Binary morphological shape-based interpolation applied to 3-D tooth reconstruction.
In this paper, we propose an interpolation algorithm using a mathematical morphology morphing approach. The aim of this algorithm is to reconstruct the n-dimensional object from a group of (n - 1)-dimensional sets representing sections of that object. The morphing transformation modifies pairs of consecutive sets such that they approach in shape and size. The interpolated set is achieved when the two consecutive sets are made idempotent by the morphing transformation. We prove the convergence of the morphological morphing. The entire object is modeled by successively interpolating a certain number of intermediary sets between each two consecutive given sets. We apply the interpolation algorithm for three-dimensional tooth reconstruction.


Trends in Cancer Incidence in US Adolescents and Young Adults, 1973-2015.
Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking. To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time. This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019. Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer. A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P < .001). Kidney carcinoma increased at the greatest rate for both male (APC, 3.572; 95% CI, 3.049-4.097; P < .001) and female (APC, 3.632; 95% CI, 3.105-4.162; P < .001) AYAs. In this cross-sectional, US population-based study, cancer in AYAs was shown to have a unique epidemiological pattern and is a growing health concern, with many cancer subtypes having increased in incidence from 1973 to 2015. Continued research on AYA cancers is important to understanding and addressing the distinct health concerns of this population.


Effects of adenosine on rate-dependent atrioventricular nodal function. Potential roles in tachycardia termination and physiological regulation.
Adenosine is well known to depress atrioventricular (AV) nodal conduction, but the potential interactions between adenosine and functional AV nodal properties have not been explored. The purpose of the present study was to determine (1) whether exogenous adenosine modifies the rate-dependent properties of the AV node, (2) to what extent such changes underlie the actions of adenosine in an in vitro model of AV reentrant tachycardia (AVRT), and (3) the potential role of endogenous adenosine in rate-induced AV nodal responses. The functional properties of AV nodal recovery (defining the conduction delay of a single premature activation), facilitation (effect of short cycles on subsequent nodal recovery), and fatigue (slowly developing AV nodal delay at a rapid rate) were studied selectively in isolated, superfused rabbit and guinea pig cardiac preparations. Exogenous adenosine increased AV nodal fatigue and attenuated facilitation, resulting in tachycardia-dependent increases in AH interval and AV nodal effective refractory period (AVERP). In experimental AVRT, adenosine caused greater increases in tachycardia cycle length (T) and AVERP as tachycardia rate increased. AVRT was sustained when AVERP/T was < 1, and adenosine suppressed AVRT by increasing the slope of the AVERP/T versus tachycardia rate relation, causing the critical ratio of 1 to be attained at slower rates. A mathematical model incorporating quantitative descriptors of recovery, facilitation, and fatigue accounted for changes in AH interval, AVERP, tachycardia cycle length, and AVERP/T under control conditions and in the presence of adenosine. In the absence of exogenous adenosine, 8-phenyltheophylline (10 mumol/L), an adenosine receptor antagonist, did not alter recovery or facilitation but significantly reduced rate-related fatigue (by 31 +/- 8%, mean +/- SEM, P < .05, in rabbit hearts; 46 +/- 5%, P < .01, in guinea pig hearts). Combined inhibition of adenosine deaminase (with erythro-9-[2-hydroxy-3-nonyl]-adenine hydrochloride, 5 mumol/L) and adenosine uptake (with dipyridamole, 1 mumol/L) increased fatigue in the absence of exogenous adenosine by 57 +/- 20% (P < .05). We conclude that (1) exogenously administered adenosine increases AV nodal fatigue and reduces facilitation, without altering AV nodal recovery; (2) these changes cause rate-dependent AV nodal depression, which plays a role in adenosine's actions on experimental AVRT; and (3) endogenous adenosine receptor activation plays a role in physiological AV nodal fatigue. Adenosine's ability to terminate reentrant supraventricular tachycardia may be due, at least in part, to its ability to enhance the physiological conduction slowing that results from sustained increases in AV nodal activation rate.


Dielectric properties and emissivity of seawater at C-band microwave frequency.
Microwave remote sensing applications over ocean using radar and radiometers, a precise knowledge of emissivity and reflectivity, are required. Emissivity of ocean surface is a function of the surface configuration, frequency of radiation, temperature and its dielectric properties. The emissivity of a smooth ocean surface at a particular wavelength is determined by its complex dielectric properties. In present study, laboratory measurements of complex dielectric properties, real part epsilon', and imaginary part epsilon", of surface seawater samples collected from Bay of Bengal and Arabian Sea are carried out. Measurements of these seawater samples are done at 5 GHz and 30 degrees C using an automated C-band microwave bench set up. The salinity of samples is also measured using autosalinometer. The salinity values are used to determine epsilon' and epsilon" using the Debye equations. The normal incidence emissivity and brightness temperature values for smooth sea surface are reported for surface samples. The dielectric constant epsilon' decreases and dielectric loss increases with increase in salinity at 5 GHz and 30 degrees C. At normal incidence, emissivity is almost constant for varying salinities.


Cetuximab-Containing Combinations in Locally Advanced and Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.
Cetuximab remains to date the only targeted therapy approved for the treatment of head and neck squamous cell carcinoma (HNSCC). The EGFR pathway plays a key role in the tumorigenesis and progression of this disease as well as in the resistance to radiotherapy (RT). While several anti-EGFR agents have been tested in HNSCC, cetuximab, an IgG1 subclass monoclonal antibody against EGFR, is the only drug with proven efficacy for the treatment of both locoregionally-advanced (LA) and recurrent/metastatic (R/M) disease. The addition of cetuximab to radiotherapy is a validated treatment option in LA-HNSCC. However, its use has been limited to patients who are considered unfit for standard of care chemoradiotherapy (CRT) with single agent cisplatin given the lack of direct comparison of these two regimens in randomized phase III trials and the inferiority suggested by metanalysis and phase II studies. The current use of cetuximab in HNSCC is about to change given the recent results from randomized prospective clinical trials in both the LA and R/M setting. Two phase III studies evaluating RT-cetuximab vs. CRT in Human Papillomavirus (HPV)-positive LA oropharyngeal squamous cell carcinoma (De-ESCALaTE and RTOG 1016) showed inferior overall survival and progression-free survival for RT-cetuximab combination, and therefore CRT with cisplatin remains the standard of care in this disease. In the R/M HNSCC, the EXTREME regimen has been the standard of care as first-line treatment for the past 10 years. However, the results from the KEYNOTE-048 study will likely position the anti-PD-1 agent pembrolizumab as the new first line treatment either alone or in combination with chemotherapy in this setting based on PD-L1 status. Interestingly, cetuximab-mediated immunogenicity through antibody dependent cell cytotoxicity (ADCC) has encouraged the evaluation of combined approaches with immune-checkpoint inhibitors in both LA and R/M-HNSCC settings. This article reviews the accumulated evidence on the role of cetuximab in HNSCC in the past decade, offering an overview of its current impact in the treatment of LA and R/M-HNSCC disease and its potential use in the era of immunotherapy.


Mothers' coping styles during times of chronic security stress: effect on health status.
In this study, we investigated the coping behaviors used by Israeli mothers to manage various sources of stress, including security-related stress, based on a life-course perspective of women's health. A random telephone survey of 302 mothers who had children under age 18 living at home was conducted in the Negev area. Measures of stress such as domestic violence, sources of tension in everyday life, and time pressure were assessed together with indicators of exposure to the Intifada for their relationship to indicators of physiological health and depression. Factor analysis revealed three distinct coping styles: social-leisure style, loosening control style, and a restlessness style which were used by 91.4%, 68.5%, and 69.5% of the sample, respectively. Security-related stress was associated with greater reported health symptoms, particularly gynecological symptoms. A history of child abuse and domestic violence and exposure to the Intifada were associated with greater depressive symptoms, but not with physical health indicators. Other sources of stress particularly affected symptoms related to gynecological function. Most mothers used a variety of coping strategies during times of chronic security stress, some of which are health promoting and others that detract from health.


S1PR2 inhibition mitigates cognitive deficit in diabetic mice by modulating microglial activation via Akt-p53-TIGAR pathway.
Cognitive deficit is one of the challenging complications of type 2 diabetes. Sphingosine 1- phosphate receptors (S1PRs) have been implicated in various neurodegenerative and metabolic disorders. The association of S1PRs and cognition in type 2 diabetes remains elusive. Microglia-mediated neuronal damage could be the thread propagating cognitive deficit. The effects of S1PR2 inhibition on cognition in high-fat diet and streptozotocin-induced diabetic mice were examined in this work. We further assessed microglial activation and putative microglial polarisation routes. Cognitive function loss was observed after four months of diabetes induction in Type 2 diabetes animal model. JTE013, an S1PR2 inhibitor, was used to assess neuroprotection against cognitive decline and neuroinflammation in vitro and in vivo diabetes model. JTE013 (10 mg/kg) improved synaptic plasticity by upregulating psd95 and synaptophysin while reducing cognitive decline and neuroinflammation. It further enhanced anti-inflammatory microglia in the hippocampus and prefrontal cortex (PFC), as evidenced by increased Arg-1, CD206, and YM-1 levels and decreased iNOS, CD16, and MHCII levels. TIGAR, TP53-induced glycolysis and apoptosis regulator, might facilitate the anti-inflammatory microglial phenotype by promoting oxidative phosphorylation and decreasing apoptosis. However, since p53 is a TIGAR suppressor, inhibiting p53 could be beneficial. S1PR2 inhibition increased p-Akt and TIGAR levels and reduced the levels of p53 in the PFC and hippocampus of type 2 diabetic mice, thereby decreasing apoptosis. In vitro, palmitate was used to imitate sphingolipid dysregulation in BV2 cells, followed by conditioned media exposure to Neuro2A cells. JTE013 rescued the palmitate-induced neuronal apoptosis by promoting the anti-inflammatory microglia. In the present study, we demonstrate that the inhibition of S1PR2 improves cognitive function and skews microglia toward anti-inflammatory phenotype in type 2 diabetic mice, thereby promising to be a potential therapy for neuroinflammation.


Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma.
Hydrodynamic injection is an effective method for DNA delivery in mouse liver and is being translated to larger animals for possible clinical use. Similarly, phiC31 integrase has proven effective in mediating long-term gene therapy in mice when delivered by hydrodynamic injection and is being considered for clinical gene therapy applications. However, chromosomal aberrations have been associated with phiC31 integrase expression in tissue culture, leading to questions about safety. To study whether hydrodynamic delivery alone, or in conjunction with delivery of phiC31 integrase for long-term transgene expression, could facilitate tumor formation, we used a transgenic mouse model in which sustained induction of the human C-MYC oncogene in the liver was followed by hydrodynamic injection. Without injection, mice had a median tumor latency of 154 days. With hydrodynamic injection of saline alone, the median tumor latency was significantly reduced, to 105 days. The median tumor latency was similar, 106 days, when a luciferase donor plasmid and backbone plasmid without integrase were administered. In contrast, when active or inactive phiC31 integrase and donor plasmid were supplied to the mouse liver, the median tumor latency was 153 days, similar to mice receiving no injection. Our data suggest that phiC31 integrase does not facilitate tumor formation in this C-MYC transgenic mouse model. However, in groups lacking phiC31 integrase, hydrodynamic injection appeared to contribute to C-MYC-induced hepatocellular carcinoma in adult mice. Although it remains to be seen to what extent these findings may be extrapolated to catheter-mediated hydrodynamic delivery in larger species, they suggest that caution should be used during translation of hydrodynamic injection to clinical applications.


Treatment of septic encephalopathy and encephalitis - a critical appraisal.
The central nervous system is frequently involved during severe sepsis. Patients either develop septic encephalopathy characterized by delirium and coma or focal neurological signs as a consequence of septic-embolic or septic-metastatic encephalitis. In this review, a summary of currently available literature on established and some promising experimental treatment options for septic encephalopathy and encephalitis is provided, with a focus on the clinical utility of published studies. Treatment relies on proper identification of the causative pathogen and rapidly initiated adequate empirical or (after identification of the pathogen) tailored antibiotic therapy, fluid and electrolyte management. In the presence of brain abscess(es) or mycotic aneurysm(s), surgery or interventional neuroradiology must be considered. Pharmacological approaches to prevent delirium of different etiology include the use of dexmedetomidine and (with limitations) of melatonin and its derivatives. In the absence of a specific pharmacological treatment, non-pharmacological bundles of interventions (e.g. promotion of sleep, cognitive stimulation, early mobilization and adequate therapy of pain) are of proven efficacy to prevent delirium of different etiology including sepsis. Experimental promising therapies include the use of non-bacteriolytic antibiotics and the reduction of the toxic effects of microglial activation.


Asymmetric syntheses of enantiopure C(5)-substituted transpentacins via diastereoselective Ireland-Claisen rearrangements.
Asymmetric syntheses of (S,S,S)-2-amino-5-methylcyclopentanecarboxylic acid and (S,S,S)-2-amino-5-phenylcyclopentanecarboxylic acid were achieved in 9 steps from commercially available starting materials via the Ireland-Claisen rearrangement of two enantiopure β-amino allyl esters, followed by ring-closing metathesis, reduction and deprotection.


Cost-of-illness of gastroenteritis caused by rotavirus in Chinese children less than 5 years.
Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.


[Xenon - noble gas with organprotective properties].
Besides it's anaesthetic properties, xenon may induce biological effects that may protect various organs from ischaemia-reperfusion injury. Xenon is an antagonist of the NMDA-receptor and reduces the neuronal injury mediated via these receptors. In contrast to other NMDA-receptor antagonists, xenon has no neurotoxic side effects. Xenon also protects the heart in ischaemia-reperfusion situations. Xenon reduces the post-ischaemic reperfusion injury and offers cardioprotection by inducing pharmacological preconditioning. These organ protective properties of xenon might be useful in special clinical situations.


In situ nitrogen mineralization, nitrification, and ammonia volatilization in maize field fertilized with urea in Huanghuaihai region of northern China.
Nitrogen (N) fertilization potentially affects soil N mineralization and leaching, and can enhance NH3 volatilization, thus impacting crop production. A fertilizer experiment with five levels of N addition (0, 79, 147, 215 and 375 kg N ha(-1)) was performed in 2009 and 2010 in a maize field in Huanghuaihai region, China, where > 300 kg N ha(-1) has been routinely applied to soil during maize growth period of 120 days. Responses of net N mineralization, inorganic N flux (0-10 cm), NH3 volatilization, and maize yield to N fertilization were measured. During the growth period, net N mineralization and nitrification varied seasonally, with higher rates occurring in August and coinciding with the R1 stage of maize growth. Soil NO3(-)-N contributed to more than 60% of inorganic N flux during maize growth. Cumulative NH3 volatilization increased with N additions, with total NH3 volatilization during maize growth accounting for about 4% of added N. Relative to the control, mean maize yield in the fertilizer treatments increased by 17% and 20% in 2009 and 2010, respectively. However, grain yield, aboveground biomass, and plant N accumulation did not increase with added N at levels > 215 kg N ha(-1). These results suggest that the current N rate of 300 kg N ha(-1) is not only excessive, but also reduces fertilizer efficacy and may contribute to environmental problems such as global warming and eutrophication of ground water and streams.


On the disadvantages of radical acromionectomy.
We studied thirty consecutive patients who previously had a radical acromionectomy performed elsewhere. All had poor results from the procedure. Twenty-seven had persistent pain, all had marked weakness of the shoulder, and none could raise the arm above the horizontal. Eight had had serious wound complications. All objected to the appearance of the shoulder. We concluded that radical acromionectomy weakened the deltoid both by removing its lever arm and by encouraging retraction of the deltoid muscle became adherent to either the rotator cuff or the humerus, or both, and soon became fibrotic and permanently shortened. This combination of factors makes a successful reconstruction of the deltoid mechanism especially difficult.


Patterns and management of blunt abdominal aortic injury.
Blunt abdominal aortic injury (BAAI) is historically associated with significant morbidity and mortality. Our institutional experience was analyzed to define current patterns of injury and to help guide management. Adult patients with BAAI between January 2000 and July 2011 were identified from our trauma registry. Medical, radiographic, and autopsy records were reviewed for relevant clinical data. Management and outcomes were compared between patients with minimal aortic injury limited to the intima (MAI) compared to more significant aortic injury (SAI). Nine patients had MAI and 8 had SAI, including 2 dissections, 2 pseudoaneurysms, 2 branch avulsions, 1 thrombosis, and 1 transection. The MAI and SAI groups had similar demographics and patterns of injury, and all patients had significant polytrauma, with a mean injury severity score of 42. More MAI than SAI patients were managed nonoperatively (100% vs. 38%; P=0.01). All observed patients underwent repeat imaging during the index admission, 85% within 72 hours, and no observed lesions led to malperfusion, death, or progression during the index admission. One MAI progressed to a pseudoaneurysm within 8 months. Five SAI patients underwent aortic-related repairs, including 2 endovascular stent grafts, 2 open primary repairs, and 1 axillobifemoral bypass. Overall, 15 (88%) patients underwent procedures for any injury-9 required laparotomy (53%) and 2 underwent thoracotomy. There were 6 (35%) deaths, 2 attributable to aortic injury-1 from hemorrhage and 1 from hyperkalemic cardiac arrest after prolonged ischemia from infrarenal aortic occlusion. Among patients who survived the initial resuscitation, SAI was associated with a significantly higher mortality rate compared to MAI (50% vs. 0%; P=0.03). Patients with MAI are at low risk of complications and may be considered for observation. Patients with SAI requiring intervention manifest clinically and/or radiographically at presentation. Those not associated with bleeding, malperfusion, or thromboembolism may be observed with interval imaging. For all observed patients, long-term surveillance is required to document complete resolution or stability, because even MAI can progress to a more complex lesion.


Chromosomal patterns of diversity and differentiation in creepers: a next-gen phylogeographic investigation of Certhia americana.
With methods for sequencing thousands of loci for many individuals, phylogeographic studies have increased inferential power and the potential for applications to new questions. In songbirds, strong patterns of inter-chromosomal synteny, the published genome of a songbird and the ability to obtain thousands of genetic loci for many individuals permit the investigation of differentiation between and diversity within lineages across chromosomes. Here, we investigate patterns of differentiation and diversity in Certhia americana, a widespread North American songbird, using next-generation sequencing. Additionally, we reassess previous phylogeographic studies within the group. Based on ~30 million sequencing reads and more than 16,000 single-nucleotide polymorphisms in 41 individuals, we identified a strong positive relationship between genetic differentiation and chromosome size, with a negative relationship between genetic diversity and chromosome size. A combination of selection and drift may explain these patterns, although we found no evidence for selection. Because the observed genomic patterns are very similar between widespread, allopatric clades, it is unlikely that selective pressures would be so similar across such different ecological conditions. Alternatively, the accumulation of fixed differences between lineages and loss of genetic variation within lineages due to genetic drift alone may explain the observed patterns. Due to relatively higher recombination rates on smaller chromosomes, larger chromosomes would, on average, accumulate fixed differences between lineages and lose genetic variation within lineages faster, leading to the patterns observed here in C. americana.


