[Association between eating behavior and nutritional status in Chilean preschoolers].
INTRODUCCIÓN: the eating behavior is associated with the nutritional status at early ages. However, in Chile there are still no studies that evaluate this relationship in the preschool stage. to associate the nutritional status and eating behavior of Chilean preschoolers. cross-sectional study in 247 preschoolers (2-4 years) from the region of Araucanía, Chile. The nutritional status was evaluated through the anthropometric index weight/height and waist circumference/age. The Child Eating Behavior Questionnaire (CEBQ) survey was applied to mothers to assess their children's eating. one hundred and thirty were men and 117 were women with an overweight/obese percentage of 58.6% and 49.6%, respectively. Eating behavior scores pro-intake (food approach) have a positive and significant association with nutritional status) and in the food responsiveness sub-scale in the total sample. Regarding the anti-intake score (food avoidant), an inverse trend with nutritional status is shown; however, there is a negative and significant association in the satiety responsiveness scale and slowness in eating. the pro-intake eating behavior is directly associated with nutritional status, and anti-ingest score is inversely related only to certain sub-scales.


[Influence of capsaicin treating sciatic nerve on the pain threshold and the effect of acupuncture analgesia of rats].
The model of local application of 1.5% Capsaicin (Cap) on the right sciatic nerve and control of Vehicle (Veh) on the left were used. The influence of Cap on pain threshold, electroacupuncture (EA) analgesia and Fluoride-resistant acid phosphatase (FRAP) activity in the dorsal horn of spinal cord were observed. The results showed, the pain threshold of Cap treatment side rose significantly compared with the control side, FRAP in dorsal horn of spinal cord vanished, and the analgesic effect of EA at "Huantiao" of the Cap treatment side markedly decreased, compared with not only that EA at the control side but also that EA before Cap treatment. It is indicated that the C fibers of the primary afferent participate in the input of pain and EA analgesic information.


Pre-analytical issues for testosterone and estradiol assays.
In order to standardize and harmonize testosterone measurement, it is vital to identify and minimize pre-analytical error as well as standardize them when developing reference intervals. These pre-analytic issues can be separated into technical and biological factors. Technical factors to address are the type of sample (serum vs. plasma), the type of collection tube, and the processing, storage, and handling of the samples. Biological issues include addressing the age of the subject, the time of day and month the sample is drawn, and all of the possible interfering drugs the subject may be taking. We recommend that great attention be paid to these pre-analytical issues before the assay methodologies are harmonized.


Accounting for sex differences as a continuous variable in cancer treatments.
The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We propose that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- skewed extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our translational goal should be adaptation of treatment to the variable sex-effect on targetable pathways. To develop a tool that could advance this goal, we applied a Bayesian Nearest Neighbor (BNN) analysis to 8370 cancer transcriptomes from 26 different adult and 4 different pediatric cancer types to establish patient-specific Transcriptomic Indices (TI). TI precisely positions a patient's whole transcriptome on axes of mechanistic phenotypes like cell cycle signaling and immunity that exhibit skewing in the cancer population relative to sex-identified extremes (poles). Importantly, the TI approach reveals that even when TI values are identical, underlying mechanisms in male and female individuals can differ in identifiable ways. Thus, cancer type, patient sex, and TI value provides a novel and patient- specific mechanistic identifier that can be used for precision cancer treatment planning.


Dichotomy between serum free triiodothyronine and free thyroxine concentrations in familial thyroxine-binding globulin deficiency.
The mean serum total T4 (3.2 +/- 1.0 micrograms/100 ml) and T3 levels (83 +/- 29 ng/100 ml) in eight euthyroid patients with T4-binding globulin (TBG) deficiency from two families were significantly lower than those in either the unaffected relatives (P less than 0.05) or the control subjects (P less than 0.01). The lowest T4 and T3 values were found in the four hemizygotes (2.4 +/- 0.2 micrograms/100 ml and 69 +/- 25 ng/100 ml, respectively). In contrast to the absolute T4 and T3 levels, the mean percentages of free T4 and free T3 in the affected members were about twice as high as those in either the unaffected relatives or the controls. Despite an elevated percentage of free T4 in each of the TBG-deficient members, the mean absolute free T4 (FT4) level (0.89 +/- 0.20 ng/100 ml) was significantly lower than those in both control groups [1.31 +/- 0.2 ng/100 ml (P less than 0.02) and 1.24 +/- 0.30 ng/100 ml (P less than 0.01), respectively]. Serum FT4 levels were subnormal in three of four hemizygotes. In contrast to FT4, the mean FT3 level in the affected members (0.33 +/- 0.04 ng/100 ml) was significantly higher than that in either the nondeficient relatives (0.25 +/- 0.02 ng/100 ml; P less than 0.02) or the control subjects (0.26 +/- 0.04 ng/100 ml; P less than 0.02), whereas the ratio of FT3 to FT4 was about twice as high. The data suggest that in TBG deficiency, euthyroidism in maintained by a subtle equilibrium between low FT4 and high FT3 levels.


Knock down of caveolin-1 affects morphological and functional hallmarks of human endothelial cells.
Caveolin-1 (CAV1) is the principal structural component of caveolae which functions as scaffolding protein for the integration of a variety of signaling pathways. In this study, we investigated the involvement of CAV1 in endothelial cell (EC) functions and show that siRNA-induced CAV1 silencing in the human EC line EA.hy926 induces distinctive morphological changes, such as a marked increase in cell size and formation of stress fibers. Design-based stereology was employed in this work to make unbiased quantification of morphometric properties such as volume, length, and surface of CAV1 silenced versus control cells. In addition, we showed that downregulation of CAV1 affects cell cycle progression at G1/S phase transition most likely by perturbation of AKT signaling. With the aim to assess the contribution of CAV1 to typical biological processes of EC, we report here that CAV1 targeting affects cell migration and matrix metalloproteinases (MMPs) activity, and reduces angiogenesis in response to VEGF, in vitro. Taken together our data suggest that the proper expression of CAV1 is important not only for maintaining the appropriate morphology and size of ECs but it might represent a prospective molecular target for studying key biological mechanisms such as senescence and tumorigenesis.


Case report of an alleviation of pain symptoms in hypnic headache via greater occipital nerve block.
Background Hypnic headache is a rare primary headache disorder with a few hundred described cases so far. Due to the fact that this headache disease is rare, there are no placebo-controlled oral medication studies. After all reported oral medication failed to control pain symptoms of a hypnic headache disease, we were able to reduce pain intensity and frequency via two greater occipital nerve (GON) blocks. Case We report on a 74-year-old patient diagnosed with hypnic headache in our headache outpatient department two years ago. Over a course of nine months none of the recommended oral drugs had an effect in pain alleviation and we decided to try an occipital nerve injection therapy. Two GON-blocks then led to a stable and significant pain reduction over the course of six months during monthly follow-ups. Conclusion GON block can be a successful therapeutic approach for the treatment of hypnic headache when oral medication fails.


Long-Acting Reversible Contraception: An Essential Guide for Pediatric Primary Care Providers.
Long-acting reversible contraception (LARC) methods are 20% more effective than traditional contraceptives and are recommended by the American Academy of Pediatrics and American College of Obstetrics and Gynecology as first-line contraception for adolescent girls. Large studies show that LARC use reduces unintended pregnancies, increases user satisfaction, and prolongs duration of use. This article prepares the primary care provider (PCP) with knowledge on safety, efficacy, eligibility, confidentiality, anticipatory guidance, how to find a LARC provider, and guidance on common side effects so the PCP can confidently counsel adolescent patients on LARC methods.


Sarcoidosis-Lymphoma Syndrome Presenting As Bony Vertebral Metastasis: A Case Report and Literature Review.
Sarcoidosis preceding a diagnosis of lymphoma has been a reported phenomenon termed sarcoidosis-lymphoma syndrome. Skeletal metastasis is extremely rare. Here, we detail a case of sarcoidosis-lymphoma syndrome presenting as a lumbar vertebral metastasis with suspected associated intracranial lesions. A 72-year-old man with a history of follicular lymphoma presented with symptomatic central nervous system (CNS) lesions with concurrent lumbar vertebral metastases visualized with CT and MRI. Rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) with dexamethasone treatment resulted in significant radiographic regression of his intracranial lesions with dramatic symptomatic improvement. Out of concern for compression fracture of his lytic lumbar lesions, kyphoplasty with biopsy was performed showing lymphocytes that were positive for cluster-of-differentiation 10 (CD10), CD20, and B-cell lymphoma 2 (Bcl2). The patient was diagnosed with CNS and vertebral sarcoidosis-lymphoma syndrome and began treatment with high-dose methotrexate. Including the present case, only four occurrences of sarcoidosis-lymphoma syndrome with bony involvement have been described. We detail our own experience and summarize all previous literature. While rare, sarcoidosis-lymphoma may present with CNS and lytic bone involvement; in these cases, symptomatic severity, as well as an effective response to steroid treatment, underscore the importance of an accurate and prompt diagnosis.


Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast.
Signaling mucins are cell adhesion molecules that activate RAS/RHO guanosine triphosphatases and their effector mitogen-activated protein kinase (MAPK) pathways. We found that the Saccharomyces cerevisiae mucin Msb2p, which functions at the head of the Cdc42p-dependent MAPK pathway that controls filamentous growth, is processed into secreted and cell-associated forms. Cleavage of the extracellular inhibitory domain of Msb2p by the aspartyl protease Yps1p generated the active form of the protein by a mechanism incorporating cellular nutritional status. Activated Msb2p functioned through the tetraspan protein Sho1p to induce MAPK activation as well as cell polarization, which involved the Cdc42p guanine nucleotide exchange factor Cdc24p. We postulate that cleavage-dependent activation is a general feature of signaling mucins, which brings to light a novel regulatory aspect of this class of signaling adhesion molecule.


