Relatlimab-nivolumab: A practical overview for dermatologists.
Relatlimab is a human anti-lymphocyte activation gene 3 protein antibody approved for the treatment of metastatic or unresectable melanoma in combination with nivolumab, an existing programmed cell death protein 1 inhibitor. In this article, we review the clinical literature on the efficacy and therapeutic use of the immune checkpoint inhibitor relatlimab in combination with nivolumab for metastatic melanoma. We provide an overview of the mechanism of action, clinical efficacy, and safety profile of relatlimab-nivolumab through a review of recent publications on this emerging therapeutic combination. Ongoing clinical trials studying the use of relatlimab and associated areas of active investigation are also highlighted. This review strives to inform practicing dermatologists on the use of relatlimab-nivolumab as an approved first-line dual checkpoint inhibitor for metastatic melanoma in appropriate clinical cases.


Photon-in photon-out hard X-ray spectroscopy at the Linac Coherent Light Source.
X-ray free-electron lasers (FELs) have opened unprecedented possibilities to study the structure and dynamics of matter at an atomic level and ultra-fast timescale. Many of the techniques routinely used at storage ring facilities are being adapted for experiments conducted at FELs. In order to take full advantage of these new sources several challenges have to be overcome. They are related to the very different source characteristics and its resulting impact on sample delivery, X-ray optics, X-ray detection and data acquisition. Here it is described how photon-in photon-out hard X-ray spectroscopy techniques can be applied to study the electronic structure and its dynamics of transition metal systems with ultra-bright and ultra-short FEL X-ray pulses. In particular, some of the experimental details that are different compared with synchrotron-based setups are discussed and illustrated by recent measurements performed at the Linac Coherent Light Source.


Acoustofluidic platforms for particle manipulation.
There is an increasing interest in acoustics for microfluidic applications. This field, commonly known as acoustofluidics involves the interaction of ultrasonic standing waves with fluids and dispersed microparticles. The combination of microfluidics and the so-called acoustic standing waves (ASWs) led to the development of integrated systems for contact-less on-chip cell and particle manipulation where it is possible to move and spatially localize these particles based on the different acoustophysical properties. While it was initially suggested that the acoustic forces could be harmful to the cells and could impact cell viability, proliferation, or function via phenotypic or even genotypic changes, further studies disproved such claims. This review is summarizing some interesting applications of acoustofluidics in the manipulations of biomaterials, such as cells or subcellular vesicles, in works published mainly within the last 5 years.


Programmed texts: success or failure? An analysis of medical students' opinions.
It is shown that German medical textbooks have sold about nine times better than programmed texts, even if they were written by the same author and on the same subject. To explore some of the reasons why programmed texts are being used so little in comparison with conventional textbooks, 4th and 5th year medical students of the University of Berne were asked to work through a short programmed text in clinical neurology and to answer questions related to several aspects of using programmed texts and other materials. The analysis of the 212 questionnaires returned (58%) indicates that almost all students considered such a learning experience as highly useful and stimulating, but only about 25 per cent had no reservations. It is concluded that programmed medical texts may be used so little because they require students to learn in a highly standardized way, and because students need additional learning resources which provide them with conceptual framework of and sufficient information about a given area.


C4B3 allotype with a novel Ch phenotype.
The fourth component of complement (C4) has two classes of protein, C4A and C4B, both of which have many allelic forms. The serological determinants Rodgers (Rg1, Rg2) and Chido (Ch1, Ch2, Ch3) are generally associated with C4A and C4B, respectively. The C4B3 allotype has been detected in a single Canadian family that expresses a novel Ch phenotype, Ch:-1, 2, -3. There was no information for the Rg determinants, as the C4A*2B*3 haplotype would normally express Rg on the C4A protein. Other C4B3 allotypes in informative families have different Ch phenotypes, and the relationships of these within extended major histocompatibility complex haplotypes are discussed in this paper.


Selective disturbance of mental rotation by cortical stimulation.
In order to plan activity, people must imagine the spatial consequences of potential actions. Two classes of mental spatial transformation can be distinguished: Object-based spatial transformations are imagined movements of objects, such as mental rotation. Egocentric perspective transformations are imagined changes in one's viewpoint, such as imagining one's self in the position of another person. Here we report a case in which electrical stimulation of the right parietal cortex selectively interfered with performance of a mental rotation task. Interference was selective to this stimulation site, and was task specific. Performance of the perspective transformation task, and a control for visual encoding and responding, were unimpaired by stimulation. This marks the first instance of the use of direct cortical stimulation to investigate mental spatial transformations.


Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological variables.
We analysed 32 primary, 8 recurrent and 16 metastatic squamous cell carcinomas of the head and neck by flow cytometry to assess tumoural heterogeneity. Intratumoural heterogeneity was found in 9 of 30 primary tumours (30%). All heterogeneous tumours had diploid and aneuploid cell lines. DNA indices were different from those of the primary tumours in 3 of the 8 recurrent lesions (38%) and in 8 of the 12 metastatic lesions (67%). The results indicate that new cell lines evolve during the process of recurrence and metastasis. The incidence of recurrence, metastasis, and heterogeneity increased with the size of the tumour. Histologically, there were tumours in which the degree of differentiation and mode of invasion of primary lesions were not consistent with the results of flow cytometry in both homogeneous and heterogeneous tumours. In conclusion, multiple sampling for flow cytometric analysis is essential for better characterization of oral carcinomas.


Near-perfect kinetic resolution of racemic p-chlorostyrene oxide by SlEH1, a novel epoxide hydrolase from Solanum lycopersicum with extremely high enantioselectivity.
An open reading frame of sleh1, a gene encoding for a novel epoxide hydrolase from Solanum lycopersicum (SlEH1), was amplified by RT-PCR and expressed in E. coli BL21(DE3). The substrate spectrum assay showed that E. coli/sleh1 had EH activities towards all tested substrates except for racemic (rac-) 5a, and the highest enantiomeric ratio (E > 200) towards rac-2a, retaining (R)-2a with 99.1% ees and 49.2% yields and affording (R)-2b with 89.8% eep and 46.7% yieldp. Besides, E. coli/sleh1 also hydrolyzed of rac-7a-9a with moderate regioselectivities, producing (S)- or (R)-7b-9b with 40.5-51.3% eep and 69.4-75.2% yieldp. The pH optimum and stability of the purified SlEH1 were 7.5 and at a range of 6.5-8.5, and it was thermostable at or below 40 °C. Its catalytic efficiency (kcatS/KmS = 7.49 mM-1 s-1) for (S)-2a was much higher than that for (R)-2a. The gram-scale kinetic resolution of 150 mM rac-2a was carried out by E. coli/sleh1 at 20 °C for 8 h, producing (R)-2a with 98.2% ees and 45.3% overall yields after purification by silica gel column chromatography. Furthermore, the source of extremely high enantioselectivity of SlEH1 towards rac-2a was analyzed by molecular docking simulations.


catena-Poly[[(diaqua-calcium)-bis-(μ-2-fluorobenzoato)-1':1κO:O,O';1:1''κO,O':O] 2,2'-bipyridine hemi-solvate].
In the title compound, {[Ca(C(7)H(4)FO(2))(2)(H(2)O)(2)]·0.5C(10)H(8)N(2)}(n), the Ca(II) atom is coordinated by eigth O atoms from four 2-fluoro-benzoate ligands and two water mol-ecules, resulting in a distorted CaO(8) square-anti-prismatic coordination environment. The 2-fluoro-benzoate ligand bridges two symmetry-related Ca(II) atoms, giving rise to a chain structure extending along [100]. The distances between the Ca atom and its two symmetry-related counterparts are 4.054 (2) and 4.106 (2) Å. The polymeric chains are connected by classical O-H⋯N hydrogen bonds into a layer structure parallel to (010). The layers are connected by non-classical C-H⋯F hydrogen bonds into a three-dimensional supra-molecular structure. O-H⋯O and C-H⋯O inter-actions also occur. The uncoordinated 2,2'-bipyridine mol-ecule is located on a centre of symmetry at the mid-point of the bond between the two heterocycles. One of the two benzene rings is disordered over two sites with occupancy factors of 0.60 and 0.40.


A Randomized, Controlled Comparison of NCX 470 (0.021%, 0.042%, and 0.065%) and Latanoprost 0.005% in Patients With Open-angle Glaucoma or Ocular Hypertension: The Dolomites Study.
NCX 470 0.042% and 0.065% were statistically superior in intraocular pressure (IOP) lowering to latanoprost 0.005%, and NCX 470 0.021% was noninferior. All NCX 470 concentrations were safe and well tolerated. The purpose of this study was to compare varying concentrations of NCX 470 (a nitric oxide-donating bimatoprost) to latanoprost in a dose-response safety and efficacy trial. Adult patients with bilateral open-angle glaucoma or ocular hypertension were randomized to NCX 470 0.021% (n=111), 0.042% (n=108), 0.065% (n=107), or latanoprost 0.005% (n=107) once daily in the evening. IOP was measured at 8:00 am, 10:00 am, and 4:00 pm at weeks 1, 2, and 4. The primary efficacy endpoint was the reduction from baseline in mean diurnal IOP at week 4. Secondary efficacy endpoints included reductions from baseline in mean diurnal IOP at weeks 1 and 2, and reductions from baseline in time-matched IOP at 8:00 am, 10:00 am, and 4:00 pm at weeks 1, 2, and 4. Adverse events were evaluated. All concentrations of NCX 470 resulted in significant reductions of mean diurnal IOP. The 0.042% and 0.065% concentrations were statistically superior to latanoprost 0.005%, and 0.021% was noninferior to latanoprost for change from baseline in mean diurnal IOP at week 4. The 0.065% concentration was also superior to latanoprost by up to 1.4 mm Hg for reduction from baseline at 8:00 am, 10:00 am, and 4:00 pm at week 4. NCX 470 was safe and well tolerated; conjunctival hyperemia was the most frequently reported adverse event. NCX 470 demonstrated dose-dependent reductions in IOP. The 0.042% and 0.065% concentrations demonstrated significantly greater reductions from baseline in mean diurnal IOP than latanoprost 0.005% at week 4, suggesting that higher concentrations may show even greater efficacy.