Attaching-effacing Escherichia coli infections in cattle.
Diarrheagenic Escherichia coli are now broadly placed into 6 classes based on virulence mechanisms. One of these classes, enterotoxigenic E coli, is the most common cause of diarrhea in beef and dairy calves in the first 4 days of life. Two other diarrheagenic classes, enterohemorrhagic E coli (EHEC) and enteropathogenic E coli (EPEC), are important causes of disease in human beings, but less well substantiated causes of diarrhea in calves. E coli strains that cause hemorrhagic colitis and hemolytic uremic syndrome in humans, express high levels of Shiga toxin, cause attaching-effacing (A/E) lesions in intestinal epithelial cells, and possess a specific 60-MDa EHEC plasmid are known as EHEC. One feature EHEC and EPEC have in common is the causation of intestinal epithelial lesions known as attaching and effacing (A/E). Attaching-effacing E coli (AEEC) is a designation for those E coli strains known to cause A/E lesions or at least carry the genes for this trait, and therefore include organisms that fall into either the EHEC or EPEC classes. Because cattle are carriers of many different serotypes of EHEC, much emphasis has been placed on the public health and food safety concerns associated with the fecal shedding of these organisms. However, much less emphasis has been given to their roles as diarrheagenic pathogens of cattle. The goal of this article is to address the question of pathogenicity, with a review that focuses on the results of studies of natural and experimental infections with these organisms. The authors conclude that there is overwhelming evidence that many different serogroups of AEEC are diarrheagenic pathogens of calves.


Leiomyosarcoma of the kidney: a clinicopathologic study.
Leiomyosarcoma of kidney is a rare lesion for which limited data are available. Cases coded as leiomyosarcoma of the kidney from three institutions were reviewed. These cases comprised 3 men and 7 women, 40 to 75 years of age. Immunohistochemistry was performed where possible and clinical follow-up information was obtained. On immunohistochemical staining, 6 of 6 tumors expressed smooth muscle actin, desmin, calponin, and h-caldesmon, and epithelial membrane antigen was positive in 1 of 5. Tumors were negative for cytokeratin and S-100 protein. Follow-up information was available for 9 patients. Two patients had metastases at diagnosis, four developed metastases, and two had recurrent disease. Five of 9 died of disease. Two patients were alive with no evidence of disease after 19 and 60 months, and 2 patients were alive with disease after 48 months and 56 months. Comparing outcome with tumor grade, the one patient with grade 1 tumor was alive with no evidence of disease; of 5 patients with grade 2 tumor, 2 died of disease, 1 was alive with no evidence of disease, 1 was alive with disease, and 1 was alive with extensive disease; all 3 grade 3 patients died of disease. In summary, the majority of renal leiomyosarcomas are intermediate or high grade with correspondingly poor prognosis.


[Metabolism of histones and non-histone proteins in liver cell nuclei and chromatin from rats of various ages].
The metabolism of various classes of histones and nonhistone proteins in intact nuclei and in liver chromatin of albino Wistar rats aged 1, 3, 12 and 24 months, was studied. It was shown that in the course of postnatal development the metabolism of nonhistone proteins extracted with 0.14 M NaCl in murine liver is increased. Later in ontogenesis, the incorporation of labeled precursors into proteins HMG 14 and HMG 17 decreases; the specific radioactivity of proteins HMG 1 + 2 is higher in 3- and 24-month-old animals. The intensity of metabolism of nonhistone proteins and histones is higher within the composition of the chromatin complex than in the intact nucleus at all stages of postnatal development. Among other histone proteins, histones H1 are characterized by the highest level specific radioactivity in rats of all age groups.


Surface Structures of Cosmetic Standard Poly Methyl Methacrylate UV Evaluation Plates and their Influence on the in vitro Evaluation of UV Protection Abilities of Cosmetic Sunscreens.
Cosmetic standard poly methyl methacrylate (PMMA) UV evaluation plates, i.e., roughened PMMA plates, are used in the EU and the US for the in vitro evaluation of UV protection abilities of sunscreen, such as in vitro UVA-PF and critical wavelength for the Broad-spectrum approval. In our previous studies, inhomogeneity in the thickness of a pseudo-sunscreen layer applied on a flat quartz plate was observed to alter UV transmission. Thus, the surface roughness of the standard plates should have a significant influence on the in vitro evaluation. In the present study, we have analyzed the surface structures of three cosmetic standard PMMA UV evaluation plates: Helioplates HD6 (Sa = 6 µm) and ISO plates (Ra = 2 and 5 µm). A decamethylcyclopentasiloxane and 2-propanol-mixed solvent solution of acrylsilicone resin was prepared, and the solution was added dropwise onto the plates. After the evaporation of the solvents, the plates were cut and the cross section was analyzed using SEM-EDS. The distribution of silicon atoms at the cross-section suggested that the maximum depth of penetrating of acrylsilicone resin was larger than Ra for all the standard plates, and the surface structure was significantly different for each standard plate. In addition, cracks into which the acrylsilicone resin deeply penetrated were observed on the surface of some plates. Clear-solution-type pseudo-sunscreen samples in which UV absorbers and acrylsilicone resin were dissolved were deposited on the standard roughened PMMA plates. It was observed that the addition of acrylsilicone resin drastically changed the net UV transmission. The degree to which the hollows of the roughened surface were filled with the pseudo-sunscreen samples determined the variation of UV transmittance.


Age-related changes in the gut microbiota of the Chinese giant salamander (Andrias davidianus).
The composition of the intestinal microbial community may vary across developmental stages. In this study, we explored how this microbial community shifted along the intestinal tract of the Chinese giant salamander (Andrias davidianus) at various ages. Next-generation sequencing was used to sequence the bacterial 16S rRNA gene from different kind of samples, including the stomach, duodenum, ileum, and rectum. The highest mean relative abundance of the bacterial community in the gastrointestinal tract shifted in relation to age: within the first year, Bacteroidetes (47.76%) dominated the gut microbiome, whereas Proteobacteria was the most dominant at age 2 (32.88%) and age 3 (30.78%), and finally, Firmicutes was the most dominant at age 4 (34.70%). The overall richness of the gut bacterial community also generally increased from age 2 to 4. Hierarchical cluster analysis revealed that the gut microbiome at age 2 had greater variability than that at either age 3 or 4, likely representing a shift in diet from yolk or redworms as a juvenile to shrimp or crab as an adult. As these salamanders develop, their gastrointestinal tracts increase in complexity, and this compartmentalization may also facilitate an increase in microbial gut diversity.


Identification of compounds in red wine that effectively upregulate aquaporin-3 as a potential mechanism of enhancement of skin moisturizing.
In a previous clinical study, the moisture content in the stratum corneum of healthy Japanese women who consumed a beverage rich in oligomeric proanthocyanidins (OPCs) made from red wine extract was found to be higher than that in the control group. This finding suggested that OPCs can increase skin moisture content. In this study, we determined the expression level of aquaporin-3 (AQP3) in keratinocytes to elucidate the mechanism by which compounds in red wine grape increase moisture content in stratum corneum. Through in vitro studies, we confirmed that normal human epidermal keratinocytes (NHEK) incubated with red wine induced AQP3 expression. Furthermore, the supplementation of red wine fractions enriched in OPC was shown to increase AQP3 expression. Besides, the component of OPC-rich fractions that upregulated AQP3 expression was found to be a gallic acid (GA)-binding flavan-3-ol, particularly oligomeric compounds. We found that GA-binding OPC were able to upregulate AQP3 expression and that these compounds were enriched in red wine. Our findings might suggest that the mechanism of enhancement of moisture content in stratum corneum by red wine might be via the upregulation of AQP3 expression in the epidermal keratinocytes.


Kinetics of corneal epithelial regeneration. II. Epidermal growth factor and topical corticosteroids.
The kinetics of rabbit corneal epithelium regeneration were studied to determine if topical corticosteroid has an adverse effect on corneal epithelial wound healing, and if epidermal growth factor (EGF) can abrogate any adverse effect of topical corticosteroid. Healing of standardized 7 mm. central corneal epithelial wounds was determined by serial standardized color photography of the flourescein-stained defects and planimetry of the projected photographs. It has been found that topical application of 16 drops per day of vehicle or Decadron decreased the epithelial healing rate, as compared to saline drops four times daily. Decadron 0.1 per cent given hourly (16 drops daily) was no more detrimental to corneal epithelial healing rate than the vehicle similarly applied. EGF exhibited no capacity to alter the corneal epithelial healing rate when hourly drops of either the vehicle or Decadron 0.1 per cent were given. Under the conditions of these experiments, no adverse effect on corneal epithelial healing rate could be attributed to Decadron 0.1 per cent.


Particulate matter-mediated oxidative stress induces airway inflammation and pulmonary dysfunction through TXNIP/NF-κB and modulation of the SIRT1-mediated p53 and TGF-β/Smad3 pathways in mice.
Exposure to particulate matter is currently recognized as a serious aggravating factor of respiratory diseases. In this study, we investigated the effects of particulate matter (PM) on the respiratory system in BALB/c mice and NCI-H292 cells. PM (0, 2.5, 5 and 20 mg/kg) was administered to mice by intra-tracheal instillation for 7 days. After a 7 day-repeated treatment of PM, we evaluated inflammatory cytokines/cell counts in bronchoalveolar lavage fluid (BALF) and conducted pulmonary histology and functional test. We also investigated the role of TXNIP/NF-κB and SIRT1-mediated p53 and TGF-β/Smad3 pathways in PM-induced airway inflammation and pulmonary dysfunction. PM caused a significant increase in pro-inflammatory cytokines, inflammatory cell counts in bronchoalveolar lavage fluid. PM-mediated oxidative stress down-regulated thioredoxin-1 and up-regulated thioredoxin-interacting protein and activation of nuclear factor-kappa B in the lung tissue and PM-treated NCI-H292 cells. PM suppressed sirtuin1 protein levels and increased p53 acetylation in PM-exposed mice and PM-treated NCI-H292 cells. In addition, PM caused inflammatory cell infiltration and the thickening of alveolar walls by exacerbating the inflammatory response in the lung tissue. PM increased levels of transforming growth factor-β, phosphorylation of Smad3 and activation of α-smooth muscle actin, and collagen type1A2 in PM-exposed mice and PM-treated NCI-H292 cells. In pulmonary function tests, PM exposure impaired pulmonary function resembling pulmonary fibrosis, characterized by increased resistance and elastance of the respiratory system, and resistance, elastance, and damping of lung tissues, whereas decreased compliance of the respiratory system, forced expired volume and forced vital capacity. Overall, PM-mediated oxidative stress caused airway inflammation and pulmonary dysfunction with pulmonary fibrosis via TXNIP pathway/NF-κB activation and modulation of the SIRT1-mediated TGF-β/Smad3 pathways. The results of this study can provide fundamental data on the potential adverse effects and underlying mechanism of pulmonary fibrosis caused by PM exposure as a public health concern. Due to the potential toxicity of PM, people with respiratory disease must be careful with PM exposure.


