shows a slow increase in Tc at 0-15.5 GPa, and the Tc slowly decreases with pressure above 15.5 GPa, which is markedly different from that of normal superconductors because the value of Tc should simply decrease owing to the decrease in density of states (DOS) on the Fermi level, N(εF), driven by a simple shrinkage of the lattice under pressure. To ascertain the origin of such a dome-like Tc-p behavior, the crystal structure of Bi2Rh3Se2 was explored over a wide pressure range of 0-20 GPa on the basis of powder X-ray diffraction; no structural phase transitions or simple shrinkage of the lattice was observed. This result implies that the increase in Tc against pressure cannot simply be explained from a structural point of view. In other words, a direct relation between superconductivity and crystal structure was not found. On the other hand, the CDW transition became ambiguous at pressures higher than 3.8 GPa, suggesting that the Tc had been suppressed by the CDW transition in a low pressure range. Thus, the findings suggest that for Bi2Rh3Se2, Tc is enhanced through the suppression of CDW transition, which may be reasonable because the CDW-ordered state restrains the charge fluctuation to weaken the electron-phonon coupling and opens the gap to decrease the density of states on the Fermi level. The obtained dome-like Tc-p behavior indicates the possibility of Bi2Rh3Se2 being an exotic superconductor.


Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation.
Ischemic preconditioning (IPC) was first demonstrated in the heart, but this protective effect has been also recently described in the intestine. The aim of this study was to determine the effects of intestinal ischemic preconditioning on the morphology of intestine and bacterial translocation. Twenty-four male Wistar rats weighting 250 to 300 g were randomized into three groups. A control group of rats (n = 8) were subjected laparotomy. In an ischemic group (n = 8), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic clamp for 30 min. In the preconditioned group (n = 8), before the ischemia-reperfusion (I/R) period (as in ischemic group), rats were subjected to an initial 10 min of intestinal ischemia and 10 min of reperfusion. Twenty-four hours later, to evaluate whether the I/R induced intestinal injury and bacterial translocation (BT), tissue and blood samples were collected, and liver, spleen, and mesenteric lymph node specimens were obtained under sterile conditions for microbiological analysis. Samples of ileum were removed for both biochemical and histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, liver, and blood was significantly higher than other groups (P < 0.05). IPC prevented I/R-induced BT and it significantly reduced the I/R-induced intestinal injury (P < 0.05). Increased inducible nitric oxide (NO) synthase (iNOS) expression observed on the ileal specimens of the I/R group was found to be prevented by IPC. Our data suggest IPC as a key factor that reduces BT and iNOS activation in intestinal I/R. This is the first study showing that intestinal IPC blocks the cascade of events that causes BT and intestinal injury that may lead to sepsis.


Stress gastric bleeding. Prevention of experimental lesions by intravenous hyperalimentation.
Rats, weighing 125-150 gm., were restrained under a tight wire screen for one hour at 20degrees C and another hour at 4degrees C of ambient temperature. Animals receiving no infusions, or those receiving an intravenous solution of normal saline, developed 16 +/- 3 S.D. bleeding areas in their gastric mucosa. In contrast, in animals exposed to the same degree of stress who received intravenous hyperalimentation, the number of gastric stress bleeding areas counted was 4 +/- 2 S.D. These results demonstrate that the delivery of calories and protein in the form if intravenous hyperalimentation can significantly reduce the incidence of gastric stress bleeding in an experimental model (P less than .001).


The biology of myelopoiesis.
The myelopoietic system includes the hematopoietic cells derived from a common hematopoietic stem cell that includes erythroid, granulocytic, monocytic, and megakaryocytic lineages. The contributions of molecular genetic techniques to hematopoiesis in the past 5 years have led to quantum leaps in our understanding, but there is room for further research. Current concepts of stem cells and the hematopoietic microenvironment are discussed, as are committed progenitor cells and hematopoietic growth factors, particularly those concerning the neutrophilic, monocytic, and erythroid systems.


DNA-templated nickel nanostructures and protein assemblies.
We report a straightforward method for the fabrication of DNA-templated nickel nanostructures on surfaces. These nickel nanomaterials have potential to be applied as nanowires, as templated catalyst lines, as nanoscale magnetic domains, or in directed protein localization. Indeed, we show here that histidine-tagged phosducin-like protein (His-PhLP) binds with high selectivity to both Ni2+-treated surface DNA and DNA-templated nickel metal to create linear protein assemblies on surfaces. The association of His-PhLP with DNA-templated nickel ions or metal is reversible under appropriate rinsing conditions. Nanoscale DNA-templated protein assemblies might be useful in the construction of high-density protein lines for proteomic analysis, for example. Importantly, these nanofabrication procedures are not limited to linear DNA and can be applied readily to other self-assembled DNA topologies.


Multifunctionality in Two Families of Dinuclear Lanthanide(III) Complexes with a Tridentate Schiff-Base Ligand.
The employment of N-(2-carboxyphenyl)salicylideneimine in 4f metal chemistry has led to two families of dinuclear complexes depending on the lanthanide(III) used. Representative members exhibit interesting magnetic, optical, and catalytic properties.


