Capillary vascular density in the retina of hypertensive patients is associated with a non-dipping pattern independent of mean ambulatory blood pressure.
A nocturnal non-dipping pattern has been associated with hypertension-mediated organ damage (HMOD), morbidity and mortality. Retinal imaging through application of modern technologies including optical coherence tomography angiography (OCT-A) can provide detailed insights into early vascular damage. In this observational study, we investigated the relationship of microscopic vascular density in the retina measured with OCT-A and nocturnal blood pressure (BP) dipping. Retinal OCT-A and ambulatory BP monitoring (ABPM) data prospectively obtained from 142 patients referred to a tertiary hypertension clinic were analysed with regression models for associations between BP night-time dipping and retinal capillary vascular density in three different zones around the fovea. More pronounced nocturnal SBP and DBP dipping was significantly associated with increased vascular density in the central foveal area of the retina. These associations were robust to adjustment for other available risk factors including mean daytime BP. Parafoveal and whole image vascular density did not show equivalent significant associations with nocturnal BP dipping. The results were reproducible when assessed in a subgroup of patients who had concomitant type 2 diabetes. Foveal vascular density was associated with the nocturnal BP dipping pattern in hypertensive patients. These associations were robust to adjustment of relevant factors such as daytime BP. Our findings highlight the importance of nocturnal BP features reflected in ambulatory BP monitoring in the assessment of HMOD. Whether routine assessment of retinal damage markers may improve risk management of hypertensive patients remains to be determined.


The Myth Regarding the High Cost of End-of-Life Care.
Health care reform debate in the United States is largely focused on the highly concentrated health care costs among a small proportion of the population and policy proposals to identify and target this "high-cost" group. To better understand this population, we conducted an analysis for the Institute of Medicine Committee on Approaching Death using existing national data sets, peer-reviewed literature, and published reports. We estimated that in 2011, among those with the highest costs, only 11% were in their last year of life, and approximately 13% of the $1.6 trillion spent on personal health care costs in the United States was devoted to care of individuals in their last year of life. Public health interventions to reduce health care costs should target those with long-term chronic conditions and functional limitations.


Characteristic differences in barrier and hygroscopic properties between normal and cosmetic dry skin. I. Enhanced barrier analysis with sequential tape-stripping.
Cosmetic dry skin often has a lower hydration level but a similar apparent barrier function, as measured by transepidermal water loss (TEWL), than that of the normal skin. To investigate the intrinsic difference in barrier property and moisture-holding ability between the cosmetic dry and normal skin, we developed a new clinical and data analysis procedure based on sequential tape-stripping with TEWL measurement, coupled with chemical analysis for protein and natural moisturizing factors (NMF) in the stratum corneum. A clinical study consisting of 64 healthy Caucasian female subjects with normal and cosmetic dry skin was conducted according to our clinical and data collection protocols. After the baseline visual dryness assessment, 20 tape-strips were placed and removed on each test site using D-Squame tapes. TEWL was measured at baseline and after the 5th, 10th, 15th and 20th tape-strips. All tapes were analysed for protein mass via chemical extraction and the Pierce BCA protein assay, as well as using an infrared densitometry device SquameScan 850A. The stratum corneum thickness and barrier quality (water transport resistance per thickness of the stratum corneum) were decoupled from the apparent barrier function using the TEWL and protein data. A linear relationship between 1/TEWL and cumulative protein removal was observed for both normal and cosmetic dry skin. However, the slope of the linear relation was significantly steeper for normal skin, and significantly more protein was removed from cosmetic dry skin. The results showed that on average, the barrier quality of the stratum corneum of the normal skin is about 40% higher than that of the dry skin, whereas the stratum corneum of the dry skin is about 30% thicker than that of the normal skin. In addition, the amount of SC removal in sequential tape-stripping is generally non-uniform. Our results demonstrated that there are characteristic differences in the barrier property between normal and cosmetic dry skin. In comparison to the normal skin, the stratum corneum of the cosmetic dry skin is considerably thicker, however, with a lower barrier quality. The results also showed that the amount of the SC removal in sequential tape-stripping is generally non-uniform. Therefore, the number of tape strips is not a good indicator for the tape-stripping depth.


Improving Precursor Selectivity in Data-Independent Acquisition Using Overlapping Windows.
A major goal of proteomics research is the accurate and sensitive identification and quantification of a broad range of proteins within a sample. Data-independent acquisition (DIA) approaches that acquire MS/MS spectra independently of precursor information have been developed to overcome the reproducibility challenges of data-dependent acquisition and the limited breadth of targeted proteomics strategies. Typical DIA implementations use wide MS/MS isolation windows to acquire comprehensive fragment ion data. However, wide isolation windows produce highly chimeric spectra, limiting the achievable sensitivity and accuracy of quantification and identification. Here, we present a DIA strategy in which spectra are collected with overlapping (rather than adjacent or random) windows and then computationally demultiplexed. This approach improves precursor selectivity by nearly a factor of 2, without incurring any loss in mass range, mass resolution, chromatographic resolution, scan speed, or other key acquisition parameters. We demonstrate a 64% improvement in sensitivity and a 17% improvement in peptides detected in a 6-protein bovine mix spiked into a yeast background. To confirm the method's applicability to a realistic biological experiment, we also analyze the regulation of the proteasome in yeast grown in rapamycin and show that DIA experiments with overlapping windows can help elucidate its adaptation toward the degradation of oxidatively damaged proteins. Our integrated computational and experimental DIA strategy is compatible with any DIA-capable instrument. The computational demultiplexing algorithm required to analyze the data has been made available as part of the open-source proteomics software tools Skyline and msconvert (Proteowizard), making it easy to apply as part of standard proteomics workflows. Graphical Abstract.


Quantifying Multistate Cytoplasmic Molecular Diffusion in Bacterial Cells via Inverse Transform of Confined Displacement Distribution.
Single-molecule tracking (SMT) of fluorescently tagged cytoplasmic proteins can provide valuable information on the underlying biological processes in living cells via subsequent analysis of the displacement distributions; however, the confinement effect originated from the small size of a bacterial cell skews the protein's displacement distribution and complicates the quantification of the intrinsic diffusive behaviors. Using the inverse transformation method, we convert the skewed displacement distribution (for both 2D and 3D imaging conditions) back to that in free space for systems containing one or multiple (non)interconverting Brownian diffusion states, from which we can reliably extract the number of diffusion states as well as their intrinsic diffusion coefficients and respective fractional populations. We further demonstrate a successful application to experimental SMT data of a transcription factor in living E. coli cells. This work allows a direct quantitative connection between cytoplasmic SMT data with diffusion theory for analyzing molecular diffusive behavior in live bacteria.


Impaired spatial memory in aged rats is associated with alterations in inositol phospholipid metabolism.
WE have investigated changes in inositol phospholipid turnover and membrane arachidonic acid concentration in the dentate gyrus and frontal cortex of animals aged 3-6 months, 14 months or 22 months which were trained in the Morris water maze. Ageing was associated with poorer performances in the behavioural test, characterized by increased variability in retention and acquisition amongst individuals, a decrease in membrane arachidonic acid concentration and increased unstimulated inositol phospholipid metabolism in synaptosomes prepared from frontal cortex and dentate gyrus. Arachidonic acid stimulated inositol phospholipid metabolism in synaptosomes, but in the older groups, stimulation was associated with good performance in the Morris water maze. In slices prepared from frontal cortex, responsiveness of inositol phospholipid metabolism to glutamate was also age- and performance-dependent. The findings highlight a correlation between age, inositol phospholipid metabolism and performance in the Morris water maze.


Only high-affinity receptors for interleukin 2 mediate internalization of ligand.
Interleukin 2 (IL-2) receptors are expressed on activated T cells and in select T-cell leukemias. Recently, it has been demonstrated that at least two classes of receptor for IL-2 exist with markedly different affinities for ligand. All known biological actions of IL-2 have been correlated with occupancy of high-affinity sites; the function of the low-affinity sites remains unknown. Receptor-mediated endocytosis is the primary means of internalization of cell-surface receptors and their ligands. The internalization of IL-2 bound to high- and low-affinity receptor sites was studied in a human T-cell lymphotrophic virus type 1 (HTLV-1)-infected human T-cell leukemia cell line and in a cloned murine cytotoxic T-cell line (CTLL). Internalization of IL-2 occurred only when bound to high-affinity sites. In addition, an anti-receptor antibody (anti-Tac), which binds equally well to high- and low-affinity sites, demonstrated no detectable internalization. The implications of these findings as they relate to IL-2 receptor structure and function are discussed.


Vitamin D Status in Blount Disease.
Blount disease can be defined as idiopathic proximal tibial vara. Several etiologies including the mechanical theory have been described. Obesity is the only causative factor proven to be associated with Blount disease. The aim of this study is to assess if there is an association of vitamin D deficiency and Blount disease. This a retrospective study of preoperative and postoperative patients with Blount disease who were screened for vitamin D deficiency. Patients with genu varum due to confirmed vitamin D deficiency and rickets were excluded. The study patients had the following blood tests done: calcium, phosphate, alkaline phosphatase, parathyroid, and 25-hydroxyvitamin D (25(OH)D) hormones. We recruited 50 patients. The mean age of these patients was 10.4 years (SD±3.88) with average body mass index of 28.7 kg/m (±10.2). Thirty (60%) patients were diagnosed with infantile, 4 (8%) juvenile, and 16 (32%) adolescent Blount disease. Eight (16%) patients were found to be vitamin D deplete (25(OH)D levels <50 nmol/L). Of these, 8 patients, 6 were insufficient (25(OH)D levels between 30 and 50 nmol/L) and the other 2 were deficient (25(OH)D levels <30 nmol/L). This study showed that the prevalence of vitamin D deficiency in children with Blount disease was similar to that of healthy children living in Johannesburg. There is no evidence that vitamin D deficiency is a factor in causing Blount disease. Level III-retrospective study.


Hyperparathyroidism after renal transplantation.
Renal transplantation reduced circulating parathyroid hormone in recipients of renal allografts. Nevertheless, biochemical and histological evidence of mild hyperparathyroidism persisted up to eight years after renal transplantation despite good graft function.