Endoscopic colloid cyst resection in the absence of ventriculomegaly.
The absence of ventriculomegaly has been considered an overt or relative contraindication to the endoscopic resection of colloid cysts. In the past, endoscopic removal of colloid cysts in the absence of ventriculomegaly has been considered ill advised. Reports of successful endoscopic surgery in small ventricles are surfacing. We examined the combined experience of 2 high-volume endoscopic centers to characterize the outcomes of patients undergoing endoscopic removal of colloid cysts in small ventricles. We retrospectively reviewed all endoscopic colloid cyst removal procedures by the 2 senior authors (P.N., C.T.) performed at the Barrow Neurological Institute over an 8-year period. Radiographic, clinical, and interview data were recorded and analyzed. The age-adjusted relative bicaudate index was used to define small ventricles. Sixteen patients (8 female) underwent attempted endoscopic removal of a colloid cyst in the absence of ventriculomegaly. Surgery was technically successful in 15 patients. The cyst was removed completely in 13 of patients. Short-term memory loss was initially present in 3 patients and completely resolved in all but 1 patient who had presented with short-term memory loss. Temporary complications occurred in 2 patients. Normal-size ventricles are not a contraindication to endoscopic removal of third ventricular colloid cysts. Complication rates are at least comparable to those of patients with ventriculomegaly or to those undergoing open microsurgical resection.


Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T--comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model.
To develop a new macroscopic scoring system which allows for an overall judgment of experimental articular cartilage repair and compare it with four existing scoring systems and high-field magnetic resonance imaging (MRI). A new macroscopic scoring system was developed to assess the repair of cartilage defects. Cartilage repair was graded by three observers with different experience in cartilage research at 2-3 time points and compared with the protocol A of the international cartilage repair society (ICRS) cartilage repair assessment score, the Oswestry arthroscopy score, and macroscopic grading systems designed by Jung and O'Driscoll. Parameters were correlated with the two-dimensional (2D) magnetic resonance observation of cartilage repair tissue (MOCART) score based on a 9.4 T MRI as an external reference standard. All macroscopic scores exhibited high intra- and interobserver reliability and high internal correlation. The newly developed macroscopic scoring system had the highest intraobserver [0.866 ≤ intraclass correlation (ICC) ≤ 0.895] and the highest interobserver reliability (ICC = 0.905) for "total points". Here, Cronbach's alpha indicated good homogeneity and functioning of the items (mean = 0.782). "Total points" of the 2D MOCART score correlated with all macroscopic scores (all P < 0.0001). The newly developed macroscopic scoring system yielded the highest correlation for the MRI parameter "defect fill" (rho = 0.765; all P < 0.0001). "Total points" and "defect fill", two clinically relevant indicators of cartilage repair, can be reliably and directly assessed by macroscopic evaluation, using either system. These data support the use of macroscopic assessment to precisely judge cartilage repair in preclinical large animal models.


Communication rehabilitation in sub-Saharan Africa: A workforce profile of speech and language therapists.
There is an urgent global need to strengthen rehabilitation services for people with disabilities. In sub-Saharan Africa, rehabilitation services for people with communication disabilities continue to be underdeveloped. A first step in strengthening services for people with a communication disabilities is to understand the composition and conditions of the current workforce. This research describes a sample of the speech and language therapists (SLTs) working in SSA (excluding South Africa). This study explores the characteristics of this workforce, including their demographics, education, experience and geographical stability. A mixed-methods survey was used to collect data from SLTs within Anglophone countries of SSA. Completed surveys were received from 33 respondents working in 44 jobs across nine countries. Analysis included descriptive and non-parametric inferential statistics. This study reports on a subset of descriptive and quantitative data from the wider survey. A background profile of SLTs across the region is presented. Results indicated that the workforce of SLTs comprised a mix of local and international SLTs, with university-level education. Local SLTs were educated both within and outside of Africa, with more recent graduates trained in Africa. These data reflected the local emergence of speech and language therapy training in SSA. This sample comprised a mix of African and international SLTs, with indications of growing localisation of the workforce. Workforce localisation offers potential advantages of linguistic diversity and stability. Challenges including workforce support and developing culturally and contextually relevant SLT practices are discussed.


Poor data stewardship will hinder global genetic diversity surveillance.
Genomic data are being produced and archived at a prodigious rate, and current studies could become historical baselines for future global genetic diversity analyses and monitoring programs. However, when we evaluated the potential utility of genomic data from wild and domesticated eukaryote species in the world's largest genomic data repository, we found that most archived genomic datasets (86%) lacked the spatiotemporal metadata necessary for genetic biodiversity surveillance. Labor-intensive scouring of a subset of published papers yielded geospatial coordinates and collection years for only 33% (39% if place names were considered) of these genomic datasets. Streamlined data input processes, updated metadata deposition policies, and enhanced scientific community awareness are urgently needed to preserve these irreplaceable records of today's genetic biodiversity and to plug the growing metadata gap.


Oligosaccharides from Traditional Chinese Herbal Medicines: A Review of Chemical Diversity and Biological Activities.
Most of traditional Chinese herbal medicine (TCHM) substances come from medicinal plants, among which oligosaccharides have gradually attracted widespread attention at home and abroad due to their important biological activities and great medicinal potential. Numerous in vitro and in vivo experiments exhibited that oligosaccharides possess various activities, such as antitumor, anti-oxidation, modulate the gut microflora, anti-inflammatory, anti-infection, and immune-regulatory activities. Generally, biological activities are closely related to chemical structures, including molecular weight, monosaccharide composition, glycosidic bond connection, etc. The structural analysis of oligosaccharides is an important basis for studying their structure-activity relationship, but the structural diversity and complexity of carbohydrate compounds limit the study of oligosaccharides activities. Understanding the structures and biological functions of oligosaccharides is important for the development of new bioactive substances with natural oligosaccharides. This review provides a systematic introduction of the current knowledge of the chemical structures and biological activities of oligosaccharides. Most importantly, the reported chemical characteristics and biological activities of the famous TCHM oligosaccharides were briefly summarized, including Morinda officinalis, Rehmannia glutinosa, Arctium lappa, Polygala tenuifolia, Panax ginseng, Lycium barbarum and Astragalus membranaceus. TCHM oligosaccharides play an important role in nutrition, health care, disease diagnosis and prevention as well as have broad application prospects in the field of medicine.


Research Progress of a Pesticide Polymer-Controlled Release System Based on Polysaccharides.
In recent years, with the development of the nanomaterials discipline, many new pesticide drug-carrying systems-such as pesticide nano-metal particles, nano-metal oxides, and other drug-carrying materials-had been developed and applied to pesticide formulations. Although these new drug-loading systems are relatively friendly to the environment, the direct exposure of many metal nanoparticles to the environment will inevitably lead to potential effects. In response to these problems, organic nanomaterials have been rapidly developed due to their high-quality biodegradation and biocompatibility. Most of these organic nanomaterials were mainly polysaccharide materials, such as chitosan, carboxymethyl chitosan, sodium alginate, β-cyclodextrin, cellulose, starch, guar gum, etc. Some of these materials could be used to carry inorganic materials to develop a temperature- or pH-sensitive pesticide drug delivery system. Herein, the pesticide drug-carrying system developed based on polysaccharide materials, such as chitosan, was referred to as the pesticide polymer drug-carrying system based on polysaccharide materials. This kind of drug-loading system could be used to protect the pesticide molecules from harsh environments, such as pH, light, temperature, etc., and was used to develop the function of a sustained release, targeted release of pesticides in the intestine of insects, and achieve the goal of precise application, reduction, and efficiency of pesticides. In this review, the recent progress in the field of polysaccharide-based polymer drug delivery systems for pesticides has been discussed, and suggestions for future development were proposed based on the current situation.


Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors among patients with heart failure with preserved ejection fraction.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended by the American Heart Association for management of heart failure with preserved ejection fraction (HFpEF), but little is known about their in-class comparative effectiveness in real-world settings. To assess the in-class comparative effectiveness of SGLT2i for preventing HF-related and all-cause hospitalizations among patients with HFpEF. Using MarketScan® Commercial and Medicare Supplemental research databases (2012-2020), this cohort study included adults with HFpEF treated with SGLT2i. Stabilized inverse probability treatment weighted Cox proportional hazards regression was used to compare HF-related and all-cause hospitalizations in three pairwise comparisons: dapagliflozin versus canagliflozin, empagliflozin versus canagliflozin, and dapagliflozin versus empagliflozin. Subgroup and sensitivity analyses were conducted to assess robustness of the main analysis. In total, 3629 SGLT2i users (881 dapagliflozin, 1120 canagliflozin, and 1628 empagliflozin) were included. Compared with canagliflozin, dapagliflozin was associated with decreased risk of HF-related hospitalization (adjusted hazard ratio [aHR], 0.75; 95% confidence interval [CI], 0.56-1.01) and all-cause hospitalization (aHR, 0.84; 95% CI 0.73-0.97). Compared with canagliflozin, empagliflozin was associated with 55% decreased risk of HF-related hospitalization (aHR, 0.45; 95% CI 0.34-0.59) and 18% decreased risk of all-cause hospitalization (aHR, 0.82; 95% CI 0.73-0.93). Compared with empagliflozin, dapagliflozin was associated with 50% increased risk of HF-related hospitalization (aHR, 1.50; 95% CI 1.09-2.07) and a statistically nonsignificant increase in the risk of all-cause hospitalization (aHR, 1.05; 95% CI 0.92-1.20). Compared with canagliflozin or dapagliflozin use, empagliflozin use was associated with decreased risk of HF-related and all-cause hospitalizations. Compared with canagliflozin, dapagliflozin was associated with a reduced risk of HF-related and all-cause hospitalizations.


Second re-irradiation for DIPG progression, re-considering "old strategies" with new approaches.
Diffuse intrinsic pontine glioma (DIPG) is an aggressive infiltrative glioma for which no curative therapy is available. Radiation therapy (RT) is the only potentially effective intervention in delaying tumor progression, but only transiently. At progression, re-irradiation is gaining popularity as an effective palliative therapy. However, at second progression, exclusive symptomatic treatment is usually offered. Here we report two patients with DIPG at second progression who were treated with a second re-irradiation course with good response. Importantly, treatment was well tolerated with no irradiation associated acute toxicity identified.