Nonaccidental head trauma in infants.
Nonaccidental head trauma in infants is the leading cause of infant death from injury. Clinical features that suggest inflicted head trauma include the triad of the so-called shaken baby syndrome, consisting of retinal hemorrhage, subdural, and/or subarachnoid hemorrhage in an infant with little signs of external trauma. Studies have shown that, in general, the average short fall in the home is extremely unlikely to produce either subdural or retinal hemorrhage, although focal injuries such as skull fractures and epidural hemorrhage may be seen. Acceleration/deceleration, especially of the rotational type, is believed to be the most probable mechanism of injury in cases of nonaccidental head trauma. Damage to the cervicomedullary junction and the respiratory centers, with subsequent hypoxia and intracerebral edema, has also been implicated. After the initial trauma and hemorrhage, loss of cerebral autoregulation, breakdown of the blood-brain barrier, and disruption of ionic homeostasis occur, leading to brain edema and cytotoxicity. Cellular damage can involve large volumes of tissue, without respecting vascular territories. Overall, a satisfactory biomechanical model is lacking, and the criminal nature of abusive injury makes it difficult to perform systematic, controlled studies. Unfortunately, outcomes are poor, and the rate of repeated abusive episodes is high. Future research should focus on the development of a satisfactory research model and on prevention strategies.


Identification and characterization of G beta 3s2, a novel splice variant of the G-protein beta 3 subunit.
The T-allele of a polymorphism (C825T) in the gene for the G-protein beta 3 subunit (GNB3) is associated with cardiovascular and metabolic disorders, distinct cellular features and altered drug responses. The molecular mechanisms that give rise to this complex phenotype have been linked to the occurrence of G beta 3s, a splice variant of GNB3. G beta 3s is predominantly expressed in cells with the 825T-allele. In the present study we describe the identification and characterization of an additional G beta 3 splice variant referred to as G beta 3s2. Its mRNA is expressed in heart, blood cells and tumour tissue, and its expression is also tightly associated with the GNB3 825T-allele. G beta 3s2 is generated by alternative splicing using non-canonical splice sites. G beta subunits belong to the family of propeller proteins and consist of seven regular propeller blades. Transcripts for G beta 3s2 are lacking 129 bp of the coding sequence of the wild-type G beta 3 protein. Thus the predicted structure consists of only six propeller blades, which resembles the structure of G beta 3s. Co-immunoprecipitation analyses indicated that G beta 3s2 dimerizes with different G gamma subunits, e.g. G gamma 5, G gamma 8(C) and G gamma 12. In Sf9 insect cells, expression of G beta 3s2 together with G gamma 12 enhances receptor-stimulated activation of G alpha(i2). Expression of G beta 3s2 in mammalian cells activated the mitogen-activated protein kinase cascade. Together, these results suggest that G beta 3s2 is a biologically active G beta variant which may play a role in the manifestation of the complex phenotype associated with the 825T-allele.


Collagen I gel can facilitate homogenous bone formation of adipose-derived stem cells in PLGA-beta-TCP scaffold.
Cell-based tissue engineering is thought to be a new therapy for treatment of bone defects and nonunions after trauma and tumor resection. In this study, we explore the in vitro and in vivo osteogenesis of a novel biomimetic construct fabricated by using collagen I gel to suspend rabbit adipose-derived stem cells (rASCs) into a porous poly(lactic-co-glycolic)acid-beta-tricalcium phosphate (PLGA-beta-TCP) scaffold (rASCs-COL/PLGA-beta-TCP). In vitro and in vivo studies of the rASCs-COL/PLGA-beta-TCP composite (group A) were carried out compared with the single combination of rASCs and PLGA-beta-TCP (rASCs/PLGA-beta-TCP; group B), the combination of acellular collagen I gel and PLGA-beta-TCP (COL/PLGA-beta-TCP; group C), and the PLGA-beta-TCP scaffold (group D). Composites of different groups were cultured in vitro for 2 weeks in osteogenic medium and then implanted into the autologous muscular intervals for 8 weeks. After 2 weeks of in vitro culture, alkaline phosphatase activity and extracellular matrix mineralization in group A were significantly higher than in group B (p < 0.01, n = 4). In vivo osteogenesis was evaluated by radiographic and histological analyses. The calcification level was radiographically evident in group A, whereas no apparent calcification was observed in groups B, C and D (n = 4). In group A, woven bone with a trabecular structure was formed, while in group B, only osteoid tissue was observed. Meanwhile, the bone-forming area in group A was significantly higher than in group B (p < 0.01, n = 4). No bone formation was observed in groups C or D (n = 4). In conclusion, by using collagen I gel to suspend rASCs into porous PLGA-beta-TCP scaffold, osteogenic differentiation of rASCs can be improved and homogeneous bone tissue can be successfully formed in vivo.


Do HMOs make a difference? Data and methods.
This paper describes the common data source and methods used in this study. Data come from the Community Tracking Study Household Survey, a nationally representative survey of individuals conducted in 1996-1997. Focusing on the privately insured, nonelderly population, the study examines the effect of health maintenance organizations (HMOs) on access, service use, and consumer assessments, as well as how these effects differ across population subgroups. Multivariate models control for population characteristics and location differences between HMO and non-HMO enrollees. Tests for endogeneity of plan type (selection bias) indicated that this did not pose a threat to the analysis.


Design and implementation of a multifrequency near-infrared diffuse optical tomography system.
The design and implementation of a multifrequency and multispectral diffuse optical tomography system is described. Four wavelengths are utilized: 665, 785, 808, and 830 nm. The system is based on a network analyzer, which provides rf modulation signals for the laser diodes, as well as measures the amplitude and the phase of the detected signals. Six different modulation frequencies ranging from 110 to 280 MHz are used. The details of instrumentation, calibration, data acquisition, and performance of the system are given. A finite element algorithm is used to solve the diffusion equation, and an inverse solver based on this forward solver is implemented to calculate the absorption and scattering maps from the acquired data. Data acquisition for one wavelength is completed in less than 2.5 min for a single modulation frequency. The measurement repeatability is 0.5% in ac intensity and 0.2 deg in phase. The performance of the system is evaluated with phantom studies. A multifrequency reconstruction algorithm is used, in which a single absorption and scattering image pair is obtained using the whole dataset obtained at different modulation frequencies. It is shown that the multifrequency reconstruction approach provides superior image quality compared to the single frequency counterpart.