[Cushing's syndrome and adrenal suppression by means of intranasal use of dexamethasone preparations].
In two 15-year-old boys with bronchial asthma and allergic rhinitis, bronchospasm disappeared with prolonged use of intranasal dexamethasone ointment and drops respectively. Both showed cushingoid features and total or partial suppression of adrenocortical function. The first patient died during a sudden and unexpected asthma crisis one week after withdrawal of the 0.25% dexamethasone ointment he had been taking at the rate of 1.8 mg/day for one year. The second boy recovered near-normal adrenocortical function 3 months after gradual withdrawal of the 0.01% dexamethasone nose drops he had been on at an average daily dose of 0.5 mg, for the past 6 years. An acute trial in 10 normal volunteers showed marked short-term suppression of endogenous cortisol production after a single intranasal ointment application containing 0.9 mg dexamethasone. Long-term use of dexamethasone preparations on the nasal mucosa may be dangerous by inhibiting hypophyseal-adrenocortical function. Abrupt withdrawal may lead to sudden relapse of a potentially life-threatening accompanying disease such as bronchial asthma.


A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2.
Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. Number: NCT01821833.


Distinct bacterial colonization patterns of Escherichia coli subtypes associate with rheumatoid factor status in early inflammatory arthritis.
The aetiology of RA is unknown; however, bacterial exposure, particularly to Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae, has been linked to disease pathogenesis. The strongest association was observed for RF(+) RA. We compare colonization patterns of these bacteria, and the anti-bacterial antibody levels in early onset RF(+) and RF(-) inflammatory arthritis. Bacteria isolated from stool and urine of early-stage RF(+) and RF(-) patients recruited to the Early Arthritis Registry were biochemically identified and genotyped. IgM and IgA anti-bacterial and RF antibodies were assessed by ELISA. Differences in the types of colonizing pathogenic E. coli were identified. RF(+) patients were more commonly colonized with phylogenetic Group D E. coli, whereas RF(-) patients were more commonly colonized with phylogenetic Group B2 E. coli and these individuals also had lower joint scores and inflammatory markers yet higher IgA anti-E. coli antibody responses. These studies link the type of colonizing bacteria in the gut and urine with the immune response (anti-bacterial and RF) in early-onset inflammatory arthritis and provide evidence for a role of the host-pathogen response in the aetiology of RF.


Linking components between capsomers in the adenovirus capsid.
The interhexonal space within the adenovirus capsid is bridged by interhexonal connective elements. These linking components have been detected also between pentons and the five peripentonal hexons surrounding them. According to the results obtained by Markham's rotational integration technique the connective elements between the capsomers are interlacing the whole virion. It could be confirmed in several cases that the linking elements consisted of two approximately parallel elements. This means that each hexon is linked by six times two parallel linking components with its six nearest neighbours in the virus capsid.


Amplification of feline sarcoid-associated papillomavirus DNA sequences from bovine skin.
Feline sarcoids are uncommon dermal neoplasms that are thought to be caused by papillomaviral (PV) infection. Feline sarcoid-associated PV (FeSarPV) has been consistently detected in sarcoids from North American and New Zealand cats but has not been detected within any other feline sample. This suggests that feline sarcoids may develop due to cross-species infection by a PV from an unidentified reservoir host. While there is some epidemiological evidence to suggest that cattle are the reservoir host of FeSarPV, this PV has never been identified within any bovine sample. In this study both consensus PCR primers and primers specific to FeSarPV were used to investigate the presence of PV DNA within five fibropapillomas and 18 samples of inflammatory skin disease from cattle. Consensus primers amplified bovine PV-2 DNA from four fibropapillomas, but none of the dermatitis samples. However, specific primers amplified FeSarPV DNA from four fibropapillomas and five inflammatory skin lesions. To the best of our knowledge this is the first time that FeSarPV has been detected within any sample other than a feline sarcoid. The ability of FeSarPV to asymptomatically infect bovine skin suggests that cattle are the reservoir host of this PV and feline sarcoids could be the result of cross-species infection of a dead-end host by a bovine PV.


Diversity-Aware Multi-Video Summarization.
Most video summarization approaches have focused on extracting a summary from a single video; we propose an unsupervised framework for summarizing a collection of videos. We observe that each video in the collection may contain some information that other videos do not have, and thus exploring the underlying complementarity could be beneficial in creating a diverse informative summary. We develop a novel diversity-aware sparse optimization method for multi-video summarization by exploring the complementarity within the videos. Our approach extracts a multi-video summary, which is both interesting and representative in describing the whole video collection. To efficiently solve our optimization problem, we develop an alternating minimization algorithm that minimizes the overall objective function with respect to one video at a time while fixing the other videos. Moreover, we introduce a new benchmark data set, Tour20, that contains 140 videos with multiple manually created summaries, which were acquired in a controlled experiment. Finally, by extensive experiments on the new Tour20 data set and several other multi-view data sets, we show that the proposed approach clearly outperforms the state-of-the-art methods on the two problems-topic-oriented video summarization and multi-view video summarization in a camera network.


Pox viruses as eukaryotic cloning and expression vectors: future medical and veterinary vaccines.
It was proposed at the beginning of this article that the use of poxviruses as expression vectors provided a means of optimizing the conditions and prerequisites of vaccination and of elucidating a number of the associated problems. These advantages will now be summarized. Vaccinia virus recombinants carrying one or more multiple foreign genes have been shown to induce a sufficient immune response to that antigen in laboratory animals to protect against subsequent challenge by the infectious agent. In those animals tested the duration of immunity has been long-lasting with no apparent detrimental side-effects. Vaccinia virus is very stable in normal environmental situations and no cold-chain is required in the distribution network. There is no evidence for genetic instability of the vaccinia 'carrier' strain nor of loss of the inserted genetic elements. The vaccine is administered intradermally and it is proposed that one inoculation will be sufficient to induce immunity to multiple disease antigens; however, re-inoculation at a later time with the same or new antigenic determinants is not precluded. The efficiency of vaccinia virus as the vaccine strain used to eliminate the disease of smallpox with minimal side-effects is well documented. The recent studies described here on the development of vaccinia as a viral vector confer other advantages. Since the expression of the inserted genetic element is under vaccinia virus control, different levels of expression can be engineered by substituting the promoter sequence placed proximal to the insert. This leads to the possibility of high levels of expression when required for a single antigen or more modulated levels when multiple foreign antigens are expressed and 'genetic overload' could become a problem. Much work remains to be done on the body's immune response to this proposed genetic intrusion. The ability to insert large amounts of genetic information without disrupting virus replication and assembly indicates a great degree of flexibility in the genome strategy of the virus. This may indicate that the replication system can be further disrupted to eliminate or modify those sequences coding for virulence and wide host range to make the poxvirus vector as safe as possible for vaccine use. One of the reasons traditional vaccine strategy has failed for some virus groups is the degree of variability found in virus strains in nature. Influenza viruses are a good example, as are the bluetongue virus group, rotaviruses and bunyaviruses.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term follow-up study of elderly patients with covered stent implantation after coronary perforation.
To evaluate the long-term efficacy of covered stent implantation in the treatment of elderly patients with coronary perforation while undergoing percutaneous coronary intervention (PCI). From June 2004 to June 2012, our center has followed ten elderly patients (age ≥ 60 years) who sustained coronary perforation during PCI. The major adverse cardiac events (MACE) were observed as well. The patients were advised to take 75 mg/day Clopidogrel for two years, and indefinite use of 100 mg/day enteric-coated aspirin. Six out of the 10 patients aged from 60 to 76 years old (mean 68.6 ± 5.2 years) were male, four were female. The average diameter of the implanted stents was 3.3 ± 0.3 mm, and the average length was 22.1 ± 3.7 mm. All the ruptures were successfully sealed without intra-procedural death. The follow-up duration ranged from 0.6 to 67 months (mean 31.7 ± 24.5 months). One patient died of multiple organ failure due to lung infection in 19 days after PCI; one died of cardiac sudden death in 13 months after PCI; one had angina pectoris in 53 months after PCI; one underwent multi-slice CT examination in six months after PCI, and no in-stent restenosis was found. The other four patients received angiography follow-up, and the results showed that three patients had no intra-stent restenosis, while one had left anterior descending (LAD) restenosis in the covered stent in 67 months after PCI. The in-hospital mortality was 10% (1/10). The MACE rate in 12 months after PCI was 10% (1/10). During the entire followed-up period, the restenosis rate in target vessels was 20% (1/5), mortality was 20% (2/10), and the MACE rate was 40% (4/10). Treatment of coronary perforation by using covered stents can achieve favorable long-term results; a two-year dual antiplatelet therapy (DAPT) after PCI can effectively prevent intra-stent thrombosis.


Bilingual Supports for Clinicians: Where Do We Go From Here?
Purpose The purpose of this study was to identify and define the support needs of bilingual speech-language pathologists working in one urban school district and to investigate the experiences of the clinicians engaged in a professional learning community (PLC) format within their public school system. Method Twenty-three bilingual speech-language pathologists met in a PLC over the course of 5 months, with a total of four sessions that were a mix of in person and virtual. The participants engaged in group discussions and activities alongside their peers to address self-identified areas of support and need. Additionally, initial and final focus group and exit slip data following the PLC were collected to inform the discussion topics of the PLC and gather final impressions. Constant comparative analysis was utilized to analyze focus group and exit slip data. Results When looking across the experiences of the clinicians in the district, the three themes that emerged from the data were systemic obstacles, professional obstacles, and supports. The three themes that emerged from the speech-language pathologists' experiences in the PLC included their positive experiences, the challenges with participation, and the positive outcomes from exposure to new techniques and earning platforms. Conclusion The findings of this study suggest that bilingual clinicians benefit from a PLC model when addressing specific areas of need.