Two Diterpene Synthases for Spiroalbatene and Cembrene A from Allokutzneria albata.
Two bacterial diterpene synthases from the actinomycete Allokutzneria albata were investigated, resulting in the identification of the structurally unprecedented compound spiroalbatene from the first and cembrene A from the second enzyme. Both enzymes were thoroughly investigated in terms of their mechanisms by isotope labeling experiments, site-directed mutagenesis, and variation of the metal cofactors and pH value. For spiroalbatene synthase, the pH- and Mn2+ -dependent formation of the side product thunbergol was observed, which is biosynthetically linked to spiroalbatene.


[A nutrition survey of a group of athletes with particular reference to magnesium, zinc and copper intake, and to the relative intra- and extra-cellular levels].
The aim of the present study was to evaluate the dietary habits in a group of athletes (footballers) compared with sedentary subjects matched for sex, age and body mass index. All subjects kept a record of food eaten for seven consecutive days using various models for portion sizes. Daily nutrient intake was then computed and was expressed as either total intake, or percent of the recommended daily dietary allowances (LARN). For each subject, a 20-ml blood sample and a 24h urine sample was collected for analysis of magnesium, zinc and copper. The three elements were measured both in plasma and in erythrocytes, monocytes and neutrophils. The athletes eat significantly more sheets than controls (22.5% of total kcal vs 15.2%, p less than 0.01) and significantly less cereals (22.5% vs 31.7%, p less than 0.01). Concerning the nutrient composition, in both groups the lipid intake was higher than that recommended and this trend was more pronounced in the athletes (+ 43.2% vs + 16.1% in the controls). In addition, the diet was particularly rich in animal fats with a mean intake of 21.0% of total kcal in the athletes and 20.9% in the sedentary group (recommended value was 12.5% and 14%, respectively). A parallel reduction in vegetal protein intake was observed in the trained group, and the difference was significant (4.3% of kcal in the athletes and 5.2% in the controls, p less than 0.01). Furthermore, in the athletes the soluble carbohydrate intake was higher than the recommended levels (+ 110%) and significantly higher than that eaten by the controls (21.0% vs 16.4% of kcal, p less than 0.01), with parallel decrease of polysaccharides intake.(ABSTRACT TRUNCATED AT 250 WORDS)


Transannular [6 + 4] and Ambimodal Cycloaddition in the Biosynthesis of Heronamide A.
The transannular [6 + 4] cycloaddition proposed as a step in the biosynthesis of heronamide A has been modeled using density functional theory. The proposed cycloaddition is highly stereoselective, affording a single product. The reaction proceeds through an ambimodal transition state that directly leads to a [4 + 2] adduct in addition to the observed [6 + 4] adduct. Interconversion of these adducts is possible via a facile Cope rearrangement. The [6 + 4] adduct is thermodynamically more stable than the [4 + 2] adduct by 5.2 kcal mol(-1) due to a combination of the ring and steric strain in the [4 + 2] product. The results strongly support the plausibility of the proposed transannular [6 + 4] cycloaddition in the biogenesis of heronamide A and may provide insights to designing substrates that selectively undergo [6 + 4] cycloaddition to form unbridged 10-membered rings.


Dibutylone (bk-DMBDB): Intoxications, Quantitative Confirmations and Metabolism in Authentic Biological Specimens.
The number of emerging novel stimulants modified based on beta-keto variations of amphetamine-like substances continues to rise. Dibutylone reports described in the medical and toxicological literature are limited, therefore little information is available in terms of quantitative confirmation or metabolism. During this study, authentic human specimens, including blood, urine, vitreous humor, oral fluid and liver were quantitatively and qualitatively analyzed for the presence of dibutylone and butylone, with paired case history and demographic information. Dibutylone concentrations were variable across all specimen types, specifically ranging from 10 to 1,400 ng/mL in postmortem blood specimens. The metabolic profile of dibutylone was mapped by in vitro incubation with human liver microsomes (HLM). Samples were analyzed using a SCIEX TripleTOF® 5600+ quadrupole time-of-flight mass spectrometer. Data processing was conducted using MetabolitePilot™. Authentic human specimens, including blood, urine, vitreous humor, oral fluid and liver, were utilized for in vivo verification of five HLM-generated metabolites in analytically confirmed cases of dibutylone use. Butylone was confirmed as a metabolite of dibutylone, but issues involving co-ingestion of these two novel stimulants or potential co-existence from synthesis lead to ineffectiveness as a true biomarker. Hydrogenation of the beta-ketone of dibutylone resulted in the most prominent metabolite found in human specimens, and its uniqueness to dibutylone over other stimulants leads to its classification as an appropriate biomarker for dibutylone ingestion. This is the first study to map the metabolic profile of dibutylone, including verification in authentic specimens, confirming metabolic conversion to butylone and identifying biomarkers more useful in forensic toxicological drug testing.


Anal canal and rectal condylomatosis: exhaustive proctological examination and STD patients.
Infection of the anorectal area with some subtypes of HPV virus results in local involvement that appears as warty, papillary, condylomatous lesions. Patients exposed to high-risk HPV types, such as HPV-16, -18, and -31, are at risk for developing high-grade dysplasias or carcinomas. We reviewed 15 years (1991 - 2006) of patient records from our proctological unit and STD center and found 1,122 patients affected by anorectal condylomatosis. This study supports the importance of an exhaustive proctological examination in patients suffering from condylomatosis of the genital area, especially of the perianal zone, and in patients examined in the STD clinic, even for other reasons. An unknown anorectal condylomatosis is a frequent cause of relapse of anogenital warts. Anal warts should be examined by proctoscopy to assess the full extent of the lesions and prevent possible complications.


Mechanisms of aortic smooth muscle hyporeactivity after prolonged hypoxia in rats.
The aim of this study was to determine whether the effects of hypoxia on aortic contractility reflect a decrease in smooth muscle activation [phosphorylation of the 20-kDa myosin regulatory light chain (LC(20))], the capacity for myofibrillar ATP hydrolysis (mATPase activity), or both. Our results indicate that, in endothelium-denuded aortic rings from rats exposed to hypoxia for 48 h (inspired O(2) concentration = 10%), contractions to phenylephrine and potassium chloride (KCl) are impaired compared with rings from normoxic rats. The proportion of phosphorylated to total LC(20) during aortic contraction induced by 10(-5) M phenylephrine was reduced after hypoxia (51.4 +/- 5.4% in normoxic control rats vs. 32.5 +/- 4.7% in hypoxic rats, P < 0.01). Aortic mATPase activity was also decreased (maximum ATPase rate = 29.6 +/- 3.4 and 20.7 +/- 3.7 nmol. min(-1). mg protein(-1) in control and hypoxic rats, respectively, P < 0.05). Neither proliferation nor dedifferentiation of aortic smooth muscle was evident in this model; immunostaining for smooth muscle expression of the proliferating cell nuclear antigen was negative and smooth muscle-specific isoforms of myosin heavy chains, h-caldesmon, and calponin were increased, not decreased, after hypoxic exposure. Decreased aortic reactivity after hypoxia is associated with both impairment of smooth muscle activation and diminished capacity of the actomyosin complex, once activated, to hydrolyze ATP. These changes cannot be attributed to smooth muscle dedifferentiation or to reduced contractile protein expression.


Induction of cytokines and chemokines by Toll-like receptor signaling: strategies for control of inflammation.
Recognition of the pathogen-associated molecular pattern (PAMP) by host Toll-like receptors (TLR) is an important component of the innate immune response for countering against invading viruses, bacteria, and fungi. Upon PAMP recognition, the TLR induces intracellular signaling cascades that involve adapter, signalosome, and transcription factor complexes and result in the production of both pro- and anti-inflammatory cytokines and chemokines. An inflammatory response for a short duration can be beneficial because it helps to clear the infectious agent. However, prolonged inflammation can be detrimental because it may cause host toxicity and tissue damage. Indeed, excessive production of inflammatory cytokines and chemokines via TLR pathways is often associated with many inflammatory and autoimmune diseases. Therefore, fine control of inflammation in the TLR pathway is highly desirable for effective host defense. In this article, we review intrinsic control mechanisms that include a balance between pro-inflammatory and anti-inflammatory cytokines and chemokines, production of host effectors, and regulation at the level of adapter, signalosome, and transcription factor complexes in the TLR pathways. We also discuss how understanding of the TLR signaling steps leads to the development of small-molecule drugs that can interfere with the formation of active adapter, signalosome, and adapter complexes.


Multi-chord IR-visible two-color interferometer on KSTAR.
Major parts of an IR-visible two-color interferometer (TCI) on KSTAR have been upgraded for the multi-chord operation: (1) a diode-pumped-solid-state (DPSS) laser (660 nm) replacing the former HeNe laser (633 nm), (2) vacuum-compatible vibration isolator with titanium retro-reflectors, and (3) full digital phase comparator for multi-chord real-time density signals. The commercial compact DPSS laser suits the multiple chord configuration with its strong beam power (500 mW) and long coherent length (>100 m). Ti retro-reflectors are mounted on vacuum-compatible vibration isolators. The isolators are essential for the visible beams to avoid any fringe skips due to their short wavelength, considering the speed of the mechanical vibration (up to hundreds of μm). Field-programmable-gate-array (FPGA) modules count the entire fringes fast enough with a signal output rate up to 1.25 MHz, solving the fringe skip issues. The FPGA module enables the full digital processing of the phase comparator with a CORDIC algorithm after the sampling rate of 160 MS/s for the 40 MHz intermediate frequency of each beam. The full digital signals are transferred to the main plasma control system in real-time. Stable single-input-single-output operation of the KSTAR density control was demonstrated with the TCI. The real-time density profile control is also promising in the near future, with multiple actuators such as pellets and gas puffings.