Genomic and proteomic characterization of SuMu, a Mu-like bacteriophage infecting Haemophilus parasuis.
Haemophilus parasuis, the causative agent of Glässer's disease, is prevalent in swine herds and clinical signs associated with this disease are meningitis, polyserositis, polyarthritis, and bacterial pneumonia. Six to eight week old pigs in segregated early weaning herds are particularly susceptible to the disease. Insufficient colostral antibody at weaning or the mixing of pigs with heterologous virulent H. parasuis strains from other farm sources in the nursery or grower-finisher stage are considered to be factors for the outbreak of Glässer's disease. Previously, a Mu-like bacteriophage portal gene was detected in a virulent swine isolate of H. parasuis by nested polymerase chain reaction. Mu-like bacteriophages are related phyologenetically to enterobacteriophage Mu and are thought to carry virulence genes or to induce host expression of virulence genes. This study characterizes the Mu-like bacteriophage, named SuMu, isolated from a virulent H. parasuis isolate. Characterization was done by genomic comparison to enterobacteriophage Mu and proteomic identification of various homologs by mass spectrometry. This is the first report of isolation and characterization of this bacteriophage from the Myoviridae family, a double-stranded DNA bacteriophage with a contractile tail, from a virulent field isolate of H. parasuis. The genome size of bacteriophage SuMu was 37,151 bp. DNA sequencing revealed fifty five open reading frames, including twenty five homologs to Mu-like bacteriophage proteins: Nlp, phage transposase-C-terminal, COG2842, Gam-like protein, gp16, Mor, peptidoglycan recognition protein, gp29, gp30, gpG, gp32, gp34, gp36, gp37, gpL, phage tail tube protein, DNA circulation protein, gpP, gp45, gp46, gp47, COG3778, tail fiber protein gp37-C terminal, tail fiber assembly protein, and Com. The last open reading frame was homologous to IS1414. The G + C content of bacteriophage SuMu was 41.87% while its H. parasuis host genome's G + C content was 39.93%. Twenty protein homologs to bacteriophage proteins, including 15 structural proteins, one lysogeny-related and one lysis-related protein, and three DNA replication proteins were identified by mass spectrometry. One of the tail proteins, gp36, may be a virulence-related protein. Bacteriophage SuMu was characterized by genomic and proteomic methods and compared to enterobacteriophage Mu.


Venomous snake husbandry in Thailand.
A captive breeding program for venomous Thai snakes was established at the Queen Saovabha Memorial Institute at Bangkok, Thailand. This was necessary to secure a stable, healthy, and species-confirmed source of snake venom for antivenom production. In 1994, wild-caught specimens were collected, sexed, quarantined, and housed appropriately. All data in this report, with the exclusion of Table 6, were collected from 1994 to 1997. Two species were bred successfully in captivity to date during this study period. Although captive breeding has not yet been achieved with all species and subspecies, our early success was encouraging.


Improvement in renal functions with transcatheter aortic valve implantation.
In recent years, emerging transcatheter aortic valve implantation (TAVI) has become an alternative for surgery. However, with advanced age, several co-morbid factors together with contrast agent usage can cause deterioration in renal function and increase in the risk of acute kidney injury (AKI) with poor prognosis in patients with AKI. Therefore, many patients cannot benefit from this treatment. In this study, we aim to examine the effects of TAVI on renal functions. Seventy patients, mean age of 77.6 years, underwent TAVI between July 2011 and December 2012. Estimated glomerular filtration rate (eGFR) was calculated by using the Cockcroft and Gault Formula. Patients were monitored for 48 h for urine output. Stage 1 AKI, according to the VARC-2 AKIN system, developed in only five (7.1%) of the patients after the procedure. There was a statistically significant increase between the mean 1(st) month eGFRs before (68.2 vs. 61.0, P < 0.01) and after (68.2 vs. 63.6, P < 0.05) the TAVI in the cohort. After TAVI (48.5 mL/min, P < 0.01) and the 1(st) month (52.1 mL/min, P < 0.01), the eGFR of the 36 (51.4%) patients diagnosed with chronic kidney disease before the procedure showed a statistically significant increase in renal functions. The hospital mortality rate was higher in the group which developed AKI (P < 0.01). First month eGFR showed a more statistically significant increase than pre-TAVI eGFR (62.8 and 69.8, P < 0.05, respectively) in AKI developing patients and this difference - though statistically not significant - continued into the sixth month. In this study, we showed that the treatment of aortic stenosis through TAVI allows improvement of renal functions, and that AKI rates will be lower with careful patient selection, proper pre-procedural hydration, and careful use of contrast agent.


Melanosis of the vulva. A clinical simulator of malignant melanoma.
Eight patients with melanosis of the vulva are presented in order to illustrate the characteristic clinical and histopathologic features of the condition. Despite clinical features that may be indistinguishable from those of malignant melanoma, the patchy pigmentation of melanosis that is seen mostly on the vulva, but also on the penis, shows wholly different histologic changes than those of melanoma, namely, a slightly increased number of typical melanocytes arranged as solitary units at the dermal-epidermal junction of a hyperpigmented epidermis. It is important to identify melanosis of the vulva for what it is, because overdiagnosis of it as malignant melanoma may result in needless radical surgery.


Maternal depression as a risk factor for children's inadequate housing conditions.
Depression among mothers with young children is an important public health issue that not only has implications for their own well-being, but can also potentially affect their children's health and developmental trajectories. This study explored the extent to which maternal depression is a risk factor for inadequate housing conditions related to utilities, a noteworthy risk factor for poor child health. Using data on 2965 mothers and children from a national urban cohort of U.S. births in 1998-2000, we estimated multivariate logistic regression models of associations between maternal depression during the postpartum year and a U.S. Department of Housing and Urban Development (HUD) measure of severely inadequate housing due to heating issues, as well as a broader measure of energy insecurity that encompasses various types of utility problems. We also considered outcomes that incorporated housing instability and food insecurity in conjunction with housing inadequacy. Mothers who experienced depression had about 60% higher odds of experiencing severely inadequate housing due to heat (OR: 1.57) and 70% higher odds of experiencing energy insecurity (OR: 1.69) compared to mothers who did not experience depression. Maternal depression was even more strongly associated with multiple hardships in the forms of housing inadequacy plus housing instability and/or food insecurity than it was with housing inadequacy. This study provides robust evidence that maternal depression is a risk factor for inadequate housing and multiple hardships during a critical period of children's development. The findings suggest that policy efforts should not occur in mental health, housing, and food security silos.


Fibrin gels exhibit improved biological, structural, and mechanical properties compared with collagen gels in cell-based tendon tissue-engineered constructs.
The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair.


Improved detection of metastases to lymph nodes and estrogen receptor determination.
We present a new method for detection of micrometastases to axillary lymph nodes and estrogen receptor determination. Cellular suspensions from primary infiltrating ductal breast carcinoma or level I axillary lymph nodes of patients who underwent mastectomies were obtained, by loosely grinding fresh tumors or lymph nodes through a grid and then transferring the matrix to a slide using cytocentrifugation. Tumor samples were analyzed for estrogen receptor status using an immunocytochemical kit and compared with the dextran-coated charcoal method. Thirty-eight of 48 correlated (20 were estrogen positive, and 18 were estrogen negative). Seven of 46 were estrogen positive while results from the dextran-coated charcoal method were estrogen negative. One of 46 was estrogen negative, while the results from the dextran-coated charcoal method were estrogen positive. Lymph node slide preparations were stained to detect tumor cells using antikeratin monoclonal antibodies. Three of 8 node-negative patients were found to have micrometastases. Four of 15 node-positive patients had additional nodes with tumor. Our method combines the advantages of serial sectioning and immunohistochemical staining.


Maintenance and mobility of hemoglobin and water within the human erythrocyte after detergent disruption of the plasma membrane.
Is an intact plasma membrane responsible for keeping hemoglobin and water within the human erythrocyte? If not, what is responsible? How free is Hb to move about within the erythrocyte? To answer these questions erythrocytes were taken for phase contrast microscopy, transmission electron microscopy (TEM), determination of water-holding capacity, and proton NMR studies both before and after membrane disruption with a nonionic detergent (Brij 58). Addition of 0.2% Brij to a D2O saline solution of hemoglobin (Hb) caused particles of Hb to appear and to aggregate. This aggregation of Hb caused the amplitude of the Hb proton NMR spectra to decrease. Thus, the less mobile the Hb the lower the Hb proton spectra amplitude. Erythrocytes washed in D2O saline showed proton NMR spectra of relatively low amplitude. Addition of Brij (0.2%) to these erythrocytes caused increased Hb mobility within these erythrocytes. The TEM of fixed and thin-sectioned erythrocytes treated with Brij showed disruption of the plasma membrane of all erythrocytes regardless of whether or not they had lost Hb. Brij-permeabilized erythrocytes washed in D2O saline or in a D2O K buffer maintained a higher heavy water-holding capacity upon centrifugation as compared to nonpermeabilized erythrocytes. The TEM of Brij-treated and washed erythrocyte "shells" revealed a continuous submembrane lamina but no other evidence of cytoskeletal elements. The water-holding capacity of the erythrocyte can be accounted for by the water-holding capacity of hemoglobin. The evidence favors a relatively immobile state of Hb and of water in the erythrocyte that is not immediately dependent on an intact plasma membrane but is attributed to interactions between Hb molecules and the submembrane lamina.