[The effect of maternal medications, hypertension/pre-eclamptic toxemia and diabetes mellitus on neonatal hearing screening].
The effects of maternal medications and disease on neonatal hearing screening have scarcely been investigated. To verify the effect of maternal medications and disease during gestation on the results of the first otoacoustic emissions (OAE) test. We recorded perinatal and hearing screening data, medications during pregnancy and Labor (119 kinds of medication), hypertension/pre-eclamptic toxemia (HTN/PET) and diabetes mellitus (DM). Of the 2306 infants studied, 214 (9.3%) failed the first OAE test. Vaginal delivery (VD) and cesarean delivery (CD) infants were analyzed separately. Multivariate logistic regression analysis showed: Independently significant variables associated with failed first OAE in VD infants included: Birth weight (BW) >4000g [OR 2.2 (1.1-4.3) p=0.026]; decreasing age at first OAE [OR 0.31 (0.17-0.6) p<0.001] and maternal DM [OR 2.2 (1.0-4.84) p=0.049]. The findings for CD infants were: male gender [OR 1.91 (1.24-2.96) p=0.004); decreasing age at first OAE [OR 0.34 (0.21-0.55) p<0.001]; maternal HTN/PET [OR 2.3 (1.22-4.3) p=0.01 and small-for-gestational-age (SGA) status [OR 2.9 (1.1-7.56) p=0.03]. Increased failure on first OAE occurs in VD infants with BW >4,000g, early first OAE and DM; and in CD infants with male gender, early first OAE, HTN/PET and SGA status. It is yet to be determined whether postponing of first OAE beyond 48 hours of age will allow the reduction of false positive results on first OAE.


Correction of hypoxia and hypercapnia in COPD patients: effects on cerebrovascular flow.
To assess the responsiveness of cerebral blood flow to arterial carbon dioxide tension (Pa,CO2), arterial oxygen tension (Pa,O2), and pH modifications, in chronic hypercapnia, we measured middle cerebral blood flow velocity (CBFV) by transcranial Doppler ultrasound in 13 chronically hypercapnic, long-term ventilated patients with chronic obstructive pulmonary disease (COPD), in the following conditions: 1) breathing room air; 2) with oxygen supplementation; 3) during mechanical noninvasive intermittent positive pressure ventilation (nIPPV) with O2 enrichment. Under baseline conditions (room air), the CBFV was within the normal range. During oxygen administration, a statistically significant increase was obtained in Pa,O2 (6.5 +/- 0.6 vs 11.2 +/- 1.9 kPa (49.1 +/- 4.3 vs 84.3 +/- 14.6 mmHg)), without relevant variations in: CBFV (54.2 +/- 9.1 cm.s-1), Pa,CO2 (8.6 +/- 1.0 kPa (64.7 +/- 7.7 mmHg)) and hydrogen ion concentration [H+] (42.9 +/- 2.9 nM), compared to baseline values (CBFV = 52.8 +/- 10.7 cm.s-1; Pa,CO2 = (8.4 +/- 0.9 kPa (63.1 +/- 7.1 mmHg; [H+] = 41.8 +/- 2.8 nM). After nIPPV, Pa,O2 did not increase any further (10.6 +/- 1.7 kPa (79.2 +/- 12.7 mmHg)), while CBFV (40.9 +/- 12.6 cm.s-1), Pa,CO2 (7.5 +/- 1.3 kPa (56.2 +/- 9.4 mmHg)) and [H+] (39.1 +/- 4.6 nM) showed a significant reduction compared to oxygen therapy (p < 0.01). We therefore conclude that in chronically hypercapnic long-term ventilated patients cerebral blood flow depends mainly on changes in Pa,CO2 and [H+], whilst oxygen does not seem to interfere with cerebral flow velocity. The reduction of Pa,CO2, due to mechanical ventilation, may determine cerebral blood vessel constriction, with possible impairment of cerebral functions.


The epidemiology of squamous cell carcinoma of the perineal region of sheep: abattoir and flock studies.
The roles of age, tail length and the Mules operation in the epidemiology of squamous cell carcinoma in ewes were studied. The prevalence of the disease in adult sheep slaughtered at 2 abattoirs was 0.08%. No cases occurred in lambs. Of all adult sheep condemnations before slaughter, 38.5% were due to squamous cell carcinoma. Of these sheep, 73.3% had a single lesion of the vulva (62.9%), tail (6.6%), or anus (3.8%), while 26.7% had lesions at more than one site. The number of lesions was significantly greater (p less than 0.01) in sheep with a radical Mules operation than in those with a modified Mules operation or not mulesed. Tails were significantly shorter (p less than 0.01) in affected than unaffected sheep. Small keratinised outgrowths on the skin of the tail and perineum were considered on histological grounds to be precursors of squamous cell carcinomas. On one affected farm 4% of ewes were culled in one year for gross lesions of squamous cell carcinomas. A further 3.5% of sheep with gross lesions and 25.3% with precursor lesions remained in the flock, undetected by the farmer. Gross lesions were not observed in ewes under 3 years of age, whereas precursors occurred in all age groups, including one-year-old ewes. The prevalence of lesions increased with age, from 0.43% in 5-year-old ewes to 5.14% in 6-year-old and 41% in 7-year-old ewes. Discriminant analysis indicated that age of ewe, tail length and the width of the healed Mules operation were important determinants of squamous cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)


Charging effects in the inductively shunted Josephson junction.
The choice of impedance used to shunt a Josephson junction determines if the charge transferred through the circuit is quantized: a capacitive shunt renders the charge discrete, whereas an inductive shunt gives continuous charge. This discrepancy leads to a paradox in the limit of large inductances L. We show that while the energy spectra of the capacitively and inductively shunted junction are vastly different, their high-frequency responses become identical for large L. Inductive shunting thus opens the possibility to observe charging effects unimpeded by charge noise.


Directing the Activation of Donor-Acceptor Cyclopropanes Towards Stereoselective 1,3-Dipolar Cycloaddition Reactions by Brønsted Base Catalysis.
The first stereoselective organocatalyzed [3+2] cycloaddition reaction of donor-acceptor cyclopropanes is presented. It is demonstrated that by applying an optically active bifunctional Brønsted base catalyst, racemic di-cyano cyclopropylketones can be activated to undergo a stereoselective 1,3-dipolar reaction with mono- and polysubstituted nitroolefins. The reaction affords functionalized cyclopentanes with three consecutive stereocenters in high yield and stereoselectivity. Based on the stereochemical outcome, a mechanism in which the organocatalyst activates both the donor-acceptor cyclopropane and nitroolefin is proposed. Finally, chemoselective transformations of the cycloaddition products are demonstrated.


Brief ultrasonication improves detection of biofilm-formative bacteria around a metal implant.
Biofilms are complex microenvironments produced by microorganisms on surfaces. Ultrasonication disrupts biofilms and may make the microorganism or its DNA available for detection. We determined whether ultrasonication could affect our ability to detect bacteria adherent to a metal substrate. A biofilm-formative Staphylococcus aureus strain was used for an in vitro implant infection model (biofilm-formative condition). We used quantitative culture and real time-polymerase chain reaction to determine the influence of different durations of ultrasound on bacterial adherence and viability. Sonication for 1 minute increased the yield of bacteria. Sonication longer than 5 minutes led to fewer bacterial colonies by conventional culture but not by polymerase chain reaction. This suggests short periods of sonication help release bacteria from the metal substrate by disrupting the biofilm, but longer periods of sonication lyse bacteria prohibiting their detection in microbiologic cultures. A relatively short duration of sonication may be desirable for maximizing detection of biofilm-formative bacteria around implants by culture or polymerase chain reaction.


Unhoused and unhireable? Examining employment biases in service contexts related to perceived warmth and competence of people experiencing houselessness.
Lack of safe and stable housing is a pernicious and growing social concern, and stereotypes about individuals experiencing houselessness are generally quite negative. Little scholarly work has examined housing insecurity and its associated stereotypes in employment contexts. The purpose of the current research was to examine, in the context of the hospitality industry, whether housing status influences hiring managers' perceptions of hireability (Study 1) and customers' evaluations of an organization and its employees (Study 2) using the stereotype content model. Across two experimental studies, we assessed participant attitudes toward individuals experiencing houselessness. In Study 1, we instructed 148 hotel managers to listen to a hypothetical job interview with either an unhoused or housed job applicant, and then complete measures of hireability. In Study 2, we instructed 139 hotel customers to observe a hypothetical interaction with either an unhoused or housed employee, and then evaluate the employee and the organization. Study 1's findings suggested an indirect effect of housing status on perceived hireability through warmth, and this indirect relationship was moderated by gender. Men who were houseless were rated lower in warmth, and thus lower in hireability, than non-houseless men or women regardless of their housing status. However, houseless men were perceived by customers as warmer than non-houseless men as employees, driving higher evaluations of the organization and the employee (Study 2). Hiring initiatives targeted at providing short-term housing for unhoused employees will benefit employees, employers, and the larger communities they encompass.


Design of floating bilayer tablets of diltiazem hydrochloride and lovastatin.
The purpose of the study is to design bilayer floating tablets of diltiazem HCI and lovastatin to give immediate release of lovastatin and controlled release of diltiazem HCl and to study the influence of presence of one drug on the release pattern of other drug. The bilayer tablets consist of sodium starch glycolate as superdisintegrant for lovastatin in the immediate release layer and hydroxypropyl methylcellulose (HPMC) K4M and Xanthan gum as release-retarding agents for diltiazem HCl in the controlled release layer. Sodium bicarbonate was used as the gas generating agent. Dicalcium phosphate was used as the channeling agent. The direct compression method was employed for preparation of the bilayer tablets. Various physicochemical parameters were evaluated for the prepared tablets. The physicochemical parameters were found to be within range. There was significant difference in drug release and floating lag time (P < 0.05). All the formulations showed good matrix integrity. All the formulations released lovastatin within 30 min. The diffusion exponent for diltiazem HCl was found to be independent of polymer concentration. The release pattern of diltiazem HCI was fitted to different models based on coefficient of correlation (R). All the formulations followed the Higuchi model, except F1 which followed the Peppas model. HPMC K4M and Xanthan gum retarded the release of diltiazem HCl for 12 h. The release of one drug remained unaffected in presence of the other drug. In conclusion, such kind of combined dosage forms can effectively be formulated to deliver more than one drug so as to have improved patient compliance and better disease management.


[New public health approach to STIs prevention].
International Conference on Population and Development (1994) recommended that the scope of reproductive health should be broadened beyond family planning and maternal care. It should include prevention and management of HIV/AIDS/STIs and many others issues. The arguments for this shift and some organizational rules for health reproductive system performance are presented.