Proportional hazards model with a change point for clustered event data.
In many epidemiology studies, family data with survival endpoints are collected to investigate the association between risk factors and disease incidence. Sometimes the risk of the disease may change when a certain risk factor exceeds a certain threshold. Finding this threshold value could be important for disease risk prediction and diseases prevention. In this work, we propose a change-point proportional hazards model for clustered event data. The model incorporates the unknown threshold of a continuous variable as a change point in the regression. The marginal pseudo-partial likelihood functions are maximized for estimating the regression coefficients and the unknown change point. We develop a supremum test based on robust score statistics to test the existence of the change point. The inference for the change point is based on the m out of n bootstrap. We establish the consistency and asymptotic distributions of the proposed estimators. The finite-sample performance of the proposed method is demonstrated via extensive simulation studies. Finally, the Strong Heart Family Study dataset is analyzed to illustrate the methods.


Receptor plasticity in the human brain: some autoradiographic studies.
Receptor modifications in human postmortem material were studied by quantitative autoradiography. Alterations of several neurotransmitter receptors in neurodegenerative diseases such as senile dementia and Huntington's chorea, in lesions of specific brain pathways, like the visual pathway or after drug treatments, were examined. In all these situations alterions of the density or localization of receptors were seen using autoradiography. The results suggest that several mechanisms of receptor adaptation operate in the human brain. These mechanisms include: compensatory changes in receptor density as a consequence of cell loss, in some cases preceding the neuropathological changes; differential alterations in receptors depending on their location in a given pathway, for example in the visual pathway or selective homologous or heterologous modification of receptors after drug treatment.


Basics of Compounding: Standardization of Compounded Medications.
The feasibility of standardizing concentrations of compounded drug preparations to attempt to minimize adverse events of both nonsterile and sterile compounded preparations has been discussed. It is critical that a wide variety of opinions and potential "unintended consequences" be aired in the public before an issue like this is recommended to become a standard. In this article, we combine the thoughts and recommendations of many practicing compounding pharmacists from both community and hospital practice sites that have contributed to this topic through the International Journal of Pharmaceutical Compounding's Compounders' Network List, a complimentary listserve for our subscribers to share information; ask questions; and provide answers, comments, and opinions. We discuss the advantages, disadvantages, and unintended consequences of standardized concentrations and provide input from numerous practitioners who are "on the front lines" daily.


Binding characteristics of thyroxin binding globulin in serum of normal, pregnant, and severely ill euthyroid patients.
Serum from normal, pregnant, and severely ill patients was stripped of endogenous thyroid hormones and diluted 1100-fold in barbital buffer. We then used it to study the binding characteristics of thyroxin binding globulin (TBG), noting significant differences in binding capacities among the groups. The mean (+/- SD) triiodothyronine/thyroxin ratio for binding capacity was 18 +/- 4 for normal subjects. The ratio was significantly increased in pregnant patients, 21 +/- 4 (p less than 0.05), and significantly lower in severely ill patients, 12 +/- 4 (p less than 0.05). When serum was diluted before assay, to give a uniform TBG concentration among groups, these apparent differences in binding characteristics were eliminated. It therefore is unlikely that different molecular species of TBG account for the variations in binding characteristics in these clinical states. Apparently, the distribution of thyroxin and triiodothyronine among the binding sites on TBG changes with variations in TBG concentration. This may explain the discrepancies observed in the concentrations of free thyroid hormones as estimated by various methodologies.


Core binding factor beta plays a critical role by facilitating the assembly of the Vif-cullin 5 E3 ubiquitin ligase.
The HIV-1 virion infectivity factor (Vif) targets the cellular cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) for degradation via the host ubiquitin-proteasome pathway. Vif recruits a cellular E3 ubiquitin ligase to polyubiquitinate A3G/F. The activity of Vif critically depends on the cellular core binding factor beta (CBFβ). In this study, we investigated the Vif-CBFβ interaction and the role of CBFβ in the E3 ligase assembly. Vif-CBFβ interaction requires an extensive region of Vif spanning most of its amino terminus and zinc finger region, and cullin 5 (Cul5) binding enhances the stability of the Vif-CBFβ interaction. Our results further demonstrate that CBFβ plays a critical role in facilitating Cul5 binding to the Vif/elongin B/elongin C complex. Vif, with or without bound substrate, is unable to bind Cul5 in the absence of CBFβ. These studies support the notion that CBFβ serves as a molecular chaperone to facilitate Vif-E3 ligase assembly. The host antiviral restriction factors A3G/F inhibit viral replication. The HIV-1 protein Vif targets A3G/F for degradation. This immune evasion activity of Vif is dependent on the cellular factor CBFβ. Multiple regions of Vif are known to be important for Vif function, but the mechanisms are unclear. The studies described here provide important information about the Vif-CBFβ interaction interface and the function of CBFβ in E3 ligase assembly. In particular, our comprehensive Vif-CBFβ interface mapping results help to delineate the role of various Vif regions, determining if they are important for binding CBFβ or A3G/F. Furthermore, our studies reveal an important potential mechanism of CBFβ that has not been shown before. Our results suggest that CBFβ may serve as a molecular chaperone to enable Vif to adopt an appropriate conformation for interaction with the Cul5-based E3 ligase. This study advances our understanding of how CBFβ facilitates the Vif-mediated degradation of APOBEC3 proteins.


UV cross-linking of polypeptides associated with 3'-terminal exons.
Association of nuclear proteins with chimeric vertebrate precursor RNAs containing both polyadenylation signals and an intron was examined by UV cross-linking. One major difference in cross-linking pattern was observed between this chimeric precursor RNA and precursors containing only polyadenylation or splicing signals. The heterogeneous nuclear ribonucleoprotein (hnRNP) polypeptide C cross-linked strongly to sequences downstream of the A addition site in polyadenylation precursor RNA containing only the polyadenylation signal from the simian virus 40 (SV40) late transcription unit. In contrast, the hnRNP C polypeptide cross-linked to chimeric RNA containing the same SV40 late poly(A) cassette very poorly, at a level less than 5% of that observed with the precursor RNA containing just the poly(A) site. Observation that cross-linking of the hnRNP C polypeptide to elements within the SV40 late poly(A) site was altered by the presence of an upstream intron suggests differences in the way nuclear factors associate with poly(A) sites in the presence and absence of an upstream intron. Cross-linking of C polypeptide to chimeric RNA increased with RNAs mutated for splicing or polyadenylation consensus sequences and under reaction conditions (high magnesium) that inhibited polyadenylation. Furthermore, cross-linking of hnRNP C polypeptide to precursors containing just the SV40 late poly(A) site was eliminated in the presence of competing poly(U); polyadenylation, however, was unaffected. Correlation of loss of activity with high levels of hnRNP C polypeptide cross-linking raises questions about the specificity of the interaction between the hnRNP C polypeptide and polyadenylation precursor RNAs in vitro.


[Studies on the influence of pentosanepolysulfate and a combination of pentosanepolysulfate, metamizol and paracetamol on inflammatory liability (author's transl)].
The influence of pentosanepolysulfate (SP 54) and a combination of pentosanepolysulfate, metamizol and paracetamol (Probaphen) on the course of an experimentally induced erythema caused by intracutaneous injection of a lipopolysaccharide from Pseudomonas has been studied in man. The intramuscular injection of Probaphen as well as SP 54, separately given, showed a significant antiinflammatory effect. A similar effect was also achieved after administration of Probaphen suppositories. Probaphen shortened the inflammatory reaction more effectively than did SP 54 alone. The oral application of Probaphen, however, did not influence the course of inflammation.


Population genetic structure of Anopheles arabiensis (Diptera: Culicidae) in a rice growing area of central Kenya.
Studies were conducted to examine the population genetic structure of Anopheles arabiensis (Patton) in Mwea Rice Irrigation Scheme and surrounding areas in Central Kenya, under different agricultural systems. This study was motivated by observed differences in malaria transmission indices of An. arabiensis within the scheme compared with adjacent nonirrigated areas. Agricultural practices can modify local microclimate and influence the number and diversity of larval habitats and in so doing may occasion subpopulation differentiation. Thirty samples from each of the three study sites were genotyped at eight microsatellite loci. Seven microsatellite loci showed high polymorphism but revealed no genetic differentiation (FST = 0.006, P = 0.312) and high gene flow (Nm = 29-101) among the three populations. Genetic bottleneck analysis showed no indication of excess heterozygosity in any of the populations. There was high frequency of rare alleles, suggesting that An. arabiensis in the study area has a high potential of responding to selective pressures from environmental changes and vector control efforts. These findings imply that An. arabiensis in the study area occurs as a single, continuous panmictic population with great ability to adapt to human-imposed selective pressures.


Non-Model-Based Control of a Wheeled Vehicle Pulling Two Trailers to Provide Early Powered Mobility and Driving Experiences.
Non-model-based control of a wheeled vehicle pulling two trailers is proposed. It is a fun train for disabled children consisting of a locomotive and two carriages. The fun train has afforded opportunities for both disabled and able bodied young people to share an activity and has provided early driving experiences for disabled children; it has introduced them to assistive and powered mobility. The train is a nonlinear system and subject to nonholonomic kinematic constraints, so that position and state depend on the path taken to get there. The train is described, and then, a robust control algorithm using proportional-derivative filtered errors is proposed to control the locomotive. The controller was not dependent on an accurate model of the train, because the mass of the vehicle and two carriages changed depending on the number, size, and shape of children and wheelchair seats on the train. The controller was robust and stable in uncertainty. Results are presented to show the effectiveness of the approach, and the suggested control algorithm is shown to be acceptable without knowing the exact plant dynamics.


Influence of participant and reviewer characteristics in application scores for a hematology research training program.
The American Society of Hematology Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. The objectives were to compare application scores based on applicant and reviewer sex and underrepresented minority (URM) status. We included applications to CRTI from 2003 to 2019. The application scores were transformed into a scale from 0 to 100 (100 was the strongest). The factors considered were applicant and reviewer sex and URM status. We evaluated whether there was an interaction between the characteristics and time related to application scores. In total, 713 applicants and 2106 reviews were included. There was no significant difference in scores according to applicant sex. URM applicants had significantly worse scores than non-URM applicants (mean [standard error] 67.9 [1.56] vs 71.4 [0.63]; P = .0355). There were significant interactions between reviewer sex and time (P = .0030) and reviewer URM status and time (P = .0424); thus, results were stratified by time. For the 2 earlier time periods, male reviewers gave significantly worse scores than did female reviewers; this difference did not persist for the most recent time period. The URM reviewers did not give significantly different scores across time periods. URM applicants received significantly lower scores than non-URM applicants. The impact of reviewer sex and URM status changed over time. Although male reviewers gave lower scores in the early periods, this effect did not persist in the late period. Efforts are required to mitigate the impact of applicant URM status on application scores.


