Genomic Patterns of Homozygosity in Chinese Local Cattle.
Genome-wide single nucleotide polymorphism (SNP) arrays can be used to explore homozygosity segments, where two haplotypes inherited from the parents are identical. In this study, we identified a total of 27,358 runs of homozygosity (ROH) with an average of 153 ROH events per animal in Chinese local cattle. The sizes of ROH events varied considerably ranging from 0.5 to 66 Mb, with an average length of 1.22 Mb. The highest average proportion of the genome covered by ROH (~11.54% of the cattle genome) was found in Nanda cattle (NDC) from South China, whereas the lowest average proportion (~3.1%) was observed in Yanhuang cattle (YHC). The average estimated FROH ranged from 0.03 in YHC to 0.12 in NDC. For each of three ROH classes with different sizes (Small 0.5-1 Mb, Medium 1-5 Mb and Large >5 Mb), the numbers and total lengths of ROH per individual showed considerable differences across breeds. Moreover, we obtained 993 to 3603 ROH hotspots (which were defined where ROH frequency at a SNP within each breed exceeded the 1% threshold) among eight cattle breeds. Our results also revealed several candidate genes embedded with ROH hotspots which may be related to environmental conditions and local adaptation. In conclusion, we generated baselines for homozygosity patterns in diverse Chinese cattle breeds. Our results suggested that selection has, at least partially, played a role with other factors in shaping the genomic patterns of ROH in Chinese local cattle and might provide valuable insights for understanding the genetic basis of economic and adaptive traits.


Novel 5-azaindolocarbazoles as cytotoxic agents and Chk1 inhibitors.
We describe here an efficient synthesis of new 5-azaindolocarbazoles designed for cytotoxic and Chk1 inhibiting properties. The synthesis of 'symmetrical' and 'dissymmetrical' structures is discussed. Concerning the dissymmetrical 5-azaindolocarbazoles derivatives, with both an indole moiety and a 5-azaindole moiety, the synthesis was achieved using two very efficient key steps. The first one is a Stille reaction with a 3-trimethylstannyl-5-azaindole derivative and the second one a photochemical step leading to the proposed polycyclic structure. Various pharmacomodulations were performed to investigate the structure-activity relationships (SAR). Several substituents such as OBn, OH, and methylenedioxy groups were successfully introduced on the indole moiety of the 5-azaindolocarbazole. Compounds with or without substituents on the nitrogen atom of the maleimide were prepared, as well as derivatives with glucopyranosyl substituent on the nitrogen atom of the indole moiety. The cytotoxicity of these new compounds was evaluated on two cell lines (L1210, HT29). Several compounds showed cytotoxicity in the sub-micromolar range. Among the most cytototoxic was the 1,3-dioxolo[4,5-b]-6-(2-dimethylaminoethyl)-1H-pyrido[3',4':4,5]pyrrolo[3,2-i]pyrrolo[3,4-g]carbazole-5,7(6H,12H)-dione (35, IC(50)=195 nM on L1210). The compounds were also investigated for their Chk1 inhibiting activity. Compounds without any substitution on the maleimide moiety were the most potent. This is the case of compounds 45-47 with IC(50) of, respectively, 72, 27, and 14nM toward Chk1. Compound 46, which exhibits moderate cytotoxicity, appears to be a good candidate for development in a multi-drug anticancer therapy.


Did Mozart have a chronic extradural haematoma?
When Mozart died at the age of 36, was he suffering from the belated complications of a calcified extradural haematoma? This theory took shape during the identification process of the skull owned by the Mozarteum, when the print of calcified extradural haematoma was discovered on the left inner temporoparietal calvarial surface of the skull. This print looks like a rosette, with three distinct concentric areas. The first outer area is striated, the second middle one is granular and scattered with bony deposits, the third central one is marked with vascular grooves.


The forecasting model research of rural energy transformation in Henan Province based on STIRPAT model.
In order to find the model of rural energy transformation in Henan Province. In this paper, Tapio decoupling model is employed to investigate the pivotal factors affecting rural power consumption (PC) and total energy consumption (TEC) in Henan Province. In addition, PSO-BP is used to predict the values of each influencing factor in 2020-2025. Last, the STIRPAT model is used to forecast TEC and PC from 2020 to 2025 based on the data of rural energy consumption in Henan Province from 2009-2019. The results show that other factors besides population promote TEC and PC to different degrees. Moreover, the influencing factors, TEC and PC, form a virtuous cycle of mutual promotion. Then, TEC and PC consumption show an increasing trend year by year in 2020-2025. It is worth noting that after 2022, the variation of PC is greater than that of TEC. To sum up, improving rural electrification level is a necessary way to realize its low-carbon energy transition.


Melatonin inhibits NaIO3-induced ARPE-19 cell apoptosis via suppression of HIF-1α/BNIP3-LC3B/mitophagy signaling.
Age-related macular degeneration (AMD) leads to gradual central vision loss and eventual irreversible blindness. Melatonin, an endogenous hormone, exhibits anti-inflammatory and antitumor effects; however, the role it plays in AMD remains unclear. Herein, we investigated the anti-AMD molecular mechanism of melatonin after sodium iodate (NaIO3) treatment of ARPE-19 cells in vitro and in animal models with the goal of improving the therapeutic effect. The in vitro results showed that melatonin protected against NaIO3-induced cell viability decline, mitochondrial dysfunction and apoptosis in ARPE-19 cells, and melatonin also alleviated NaIO3-induced reactive oxygen species (ROS) production, mitochondrial dysfunction and mitophagy activation. Melatonin reduced NaIO3-induced mitophagy activation through HIF-1α-targeted BNIP3/LC3B transcription, whereas ROS inhibition realized with N-acetylcysteine (NAC, a ROS inhibitor) combined with melatonin reduced the effect of NaIO3 on mitophagy. An animal model of AMD was established to confirm the in vitro data. Mouse tail vein injection of NaIO3 and melatonin was associated with enhanced repair of retinal layers within 7 days, as observed by optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining. A reduction in BNIP3 and HIF-1α levels, as determined by immunohistochemistry (IHC) assay, was also observed. These results indicate that melatonin attenuated NaIO3-induced mitophagy of ARPE-19 cells via reduction in ROS-mediated HIF-1α targeted BNIP3/LC3B signaling in vitro and in vivo. Melatonin may be a potential therapeutic drug in the treatment of AMD.


Frequency of Perceived Poststress Symptoms in Inpatients, Outpatients and Healthy Controls: The Role of Perceived Exhaustion and Stress.
Poststress symptoms occur as a consequence of stress, most commonly during leisure periods such as weekends and vacations. However, the prevalence and the pathological mechanisms of poststress symptoms are poorly understood. Here, we compared the frequency of poststress symptoms in healthy controls (n = 984), outpatients (n = 420), and inpatients (n = 101). In outpatients, demographic factors, psychosocial stress, and perceived exhaustion were tested as predictors of poststress symptoms with multivariate regression analysis. Poststress symptoms and perceived exhaustion were assessed using 2 Neuropattern Questionnaires (the NPQ - Patient Questionnaire and the NPQ - Symptom List), and psychosocial stress was evaluated using the Patient Health Questionnaire (PHQ). Poststress symptoms appeared in 2.9% of healthy controls, 20.0% of outpatients, and 34.7% of inpatients. Predictors were educational level, psychosocial stress, and perceived exhaustion. Poststress symptoms differed primarily between exhausted (75.0%) and nonexhausted patients (25.0%). Poststress symptoms are rather common in clinical populations, and they are primarily associated with the degree of perceived exhaustion. Preliminary evidence suggests that poststress symptoms are possibly related to depletion of norepinephrine stores, which may facilitate a stratified preventive and therapeutic treatment of these subjects.


A case of dual ectopic thyroid accompanied by positive antithyroid antibodies.
Ectopic thyroid tissue is an uncommon congenital aberration that is seldom present at two different sites simultaneously. The patient was a 32-year-old woman with dual ectopic thyroid accompanied by positive antithyroid antibodies. The simultaneous occurrence of dual ectopic thyroid and positive antithyroid antibodies has been documented in only two cases: the case discussed here and one previous case. The cervical ectopic thyroid was followed up by ultrasound, which showed an increase in the size of the lesion and an internal echo texture that became slightly heterogeneous after the patient had her second child. We speculated that these changes resulted from the changes in hormone demand brought on by pregnancy and parturition.


Will Vanadium-Based Electrode Materials Become the Future Choice for Metal-Ion Batteries?
Metal-ion batteries have emerged as promising candidates for energy storage system due to their unlimited resources and competitive price/performance ratio. Vanadium-based compounds have diverse oxidation states rendering various open-frameworks for ions storage. To date, some vanadium-based polyanionic compounds have shown great potential as high-performance electrode materials. However, there has been a growing concern regarding the cost and environmental risk of vanadium. In this Review, all links in the industry chain of vanadium-based electrodes were comprehensively summarized, starting with an analysis of the resources, applications, and price fluctuation of vanadium. The manufacturing processes of the vanadium extraction and recovery technologies were discussed. Moreover, the commercial potentials of some typical electrode materials were critically appraised. Finally, the environmental impact and sustainability of the industry chain were evaluated. This critical Review will provide a clear vision of the prospects and challenges of developing vanadium-based electrode materials.


Erbium:YAG laser resurfacing in Asians.
Although laser resurfacing has become increasingly popular in the treatment of Caucasian skin, concerns about healing and postinflammatory pigmentary changes have limited its use in Asian skin. The purpose of this study was to determine the efficacy and safety of the Erbium(ER):YAG laser used in the treatment of Asian skin. Fifty Asian individuals with Rhytids, scars, pigmentary alteration, and a variety of cutaneous growth were treated with the Erbium:YAG laser. Patients were evaluated for clinical efficacy, wound healing, post-operative erythema, and post-inflammatory pigmentary changes. Significant improvement was noted in all individuals. Shorter periods for re-epithelization and erythema duration were noted when compared to previously reported results following carbon dioxide laser resurfacing. The Erbium:YAG laser is safe and effective in the treatment of Asian skin.