The effect of two-month treatment with Zataria multiflora on inflammatory cytokines, pulmonary function testes and respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD).
Zataria multiflora Boiss. (Z. multiflora) is a valuable medicinal plant that has been used in Iranian traditional and folk medicine as an antiseptic, carminative, diaphoretic, diuretic, anti-spasmodic and analgesic herbal medicine. This plant has been also used to relieve cough in common cold and respiratory tract disorders. The previous studies reported the pharmacological effects of Z. multiflora such as anti-inflammatory and anti-oxidant properties in respiratory disorders in animal models and clinical studies. The effects of Z. multiflora extract on inflammatory cytokines, pulmonary function tests (PFT), and respiratory symptoms in chronic obstructive pulmonary diseases (COPD) patients were investigated. COPD patients (41 cases) were divided to three groups including placebo group (P) and groups received 3 and 6 mg/kg/day Z. multiflora extract (Z3 and Z6) for two months. Inflammatory cytokines, PFT values, and respiratory symptoms were assessed before treatment (stage 0), one (stage I) and two (stage II) months after treatment. Serum levels of TNF-α and IL-8 were significantly decreased after two months treatment compared to baseline values in Z3 and Z6 groups. The PFT values including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were significantly increased during two months treatment with Z3 and Z6. The peak expiratory flow (PEF) was also significantly increased after one-month treatment with Z6. The respiratory symptoms including cough, chest tightness, modified medical research council (mMRC) dyspnea scale were significantly improved after one and two treatments with both doses of Z. multiflora compared to baseline values. The results suggest the potential therapeutic effect of Z. multiflora in COPD patients through reduction of inflammatory cytokines, increasing PFT values and improvement of respiratory symptoms.


Evolution of purely infratentorial PML under HAART--negative outcome under rapid immune reconstitution.
Progressive multifocal leukoencephalopathy (PML) caused by the polyomavirus JC is a well-recognised complication of AIDS. Purely infratentorial manifestations are rare. Introduction of highly active antiretroviral therapy (HAART) has been associated with a reduction in morbidity and an improvement in overall survival among HIV-infected individuals. Recently, several reports have described adverse events in patients with PML who begin HAART and show evidence for immune reconstitution. We describe the clinical course of two patients with PML with purely infratentorial manifestation, whose clinical course deteriorated despite the successful introduction of HAART. Possible underlying immunological mechanisms are discussed.


Thirty-year follow-up after Wagner resurfacing hip arthroplasty: Case report.
Wagner hip arthroplasty has been used as a resurfacing and thereby bone-preserving method for the treatment of disabling osteoarthritis particularly in younger individuals. The underlying rationale was to replace exclusively diseased tissue, to restore anatomy and function and to optimize range of motion and stress transfer to the proximal femur. Wagner's approach was designed to reduce the risk of infection and to make later revisions easier. The technique was however associated with a high revision rate due to early aseptic wear induced component loosening and neck fractures. Nevertheless, we report a case of a 30 years follow-up of a Wagner resurfacing hip arthroplasty.


Topical glutamine therapy in experimental inflammatory bowel disease.
This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.


The treatment of unstable metacarpal and phalangeal shaft fractures with flexible nonlocking and locking intramedullary nails.
Metacarpal and phalangeal shaft fracture fixation can be achieved by closed IM nailing. This technique provides sufficient stability to commence early unsupported joint motion and minimize soft-tissue irritation and scar formation. Stability is enhanced by proximal nail locking; a measure that extends the indications to spiral and comminuted fractures. The surgical technique is simple but requires attention to detail.


Synthesis, physical properties, and anion recognition of two novel larger azaacenes: benzannelated hexazaheptacene and benzannelated N,N'-dihydrohexazaheptacene.
Two novel larger azaacenes with six or ten N atoms in their backbones, benzannelated 9,11,13,22,24,26-hexazatetrabenzo[a,c,l,n]heptacene (HATBH, 1) and benzannelated 9,26-dihydro-9,11,13,22,24,26-hexaza-tetrapyrido[3,2-a: 2',3'-c: 3'',2''-l: 2''',3'''-n]heptacene (DHATPH, 2), have been successfully synthesized in two steps. The theoretical band gaps estimated through DFT calculations for HATBH (1) and DHATPH (2) are 1.949 eV and 2.278 eV, which are close to the experimentally obtained optical band gaps (2.14 eV and 2.39 eV). Interestingly, HATBH (1) can act as efficient anion sensor for F(-) and H2PO4(-) , while DHATPH (2) selectively responds to F(-) among the ten different anions used (F(-), Cl(-), Br(-), I(-), PF6(-), HSO4(-), NO3(-), BF4(-), AcO(-), and H2PO4(-)). Our synthetic strategy could offer a promising and easy way to obtain even larger azaacenes.


[Vesicular contact dermatitis due to Paederus in Cameroon and review of the literature].
This irritant blister dermatitis is caused by the genus Paederus whose geographical distribution is worldwide, with a higher incidence in tropical areas. It is induced by direct skin contact with pederin, a blistering and caustic substance found in the abdomen (coelome) of Paederus insects (insect order Coleoptera: family Staphylinidae). The diagnosis is based on the presence of typical clinical features combined with compatible epidemiological features. Our goal is to describe the epidemiological and clinical features of this irritant contact dermatitis in Cameroon through a retrospective study conducted at the end of the rainy season at the Oku Hospital in Northwest Cameroon and to also include cases reported at the medical center of the French Embassy in Yaounde during this same timeframe. In addition, we conducted a literature review of paederus dermatitis. Nineteen patients were included in this study. More than half of the patients presented with more than two lesions predominantly localized to the face or the neck; less than half had complications manifesting as either localized or respiratory reactions and three patients presented periorbital involvement. This study confirms the presence of paederus dermatitis in Cameroon. It is mainly localized in the unusual geoclimatic region of the western high mountains within the country, as well as the usual warm, moist areas of Yaounde. The clinical evolution of this dermatitis is usually one of spontaneous and uneventful resolution with complications being rare. Curative treatment is one of localized topical therapies while oral antibiotic therapy should be reserved for more complicated cases.


Breath-holding endurance as a predictor of success in smoking cessation.
A pretreatment test of breath-holding endurance predicted end-of-treatment outcome in 56 Smokers Clinic clients (r = .44; p less than .001). The cut off points derived by discriminant analysis were 32 seconds for men and 20 seconds for women, which correctly classified 78.6% of cases. The breath-holding test might sample the type of endurance necessary to withstand the discomfort associated with cigarette withdrawal and may also be relevant to success in quitting other addictive behaviours. However, alternative explanations are possible and more data are needed.


Language and country preponderance trends in MEDLINE and its causes.
The authors characterized the output of MEDLINE papers by language and country of publication during a thirty-four-year time period. We classified MEDLINE's journal articles by country of publication (Anglos/Non-Anglos) and language (English/Non-English) for the years 1966 and from 1970 to 2000 at five-year intervals. Eight English-speaking countries were considered Anglos. Linear regression analysis of number of papers versus time was performed. The global number of papers increased linearly at a rate of 8,142 papers per year. Anglo and English papers also increased linearly (6,740 and 9,199, respectively). Journals of Non-Anglo countries accounted for 25% of the English language increase (2,438 per year). Only Non-English papers decreased at a rate of 1,056 fewer papers per year. These trends have led to overwhelming shares of English and Anglo papers in MEDLINE. In 2000, 68% of all papers were published in the 8 Anglo countries and 90% were written in English. The Anglo and English preponderances appear to be a consequence of at least two phenomena: (1) editorial policy changes in MEDLINE and in some journals from Non-Anglo countries and (2) factors affecting Non-Anglo researchers in the third world (publication constraints, migration, and undersupport). These are tentative conclusions that need confirmation.


Biologic Options for Glenohumeral Arthritis.
Biologic options for glenohumeral arthritis include intra-articular injections as well as allograft interposition arthroplasty. The objectives of these treatments are reduction of pain and maintenance/improvement in function, while delaying the need for arthroplasty. This article reviews the current evidence for hyaluronic acid injection, platelet-rich plasma injection, and allograft interposition arthroplasty in the young patient with glenohumeral arthritis.


Differential finger movements and hand preference.
In an attempt to replicate a study by Kimura and Vanderwolf (1970), normal left-handed and right-handed subjects were asked to flex a single finger or pairs of fingers at the middle joint. Both hands were found to be equally proficient at this task and no differences between right- and left-handers were found. When left-handers were divided into inverters and non-inverters according to hand-writing posture, a left hand superiority was a found for the right-handed and the left-inverted subjects, while the left-non-inverters showed a right hand superiority. Paired finger flexion was found to be more useful in discriminating between the handedness groups. These findings support the idea that the neural mechanism for hand preference is not based on an asymmetry in the control of fine movement. They also support the theory that two separate groups of left-handers exist, and the they can be differentiated by their handwriting postures.


Mechanisms of Phaeocystis globosa blooms in the Beibu Gulf revealed by metatranscriptome analysis.
The haptophyceae Phaeocystis globosa is a species responsible for harmful algal blooms in the global ocean, forming blooms in the Beibu Gulf annually since 2011. This species can alternate between solitary free-living cells and colonies. Colonies are the dominant morphotype during blooms. To date, the underlying mechanism of P. globosa blooms in the Beibu Gulf is poorly understood. After combining results of ecological surveys, laboratory studies, and metatranscriptome and bioinformatics analyses, it was found that low temperatures, high nitrate, and low organic phosphorus induced P. globosa blooms in the Beibu Gulf. Additionally, the unique genetic and physiological characteristics that allow P. globosa to stand out as a dominant species in such an environment include (1) several genes encoding high-affinity nitrate transport proteins that could be highly expressed under sufficient nitrate conditions; (2) energy metabolism genes involved in photosynthesis and oxidative phosphorylation that were actively expressed at low temperatures to carry out carbon and energy reversion and produce sufficient ATP for various life activities, individually; (3) abundant glycan synthesis genes that were highly expressed at low temperatures, thus synthesizing large quantities of proteoglycans to construct the mucilaginous envelope forming the colony; (4) cells in colonies exhibited active gene expression in DNA replication contributing to a faster growth rate, which could help P. globosa occupy niches quickly; and (5) the energy and material expenditure was redistributed in colonial cells accompanied with chitin filaments and flagella degraded, more expenditure was used for the synthesis of the mucilaginous envelope and the rapid proliferation.