The Worst Performance Rule, or the Not-Best Performance Rule? Latent-Variable Analyses of Working Memory Capacity, Mind-Wandering Propensity, and Reaction Time.
The worst performance rule (WPR) is a robust empirical finding reflecting that people's worst task performance shows numerically stronger correlations with cognitive ability than their average or best performance. However, recent meta-analytic work has proposed this be renamed the "not-best performance" rule because mean and worst performance seem to predict cognitive ability to similar degrees, with both predicting ability better than best performance. We re-analyzed data from a previously published latent-variable study to test for worst vs. not-best performance across a variety of reaction time tasks in relation to two cognitive ability constructs: working memory capacity (WMC) and propensity for task-unrelated thought (TUT). Using two methods of assessing worst performance-ranked-binning and ex-Gaussian-modeling approaches-we found evidence for both the worst and not-best performance rules. WMC followed the not-best performance rule (correlating equivalently with mean and longest response times (RTs)) but TUT propensity followed the worst performance rule (correlating more strongly with longest RTs). Additionally, we created a mini-multiverse following different outlier exclusion rules to test the robustness of our findings; our findings remained stable across the different multiverse iterations. We provisionally conclude that the worst performance rule may only arise in relation to cognitive abilities closely linked to (failures of) sustained attention.


Changes in irradiance and vapour pressure deficit under drought induce distinct stomatal dynamics between glasshouse and field-grown poplars.
Recent research has shown that plant acclimation to diverse patterns of light intensity modifies the dynamics of their stomatal response. Therefore, whether plants are grown in controlled conditions or in the field may impact their stomatal dynamics. We analysed the stomatal dynamics of two Populus euramericana and two Populus nigra genotypes grown in the field under contrasting water availability. By comparing their stomatal dynamics with that of the same genotypes grown in a glasshouse, we were able to test whether differences between these growing conditions interacted with genotypic differences in affecting stomatal dynamics and responses to soil water deficit. We found that, despite higher stomatal density and smaller size, in the field stomatal dynamics were much slower than in the glasshouse. Overall, differences among genotypes and their response to soil water deficit were much less pronounced in the field compared with the glasshouse. These results indicate that stomatal dynamics are regulated by both genotype-specific and environmental factors. Moreover, having slower stomata may be advantageous under some conditions. While stomatal dynamics were linked with whole-plant transpiration per leaf area in both experiments, the contribution of stomatal morphology varies dependent on the environmental conditions.


Physical activity, sleep disorders, and type of work in the prevention of cognitive function decline in patients with hypertension.
Hypertensive patients are likelier to have cognitive function decline (CFD). This study aimed to explore physical activity level, sleep disorders, and type of work that influenced intervention effects on cognitive function decline in hypertensive patients and to establish a decision tree model to analyze their predictive significance on the incidence of CFD in hypertensive patients. This cross-sectional study recruited patients with essential hypertension from several hospitals in Shandong Province from May 2022 to December 2022. Subject exclusion criteria included individuals diagnosed with congestive heart failure, valvular heart disease, cardiac surgery, hepatic and renal dysfunction, and malignancy. Recruitment is through multiple channels such as hospital medical and surgical outpatient clinics, wards, and health examination centers. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Moreover, we obtained information on the patients' type of work through a questionnaire and their level of physical activity through the International Physical Activity Questionnaire (IPAQ). The logistic regression analysis results indicate that sleep disorder is a significant risk factor for CFD in hypertension patients(OR:1.85, 95%CI:[1.16,2.94]), mental workers(OR:0.12, 95%CI: [0.04,0.37]) and those who perform both manual and mental workers(OR: 0.5, 95%CI: [0.29,0.86]) exhibit protective effects against CFD. Compared to low-intensity, moderate physical activity(OR: 0.53, 95%CI: [0.32,0.87]) and high-intensity physical activity(OR: 0.26, 95%CI: [0.12,0.58]) protects against CFD in hypertension patients. The importance of predictors in the decision tree model was ranked as follows: physical activity level (54%), type of work (27%), and sleep disorders (19%). The area under the ROC curves the decision tree model predicted was 0.72 [95% CI: 0.68 to 0.76]. Moderate and high-intensity physical activity may reduce the risk of developing CFD in hypertensive patients. Sleep disorders is a risk factor for CFD in hypertensive patients. Hypertensive patients who engage in mental work and high-intensity physical activity effectively mitigate the onset of CFD in hypertensive patients.


Effects of alpha-deuteration and of aza and thia analogs of L-tryptophan on formation of intermediates in the reaction of Escherichia coli tryptophan indole-lyase.
Tryptophan indole-lyase catalyzes the hydrolytic cleavage of L-tryptophan to indole and ammonium pyruvate. After the enzyme is mixed with L-tryptophan in the rapid-scanning stopped-flow spectrophotometer, there is an absorbance increase at 505 nm in the pre-steady state attributed to formation of a quinonoid intermediate, which occurs in at least three consecutive first-order phases. Reaction with [alpha-2H]-L-tryptophan results in significant primary kinetic isotope effects on the first two phases, and there is a significant isotope effect on the amplitude of the absorbance increase in the second phase. This result suggests that proton transfer to carbon to form the indolenine intermediate is relatively slow and is probably at least partially rate-determining. Reaction of L-tryptophan in the presence of benzimidazole results in a rapid increase in absorbance in the first phase, followed by a decrease in absorbance in the second phase, with rate constants very similar to those observed without benzimidazole. We have also examined aza and thia analogs of L-tryptophan, with the benzene ring of the indole replaced by pyridine or thiophene. Both 4,5-thiatryptophan and 6,7-thiatryptophan form quinonoid intermediates in the reaction with tryptophan indole-lyase; however, 6,7-thiatryptophan is a better substrate (kcat/K(m) = 32% of L-trp) for tryptophan indole-lyase than is 4,5-thiatryptophan (kcat/K(m) = 4% of L-trp). Benzimidazole affects the pre-steady-state reaction of 6,7-thiatryptophan in a way similar to L-tryptophan, while benzimidazole does not affect the pre-steady-state reaction of 4,5-thiatryptophan. 4-Aza-, 5-aza-, 6-aza-, and 7-aza-L-tryptophan are all very slow substrates (kcat < 1% of L-trp) for Escherichia coli tryptophan indole-lyase. beta-Indazolyl-L-alanine is a relatively good substrate and exhibits a quinonoid intermediate in its reaction with tryptophan indole-lyase. 6-Aza- and 7-azatryptophan accumulate quinonoid intermediates in the reaction with tryptophan indole-lyase, whereas 4-aza- and 5-azatryptophans do not significantly accumulate quinonoid intermediates, and these latter compounds exhibit very high K(m) values. Addition of benzimidazole does not change the rapid-scanning stopped-flow spectra of 6-aza- and 7-azatryptophan. This suggests that the rate-determining step in the reaction changes depending on the position and type of heteroatom substitution. For 6-aza- and 7-azatryptophan, the very slow rates of elimination may be due to slow C-protonation of the azaindole, while for 4,5-thiatryptophan, the elimination of thienopyrrole is probably slow. Of all analogs examined, 6,7-thiatryptophan is most similar to tryptophan in its reaction with E. coli tryptophan indole-lyase.


Influenza Virus Infection Enhances Antibody-Mediated NK Cell Functions via Type I Interferon-Dependent Pathways.
Natural killer (NK) cells are an important component in the control of influenza virus infection, acting to both clear virus-infected cells and release antiviral cytokines. Engagement of CD16 on NK cells by antibody-coated influenza virus-infected cells results in antibody-dependent cellular cytotoxicity (ADCC). Increasing the potency of antibody-mediated NK cell activity could ultimately lead to improved control of influenza virus infection. To understand if NK cells can be functionally enhanced following exposure to influenza virus-infected cells, we cocultured human peripheral blood mononuclear cells (PBMCs) with influenza virus-infected human alveolar epithelial (A549) cells and evaluated the capacity of NK cells to mediate antibody-dependent functions. Preincubation of PBMCs with influenza virus-infected cells markedly enhanced the ability of NK cells to respond to immune complexes containing hemagglutinin (HA) and anti-HA antibodies or transformed allogeneic cells in the presence or absence of a therapeutic monoclonal antibody. Cytokine multiplex, RNA sequencing, supernatant transfer, Transwell, and cytokine-blocking/cytokine supplementation experiments showed that type I interferons released from PBMCs were primarily responsible for the influenza virus-induced enhancement of antibody-mediated NK cell functions. Importantly, the influenza virus-mediated increase in antibody-dependent NK cell functionality was mimicked by the type I interferon agonist poly(I·C). We conclude that the type I interferon secretion induced by influenza virus infection enhances the capacity of NK cells to mediate ADCC and that this pathway could be manipulated to alter the potency of anti-influenza virus therapies and vaccines.IMPORTANCE Protection from severe influenza may be assisted by antibodies that engage NK cells to kill infected cells through ADCC. Studies have primarily focused on antibodies that have ADCC activity, rather than the capacity of NK cells to become activated and mediate ADCC during an influenza virus infection. We found that type I interferon released in response to influenza virus infection primes NK cells to become highly reactive to anti-influenza virus ADCC antibodies. Enhancing the capacity of NK cells to mediate ADCC could assist in controlling influenza virus infections.