Density functional study of lithium hexamethyldisilazide (LiHMDS) complexes: effects of solvation and aggregation.
The title compound, lithium hexamethyldisilazide (LiHMDS), has been studied using modern quantum-chemical methods in the form of the B3LYP approach. Monomers, dimers, trimers, and tetramers, microsolvated with up to four THF molecules have been considered. The choice of model complex is seen to be important-for instance, the simpler water molecule is shown to be an inappropriate substitute for the THF solvent. Calculated lithium NMR shieldings are reported, but by themselves, they seem to be insufficient for unequivocal assignments of the different species. The energetics of aggregation and solvation have been studied. Temperature effects are seen to be important, and the degrees of solvation and aggregation are higher at 0 K than at 298 K. The highest degree of THF solvation for the monomer and dimer is found to be three (0 K) and two (298 K), respectively. The highest possible degree of aggregation for unsolvated LiHMDS is four. However, in nonpolar solvents, formation of the LiHDMS dimer from the trimer is thermodynamically preferred. The pathway is likely to involve an intermediate tetramer. In THF solution, di-solvated monomers and dimers are the most likely species.


Bipolar Electric Field Pulses in the Martian Magnetosheath and Solar Wind; Their Implication and Impact Accessed by System Scale Size.
The scale size of the plasma boundary region between the sheath and ionosphere in the Martian system is often similar to the gyro-radii of sheath protons, ∼200 km. As a result, ion energization via kinetic structures may play an important role in modifying the ion trajectories and thus be important when evaluating the large-scale dynamics of the Martian system. In this paper, we report observations made with the MAVEN Langmuir Probe and Waves instrument of solitary bipolar electric field structures, and assess their potential role in ion energization in the Martian system. The observed structures appear as short duration (∼0.5 ms) bipolar electric field pulses of ∼1-25 mV/m, and are frequently observed in the upstream solar wind and inside the sheath. The study presented in this paper suggests that the bipolar electric field structures observed at Mars have an average electrostatic potential drop of ∼0.07 V. The estimated upper rate at which these structures could further energize the protons is estimated, assuming the protons gain the full 0.07 eV, to be ∼0.13 eV per gyration, or a change in proton energy of ∼0.3%, and a corresponding change in the gyroradius of ∼0.3 km. These numbers imply that to first order the bipolar structures are not a significant source of ion energization in the Martian magnetosheath.


Finite element analysis of the effects of pedicle screw fixation nut loosening on lumbar interbody fusion based on the elasto-plateau plasticity of bone characteristics.
Cylindrical cages and pedicle screw fixation (PSF) have been used for the setting of a lumbar interbody fusion. To investigate the effects of PSF-nut loosening on lumbar interbody fusion based on the elasto-plateau plasticity of bone characteristics. The stress-strain curves of bone materials beneath the cages show linear elastic behavior before yielding and then seem to be plateau plastic deformation with further compression strain until opposing cell walls contact. Cancellous bone was assumed to be linearly elastic followed by nonlinearly plastic such as crushable foam behavior. The deformation and failure processes caused by loosening of PSF-nuts, in particular, are addressed by means of finite element analysis. Two finite element models, including anterior (or posterior) lumbar interbody fusion for the human lumbar L4-L5 segments, were constructed. In the respective models, 2 types of PSF were considered such as a solid PSF without relative movement between rod and screw, and a tightened PSF with relative axial movement of the rod between them due to the slight loosening of 2 nuts of L4. The slight loosening of nuts showed much greater levels of bone strain with relative motion at the bone-implant interface compared with the PSF with firmly tightened nuts. The loosening 2 of the 4 nuts imposed an excessive burden on the remaining screws. By the consideration of the elasto-plateau plastic behavior of cancellous bone and the relative motion at the contact interface between screw and rod, much more exact behaviors of bone failure were predicted. Slight loosening of the nut would cause a possible risk of segmental instability. With difficulty in either tightening the nut firmly during actual operation or keeping the nut-locking mechanism functioning perfectly in the postoperative state, an enhanced design methodology with more effective locking mechanism is required. Slight PSF-nut loosening may increase risks of failure processes such as rod migration, rod breakage, screw breakage, screw loosening or cage loosening. Different mechanisms however, can be considered; rod breakage and screw breakages are related to the higher stress level of the rod and screw while rod migration is associated with slight nut-loosening. Especially, in the case of a nonsymmetric nut-loosening the risk would be increased. Thus, further study is necessary for improving the current design of PSFs.


Multi-modality imaging to assess left atrial size, anatomy and function.
The left atrium (LA) anterior-posterior diameter was one of the first standardised echocardiographic parameters. However, the clinical importance of LA size assessment has been neglected for some time. Recent population-based studies have demonstrated the prognostic value of LA size for long-term outcome. Furthermore, with new dedicated techniques such as tissue Doppler imaging, it has become feasible to assess (regional) LA function. In addition, the introduction of catheter ablation procedures has changed the treatment of patients with drug-refractory atrial fibrillation (AF) dramatically. New image integration systems have become available for these catheter ablation procedures. With the use of image integration systems, a real anatomical "roadmap" of the LA is provided for catheter ablation procedures. All these factors may explain the renewed interest in LA anatomy. In this article, the importance of assessment of LA size and LA anatomy is discussed. Furthermore, the various imaging modalities that are available for the non-invasive visualisation of the LA will be reviewed. In addition, the role of these imaging techniques in catheter ablation procedures for AF will be discussed.