Anomeric specificity of liver glycogenolysis.
In rat liver slices incubated in the absence of exogenous D-glucose, both the basal and glucagon-stimulated output of D-glucose resulted in the production of a greater relative amount of alpha-D-glucose than that found at anomeric equilibrium. Comparable results were obtained in isolated hepatocytes. In these experiments, the rate of glycogenolysis largely exceeded that of glycogen synthesis. These findings indicate that liver glycogenolysis represents an alpha-stereospecific process.


The potent different risk factors for cerebral infarction in young patients with and without type 2 diabetes: subanalysis of the Young Cerebral Infarction Study (YCIS).
To compare risk factors, stroke characteristics, and short-term prognosis between diabetic and nondiabetic young ischemic stroke patients to provide information for patient management, counseling, and future research in these patient groups. All consecutive patients between the ages of 18 and 45 years with first-ever cerebral infarction during 2001-2010 were recruited to participate in the study. Using multivariate logistic regression modeling, demographic characteristics, cerebrovascular risk factors, clinical events, stroke subtypes, and outcome in ischemic stroke patients with and without diabetes were compared. Logistic regression analysis adjusted for confounders confirmed the following independent susceptibility markers: in a substudy of young patients with and without diabetes, the predictors of short-term outcome were more likely to be TOAST subtype, initial stroke severity and serum uric acid, and age at onset, dyslipidemia, initial stroke severity and serum fibron levels correlate with a higher risk for incident stroke in young with diabetes. Our findings suggest that diabetic and nondiabetic ischemic stroke patients exhibit a distinct risk-factor and etiologic profile and may help clinicians to assess prognosis more accurately.


[The conservative mitral valve surgery (author's transl)].
From 1969 to 1976 at Harefield Hospital 260 patients underwent conservative mitral valve surgery. The different techniques used are described. Of the 223 patients followed up (1 to 8 years, mean follow up 48 months) 73% are asymptomatic, 20% are improved and 7% are the same or worse. A conservative operation is possible in approximately 85% of the cases and according to our results this should be the operation of choice in mitral valve surgery.


Serum HE4 as a diagnostic and prognostic marker for lung cancer.
We evaluated the diagnostic and prognostic efficacy of human epididymis protein 4 (HE4) for lung cancer patients by using our novel enzyme-linked immunosorbent assay (ELISA) system. We measured serum HE4 levels of cancer patients including 49 lung cancer and 18 ovarian cancer patients. Furthermore, we evaluated the relationship between serum HE4 levels and overall survival after chemotherapy of 24 lung cancer patients. Serum HE4 levels were significantly higher for non-small, small cell lung cancer and ovarian cancer patients than for healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated for differentiation of lung cancer patients and healthy controls. AUC for serum HE4 was 0.988 for differentiating lung cancer patients from healthy controls, with a cutoff value of 6.56 ng/ml (sensitivity = 89.8%, specificity = 100%). Serum HE4 levels were elevated in 36/40 (90.0%) non-small cell lung cancer patients, 8/9 (88.9%) small cell lung cancer patients and 8/18 (44.4%) ovarian cancer patients. High levels of serum HE4 (>15 ng/ml) after chemotherapy were significantly correlated with worse overall survival after the treatment. These findings suggest that serum HE4 is a potential diagnostic and prognostic marker for lung cancer patients.


High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR.
Intrauterine growth restriction (IUGR) and postnatal nutrition are risk factors for cardiovascular and renal diseases in both humans and animals. The long-term renal effects of protein intake early in life remain unknown. The objective was to evaluate the effects of a neonatal feeding with high protein (HP) milk on renal functions and structure in IUGR male rats. Maternal gestational low protein diet was used to produce IUGR. At day 5, IUGR pups were gastrostomized in the "pup-in-the cup" model and received either normal protein (NP) milk or HP (+50% protein content) milk until day 21. After weaning, the animals were fed the same standard diet. Renal functions and structure were assessed at postnatal day 18 (D18) and in adult offspring. During the preweaning period, the postnatal weight gain between the two groups was unaffected. On D18, kidneys from HP offspring were heavier with significant glomerular hypertrophy (+40%, P < 0.05). HP diet was associated with significant proteinuria and glomerulosclerosis (+49%, P < 0.05). Glomerular number was unaltered. Neonatal HP feeding following IUGR affects renal functions and structure at adulthood. These alterations may result from a single nephron glomerular hyperfiltration.


Maternal pinealectomy increases depressive-like responses in Siberian hamster offspring.
This study investigated the effect of maternal pinealectomy and postnatal pinealectomy on affective responses. Siberian hamsters were born to either pinealectomized or sham-operated dams and then underwent pinealectomy or a sham operation. Maternal pinealectomy increased depressive-like responses of offspring in the forced swim test. Maternal pinealectomy increased rearing behaviour and postnatal pinealectomy increased locomotor behaviour in the open field test. These results suggest that prenatal melatonin organizes adult affective responses.


Determination of molsidomine in plasma by high-performance liquid column chromatography.
A high-performance liquid chromatographic method is described for the analysis of the anti-anginal compound 5-ethoxycarbonyl-3-morpholinosydnonimine (Molsidomine) in human and dog plasma. The drug was extracted from plasma into chloroform and the analysis was carried out on a reversed-phase column, the column effluent being monitored by UV absorption at 312 nm. The method is sensitive (2 +/- 0.3 ng/ml) and specific. The method was applied to a study in which human volunteers received an aqueous solution of the drug and then, on a separate occasion, a tablet formulation. Peak plasma levels of 20--30 ng/ml (tablet) and 10--19 ng/ml (aqueous solution) were obtained following a 2-mg oral dose.


Impurities in the [18O]water target and their effect on the yield of an aromatic displacement reaction with [18F]fluoride.
Fluorine-18 in the form of fluoride ion has widespread utility in PET radiochemistry. This paper explores the effect of possible metal ion contamination of the water on the yield of the displacement of a nitro group off of dinitrobenzene by fluoride has been investigated as a model reaction for fluoride displacement. The metal ions were found to have a profound effect if they were at the level of the carbonate added to the synthetic procedure. The yields from the reaction are best fit by a model in which the metal ions complex the carbonate ion and thus reduce the pH which in turn reduces the efficiency of the reaction. The formation of [18F]fluoroacetate in the target was explored as a mode for making the fluoride in the target unreactive. It was found that essentially no fluoroacetate was formed under our irradiation conditions. The sources of carrier fluoride were examined. It was found that carrier fluoride was introduced during the transfer of water into and out of the target and not during the irradiation.


Herpes type 2 infection with unusual generalised manifestations and delayed diagnosis in an adult male.
A case of severe generalised herpes simplex type 2 infection is described in an adult male who had known exposure to herpes. The patient first complained of headache, fever and neurological symptoms, and three to six days later of conjunctivitis, severe pharyngitis, arthralgia and vesicular lesions about the body. During the first 14 days of illness, including three in hospital, the patient was diagnosed as having infection with varicella virus, vesicular stomatitis virus, or hand-foot-and-mouth disease virus. The diagnosis of infection with herpesvirus was not considered until herpesvirus was visualised in vesicular fluid by electron microscopy six weeks after onset. HSV-2 was then repeatedly isolated from vesicular fluids over the next four years. Detailed serological tests on the patient's sequential serum samples demonstrated a specific and continued response to HSV-2. He possibly acquired the virus iatrogenically, either by oral droplet transmission into or finger contamination of a PPD injection site, from the nurse who administered the injection and then palpated the site.


Route of progesterone administration for luteal phase support may affect outcome of controlled ovarian hyperstimulation for IVF with ICSI using GnRH antagonist.
This study evaluated the impact of route of progesterone administration as luteal phase support on the outcome of assisted conception cycles. Intramuscular progesterone in oil (IMP) at 100 mg daily was administered to 903 women following oocyte retrieval whereas vaginal progesterone gel (VMP) at 90 mg was administered twice daily to 1,110 women. Retrospective analysis was performed according to the type of GnRH analogue used. Implantation (IR), clinical pregnancy (CPR) and biochemical pregnancy rates (BPR) were main outcomes. In GnRH agonist cycles, neither IR, CPR or BPR differed according to the route of progesterone. However, in GnRH antagonist cycles, IR and CPR were significantly lower in VMP group compared to IMP group. BPR also was significantly higher in VMP group compared to IMP group. Our results suggest that route of progesterone administration for luteal phase support can be an important prognostic factor according to the type of GnRH analogue used for controlled ovarian hyperstimulation.


Approaches for the Evaluation of the National Cancer Institute's Summer Curriculum in Cancer Prevention: lessons from the all-Ireland NCI cancer consortium.
The NCI Summer Curriculum in Cancer Prevention (SCCP) has provided interdisciplinary training in cancer prevention and control to cancer health-care professionals, including nurses, physicians, and scientists, since 1986. It has trained over 1,200 participants, 256 of them from Ireland and Northern Ireland through two summer courses: a 4-week course on Principles and Practice of Cancer Prevention and Control (PP) and 1-week on Molecular Prevention (MP). This report is our attempt to measure achievements and level of satisfaction among alumni from the island of Ireland upon return to their home institution. A questionnaire was developed to assess this. Our analysis found statistically significant differences in the types of accomplishments reported among respondents of the MP and PP courses as well as statistically significant differences in their level of satisfaction. More data are needed to better explain the differences observed as well as level of resources available to alumni upon their return home.