A general method for synthesis of GPI anchors illustrated by the total synthesis of the low-molecular-weight antigen from Toxoplasma gondii.
Building blocks: a new, general synthetic strategy, which allows the construction of branched glycosylphosphatidylinositols (GPIs), enables the synthesis of parasitic glycolipid 1 from Toxoplasma gondii. In addition, the structure is further confirmed by recognition of monoclonal antibodies.


Chromatographic determination of aliphatic aldehydes in human serum after pre-column derivatization using 2,2'-furil, a novel fluorogenic reagent.
A novel, highly sensitive and selective fluorimetric liquid chromatographic method for simultaneous determination of medium chain aliphatic aldehydes was developed. The method was based on the derivatization of aliphatic aldehydes with 1,2-di(2-furyl)-1,2-ethanedione (2,2'-furil), a novel fluorogenic reagent, to form highly fluorescent difurylimidazole derivatives. The fluorescence derivatives were separated in less than 20min on a reversed-phase ODS column using an isocratic elution with a mixture of methanol-water (80:20, v/v%). The detection limits were from 0.19 to 0.50nM (1-10fmol/injection) at a signal-to-noise ratio (S/N) of 3. This method was successfully applied for monitoring of aliphatic aldehydes in healthy human sera by a simple pretreatment procedure without interferences from serum constituents.


Protein epitope mimetic macrocycles as biopharmaceuticals.
Fully synthetic medium-sized macrocyclic peptides mimicking the key β-hairpin and α-helical protein epitopes relevant in many protein-protein interactions have emerged as a novel class of drugs with the potential to fill an important gap between small molecules and proteins. Conformationally stabilized macrocyclic scaffolds represent ideal templates for medicinal chemists to incorporate bioactive peptide and protein pharmacophores in order to generate novel drugs to treat diseases with high unmet medical need. This review describes recent approaches to design and generate large libraries of such macrocycles, for hit identification, and for their efficient optimization. Finally, this review describes some of the most advanced protein epitope mimetic (PEM) macrocycles in clinical development.


Artificial, non-antibody binding proteins for pharmaceutical and industrial applications.
Using combinatorial chemistry to generate novel binding molecules based on protein frameworks ('scaffolds') is a concept that has been strongly promoted during the past five years in both academia and industry. Non-antibody recognition proteins derive from different structural families and mimic the binding principle of immunoglobulins to varying degrees. In addition to the specific binding of a pre-defined target, these proteins provide favourable characteristics such as robustness, ease of modification and cost-efficient production. The broad spectrum of potential applications, including research tools, separomics, diagnostics and therapy, has led to the commercial exploitation of this technology by various small- and medium-sized companies. It is predicted that scaffold-based affinity reagents will broaden and complement applications that are presently covered by natural or recombinant antibodies. Here, we provide an overview on current approaches in the biotech industry, considering both scientific and commercial aspects.


Fluctuating asymmetry of finger lengths, digit ratio (2D:4D), and tattoos: A pre-registered replication and extension of Koziel et al. (2010).
Tattoos bring risks yet no obvious evolutionary benefit. Koziel et al. (2010) reported increased fluctuating symmetry (a proxy for low developmental instability) in tattooed men, suggesting they could serve as fitness indicators. We replicate and extend the findings of Koziel et al. by examining fluctuating asymmetry of finger lengths and digit ratio (2D:4D) (a putative indicator of prenatal testosterone exposure) as predictors of adult tattoo prevalence. We used an online survey with a correlational design. Participants were recruited from the UK and Poland via university participant pools and social media. Data were available for presence/absence of tattoos and at least one predictor variable (composite Fluctuating Asymmetry [cFA], right-hand digit ratio [R2D:4D] and left-hand digit ratio [L2D:4D]) for n = 186 males and n = 997 females. We firstly assessed presence/absence of tattoos; when at least one tattoo was present, we also examined overall number and highest visibility. Greater cFA was associated with lower likelihood of having tattoos in males, though in females greater cFA was associated with higher numbers of tattoos. R2D:4D and L2D:4D correlated negatively with number of tattoos in males, and a positive correlation between L2D:4D and number of tattoos was observed in females. However, these latter findings did not remain significant after controlling for covariates. Tattoos may act as fitness indicators in males, though this explanation appears not to extend to females. Prenatal testosterone may also play a role, though doubt is cast on this premise because 2D:4D effects did not remain statistically significant after controlling for covariates.


Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells.
Aggregation of Fc gamma RII (CD 32), a low affinity receptor for immunoglobulin G (IgG), on the monocytic cell line THP-1 induces protein tyrosine kinase (PTK) activity. Several distinct cellular proteins, including Fc gamma RII itself, are phosphorylated on tyrosine following cross-linking of the receptor. Fc gamma RII lacks intrinsic PTK activity. In this report we demonstrate that a kinase activity was coprecipitated with Fc gamma RII in THP-1 cells. The kinetics of the receptor-associated kinase activity paralleled the appearance of tyrosine phosphorylation events observed following Fc gamma RII activation of THP-1 cells. Several proteins were associated with the receptor. Reimmunoprecipitation analysis demonstrated that lyn gene products were among the proteins coprecipitated with Fc gamma RII. p59hck (Hck) and p56lyn (Lyn) were the most abundant Src-related PTKs (Src-PTKs) in THP-1 cells. Enzymatic activity of both kinases, as measured by an in vitro kinase assay, was increased following specific cross-linking of Fc gamma RII. Furthermore, Fc gamma RII was specifically associated with both enzymes following its engagement and served as a substrate for both of these kinases. The association of Fc gamma RII with Src-PTK was specific for Fc gamma RII activation of THP-1 cells, since activation of cells via the high affinity Fc gamma receptor, Fc gamma RI (CD 64), did not result in association of Fc gamma RII with Hck or Lyn. Our data demonstrate a functional and physical association of Fc gamma RII with Hck and Lyn consistent with the involvement of Src-PTK in Fc gamma RII-mediated signal transduction.


Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease.
Insulin resistance is associated with cardiovascular disease risk and worsened kidney function. Patients with CKD have higher levels of insulin resistance. Elevated levels of copeptin (a surrogate for vasopressin levels) have been associated with an increased incidence and progression of CKD, and with incident diabetes mellitus. The purpose of our study was to examine the relationship between insulin resistance, copeptin, and CKD. We performed a cross-sectional study to investigate if insulin resistance was associated with higher copeptin levels in nondiabetic patients with stage 3-4 CKD versus controls. We measured plasma copeptin levels and used data from 52 patients with stage 3-4 CKD and 85 controls (eGFR ≥60 ml/min per 1.73 m2) enrolled in the Insulin Resistance in Chronic Kidney Disease (IRCKD) study. We then used a multivariable linear-regression model to assess the independent relationship between peripheral or hepatic insulin resistance and copeptin across levels of eGFR. We found that in patients with CKD (eGFR of 30-60 ml/min per 1.73 m2), but not in controls, peripheral insulin resistance was significantly correlated with higher levels of log copeptin (r=-0.21, P=0.04). In patients with CKD, when adjusted for age, sex, BMI, serum osmolality, log IL6, and log leptin/adiponectin ratio, each 1 SD decrease in insulin sensitivity was associated with a 39% increase in serum copeptin levels. The relationship between hepatic insulin resistance, copeptin, and eGFR is similar between controls and patients with reduced eGFR. Peripheral insulin resistance is associated with elevated copeptin levels in nondiabetic patients with stage 3-4 CKD. Further research into how the interaction between peripheral insulin resistance and elevated vasopressin affects CKD progression could be of interest.


Inhibition by neosurugatoxin and omega-conotoxin of acetylcholine release and muscle and neuronal nicotinic receptors in mouse neuromuscular junction.
Neosurugatoxin and omega-conotoxin, known to be specific ligands for the neuronal nicotinic receptor and Ca2+ channel, respectively, were previously claimed to exert no depressant action on the mouse neuromuscular junction. It was found that in preparations partially blocked with tubocurarine or with low Ca(2+)-high Mg2+ Tyrode's, both toxins, at 3-10 microM, depressed indirect twitches and either produced wanings (neosurugatoxin) or waxings (omega-conotoxin) of indirectly elicited tetanic contractions whilst in normal Tyrode's the contractile forces were not changed. In normal Tyrode's, neosurugatoxin decreased the amplitudes of spontaneous and evoked endplate potentials and enhanced the run-down of endplate potentials as did tubocurarine though with lesser potency. By contrast, omega-conotoxin (10 microM) decreased the amplitude of the evoked but not of the spontaneous endplate potential in low Ca(2+)-high Mg2+ Tyrode's, and produced facilitation of endplate potentials, instead of run-down, on repetitive stimulations. Higher concentrations of omega-conotoxin appeared to depress quantal release in normal Tyrode's. The effects were all reversible. The prolonged endplate depolarization found in preparations treated with neostigmine or 3,4-diaminopyridine, was partially depressed by both toxins. The results suggest that neosurugatoxin blocks the neuron and muscle nicotinic receptors in the neuromuscular junction with comparable potency. The pharmacology of the nicotinic receptor on motor nerve terminal seems more similar to the muscle nicotinic receptor than to that on autonomic ganglia or brain. On the other hand, omega-conotoxin seems to block a small fraction of Ca2+ channels on the motor nerve and decreases the quantal release of evoked endplate potentials.