Regioselective functionalization of starch: synthesis and 1H NMR characterization of 6-O-silyl ethers.
A high regioselective 6-O silylation of starch by using thexyldimethylchlorosilane (TDSCl, chlorodimethyl-(2,3-dimethylbut-2-yl)silane) as bulky silylating agent in the reaction system N-methylpyrrolidone (NMP)/ammonia was carried out and investigated. The control of the degree of substitution (DSSi), the control of the regioselectivity, and the control of the reaction pathway are described in detail. After peracetylation of the silyl ethers of starch, the distribution of the silyl and acetyl substituents was characterized not only in the anhydroglucose repeating units (AGU) but also in the nonreducing end groups (NEG) by means of multidimensional 1H NMR techniques. In both cases, the silyl substituents were detected exclusively in the 6-O position, and the acetyl groups in the 2-O and 3-O positions of the AGU and in the 2-O, 3-O, and 4-O positions of the NEG, respectively. The described 6-O-thexyldimethylsilyl (TDS) units are potentially protecting groups of the primary OH position of starches.


Glucocorticoids impair bone resorptive activity and viability of osteoclasts disaggregated from neonatal rat long bones.
It is generally believed that glucocorticoids cause osteoporosis through a combination of decreased bone formation and increased bone resorption. However, the direct effect of glucocorticoids on osteoclasts has not been determined. We therefore tested the effects of hydrocortisone and dexamethasone on bone resorption by osteoclasts disaggregated from neonatal rat long bones. Hydrocortisone and dexamethasone caused a dose-dependent inhibition of osteoclastic bone resorption in the range 10(-7) to 10(-5) M, and 10(-9) to 10(-6) M, respectively, at concentrations likely to occur during therapy and disease. Inhibition of bone resorption was found to be associated with impaired osteoclast survival: osteoclast numbers were reduced to approximately 25% of control values by 10(-6) M hydrocortisone and 10(-7) M dexamethasone. Osteoclast cytotoxicity by glucocorticoids was completely antagonized by progesterone, which itself had no effect on osteoclast survival. Analysis of the time course of these inhibitory effects showed a nonsignificant reduction in survival by 6 h and marked inhibition of survival by 12 h. We could detect no specific changes in osteoclast morphology in association with this impaired viability. The relative potencies of the glucocorticoids for impairment of osteoclast viability was similar to their relative affinities for binding the glucocorticoid receptor, and this, together with inhibition by progesterone, suggests a receptor-mediated mechanism. Such a receptor-mediated cytotoxic action of glucocorticoids has only previously been reported with lymphoid cells. The sensitivity of osteoclasts to the lethal effects of glucocorticoids suggests that glucocorticoids may have a role in physiology as inhibitors of osteoclastic bone resorption.


A contractile electronic switch made of DNA.
Double-helical DNA has been shown to conduct both electrons and electron holes, the latter over distances of >20 nm. DNA is thus a material of significant interest for the bottom-up construction of nanocircuitry. Here, we describe a contractile DNA nanoswitch, which can toggle between a structurally extended "off" state and a contracted "on" state, with a 40-fold conductivity difference between the two. To turn on, two short motifs of guanine-guanine mismatches in an otherwise standard double helix synapse to form a conductive G-quadruplex, bypassing an insulating element within the helix. This switch can be turned repeatedly on by treatment with millimolar concentrations of K(+) and turned off by sequestration of the K(+) by a crown ether. Circular dichroism and thymine-thymine photocross-linking experiments reveal that strand orientations within the on state G-quadruplex are wholly antiparallel and that the two conductive double-helices interface with the same face of the quadruplex. Although this DNA nanoswitch is chemically gated, it should be adaptable to other kinds of gating and thus serve as a prototype for increasingly sophisticated and complex electronic devices made of DNA.


Pathological and physiological hypertrophies are regulated by distinct gene programs.
This study aims to investigate changes that occur during progression and establishment of physiological and pathological cardiac hypertrophy, by microarray technology and functional annotations. Myocardial infarction leading to heart failure was induced in rats, with animals killed 1, 3, 7, 14, 42, and 92 days after coronary artery ligation. A second group was subjected to daily treadmill exercise and killed 1, 4, 24, and 48 h after a single exercise bout, or after 28 or 56 days of exercise training. Physiological hypertrophy was associated with less transcriptional alternation than pathological hypertrophy, indicating that posttranscriptional and translational regulation may be more important. The main difference between the two types of hypertrophy was that myocardial infarction was associated with downregulation of genes related to fatty acid metabolism, whereas no such change occurred after exercise training. Thus, fatty acid metabolism may distinguish adverse maladaptive hypertrophy from beneficial adaptive hypertrophy. This study points to specific genes and gene classes related to biological processes that may be important in these well-characterized rat models of physiological and pathological cardiac hypertrophy.


Circular retrotransposition products generated by a LINE retrotransposon.
Non-long terminal repeat (non-LTR) retrotransposons are highly abundant elements that are present in chromosomes throughout the eukaryotic domain of life. The long interspersed nuclear element (LINE-1) (L1) clade of non-LTR retrotransposons has been particularly successful in mammals, accounting for 30-40% of human genome sequence. The current model of LINE retrotransposition, target-primed reverse transcription, culminates in a chromosomally integrated end product. Using a budding yeast model of non-LTR retrotransposition, we show that in addition to producing these 'classical', chromosomally integrated products, a fungal L1 clade member (Zorro3) can generate abundant, RNA-derived episomal products. Genetic evidence suggests that these products are likely to be formed via a variation of target-primed reverse transcription. These episomal products are a previously unseen alternative fate of LINE retrotransposition, and may represent an unexpected source for de novo retrotransposition.