A Five-Gene Signature Associated With DNA Damage Repair Molecular Subtype Predict Overall Survival for Hepatocellular Carcinoma.
Background: DNA damage repair (DDR) is an important mechanism for the occurrence and development of hepatocellular carcinoma (HCC), but its impact on prognosis has not been fully understood. Materials and methods: A total of 904 HCC patients were included in our study, TCGA (n = 370) and GSE14520 (n = 239) were merged into a large-sample training cohort (n = 609). The training cohort was clustered into C1 and C2 based on prognostic DDR-related genes, the differentially expressed genes (DEGs) between C1 and C2 were identified by the Wilcoxon signed-rank test referred to criteria (|log2FC|≥1 and FDR< 0.05). The univariate Cox analysis was used to screen the prognostic-related DEGs, and Lasso penalized Cox regression analysis was used to construct the risk score. The patients were clarified into high- and low-risk groups based on the median risk score. ICGC (n = 231) and GSE116174 (n = 64) cohorts were used for external validation of the risk score's prognostic value. Results: The Kaplan-Meier survival analysis showed that the high-risk group had a significantly reduced overall survival (OS) compared to the low-risk group in the three independent cohorts, and the time-dependent ROC curve showed that the five-gene (STMN1, PON1, PLOD2, MARCKSL1, and SPP1) risk score with a high accuracy in predicting OS. The patients with AFP >300 ng/ml, tumor poor differentiation (grade 3-4), micro and macro vascular tumor invasion, advanced stage (AJCC III-IV, BCLC stage B-C, and CLIP score >2) exhibited a higher risk score. Subgroup survival analysis found that the risk score was applicable to patients with different clinical characteristics. GO and KEGG functional enrichment analysis revealed that cell cycle, p53 signaling, TNF signaling-related pathways were upregulated in the high-risk group. The higher infiltration level of activated CD4 T cell, CD56 bright natural killer cell, plasmacytoid dendritic cell, and type 2 T helper cells were found to lead an unfavorable impact on the OS of HCC patients, and these four kinds of immune cells exhibited a higher infiltration level in the high-risk group. Conclusion: The five-gene risk score proposed in the research may provide new insights into the individualized evaluation of HCC prognosis.


Homeopathy: from Hahnemann to the present.
The foundations and philosophical underpinnings of homeopathy are discussed within the framework of a nineteenth century medical controversy. During this era, Hahnemannian doctrine rose in response to the need for conservative healing practices yet faced a decline as key spokesmen of orthodox medicine successfully articulated its shortcomings. These historical events relegated homeopathy to the status of an eclectic medical art. Its greatest discoveries and contributions, such as the medicinals founded by Hahnemann and the attitude of patient education have become incorporated into modern day medical practice.


Morphometric studies on the rat liver in biliary obstruction.
The common bile ducts of the Wistar rats were ligated and severed, and liver biopsies were done weekly for 7 postoperative weeks. Light and electron microscopic specimens were prepared for the morphometric studies. The volume ratio of the hepatic parenchyma decline with the lapse of time after bile duct ligation. However, elevated mean sectional area of the nucleus, increased mitotic index and unchanged estimated weight of the hepatic parenchyma after biliary obstruction suggested that lost hepatocytes were compensated by regeneration. Mitochondrial swelling and curling of the cristae were noted in biliary obstruction in general. Moreover, both the number and volume ratio of the mitochondria were increased corresponding to the duration of biliary obstruction. These changes were interpreted as an adaptation process to mitochondrial dysfunction.


Across the Board: Federico Bella on Electrochemical Nitrogen Reduction.
In this series of articles, the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. This entry features Prof. F. Bella, who discusses the electrochemical reduction of nitrogen to produce ammonia through the addition of protons and electrons under mild conditions (25 °C, 1 atm). This reaction has the potential to replace the energy-intensive traditional Haber-Bosch process but faces several challenges and pitfalls.


Fine needle aspiration cytology of salivary gland lesions.
247 salivary gland lesions were subjected to fine needle aspiration (FNA) cytology; 179 were designated as neoplastic lesions and 68 as non-neoplastic. Based on cytomorphologic features, the neoplastic and non-neoplastic lesions were subcategorised. All but 36 of the neoplastic lesions were subjected to histopathologic study. The overall diagnostic accuracy of FNA cytology for neoplastic lesions was 91%. The sensitivity rate for detecting malignant tumours was 87.8% and the specificity 98.0%. There was 100% sensitivity for cytodiagnosis of benign tumours. The high sensitivity and specificity of cytodiagnosis makes FNA cytology a valuable diagnostic modality in the evaluation of salivary gland lesions.


Hematologic findings associated with thrombocytopenia during the acute phase of exanthem subitum confirmed by primary human herpesvirus-6 infection.
To elucidate the mechanism underlying thrombocytopenia during the acute phase of exanthem subitum (ES), the associated hematological findings were investigated. Five infants with thrombocytopenia during the acute phase of ES serologically confirmed by primary human herpesvirus-6 (HHV-6) were examined and followed-up. Thrombocytopenia was accompanied by neutropenia, leukopenia, and decreased reticulocyte fraction during the acute phase. These changes were self-limiting, and the sequential changes of platelet, neutrophil count, and reticulocyte fraction were closely linked. Slight but significant decreases in hemoglobin in the convalescent phase and mild increases in atypical lymphocytes after subsidence of the fever were observed. Hemophagocytosis and increase in atypical lymphocytes in the bone marrow suggested that bone marrow cells were influenced by primary HHV-6 infection. Platelet-associated immunoglobulin G and indirect antiplatelet antibody were negative. Plasma levels of fibrinogen and D-dimer of fibrinogen degradation products were within normal ranges. Thrombocytopenia is a complication of ES, and this may result from bone marrow suppression rather than from immune-mediated peripheral consumption seen in acute idiopathic thrombocytopenic purpura or from disseminated intravascular coagulation.


Putative convertase involved in the proteolytic conversion of rat proalbumin to serum albumin.
We have found a proteolytic activity in Golgi membranes which efficiently converts [35S]methionine-labeled proalbumin, isolated from pulse-labeled rat hepatocytes in culture, to serum albumin in an in vitro assay system. The proalbumin-converting activity was dependent on Ca2+ and the maximum activity was observed at pH 5.5-6.0. Since the enzyme activity was found to be resistant not only to both leupeptin and E-64 but also to thiol-blocking reagents, it is unlikely that cathepsin B is involved in the proteolytic conversion of proalbumin occurring in the Golgi complex.


Comprehensive quantitative analysis of erythrocytes and leukocytes using trace volume of human blood using microfluidic-image cytometry and machine learning.
A diagnostic test based on microfluidic image cytometry and machine learning has been designed and applied for accurate classification of erythrocytes and leukocytes, including a unique fully-automated 5-part quantitative differentiation into neutrophils, lymphocytes, monocytes, eosinophils, and basophils, using minute amounts of whole blood in a single counting chamber. A low-cost disposable multilayer microdevice for microfluidic image cytometry was developed that comprises a 1 mm × 22 mm × 70 μm (w × l × h) rectangular microchannel, allowing the analysis of trace volume of blood (20 μL) for each assay. Automated analysis of digitized binary images applying a border following algorithm was performed allowing the qualitative analysis of erythrocytes. Bright-field imaging was used for the detection of erythrocytes and fluorescence imaging for 5-part differentiation of leukocytes after acridine orange staining, applying a convolutional neural network enabling unparalleled speed for identification and automated morphology classification yielding 98.57% accuracy. Blood samples were obtained from 30 volunteers and count values did not significantly differ from data obtained using a commercial automated hematology analyzer.


Intrastromal diathermal keratostomy: a new micropenetrating clear-cornea glaucoma procedure.
The filtering intrastromal diathermal keratostomy (IDK) was developed to comply with the call for a low postoperative intraocular pressure (IOP) and a bleb morphology without a thin, cystic appearance. A diathermal microkeratostomy (150 to 200 microm) was created into the anterior chamber, anterior to the Schwalbe line through the floor of a surgical corneoscleral tunnel incision into the subconjunctival space. A newly developed, bipolar diathermal microneedle was used to create the keratostomy, replacing the Holmium laser used previously. Subconjunctival injections of 3 microg mitomycin C were used in each eye 1 week before the IDK to obtain maximum antiproliferative effect at the time of the operation. Nine patients (10 eyes) with complicated, refractory primary and secondary open-angle glaucoma are discussed. Histologic examination of the IDK and clinical postoperative ultrasound biomicroscopy showed an optimal appearance of the diathermal microkeratostomy. After 34 months (range 24 to 42 mo) the mean IOP was 11 mm Hg (SD+/-3, range 6 to 16) without medication in all 10 eyes. IDK revision with internal needling of postoperative subconjunctival fibrosis through the tunnel incision was performed in 5 eyes after an average of 3 months (range 0.2 to 7 mo). After 33 months (range 19 to 38 mo), the postrevision mean IOP was 10 mm Hg (SD+/-2, range 8 to 14) without medication in all 5 eyes. All 10 eyes showed noncystic diffuse blebs with optimal spongy subepithelial morphology: in 2 eyes the blebs were totally avascular and in 8 eyes they were relatively avascular. The preliminary results of the new clear-cornea IDK seem promising because of postoperative IOP of about 10 mm Hg despite a low dose of mitomycin C and noncystic bleb morphology.