Adjustment problems and maladaptive relational style: a mediational model of sexual coercion in intimate relationships.
Four hundred and fifty-three married or cohabitating couples participated in the current study. A meditational model of men's perpetration of sexual coercion within an intimate relationship was examined based on past theories and known correlates of rape and sexual coercion. The latent constructs of adjustment problems and maladaptive relational style were examined. Adjustment problem variables included perceived stress, perceived low social support, and marital discord. Maladaptive relational style variables included psychological aggression, dominance, and jealousy. Sexual coercion was a combined measure of men's reported perpetration and women's reported victimization. As hypothesized, adjustment problems significantly predicted sexual coercion. Within the meditational model, adjustment problems were significantly correlated with maladaptive relational style, and maladaptive relational style significantly predicted sexual coercion. Once maladaptive relational style was introduced as a mediator, adjustment problems no longer significantly predicted sexual coercion. Implications for treatment, limitations, and future research are discussed.


[Mitochondrial DNA polymorphism in the natural populations of the Drosophila virilis species group].
Restriction fragment length polymorphism (RFLP) analysis has been used to evaluate mitochondrial DNA (mtDNA) variation in 12 sibling species forming the Drosophila virilis species group. The variation thresholds corresponding to the interspecific and interstrain levels have been determined. The results indicate that interspecific hybridization has significantly contributed to the evolutionary history of the virilis species group.


Bone regeneration enhancement by ultra-violet (UV) treatment for uHA/PLLA absorbable mesh.
The purpose of this study was to evaluate the effect of bone regeneration enhancement by ultra-violet (UV) treatment of an unsintered hydroxyapatite (u-HA)/poly-l-lactic acid (PLLA) mesh in rabbitnasal bone. Thirty adult male Japanese white rabbits (12-16 weeks, 2.5-3.0 kg) were used in this study. After incising along the nasal bone, 6 × 6 × depth 1 mm two bone defects were made on both sides. In the UV group (n = 30), the defects were covered with uHA/PLLA mesh, treated by UV (wavelength 172 nm, tube wall illumination 13 mW/cm2, period 8 min, intensity 6.26 J/cm2) and screwed. In the control group (n = 30), untreated uHA/PLLA was applied in a similar manner. The rabbits were sacrificed at 1, 2, 3, 4 and 6 weeks postoperatively, and formalin-fixed specimens were frozen. The specimens were stained with haematoxylin and eosin. For immunohistochemical analysis, the specimens were treated with anti-alkaline phosphatase (ALP). Finally, bone ratio and ALP expression were evaluated microscopically. The UV group had a significantly higher number of ALP stained cells than the control group after 1, 2, and 3 weeks (P < 0.05). The bone ratio was also significantly higher in the UV group than in the control group after 1, 2, 3, and 4 weeks (P < 0.05). This study suggests that bone regeneration can be enhanced by UV treatment using an uHA/PLLA mesh.


Measurement of thiamylal and thiopental in plasma by electron capture and flame photometric gas-liquid chromatography.
We describe an isothermal gas-liquid chromatographic procedure developed for measuring thiamylal and thiopental in plasma. The unchanged drug is extracted into ethyl acetate from acidified plasma, together with an internal standard. The solvent is removed, the residue methylated, aliquots, diluted with benzene, are injected into a 183-cm gas-liquid chromatographic column containing 3% OV-17. Sensitivity of detection is in the nanogram to picogram range.


Genetic mapping of nth, a gene affecting endonuclease III (thymine glycol-DNA glycosylase) in Escherichia coli K-12.
The nth gene of Escherichia coli affects the production of endonuclease III, a glycosylase-endonuclease that attacks DNA damaged by oxidizing agents or by ionizing radiation. An nth insertion mutant and a deletion mutant were studied. nth is located between add and tyrS on the linkage map of E. coli K-12 and was 97% linked to tyrS in a transduction with phage P1.


The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts.
Differentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis. A cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed. 113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1). Intra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).


Imaging predictors of clinical outcomes after endovascular treatment in MRI-selected patients with acute basilar artery occlusion.
We aimed to investigate the impact of baseline infarct area and collateral status (CS), which are imaging predictors of clinical outcome following stroke, after endovascular treatment (EVT) in MRI-selected patients with acute basilar artery occlusion (BAO). Patients with acute BAO who underwent EVT within 24 h after stroke from December 2013 to February 2021 were included in this retrospective, multicenter, observational study. The baseline infarct area was evaluated by the posterior circulation of Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) using diffuse-weighted imaging (DWI), and CS was assessed by measuring the computed tomography angiography of the basilar artery (BATMAN) score and the posterior circulation collateral score (PC-CS) using magnetic resonance angiography (MRA). A Good outcome was defined as a modified Rankin scale score ≤ 3 at 3 months. For each imaging predictor, a multivariate logistic regression analysis was performed to evaluate its impact on good outcomes. A total of 86 patients were analyzed, and 37 (43.0%) had a good outcome. The latter showed significantly higher pc-ASPECTS than those without good outcomes. In multivariate analyses, a pc-ASPECTS ≥ 7 was significantly associated with good outcomes (OR, 2.98 [95% CI, 1.10-8.13], P = 0.032), while PC-CS ≥ 4 (OR, 2.49 [95% CI, 0.92-6.74], P = 0.073) and BATMAN score ≥ 5 (OR, 1.51 [95% CI, 0.58-3.98], P = 0.401) were not. In MRI-selected patients with acute BAO, pc-ASPECTS on DWI was an independent predictor of clinical outcomes after EVT, while the MRA-based CS assessments were not.


The role of ligand-receptor interactions in disease.
Ligand-receptor interactions play a determining role in many cell biological interactions. Mutations of ligands or receptors can both cause a disturbance in these interactions. In this paper an example will be given of these types of defects. Finally it will be speculated which role receptor mechanisms may play in the field of dermatology.


Sporophyte and gametophyte development of Platycerium coronarium (Koenig) Desv. and P. grande (Fee) C. Presl. (Polypodiaceae) through in vitro propagation.
The sporophyte and gametophyte development of Platycerium coronarium and P. grande were compared through ex situ propagation using in vitro culture technique and under greenhouse and field conditions. The morphology of the sporophyte and gametophyte, type of spore germination and prothallial development of P. coronarium and P. grande were documented. Gametophytes of P. coronarium and P. grande were cultured in vitro using different media. The gametophytes were then transferred and potted in sterile chopped Cyathea spp. (anonotong) roots and garden soil for sporophyte formation. Sporophytes (plantlets) of the two Platycerium species were attached on the slabs of anonotong and on branches and trunks of Swietenia macrophylla (mahogany) under greenhouse and field conditions. Sporophyte morphology of P. coronarium and P. grande varies but not their gametophyte morphology. P. coronarium and P. grande exhibited rapid spore germination and gametophyte development in both spore culture medium and Knudson C culture medium containing 2% glucose. Gametophytes of P. coronarium and P. grande transferred to potting medium produced more number of sporophytes while the gametophytes inside the culture media did not produce sporophytes. Sporophytes of P. grande attached on mahogany branches produced more number of leaves with bigger leaf area than those attached on anonotong slabs. Likewise, sporophytes of P. coronarium attached on mahogany branches and anonotong slabs did not develop new leaves during two weeks monitoring and are still in a period of adjustment to its environment. Sporophytes of P. grande grown or attached on the trunk of mahogany trees in the field and under shaded environment favored their growth.


Foreign body lodged in distal phalanx of left index finger-taser dart.
We report a case of a Taser dart presenting as a radio opaque foreign body to familiarize the Emergency Radiology community with the appearance of this non-lethal weapon which is being deployed in large numbers by police and security forces world wide.


The utility of ultrasonography in the management of undescended testis in a developing country.
The use of ultrasonography to localize the testis in children with undescended testis is still controversial. This study was designed to determine the value of ultrasound in the preoperative assessment of children with undescended testis in a resource-limited setting. A retrospective evaluation of all boys undergoing operation for undescended testes at the University of Nigeria Teaching hospital Enugu from June 2005 to December 2009 was performed. The operative findings were compared with the preoperative findings on clinical and ultrasound examinations. Overall, 49 boys with 60 undescended testes (unilateral in 38, and bilateral in 11 cases) were operated on during the study period. The median age of the patients was 5 (range, 1-14) years. At operation, 39 (65%) testes were located at the inguinal region, 17 (28.3%) were intra-abdominal, and 4 (6.7%) were vanishing testes. Of the inguinal testes, 30 (77%) were clinically palpable, and 38 (97.4%) accurately localized by ultrasound (p = 0.006). The intra-abdominal testes, the vanishing testes, and one inguinal testis were not identified with ultrasound. However, two testes identified as inguinal by ultrasound were found intraabdominal at operation, and two of the vanishing testes were recognized as viable testes by ultrasound. Ultrasound may identify some otherwise nonpalpable inguinal testes and hence affect therapeutic approach. It may, however, be unhelpful in truly abdominal and vanishing testes.


Intestinal vascular responses to dopamine during fentanyl-nitrous oxide anaesthesia, supplemented with dixyrazin.
Intestinal haemodynamics in response to continuous i.v. administration of dopamine were investigated in cats anaesthetized with fentanyl-nitrous oxide either with or without supplement of dixyrazin. A dose-dependent vasodilatation was observed in the dopamine dose range 2.5-35 micrograms . kg-1 . min-1 and the subsequent maximal intestinal blood flow increase was 121%. No net intestinal vasoconstriction was evident even at the largest dopamine doses, although the vascular response reached a plateau at 17.5 micrograms . kg-1 . min-1. Control experiments during chloralose anaesthesia gave similar results. Changes in mean arterial pressure and heart rate were small. Renal blood flow was virtually unchanged at dopamine doses below 10 micrograms . kg-1 . min-1, while renal vasoconstriction was evident following dopamine doses above that level. The addition of i.v. dixyrazin (0.15-0.30 mg . kg-1) to the fentanyl-nitrous oxide anaesthesia substantially potentiated the intestinal vasodilator response to i.v. dopamine and the maximal blood flow increase was 183% at 10-15 micrograms . kg-1 . min-1. In vitro experiments using mesenteric resistance vessels from the rat demonstrated a dose-dependent relaxation to dopamine. At very large doses this response was counteracted, but not reversed into vasoconstriction by dopamine-induced alpha-adrenergic stimulation.