Paper mill effluent decolorization by fifty streptomyces strains.
Fifty actinomycete strains isolated from lignocellulosic substrates were examined for the ability to remove the color from a paper mill effluent obtained after semichemical alkaline pulping of wheat straw. Streptomyces sp. strains UAH 15, UAH 23, UAH 30, and UAH 51 were selected for their ability to decolorize the effluent in a liquid medium containing 1% (wt/vol) glycerol, 0.2% (wt/vol) ammonium sulfate, and 80% (vol/vol) effluent. The highest levels of decolorization achieved after the strains grew were 60 to 65%. Strains UAH 30 and UAH 51 were selected for further study because of their different patterns of effluent decolorization during growth. Fractionation of the decolorized effluent by gel permeation chromatography demonstrated that there were reductions in the levels of absorbance of the high- and medium-molecular-weight compounds. These fractions were mainly responsible for the color of the effluent, while the last fractions, the low-molecular-weight compounds, could have been responsible for the residual color of the decolorized effluent. Thin-layer chromatography revealed significant differences among the patterns of bands corresponding to the acidified supernatants obtained after precipitation of alkali-lignin from the effluent samples decolorized by different Streptomyces strains.


Multi-level combinatoriality in magpie non-song vocalizations.
Comparative studies conducted over the past few decades have provided important insights into the capacity for animals to combine vocal segments at either one of two levels: within- or between-calls. There remains, however, a distinct gap in knowledge as to whether animal combinatoriality can extend beyond one level. Investigating this requires a comprehensive analysis of the combinatorial features characterizing a species' vocal system. Here, we used a nonlinear dimensionality reduction analysis and sequential transition analysis to quantitatively describe the non-song combinatorial repertoire of the Western Australian magpie (Gymnorhina tibicen dorsalis). We found that (i) magpies recombine four distinct acoustic segments to create a larger number of calls, and (ii) the resultant calls are further combined into larger call combinations. Our work demonstrates two levels in the combining of magpie vocal units. These results are incongruous with the notion that a capacity for multi-level combinatoriality is unique to human language, wherein the combining of meaningless sounds and meaningful words interactively occurs across different combinatorial levels. Our study thus provides novel insights into the combinatorial capacities of a non-human species, adding to the growing evidence of analogues of language-specific traits present in the animal kingdom.


Synthesis and molecular structures of some new titanium(IV) aryloxides.
The coordination chemistry of model phenolic ligands (pyrocatechol, salicylic acid, and 2,2'-biphenol) that are able to form respectively five-, six-, or seven-membered rings with titanium(IV) alkoxides is investigated. With pyrocatechol, a polynuclear complex containing 10 Ti atoms was characterized with a not very common doubly bridging mu3-(O,O,O',O') coordination mode. With salicylic acid, a monomeric tris(chelate) complex was obtained. With 2,2'-biphenol, a polynuclear complex containing six Ti atoms was obtained showing both mu2-(O,O') and mu2-(O,O,O') coordination modes for the ligands. Intermolecular interactions in the solid state for these three new compounds are also quantitatively discussed using the partial charge model.


Association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity.
The aim of this study was to evaluate the association of A1166C polymorphism in angiotensin II type 1 receptor (AT(1)R) gene with baroreflex sensitivity (BRS in ms/mm Hg; BRSf in mHz/mm Hg) in man. BRS and BRSf were determined by a spectral method in 135 subjects (19-26 years) at a frequency of 0.1 Hz. Genotypes were detected by means of polymerase chain reaction and restriction analysis using enzyme DdeI. We compared BRS and BRSf among genotypes of this polymorphism. The frequency of genotypes of AT(1)R A1166C polymorphism was: 45.9 % (AA, n=62), 45.9 % (AC, n=62), 8.2 % (CC, n=11). Differences in BRS (p<0.05) and BRSf (p<0.01) among genotypes of this single nucleotide polymorphism were found (Kruskal-Wallis: BRS - AA: 7.9+/-3.3, AC: 8.6+/-3.6, CC: 5.9+/-2.3 ms/mm Hg; BRSf - AA: 12.0+/-4.0, AC: 12.0+/-5.0, CC: 8.0+/-3.0 mHz/mm Hg). Compared to carriers of other genotypes (AA+AC) the homozygotes with the less frequent allele (CC) showed significantly lower BRSf (Mann-Whitney: BRSf - AA+AC: 12.0+/-4.0, CC: 8.0+/-3.0 mHz/mm Hg; p<0.01) and borderline lower BRS (BRS - AA+AC: 8.2+/-3.5, CC: 5.9+/-2.5 ms/mm Hg; p=0.07). We found a significant association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity. Homozygosity for the less frequent allele was associated with decreased baroreflex sensitivity.


Capillary-Assisted Fabrication of Thin-Film Nanocomposite Membranes for Improved Solute-Solute Separation.
Efficient separation of harmful contaminants (e.g., per- and polyfluoroalkyl substances, PFASs) from valuable components (water and nutrients) is essential to the resource recovery from domestic wastewater for agricultural purposes. Such selective recovery requires precise separation at the angstrom scale. Although nanofiltration (NF) has the potential to achieve solute-solute separation, the state-of-the-art polyamide (PA) membranes are typically constrained by limited precision of solute-solute selectivity and their well-documented permeability-selectivity trade-off. Herein, we present a novel capillary-assisted interfacial polymerization (CAIP) approach to generate metal-organic framework (MOF)-PA nanocomposite membranes with reduced surface charges and more uniform pore sizes that favor solute selectivity by enhanced size exclusion. By uniquely regulating the PA-MOF interactions using the capillary force, CAIP results in effective exposure of MOF nanochannels on the membrane surface and a PA matrix with a high cross-linking gradient in the vertical direction, both of which contribute to an exceptional water permeance of ∼18.7 LMH/bar and an unprecedentedly high selectivity between nutrient ions and PFASs. Our CAIP approach breaks new ground for utilizing nanoparticles with nanochannels in fabricating the next-generation, fit-for-purpose NF membranes for improved solute-solute separations.