[Advances of chromatogram retention time alignment algorithms in proteomics].
Chromatography is a basic process in the current proteomics workflow, and the retention time alignment of the chromatogram is one of the important steps to effectively improve the identification and quantification accuracy. After years of development, a series of algorithms for retention time alignment have been developed. This review summarizes the advances of chromatographic retention time alignment algorithms and tools for proteomics analysis from the perspective of proteomics users, and discusses the development and future application directions.


A longitudinal study of sociodemographic predictors of hemoglobin A1c.
This research examined sociodemographic predictors of hemoglobin A1c (HbA1c) among diabetic patients in an outpatient urban medical center. All patients with diabetes during a 7.5-year period were selected. Regression analyses determined the association of the last HbA1c level with insurance, ethnicity, age, gender, marital status, employment, socialsecuritynumber (present/absent), and number of clinic visits. Patients (N=748) were followed an average of 3.2 years. After multivariate adjustment, the following variables predicted a higher value for the last HbAlc (P < 0.05): Absence of insurance, African American ethnicity, Hispanic ethnicity, younger age, and fewer clinic visits per year. These relationships to HbA1c persisted after adjustment for follow-up duration and after limiting the analysis to patients with type 2 diabetes only (N=662). In conclusion, absence ofhealthinsurance, ethnicity, young age, and fewer clinic visits are independent predictors of HbAlc and should be given consideration in diabetes research and glycemic control.


Hemodialysis using gabexate mesilate (FOY) in patients with a high bleeding risk.
The efficacy of gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, was compared with that of heparin in preventing the acceleration of bleeding after hemodialysis. Transfused blood volume (TBV) was measured 24 h before and after 24 dialyses in 14 bleeding patients with impaired hemostatic function. The predialysis TBV did not differ significantly between heparin and FOY groups; however, TBV was significantly (p less than .05) larger after heparin dialysis than after FOY dialysis. After dialysis, TBV was increased in eight of nine heparin patients, compared to only three of 15 FOY subjects (p less than .01). FOY is an effective agent and may decrease postdialysis bleeding complications in certain high-risk patients.


Molecular mechanisms that change synapse number.
Synapses are the functional units of the nervous system, and their number and protein composition undergo changes over a wide time scale. These synaptic changes manifest into differential behavioural outputs and, in turn, changes in the external conditions to the individual may elicit changes in synapses. We review here publications appeared during the last 10 years in which advances on molecular and cellular mechanisms for synapse changes have been reported. We focus on synaptic changes occurring in the time range of minutes to hours, mainly.


Sudden death due to ruptured hydatid cyst of the liver.
The cyst stage of Echinococcus granulosus is commonly located in the liver, which frequently results in a long symptomless period. We present a sudden death due to a freshly hemorrhagic hydatid cyst following blunt trauma to the liver in a 19-year-old boy. The possible mechanism was thought to be an anaphylactoid reaction to the leakage of the cyst fluid.


Depression in burn reconstruction patients: symptom prevalence and association with body image dissatisfaction and physical function.
This study investigated the prevalence and the clinical correlates of symptoms of depression among burn reconstruction patients. A sample of 224 burn reconstruction patients completed the Beck Depression Inventory (BDI), the SF-36 Health Survey and the Satisfaction with Appearance Scale. The prevalence of at least mild to moderate symptoms of depression (BDI > or =10) was 46%. Female patients were disproportionately represented in this burn reconstruction population (46%) compared to all survivors from the burn center (29%; P<.001) and compared to a national sample of burn survivors (27%; P<.001). Compared to males, female patients presented for consultation much longer after a burn injury (P<.001), tended to have smaller burns (P=.06) and were less likely to have facial burns (P=.08). Depressive symptoms were largely predicted by body image dissatisfaction (beta=.58; P<.001), with additional variance predicted by physical function (beta=-.13; P=.07). The effect of patient and burn injury variables on depressive symptoms was mediated by body image dissatisfaction and physical function. The high prevalence of significant symptoms of depression in burn reconstruction patients and their relationship with body image suggest the importance of the routine psychological screening of patients seeking reconstruction services.


Traumatic peripheral nerve injuries in children: epidemiology and socioeconomics.
Despite the negative effects of peripheral nerve injuries (PNIs) on long-term population health, their true prevalence among pediatric trauma patients is under debate. The authors investigated the prevalence of PNIs among children involved in trauma and investigated associations between PNIs and several patient characteristics. The authors performed a retrospective cohort study of pediatric trauma patients who were registered in the National Trauma Data Bank from 2009 through 2011 and who fulfilled the study inclusion criteria. They used regression techniques to investigate the association of demographic and socioeconomic factors with the rate of PNIs among these patients. Of the 245,470 study patients, 50,211 were involved in motor vehicle crashes, 3380 in motorcycle crashes, 20,491 in bicycle crashes, 18,262 in pedestrian accidents, 26,294 in other crashes (mainly involving all-terrain vehicles and snowmobiles), and 126,832 in falls. The respective prevalence of PNIs was 0.66% for motor vehicle crashes, 1% for motorcycle crashes, 0.38% for bicycle crashes, 0.42% for pedestrian accidents, 0.79% for other crashes, and 0.52% for falls. Multivariate logistic regression analysis demonstrated that the following were associated with an increased incidence of PNIs: increased patient age (OR 1.10, 95% CI 1.01-1.20), higher Injury Severity Score (OR 1.10, 95% CI 1.01-1.20), elevated systolic blood pressure at arrival at the emergency room (OR 1.10, 95% CI 1.01-1.20), and increased number of trauma surgeons at the institution (OR 1.10, 95% CI 1.01-1.20). The following were associated with lower incidence of PNIs: female sex (OR 0.94, 95% CI 0.87-1.02), rural hospitals (OR 0.94, 95% CI 0.87-1.02), and urban nonteaching hospitals (OR 0.94, 95% CI 0.87-1.02). PNIs are more common than previously identified for the pediatric trauma population. These injuries are associated with older age and increased severity of the overall injury.


[Features of uterine contractile function in intrauterine fetal death].
Experiments on 528 pregnant rats studied the specific features of uterine contractility in pre- (7.2%), postimplantation (5.69%), and intrauterine (1.14%) fetal deaths and in ablatio placentae (0.57%) which spontaneously occurred in this group of animals. By applying the multiparametric approach and the methods of the image recognition theory, the authors showed that despite its onset periods, fetal deaths resulted in reduced uterine contractility. It is concluded that the present study provides experimental evidence for the development of weak clinical uterine activity in fetal death in different periods of pregnancy. At the same time, myometrial responses to oxytocin decrease.


Sleep spectral power correlates of prospective memory maintenance.
Prospective memory involves setting an intention to act that is maintained over time and executed when appropriate. Slow wave sleep (SWS) has been implicated in maintaining prospective memories, although which SWS oscillations most benefit this memory type remains unclear. Here, we investigated SWS spectral power correlates of prospective memory. Healthy young adult participants completed three ongoing tasks in the morning or evening. They were then given the prospective memory instruction to remember to press "Q" when viewing the words "horse" or "table" when repeating the ongoing task after a 12-h delay including overnight, polysomnographically recorded sleep or continued daytime wakefulness. Spectral power analysis was performed on recorded sleep EEG. Two additional groups were tested in the morning or evening only, serving as time-of-day controls. Participants who slept demonstrated superior prospective memory compared with those who remained awake, an effect not attributable to time-of-day of testing. Contrary to prior work, prospective memory was negatively associated with SWS. Furthermore, significant increases in spectral power in the delta-theta frequency range (1.56 Hz-6.84 Hz) during SWS was observed in participants who failed to execute the prospective memory instructions. Although sleep benefits prospective memory maintenance, this benefit may be compromised if SWS is enriched with delta-theta activity.


Multiple evanescent white dot syndrome and acute zonal occult outer retinopathies.
Multiple evanescent white dot syndrome (MEWDS) is a rare, acute, multifocal retinitis located in the posterior pole. Patients with MEWDS may report photopsia, central scotoma, or decreased vision. Prodromal viral-like symptoms may be associated with this syndrome, but its etiology remains unknown. The condition is self limiting with a favorable prognosis for visual recovery within several weeks. A young, myopic, female patient presented with painless photopsia, scotoma, and subsequent vision loss secondary to MEWDS. The clinical appearance, differential diagnosis, and management of MEWDS are discussed. Careful ophthalmoscopic and angiographic interpretation along with complete history taking are the keys to diagnosing MEWDS. Ancillary testing including electroretinogram, early receptor potential, and visual fields aid in the differential diagnosis. Once the diagnosis has been established, patient reassurance is appropriate in the management of this condition.


Absorption Spectra for Disordered Aggregates of Chromophores Using the Exciton Model.
Optimizing the optical properties of large chromophore aggregates and molecular solids for applications in photovoltaics and nonlinear optics is an outstanding challenge. It requires efficient and reliable computational models that must be validated against accurate theoretical methods. We show that linear absorption spectra calculated using the molecular exciton model agree well with spectra calculated using time-dependent density functional theory and configuration interaction singles for aggregates of strongly polar chromophores. Similar agreement is obtained for a hybrid functional (B3LYP), a long-range corrected hybrid functional (ωB97X), and configuration interaction singles. Accounting for the electrostatic environment of individual chromophores in the parametrization of the exciton model with the inclusion of atomic point charges significantly improves the agreement of the resulting spectra with those calculated using all-electron methods; different charge definitions (Mulliken and ChelpG) yield similar results. We find that there is a size-dependent error in the exciton model compared with all-electron methods, but for aggregates with more than six chromophores, the errors change slowly with the number of chromophores in the aggregate. Our results validate the use of the molecular exciton model for predicting the absorption spectra of bulk molecular solids; its formalism also allows straightforward extension to calculations of nonlinear optical response.


A novel "double-coupling" strategy for iterative oligothiophene synthesis using orthogonal Si/Ge protection.
[reaction: see text] A new iterative synthesis of regioregular oligothiophenes has been developed in which "double-coupling" after each iteration minimizes deletion sequences. The method exploits the susceptibility of alpha-silyl- but not alpha-germyl-substituted thiophene derivatives toward nucleophilic ipso-protodemetalation and features an unusual "base-free" Suzuki-type cross-coupling protocol. The strategy has been designed for the solid-phase synthesis of high purity oligothiophenes using a germanium-based linker.