Low serum prealbumin concentration predicts long-term mortality in maintenance hemodialysis patients with hepatitis B and/or C virus infections.
A low serum prealbumin concentration is common in maintenance hemodialysis patients with hepatitis B and C and may be associated with mortality. In this study, we assessed Department of Nephrology and Hemodialysis predictive value of a low serum prealbumin concentration on mortality in HD patients using reused low-flux dialyzers who were infected with hepatitis B and/or C virus. We used serum prealbumin levels to predict the long-term mortality of 326 hemodialysis patients. The patients were divided into two groups: group 1 (n = 140, with hepatitis B and/or C virus infections), and group 2 (n = 186, without hepatitis virus infections). During a 5-year follow-up, there were 75 deaths due to all-cause mortality (23.0%). Mortality was significantly higher (P < 0.001) in patients with hepatitis B and/or C infection (44%) than in those without hepatitis infection (8%). Serum prealbumin was lower in the hepatitis infected group and mortality group than in non-infected group and survival group. Multivariate Cox regression analysis showed that long duration of HD and lower serum prealbumin and albumin were related to mortality in patients undergoing maintenance HD. Receiver operating characteristic curves showed that serum prealbumin had a good prognostic value in predicting mortality in both groups with hepatitis B and/or C virus infection and without hepatitis infection (AUC = 0.792 [95% confidence interval: 0.714-0.87], P < 0.001; cut-off value = 24.5 mg/dl, sensitivity = 62.3%, and specificity = 88.6%). In HD patients, serum prealbumin was a good prognostic biomarker of mortality in both groups of patients with hepatitis B and/or C virus infections and without hepatitis infections.


The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting: the impact of a controlled definition.
After coronary artery bypass grafting (CABG), 20-30% of patients are reported to suffer from cognitive decline. Studies reporting these high incidences, however, have not included an appropriate control group. We repeatedly administered a series of neuropsychological tests to 112 healthy middle-aged volunteers not undergoing surgery, and applied two widely used definitions of cognitive decline to their test results. In addition, we re-analysed the neuropsychological test data of 281 CABG patients with a definition of cognitive decline that takes into account the natural variability of test performance that was found in the volunteers. Three months after their first assessment, 14-28% of the volunteers suffered from cognitive decline according to the definitions of cognitive decline after CABG. Using the controlled definition of cognitive decline that takes the natural variability in test performance into account, we found that only 7.7% of the CABG patients suffered from cognitive decline at 3 months after their operation. These data suggest that the incidence of cognitive dysfunction after CABG has previously been greatly overestimated.


The distribution of intravenous nicardipine in rat brain after subarachnoid hemorrhage.
The distribution of intravenously injected nicardipine in rat brain was investigated, as well as the influence of subarachnoid hemorrhage on its distribution. Autoradiographic studies demonstrated the accumulation of 3H-nicardipine only in the ventricles and subarachnoid spaces around pial vessels in normal brains. Thirty minutes after subarachnoid hemorrhage, the concentration of 3H-nicardipine was higher in the ventricles and in the subarachnoid space than that found in normal brains. It is concluded that nicardipine penetrates into the subarachnoid spaces and ventricles from pial vessels and/or choroid plexus, and that subarachnoid hemorrhage increases the penetration of nicardipine from vessels into the subarachnoid space.


Distinct mutational pattern of T-cell large granular lymphocyte leukemia combined with pure red cell aplasia: low mutational burden of STAT3.
T-cell large granular lymphocyte leukemia (T-LGL) is often accompanied by pure red cell aplasia (PRCA). A high depth of next generation sequencing (NGS) was used for detection of the mutational profiles in T-LGL alone (n = 25) and T-LGL combined with PRCA (n = 16). Beside STAT3 mutation (41.5%), the frequently mutated genes included KMT2D (17.1%), TERT (12.2%), SUZ12 (9.8%), BCOR (7.3%), DNMT3A (7.3%), and RUNX1 (7.3%). Mutations of the TERT promoter showed a good response to treatment. 3 of 41 (7.3%) T-LGL patients with diverse gene mutations were revealed as T-LGL combined with myelodysplastic syndrome (MDS) after review of bone marrow slide. T-LGL combined with PRCA showed unique features (low VAF level of STAT3 mutation, low lymphocyte count, old age). Low ANC was detected in a STAT3 mutant with a low level of VAF, suggesting that even the low mutational burden of STAT3 is sufficient for reduction of ANC. In retrospective analysis of 591 patients without T-LGL, one MDS patient with STAT3 mutation was revealed to have subclinical T-LGL. T-LGL combined with PRCA may be classified as unique subtype of T-LGL. High depth NGS can enable sensitive detection of concomitant MDS in T-LGL. Mutation of the TERT promoter may indicate good response to treatment of T-LGL, thus, its addition to an NGS panel may be recommended.


Real-Time Propagation via Time-Dependent Density Functional Theory Plus the Hubbard U Potential for Electron-Atom Coupled Dynamics Involving Charge Transfer.
We present methods for combining time-dependent density functional theory and the Hubbard U potential in the framework of the real-time propagation of Kohn-Sham orbitals to describe electron-atom coupled dynamics beyond the Born-Oppenheimer approximation. The time evolution of the noncommuting nonlocal operators were realized through Crank-Nicolson's inversion method and Suzuki-Trotter's split exponentiation. The electron dynamics related to the high speed motion of an alkali atom on a conjugated carbon plane is presented. The nonequilibrium charge oscillation between a metal surface and a localized atomic orbital, as modeled with graphene and Ca, is discussed.


Repurposing anticancer drugs for COVID-19-induced inflammation, immune dysfunction, and coagulopathy.
Three cardinal manifestations of neoplasia, namely inflammation, immune dysfunction, and coagulopathy are also seen in patients with severe SARS-CoV-2 infection, providing a biological rationale for testing selected anticancer drugs for their ability to control the symptoms and/or modify the course of COVID-19.


Structural requirements of C-type natriuretic peptide for elevation of cyclic GMP in cultured vascular smooth muscle cells.
C-type natriuretic peptide (CNP), which was recently found to be a selective ligand for one of the two known natriuretic peptide receptor guanylyl cyclases (NPR-B), potently stimulates cGMP production in cultured rat vascular smooth muscle cells (VSMC) and exerts potent antiproliferative effects on the cells. To investigate the structural requirements of CNP for stimulation of cGMP accumulation via NPR-B, we prepared CNP analogs and tested them on cultured rat VSMC. Our results indicate that only the ring portion of CNP with a disulfide bond (CNP(6-22)) participates in stimulation of cGMP accumulation, especially the sequence Leu9-Lys10-Leu11 in the ring portion executes essential roles for both elevation of cGMP and selectivity of the ligand for NPR-B. We also found a good correlation between the activities of the CNP analogs for stimulation of cGMP accumulation and inhibition of DNA synthesis.


Investigating single nucleotide polymorphism (SNP) density in the human genome and its implications for molecular evolution.
We investigated the single nucleotide polymorphism (SNP) density across the human genome and in different genic categories using two SNP databases: Celera's CgsSNP, which includes SNPs identified by comparing genomic sequences, and Celera's RefSNP, which includes SNPs from a variety of sources and is biased toward disease-associated genes. Based on CgsSNP, the average numbers of SNPs per 10 kb was 8.33, 8.44, and 8.09 in the human genome, in intergenic regions, and in genic regions, respectively. In genic regions, the SNP density in intronic, exonic and adjoining untranslated regions was 8.21, 5.28, and 7.51 SNPs per 10 kb, respectively. The pattern of SNP density based on RefSNP was different from that based on CgsSNP, emphasizing its utility for genotype-phenotype association studies but not for most population genetic studies. The number of SNPs per chromosome was correlated with chromosome length, but the density of SNPs estimated by CgsSNP was not significantly correlated with the GC content of the chromosome. Based on CgsSNP, the ratio of nonsense to missense mutations (0.027), the ratio of missense to silent mutations (1.15), and the ratio of non-synonymous to synonymous mutations (1.18) was less than half of that expected in a human protein coding sequence under the neutral mutation theory, reflecting a role for natural selection, especially purifying selection.


Prognostic value of high-sensitivity cardiac troponin I early after coronary artery bypass graft surgery.
The diagnosis of periprocedural myocardial infarction (PMI) after coronary artery bypass graft (CABG) is based on biochemical markers along with clinical and instrumental findings. However, there is not a clear cutoff value of high-sensitivity cardiac troponin (hs-cTn) to identify PMI. We hypothesized that isolated hs-cTn concentrations in the first 24 h following CABG could predict cardiac adverse events (in-hospital death and PMI) and/or left ventricular ejection fraction (LVEF) decrease. We retrospectively enrolled all consecutive adult patients undergoing CABG, alone or in association with other cardiac surgery procedures, over 1 year. Hs-cTn I concentrations (Access, Beckman Coulter) were serially measured in the post-operative period and analyzed according to post-operative outcomes. 300 patients were enrolled; 71.3% underwent CABG alone, 33.7% for acute coronary syndrome. Most patients showed hs-cTn I values superior to the limit required by the latest guidelines for the diagnosis of PMI. Five patients (1.7%) died, 8% developed a PMI, 10.6% showed a LVEF decrease ≥ 10%. Hs-cTn I concentrations did not significantly differ with respect to death and/or PMI whereas they were associated with LVEF decrease ≥ 10% (p value < 0.005 at any time interval), in particular hs-cTn I values at 9-12 h post-operatively. A hs-cTn I cutoff of 5556 ng/L, a value 281 (for males) and 479 (for females) times higher than the URL, at 9-12 h post-operatively was identified, representing the best balance between sensitivity (55%) and specificity (79%) in predicting LVEF decrease ≥ 10%. Hs-cTn I at 9-12 h post-CABG may be useful to early identify patients at risk for LVEF decrease and to guide early investigation and management of possible post-operative complications.


Ultrasonography of intrahepatic bile duct adenoma with renal cell carcinoma: correlation with pathology.
Intrahepatic bile duct adenoma (BDA) is a relatively rare benign tumor. Most cases are incidentally discovered during surgery or autopsy. We report here the co-existence of renal cell carcinoma and BDA mimicking metastasis in a 30-year-old female. An isoechoic nodule with a hypoechoic rim sized 10 × 9 mm was observed by ultrasonography in S2 of the liver. On contrast-enhanced ultrasonography (CEUS), the mass was enhanced in the early vascular phase and a defect with a clear border appeared in the post-vascular phase. We present the ultrasonography findings of BDA, including those yielded by CEUS using Sonazoid, along with the gross and microscopic pathological correlation.