Nuclear receptors as potential drug targets in osteoarthritis.
Osteoarthritis is amongst the major causes of disability worldwide, but no medications that can slow or stop progression of this disorder have been identified. Recent evidence suggests roles for a variety of members of the nuclear receptor family of ligand-activated transcription factors in various forms of osteoarthritis. Since nuclear receptors are amongst the major classes of drug targets, these studies suggest that modulators of nuclear receptor activity might provide novel strategies to treat osteoarthritis. This review focuses on recent advances in our understanding of the role of nuclear receptors in osteoarthritis onset and progression, as well as their therapeutic implications. Future studies should continue to examine the possible roles of additional nuclear receptors in the pathophysiology of different types of osteoarthritis.


Afraid but misinformed: Conspiracist beliefs cancel the positive influence of fear of COVID-19 on vaccination intentions - Findings from a Romanian sample.
Understanding the factors that make people more likely to refuse vaccination against COVID-19 is crucial in order to design public health messages efficient in increasing vaccination rates. As COVID-19 creates risks of seriously damaging health effects, fear of this disease is as a significant determinant of vaccination intentions, as indicated by past research. Nevertheless, this positive influence may be limited in people who do not consider vaccines as a solution to protect against COVID-19, especially those who hold conspiracist beliefs about the new coronavirus and, implicitly, about the newly developed vaccines. The present study examined in a cross-sectional design on a convenience sample (N = 564) the joint effect of fear of COVID-19 and conspiracist beliefs on vaccination intentions, advancing past research on their independent influences. Furthermore, we investigated and controlled the effects of perceived risk of catching COVID-19, trust in medical experts, attitude towards vaccination and socio-demographical characteristics (i.e., gender, age, and education), previously found to be associated to COVID-19 vaccination intentions. We also tested the effect of ambivalence towards vaccination, i.e., the degree to which people simultaneously hold positive and negative evaluations of this intervention, as the widespread misinformation on the new coronavirus and its vaccines may induce ambivalence on this latter issue in many people. The results showed that the positive effect of fear of COVID-19 on vaccination intentions emerged only in participants who tend not to endorse conspiracist ideas on the new coronavirus. Moreover, higher vaccine hesitancy was found in participants with higher ambivalence towards vaccination, in those who perceive the risk of being contaminated by the new coronavirus as low, and in those with more negative attitudes towards vaccines in general. Vaccine ambivalence also emerged as a mediator of the negative effects of conspiracist beliefs about COVID-19 on vaccination intentions. This pattern of findings suggests the public messages emphasizing the risks of COVID-19 should also combat misinformation in order to maximize vaccine uptake.


Mycophenolic acid attenuates tumor necrosis factor-alpha-induced endothelin-1 production in human aortic endothelial cells.
Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in solid organ transplant recipients. Endothelin-1 (ET-1) is implicated in the pathogenesis of atherosclerosis and is one of the potential therapeutic targets. This study was conducted to evaluate the effect of mycophenolic acid (MPA), an immunosuppressant for the transplant recipients, on tumor necrosis factor-alpha (TNF-alpha)-induced ET-1 production in aortic endothelial cells. In cultured human aortic endothelial cells, TNF-alpha increased ET-1 through AP-1 and NF-kappaB, whereas MPA attenuated it by reducing both AP-1 and NF-kappaB DNA-binding activities. TNF-alpha increased ET-1 via c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not extracellular signal-regulated kinase. N-acetylcysteine that downregulated TNF-alpha-induced reactive oxygen species (ROS) inhibited JNK activation, but not p38 MAPK. N-acetylcysteine, SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated TNF-alpha-induced DNA-binding activities of both AP-1 and NF-kappaB. MPA inhibited JNK and p38 MAPK activations as well as ROS generation. N-acetylcysteine, SP600125, SB203580 and MPA had no effect on either TNF-alpha-induced IkappaBalpha degradation or p65 nuclear translocation, but attenuated p65 Ser276 phosphorylation. MPA attenuated TNF-alpha-induced ET-1 production through inhibitions of ROS-dependent JNK and ROS-independent p38 MAPK that regulated NF-kappaB as well as AP-1. These findings suggest that MPA could have an effect of amelioration of atherosclerosis.


Communication, quality of life and age: results of a 5-year prospective study in breast cancer patients.
Previous studies have employed short follow-up periods or examined only certain aspects of quality of life (QoL). This study aimed to examine the effect of communication on breast cancer patients' QoL and to investigate the role of age in this relationship. In a prospective, observational study breast cancer patients were sent questionnaires, including the European Organisation for Research and Treatment of Cancer QLQ-C30, over 5 years. Forty-five per cent of the sample reported that some aspect of the communication they received was unclear and 59% wanted to speak with medical staff more. Patients under 50 years rated social and psychological help as more important, they were more aware of such services, had greater contact with support groups but were less satisfied with the information they received. Seventeen of the 27 QoL variables were significantly worse (P <0.01), up to 4 years after diagnosis, for those patients reporting unclear information. For patients over 50 years, QoL was significantly (P <0.001) worse when communication was unsatisfactory. Operation method or arm problems did not mitigate the association between communication and QoL. Communication is clearly a vital clinical skill that may play a role in patient QoL.