Feasibility of percutaneous radiofrequency ablation for intrathoracic malignancies: a large single-center experience.
Radiofrequency ablation (RFA) has become an accepted alternative for treating intrathoracic malignancies; however, the incidence and characteristics of peri- and postprocedural complications are not well described. The purpose of the study was to assess the safety and technical feasibility of percutaneous RFA in unresectable intrathoracic malignancies. Percutaneous RFA was performed in patients with intrathoracic malignancies between June 2001 and December 2004. In total, 366 tumors were treated in 137 patients in 211 sessions. All patients were nonsurgical candidates or had refused surgery. Three hundred and thirty-six lesions were subjected to RFA for the treatment of metastases and 30 lesions for primary lung carcinoma. Although no procedural mortality occurred, 2 patients died during the course of the study because of intractable pneumothorax and massive hemoptysis (0.9%). The overall major complication rate was 17.1% (pneumothoraces requiring tube drainage in 25, pleuritis in 6, pleural effusion requiring tube drainage in 4, lung abscess in 1, and intrapulmonary hemorrhage with hemothorax in 1). Minor complications included pneumothoraces not requiring tube drainage in 108 sessions, pleural effusion without drainage in 34, hemosputum in 9, nausea and/or vomiting in 3, subcutaneous emphysema in 3, cough in 2, skin burn in 2, atelectasis in 1, and subileus in 1. High fever and/or chest pain were seen in 33.8% and 39.3% of patients, respectively. With over 200 procedures, RFA appears to be a safe and minimally invasive option with negligible mortality and little morbidity in selected patients with unresectable intrathoracic malignancies.


The effectiveness of three-phase physiotherapy program in children with clubfoot after Ponseti treatment.
Clubfoot is a foot disorder frequently seen. Although, there are several studies about the efficiency of physiotherapy in the treatment of clubfoot, physiotherapy programs may be more efficient if the treatment apply step by step similar to the logic of the serial casting progression of the involved foot. Therefore, the aim of this study was to determine the effectiveness of three-phase physiotherapy program in children with clubfoot. Fifty-seven patients (37 males, 20 females; 7.26 ± 1.27 years) with clubfoot which had Ponseti treatment before were included. The ankle dorsiflexion (DF) and plantar flexion (PF) ranges of motion (ROM), one-leg standing time, sit-to-stand test, The Oxford Ankle Foot Questionnaire (OxAFQ) and treatment satisfaction were evaluated before and after treatment. A three-phase physiotherapy program was applied for 3 months. DF, PF, one-leg standing time, sit-to-stand test, treatment satisfaction and all parameters of OxAFQ except 'Emotional' parameter of OxAFQ-Children significantly improved after treatment (p < 0.05). The three-phase physiotherapy program increased the ankle range of motion, improved functional status and treatment satisfaction in children with clubfoot. The three-phase physiotherapy might be a reasonable treatment for clubfoot. Although, there is a need for long-term studies to understand its effects on preventing relapse.


The impact of the environment on height in Europe: conceptual and theoretical considerations.
The purpose of this review is to assess whether information available to evaluate the impact of the environment and, more specifically, socio-economic factors on height in European countries is sufficient. It is proposed that studies based on measurements taken 25 years ago or more are unsatisfactory for assessing the current situation. There is a widespread assumption that sufficient information is available for assessing the issue. However, on inspection, there are very few environmental factors for which sufficient material on their effects on height has been published. In many studies to evaluate the effect of the environment an ecological design is used and a post hoc interpretation is made. It is concluded that this type of study is helpful only for generating hypotheses. When inspecting analytical studies on the association between socio-economic factors and height it is observed that the reports identified are only the tip of the iceberg of published reports on the subject and include studies from less than half the European countries. In many of these papers the independent variables are not defined in the same manner and a formal comparison is difficult to make. Given the current deficiencies, it is worthwhile to discuss in auxological epidemiology whether it is relevant to tackle the issue proposed in this review. If the answer is yes, it is necessary to identify the best course of action. Possible avenues to explore are the potential and the barriers for harmonizing the investigation of socio-economic factors in growth studies, and the organization of a registry of reports on growth and social factors. At a more modest level, a collaborative report examining the availability of information and gaps on this topic among European countries could be helpful.


Levels of some trace elements and rheumatoid factor in sheep with brucellosis.
Brucellosis is a zoonotic disease that is encountered in sheep rather frequently. In this study, 100 sheep diagnosed with brucellosis that had aborts and 40 healthy sheep were used as materials. Analyses for Cu, Zn, Fe, Cr, Ca, Mg, and K were performed with the atomic absorption spectrophotometric method on blood collected from vena jugularis of all the sheep and rheumatoid factor levels were determined by the nephelometry method. Although it was found that Cu, Ca, and rheumatoid factor values in the sera of the sheep with brucellosis were high when compared to the control group (p<0.001, p<0.05, p<0.001, respectively), their serum Zn values were low (p<0.05). No significant changes in serum Cr, Fe, K, and Mg levels were found.


Patient removals from general practitioner lists in Northern Ireland: 1987-1996.
Being struck off a general practitioner's list is a major event for patients and a subject for much media attention. However, it has not hitherto received much research attention. To quantify the numbers of patients removed at doctors' request in Northern Ireland between 1987 and 1996. To describe the characteristics of those removed and to determine if the rate of removal has increased. This is a descriptive epidemiological study involving a secondary data analysis of records held by the Central Services Agency. Six thousand five hundred and seventy-eight new patients were removed at general practitioner (GP) request between 1987 and 1996. This equated to 3920 removal decisions, a rate of 2.43 per 10,000 person-years. The very young and young adults had the highest rates of removal; most of the young being removed as part of a family. Ten point six per cent of removed patients had a repeat removal, and 16.3% of first removal decisions required an assignment to another practice. Family removals have decreased and individual removals have increased over the 10 years. Disadvantaged and densely populated areas with high population turnover were associated with higher rates of removal, though heterogeneity is evident between general practitioners serving similar areas. Compared to the period 1987 to 1991, removal rates for the years 1992 to 1993 were reduced by 20.0% (95% confidence interval (CI) for rate ratio (RR) 0.73-0.87), and those for the years 1994 to 1996 increased by 8% (95% CI = 1.01-1.16). The greatest increase was in the over-75 years age group (standardized RR = 1.60; 95% CI = 1.57-1.62). Removals are relatively rare events for both patients and practices, though they have been increasing in recent years. Further research is needed to understand the processes that culminate in a removal.


Tactile Gap Detection Deteriorates during Bimanual Symmetrical Movements under Mirror Visual Feedback.
It has been suggested that incongruence between signals for motor intention and sensory input can cause pain and other sensory abnormalities. This claim is supported by reports that moving in an environment of induced sensorimotor conflict leads to elevated pain and sensory symptoms in those with certain painful conditions. Similar procedures can lead to reports of anomalous sensations in healthy volunteers too. In the present study, we used mirror visual feedback to investigate the effects of sensorimotor incongruence on responses to stimuli that arise from sources external to the body, in particular, touch. Incongruence between the sensory and motor signals for the right arm was manipulated by having the participants make symmetrical or asymmetrical movements while watching a reflection of their left arm in a parasagittal mirror, or the left hand surface of a similarly positioned opaque board. In contrast to our prediction, sensitivity to the presence of gaps in tactile stimulation of the right forearm was not reduced when participants made asymmetrical movements during mirror visual feedback, as compared to when they made symmetrical or asymmetrical movements with no visual feedback. Instead, sensitivity was reduced when participants made symmetrical movements during mirror visual feedback relative to the other three conditions. We suggest that small discrepancies between sensory and motor information, as they occur during mirror visual feedback with symmetrical movements, can impair tactile processing. In contrast, asymmetrical movements with mirror visual feedback may not impact tactile processing because the larger discrepancies between sensory and motor information may prevent the integration of these sources of information. These results contrast with previous reports of anomalous sensations during exposure to both low and high sensorimotor conflict, but are nevertheless in agreement with a forward model interpretation of perceptual modulations during goal directed movement.


Outcomes of cardiothoracic surgery in women with Turner syndrome.
To describe short- and mid-term surgical outcomes of patients with Turner syndrome (TS) after cardiovascular interventions. All individuals >12 years of age at the time of surgical repair for cardiovascular disease (valve or coarctation repairs, aortic disease, aortic dissection) from 2002 to 2022 were eligible. The primary endpoint was complications or death within 30 days of intervention. Secondary outcomes included late complications and reinterventions within six months. Combined data from the University of Texas Health Science Center at Houston and the Turner Syndrome Society of the United States were included in the analysis. We identified 22 patients who met the inclusion criterion. The median age was 46 years (range, 21-75 years), with 86% having estrogen replacement therapy. The most common medical condition was hypertension (77%), followed by hypothyroidism (59%). The most frequent indication for surgery was aortic root or ascending aortic aneurysms (68%), followed by symptomatic aortic stenosis in patients with bicuspid aortic valve (64%), coarctation of aorta (45%), and acute aortic dissection (18%). Respiratory complications were the most common (68%). Pleural effusions were the most frequent found sign on imaging studies (68%). Thoracentesis, or chest tube placement, was required in 33% (5/15). Respiratory failure requiring specific support with high flow oxygen and/or thoracentesis occurred in 36% (8/22). Patients with TS may be at an increased risk for postoperative complications after aortic surgery. Bicuspid aortic valve (59%) and coarctation of the aorta (45%) were the most common congenital malformations among our study group. Our study showed that respiratory complications were the most common, with pleural effusions being the most common post-surgery complication.