Quality Implementation in Health Physics Unit, Cosenza Hospital. Accreditation Program as Quality Improvement instrument.
Achieving high levels of quality in healthcare, which could be measurable, is increasingly important at present and is dictated by the radical changes of the welfare system imposed today by the well known economic constraints. However, even in the ongoing legislation, the practices concerning the verification and review of the quality of health care has had a major impact in the galaxy of Health. On the one hand, the citizen is developing an awareness of the possibilities of choice (Empowerment) between a plurality of providers of healthcare services, on the other hand providers themselves are obliged, within the logic of a global market, to retrain their offers to respond satisfactorily to the needs of citizens. The purpose of this study was to demonstrate how the adoption of Operational Procedures, following the granting of a certificate of accreditation to the Unit of Medical Physics, has changed the approach to the work on the part of health workers, in the direction of a dynamic quality improvement.


Expression profile analysis reveals hub genes that are associated with immune system dysregulation in primary myelofibrosis.
Primary myelofibrosis (PMF) is a familiar chronic myeloproliferative disease with an unfavorable prognosis. The effect of infection on the prognosis of patients with PMF is crucial. Immune system dysregulation plays a central role in the pathophysiology of PMF. To date, very little research has been conducted on the molecular mechanism of immune compromise in patients with PMF. To explore potential candidate genes, microarray datasets GSE61629 and 26049 were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PMF patients and normal individuals were evaluated, gene function was measured and a series of hub genes were identified. Several significant immune cells were selected via cell type enrichment analysis. The correlation between hub genes and significant immune cells was determined. A total of 282 DEGs were found, involving 217 upregulated genes and 65 downregulated genes. Several immune cells were found to be reduced in PMF, such as CD4+ T cells, CD4+ Tems, CD4+ memory T cells. Gene Ontology (GO) enrichment analysis of DEGs reflected that most biological processes were associated with immune processes. Six hub genes, namely, HP, MPO, MMP9, EPB42, SLC4A1, and ALAS2, were identified, and correlation analysis revealed that these hub genes have a negative correlation with immune cell abundance. Taken together, the gene expression profile of whole blood cells in PMF patients indicated a battery of immune events, and the DEGs and hub genes might contribute to immune system dysregulation.


Partial amino acid sequence of human thrombospondin as determined by analysis of cDNA clones: homology to malarial circumsporozoite proteins.
A lambda gt 11 library prepared from human umbilical vein endothelial cell RNA was screened for cDNAs encoding thrombospondin. Reagents included a monospecific antibody to human thrombospondin and a mixture of four synthetic oligodeoxyribonucleotides derived from an amino acid sequence near the NH2 terminus of mature human thrombospondin. Two series of cDNA clones coding for sequences at the 5' and 3' ends of thrombospondin mRNA, respectively, were isolated. The nucleotide sequence of a 1.3-kilobase (kb) 5' clone (lambda TS-33) coded for 99 bases of 5' untranslated RNA, a signal peptide of 18 amino acids, and the first 379 amino acids of thrombospondin. Northern blot analysis with lambda TS-33 detected a single mRNA species of approximately 6.0 kb in rat aortic smooth muscle cell RNA. Thrombospondin mRNA levels increased rapidly, but transiently, in quiescent smooth muscle cells treated with platelet-derived growth factor. The kinetics of this response were very similar to those of the thrombospondin protein to this growth factor. There was significant homology in amino acid sequence between thrombospondin and a conserved region in the circumsporozoite protein of two malarial sporozoites. This region of thrombospondin may therefore represent a potential recognition site for a cell surface thrombospondin receptor.


The population dynamics of cancer: a Darwinian perspective.
Carcinogenesis, at least for some types of cancer, can be interpreted as the consequence of selection of mutated cells similar to what, in the theory of evolution, occurs at the population level. Instead of considering a population of organisms, we can refer to a population of cells belonging to multicellular organisms. Many carcinogens are mutagens, and the observed geographic distribution of cancer is, at least in part, attributable to environmental mutagens. However, the rapid change in risk for some cancers after migration suggests that carcinogenesis involves--in addition to mutations--some late event that most probably consists of the selection of cells already carrying mutations. We review a few examples of such selective pressures: finasteride in prostate cancer, vitamin supplementation in smokers, acquired resistance to chemotherapy, peripheral resistance to insulin, and sunlight and mutations in melanoma. A disease model for such a hypothesis is represented by Paroxysmal Nocturnal Hemoglobinuria (PNH). Mutations can be present at birth, as in the case of PNH, and can have a frequency much higher than the occurrence of the corresponding disease (PNH or lymphocytic leukaemia in children). However, PNH does not require a mutator phenotype, only a mutant phenotype followed by selection. A characteristic feature of cancer, instead, is likely to be the development of the mutator phenotype. We propose a 'Darwinian' model of carcinogenesis. If the model is correct, it suggests that prevention is more complex than avoiding exposure to mutagens. Mutations and genetic instability can be already present at birth. Mutations can be selected in the course of life if they increase survival advantage of the cell under certain environmental circumstances. In addition, gene-environment interactions cannot be interpreted according to a simplified linear model (based on the 'analysis of variance' concept); experimental work suggests that a more comprehensive non-linear interpretation based on the idea of 'norm of reaction' is needed.


Some properties of subunits of DNA gyrase from Pseudomonas aeruginosa PAO1 and its nalidixic acid-resistant mutant.
Subunits A and B of DNA gyrase were purified from Pseudomonas aeruginosa PAO1 and its mutant, which was resistant to nalidixic acid. Inhibition tests of DNA gyrases reconstituted with a combination of subunits from the two strains showed that an alteration of subunit A but not subunit B caused bacteria to resist fluoroquinolones.


Alcohol: Immunomodulatory Effects and Cancer.
Alcohol consumption has been linked to numerous pathologic conditions, including infectious diseases and several types of cancer. Alcohol exerts its modulatory effects on the immune system (IS) in a dose- and time-dependent manner. Numerous studies indicate that these alterations affect responses such as peripheral inflammation or decreased antibody production and promote chronic inflammation, leading to cell death. The molecular mechanisms underlying these effects involve generating an oxidative tissue environment, producing cell damage-associated molecular patterns (DAMPs), and activating pattern recognition receptors. In particular, toll-like receptors and their signaling system emerge as central elements whose activity is altered by alcohol intake. There is also some epidemiological evidence demonstrating the causal role of alcohol in the development of various types of cancer, such as head-and-neck cancer, esophageal cancer, colorectal cancer, liver cancer, and breast cancer. Most recent evidence suggests that factors related to alcohol consumption and cancer include increased levels of acetaldehyde, production of reactive oxygen species, alteration in DNA methylation, and modifications in retinoid metabolism. In addition, changes associated with alcohol use on the IS and intestinal microbiota may favor the growth of some types of tumors.


Lipopolysaccharide dose response in baboons.
A lipopolysaccharide (LPS) dose-response study in an experimental baboon endotoxemia model is presented to define the relevance of this model compared with human endotoxemia. We describe acute and subacute endotoxemic models in baboons, the first evoked by bolus injection of LPS (1 mg, 0.1 mg, or 4 ng per kg of Escherichia coli LPS), and the second evoked by infusion of 1.5 mg/kg of E. coli LPS over 30 min. We report the analysis of LPS clearance, the kinetics of tumor necrosis factor, interleukin (IL) 6, and IL-8 expression on the protein as well as on the mRNA level, change in blood counts (white and red blood cells and circulating platelets), and several hemodynamic parameters such as temperature, cardiac index, heart rate, and mean arterial pressure via multiple sampling. The resulting data are compared with previously published human data. Our results show that the LPS-induced kinetics of cytokine release, as well as of hemodynamic and hematologic changes in baboons, were similar to those observed in humans, even though baboons required a approximately 104-fold higher initial LPS dose to develop these manifestations. Hence, we demonstrate that endotoxemia in baboons qualitatively, yet not quantitatively, resembles endotoxemia in humans and, therefore, proves to constitute a useful model for studying the pathogenic mechanisms of sepsis in relation to humans.


Effects of wearing functional foot orthotic on pelvic angle among college students in their 20s with flatfoot.
[Purpose] This study examined the impact of wearing a functional foot orthotic on the pelvic angle of young adults who have flatfoot. [Subjects and Methods] A total of 15 college students diagnosed with flatfoot were included in the study. Changes in the pelvic angle in the stance period during walking before and after orthotic use were measured using a VICON Motion System (VICON, Hansung, Korea). The data were analyzed using SPSS 12.0 for Windows. [Results] In the experimental group, the pelvic angle during the mid-stance and mid-swing periods of the gait cycle significantly decreased on the left and right sides after wearing the orthotic, compared to the measurements taken before orthotic usage. The pelvic angle change on the left and right sides also decreased after wearing the orthotic, though this difference was not significant. [Conclusion] The pelvic angle of college students with flatfoot decreased after they wore orthotics. This implies that wearing orthotic shoes can greatly benefit individuals during normal walking by promoting passive changes that decrease the pelvic angle.


Long COVID in Uganda: Electrographic findings among patients at risk.
COVID-19 has a significant cardiovascular involvement. Electrocardiographic (ECG) abnormalities among people at a risk of Long COVID in Uganda was investigated. A cross-sectional study was conducted from February to June 2022 at the post COVID - 19 clinic in Mulago National Specialized Hospital, Kampala. A standard resting ECG was performed on individuals at least 2 months following acute COVID-19, with a negative SARS-CoV-2 reverse-transcription polymerase chain reaction. Sociodemographic and clinical characteristics as well as vital signs were recorded for all study participants. Of the 244 study participants, 117 (47.9%) were female. The median age of all the participants was 33.0 (interquartile range: 26.0 - 43.5) years. Twenty-five (10.2%) participants had a history of smoking while 117 (48%) had a history of alcohol intake. In total, 46 (18.9%) had abnormal ECG findings (95% Confidence Interval (CI): 14.39 - 24.29) and non-specific T-wave inversion (n = 16, 34%) was the most frequent ECG abnormality. The proportion of participants with ECG abnormalities was 48% lower among females (adjusted prevalence ratio (aPR): 0.52, 95% CI: 0.28 - 0.96, p value < 0.05) and 2-fold greater for those with a history of smoking (aPR: 2.03, 95% CI:1.096 - 3.776, p value < 0.05). One in five Ugandans who were checked at the clinic at a risk of Long COVID showed ECG abnormalities. ECG screening is suggested to be integrated into the follow-up care of those at a risk of Long COVID.