Investigating the generation and propagation evolution of orange optical vortices using continuous-wave KGW Raman lasers with astigmatic mode transformations.
Various high-order orange beams (HOBs) at 588 nm are produced via off-center pumped Nd:YVO4/KGW Raman lasers. We experimentally confirm that the HOBs can be fairly sustained at the incident pump power of 2.88 W, where the average output powers are overall from 300 mW to 160 mW with increasing the off-center displacements from 0.14 mm to 0.21 mm. The HOBs are further transformed by using an astigmatic mode converter to generate a variety of structured lights with optical vortices. Moreover, theoretical wave functions are analytically derived to characterize the propagation evolution of the converted HOBs. The experimental patterns for all propagating positions are excellently reconstructed by the derived wave functions, and the evolution of phase structures is numerically calculated to manifest the robust optical vortices.


Interpreting three-dimensional structures from two-dimensional images: a web-based interactive 3D teaching model of surgical liver anatomy.
Given the increasing number of indications for liver surgery and the growing complexity of operations, many trainees in surgical, imaging and related subspecialties require a good working knowledge of the complex intrahepatic anatomy. Computed tomography (CT), the most commonly used liver imaging modality, enhances our understanding of liver anatomy, but comprises a two-dimensional (2D) representation of a complex 3D organ. It is challenging for trainees to acquire the necessary skills for converting these 2D images into 3D mental reconstructions because learning opportunities are limited and internal hepatic anatomy is complicated, asymmetrical and variable. We have created a website that uses interactive 3D models of the liver to assist trainees in understanding the complex spatial anatomy of the liver and to help them create a 3D mental interpretation of this anatomy when viewing CT scans. Computed tomography scans were imported into DICOM imaging software (OsiriX) to obtain 3D surface renderings of the liver and its internal structures. Using these 3D renderings as a reference, 3D models of the liver surface and the intrahepatic structures, portal veins, hepatic veins, hepatic arteries and the biliary system were created using 3D modelling software (Cinema 4D). Using current best practices for creating multimedia tools, a unique, freely available, online learning resource has been developed, entitled Visual Interactive Resource for Teaching, Understanding And Learning Liver Anatomy (VIRTUAL Liver) (http://pie.med.utoronto.ca/VLiver). This website uses interactive 3D models to provide trainees with a constructive resource for learning common liver anatomy and liver segmentation, and facilitates the development of the skills required to mentally reconstruct a 3D version of this anatomy from 2D CT scans. Although the intended audience for VIRTUAL Liver consists of residents in various medical and surgical specialties, the website will also be useful for other health care professionals (i.e. radiologists, nurses, hepatologists, radiation oncologists, family doctors) and educators because it provides a comprehensive resource for teaching liver anatomy.


[A new radiopharmaceutical for osteoarthral cartilage imaging: preparation and animals experiment of 99mTc-CS].
The objective of this research work is to prepare a new and reliable radiopharmaceutical for osteoarthral cartilage imaging. Chondroitin sulfate (CS) was labeled directly with 99mTc by "pretinning" method, the labeling efficiency was 79.30% +/- 1.72% and radiochemical purity was 90.12% +/- 1l.23% after filtration by use of asepsis filter membrane. The biodistribution of 99Tc-CS was studied at 10, 30 min and 1, 2, 3, 4, 5, 6, 7, 8, 9 h respectively after caudal vein injection in normal mice,which showed that the radiolabeled product was washed out from blood quickly, and it was mainly excreted through kidney, but 99mTc-CS had distinctive characteristic of philo- cartilage. Scintigraphy of 99mTc-CS was performed on the rabbit with ostarthritis at 5 h after intravenous injection; the scintigram was clear,and the focus showed increased radiopharmaceutical uptake. The radioactivity ratio of the injured/uninjured side (T/NT) calculated over the region of interest (ROI) was 3.0 +/- 0.6 (P < 0.05). These results indicate that 99mTc-CS is an easily prepared compound with the characteristic of high philo-cartilage and it may be a new ideal cartilage imaging agent.


Monitoring peripheral perfusion in sepsis associated acute kidney injury: Analysis of mortality.
Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.


LASIK for myopia with Aspheric "aberration neutral" ablations using the ESIRIS laser system.
To evaluate the clinical outcomes of LASIK using optimized "aberration neutral" ablation profiles. Laser in situ keratomileusis was performed in 231 eyes (120 patients) with a mean spherical equivalent refraction of -4.12+/-2.26 diopters (D) (range: -0.37 to -9.50 D) using a SCHWIND Pendular microkeratome with a 130-microm cutting head and the SCHWIND ESIRIS excimer laser. In all cases, pre- and postoperative autorefractor measurements, manifest refraction, best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), topography and corneal wavefront analysis, and ocular wavefront analysis as well as complications were analyzed. Ablations were calculated using the ORK-CAM software. Clinical outcomes were evaluated in terms of efficacy, predictability, stability, refractive outcome, safety, and wavefront aberrations. At 3 months, mean spherical equivalent refraction was -0.10+/-0.33 D (range: +0.86 to -1.18 D). Of 231 eyes, 201 (87%) were within +/-0.50 D of attempted correction. Uncorrected visual acuity was 20/16 or better in 71% (164 eyes), 20/20 or better in 92% (213 eyes), and 20/32 or better in 100%. Average root-mean-square higher order aberrations increased 0.05 microm after treatment, mean spherical aberration increased 0.08 microm after treatment, and mean coma increased 0.04 microm after treatment (all for 6.0-mm analysis diameter). Our results show that non-customized "aberration neutral" ablation profiles derived from wavefront analysis are able to minimize the amount of induced aberrations of both the cornea and the eye.


Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.
Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).