Outcome for children born after in utero laser ablation therapy for severe twin-to-twin transfusion syndrome.
To examine the postnatal development of a group of children born after in utero laser ablation therapy for severe twin-to-twin transfusion syndrome. Retrospective cohort outcome study involving assessment of neurodevelopment and physical well being. Harris Birthright Centre, King's College Hospital, London. Twins and singleton survivors treated via laser ablation therapy for twin-to-twin transfusion syndrome over a four-year period. Of 54 families contacted to participate in the study, who had been treated for twin-to-twin transfusion syndrome during a four-year period, 24 families attended for paediatric assessment; 12 pairs of twins and 12 singleton survivors were assessed for perinatal, neurological and neurodevelopmental outcome using the Griffiths scales of mental development. A further 20 families were assessed via a proforma after contact with their general practitioner. A comparison of these groups showed no significant differences in sociodemographic factors or severity of disease between responders (44 families, 81.5%) and non-responders (10 families). The group of children assessed by a paediatrician had low birthweight (1619g donor, 1814g recipient, 1877g singleton) and had been born preterm (33 weeks twins, 31.2 weeks singleton) with attendant increased resuscitation, neonatal unit admission (mean 40 days) and instrumental delivery. Mean Griffiths scores were within the normal range of ability (91.2 donor vs 97.7 recipient and 101.6 singletons) with the only significant difference being in the locomotor subscale where donor (82.6) and recipient (85.3) were less than singletons: -99.1 (P < 0.05). There was no cerebral palsy in the singleton survivors, but there were five cases in the twin group. All except one affected child (with quadriplegia) had mean Griffiths scores in the normal range. In the GP proforma group there was one case, in a twin, of cerebral palsy. The overall cerebral palsy rate was 9%: 0% in the singleton survivors group and 13.3% in the twin survivors group. This pilot data highlights the need for careful long term follow up of children affected by twin-to-twin transfusion syndrome.


The growth of education differentials in marital dissolution in the United States.
Recent data suggest that overall divorce rates in the United States have been declining since the 1980s, while research examining marriages formed prior to 2004 suggests that divorce rates historically have not declined equally across the socioeconomic spectrum. Understanding recent differentials by education helps explore growing inequality over time given the well-documented negative consequences of divorce for women. This study examines marital dissolution and divorce rates in the new millennium to understand trends by marital cohort and educational attainment. To understand recent trends in marital stability, this study uses the 2006-2019 National Survey of Family Growth female dataset to assess the likelihood of marital dissolution and divorce by the 5th and 10th anniversary. Life tables and discrete-time event-history analyses are used to measure marital dissolution over time and by educational attainment while controlling for risk factors that may explain differentials. Overall marital dissolution and divorce rates are declining over time. However, this downward trend is driven by those with higher education; those with the least education are seeing rising marital dissolution rates, even when controlling for correlated risk factors. The greater divide when examining marital dissolution as compared to formal divorce also illustrates the lower propensity of the least educated to formalize their dissolution. Overall dissolution trends hide important - and growing - differentials by educational attainment. Declines in dissolution are not equally distributed across social classes; those women who are most vulnerable to divorce are least likely to be able to recover from its negative consequences.


Conservative Treatments for Lumbar Disc Herniation at L3-4 or L4-5 Were More Likely to Fail When Ipsilateral Foraminal Stenosis Was Present at the Caudally Adjacent Segment.
Conservative treatments are important in lumbar disc herniation (LDH), but predictors for poor outcomes are unclear. Consecutive patients with unilateral single-level LDH at L3-4 or L4-5 were enrolled. Baseline clinical data were collected, and lumbar spine magnetic resonance imaging was evaluated. Foraminal stenosis was evaluated using Lee's approach and further categorized as absence (grade 0 and 1) or presence (grade 2 or 3). Each patient underwent conservative treatments (oral meloxicam and dexamethasone, corset, back extension exercise, physiotherapy, and manual therapy) for 6 weeks. Conservative treatments were defined as failed if a patient underwent surgery within 6 weeks or reported poor recovery at 6-week follow-up. Multivariate logistic regressions were used to examine the associations of failed conservative treatments with baseline characteristics and magnetic resonance imaging findings. The study included 222 patients (mean age 45.5 ± 9.8 years). Of patients, 48 (21.6%) had concurrent ipsilateral foraminal stenosis at the caudal segment, and conservative treatments failed in 39 (17.6%). At baseline, patients with LDH and caudal foraminal stenosis were older (50.79 ± 6.14 years vs. 44.10 ± 10.13 years, P < 0.001), had greater leg pain (7.06 ± 1.17 vs. 6.39 ± 1.40, P = 0.003), and had a higher rate of positive straight leg raising test (54.2% vs. 33.3%, P = 0.008) than patients without caudal foraminal stenosis. In multivariate regression, failure of conservative treatments was associated with positive straight leg raising test (odds ratio 2.26, P = 0.046), and caudal foraminal stenosis (odds ratio 3.20, P = 0.007). In the presence of caudal foraminal stenosis and positive SLR test, conservative treatments were more likely to fail in patients with LDH.


Changes in the local cerebral metabolic rate for glucose in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease.
Nine adult monkeys (Macaca fascicularis) were used in this study. Five animals were used as controls. Three animals were injected intravenously daily with 0.5 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over a 4-day period; one animal was injected weekly over a 4-week period. Neurological examination of the MPTP-treated animals revealed a flexed posture of trunk and extremities, bradykinesia, increased tone without cogwheel rigidity, loss of vestibular righting reflexes, decreased vocalization and swallowing, failure of upgaze and abnormal pursuit eye movements. Reflexes were hyperactive. The compound 2-deoxy-D-[14C]glucose (2-DG) was utilized for the determination of the local cerebral metabolic rate for glucose (lCMRg). A generalized decrease in lCMRg was noted in all cerebral cortical areas as compared to control values. The cerebellar cortex demonstrated no change in lCMRg. Areas that demonstrated a significant increase in lCMRg were: the internal and external segments of the globus pallidus (P less than 0.01), the pars compacta and the pars reticulata of the substantia nigra (P less than 0.05). Areas that demonstrated a significant decrease in lCMRg were: the head of the caudate nucleus (P less than 0.05), the anterior dorsomedial putamen (P less than 0.05) and the anterior segment of the subthalamic nucleus (P less than 0.05). The 2-DG analysis of the MPTP primate model of Parkinson's disease is particularly suited to demonstrate areas in the central nervous system that are affected by this neurotoxin. Further studies of these areas may lead to a better understanding of the mechanisms that underlie the clinical symptomatology of Parkinson's disease.


Complex mandibular rehabilitation of a self-inflicted gunshot wound: a clinical report.
This report describes the surgical and prosthodontic rehabilitation of a patient traumatized by a self-inflicted gunshot wound to the mandible which required rehabilitation with a free fibula microvascular graft, single stage dental implant placement, and rehabilitation with CAD/CAM and laser assembled prosthetic components.


Synthesis of (+)-DGDP and (-)-7-epialexine.
The partial reduction of electron deficient pyrroles is an extremely versatile method that allows us to prepare substituted pyrrolidines and pyrrolizidines with trans-diol stereochemistry on the five membered ring.


CRISPR/Cas9 cleavage triggered ESDR for circulating tumor DNA detection based on a 3D graphene/AuPtPd nanoflower biosensor.
Circulating tumor DNA (ctDNA) plays an important role in the early diagnosis and prognosis of several cancers and is a credible biomarker for predicting the response to therapy. Additionally, the fact that the strategy used to detect ctDNA is non-invasive also adds to the advantages of using ctDNA for predicting disease diagnosis and prognosis. However, low abundance in peripheral blood and the high background of wild-type DNA impair the precise and specific measurement of ctDNA. In this study, we developed a novel 3D GR/AuPtPd nanoflower sensing platform based on CRISPR/Cas9 cleavage-triggered entropy-driven strand displacement reaction (ESDR) for the effective detection of ctDNA. Low levels of ctDNA could be detected using this method as the ESDR amplification does require complicated operation procedures and stringent reaction conditions. By combining the advantages of the site-specific cleavage by "gene magic scissors," Cas9/sgRNA, with those of the rapid amplification kinetics of entropy-driven strand displacement, our method resulted in amplification efficiency as well as high specificity for discriminating single-nucleotide mismatches. The 3D GR/AuPtPd nanoflower-based electrochemical biosensor displayed high specificity and worthy performance in assays with human serum. Therefore, this pioneered method provides a new paradigm for efficient ctDNA detection and shows great potential for use in clinical and diagnostic applications.


Multinucleated giant cells elicited around hydroxyapatite particles implanted in craniotomy defects are not osteoclasts.
The nature of the multinucleated giant cells (MNGC) elicited in contact with implantable biomaterials is still indecisive. In Wistar rats the MNGC recruited after the implantation of hydroxyapatite (HA) particles in standardized skull defects were examined morphologically (at both the light and electron microscope levels), enzymatically (tartrate-resistant acid phosphatase and non-specific esterase), and after a challenge with salmon calcitonin. The MNGC were of great size and contained abundant mitochondria, vacuoles, and vesicles throughout the cytoplasm; they were either tightly apposed to the HA surface or had long and thin processes penetrating the material. When processed for tartrate-resistant acid phosphatase, only a few cells were weakly stained. The staining was totally suppressed when samples were pretreated with cyanuric chloride in the MNGC but not in the host osteoclasts. Calcitonin induced the withdrawal of the host osteoclasts from the bone surface while the MNGC remained in contact with the HA material. The MNGC recruited to HA particles did not exhibit the morphologic, enzymatic and functional characteristics of the osteoclasts, and consequently must be regarded as macrophage polykaryons.