T-Cell Epitope Immunotherapy in Mouse Models of Food Allergy.
Food allergy has been rising in prevalence over the last two decades, affecting more than 10% of the world population. Current management of IgE-mediated food allergy relies on avoidance and rescue medications; research into treatments that are safer and providing guaranteed and durable curative effects is, therefore, essential. T-cell epitope-based immunotherapy holds the potential for modulating food allergic responses without IgE cross-linking. In this chapter, we describe the methods in evaluating the therapeutic capacities of immunodominant T-cell epitopes in animal models of food allergy. Moreover, we explain in detail the methods to measure the allergen-specific antibody levels, prepare single-cell suspension from spleen, and prepare small intestine for immunohistochemical analysis of eosinophils and Foxp3+ cells.


Shear bond strengths between different zirconia cores and veneering ceramics and their susceptibility to thermocycling.
The purpose of this study was to evaluate the shear bond strength between various commercial zirconia core and veneering ceramics, and to investigate the effect of thermocycling. The Schmitz-Schulmeyer test method was used to evaluate the core-veneer shear bond strength (SBS) of three zirconia core ceramics (Cercon Base, Vita In-Ceram YZ Cubes, DC-Zirkon) and their manufacturer recommended veneering ceramics (Cercon Ceram S, Vita VM9, IPS e.max Ceram). A metal ceramic system (Degudent U94, Vita VM13) was used as a control group for the three all-ceramic test groups (n = 30 specimens/group). Half of each group (n = 15) was thermocycled (5-55 degrees C, 20,000 cycles). Subsequently, all specimens were subjected to shear force in a universal testing machine. Fractured specimens were evaluated microscopically to determine the failure mode. The initial mean SBS values in MPa+/-S.D. were 12.5+/-3.2 for Vita In-Ceram YZ Cubes/Vita VM9, 11.5+/-3.4 for DC-Zirkon/IPS e.max Ceram, and 9.4+/-3.2 for Cercon Base/Cercon Ceram S. After thermocycling mean SBS values of 11.5+/-1.7 MPa for DC-Zirkon/IPS e.max Ceram, 9.7+/-4.2 MPa for Vita In-Ceram YZ Cubes/Vita VM9, and 9.6+/-4.2 MPa for Cercon Base/Cercon Ceram S were observed. Neither the differences between the SBS values of the all-ceramic test groups nor the influence of thermocycling on all groups were statistically significant. Irrespective of thermocycling the metal ceramic control group (27.6+/-12.1 MPa, 26.4+/-13.4 MPa) exhibited significantly higher mean SBS than all three all-ceramic groups tested. The all-ceramic groups showed combined failure modes as cohesive in the veneering ceramic and adhesive at the interface, whereas the metal ceramic group showed predominately cohesive fractures. The results indicated that the SBS between zirconia core and veneering ceramics was not affected by thermocycling. None of the zirconia core and veneering ceramics could attain the high bond strength values of the metal ceramic combination.


Intermittent and chronic ultraviolet light exposure and uveal melanoma: a meta-analysis.
To examine the association between ultraviolet light exposure and uveal melanoma. Meta-analysis. A review of 133 published reports on risk factors for uveal melanoma revealed 12 studies that provided sufficient information to calculate odds ratios (ORs) and standard errors for ultraviolet light exposure factors. Data from these studies were extracted and categorized into intermittent ultraviolet exposure factors (welding, outdoor leisure, photokeratitis) and chronic ultraviolet exposure factors (occupational sunlight exposure, birth latitude, lifetime ultraviolet exposure index). Summary statistics were calculated for all risk factors reported by > or =4 independent studies. Welding, outdoor leisure, photokeratitis, occupational sunlight exposure, birth latitude, and lifetime ultraviolet exposure index. For intermittent ultraviolet exposure, welding was found to be a significant risk factor (5 studies, 1137 cases; OR, 2.05 [95% confidence interval [CI], 1.20-3.51]). Outdoor leisure was found to be nonsignificant (4 studies, 1332 cases; OR, 0.86 [95% CI, 0.71-1.04]). Photokeratitis conferred susceptibility in 3 reports studying this variable, but there were too few studies to validate meta-analyses. For chronic ultraviolet exposure, meta-analysis found occupational sunlight exposure to be a borderline nonsignificant risk factor for development of uveal melanoma (4 studies, 572 cases; OR, 1.37 [95% CI, 0.96-1.96]). Latitude of birth was found to be nonsignificant (5 studies, 1765 cases; OR, 1.08 [95% CI, 0.67-1.74]). This meta-analysis yielded inconsistent results associating ultraviolet light with development of uveal melanoma. There was evidence implicating welding as a possible risk factor for uveal melanoma.


The Effectiveness of Wearable Devices as Physical Activity Interventions for Preventing and Treating Obesity in Children and Adolescents: Systematic Review and Meta-analysis.
The prevalence of obesity in children and adolescents remains a global public health issue. Wearable devices may offer new opportunities for prevention and intervention in obesity. Previous systematic reviews have only examined the effect of the wearable device interventions on preventing and treating obesity in adults. However, no systematic review has provided an evaluation of wearable devices as physical activity interventions for preventing and treating obesity in children and adolescents. The purpose of this review and meta-analysis was to evaluate the effectiveness of wearable devices as physical activity interventions on obesity-related anthropometric outcomes in children and adolescents. Research articles retrieved from PubMed, EMBASE, Cochrane Library, Scopus, and EBSCO from inception to February 1, 2021, were reviewed. The search was designed to identify studies utilizing wearable devices for preventing and treating obesity in children and adolescents. The included studies were evaluated for risk of bias following the Cochrane recommendation. Meta-analyses were conducted to evaluate the effectiveness of wearable devices as physical activity interventions on body weight, body fat, BMI z-score (BMI-Z), BMI, and waist circumference. Subgroup analyses were performed to determine whether the characteristics of the interventions had an impact on the effect size. A total of 12 randomized controlled trials (3227 participants) were selected for meta-analysis. Compared with the control group, wearable device interventions had statistically significant beneficial effects on BMI (mean difference [MD] -0.23; 95% CI -0.43 to -0.03; P=.03; I2=2%), BMI-Z (MD -0.07; 95% CI -0.13 to -0.01; P=.01; I2=81%), body weight (MD -1.08; 95% CI -2.16 to -0.00; P=.05; I2=58%), and body fat (MD -0.72; 95% CI -1.19 to -0.25; P=.003; I2=5%). However, no statistically significant effect was found on waist circumference (MD 0.55; 95% CI -0.21 to 1.32; P=.16; I2=0%). The subgroup analysis showed that for participants with overweight or obesity (MD -0.75; 95% CI -1.18 to -0.31; P<.01; I2=0%), in the short-term (MD -0.62; 95% CI -1.03 to -0.21; P<.01; I2=0%), wearable-based interventions (MD -0.56; 95% CI -0.95 to -0.18; P<.01; I2=0%) generally resulted in greater intervention effect size on BMI. Evidence from this meta-analysis shows that wearable devices as physical activity interventions may be useful for preventing and treating obesity in children and adolescents. Future research is needed to identify the most effective physical activity indicators of wearable devices to prevent and treat obesity in children and adolescents.


NanoString nCounter® Approach in Breast Cancer: A Comparative Analysis with Quantitative Real-Time Polymerase Chain Reaction, In Situ Hybridization, and Immunohistochemistry.
Accurate testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is essential for breast cancer treatment. At present, immunohistochemistry (IHC)/florescence in situ hybridization (FISH) are widely accepted as the standard testing methods. To investigate the value of NanoString nCounter®, we performed its comparative analysis with IHC/FISH and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the assessment of ER, PR, and HER2. Data on IHC/FISH results for ER, PR, and HER2 in 240 patients from a single tertiary hospital in Korea were collected and compared with NanoString nCounter® and qRT-PCR results at a single institution. Expression levels for each gene using NanoString nCounter® showed good correlation with the corresponding data for protein expression by IHC (p<0.001) and gene amplification status for HER2 (p<0.001). Comparisons between gene expression and IHC data showed good overall agreement with a high area under the curve (AUC) for ESR1/ER (AUC=0.939), PgR/PR (AUC=0.796), and HER2/HER2 (AUC=0.989) (p<0.001). The quantification of ER, PgR, and HER2 mRNA expression with NanoString nCounter® may be a viable alternative to conventional IHC/FISH methods.