Hexaphenyltriphenylene-Based Multicomponent Metallacages: Host-Guest Complexation for White-Light Emission.
A hexaphenyltriphenylene-based hexatopic pyridyl ligand is designed and used to prepare three hexagonal prismatic metallacages via metal-coordination-driven self-assembly. Owing to the planar conjugated structures of the hexaphenyltriphenylene skeleton, such metallacages show good host-guest complexation with a series of emissive dyes, which have been further used to tune their emission in solution. Interestingly, based on their complementary emission colors, white light emission is achieved in a mixture of the host metallacages and the guests.


Expression of Smad7 inhibits fibrogenic responses of keratocytes to transforming growth factor β2.
Transforming growth factor β (TGFβ) is one of the most important growth factors in the development of fibrosis and scarring on cornea. Smad7, an inhibitory Smad, can inhibit TGFβ signal transduction. In recent years, effects of lentiviral-mediated Smad7 on inhibition of fibrosis on some organs have been studied, while little is known about the effects on cornea. This study aimed to determine the effects of lentiviral-mediated Smad7 gene expression on keratocyte proliferation and fibrosis induced by TGF β2 in vitro. Keratocytes were cultured from corneal tissue isolated from Sprague-Dawley (SD) rats and transfected with Smad7 expressing lentiviral vector (Lv-Smad7) or non-functioning control vector (Lv-blank). Following the exposure to TGFβ2, keratocytes were processed for immunoblotting to assess the phosphorylation of Smad2 as down-stream event of TGFβ/Smad signaling. Expression of fibrotic markers α-smooth muscle actin (α-SMA), type III collagen (collagen III) were measured by Western blotting and quantitative real time polymerase chain reaction (PCR). Overall cell proliferation was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the expression of cell cycle-related marker Ki67 at both mRNA and protein levels. The Smad7 gene transfer suppressed TGFβ/Smad signaling in keratocytes by down-regulating phosphorylation of Smad2. Markers of cell proliferation and fibrosis including Ki67, α-SMA, collagen III were inhibited by introduction of Smad 7 into TGFβ exposed keratocytes. Consequently, the rate of cell proliferation was attenuated. Smad7 gene transfer inhibited fibrogenic responses of keratocytes to TGFβ2.


Ten Years After the ADA Amendment Act (2008): The Relationship Between ADA Employment Discrimination and Substance Use Disorders.
Title I of the Americans with Disabilities Act (ADA) provides protection against discrimination on the basis of disability. This article explores how the courts have dealt with provisions limiting these protections for persons with substance use disorders. Specifically, the ADA allows employees with substance use disorders to be held to the same standards as other employees, suggesting that employers may not be required to provide reasonable accommodations. Moreover, employees "currently engaging in the illegal use of drugs" are excluded from ADA coverage. This article reviewed all published federal appellate court opinions involving cases in which a substance use disorder was the basis for a claim of employment-related discrimination in violation of the ADA. In 26 cases identified, the lower courts ruled in favor of the employer 25 times, and the appellate courts reversed four of these rulings. The cases highlight three important limitations of ADA protections for persons with substance use disorders: the dilemma of needing to prove that one's substance use disorder limits major life activities while simultaneously arguing that one is qualified for the job; expansive interpretations of "current" drug use and the period of sobriety needed to qualify for ADA protections; and restrictions on the extent to which a qualifying disability can serve as a legal excuse for substance use-related misconduct. The protections afforded by the ADA for individuals with substance use disorders are restricted by what appears to be the statute's moralizing on drug and alcohol use and those who use these substances.


Evaluation of the Impact of Virtual Reality-Enhanced Cardiac Rehabilitation on Depressive and Anxiety Symptoms in Patients with Coronary Artery Disease: A Randomised Controlled Trial.
The aim of this study was to assess the efficacy of virtual reality (VR)-enhanced cardiac rehabilitation (CR) in reducing the intensity of depression and anxiety symptoms in patients undergoing phase II of CR in ambulatory conditions. One hundred participants (mean age 65.7 years) were divided randomly into two groups. Both groups took part in eight sessions of standard CR (three times per week). The experimental group was additionally supported by eight sessions of VR therapy using the VR TierOne device and the control group by eight sessions of Schultz Autogenic Training. The Hospital Anxiety and Depression Scale (HADS) was used as the primary outcome measure. The Perception of Stress Questionnaire was used as the secondary outcome measure. The data from 77 participants were subject to analysis. Post-intervention, in the experimental group, the overall HADS score was statistically significantly reduced by 13.5%, HADS-Depression by 20.8%, and the general stress level by 12.8% (p < 0.05). In the control group, the scores of the HADS, HADS-Anxiety and the general stress level were statistically significantly higher, by 4.8%, 6.5%, and 4.9%, respectively. VR-enhanced CR for individuals with cardiovascular disease reduced the level of anxiety and depression symptoms compared to standard CR.


Doses, fractionations, constraints for stereotactic radiotherapy.
This paper describes how to select the most appropriate stereotactic radiotherapy (SRT ) dose and fractionation scheme according to lesion size and site, organs at risk (OARs) proximity and the biological effective dose. In single-dose SRT, 15-34 Gy are generally used while in fractionated SRT 30 and 75 Gy in 2-5 fractions are administered. The ICRU Report No. 91, which is specifically dedicated to SRT treatments, provided indications for dose prescription (with its definition and essential steps), dose delivery and optimal coverage which was defined as the best planning target volume coverage that can be obtained in the irradiated district. Calculation algorithms and OAR s dose constraints are provided as well as treatment planning system characteristics, suggested beam energy and multileaf collimator leaf size. Finally, parameters for irradiation geometry and plan quality are also reported.