BDNF controls object recognition memory reconsolidation.
Reconsolidation restabilizes memory after reactivation. Previously, we reported that the hippocampus is engaged in object recognition memory reconsolidation to allow incorporation of new information into the original engram. Here we show that BDNF is sufficient for this process, and that blockade of BDNF function in dorsal CA1 impairs updating of the reactivated recognition memory trace.


A Novel Approach for Analyzing the Effects of Almen Intensity on the Residual Stress and Hardness of Shot-Peened (TiB + TiC)/Ti-6Al-4V Composite: Deep Learning.
In the present study, the experimental data of a shot-peened (TiB + TiC)/Ti-6Al-4V composite with two volume fractions of 5 and 8% for TiB + TiC reinforcements were used to develop a neural network based on the deep learning technique. In this regard, the distributions of hardness and residual stresses through the depth of the materials as the properties affected by shot peening (SP) treatment were modeled via the deep neural network. The values of the TiB + TiC content, Almen intensity, and depth from the surface were considered as the inputs, and the corresponding measured values of the residual stresses and hardness were regarded as the outputs. In addition, the surface coverage parameter was assumed to be constant in all samples, and only changes in the Almen intensity were considered as the SP process parameter. Using the presented deep neural network (DNN) model, the distributions of hardness and residual stress from the top surface to the core material were continuously evaluated for different combinations of input parameters, including the Almen intensity of the SP process and the volume fractions of the composite reinforcements.


Efficacy of Labial Split-Thickness Eversion Periosteoplasty for Soft Tissue Management in Posterior Mandibular Horizontal Ridge Augmentation Procedures: A Prospective Clinical Study.
Purpose: To evaluate the efficacy of split-thickness labial eversion periosteoplasty (EPP) for soft tissue closure in horizontal ridge augmentation of posterior mandibular regions using a bone shell onlay grafting technique. Materials and Methods: Sixteen patients (12 female and 4 male; mean age: 46.2 ± 8.7 years) with 18 horizontal bone defects in posterior mandibular regions were included for lateral onlay bone grafting using the bone shell technique. After lateral bone augmentation, the EPP was used for soft tissue closure and was prospectively followed up for wound healing efficacy using a modified scoring index. The scoring index included dichotomous (yes: 0 / no: 1) evaluation of the following items: (1) bleeding on palpation or spontaneously, (2) tissue color difference, (3) presence of hematoma, (4) presence of granulation tissue, (5) incomplete incision margin closure, (6) dehiscence with visible augmentation material, (7) presence of exudation, and (8) presence of suppuration. In addition, a visual analog scale (VAS) was used to quantify and record the amount of pain and swelling (0 = no pain/swelling and 5 = severe pain/swelling); VAS scores of 0, 1, and 2 were rated as 1 in the dichotomous scoring index, and VAS scores of 3, 4, and 5 were rated as 0. A summarized wound healing score consisting of all 10 items was assessed at days 2, 7, and 14 and at months 1 and 4 postoperatively, including a comparison of the follow-up evaluations. Results: The summarized healing score increased significantly (P < .01) between day 2 (score: 6.6 ± 1.1) and day 7 (score: 8.9 ± 1.0) but showed little difference between day 14 (score: 9.6 ± 0.6) and the 1- and 4-month follow-ups (score: 10.0 ± 0). There was no wound dehiscence and no incomplete incision margin adaptation. For the individual parameters evaluated, bleeding on palpation, hematoma, and exudation were the most frequent side effects at day 2 at 50%, 100%, and 22.2%, respectively, and at day 7 at 16.7%, 55.6%, and 22.2%, respectively. The average pain score and the swelling/edema score were initially 4.0 ± 0 and 3.0 ± 0.77 on day 2, with a significant decrease (P < .001) by day 7 (pain: 2.0 ± 0; edema/swelling: 2.0 ± 0.59) and day 14 (pain: 1.0 ± 0.42; edema/swelling: 2.0 ± 0.79) and complete absence (score: 0) at months 1 and 4. Conclusions: Labial split-thickness EPP facilitates flap advancement and enables tight soft tissue coverage in large horizontal posterior mandibular bone augmentations as a result of offset double-layer wound closure. Although this procedure is shown to be surgically demanding, the postoperative complication rate may be reduced significantly.


Chromosomal deletions mediated by CRISPR/Cas9 in Helicoverpa armigera.
Helicoverpa armigera, cotton bollworm, is one of the most disastrous pests worldwide, threatening various food and economic crops. Functional genomic tools may provide efficient approaches for its management. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, dependent on a single guide RNA (sgRNA), has been used to induce indels for targeted mutagenesis in cotton bollworm. However, genomic deletions may be more desirable to disrupt the function of noncoding genes or regulatory sequences. By injecting two sgRNAs with Cas9 protein targeting different exons, we obtained predictable genomic deletions of several hundred bases. We achieved this type of modification with different combinations of sgRNA pairs, including HaCad and HaABCC2. Our finding indicated that CRISPR/Cas9 can be used as an efficient tool to engineer genomes with chromosomal deletion in H. armigera.


Stress up-regulates neuronal expression of the herpes simplex virus type 2 large subunit of ribonucleotide reductase (R1; ICP10) by activating activator protein 1.
Herpes simplex virus type 2 (HSV-2) genes expressed in neuronal cells in response to stress stimuli that trigger latency reactivation are largely unknown. Using a chloramphenicol acetyltransferase (CAT) reporter assay we found that stress caused a significant (P < .001) increase in ICP10 expression in neuronal cells. Up-regulation correlated with activator protein (AP)-1 activation, notably c-Jun and c-Fos that bind cognate elements in the ICP10 promoter. It was blocked by mutation of the AP-1 motifs in the ICP10 promoter. ICP10 expression protected neuronal cells from stress-induced apoptosis. The data suggest that ICP10 may contribute to HSV-2 reactivation by increasing neuronal survival.


Comparison of de-duplication methods used by WHO Global Antimicrobial Resistance Surveillance System (GLASS) and Japan Nosocomial Infections Surveillance (JANIS) in the surveillance of antimicrobial resistance.
A major issue in the surveillance of antimicrobial resistance (AMR) is "de-duplication" or removal of repeated isolates, for which there exist multiple methods. The World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS) requires de-duplication by selecting only the first isolate of a given bacterial species per patient per surveillance period per specimen type per age group, gender, and infection origin stratification. However, no study on the comparative application of this method has been reported. The objective of this study was to evaluate differences in data tabulation between the WHO GLASS and the Japan Nosocomial Infections Surveillance (JANIS) system, which counts both patients and isolates after removing repeated isolates of the same bacterial species isolated from a patient within 30 days, regardless of specimen type, but distinguishing isolates with change of antimicrobial resistance phenotype. All bacterial data, consisting of approximately 8 million samples from 1795 Japanese hospitals in 2017 were exported from the JANIS database, and were tabulated using either the de-duplication algorithm of GLASS, or JANIS. We compared the tabulated results of the total number of patients whose blood and urine cultures were taken and of the percentage of resistant isolates of Escherichia coli for each priority antibiotic. The number of patients per specimen type tabulated by the JANIS method was always smaller than that of GLASS. There was a small (< 3%) difference in the percentage of resistance of E. coli for any antibiotic between the two methods in both out- and inpatient settings and blood and urine isolates. The two tabulation methods did not show considerable differences in terms of the tabulated percentages of resistance for E. coli. We further discuss how the use of GLASS tabulations to create a public software and website that could help to facilitate the understanding of and treatment against AMR.


DN-p73 is activated after DNA damage in a p53-dependent manner to regulate p53-induced cell cycle arrest.
p53 and p73 genes are both activated in response to DNA damage to induce either cell cycle arrest or apoptosis, depending on the strength and the quality of the damaging stimulus. p53/p73 transcriptional activity must be tightly regulated to ensure that the appropriate biological response is achieved and to allow the cell to re-enter into the cell cycle after the damage has been repaired. In addition to multiple transcriptionally active (TA) isoforms, dominant negative (DN) variants, that lack the amino-terminal transactivation domain and function as trans-repressors of p53, p63 and p73, are expressed from a second internal promoter (P2-p73Pr). Here we show that, in response to a non apoptotic DNA damage induced by low doses of doxorubicin, p53 binds in vivo, as detected by a p53-specific chromatin immunoprecipitation assay, and activates the P2-p73 promoter. DN-p73alpha protein accumulates under the same conditions and exogenously expressed DN-p73alpha is able to counteract the p53-induced activation of the P2-p73Pr. These results suggest that DN-p73 may contribute to the autoregulatory loops responsible for the termination of p53/p73 responses in cells that do not undergo apoptosis. Accordingly, the activation of the P2-p73Pr is markedly enhanced in both p73-/- murine fibroblasts and in human cells in which p73 transcripts are selectively knocked-out by p73-specific small interfering RNAs.


Climate Change and the Arboviruses: Lessons from the Evolution of the Dengue and Yellow Fever Viruses.
The impact of anticipated changes in global climate on the arboviruses and the diseases they cause poses a significant challenge for public health. The past evolution of the dengue and yellow fever viruses provides clues about the influence of changes in climate on their future evolution. The evolution of both viruses has been influenced by virus interactions involving the mosquito species and the primate hosts involved in virus transmission, and by their domestic and sylvatic cycles. Information is needed on how viral genes in general influence phenotypic variance for important viral functions. Changes in global climate will alter the interactions of mosquito species with their primate hosts and with the viruses in domestic cycles, and greater attention should be paid to the sylvatic cycles. There is great danger for the evolution of novel viruses, such as new serotypes, that could compromise vaccination programs and jeopardize public health. It is essential to understand (a) both sylvatic and domestic cycles and (b) the role of virus genetic and environmental variances in shaping virus phenotypic variance to more fully assess the impact of global climate change.