Lactoferrin secretion in alcoholic pancreatic disease.
Lactoferrin, a nonenzyme protein normally secreted in small amounts in pancreatic juice, has been reported by several investigators to be secreted in large amounts in chronic pancreatitis. Whether this increased secretion first occurs at an early or late stage of alcoholic pancreatic disease is unknown. In this study we measured lactoferrin and enzyme outputs in duodenal juice from 10 healthy subjects and three groups of alcoholic subjects: asymptomatic chronic alcoholics without evidence, clinically or biochemically, of pancreatitis (10), those recovered from acute pancreatitis (8), and those with established chronic pancreatitis (8). A multilumen, marker-perfused duodenal catheter was used to aspirate basal pancreatic secretions at the ligament of Treitz. The mean ( +/-SE) lactoferrin concentration in duodenal juice for the four groups of subjects was: healthy, 0.7 +/- 0.1 micrograms/ml; asymptomatic alcoholics, 5.5 +/- 1.5 micrograms/ml; alcoholics who had recovered from acute pancreatitis, 7.4 +/- 0.8 micrograms/ml; and alcoholics with chronic pancreatitis 7.1 +/- 1.9 micrograms/ml. The three groups of alcoholics each had a greater lactoferrin concentration than the normals (P less than 0.005). The output of lactoferrin in the four groups paralleled the concentration in that the three groups of alcoholics had a significantly greater output: healthy subjects, 3.4 +/- 0.5 micrograms/kg/hr; asymptomatic alcoholics, 25.7 +/- 7.4 micrograms/kg/hr; alcoholics recovered from acute pancreatitis, 80.1 +/- 27 micrograms/kg/hr; and alcoholics with chronic pancreatitis, 90.9 +/- 32 micrograms/kg/hr. The output of chymotrypsin and trypsin in the four groups of subjects revealed increased secretory rates in the asymptomatic alcoholics and the alcoholics recovered from acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)


The dark side of a success story: microRNAs of the C19MC cluster in human tumours.
MicroRNAs are a class of macromolecules of rapidly emerging significance for the pathogenesis of numerous human diseases, including cancer. Moreover, many of them hold great promise as valid biomarkers because of their high extracellular stability. Chromosome 19 harbours the largest cluster of microRNA genes known so far, which has developed in a very short time during mammalian evolution. Thus, in terms of evolution, gain of this cluster is an apparent success story. Nevertheless, we know very little about how functions of its microRNAs have contributed to this success and apparently, at least some of them can turn from Jekyll into Hyde and contribute to tumourigenesis. Recent work published in the Journal of Pathology by Fornari and colleagues, addressed here, reveals how members of that cluster are involved in the molecular pathogenesis of hepatocellular carcinomas.


The fox, the hedgehog, and hypnosis.
Isaiah Berlin's contrast between the fox, who "knows many things," and the hedgehog, who "knows one big thing," is the starting point for a consideration of monolithic and pluralistic approaches to hypnosis.


Segmentation of Chronic Subdural Hematomas Using 3D Convolutional Neural Networks.
Chronic subdural hematomas (cSDHs) are an increasingly prevalent neurologic disease that often requires surgical intervention to alleviate compression of the brain. Management of cSDHs relies heavily on computed tomography (CT) imaging, and serial imaging is frequently obtained to help direct management. The volume of hematoma provides critical information in guiding therapy and evaluating new methods of management. We set out to develop an automated program to compute the volume of hematoma on CT scans for both pre- and postoperative images. A total of 21,710 images (128 CT scans) were manually segmented and used to train a convolutional neural network to automatically segment cSDHs. We included both pre- and postoperative coronal head CTs from patients undergoing surgical management of cSDHs. Our best model achieved a DICE score of 0.8351 on the testing dataset, and an average DICE score of 0.806 ± 0.06 on the validation set. This model was trained on the full dataset with reduced volumes, a network depth of 4, and postactivation residual blocks within the context modules of the encoder pathway. Patch trained models did not perform as well and decreasing the network depth from 5 to 4 did not appear to significantly improve performance. We successfully trained a convolutional neural network on a dataset of pre- and postoperative head CTs containing cSDH. This tool could assist with automated, accurate measurements for evaluating treatment efficacy.


Real time corner detection for miniaturized electro-optical sensors onboard small unmanned aerial systems.
This paper describes the target detection algorithm for the image processor of a vision-based system that is installed onboard an unmanned helicopter. It has been developed in the framework of a project of the French national aerospace research center Office National d'Etudes et de Recherches Aérospatiales (ONERA) which aims at developing an air-to-ground target tracking mission in an unknown urban environment. In particular, the image processor must detect targets and estimate ground motion in proximity of the detected target position. Concerning the target detection function, the analysis has dealt with realizing a corner detection algorithm and selecting the best choices in terms of edge detection methods, filtering size and type and the more suitable criterion of detection of the points of interest in order to obtain a very fast algorithm which fulfills the computation load requirements. The compared criteria are the Harris-Stephen and the Shi-Tomasi, ones, which are the most widely used in literature among those based on intensity. Experimental results which illustrate the performance of the developed algorithm and demonstrate that the detection time is fully compliant with the requirements of the real-time system are discussed.


Denaturing high-performance liquid chromatography using the WAVE DNA fragment analysis system.
Denaturing high-performance liquid chromatography (DHPLC) is a chromatographic mutation analysis technique that is based on temperature-dependent separation of DNA containing mismatched base pairs from polymerase chain reaction (PCR)-amplified DNA fragments. The WAVE system, developed for DHPLC analysis, allows for unattended analysis of 96 samples directly from a PCR plate under a number of different conditions. It utilizes a Peltier cooling platform to maintain sample integrity. Sample detection is achieved via UV absorbance at 260 nm, thereby avoiding the cost, safety, variability, or waste disposal issues associated with radioisotopic, enzyme-linked, or fluorescence detection systems. There are four key aspects to successfully detecting mutations on the WAVE: (1) PCR primer design, (2) PCR protocol, (3) separation gradient, and (4) separation temperature. Provided these procedures are carried out correctly, almost 100% detection of single-nucleotide polymorphisms (SNPs) and small deletion/insertion mutations can be achieved. For this reason, DHPLC is a powerful tool for identifying mutations in candidate genes for hypertension.


Exploring how positive and negative social exchanges relate to posttraumatic stress disorder severity among previously deployed men service members/veterans.
Research in civilians and women shows negative social support is more deleterious for posttraumatic stress disorder (PTSD) symptoms than are the buffering effects of positive social support. However, this is understudied in male military samples. Moreover, appraisals of social support appear to be the mechanism of the association of social support type and PTSD severity, but appraisals as mediators have not been explored in military samples. Previously deployed male service members/veterans (SM/Vs; n = 333) completed a demographic inventory, the Positive and Negative Social Exchange Scale, which assesses positive and negative social support and their appraisals, and the PTSD Checklist-5. Path analyses examined associations of positive and negative social support with PTSD severity and whether appraisals mediated these associations. The magnitude of the association of negative social support and PTSD symptom severity (standardized estimate = .33; SE = .06, p < .001) was statistically greater than the association of positive social support and PTSD symptom severity (standardized estimate = -.26; SE = .06, p < .001). Higher positive support was associated with higher appraisals, and in turn, higher appraisals were associated with lower PTSD severity, suggesting mediation. In contrast, the association of negative social support with PTSD was direct. Causality cannot be inferred. Positive support exhibits a weaker relationship with PTSD because its effect is dependent on how an individual appraises the support whereas negative support has a direct relationship with PTSD regardless of appraisals. Findings suggest positive support interventions should focus on individual perceptions whereas negative support interventions should focus on decreasing how often these interactions occur. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


The Contribution of Stress and Distress to Cardiovascular Health in Adult Survivors of Childhood Cancer.
Childhood cancer survivors are at risk for cardiovascular morbidity and mortality that is not fully explained by cancer-directed therapies. We examined the contribution of emotional stress and distress to cardiac health in adult survivors of childhood cancer. Participants included 3,267 adult survivors enrolled in the St. Jude Lifetime Cohort Study [median (range) 29.9 (18.1-64.5) years of age; 7.7 (0-24.8) years at diagnosis; 48.4% female]. Survivors completed comprehensive medical assessments and standardized measures of depression, anxiety, posttraumatic stress symptoms (PTSS), and perceived stress. Cardiovascular-related conditions included hypertension, diabetes, dyslipidemia, cardiomyopathy, dysrhythmia, myocardial infarction (severity graded 0-4), and metabolic syndrome (yes/no). Multivariable modified Poisson models examined associations between symptoms of stress/distress and cardiovascular outcomes. Longitudinal associations between stress/distress and new-onset cardiovascular outcomes, defined as a change from grade ≤1 at initial evaluation to grade ≥2 at follow-up (median 3.9 years) were examined in 1,748 participants. In multivariable cross-sectional models, stress/distress was associated with hypertension [risk ratio (RR) = 1.24; 95% confidence interval (CI), 1.07-1.43], dyslipidemia (RR = 1.29; 95% CI, 1.03-1.61), and metabolic syndrome (RR = 1.35; 95% CI, 1.17-1.54) independent of known cardiovascular risk factors. In longitudinal models, stress/distress was associated with new-onset dysrhythmia (RR = 2.87; 95% CI, 1.21-6.78), perceived stress with hypertension (RR = 1.42; 95% CI, 1.04-1.95), and PTSS and anxiety with dyslipidemia (RR = 1.72; 95% CI, 1.13-2.62; RR = 1.54; 95% CI, 1.01-2.35, respectively). Stress/distress is independently associated with adverse cardiovascular outcomes among childhood cancer survivors. Improving psychological health may serve as a potential intervention target for optimizing cardiac health among childhood cancer survivors.


Have we reduced the risk of getting cancer or of dying from cancer? An update.
We have examined trends in cancer mortality, incidence and survival in the United States to update our earlier work and respond to criticisms. [Bailar, J.C., Smith, E.M.: New Engl. J. Med. 314, 1226 (1986).] Here we concentrate on the years 1975-1984, and show that overall cancer mortality has increased, incidence has increased and case survival is virtually unchanged. This generally unfavorable picture is scarcely changed when lung cancer is excluded from the trends. While trends for individual cancers have been mixed, overall progress in both curative treatment and prevention has been minimal. This evaluation does not deny the marked progress in treating some uncommon forms of cancer, improved palliation, reduced extent or severity of treatment, or benefits of cancer research that can be applied in other areas of medicine. While our finding of limited progress is not new, we believe that it requires increased attention in setting the course of future research initiatives, demonstration programs, medical training and clinical practice.