Rates of prostate-specific antigen testing in general practice in England and Wales in asymptomatic and symptomatic patients: a cross-sectional study.
To assess the rate of prostate-specific antigen (PSA) testing for prostate cancer in general practice in asymptomatic and symptomatic patients. The cross-sectional study took place in England and Wales, was population-based and covered 469 159 men aged 45-84 years. Pathology data on PSA tests requested between 19 November 1999 and 31 May 2002 by general practitioners (GPs) were provided by 28 pathology laboratories. The practices recorded reasons for the tests between 1 December 2001 and 31 May 2002. In all, 391 practices in which all GP partners participated were included in the analyses. The overall annual rate of testing in men with no previous diagnosis of prostate cancer was estimated to be 6%, of which the annual rates of asymptomatic, symptomatic and re-testing were 2.0%, 2.8% and 1.2%, respectively, after adjusting for missing values. The rate decreased with increasing social deprivation, and with increasing proportions of black and Asian populations. The overall rate of PSA testing increased significantly from 1999 to 2002. If the recommendations of the National Health Service Prostate Cancer Risk Management Programme were applied, 14% of asymptomatic tests and 23% of symptomatic tests would have led to a referral. As the rate of PSA testing is increasing and there are uncertainties about the benefit of screening, the workload and costs in general practice and hospitals should be monitored.


The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA): Data on mortality, by HIV status and stage on the HIV care continuum, among the general population in seven longitudinal studies between 1989 and 2014.
Timely progression of people living with HIV (PLHIV) from the point of infection through the pathway from diagnosis to treatment is important in ensuring effective care and treatment of HIV and preventing HIV-related deaths and onwards transmission of infection. Reliable, population-based estimates of new infections are difficult to obtain for the generalised epidemics in sub-Saharan Africa. Mortality data indicate disease burden and, if disaggregated along the continuum from diagnosis to treatment, can also reflect the coverage and quality of different HIV services. Neither routine statistics nor observational clinical studies can estimate mortality prior to linkage to care nor following disengagement from care. For this, population-based data are required. The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa brings together studies in Kenya, Malawi, South Africa, Tanzania, Uganda, and Zimbabwe. Eight studies have the necessary data to estimate mortality by HIV status, and seven can estimate mortality at different stages of the HIV care continuum. This data note describes a harmonised dataset containing anonymised individual-level information on survival by HIV status for adults aged 15 and above. Among PLHIV, the dataset provides information on survival during different periods: prior to diagnosis of infection; following diagnosis but before linkage to care; in pre-antiretroviral treatment (ART) care; in the first six months after ART initiation; among people continuously on ART for 6+ months; and among people who have ever interrupted ART.


Driving violations and health promotion behaviors among undergraduate students: Self-report of on-road behavior.
The purposes of this study are to characterize Israeli undergraduate students' driving violations in the terms of problem behavior theory and to identify whether there is any relationship between driving violations and health risk behaviors, daring behaviors, excitement seeking, and health promotion behaviors. This study is based on a structured self-reported anonymous questionnaire distributed to undergraduate students in an academic institution. The sample included 533 undergraduate students (374 females and 159 males). The mean age was 23.4 (SD = 1.4, range = 5). A higher prevalence of self-reported driving violations was found among males in comparison to females. All substance use measures were positively related to driving violations; for example, use of cigarettes (OR = 4.287, P <.001) and water pipes (odds ratio [OR] = 3.000, P <.001) as well as binge drinking (OR = 5.707, P <.001) and regular cannabis smoking (OR = 5.667, P <.001) raise the probability of committing rare driving violations. The strongest predictive factors for the frequent driving violations group were alcohol consumption-related variables: binge drinking (OR = 2.560, P <.01) and drunkenness (OR = 2.284, P <.05). Strong odd ratios were also found between the frequent driving violations group and selling or dealing drugs (12.143, P <.001), and stealing something valuable (13.680, P <.001). The strongest predicted variable for the rare driving violations group was physical confrontation due to verbal disagreement (3.439, P <.05) and the concept that selling or dealing drugs is socially acceptable (2.521, P <.05). The probability of executing rare driving violations was higher for subjects who reported intense physical workout regimens (OR = 1.638, P <.05). Problem behavior theory succeeded in explaining health risk behavior and driving violations. This study shows that bachelors tend to be more involved in risk behaviors, such as substance use, excitement-seeking behaviors, and daring behaviors and are active physically and thus constitute a risk group for driving violations. As such, intervention resources should be directed toward this group.


Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors: results from a randomized, multicenter, open-label, phase I study.
Pasireotide (SOM230), a novel multireceptor ligand somatostatin analog (SSA), binds with high affinity to four of the five somatostatin receptor subtypes (sst1-3, 5). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics profiles of pasireotide long-acting release (LAR) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor (GEP NET) refractory to other SSAs. In this randomized, multicenter, open-label, phase II study, patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were randomly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20, 40, or 60 mg once every 28 days for 3 months. Forty-two patients received pasireotide LAR. Adverse events were reported by 34 (81 %) patients, with the most frequently reported including diarrhea, fatigue, abdominal pain, and nausea. Mean fasting glucose levels were increased compared with baseline at all points throughout the study. After the third injection of pasireotide LAR, the median trough plasma concentrations on day 84 were 4.82, 12.0, and 19.7 ng/mL in the 20-, 40-, and 60-mg treatment groups, respectively. Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections (accumulation ratios were approximately 1 from all dose levels). This study demonstrated that a new, once-monthly, intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET. Steady state levels of plasma pasireotide were achieved after three injections.


[A Case of Curative Resection for Advanced Pancreatic Acinar Cell Carcinoma with Liver Metastasis and Involvement of the Superior Mesenteric Artery after Chemoradiotherapy Following Systemic Chemotherapy].
A 52-year-old man was initially diagnosed with an unresectable acinar cell carcinoma of the pancreas with liver metastasis and involvement of the superior mesenteric artery. After 5 courses of systemic chemotherapy(gemcitabine and S-1), the size of the pancreatic tumor had decreased from 31mm to 19mm and the liver metastasis had disappeared. We initiated chemoradiotherapy( CRT: S-1+56 Gy)for further local treatment. After CRT the size of the pancreatic tumor decreased to 13mm and his serum CA 19-9 level decreased from 677.2 U/mL to 38.1 U/mL. After 2months of S-1 administration, we performed subtotal stomach-preserving pancreaticoduodenectomy with D2 lymph node dissection. Histopathological examination revealed that most of the pancreatic cancer was replaced by fibrosis and only a few atypical epithelial cells existed. No cancer cells were found at the surgical margin. The patient remains alive without any signs of recurrence 59 months after the systemic chemotherapy and 51 months after the surgical resection.


Systematic assessment of variability in the proteome of iPSC derivatives.
The use of induced pluripotent stem cells (iPSC) to model human complex diseases is gaining popularity as it allows investigation of human cells that are otherwise sparsely available. However, due to its laborious and cost intensive nature, iPSC research is often plagued by limited sample size and putative large variability between clones, decreasing statistical power for detecting experimental effects. Here, we investigate the source and magnitude of variability in the proteome of parallel differentiated astrocytes using mass spectrometry. We compare three possible sources of variability: inter-donor variability, inter- and intra-clonal variability, at different stages of maturation. We show that the interclonal variability is significantly smaller than the inter-donor variability, and that including more donors has a much larger influence on statistical power than adding more clones per donor. Our results provide insight into the sources of variability at protein level between iPSC samples derived in parallel and will aid in optimizing iPSC studies.


Epidemiologic associations with cerebral palsy.
To estimate epidemiologic risk factors for cerebral palsy. Data were collected by linkage to state-based perinatal repositories and cerebral palsy registers and using a maternal questionnaire. The cohort included 587 individuals with cerebral palsy and 1,154 non-cerebral palsy controls. The following factors were associated with cerebral palsy: recorded maternal infection during pregnancy (41.4% patients compared with 31.3% controls; odds ratio [OR] 1.55, 95% confidence interval 1.26-1.91), small for gestational age ([birth weight less than third customized centile] 43.9% patients compared with 6.3% controls; OR 11.75, 6.25-22.08), gestational age less than 32 weeks (29.3% patients compared with 0.7% controls; OR 59.20, 28.87-121.38), multiple birth (OR 6.62, 4.00-10.95), a relative with cerebral palsy (OR 1.61, 1.12-2.32), breech position (13.7% patients compared with 6.0% controls; OR 2.48, 1.76-3.49), bleeding at any time in pregnancy (29.3% patients compared with 16.9% controls; OR 2.04, 1.61-2.58), male sex (58.8% patients compared with 45.8% controls; OR 1.68, 1.38-2.06), multiple miscarriage (7.7% patients compared with 3.5% controls; OR 2.30, 1.38-3.82), smoking (14.0% patients compared with 10.6% controls; OR 1.37, 1.02-1.85), and illicit drug use (3.3% patients compared with 1.5% controls; OR 2.22, 1.14-4.30). Factors not associated with cerebral palsy were "disappearing twin," diabetes, maternal body mass index, hypertension, alcohol consumption, anemia, maternal hypothyroidism, forceps or vacuum delivery, and maternal age. Preterm birth, intrauterine growth restriction, perinatal infection, and multiple birth present the largest risks for a cerebral palsy outcome. Reassuringly, upper respiratory tract and gastrointestinal infections during pregnancy were not associated with cerebral palsy. II.


Women with phenylketonuria: successful management of pregnancy and implications.
Dietary management of five pregnancies in two women (sisters) with classical phenylketonuria (PKU) is described. One child died neonatally of congenital heart disease and one pregnancy miscarried. Of the three surviving children the only physically and mentally normal child, followed up to eight years, was born after a carefully planned pregnancy with strict dietary control preconceptually and throughout pregnancy. One pregnancy treated dietetically from six weeks gestation resulted in a child mentally normal at seven years but born with oesophageal atresia. The third surviving child is microcephalic and mentally retarded but dietetic treatment did not commence till 28 weeks gestation. It is concluded that to be effective, dietary control must be instituted preconceptually.


Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83.
The purpose of this study was to determine whether administration of the microorganism Eubacterium rectale (E. rectale) could regulate dendritic cell (DC) activation and systemic inflammation in herpes simplex virus type 1-induced Behçet's disease (BD). E. rectale, butyrate-producing bacteria, was administered to BD mice. Peripheral blood leukocytes (PBL) and lymph node cells were isolated and analyzed by flow cytometry. 16S rRNA metagenomic analysis was performed in the feces of mice to determine the differences in the composition of the microbial population between normal and BD mice. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of DC activation marker CD83 positive cells was significantly increased in PBL of BD mice. Frequencies of CD83+ cells were also significantly increased in patients with active BD. 16S rRNA metagenomic analysis revealed different gut microbiota composition between normal and BD mice. The administration of E. rectale to BD mice reduced the frequency of CD83+ cells and significantly increased the frequency of NK1.1+ cells with the improvement of symptoms. The co-administration of colchicine and E. rectale also significantly reduced the frequency of CD83+ cells. Differences in gut microbiota were observed between normal mice and BD mice, and the administration of E. rectale downregulated the frequency of CD83, which was associated with BD deterioration. These data indicate that E. rectale could be a new therapeutic adjuvant for BD management.


Effect of three proteinaceous foreign materials on infected and subinfected wound models.
A model was devised to determine the effects of several foreign bodies (microcrystalline collagen hemostat (MCCH), blood clot, catgut suture) on S. aureus wound contamination and wound infection. In a subinfected wound model, MCCH, when compared with the other foreign bodies, showed an increase in the number of wounds classified as "contaminated," but 84 percent of these wounds yielded bacterial counts below the level accepted for biologically significant wound infection (10 to the 5th power bacteria per gram tissue). The number of "infected" wounds was not significantly greater than the number found in the uninoculated control group. In the infected wound model, all groups of inoculated animals showed significant infections. The severity of the wound infection was unaffected by the presence of catgut suture, clotted blood, or MCCH. Higher levels were not seen for the MCCH animals than for the inoculated control animals. We did not see in these experimental wound studies with MCCH a significant aggravation of wound contamination or wound infection during the 48 hour period following inoculation with varying dose levels of S. aureus. Further studies would be necessary to determine the possible bacteriological response after 48 hours.


Mining the pharmacogenomics literature--a survey of the state of the art.
This article surveys efforts on text mining of the pharmacogenomics literature, mainly from the period 2008 to 2011. Pharmacogenomics (or pharmacogenetics) is the field that studies how human genetic variation impacts drug response. Therefore, publications span the intersection of research in genotypes, phenotypes and pharmacology, a topic that has increasingly become a focus of active research in recent years. This survey covers efforts dealing with the automatic recognition of relevant named entities (e.g. genes, gene variants and proteins, diseases and other pathological phenomena, drugs and other chemicals relevant for medical treatment), as well as various forms of relations between them. A wide range of text genres is considered, such as scientific publications (abstracts, as well as full texts), patent texts and clinical narratives. We also discuss infrastructure and resources needed for advanced text analytics, e.g. document corpora annotated with corresponding semantic metadata (gold standards and training data), biomedical terminologies and ontologies providing domain-specific background knowledge at different levels of formality and specificity, software architectures for building complex and scalable text analytics pipelines and Web services grounded to them, as well as comprehensive ways to disseminate and interact with the typically huge amounts of semiformal knowledge structures extracted by text mining tools. Finally, we consider some of the novel applications that have already been developed in the field of pharmacogenomic text mining and point out perspectives for future research.


[Serum level of various biologically active substances and their connection with vessel permeability in hemorrhagic fever with kidney syndrome].
Content of total free serotonin, histamine, kallikrein and prekallikrein was studied in blood of 45 patients with hemorrhagic fever accompanied by kidney syndrome; vessel permeability was also evaluated by means of radiological procedure. Analysis of correlation between vessel permeability and content of these biologically active substances in blood was carried out. Content of kallikrein was distinctly increased in blood plasma of the patients; content of serotonin and histamine was less markedly altered. Vessel permeability was elevated during all the disease periods; it was especially high in the period of oligoanuria. Analysis of the data obtained showed that an increase in vessel permeability correlated most distinctly with augmented content of kallikrein in the blood, while correlation between vessel permeability and content of histamine and free serotonin was less distinct.


Self- and proxy-reported impaired social interaction in young adults with simple congenital heart defects.
Simple Congenital Heart Defects such as septal defects constitute a large proportion of Congenital Heart Defects. New research has demonstrated more co-morbidities than previously thought. In particular, co-morbidities involving neurocognitive, psychiatric, and social difficulties have been described. Neurocognitive and psychiatric morbidities affect social interaction. Social interaction is important in everyday social life (education, work life, family life). In this study, we investigated social interaction through self- and proxy-answered Social Responsiveness Scale 2 (SRS-2) in young adults with simple Congenital Heart Defects and compared their social interaction profile to healthy matched controls. We included a total of 80 patients with either atrial or ventricular septal defect (age 26.6 years) and 38 heart-healthy, age, sex, and ISCED educational matched controls (age: 25.3 years). A close relative proxy from each participant took part in the study as well. All participants answered the Social Responsiveness Scale 2 (SRS-2) (n = 225). Our primary and secondary outcomes were the SRS-2 Total score and the SRS-2 sub-scores. In the Congenital Heart Defects group, 31.3% had a Total score above 60 compared to 7.9% in the control group (p = 0.005, RR = 3.96). The participants with a septal defect had a higher Total score (52.5 vs. 45.5, p = 0.004), a higher Social Cognition sub-score (55.0 vs. 47.0, p = 0.0004), and a higher Social Motivation sub-score (50.0 vs. 45.0, p = 0.003) than the heart-healthy participants. We found no difference between the two groups regarding the sub-scores of Social Awareness and Social Communication. A multiple linear regression model showed that the variable that explained most of the variation in Total Score was having a previously diagnosed psychiatric disorder. We found that young adults with atrial or ventricular septal defects have a fourfold increased risk of social interaction difficulties compared to heart-healthy peers. They have a social interaction profile, with difficulties in social cognition and social motivation, and preserved social awareness and social communication. Psychiatric morbidity explained most of the variation in social interaction problems. As social difficulties and psychiatric morbidities are intertwined, social interaction difficulties could be an indication of already underlying psychiatric morbidities or a risk factor for future psychiatric morbidity.


Immunosuppressor factor(s) produced by decidua-associated suppressor cells: a proposed mechanism for fetal allograft survival.
Mechanisms that explain failure of rejection of the antigenic fetus by the mother appear to lie at the fetomaternal interface. Successful pregnancies have been correlated with the presence of decidua-associated suppressor cells. Supernatants from these cells were tested for their ability to suppress the proliferation of interleukin 2-dependent cells and were also subjected to high-performance liquid chromatography. Decidual supernatant was found to have peak suppressive activity at two molecular weights (43,000 and 21,000 daltons). The activity of decidual supernatant was directed specifically at interleukin 2-dependent cells and interfered with interleukin 2 action. The importance of this mechanism in graft rejection is well known. Decidual supernatant may thus prevent fetal allograft rejection by preventing the maternal cytotoxic effectors from receiving the interleukin 2-dependent help that they need to proliferate and remain actively cytolytic.


Impact of Internal Carotid Stenosis Treatment on Cerebral Blood Flow Volume: A Comparative Study between Preoperative and Postoperative Values.
BACKGROUND Among patients with ICA stenosis, there are some cases with elevated, undisrupted, and diminished cerebral blood flow (CBF). The aim of this study was to assess the influence of ICA stenosis treatment on postoperative CBF changes in relation to preoperative CBF values. MATERIAL AND METHODS We qualified 58 patients ≥65 years old (28 males, 30 females, mean age 71.02±6.34 years) for surgical intervention due to symptomatic ≥70% ICA stenosis. In all patients, a flow volume in all extracranial arteries (internal carotid [ICA], external carotid [ECA], and vertebral arteries [VA]) was measured preoperatively and 2-3 days following the surgery. The CBF values were compared with the ones established for a healthy population of the same age. RESULTS Preoperatively, there were 3 subgroups of patients, comparing to healthy population: with elevated CBF - "significant compensation," with undisrupted CBF - "mild compensation," and with diminished CBF - "no compensation." Postoperatively, a significant CBF increase was observed in patients with preoperative "no" and "mild compensation" - 277.18±154.26 ml/min (P=0.0000001) and 221.56±98.8 ml/min (P=0.0000001). In a "significant compensation" group, there was no flow increase observed (CBF change of 2.57±58.5 ml/min, P=0.954) - a redistribution of flow was observed. CONCLUSIONS In patients with lower preoperative CBF values, surgical treatment caused a significant increase in global cerebral inflow, which was more prominent in patients with the lowest preoperative CBF. In patients with high preoperative CBF, surgical treatment resulted in a flow redistribution, but did not cause a CBF increase. Volumetric flow assessment in DUS can predict hemodynamic benefit from surgery in terms of CBF increase.


Gastrointestinal manifestations of diabetic ketoacidosis.
The evaluation of gastrointestinal symptoms in patients with diabetic acidosis frequently challenges the physician's clinical acumen. Faced with a seriously ill patient, he must judge whether the abdominal pain, nausea, or vomiting are a consequence of the metabolic decompensation, and hence likely to resolve with correction of the ketoacidosis, or if these symptoms signal a serious underlying intra-abdominal process (e.g., cholecystitis, appendicitis, etc.) which may have precipitated the development of ketoacidosis. The pathogenesis of the reversible gastrointestinal symptoms which frequently accompany diabetic acidosis has not been rigorously defined and may be multifactorial, involving metabolic, humoral, and neural processes. Careful attention to the medical history and abdominal examination greatly facilitates distinguishing patients with intra-abdominal pathology from those with reversible symptoms secondary to ketoacidosis. Similarly, the judicious use of laboratory tests (electrocardiography, blood counts, urinalysis, serum enzyme profile, and abdominal roentgenograms) materially aids in differential diagnosis. Finally, clinical suspicion of an acute abdominal process should prompt early surgical consultation and, if required, surgical intervention as the acidosis is being brought under control.