Role of BvgA phosphorylation and DNA binding affinity in control of Bvg-mediated phenotypic phase transition in Bordetella pertussis.
To investigate the mechanism by which the Bordetella BvgAS phosphorelay controls expression of at least three distinct phenotypic phases, we isolated and characterized two B. pertussis mutants that were able to express Bvg- and Bvg(i) phase phenotypes but not Bvg+ phase phenotypes. In both cases, the mutant phenotype was due to a single nucleotide change in bvgA resulting in a single amino acid substitution in BvgA. In vitro phosphorylation assays showed that BvgA containing the T194M substitution was significantly impaired in its ability to use either BvgS or acetyl phosphate as a substrate for phosphorylation. Binding studies indicated that this mutant protein was able to bind an oligonucleotide containing a high-affinity BvgA binding site in a manner similar to wild-type BvgA, but was defective for binding the fhaB promoter in the absence of RNA polymerase (RNAP). By contrast, BvgA containing the R152H substitution had wild-type phosphorylation properties but was severely defective in its ability to bind either the high-affinity BvgA binding site-containing oligonucleotide or the fhaB promoter by itself. Both mutant BvgA proteins were able to bind the fhaB promoter in the presence of RNAP however, demonstrating the profound effect that RNAP has on stabilizing the ternary complexes between promoter DNA, BvgA and RNAP. Our results are consistent with the hypothesis that BvgAS controls expression of multiple phenotypic phases by adjusting the intracellular concentration of BvgA-P and they demonstrate the additive nature of BvgA binding site affinity and protein-protein interactions at different Bvg-regulated promoters.


Scrotal Ultrasound for Pain: Low Frequency of Absolute Surgical Indications.
To examine the results of scrotal ultrasounds (US) conducted for scrotal or testicular pain and review the pathologic findings of orchiectomies done for lesions that were suspicious for malignancy on US. We retrospectively reviewed the indications and findings of all scrotal US completed at our institution from 2002 to 2014. If a patient underwent an orchiectomy for an intratesticular lesion that was concerning for malignancy on US, the pathology report was also reviewed. There were 18,593 scrotal US performed, with 7,668 (41.2%) conducted for scrotal pain. Of the US performed for pain, 80.4% revealed benign or normal findings, and only 2.2% demonstrated a finding that is an absolute indication for surgery (intratesticular lesion suspicious for malignancy 0.8%, abscess 0.7%, torsion 0.6%, infiltrative process such as lymphoma 0.1%). For those patients undergoing an orchiectomy, 75% had malignancy on pathologic analysis. The majority of the 7668 US performed to evaluate scrotal or testicular pain reveal normal or benign findings. A low percentage demonstrates a finding that necessitates urgent or emergent surgery.


[Efficacy and safety of temporary bypass grafting in carotid endarterectomy].
The authors analysed interrelationship between the use of temporary bypass grafting during operations of carotid endarterectomy and the frequency of the development of ischaemic complications (stroke and transitory ischaemic attacks in the early postoperative period). It was shown that in the group wherein a temporary bypass graft was established only by the criterion of decreasing retrograde pressure ischaemic complications were encountered in ten (4.4%) patients and in the group wherein temporary shunts were established by the criterion of a simultaneous decrease in cerebral oxygenation and retrograde pressure - in two (0.9%) patients (OR 5.28; 95% CI 1.22-24.38; p=0.03). It was demonstrated that using temporary bypass grafting in cases of isolated assessment of the parameters of cerebral oxygenation and retrograde pressure increased the frequency of the development of shunt-related ischaemic complications as compared with the patients in whom shunts were not used due to lack of a synchronous decrease in these parameters (13.5 vs 1.5%, respectively; OR 10.0; 95% CI 1.1-82.2; p=0.039). The findings of the carried out retrospective analysis suggested that the main predictor of the development of the outcome 'stroke + transitory ischaemic attack' was the use of a temporary internal shunt during the main stage of the operation (p<0.00001).


Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways.
Shaofu Zhuyu decoction (SFZYD, also known as Sobokchugeo-tang), a classical prescription drug in traditional East Asian medicine, has been used to treat blood stasis syndrome (BSS). Hepatic steatosis is the result of excess caloric intake, and its pathogenesis involves internal retention of phlegm and dampness, blood stasis, and liver Qi stagnation. To evaluate the effects of treatment with SFZYD on obesity-induced inflammation and hepatic steatosis, we fed male C57BL/6N mice a high fat diet (HFD) for 8 weeks and then treated them with SFZYD by oral gavage for an additional 4 weeks. The results of histological and biochemical examinations indicated that SFZYD treatment ameliorates systemic inflammation and hepatic steatosis. A partial least squares-discriminant analysis (PLS-DA) scores plot of serum metabolites showed that HFD mice began to produce metabolites similar to those of normal chow (NC) mice after SFZYD administration. We noted significant alterations in the levels of twenty-seven metabolites, alterations indicating that SFZYD regulates the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism. Increases in the levels of TCA cycle intermediate metabolites, such as 2-oxoglutaric acid, isocitric acid, and malic acid, in the serum of obese mice were significantly reversed after SFZYD treatment. In addition to inducing changes in the above metabolites, treatment with SFZYD also recovered the expression of genes related to hepatic mitochondrial dysfunction, including Ucp2, Cpt1α, and Ppargc1α, as well as the expression of genes involved in lipid metabolism and inflammation, without affecting glucose uptake or insulin signaling. Taken together, these findings suggest that treatment with SFZYD ameliorated obesity-induced systemic inflammation and hepatic steatosis by regulating inflammatory cytokine and adipokine levels in the circulation and various tissues. Moreover, treatment with SFZYD also reversed alterations in the levels of metabolites of the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism.


Object orientedness: the person or the thing.
Infant observation indicated that there is an individual variation in development characterized by orientedness either toward the animate or toward the inanimate world. These variants, which are manifest as early as the second month of life, influence the surrounds, the continuing developmental processes, and certain aspects of character formation. Each variation in orientedness evokes a preferred way of processing percepts and situations.


New 7-Chloro-9-methyl-2-phenyl-3,4-dihydro-β-carbolin-2-iums as Promising Fungicide Candidates: Design, Synthesis, and Bioactivity.
As our further research, a series of new 7-chloro-9-methyl-2-phenyl-3,4-dihydro-β-carbolin-2-iums were designed and synthesized. Twelve compounds were found with excellent inhibition activity in vitro on three to five out of six phytopathogenic fungi, superior to standard drugs thiabendazole and/or azoxystrobin. Especially, 18 displayed the highest activity against three out of the fungi and the highest comprehensive activity for all of the fungi. The test in vivo revealed that 18 at 50 μg/mL was able to completely control Physalospora piricola infections in apples over 8 days. Scanning/transmission electron microscopic observations found that 18 could damage the hyphal integrity and cell membrane structure of P. piricola. The safety evaluation showed that 18 had no effect on the germination rate of cowpea seed at ≤200 μg/mL. The SAR revealed that the combination of 7-Cl and 2'- or 4'-alkyl is conducive to improvement of the activity. Thus, 7-chloro-9-methyl-2-phenyl-3,4-dihydro-β-carbolin-2-ium is a promising antifungal lead scaffold.


Detecting spatially highly resolved network modules: a multi subject approach.
The connectivity analysis of spatially highly resolved data results in networks comprising an immense number of nodes and edges which makes it hard or even impossible to investigate the high-dimensional (HD) network as a whole. A solution to this problem is offered by a connectivity-based segmentation of the HD networks into subsets of functionally similar nodes (network modules) that exhibit pronounced interaction. However, an investigation of the results at group level is problematic as identified modules are not assigned to each other across different subjects. In this work, we propose a rearrangement of the subject-specific networks into an integrative tensor which is subsequently decomposed into additive factors. This reorganization provides subject-independent networks together with subject-specific loadings enabling a group-wide segmentation of the resulting networks at the large scale.


Suberanilohydroxamic Acid. Aton Pharma.
Aton Pharma Inc, under license from the Memorial Sloan-Kettering Cancer Center, is developing suberanilohydroxamic acid (SAHA), a cytodifferentiating agent and histone deacetylase inhibitor, as a potential cancer chemopreventive.


Cyclic activity of the pituitary prolactin cells and plasma prolactin levels in the oestrous cycle of the ewe.
The relative proportions of prolactin cells, somatotrophs and gonadotrophs were determined in the adenohypophyses of 28 Merino ewes on selected days during the oestrous cycle. Plasma prolactin levels were measured in 16 of the animals at 3-hr intervals during the 24 hr before autopsy. From Days 1 to 5 of the cycle (Day 0=day of ovulation), plasma prolactin levels were 20-40 ng/ml and the prolactin cells were filled with granules. Plasma levels increased to 168 ng/ml between Days 6 and 9, and marked degranulation of the prolactin cells occurred. The greatest degranulation was found on Days 16 and 0, and was associated with a prolactin surge to a concentration of 610 ng/ml. The rise in plasma prolactin and intensive degranulation of prolactin cells at the time of ovulation and formation of the CL suggest that prolactin is important at this stage of the oestrous cycle.


Current status and future potential of ex vivo lung perfusion in clinical lung transplantation.
Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the waitlist continues to rise, the number of transplants performed remains limited by the number of suitable organ donors. Ex vivo lung perfusion (EVLP) emerged as a method of addressing the organ shortage by allowing the evaluation and potential reconditioning of marginal donor lungs or minimizing risks of prolonged ischemic time due to logistical challenges. The currently available FDA-approved EVLP systems have demonstrated excellent outcomes in clinical trials, and retrospective studies have demonstrated similar post-transplant survival between recipients who received marginal donor lungs perfused using EVLP and recipients who received standard criteria lungs stored using conventional methods. Despite this, widespread utilization has plateaued in the last few years, likely due to the significant costs associated with initiating EVLP programs. Centralized, dedicated EVLP perfusion centers are currently being investigated as a potential method of further expanding utilization of this technology. In the preclinical setting, potential applications of EVLP that are currently being studied include prolongation of organ preservation, reconditioning of unsuitable lungs, and further enhancement of already suitable lungs. As adoption of EVLP technology becomes more widespread, we may begin to see future implementation of these potential applications into the clinical setting.