Earthworm numbers, biomass and respiratory metabolism in a beech woodland-Wytham Woods, Oxford.
The mean annual population density of earthworms was found to be 164.6 m-2 during a period of detailed study between October 1971 and September 1972. In a year of less detailed study between November 1972 and October 1973 the population density was 117.5 m-2 (139.8 m-2 when the type of extraction method was allowed for). Mean biomass densities in the two years of investigation were 41.0 g preserved wet wt m-2 (1971-1972) and 38.6 (possibly 39.2) g preserved wet wt m-2 (1972-1973).Comparison of the Brogden's Belt population and biomass densities with those reported from other woodlands indicates that soil type is more important than leaf litter type in determining the numerical abundance of earthworms. Population densities are lower in beechwoods on mor soils, mor soils also support significantly fewer species. As with numbers, mean biomass density in beechwoods on mor soils was significantly lower than that occurring in beechwoods on mull soils; the latter, in turn, being lower than those found in mixed deciduous woods on mull soils. Unlike population density biomass density is influenced by both soil and litter type, this is discussed by reference to mean body weights and food quality as reflected by tannin, nitrogen and carbohydrate content.The annual respiratory metabolism of the Brogden's Belt earthworms was calculated to be between 10.7 and 13.41 O2 m-2 a-1, which is equivalent to between 4.1 and 5.1% of the total soil metabolism. A production/biomass ratio of 0.49-0.58 was estimated, as was a net population efficiency of 22%.


Hypercrosslinking porous polymer layers on TiO2-graphene photocatalyst: Enhanced adsorption of water pollutants for efficient degradation.
Solar-driven photocatalysis offers an environmentally friendly and sustainable approach for the degradation of organic pollutants in water without chemical additives, but the low specific surface area and adsorption capacity of common photocatalysts restricts the surface reactions with the contaminants. Herein, we hypercrosslinked polymer layers on TiO2-graphene surface to enlarge the specific surface area from 136 to 988 m2/g, leading to a high adsorption capacity of sulfadiazine as 54.3 mg/g, which is 15.5 times that of TiO2-graphene (3.5 mg/g). The adsorption kinetics reveals the combination of physical and chemical adsorption by porous benzene-based polymer for sulfadiazine enrichment. Besides, the polymer layers with broad light absorption enable the composite to function efficiently as visible-light-driven photocatalysts. Thus, the as-designed composite exhibits excellent performance for sulfadiazine removal by integrating the adsorptive and photocatalytic processes, especially for the diluted sulfadiazine solution. More importantly, the porous polymer layer can function as a filter for weakening the interference of TiO2 surface with the natural matters from complex water matrices. Based on the identification of dominant reactive species, the possible attacking pathway and the sulfadiazine subsequent degradation are presented. Further, the enhanced adsorption and photodegradation efficiency can also be achieved for the removal of other typical pollutants such as 4-chlorophenol and methylene blue. This study highlights an adsorption-enhanced-degradation mechanism for water pollutants that can direct the design of high-performance photocatalysts under visible light.


Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression.
Adinazolam, a triazolobenzodiazepine, was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives. Forty-eight patients entered the study, and 35 completed 6 weeks of evaluation. Patients were well matched in each of the groups. Initially, the adinazolam group showed more improvement than the placebo group, but this trend did not persist beyond day 7. The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups, and final scores were significantly better for amitriptyline. Depressive symptoms in the amitriptyline dropout group appeared improved, whereas in the adinazolam and placebo dropout groups they were unchanged or worse. Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo. Thus, amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo.


Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice.
Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with delicate RAS-like nuclear changes are follicular adenomas when they are noninvasive, follicular carcinomas when invasive, and follicular variant PTCs when they have fully developed PTC-type nuclear features in Asian practice. The different diagnostic threshold of PTC nuclear features resulted in a high (50-90%) incidence of BRAFV600E mutation of PTCs in most Asian countries, whereas it was low (35-50%) in most Western patient cohorts. The contamination of indolent RAS-like tumors in the malignant PTC category in Western patient cohorts explains why the BRAFV600E gene test identifies aggressive PTCs. However, the BRAFV600E test has no prognostic value for Asian PTC patients because most biologically benign or low-risk RAS-like tumors are excluded from PTC. All prognostic analyses of thyroid carcinomas before 2017 must be re-evaluated because most clinical guidelines were established based on data obtained from Western patient cohorts where a significant number of indolent RAS-like tumors were misclassified in the malignant category.


Combined effects of oestrogen receptor antagonists on in vitro vitellogenesis.
Some environmental compounds are known to have anti-oestrogenic activity and their modes of action (MoA) are believed to include competitive inhibition of 17β-estradiol (E2) binding to the oestrogen receptor (ER) or interference with ER-dependent processes. The presence of multiple compounds having the same MoA may cause concern, as exposure to multiple compounds at concentrations below their threshold for effect can interact with cellular targets to cause effects in combination. The combined effect of mixtures can be assessed using prediction models such as concentration addition (CA) and independent action (IA). The objective of the present study was to determine if the CA and IA prediction models could accurately characterise the combined effects of mixtures of ER antagonists in rainbow trout (Oncorhynchus mykiss) hepatocytes using the ER-mediated production of the oestrogenic biomarker vitellogenin (Vtg) as a screening assay. Model anti-oestrogens (4-hydroxytamoxifen and ZM 189.154) and environmentally relevant compounds (PCBs and PAHs) were tested to ensure inclusion of compounds from different chemical classes and with different MoAs. All eleven tested compounds had the ability to reduce the in vitro E2-induced production of Vtg in a concentration-dependent manner. The potency of the tested compounds differed by four orders of magnitude based on the concentrations for 50% inhibition (IC(50)). The observed order of potency was 2,3,7,8-tetrachlorodibenzo-p-dioxin>4-hydroxytamoxifen>3,3',4,4',5-pentachlorobiphenyl>benzo(k)fluoranthene>3,3',4,4'-tetrachlorobiphenyl>β-naphthoflavone>ZM 189.154>indeno[1,2,3-cd]pyrene>benzo(b)fluoranthene>benzo(a)pyrene>benzo(a)anthracene. The CA and IA models were able to predict the combined effects of mixtures of ER antagonists with similar MoA. The mixtures of certain ER-antagonists with different and/or complex MoA caused deviations from both the CA and the IA model by causing higher anti-oestrogenic activity than predicted from the potency of the compounds alone. The rationale for these deviations warrants additional studies to assess the potential impacts on the health of organisms.


Reduced caveolin-1 promotes hyperinflammation due to abnormal heme oxygenase-1 localization in lipopolysaccharide-challenged macrophages with dysfunctional cystic fibrosis transmembrane conductance regulator.
We have previously reported that TLR4 signaling is increased in LPS-stimulated cystic fibrosis (CF) macrophages (MΦs), contributing to the robust production of proinflammatory cytokines. The heme oxygenase-1 (HO-1)/CO pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. In this study, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules enhances CAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations re-established HO-1 and CAV-1 cell surface localization in CF MΦs. Consistent with restoration of HO-1/CAV-1-negative regulation of TLR4 signaling, genetic or pharmacological (CO-releasing molecule 2) induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counterregulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1-dependent mechanism, exacerbating the CF MΦ response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease.


Rapid, specific, and sensitive detection of spoilage molds in orange juice using a real-time Taqman PCR assay.
The outgrowth of spoilage organisms, including molds and yeasts, results in significant financial loss to the food industry and wastes natural resources. The objective of this study was to develop a rapid, specific, and sensitive real-time PCR method for detecting spoilage molds during screening of raw materials and final product quality control analysis. The 18S rRNA gene was used to develop PCR primers and probe. With this set of primers and probe, less than 1,000 mold cells per milliliter of orange juice (10 cells per reaction) were detected with the real-time PCR system within 6 to 7 h. No cross-reactivity was found with other common foodborne bacteria, yeasts, or food ingredients. This technique is significantly faster than current detection and identification procedures, which take from days to weeks.


Ovarian actinomycosis developed during the use of a plastic intrauterine contraceptive device.
The case of a primary ovarian actinomycosis developed during the use of a Szontágh--Szereday type plastic IUD is presented. After a radical operation the patient was discharged in a good condition but 40 days later had to be readmitted because of a pelvic and abdominal wall abscess. After local surgery and massive penicillin treatment she is free of complaints. It is assumed that the IUD had a pathomechanical role.


A novel missense mutation of TNNI2 in a Chinese family cause distal arthrogryposis type 1.
The distal arthrogryposis (DA) syndromes are a group of disorders characterized by congenital contractures of limbs. According to phenotypical characteristics, DA syndromes have been clinically classified into 10 types. Currently, at least nine disease causing genes have been identified for different types of DA. Here, we report a 3-generation Chinese pedigree with three DA affected members. We performed whole exome sequencing on two affected and one unaffected individuals of this family and successfully identified a novel missense mutation in TNNI2 as the pathogenic mutation. The TNNI2 gene encodes a subunit of the troponin complex, a contractile machinery of the muscle. The mutation p.F178C that could change the H-bond formation of a neighboring residue occurs at a highly conserved position, suggesting that this variation probably affects the TNNI2 protein function. Our study also demonstrates the power of whole exome sequencing in causal mutation identification for phenotypically variable and genetically heterogeneous disorders.