The lymphocyte surface antigen CD38 acts as a nicotinamide adenine dinucleotide glycohydrolase in human T lymphocytes.
The extracellular domain of the lymphocyte surface antigen CD38 has been recently shown to share a high sequence homology with a nicotinamide adenine dinucleotide (NAD+)-specific hydrolyzing enzyme cloned from the ovotestis of the gastropod Aplysia (E. States, D.J., Walseth, T.F., Lee, H. C., Trends Biochem. Sci. 1992. 17:495). In agreement with this finding, we present here evidence that CD38-overexpressing T cells, such as human thymocytes and cells from the human HPB-ALL T cell line, exhibit a NAD(+)-hydrolyzing enzymatic activity present on the outer surface of the cell membrane. In contrast, T lymphocytes with relatively low levels of CD38 marker, such as the human Jurkat cell line, display a lower activity. This suggests a relationship between ecto-NAD+ glycohydrolase activity and CD38 expression, as confirmed here when comparing wild-type Jurkat cells and a Jurkat cell variant overexpressing the CD38 molecule. Moreover, CD38 immunoprecipitates from thymocytes behave as an authentic NAD+ glycohydrolase enzyme: it transforms NAD+ stoichiometrically into nicotinamide plus adenosine 5'-diphosphoribose. Altogether these results strongly support the assumption that CD38 is actually a lymphocyte-specific NAD(+)-hydrolyzing enzyme, a finding that give new prospects to understand the in vivo function of this cell membrane protein.


Efficient copper-free Sonogashira coupling of aryl chlorides with palladium on charcoal.
Palladium on charcoal serves as an efficient and reusable solid supported catalyst for the Sonogashira coupling of aryl chlorides with terminal acetylenes in the presence of a bulky, electron-rich biphenyl type ligand (XPhos), without copper co-catalyst.


Noise Produced by Neonatal Ventilators Inside and Outside of the Incubators.
Insufficient data are available about the noise produced by modern neonatal ventilators. We aimed to measure their noise under different ventilatory modes and parameters. This was a bench study measuring the noise produced by 9 neonatal ventilators set in conventional or high-frequency oscillatory ventilation (HFOV), nasal mask-delivered CPAP with variable- or continuous-flow configuration, or bi-level positive airway pressure (considered as noninvasive ventilation [NIV]). Conventional ventilation and HFOV were tested in 2 distinct settings with moderate or higher parameters. Sound measurements were performed inside and outside an incubator mimicking the clinical setting and using a high-end meter meeting the international ISO 226:2003 standard. Four ventilators remained below the internationally recommended safety threshold but only for measurements outside the incubator. Conventional ventilation (49.1 [3.4] dBA) and HFOV (56.3 [5.2] dBA) were the least and most noisy respiratory support technique, respectively. Noise was greater inside than outside the incubators (P < .0001) and different between the ventilators (P < .0001); better results were achieved by Servo-u and Fabian family devices for conventional ventilation; by fabian HFO for HFOV; and by Servo-u, VN500, and fabian family devices for CPAP and NIV. Noise levels were similar when using moderate or higher parameters in conventional ventilation (P = .81) and in HFOV (P = .45). Modern ventilators often produce relevant noise, independent of the respiratory support modality, with acceptable noise levels being measured only outside the incubator. Better results were achieved with Servo-u, VN500, and Fabian family devices.


Minireview: the role of the vacuolar ATPase in nematodes.
The vacuolar ATPase enzyme complex (V-ATPase) pumps protons across membranes, energised by hydrolysis of ATP. It is involved in many physiological processes and has been implicated in many different diseases. While the broader functions of V-ATPases have been reviewed extensively, the role of this complex in nematodes specifically has not. Here, the essential role of the V-ATPase in nematode nutrition, osmoregulation, synthesis of the cuticle, neurobiology and reproduction is discussed. Based on the requirement of V-ATPase activity, or components of the V-ATPase, for these processes, the potential of the V-ATPase as a drug target for nematode parasites, which cause a significant burden to human health and agriculture, is also discussed. The V-ATPase has all the characteristics of a suitable drug target against nematodes, however the challenge will be to develop a high-throughput assay with which to test potential inhibitors.


Near fatal stent thrombosis in an aneurysmatic RCX as first manifestation of heparin induced thrombocytopenia (HIT) without thrombocytopenia.
Thrombosis resulting from heparin-induced thrombocytopenia (HIT) occurs in about 2% of patients without a significant decrease in platelet counts. We report on such a near fatal thrombotic event caused by coronary intervention. A supposedly "completely healthy" 53-year-old patient was admitted to hospital with covered rupture of an aneurysm of the Aorta descendens. He was successfully operated on and underwent coronary angiography due to NSTEMI six days later. Immediately after intervention of a 90% RCX stenosis he developed ventricular flutter, was defibrillated, and re-angiography showed partial occlusion of the RCX stent. Lots of white thrombi could be retrieved by aspiration catheter and gave reason for a HIT without thrombocytopenia. The detection of platelet factor 4/heparin complex antibodies by immunoassay supported and the subsequent Heparin Induced Platelet Activation Assay proved this diagnosis. The clinical event of an acute stent thrombosis should alarm the interventional team to the diagnosis of HIT even with a normal platelet count.


Coal smoke, gestational cadmium exposure, and fetal growth.
Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) μg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.


Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement.
All GABA(A) receptor (GABAR) subunits include an invariant proline in a consensus motif in the first transmembrane segment (M1). In receptors containing bovine alpha1, beta1 and gamma2 subunits, we analyzed the effect of mutating this M1 proline to alanine in the alpha1 or beta1 subunit using 3 different expression systems. The beta1 subunit mutant, beta1(P228A), reduced the EC(50) for GABA about 10-fold in whole cell recordings in HEK293 cells and L929 fibroblasts. The corresponding alpha1 subunit mutant (alpha1(P233A)) also reduced the GABA EC(50) when expressed in Xenopus oocytes; alpha1(P233A)beta1gamma2S receptors failed to assemble in HEK293 cells. Binding of [(3)H]flumazenil and [(3)H]muscimol to transfected HEK293 cell membranes showed similar levels of receptor expression with GABARs containing beta1 or beta1(P228A) subunits and no change in the affinity for [(3)H]flumazenil; however, the affinity for [(3)H]muscimol was increased 6-fold in GABARs containing beta1(P228A) subunits. In L929 cells, presence of the beta1(P228A) subunit reduced enhancement by barbiturates without affecting enhancement by diazepam or alfaxalone. Single channel recordings from alpha1beta1gamma2S and alpha1beta1(P228A)gamma2L GABARs showed similar channel kinetics, but beta-mutant containing receptors opened at lower GABA concentrations. We conclude that the beta1 subunit M1 segment proline affects the linkage between GABA binding and channel gating and is critical for barbiturate enhancement. Mutation of the M1 proline in the alpha1 subunit also inhibited receptor assembly.


Biosensors in fish production and quality control.
Fishery products are important not only from a nutritional point of view, but also as an item of international trade and foreign exchange earner for a number of countries in the world. Fish and shellfish are highly perishable, and prone to vast variations in quality due to differences in species, environmental habitats, feeding habits, etc. In addition, they can also function as carriers of several microbial and other health hazards. Therefore, maintenance of quality is of utmost importance in production and trade of fishery products. Most of the current quality control techniques are time consuming and cumbersome. There is an excellent scope for the application of biosensors in the seafood industry including the rapidly expanding aquaculture operations for fast assessment of quality. This article discusses the scope of applications biosensors in the seafood industry.


RNAi-mediated down-regulation of SHATTERPROOF gene in transgenic oilseed rape.
Oilseed rape is one of the important oil plants. Pod shattering is one of the problems in oilseed rape production especially in regions with dry conditions. One of the important genes in Brassica pod opening is SHATTERPROOF1 (SHP1). Down-regulation of BnSHP1 expression by RNAi can increase resistance to pod shattering. A 470 bp of the BnSHP1 cDNA sequence constructed in an RNAi-silencing vector was transferred to oilseed rape cv. SLM046. Molecular analysis of T2 transgenic plants by RT-PCR and Real-time PCR showed that expression of the BnSHP alleles was highly decreased in comparison with control plants. Morphologically, transgenic plants were normal and produced seeds at greenhouse conditions. At ripening, stage pods failed to shatter, and a finger pressure was needed for pod opening.


Persistence of ecologically similar fungi in a restricted floral niche.
Fungi in the genera Knoxdaviesia and Sporothrix dominate fungal communities within Protea flowerheads and seed cones (infructescences). Despite apparently similar ecologies, they show strong host recurrence and often occupy the same individual infructescence. Differences in host chemistry explain their host consistency, but the factors that allow co-occupancy of multiple species within individual infructescences are unknown. Sporothrix splendens and K. proteae often grow on different senescent tissue types within infructescences of their P. repens host, indicating that substrate-related differences aid their co-occupancy. Sporothrix phasma and K. capensis grow on the same tissues of P. neriifolia suggesting neutral competitive abilities. Here we test the hypothesis that differences in host-tissues dictate competitive abilities of these fungi and explain their co-occupancy of this spatially restricted niche. Media were prepared from infructescence bases, bracts, seeds, or pollen presenters of P. neriifolia and P. repens. As expected, K. capensis was unable to grow on seeds whilst S. phasma could. As hypothesised, K. capensis and S. phasma had equal competitive abilities on pollen presenters, appearing to explain their co-occupancy of this resource. Growth of K. proteae was significantly enhanced on pollen presenters while that of S. splendens was the same as the control. Knoxdavesia proteae grew significantly faster than S. splendens on all tissue types. Despite this, S. splendens was a superior competitor on all tissue types. For K. proteae to co-occupy infructescences with S. splendens for extended periods, it likely needs to colonize pollen presenters before the arrival of S. splendens.


Hydrological connectivity and herbivores control the autochthonous producers of coastal salt marshes.
Sea-level rise and overfishing could enhance the strength of hydrological connectivity and the presence of herbivores, resulting in salt marsh loss through physical stress and trophic cascade effects. Our aim was to estimate the effects of these two stresses on autochthonous producers. Survivorship and biomass of Suaeda salsa (S. salsa) were the lowest in areas with high hydrological connectivity, whereas the highest biomass was observed in the areas with moderate connectivity. The biomass of benthic microalgae was higher under low hydrological connectivity and no herbivores. The interactive effects between hydrological connectivity and herbivores on S. salsa but not on benthic microalgae were observed. Herbivores were somewhat (28%) important for the survival of initial S. salsa seedlings, while hydrological connectivity controlled (50%) the biomass of benthic microalgae. Our study highlights that, the autochthonous producers in coastal salt marshes may disappear due to strong hydrological connectivity and the excessive presence of herbivores.