Application of the dynamic mean field theory to fluid transport in slit pores.
We explore the applicability of the lattice model and dynamic mean field theory as a computationally efficient tool to study transport across heterogeneous porous media, such as mixed matrix membranes. As a starting point and to establish some basic definitions of properties analogous to those in the off-lattice systems, we consider transport across simple models of porous materials represented by a slit pore in a chemical potential gradient. Using this simple model, we investigate the distribution of density and flux under steady state conditions, define the permeability across the system, and explore how this property depends on the length of the pore and the solid-fluid interactions. Among other effects, we observe that the flux in the system goes through a maximum as the solid-fluid interaction is varied from weak to strong. This effect is dominated by the behavior of the fluid near the walls and is also confirmed by off-lattice molecular dynamics simulations. We further extend this study to explore transport across heterogeneous slit pore channels composed of two solids with different values of solid-fluid interaction strengths. We demonstrate that the lattice models and dynamic mean field theory provide a useful framework to pose questions on the accuracy and applicability of the classical theories of transport across heterogeneous porous systems.


[Carcinoma of the extrahepatic bile ducts].
In the last 5 years 25 patients (11 men, 14 women) with carcinoma of the extrahepatic biliary duct were studied. The most frequent localization of the carcinoma was the hepatic hilum. D.C.P. according to Whipple was possible only in one patient, while in 20 patients a palliative approach with external and internal biliary derivations was the choice. In the remaining 4 patients an explorative laparotomy with biopsy was performed. It is concluded that palliative resection allows for a better quality of life.


Growth factors in bladder wound healing.
Surgical and traumatic injuries to the bladder initiate a complex series of biological processes that result in wound healing. This process involves cellular proliferation, migration and differentiation; removal of damaged tissue; and production of extracellular matrix all of which may be controlled by growth factors. In skin, keratinocyte growth factor (KGF) is induced following incisional injury. We hypothesize that in bladder wound healing KGF and other growth factors are induced to modulate tissue repair. We have created a model of surgical bladder injury in the rodent. At 12, 24 and 48 hrs and 5 and 7 days after injury, the bladder was bisected and total RNA extracted from the anterior or wounded half and posterior or non-wounded half. Histological analysis of the bladder wound was performed with Mason's Trichrome and immunohistochemistry against smooth muscle alpha actin. RNase protection assays were performed to examine the expression of KGF, transforming growth factor (TGF)alpha and TGF beta 2 and 3 as well as the receptors for KGF and epidermal growth factor (EGF). Lastly, the effects of the exogenous administration of KGF on the bladder was tested on neonatal mice by daily injections of 5 micrograms KGF per gram body weight for 5 days. At 12 hours after injury KGF mRNA expression in the anterior wounded bladder half and posterior non-wounded bladder half was 8 and 6 times higher respectively, compared to unoperated control bladders. A similar response was seen for TGF alpha, where the 12 hour mRNA expression was 4.5 times higher in the anterior wounded bladder half and 3.5 times higher in the posterior non-wounded bladder half compared to unoperated control bladders. The nadir mRNA expression for both KGF and TGF alpha occurred at 7 days after bladder injury and was the same as in unoperated control bladders. EGFR mRNA expression was approximately 2 times higher in both the anterior wounded and posterior non-wounded bladder halves compared to the nadir levels which occurred at 24 hours after injury. TGF beta 2 and beta 3 mRNA levels did not significantly change in either the anterior wounded or posterior non-wounded bladder halves. Exogenous KGF stimulation resulted in a marked urothelial proliferation when compared to age matched control animals. During the early phases of bladder wound healing (12-24 hours post injury), mRNA for KGF and TGF alpha increased, whereas TGF beta 2 and beta 3 and the KGFR and EGFR remain unchanged. Additionally, exogenous KGF has a direct effect on urothelial proliferation. KGF and TGF alpha warrant further study as potential mediators of bladder wound healing.


Validation of neoclassical bootstrap current models in the edge of an H-mode plasma.
Analysis of the parallel electric field E(parallel) evolution following an L-H transition in the DIII-D tokamak indicates the generation of a large negative pulse near the edge which propagates inward, indicative of the generation of a noninductive edge current. Modeling indicates that the observed E(parallel) evolution is consistent with a narrow current density peak generated in the plasma edge. Very good quantitative agreement is found between the measured E(parallel) evolution and that expected from neoclassical theory predictions of the bootstrap current.


Improving Breast Cancer Surgical Treatment Decision Making: The iCanDecide Randomized Clinical Trial.
Purpose This study was conducted to determine the effect of iCanDecide, an interactive and tailored breast cancer treatment decision tool, on the rate of high-quality patient decisions-both informed and values concordant-regarding locoregional breast cancer treatment and on patient appraisal of decision making. Methods We conducted a randomized clinical trial of newly diagnosed patients with early-stage breast cancer making locoregional treatment decisions. From 22 surgical practices, 537 patients were recruited and randomly assigned online to the iCanDecide interactive and tailored Web site (intervention) or the iCanDecide static Web site (control). Participants completed a baseline survey and were mailed a follow-up survey 4 to 5 weeks after enrollment to assess the primary outcome of a high-quality decision, which consisted of two components, high knowledge and values-concordant treatment, and secondary outcomes (decision preparation, deliberation, and subjective decision quality). Results Patients in the intervention arm had higher odds of making a high-quality decision than did those in the control arm (odds ratio, 2.00; 95% CI, 1.37 to 2.92; P = .0004), which was driven primarily by differences in the rates of high knowledge between groups. The majority of patients in both arms made values-concordant treatment decisions (78.6% in the intervention arm and 81.4% in the control arm). More patients in the intervention arm had high decision preparation (estimate, 0.18; 95% CI, 0.02 to 0.34; P = .027), but there were no significant differences in the other decision appraisal outcomes. The effect of the intervention was similar for women who were leaning strongly toward a treatment option at enrollment compared with those who were not. Conclusion The tailored and interactive iCanDecide Web site, which focused on knowledge building and values clarification, positively affected high-quality decisions largely by improving knowledge compared with static online information. To be effective, future patient-facing decision tools should be integrated into the clinical workflow to improve decision making.


The effects of loading and estrogen on rat bone growth.
This study evaluated the contributions of locomotive loading and estrogen to the development of diaphysis of rat femur. A randomized 2x2 study design was used. Altogether, 70 female Sprague-Dawley rats were used, of which 10 were euthanized at entry. Of the remaining rats, 16 served as controls, and the rest, 44, underwent a unilateral sciatic neurectomy. The effect of estrogen was removed by ovariectomizing one-half of the neurectomized rats. After 27 wk, the animals were euthanized, and the femora were excised. Irrespective of loading or estrogen, the femur length and mineral mass increased by 142 and 687%, respectively. Axial growth was not modulated either by locomotive loading or estrogen, but the loading resulted in direction-specific changes in the cross-sectional geometry. The estrogen-related gains were evident on the endocortical surface, while the loading-related gains occurred on the periosteal surface. The loading and estrogen were significantly associated with increased bone strength (21 and 15%, respectively) in the mediolateral direction, but not in the anteroposterior direction. Axial growth and accrual of bone mineral mass of the rat femur are largely independent of locomotive loading or estrogen, whereas these factors specifically account for the femur function, as either a mechanical lever or a mineral reservoir for reproduction, respectively.


Choroidal Anatomic Alterations After Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: A Multicenter Study.
To study the early anatomic choroidal alterations in eyes with chronic central serous chorioretinopathy (CSCR) undergoing photodynamic therapy (PDT). Multicenter retrospective cohort study. A total of 77 patients and 81 eyes with chronic CSCR treated with PDT and 64 untreated fellow eyes were evaluated. Central macular thickness (CMT) and choroidal features including subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were analyzed. Choroidal vascularity index (CVI) was calculated in all study eyes at baseline and at 1- and 3-months post-PDT. In eyes receiving PDT, Snellen visual acuity (VA) significantly improved at months 1 and 3 (P < .001). CMT and SFCT showed a significant reduction from baseline at months 1 and 3 (P < .001), whereas TCA and LCA showed a significant decrease only at the 1-month follow-up visit. Baseline mean TCA and LCA were 2.30 ± 1.41 mm2 and 1.23 ± 0.73 mm2, respectively, and decreased to 2.07 ± 1.21 mm2 and 1.08 ± 0.63 mm2 at the 1-month follow-up visit, respectively (P = .01). No significant changes were recorded for SCA and CVI. In the fellow eye group, VA, CMT, and all choroidal parameters showed no differences between baseline and any follow-up visits (all P > .05). After PDT for chronic CSCR we observed sustained reductions in CMT and SFCT, while reductions in TCA and LCA were only noted at the 1-month follow-up interval. These choroidal parameters may provide additional quantitative biomarkers to evaluate the anatomic response to therapy but await further prospective validation.


Comparison of plasma and saliva concentrations of lamotrigine in healthy volunteers.
The relationship between lamotrigine (CAS 84057-84-1) concentrations in saliva and plasma in healthy volunteers were examined, as well as the possibility of using saliva to monitor levels for effective therapy. The study was performed with 14 healthy volunteers, mean age 23 +/- 2 (SD) years. After single oral doses of 200 mg, plasma and stimulated saliva samples were collected simultaneously at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and 96 h. The pH values of saliva samples were recorded. Lamotrigine concentrations were determined by a validated HPLC method. Fraction of drug bound to plasma proteins was calculated mathematically by the modified Henderson-Hasselbalch equation. Linear regression was used to evaluate the correlations. The remnant of orally administered drug contaminated the saliva samples and gave spuriously high values for up to 2 h, which were omitted. There was significant correlation (r2 = 0.677, p < 0.0001) between plasma and saliva concentrations from 2-96 h after administration. The mean ratio of saliva to plasma concentration was 0.426 +/- 0.153 (mean +/- SD). Protein binding, calculated from the concentrations in saliva was 57.5 +/-15.1% (mean +/- SD). Noncompartmental analysis was conducted with the program Kinetica. Plasma t1/2 and MRT were not significantly different from those found from saliva. The mean values of lamotrigine peak saliva concentrations (C(max)), areas under the curve of concentration versus time from zero to infinity (AUC(0-->infinity)), and areas under the curves of the product of time and concentration versus time from zero to infinity (AUMC(0-->infinity) were proportionally lower than in plasma. The results support the use of saliva concentration as a convenient, painless and noninvasive alternative to plasma for monitoring lamotrigine therapy.