The chaperonin containing TCP-1 (CCT) displays a single-ring mediated disassembly and reassembly cycle.
The chaperonin-containing TCP-1 (CCT) assists in the folding of actins and tubulins in eukaryotic cells. CCT is composed of 8 subunit species encoded by separate genes. CCT purifies as a single hetero-oligomeric protein complex of 950 kDa through multiple chromatographic and antibody affinity procedures. The CCT 16-mer contains 7 polypeptide species in equimolar amounts (CCTalpha, beta, gamma, delta, epsilon, zeta, eta), together with another subunit (CCTtheta) which is around half-molar. Here we show, by in vitro translation of CCT subunit mRNAs in rabbit reticulocyte lysate, that none of the CCT subunit proteins are themselves folded by CCT. However, the newly translated CCT subunits can incorporate into the endogenous CCT complex present in the lysate via a mechanism involving a nucleotide-dependent disassembly reaction to produce single-rings and then a reassembly reaction whereby free CCT subunits assemble onto these single-rings. This cycling behaviour is an inherent property of the CCT chaperonin complex and provides a powerful method for introducing single amino acid residue changes into this 8578 residue protein complex.


Research on the biological mechanism and potential application of CEMIP.
Cell migration-inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family that degrades hyaluronic acid (HA) and remodels the extracellular matrix. In recent years, some studies have reported that CEMIP can promote the proliferation, invasion, and adhesion of various tumor cells and can play an important role in bacterial infection and arthritis. This review focuses on the pathological mechanism of CEMIP in a variety of diseases and expounds the function of CEMIP from the aspects of inhibiting cell apoptosis, promoting HA degradation, inducing inflammatory responses and related phosphorylation, adjusting cellular microenvironment, and regulating tissue fibrosis. The diagnosis and treatment strategies targeting CEMIP are also summarized. The various functions of CEMIP show its great potential application value.


Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion.
Neuronal cell death and the failure of axonal regeneration cause a permanent functional deficit following spinal cord injury (SCI). Administration of recombinant glial cell line-derived neurotrophic factor (GDNF) has previously been reported to rescue neurons following severe SCI, resulting in improved hindlimb locomotion in rats. In this study, thus, GDNF gene therapy using an adenoviral vector (rAd-GDNF) was examined in rats following SCI induced by dropping the NYU weight-drop impactor from a height of 25 mm onto spinal segment T9-T10. To evaluate the efficacy of intraspinal injection of recombinant adenovirus into the injured spinal cord, we observed green fluorescent protein (GFP) gene transfer in the contused spinal cord. GFP was effectively expressed in the injured spinal cord, and the most prominently transduced cells were astrocytes. The expression of GDNF was detected only in rats receiving rAd-GDNF, not the controls, and remained detectable around the injured site for at least 8 days. Open-field locomotion analysis revealed that rats receiving rAd-GDNF exhibited improved locomotor function and hindlimb weight support compared to the control groups. Immunohistochemical examination for the neuronal marker, calcitonin gene-related peptide (CGRP), showed an increase in CGRP+ neuronal fibers in the injured spinal cord in rats receiving rAd-GDNF treatment. Collectively, the results suggest that adenoviral gene transfer of GDNF can preserve neuronal fibers and promote hindlimb locomotor recovery from spinal cord contusion. This research should provide information for developing a clinical strategy for GDNF gene therapy.


Prophylaxis of deep vein thrombosis in trauma patients.
Orthopedists who use prophylaxis for deep vein thrombosis (DVT) in total joint arthroplasty are often called on to care for trauma patients. Much less is known or published about the effects of such prophylaxis in the trauma patient than in the arthroplasty patient. The questions to ask are: what is the incidence of DVT in trauma patients; what are the benefits of DVT prophylaxis; and what are the risks of DVT prophylaxis, and do the risks outweigh the benefits?


A Community-Based Approach to Longitudinal Language Research With Racially and Ethnically Minoritized Autistic Young Adults: Lessons Learned and New Directions.
Language and autism research each typically excludes racially and ethnically minoritized (REM) autistic individuals. In addition, in the case of autistic individuals with language impairment, investigators often approach caregivers to discuss research participation, rather than autistic individuals themselves. This gap limits the ecological validity of language research in autism. To address this gap, this clinical focus article describes strategies for engaging REM autistic young adults with language impairment using lessons learned from 5 years of longitudinal research with this population. This approach involved an ongoing community partnership, as well as participatory partnerships with REM autistic individuals and community stakeholders, consistent with a "slow science" approach. The approach yielded excellent retention of participants over 5 years and led to co-development of research projects aimed at priorities described by REM autistic individuals and their families, including understanding self-determination, social determinants of health, and language variability in autistic REM individuals with language impairment. Findings support the utility of community-based methods with autistic REM young adults with language impairment, with key takeaways for diversifying research while replicating, extending, and building theory.


Evaluating the Ameliorative Potential of Quercetin against the Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats.
The current study deals with the effect of a dietary flavanoid quercetin on fibrotic lung tissue in rats. Bleomycin was administered by single intratracheal instillation to Wistar rats to induce lung fibrosis. The pathologies associated with this included significantly reduced antioxidant capacity, ultimately leading to protracted inflammation of the lung tissue. The hallmark of this induced fibrosis condition was an excessive collagen deposition in peribronchial and perialveolar regions of the lung. Oral quercetin treatment over a period of twenty days resulted in significant reversal of the pathologies. The antioxidant defense in lung tissue was revived. Moreover, activity of the collagenase MMP-7, which was high in fibrotic tissue, was seen restored after quercetin administration. Trichome staining of lung tissue sections showed high collagen deposition in fibrotic rats, which may be a direct result of increased mobilization of collagen by MMP-7. This was appreciably reduced in quercetin treated animals. These results point towards an important protective role of quercetin against idiopathic lung fibrosis, which remains a widely prevalent yet incurable condition in the present times.


Soy isoflavone supplementation improves longitudinal bone growth and bone quality in growing female rats.
The aim of this study was to investigate the effects of soy isoflavone on tibia length, bone mineral density (BMD), and structural parameters in growing female rats. Three-week-old female Sprague-Dawley rats were randomly assigned to four experimental groups: control (CON: distilled water gavage); low-dose isoflavone (low-IF: 10 mg/kg body weight [BW]/d gavage); high-dose isoflavone (high-IF: 50 mg/kg BW/d gavage); and 17 β-estradiol (E2: subcutaneous injection of 10 μg). All animals received a soy-free diet and vaginal opening was monitored daily. After an 8-wk treatment period, bone-related parameters (alkaline phosphatase [ALP], osteocalcin [OC], N-terminal telopeptide [NTx], bone length, failure load, stiffness, BMD, and structural parameters) were analyzed. Serum ALP levels of the high-IF group were higher than those of the CON group (P < 0.05); however, serum OC levels of the high-IF group were lower than those of the CON, low-IF, and E2 groups (P < 0.05). The tibias and femurs of the low-IF group were longer than those of the CON and high-IF groups (P < 0.05). Bone volume, trabecular number, and BMD of trabecular bone of the high-IF and E2 groups were higher than those of the CON and low-IF groups (P < 0.05). The trabecular thickness of the high-IF group was higher than that of the CON and low-IF groups (P < 0.05). The failure load of the high-IF group was higher than those of the CON group (P < 0.05). Age and body weight at vaginal opening of the E2 group were significantly lower than those of the CON, low-IF, and high-IF groups (P < 0.05). This study suggests that 8 wk of low-dose supplementation with soy isoflavone stimulates longitudinal bone growth. Additionally, high-dose supplementation with soy isoflavone may improve bone quality (BMD and structural parameters) in growing female rats.


Is surface dysgraphia tied to semantic impairment? Evidence from a case of semantic dementia.
Recent models of lexical processing suggest that written spelling partly depends upon the semantic system. According to these models, a deterioration in word meanings would necessarily lead to a spelling impairment, especially for low-frequency and orthographically irregular words. We report a case study of a patient (MK) with semantic dementia who presents impairments in knowledge of word meanings and surface dysgraphia. By specifically identifying concepts that are still known or that are partially or completely deteriorated, we show that the patient's spelling deficit is highly correlated with word comprehension. These data confirm that surface dysgraphia is directly linked to the breakdown in semantic memory.


In-hospital versus postdischarge major adverse events within 30 days following lower extremity revascularization.
Studies using hospital discharge data likely underestimate postoperative morbidity and mortality after lower extremity revascularization because they fail to capture postdischarge events. However, the degree of underestimation and the timing of postdischarge complications are not well-characterized. We used the American College of Surgeons National Surgical Quality Improvement Program procedure-targeted vascular databases from 2011 to 2015 to tabulate 30-day adverse events (in hospital and after discharge) for lower extremity bypass (LEB) and percutaneous vascular interventions (PVIs) performed for claudication and chronic limb-threatening ischemia (CLTI). A total of 14,125 patients underwent lower extremity revascularization, 8909 patients (63%) with LEB and 5216 (37%) with PVI. For CLTI, total 30-day mortality was similar between PVI and LEB (2.3% vs 2.1%; P = .61), but in-hospital deaths only accounted for 43% of PVI mortality and only 65% of LEB mortality (P ≤ .001). Major adverse cardiac events occurred in 2.9% of PVI patients and 4.6% of LEB patients (P < .001), with postdischarge events accounting for 37% of PVI events and 18% of LEB (P ≤ .001). Although the 30-day reoperation rates were 14% for PVI and 18% for LEB (P < .001), almost one-half occurred after discharge (PVI 46% vs LEB 44%; P = .55). Any postoperative major adverse events (MAEs) occurred in 22% of patients after PVI and 31% after LEB, with more than one-half occurring after discharge (PVI 56% vs LEB 53%; P = .17). For claudicants, total 30-day mortality was 0.4% for PVI and 0.7% for LEB (P = .32), with the vast majority of events occurring after discharge (PVI 90% vs LEB 50%; P = .049). The 30-day reoperation rates were 5.2% for PVI and 8.0% for LEB (P < .001), with more than one-half occurring after discharge (PVI 63% vs LEB 53%; P = .09). Any MAEs occurred in 7.0% of patients after PVI and 17% after bypass, with the majority occurring after discharge (PVI 65% vs LEB 63%; P = .66). Most MAEs occur less frequently after PVI than LEB. However, a significant number of major of adverse events after lower extremity revascularization occur after leaving the hospital, especially after PVI, which may overestimate its benefits compared with LEB if only in-hospital data are evaluated. These data demonstrate the importance of reporting 30-day rather than in-hospital outcomes when evaluating postoperative adverse events.