Psychologic factors and oral lichen planus. A psychometric evaluation of 100 cases.
The purpose of this study was to analyze the importance of psychologic factors in patients with oral lichen planus, and attempts were made to identify possible personality features characteristic of patients with oral lichen planus. The study involved 100 patients with oral lichen planus (group 1) and 50 control subjects (group 2). We applied the following psychometric tests to both groups: Spielberger State-Trait Anxiety Inventory, Cattell Personality Questionnaire 16PF, Hassanyeh Rating of Anxiety-Depression-Vulnerability, Beck Depression Inventory, Raskin Depression Screen, and Covi Anxiety Screen. The patients with oral lichen planus were found to exhibit greater anxiety, as reflected by statistically significant scores with the anxiety tests that were used (Spielberger State-Trait Anxiety Inventory, Cattell Personality Questionnaire 16PF, Hassanyeh Rating of Anxiety-Depression-Vulnerability, and Covi Anxiety Screen). The patients with oral lichen planus likewise exhibited greater depression than the controls in all 3 depression tests applied (Beck Depression Inventory, Hassanyeh Rating of Anxiety-Depression-Vulnerability, and Raskin Depression Screen) and were more vulnerable to psychic disorders on the basis of the PD subscales (vulnerability) of the Hassanyeh questionnaire. Three features (conformity to the group, astuteness, and rebelliousness) defined the personalities of our patients with oral lichen planus, according to the Cattell 16PF questionnaire. Finally, those patients with erosive lichen planus exhibited higher depression scores than patients with nonerosive lichen planus. Despite the higher anxiety scores observed in patients with oral lichen planus, it was not established that the observed psychologic alterations constitute a direct etiologic factor of oral lichen planus; nor was it established that such alterations are a consequence of oral lichen planus and its lesions.


Thione-thiol rearrangement: miyazaki-newman-kwart rearrangement and others.
Thione-to-thiol rearrangements represent a general route for the synthesis of sulfur compoundsfrom hydroxyl functionalities. In particular, the Miyazaki-Newman-Kwart rearrangementhas been widely used for the synthesis of aromatic thiols from the corresponding phenols.


Chronic changes in thyroid hormones do not affect brain adenosine receptors.
1. In this study, the authors examined the effects of chronic (14 days) changes in thyroid function on a major neuromodulatory receptor system in the brain- the adenosinergic system. While previous investigators have examined the effects of alteration in thyroid function on adenosine receptors in peripheral tissues (adipocytes), this is the first study to examine such effects in brain. 2. Three groups of male Sprague-Dawley rats were treated for 14 days with either a) oral PTU (0.00625%), iodine-free diet, and i.p. saline injections, b) i.p. saline injections, or c) i.p. triiodothyronine (25 micrograms/100 g) injections. 3. These manipulations reliably resulted in the production of hypothyroidism (TSH 30.2 +/- 8.6 ng/ml), euthyroidism (TSH 2.1 +/- 0.9), and hyperthyroidism (TSH < 0.4). 4. Treatment had no significant effect on the Bmax or Kd of [3H]DPCPX (A1-antagonist) binding to homogenates from cerebral cortex, cerebellum or hippocampus; similarly, no effect on [3H]CGS-21680 (A2-agonist) binding to striatal homogenates was noted. 5. Similarly, quantitative autoradiographic studies failed to reveal consistent regional alterations unique to either hypo- or hyperthyroidism. 6. Incubation of sections with GppNHp resulted in the expected reduction (approximately 40%) in agonist binding, but there was no differential effect seen for either the hypo- or hyperthyroid tissues. 7. These preliminary findings suggest that alterations in brain adenosine receptors or G-protein-receptor coupling are unlikely to be requisite correlates of abnormal thyroid hormone levels.


Brief courses of palliative radiotherapy for metastatic bone pain: a pilot cost-minimization comparison with narcotic analgesics.
The use of radiotherapy to treat metastatic bone pain is being challenged by claims of high cost and by more readily available, noninvasive treatment approaches. The authors assessed the effectiveness of brief courses of radiotherapy in reducing pain and estimated cost data for a pilot comparison between radiotherapy and narcotic analgesics in patients with cancer. A representative group of outpatients undergoing brief courses of radiotherapy with Karnofsky scores above 70 and without serious comorbidities were recruited from 1995 through 1996. Patients indicated their pain at rest and with movement on a scale of from 1 to 10 both before and up to 12 months after radiotherapy. Radiotherapy costs were estimated from Medicare-allowable charges. Narcotic analgesia costs were estimated from published values. In 66 patients with 131 individually treated sites, median at rest pain score decreased by about 4 points after treatment (5.58 [-/+3.28] before treatment vs. 1.55 [-/+1.8] after treatment; p < 0.05). Median with movement pain score was about 5 points lower after treatment (7.32 [-/+2.72] before treatment vs. 1.94 [-/+2.07] after treatment; p < 0.05). No differences were found when stratifying by type of pain, tumor histologic type, or skeletal site. The estimated cost per patient ranged from $1,200 to $2,500 for radiotherapy. This compares with an estimated cost of $9,000 to $36,000 for 9 months of narcotics. In this pilot study, a brief course of radiotherapy significantly reduced pain and appeared to be cost effective when compared with narcotic analgesia. A full economic evaluation is warranted.


Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.
Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way.


Nonspecific effect of m7GMP on protein-RNA interactions.
Cap analogs m7GMP and m7GDP inhibit binding of eukaryotic initiation factors to reovirus capped mRNA but also inhibit complex formation involving uncapped mRNA or 18 S rRNA. Furthermore, Escherichia coli DNA-dependent RNA polymerase binds 18 S rRNA and this interaction is also blocked by m7GMP. These results indicate that inhibition by cap analogs is not a stringent test for putative cap-specific binding between proteins and mRNA.


Successful surgical repair of aortic atresia associated with normal left ventricle.
Surgical repair of aortic atresia with a large ventricular septal defect and a normally developed left ventricle was accomplished in a 14 month old infant. Palliative surgery at age 23 days consisted of bilateral banding of pulmonary artery branches and replacement of the ductus arteriosus with a Goretex conduit. Corrective surgery was accomplished by closure of the ventricular septal defect, insertion of a valved conduit between the apex of the left ventricle and the subdiaphragmatic aorta, removal of the pulmonary artery bands and division of the pulmonary-aortic conduit. The patient has a mild coarctation of the aorta and remains asymptomatic at 2 years of age.


Transport of glucose and cellobiose by Candida wickerhamii and Clavispora lusitaniae.
The cellular location of beta-1,4-glucosidase activity from, as well as the transport of glucose and cellobiose into, cells of Clavispora lusitaniae NRRL Y-5394 and Candida wickerhamii NRRL Y-2563 was investigated. The beta-glucosidase from Cl. lusitaniae appeared to be a soluble cytoplasmic enzyme. This yeast transported both glucose and cellobiose when grown in medium containing cellobiose as the sole carbon source. Glucose, but not cellobiose, uptake was observed for cells grown on glucose. The Ks and Vmax values for cellobiose transport were different when Cl. lusitaniae was cultured either aerobically (0.11 mM, 6.28 nmol.min-1.mg-1) or anaerobically (0.25 mM, 3.88 nmol-1.min-1.mg-1). The Ks and Vmax values for glucose transport (0.23-1.10 mM and 17.2-33.9 nmol.min-1.mg-1) also differed with the various growth conditions. The beta-glucosidase from C. wickerhamii was extracytoplasmically located. This yeast transported glucose, but not cellobiose, under all growth conditions tested. The Ks for glucose uptake was 0.13-0.28 mM when C. wickerhamii was cultured on cellobiose and 0.25-0.30 mM when cultured on glucose. The Vmax values for glucose uptake were greater for cells cultured on cellobiose (35.0-37.9 nmol.min-1.mg-1) than for cells cultured on glucose (15.6-21.4 nmol.min-1.mg-1). Cellobiose did not inhibit glucose uptake in either yeast. Glucose partially inhibited cellobiose transport in C. lusitaniae, but only if the yeast was grown aerobically. In both yeasts, sugar transport was sensitive to carbonyl cyanide p-trifluoromethoxyphenylhydrazone and 1799, but insensitive to valinomycin.


Engineered lipid liquid crystalline nanoparticles as an inhaled nanoplatform for mucus penetration enhancement.
Nanocarrier-assisted pulmonary drug delivery system has been widely employed for lung local disease treatment due to its enhanced drug lesion accumulation and reduced systematical side effects. However, the mucus barriers covered on the epithelia of trachea and bronchial tree construct a dense barrier for inhaled nanocarrier transport, which compromises the therapeutical effects. In this study, a lipid liquid crystalline nanoparticle NLP@Z with surface zwitterion material hexadecyl betaine (HB) modification and N-acetylcysteine (NAC) encapsulation was presented to exert the combination strategy of mucus-inert surface and mucus degradation. The HB modification endowed NLP@Z mucus-inert surface to inhibit the interaction between NLP@Z and mucins, and the encapsulated NAC could effectively degrade the mucins and further decrease the mucus viscosity. This combination strategy was proved to significantly promote the mucus penetration performance and enhance epithelial cell uptake. In addition, the proposed NLP@Z was equipped with desired nebulization property, which could be served as a potential pulmonary delivery nanoplatform. In summary, the proposed NLP@Z highlights the employment of the combination strategy for mucus penetration enhancement in pulmonary delivery, which may become a versatile platform for lung disease therapy.


A novel mutation of GATA4 (K300T) associated with familial atrial septal defect.
The GATA-binding protein 4 gene (GATA4) encodes a zinc-finger transcription factor that plays a key role in embryogenesis and cardiac development. Variants in the GATA4 gene have been implicated in several congenital heart diseases (CHD), such as the tetralogy of Fallot (ToF), atrial septal defect (ASD), ventricular septal defect (VSD), atrioventricular septal defect (AVSD), and dilated cardiomyopathy (DCM). We studied a four-generation Chinese ASD family and identified a novel GATA4 mutation (c.A899C, p.K300T) in all surviving affected members and two carriers with incomplete penetrance. Bioinformatics programs (PolyPhen-2, SIFT, and MutationTaster) predicted the mutation to be deleterious. The lysine at the mutation position was highly conserved from Drosophila to humans and was recognized as a methylation location in the GATA4 protein. The involvement of the lysine methylation in cardiogenesis by attenuating the transcriptional activity of GATA4 in mice has been previously examined. Our study broadens the mutation spectrum of the GATA4 gene and reveals for the first time a mutation at the methylation position of GATA4 associated with ASD.