Reconstructing viral haplotypes using long reads.
Most RNA viruses lack strict proofreading during replication. Coupled with a high replication rate, some RNA viruses can form a virus population containing a group of genetically related but different haplotypes. Characterizing the haplotype composition in a virus population is thus important to understand viruses' evolution. Many attempts have been made to reconstruct viral haplotypes using next-generation sequencing (NGS) reads. However, the short length of NGS reads cannot cover distant single-nucleotide variants, making it difficult to reconstruct complete or near-complete haplotypes. Given the fast developments of third-generation sequencing technologies, a new opportunity has arisen for reconstructing full-length haplotypes with long reads. In this work, we developed a new tool, RVHaplo to reconstruct haplotypes for known viruses from long reads. We tested it rigorously on both simulated and real viral sequencing data and compared it against other popular haplotype reconstruction tools. The results demonstrated that RVHaplo outperforms the state-of-the-art tools for viral haplotype reconstruction from long reads. Especially, RVHaplo can reconstruct the rare (1% abundance) haplotypes that other tools usually missed. The source code and the documentation of RVHaplo are available at https://github.com/dhcai21/RVHaplo. Supplementary data are available at Bioinformatics online.


Quality attributes of set yogurt made from lactoperoxidase system activated cow's milk.
The study aimed to assess the quality attributes of set yoghurt made from cow's milk preserved by lactoperoxidase system (LPs). Fresh cow's milk was collected from Datto milk collection center and samples were grouped to control and LPs activated. Set yoghurt was prepared immediately for the controlled samples, but in LPs activated milk, sample was kept for 9 h at 25 °C ± 2 before yoghurt was made. LP enzyme was activated within 2 h after milking by adding 1 mg/ml of sodium thiocyanate (SCN_) and hydrogen peroxide (H2O2). Totally, 36 L of cow's milk was used and the experiment was done in triplicates. Titratable acidity (TA) and pH were assessed every 30 min until coagulation formed. Yoghurt samples were stored for 21 days and different parameters were assessed including incubation duration, pH, TA, microbiological quality and sensory attributes. The results revealed that LPs partially suppressed the rate of acid production during incubation of cultured milk. Yoghurt made from LPs treated milk had significantly (P < 0.05) higher pH and lower TA values. Similarly, yoghurt made from LPs treated milk had lower total bacterial counts at 24-h, 72-h and 7-days of storages. Additionally, yoghurt from LPs activated milk had lower yeast and mold counts at 24-h and 7-days. Yoghurt made from LPs activated milk received better scores for the sensory attributes. In general, LPs activated milk can be used for making set yoghurt without a negative effect. Further studies are needed to illustrate the LPs activated milk fitness in making other cultured milk products.


Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes.
Polycystic ovary syndrome (PCOS) is a disorder of irregular menses, hyperandrogenism and/or polycystic ovary morphology. A large proportion of women with PCOS also exhibit insulin resistance, β-cell dysfunction, impaired glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that genetic variants that predispose to risk of T2D also result in risk of PCOS. Variants robustly associated with T2D in candidate gene or genome-wide association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years. Metabolic, reproductive and anthropomorphic data were examined as a function of the T2D variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. There was a nominal association between variants in KCNJ11 and risk of PCOS. However, a risk score of 33 independent T2D-associated variants from GWAS was not significantly associated with PCOS. T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes risk variants are not important risk variants for PCOS.


Induction of DNA damage by menadione (2-methyl-1,4-naphthoquinone) in primary cultures of rat hepatocytes.
The cytotoxicity of menadione (2-methyl-1,4-naphthoquinone) had been investigated using primary cultures of rat hepatocytes. Menadione was found to induce DNA strand breaks which were actively repaired by the cells. Dicoumarol, an inhibitor of DT diaphorase, did not potentiate menadione-induced DNA strand breaks. Neither had metyrapone, an inhibitor of cytochrome P-450 dependent monooxygenases, any effect on the extent of DNA damage. Covalent binding of menadione metabolite(s) to DNA was detected in the cultured hepatocytes and, in addition, hepatic microsomes were also found to metabolize menadione to DNA-binding products. The extent of binding of menadione to DNA in vitro, was markedly decreased by inclusion of the hepatic cytosol fraction, or reduced glutathione, in the incubations. In the presence of dicoumarol, menadione was also found to induce cell membrane damage. It also caused a rapid loss in cellular glutathione which was augmented by the presence of dicoumarol. The results suggest that both the cell membrane damage and DNA damage induced by menadione are mediated by one-electron reduction of the quinone to free radical intermediate(s). DT diaphorase appears to protect the cell from membrane damage, whereas reduced glutathione may have an important role in the prevention of DNA damage.


Nitrated lipids decompose to nitric oxide and lipid radicals and cause vasorelaxation.
Nitric oxide-derived oxidants such as nitrogen dioxide and peroxynitrite have been receiving increasing attention as mediators of nitric oxide toxicity. Indeed, nitrated and nitrosated compounds have been detected in biological fluids and tissues of healthy subjects and in higher yields in patients under inflammatory or infectious conditions as a consequence of nitric oxide overproduction. Among them, nitrated lipids have been detected in vivo. Here, we confirmed and extended previous studies by demonstrating that nitrolinoleate, chlolesteryl nitrolinoleate, and nitrohydroxylinoleate induce vasorelaxation in a concentration-dependent manner while releasing nitric oxide that was characterized by chemiluminescence-and EPR-based methodologies. As we first show here, diffusible nitric oxide production is likely to occur by isomerization of the nitrated lipids to the corresponding nitrite derivatives that decay through homolysis and/or metal ion/ascorbate-assisted reduction. The homolytic mechanism was supported by EPR spin-trapping studies with 3,5-dibromo-4-nitrosobenzenesulfonic acid that trapped a lipid-derived radical during nitrolinoleate decomposition. In addition to provide a mechanism to explain nitric oxide production from nitrated lipids, the results support their role as endogenous sources of nitric oxide that may play a role in endothelium-independent vasorelaxation.


Transcriptomic profiling of rose flower under treatment of various phytohormones and plant growth regulators.
Rose is one of the most important ornamental plants, accounting for one-third of the world's fresh cut flower market. The vase life refers to the period of a cut flower retaining its appearance in a vase. During this period, the rose was subjected to a variety of abiotic and biotic stresses, resulting in a reduction in the life of cut flowers. Numerous studies have been carried out on cut rose, which proves the effects of various plant hormones on post-harvest dehydration, petal senescence and abscission, disease and vase life of cut rose flowers. In addition, the natural or synthetic hormones or its inhibitor have been successfully used in cut flower preservatives to extend the vase life of rose. However, there is still a lack of systematic and in-depth research on the expression of rose genes related to plant hormone response. Here we analyzed the gene expression changes of the rose flower under treatment of 11 different plant hormones or its inhibitors in order to provide reference for rose studies.


Selective release of gastric inhibitory polypeptide by intraduodenal amino acid perfusion in man.
Intraduodenal amino acids are known to stimulate the release of gastric inhibitory polypeptide and cholecystokinin. In order to separate and quantitate gastric inhibitory polypeptide secretion selectively, 12 normal subjects received an intraduodenal perfusion of a mixed amino acid solution (158 mM) containing either methionine, phenylalanine, tryptophan, and valine (perfusate 1), or an amino acid solution containing arginine, histidine, isoleucine, leucine, lysine, and threonine (perfusate 2). Serum concentrations of gastric inhibitory polypeptide and insulin were significantly greater in the group receiving perfusate 2 (P less than 0.001). In contrast, after administration of amino acid perfusate 1, there was only a slight increase in serum gastric inhibitory polypeptide concentration and insulin secretion increased only slightly. Mean trypsin and bilirubin outputs in the group receiving perfusate 1 were nearly 3 times greater than the outputs of the group receiving the other amino acid mixture. This study expands the importance of intraduodenal amino acid mixtures in stimulating secretion of gastric inhibitory polypeptide and insulin and quantitatively separates gastric inhibitory polypeptide release from release of hormones that stimulate pancreatic enzyme secretion, such as cholecystokinin.


Segmentation of elastic fibres in images of vessel wall sections stained with Weigert's resorcin-fuchsin.
The elastic fibres are an essential component of the extracellular matrix in blood vessel walls that allows a long-range of deformability and passive recoil without energy input. The quantitative determination of elastic fibres will provide information on the state of the vascular wall and to determine the role and behaviour of this key structural element in different physiological and pathological vascular processes. We present a segmentation method to identify and quantify elastic fibres based on a local threshold technique and some morphological characteristics measured on the segmented objects that facilitate the discrimination between elastic fibres and other image components. The morphological characteristics analysed are the thickness and the length of an object. The segmentation method was evaluated using an image database of vein sections stained with Weigert's resorcin-fuchsin. The performance results are based on a ground truth generated manually resulting in values of sensitivity greater than 80% with the exception in two samples, and specificity values above 90% for all samples. Medical specialists carried out a visual evaluation where the observations indicate a general agreement on the segmentation results' visual quality, and the consistency between the methodology proposed and the subjective observation of the doctors for the evaluation of pathological changes in vessel wall. The proposed methodology provides more objective measurements than the qualitative methods traditionally used in the histological analysis, with a significant potential for this method to be used as a diagnostic aid for many other vascular pathological conditions and in similar tissues such as skin and mucous membranes.


Plants' ability to sense and respond to airborne sound is likely to be adaptive: reply to comment by Pyke et al.
Ecol. Lett. 22, 2019, 1483 demonstrated, for the first time, a rapid response of a plant to the airborne sounds of pollinators. Pyke et al. argue that this response is unlikely to be adaptive. Here we clarify some misunderstandings, and demonstrate the potential adaptive value using theoretical modelling and field observations.