Management of blood glucose and diabetes in the critically ill patient receiving enteral feeding.
Diabetes mellitus causes profound alterations in nutrient metabolism, leading to long-term systemic complications, particularly in individuals with poorly controlled disease. Nutrition support clinicians need to be aware of the effect of acute illness on stress-induced and established diabetes mellitus and the appropriate management strategies. Because enteral feeding is a vital component of critical care for many patients with diabetes mellitus, it is important to develop techniques to best manage metabolic control during enteral feeding. This article will review mechanics of blood glucose regulation, evaluation of energy sources for patients with diabetes mellitus, selection of enteral formulas and infusion routes, and glycemic control in patients receiving tube feeding. At this point, it is appropriate to use a standard formula to initiate feedings in most patients with blood glucose abnormalities. Close monitoring and judicious use of insulin are key in maintaining glucose control and avoiding complications.


Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.
Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.


Root Growth-promoting Activities of N-Acyl-L-proline Derivatives.
A number of N-acyl-L-proline derivatives were synthesized and their biological activities were investigated by using lettuce (Lactuca sativa L. cv. Sacramento) seedling test. A wide variety of these compounds promoted root growth at 25°C both under light and in darkness. Of the compounds tested, N-(2-ftuorobenzoyl)-L-proline methyl ester (4) showed the highest activity and caused a 270% increase in the root elongation compared to the control. N-(2-Naphthoyl)-L-proline methyl ester (14) promoted the root growth, while N-(1-naphthoyl)-L-proline methyl ester inhibited it. L-Proline, benzoic acid, and 2-naphthoic acid had no significant effect on lettuce seedlings. Compounds 4 and 14, and N-(2-chlorobenzoyl)-L-proline methyl ester (7) reduced the inhibitory effect of 1 ppm ABA on the root growth, while the D-isomer of 4 was less activite than compound 4. Compounds 4, 7, and 14 did not show any rescue-activity for the complete inhibition of germination that was caused by treating 10 ppm of ABA.


Pinhole Surgical Technique for treatment of marginal tissue recession: A case series.
The field of periodontal plastic surgery is always a subject of fascination for periodontists, and the importance of pink esthetics is gaining its pace. Preservation of what is existing is more important than its replacement. The same principle also applies to soft-tissue esthetic procedures thereby the concept of minimal surgical invasion came into existence. This article presents a series of five cases with 18 recession sites which were treated with a minimally invasive Pinhole Surgical Technique which resulted in overall root coverage of 96.7% after 6-month follow-up with minimal complications.


Statistical characterization of ensembles of symmetric virus particles: 3-D stochastic signal reconstruction from electron microscope images.
Stochastic models of nano-biomachines have been studied by 3-D reconstruction from cryo electron microscopy images in recent years. The image data is the projection of many heterogeneous instances of the object under study (e.g., a virus). Initial reconstruction algorithms require different instances of the object, while still heterogeneous, to have the same symmetry. This paper presents a maximum likelihood reconstruction approach which allows each object to lack symmetry while constraining the statistics of the ensemble of objects to have symmetry. This algorithm is demonstrated on bacteriophage HK97 and is contrasted with the former algorithm. Reconstruction results show that the proposed algorithm provides estimates that make more biological sense.


Bayesian Nonparametric Longitudinal Data Analysis.
Practical Bayesian nonparametric methods have been developed across a wide variety of contexts. Here, we develop a novel statistical model that generalizes standard mixed models for longitudinal data that include flexible mean functions as well as combined compound symmetry (CS) and autoregressive (AR) covariance structures. AR structure is often specified through the use of a Gaussian process (GP) with covariance functions that allow longitudinal data to be more correlated if they are observed closer in time than if they are observed farther apart. We allow for AR structure by considering a broader class of models that incorporates a Dirichlet Process Mixture (DPM) over the covariance parameters of the GP. We are able to take advantage of modern Bayesian statistical methods in making full predictive inferences and about characteristics of longitudinal profiles and their differences across covariate combinations. We also take advantage of the generality of our model, which provides for estimation of a variety of covariance structures. We observe that models that fail to incorporate CS or AR structure can result in very poor estimation of a covariance or correlation matrix. In our illustration using hormone data observed on women through the menopausal transition, biology dictates the use of a generalized family of sigmoid functions as a model for time trends across subpopulation categories.


Comparative toxicity of seven rare earth elements in sea urchin early life stages.
The widespread use of rare earth elements (REEs) in a number of technological applications raises unanswered questions related to REE-associated adverse effects. We have previously reported on the multiple impact of some REEs on the early life stages of the sea urchin Paracentrotus lividus. The present investigation was to evaluate REE toxicity to early life stages in two unrelated sea urchin species, Sphaerechinus granularis and Arbacia lixula. The comparative toxicities were tested of seven REEs, namely yttrium, lanthanum, cerium, neodymium, samarium, europium and gadolinium as chloride salts at concentrations ranging from 10-7 to 10-4 M. The evaluated endpoints included developmental defects and cytogenetic anomalies in REE-exposed embryos/larvae, and decreased fertilization success and offspring damage following sperm exposure. The results showed different toxicity patterns for individual REEs that varied according to test species and to treatment protocol, thus showing toxicity scaling for the different REEs. Further, the observed effects were compared with those reported for P. lividus either following embryo or sperm exposures. S. granularis showed a significantly higher sensitivity both compared to A. lixula and to P. lividus. This study provides clear-cut evidence for distinct toxicity patterns among a series of REEs. The differences in species sensitivity at micromolar REE levels may warrant investigations on species susceptibility to impacts along polluted coasts.


Spin, charge and lattice couplings in Cu-deficient oxysulphide BiOCu0.94S.
The electrical and magnetic properties of slightly Cu-deficient BiOCu(0.94)S are investigated using neutron diffraction, ac magnetic susceptibility, magnetization and electrical resistivity measurements. The Cu spins order in a ferromagnetic arrangement below T(C) = 250 K. An antiferromagnetic component develops below 180 K when the crystalline unit cell experiences a sharp thermal contraction upon cooling, resulting in a canted ferromagnetic spin arrangement at low temperatures. In the magnetically ordered state the electrical transport can be described using three-dimensional variable range hopping conduction. An applied magnetic field can effectively reduce the hopping barrier. Spin-charge couplings are clearly revealed when the resistivity departs from the hopping conduction and begins to increase with increasing temperatures above 250 K where the Cu spins become disordered.


[An introduction to the transmission of modern western medicine in southwestern borderland].
Yunnan is located in the southwestern border of China, neighboring South Asia and Southeast Asia. Since the end ofthe 19th century, the western medicine was introduced into Yunnan Province along with the arrival of missionaries, exerting great influence on local medicine in Yunnan, even in inland China, and has become an integral part of Chinese modern medical history. Initially, the missionaries who knew only a little medical knowledge and treated the patients effectively during their missionary work with the western medicines they carried, so as to develop the believers. At the beginning of the 20th century, Catholic Church and Christian Church began to establish Church Hospitals in Yunnan, including the "Dafashi Hospital (French Consulate Hospital)" set up in 1901, and "Fudian Hospital (French Government Hospital)" established in 1902, and many Hospitals set up in Yunnan Province. The Church Hospitals also established medical schools and nurse schools all over Yunnan, which promoted modern medical education in Yunnan, and had profound influence on modern education of western medicine in this Provence.


Cerebrospinal fluid turnover as a driver of brain clearance.
Cerebrospinal fluid (CSF) has historically been considered to function as a sink for brain-derived waste disposal. Recent work suggested that CSF interacts even more intensely with brain tissue than previously recognized, through perivascular spaces that penetrate the brain. Cardiac pulsations, vasomotion, and respiration have been suggested to drive CSF flow in these perivascular spaces, thereby enhancing waste clearance. However, the intrinsic role of CSF production in relation to its distribution volume (turnover) is not an explicit component of recent concepts on brain clearance. Here, we review the work on CSF turnover and volume, focusing on preclinical evidence. Herein, we highlight the use of MRI in establishing CSF-related parameters. We describe the impact of sleep, effect of anesthesia, aging, and hypertension on CSF turnover, and how this relates to brain clearance. Evaluation of the available evidence suggests that CSF turnover is a major determinant in brain clearance. In addition, we propose that several putative drivers of brain clearance, but also conditions associated with impaired clearance, such as aging, may actually relate to altered CSF turnover.


Cardiorespiratory Fitness Is Associated With Cognitive Performance in Older But Not Younger Adults.
Aging is associated with declines in executive function and episodic memory. Cardiorespiratory fitness (CRF) has been associated with enhanced executive function in older adults (OA), but the relationship with episodic memory remains unclear. The purpose of the study was to examine the relationship between CRF and cognition in young and OA and whether CRF mitigates age-related cognitive decline. Participants completed exercise testing to evaluate CRF (peak VO2) and neuropsychological testing to assess cognition. In OA, peak VO2 was positively related to executive function, as well as to accuracy on an experimental face-name memory task and visual episodic memory. In young adults (YA), a relationship between peak VO2 and cognition was not evident. High-fit OA performed as well as YA on executive function measures. On episodic memory measures, YA performed better than high-fit OA, who in turn performed better than low-fit OA. CRF is positively associated with executive function and episodic memory in OA and attenuates age-related cognitive decline. We provide preliminary support for the age-dependence hypothesis, which posits that cognition and CRF relationships may be most readily observed during lifetime periods of significant neurocognitive development.