Development of Phosphorothioate DNA and DNA Thioaptamers.
Nucleic acid aptamers are short RNA- or DNA-based affinity reagents typically selected from combinatorial libraries to bind to a specific target such as a protein, a small molecule, whole cells or even animals. Aptamers have utility in the development of diagnostic, imaging and therapeutic applications due to their size, physico-chemical nature and ease of synthesis and modification to suit the application. A variety of oligonucleotide modifications have been used to enhance the stability of aptamers from nuclease degradation in vivo. The non-bridging oxygen atoms of the phosphodiester backbones of RNA and DNA aptamers can be substituted with one or two sulfur atoms, resulting in thioaptamers with phosphorothioate or phosphorodithioate linkages, respectively. Such thioaptamers are known to have increased binding affinity towards their target, as well as enhanced resistance to nuclease degradation. In this review, we discuss the development of phosphorothioate chemistry and thioaptamers, with a brief review of selection methods.


[Characteristics of soil microbial variation during crop rotation period at cultivation area of Salvia miltiorrhiza in Zhongjiang of Sichuan province].
To study the characteristics of soil microbial variation during Salvia miltiorrhiza crop rotation. the conventional cultivating microbial method was used to study the microbial number and communities structure and soil microbial biomass phosphorus (SMBP) was determined by chloroform vapor extraction method. The data was then analyzed by SPSS software. With the increase of the crop rotation years, the numbers of bacteria and actinomycetes in soil also, but the fungi and SMBP decreased. Microbial mechanism of crop rotation of the planting S. miltiorrhiza is the regulation of microbial number and bacteria physiological communities, the process rebuilds the soil ecological system balance. Microbial communities in soil need at lest 2 years to get to restore, after planting S. miltiorrhiza, which consisting with traditional planting experience.


A new diterpenoid alkaloid from Delphinium gyalanum C. Marquand & Airy Shaw.
A new C19-diterpenoid alkaloid named gyalanutine A (1) and fourteen known compounds 2-15 were isolated from the plant of Delphinium gyalanum C. Marquand & Airy Shaw. Compound 1 displayed an unusual lycoctonine-type C19-diterpenoid alkaloid skeleton with the cleavage of N-C19 and C7-C17 bonds, and the construction of the N-C7 bond. Structures were identified by multiple spectroscopic analyses including 1 D, 2 D NMR, IR and HR-ESI-MS. Compounds were tested for acetylcholinesterase inhibitory and anti-inflammatory activity.


Influence of right ventricular ischemia on precordial ST depression during right coronary artery occlusion.
To determine the cause of precordial ST depression in acute inferior myocardial infarction, we evaluated the relationship between precordial ST deviation and ventricular involvement. Forty-nine patients who were admitted to the hospital with an acute inferior myocardial infarction, and 60 patients who were treated with elective angioplasty to the right coronary artery, were analyzed. All patients had single vessel disease and were divided into 2 groups (A and B) according to the site of the lesion. Patients in group A had a lesion proximal to the largest right ventricular branch, while in group B the lesion was distal to that branch. There were no differences in inferior ST elevation between the 2 groups, but precordial ST segments were more depressed in group B than in group A. A significant correlation was observed between inferior and precordial ST deviation in group B, but not in group A. These results were similar in patients with myocardial infarction and in those treated by angioplasty. These results suggest that precordial ST depression in an evolving inferior infarction is due to reciprocal ST deviation which reflects inferoposterior involvement. In addition, when inferior infarction is accompanied by right ventricular involvement the precordial ST depression is lessened.


Effects of transport gradients in a chemical vapor deposition reactor employing vapor-liquid-solid growth of ternary chalcogenide phase-change materials.
Chemical vapor deposition (CVD) with vapor-liquid-solid (VLS) growth is employed to synthesize individual Ge(2)Sb(2)Te(5) nanowires with the ultimate goal of synthesizing a large scale nanowire array for universal memory storage. A consistent challenge encountered during the synthesis is a lack of control over the composition and morphology across the growth substrate. To better understand the challenges associated with the CVD synthesis of the ternary chalcogenide, computational fluid dynamics simulations are performed to quantify 3D thermal and momentum transients in the growth conditions. While these gradients are qualitatively known to exist, they have not been adequately quantified in both the axial and radial directions when under pressure and flow conditions indicative of VLS growth. These data are not easily acquired by conventional means for the axial direction under vacuum and are a considerable challenge to accurately measure radially. The simulation data shown here provide 3D insights into the gradients which ultimately dictate the region of controllable stoichiometry and morphology. These results help explain the observed inhomogeneity of the characterized ternary chalcogenide growth products at various growth substrate locations.


Development of a novel combined nomogram model integrating deep learning radiomics to diagnose IgA nephropathy clinically.
This study aimed to develop and validate a combined nomogram model based on superb microvascular imaging (SMI)-based deep learning (DL), radiomics characteristics, and clinical factors for noninvasive differentiation between immunoglobulin A nephropathy (IgAN) and non-IgAN.We prospectively enrolled patients with chronic kidney disease who underwent renal biopsy from May 2022 to December 2022 and performed an ultrasound and SMI the day before renal biopsy. The selected patients were randomly divided into training and testing cohorts in a 7:3 ratio. We extracted DL and radiometric features from the two-dimensional ultrasound and SMI images. A combined nomograph model was developed by combining the predictive probability of DL with clinical factors using multivariate logistic regression analysis. The proposed model's utility was evaluated using receiver operating characteristics, calibration, and decision curve analysis. In this study, 120 patients with primary glomerular disease were included, including 84 in the training and 36 in the test cohorts. In the testing cohort, the ROC of the radiomics model was 0.816 (95% CI:0.663-0.968), and the ROC of the DL model was 0.844 (95% CI:0.717-0.971). The nomogram model combined with independent clinical risk factors (IgA and hematuria) showed strong discrimination, with an ROC of 0.884 (95% CI:0.773-0.996) in the testing cohort. Decision curve analysis verified the clinical practicability of the combined nomogram. The combined nomogram model based on SMI can accurately and noninvasively distinguish IgAN from non-IgAN and help physicians make clearer patient treatment plans.


Verteporfin induced SUMOylation of YAP1 in endometrial cancer.
Yes-associated protein (YAP or YAP1) has been proposed to function as an oncogene in most cancers, with nuclear localization of YAP1 correlating with poor prognosis. Photosensitizer Verteporfin has been proven as an inhibitor of YAP1 through preventing the combination of YAP1 with TEA domain transcription factor (TEAD). We showed previously that the total and phospho-levels of YAP1 were related to the clinical characteristics and outcomes in endometrial cancer (EC) patients, and that YAP1 promoted the proliferation and metastasis of EC cells in vitro cell line studies and in animal models. We also reported that Verteporfin inhibited cell growth and induced cell death through inhibiting YAP1 in EC in our previous study. However, the mechanism of how Verteporfin inhibits the function of YAP1 remains unclear. In this study, we analyzed the global effects of Verteporfin on cell function by using Reverse Phase Protein Arrays (RPPA) and Ingenuity Pathway Analysis (IPA). Furthermore, we demonstrated that Verteporfin induced the SUMOylation of YAP1 for the first time. Interestingly, we found that the SUMOylation of YAP1 was regulated by YAP1 phosphorylation. Together, our study revealed a novel mechanism by which Verteporfin inhibits the function of YAP1 through regulating YAP1 SUMOylation. Our study may provide a rationale for the clinical use of Verteporfin in endometrial cancer by targeting YAP1.


Donor age in living donor liver transplantation.
We sought to elucidate the influence of donor age in living donor liver transplantation (LDLT) using either left lobe (LL) or right lobe (RL) grafts. Recipients (n = 232) were categorized as: group O/LL (LL, donor age >50, n = 20); group Y/LL (LL, donor age < or =50, n = 140); Group O/RL (RL, donor age >50, n = 12); and group Y/RL (RL, donor age < or =50, n = 61). We compared post-LDLT graft functions. Among LL LDLT, the incidence of small-for-size syndrome was significantly greater for group O/LL compared with group Y/LL (60.0% vs 16.3%, P < .01). However, the cumulative 5-year graft survivals were 73.8% in group O and 76.7% in group Y without substantial difference. In RL LDLT, the post-LDLT morbidity and mortality were similar for group O/RL and group Y/RL. Partial liver grafts, even though LL grafts, from older donors can be used safely with caution in LDLT.


Descriptions of four new sponge-inhabiting barnacles (Thoracica: Archaeobalanidae: Acastinae).
Within the family Archaeobalanidae, the sponge-inhabiting barnacles include species from the subfamilies Acastinae and Bryozobiinae as well as from the genus Membranobalanus in the subfamily Archaeobalaninae. Members of these groups are obligatory symbionts of poriferans, but the Acastinae can also be found in association with alcyonaceans and antipatharians. Acasta sulcata Lamarck, 1818, is one of the most widely reported sponge-inhabiting barnacle species, with numerous records across the Indo-West Pacific region revealing significant morphological variation. A combined morphological and molecular approach has revealed high diversity in recent collections of sponge-inhabiting barnacles in Taiwan and Australia, and four new species, namely Acasta aspera sp. nov., Acasta huangi sp. nov., Acasta radenta sp. nov., and Acasta undulaterga sp. nov., have been described here. All four species are morphologically close to A. sulcata, and the morphological similarity between these proposed species has led to the proposal of a "sulcata species complex."


Technical note: A method for assigning animals to treatment groups with unequal count per group that equalizes mean animal weight among groups.
Pastures available for grazing studies may be of unequal size and may have heterogeneous carrying capacity necessitating the assignment of unequal numbers of animals per pasture. To reduce experimental error, it is often desirable that the initial mean BW be similar among experimental units. The objective of this note is to present and illustrate the use of a method for assignment of animals to experimental units of different sizes such that the initial mean weight of animals in each unit is approximately the same as the overall mean. Two alternative models were developed and solved to assign each of 231 weaned steers () to 1 of 12 pastures with carrying capacity ranging from 5 to 26 animals per pasture. A solution to Model 1 was obtained in which the mean weights among pastures were approximately the same but the variances among pastures were heteroskedastic, meaning that weight variances across pens were different (-value < 0.05). An alternative model was developed (Model 2) and used to derive assignments with nearly equal mean weights and homoskedastic variances among pastures.