Anterior minimally invasive subcapital osteotomy without hip dislocation for slipped capital femoral epiphysis.
A minimally invasive anterior approach appears to be an attractive alternative to achieve capital realignment without violating femoral head vascular supply and avoiding hip dislocation in slipped capital femoral epiphysis. The aim of this study was to detail the technical steps of subcapital realignment through a minimally invasive anterior approach and to report the preliminary results of this procedure in a prospective cohort of patients with stable slips. Nine patients underwent subcapital cuneiform wedge resection through a minimally invasive anterior approach without hip dislocation for moderate or severe stable slips between April 2012 and April 2013. Prophylactic stabilization of the contralateral hip was performed in all cases. A minimum 18 months follow-up was available. Clinical course was assessed using the Harris hip score and the hip range of motion. The degree of slippage as proposed by Southwick, the lateral α angle and the epiphyseal-metaphyseal distance allowed radiographic assessment. No patients were lost during follow-up, which was on average 28 months. No intraoperative complications occurred; one postoperative transient apraxia of the femoral cutaneous nerve, which completely recovered in six months, was recorded. Southwick angle, lateral α angle and epiphyseal-metaphyseal distance all improved substantially postoperatively. No cases of avascular necrosis were detected. Subcapital cuneiform wedge resection through a minimally invasive anterior approach without hip dislocation can be an easier alternative to restore proximal femoral anatomy in moderate to severe stable slips. Prospective case control studies are required to confirm these preliminary results.


Including competitive asymmetry in measures of local interference in plant populations.
Although considerable evidence exists that plant competition is generally asymmetric or "one-sided", with larger plants having a disproportionate competitive effect on smaller plants, currently employed measures of local interference generally assume that competition is "two-sided". We describe a simple measure of competitive asymmetry in which the effects of neighbors smaller than a focal individual are discounted by a constant factor, and include this variable in a composite measure of local interference. In this model competition varies between complete asymmetry (the effects of smaller plants are entirely discounted) and complete symmetry (the competitive effect of a neighbor is proportional to its size). The proposed method is applied to two natural populations and one experimental monoculture. In all cases an asymmetric model provides the best fit to the data. Completely two-sided models account for 26-39% of the variance in relative growth rate, while relatively one-sided models account for 44-57%. The increases in r 2 values resulting from the inclusion of asymmetry are significant in the two cases in which the data permit randomization tests. Our results suggest that interference is completely asymmetric in a population of Impatiens pallida, a species with very low root allocation and a shallow crown, and somewhat less asymmetric in an experimental monoculture of Ambrosia artemisiifolia and a natural stand of Pinus rigida, cases in which competition for water and nutrient resources is likely to be of greater importance.


Effectiveness of antimicrobial photodynamic therapy in restoring clinical, microbial, proinflammatory cytokines and pain scores in adolescent patients having generalized gingivitis and undergoing fixed orthodontic treatment.
The aim of the present study was to evaluate the effectiveness of photodynamic therapy (PDT) on clinical gingival inflammatory parameters, bacterial load, proinflammatory cytokine status, and pain scores in adolescent patients undergoing fixed orthodontic treatment with gingivitis. Thirty adolescent undergoing fixed orthodontic treatment with gingivitis were randomly divided into two groups: Group A - patients undergoing dental scaling (DS) with adjunctive photodynamic therapy (PDT) and Group BDS alone. Clinical gingival parameters including plaque scores, (PS), bleeding on probing (BOP) and probing depth (PD) were assessed. Visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ) were used to report the values of present pain intensity. Crevicular fluid was sampled to quantify the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α using enzyme-linked immunosorbent assay. The total bacterial counts for Porphyromonas gingivalis (P. gingivalis) and Tannerella forsythia (T. forsythia) were assessed. All examinations were performed at baseline, 1 week and 4 weeks. Both the treatment regimens reported statistically significant reduction in PS and BOP (p < 0.05). However, no significant difference was observed in PS and PD values when Group B was compared with Group A (p > 0.05). There was a statistically significant reduction noted for BOP in Group B when compared to Group A (p < 0.05). There was a statistically significant reduction in the microbial counts of T. forsythia in Group A when compared to Group B at week-1 (p < 0.05). During the 4-week follow-up, the counts for T. forsythia significantly increased. No significant changes could be seen in either of the pain scores in both the groups (p > 0.05). Both groups showed statistically significant reduction in the IL-6 and TNF-α levels. However, IL-6 was significantly reduced at 1 week, while TNF-a significantly reduced at 4 weeks of follow up among the participants in Group B. PDT has a positive effect in significantly reducing the periodontal microbial load in established gingivitis in adolescent patients undergoing fixed orthodontic treatment.


The lipoxygenase pathway in garlic (Allium sativum L.) bulbs: detection of the novel divinyl ether oxylipins.
Incubations of [1-14C]linoleic acid or [1-14C]-(9Z,11E, 13S)-13-hydropero xy-9,11-octadecadienoic acid (13-HPOD) with juice of garlic bulbs lead to the formation of one predominant labelled product, viz., the novel divinyl ether (9Z,11E, 1'E)-12-(1'-hexenyloxy)-9,11-dodecadienoic acid ('etheroleic acid'). With lesser efficiency [1-14C]alpha-linolenic acid or [1-14C](9Z,11E, 13S,15Z)-13-hydroperoxy-9,11,15-octadecatrienoic acid (13-HPOT) are converted in this way into (9Z,11E,1'E,1'E,3'Z)-12-(1',3'-hexadienyloxy)-9,11- dodecadienoic acid ('etherolenic acid'). Thus, garlic bulbs possess the activity of a new 13-hydroperoxide-specific divinyl ether synthase.


Assessing the damage caused by Deepwater Horizon: not just another Exxon Valdez.
In light of the high stakes of the Deepwater Horizon civil trial and the important precedent-setting role that the case will have on the assessment of future marine disasters, the methodologies underpinning the calculations of damage on both sides will be subjected to considerable scrutiny. Despite the importance of the case, however, there seems to be a pronounced lack of convergence about it in the academic literature. Contributions from scientific journals frequently make comparisons to the Ixtoc I oil spill off the coast of Mexico in 1979; the legal literature, by stark contrast, seems to be much more focused on the Exxon Valdez spill that occurred off the shores of Alaska in 1989. This paper accordingly calls for a more thorough consideration of other analogs beyond the Exxon Valdez spill-most notably, the Ixtoc I incident-in arriving at an assessment of the damage caused by the Deepwater Horizon disaster.


Community-acquired pneumonia in adults and children.
This article provides an overview of community-acquired pneumonia in adults and children. The epidemiology, causes, clinical presentation, diagnostic testing, site-of-care decisions, treatment, possible complications, and prevention of pneumonia are discussed.


FLAIR vascular hyperintensities predict functional outcome after endovascular thrombectomy in patients with large ischemic cores.
To establish whether collateral circulation was associated with functional outcome in stroke patients with large infarct size (Alberta Stroke Program Early CT Score [ASPECTS] ≤ 5) undergoing endovascular thrombectomy (EVT) METHODS: Consecutive patients with acute ischemic stroke due to large-vessel occlusion in the anterior circulation and an ASPECTS of ≤ 5 were analyzed. Quantification of collateral circulation was performed using a fluid-attenuated inversion recovery vascular hyperintensity (FVH)-ASPECTS rating system (score ranging from 0 [no FVH] to 7 [FVHs abutting all ASPECTS cortical areas]) by two independent neuroradiologists. Good functional outcome was defined by modified Rankin Scale (mRS) score of 0 to 3 at 3 months. We determined the association between FVH score and clinical outcome using multivariable regression analyses. A total of 139 patients (age, 63.1 ± 20.8 years; men, 51.8%) admitted between March 2012 and December 2017 were included. Good functional outcome (mRS 0-3) was observed in 65 (46.8%) patients, functional independence (mRS 0-2) was achieved in 43 (30.9%) patients, and 33 (23.7%) patients died at 90 days. The median FVH score was 4 (IQR, 3-5). FVH score was independently correlated with good outcome (adjusted OR = 1.41 [95% CI, 1.03-1.92]; p = 0.03 per 1-point increase). In stroke patients with large-volume infarcts, good collaterals as measured by the FVH-ASPECTS rating system are associated with improved outcomes and may help select patients for reperfusion therapy. • Endovascular thrombectomy can allow almost 1 in 2 patients with large infarct cores to achieve good functional outcome (modified Rankin Scale [mRS] of 0-3) and 1 in 3 patients to regain functional independence (mRS 0-2) at 3 months. • The extent of FVH score (as reflected by FLAIR vascular hyperintensity [FVH]-Alberta Stroke Program Early CT Score [ASPECTS] values) is associated with functional outcome at 3 months in this patient group.


Individually controlled aspirin in the long-term treatment of patients with chronic arterial diseases.
A simple method of measuring the biological effect of acetylsalicylic acid (ASA), based on the determination of the disaggregation rate (DR) of platelet aggregation induced by adenosine diphosphate (ADP), is described. The DR was found to correlate with the inhibition of the production of malondialdehyde (MDA) by platelets (r = 0.66, P less than 0.001). Therefore, the DR was used for laboratory monitoring of the ASA effect. The study included 63 arteriosclerotic patients--patients with ischemic heart disease (IHD), peripheral arterial disease (PAD), or cerebrovascular insufficiency (CVI) -- who were analyzed before treatment and after receiving ASA in an individually controlled dosage. Before treatment the authors found an increased level of MDA and a longer euglobulin clot lysis time in patients when compared with healthy volunteers (n = 16). Extremely different doses of ASA were required to normalize initially elevated MDA levels in patients. Normalization of the MDA level corresponds to a DR of at least 50% (in comparison with 0-13% without treatment). When judging the ASA dose individually from the 50% DR, the authors demonstrated that there were no differences in the levels of cyclooxygenase- and lipoxygenase-derived eicosanoids between healthy volunteers (n = 16) and arteriosclerotic patients receiving 100-250 mg (n = 18), 500 mg (n = 17), or 750-1500 mg ASA per day (n = 6). Thus, their results support the idea of using individually controlled ASA as the most promising way of resolving the "aspirin dilemma" and provide a simple and reproducible method of measuring the biological effect of ASA.