A high dose of albuterol does not overcome bronchoprotective subsensitivity in asthmatic subjects receiving regular salmeterol or formoterol.
Regular treatment with inhaled, long-acting beta2 -agonists is associated with subsensitivity for bronchoprotective effects. It is not known whether a high dose of short-acting beta2 -agonist could overcome this subsensitivity. The objective of this study was to investigate the acute effects of a high dose of inhaled albuterol on methacholine-induced bronchoconstriction in patients receiving regular treatment with salmeterol or formoterol. Ten stable asthmatic subjects (mean age, 34 years; FEV1, 77% of predicted value), all taking inhaled corticosteroids (methacholine PD20 < 500 microg), were recruited into a randomized, single-blind, crossover study. After an initial 1-week run-in period, subjects underwent 3 separate treatment periods each of 9 days (separated by a washout of at least 5 days) comprising inhaled placebo twice daily, inhaled salmeterol dry powder 50 microg twice daily, or inhaled formoterol dry powder 12 microg twice daily. Methacholine challenge was performed 1 hour after the first dose and after 7 days of treatment. After 9 days of treatment, a third methacholine challenge was performed 1 hour after inhalation of a single 1600 microg dose of albuterol dry powder. There was significant (P <.001) improvement in geometric mean PD20 after the first dose of active treatment as compared with placebo (78 microg) versus salmeterol (266 microg, a 3.4-fold difference [95% CI 1.9 to 6.1]) and versus formoterol (318 microg, a 4.1-fold difference [95% CI 2.3 to 7.3]). This bronchoprotection diminished with regular treatment, although it remained significant (P <.01) compared with placebo (68 microg) versus salmeterol (144 microg, a 2.1-fold difference [95% CI 1.2 to 3.8]) and versus formoterol (230 microg, 3.4-fold difference [95% CI 1.9 to 6.2]). After 9 days, the protection afforded by a single dose of albuterol after placebo pretreatment (889 microg) was significantly (P =.005) higher in comparison with albuterol protection after salmeterol pretreatment (338 microg, a 2.7-fold difference [95% CI 1.1 to 6.8]) and after formoterol pretreatment (247 microg, a 3.6-fold difference [95% 1.4 to 9.1]). Thus in stable asthmatic subjects receiving regular salmeterol or formoterol, bronchoprotective subsensitivity was not overcome by administering a high dose of albuterol. Further studies are required to evaluate the clinical relevance of this pharmacologic phenomenon when albuterol is used in acute asthma.


An introduction to the UK care pathway for children born with a cleft of the lip and/or palate.
Cleft lip and/or palate includes a spectrum of congenital disorders affecting union on the lip, alveolus, hard and/or soft palate. The management of children born with an orofacial cleft requires a complex process from a multidisciplinary team (MDT) to restore form and function. Since the Clinical Standards Advisory Group (CSAG) report in 1998, the UK has reformed and restructured cleft services to improve the outcomes for children born with a cleft.The spectrum of cleft conditions, the members of the MDT and a chronological description of the stages of cleft management from diagnosis to adulthood are described using a clinical example. This paper forms the introduction to a series of more detailed papers which span all major aspects of cleft management. The papers will cover the following topics: dental anomalies; associated medical conditions among children; orthodontic management of patients; speech assessment and intervention; role of the clinical psychologist; challenges for the paediatric dentist; genetics and orofacial clefts; surgery - primary and secondary; restorative dentistry; and global perspectives.


Hemodynamic consequences of incomplete uterine spiral artery transformation in human pregnancy, with implications for placental dysfunction and preeclampsia.
Normal human pregnancy requires a dramatic increase in uteroplacental blood flow, which is achieved by a transformation in the geometry of uterine spiral arteries, a key element in this blood supply system. The transformation is mediated by trophoblast invasion directed at converting a portion of the spiral artery into an open funnel, thereby greatly reducing resistance to flow. The converted portion lies within the depth of the decidua and part of the myometrium. Insufficient depth of trophoblast invasion in early pregnancy predisposes to inadequate perfusion of the developing placenta and fetus and may lead to preeclampsia, fetal growth restriction, and preterm delivery, sometimes referred to as the "Great Obstetrical Syndromes." We examine the hemodynamic consequences of spiral artery transformation in human pregnancy and the relationship between the degree of transformation and the corresponding change in flow rate and resistance to flow. We identify two key variables in determining the hemodynamic change: the longitudinal converted fraction of the spiral artery and the relative downstream diameter of the open funnel. Our results indicate that there is a critical threshold in the value of the converted fraction required to achieve the marked increase in uteroplacental blood flow in normal pregnancy. This finding validates common clinical observations that the depth of trophoblast invasion reflects the "adequacy" of the increase in uteroplacental blood supply required in normal human pregnancy. Our results provide a quantitative measure of that adequacy and may serve as a future diagnostic marker for high-risk pregnancy.NEW & NOTEWORTHY Human pregnancy requires dramatic increase in uteroplacental blood supply achieved by geometric transformation of uterine spiral arteries and facilitated by trophoblast invasion of these arteries to greatly reduce resistance to flow. Incomplete transformation has been associated with failed pregnancies, preeclampsia, and other pathologies, but a quantitative measure of "incompleteness" has been unavailable so far. We use a mathematical model to obtain a numerical threshold for this measure which may serve as a future diagnostic marker.


Tissue engineering: from research to dental clinics.
Tissue engineering is an interdisciplinary field that combines the principles of engineering, material and biological sciences toward the development of therapeutic strategies and biological substitutes that restore, maintain, replace or improve biological functions. The association of biomaterials, stem cells, growth and differentiation factors has yielded the development of new treatment opportunities in most of the biomedical areas, including Dentistry. The objective of this paper is to present the principles underlying tissue engineering and the current scenario, the challenges and the perspectives of this area in Dentistry. The growth of tissue engineering as a research field has provided a novel set of therapeutic strategies for biomedical applications. Indeed, tissue engineering may lead to new strategies for the clinical management of patients with dental and craniofacial needs in the future.


An anatomic study of the structure and innervation of the pronator quadratus muscle.
The pronator quadratus muscle is composed of the superficial and deep heads. However, to date there is no consensus on the variations of each head. To add to this enigma, the innervation patterns of each head have not been thoroughly studied. The present study was conducted to clarify the structure and innervation of the pronator quadratus muscle by minute dissection of 46 forearms from 26 cadavers. The origin, insertion, shape, and direction of the muscle fascicles in each head were observed. The intramuscular distribution and the innervation patterns to each head were investigated. The attachment of the deep head was examined using Masson's trichrome staining technique. Each head consisted of various muscle fascicles which differed in shape and direction. The most distal muscle fascicle extended toward the head of the ulna. On microscopic study, this most distal fascicle was observed to reach the base of the ulnar styloid process. The nerves innervating the superficial head penetrated through the deep head and ran on the anterior surface of the radius from medial to lateral. This tendency was common to all of the forearms studied. We confirmed that each head of the pronator quadratus muscle consisted of various muscle fascicles. The attachment to the base of the ulnar styloid process is considered to be an important structure that prevents the head of the ulna from impacting against the carpal bones. Knowledge of the innervation pattern to each head is critical for preserving the function of the pronator quadratus muscle during surgery for distal radial fracture.


Bombesin stimulates in vitro growth of human breast cancer independent of estrogen receptors status.
Approximately 180,000 women will be found to have breast cancer this year in the United States. Chemotherapy has limited success in advanced disease and the effect of tamoxifen appears to require a functional estrogen-receptor (ER). Our aim was to determine whether bombesin (BBS) regulates growth of human breast cancer cells. Estrogen-dependent (MCF-7), estrogen-responsive (ZR-75-1) and estrogen-independent (MDA-MB-231) human breast cancer cells were studied. Receptors were identified by cross-linking methods and radioligand binding assays; intracellular calcium ([Ca2+]i) was measured after BBS treatment to confirm functional status of the receptor; and the effect of BBS on cell growth was measured directly. All three cell lines had a high affinity BBS receptor (Kd = 1-7 nM; molecular weight 75 kDa). BBS stimulated [Ca2+]i levels as well as cell growth in all three cell lines; the trophic effect was blocked by BBS receptor antagonists. We conclude that BBS is trophic for human breast cancers independent of ER status, and that antagonism of the BBS receptor may be a useful target for hormonal therapy in ER-negative breast cancer.


Deconstructing "Atypical" Eating Disorders: an Overview of Emerging Eating Disorder Phenotypes.
Recent changes to the diagnostic framework of eating disorders (ED's) in DSM-5 were introduced to reduce the large preponderance of cases falling within the residual and undifferentiated category. However, current reports continue to illustrate overrepresentation of cases in this residual category, suggesting that clinical reality comprises more diverse ED psychopathology than is accounted for in the current diagnostic spectrum. However, with emerging evidence preliminarily delineating several additional distinct phenotypes, we aim to provide a narrative overview of emerging ED phenotypes which (i) are not currently located as a specific diagnostic category in diagnostic criteria for ED's, (ii) centrally feature ED psychopathology, and (iii) have emerging empirical evidence suggesting the distinct nature of the syndrome. A greater awareness of these emerging phenotypes will likely facilitate accurate diagnostic practice and may also serve to facilitate further empirical efforts.


[Neuroeffects of prolonged exposure to microwaves: systemic, neuronal and electron microscope study].
Cats were kept in the electromagnetic field (2375 mHz, 500 microW/cm2) for 200 h. A functional disorder was noted in the neuronal activity of the studied brain formations associated with a physical injury to axo-dendritic synapses involved in the promotion of the morphological relationship between the brain departments.


CEST MRI of 3-O-methyl-D-glucose uptake and accumulation in brain tumors.
3-O-Methyl-D-glucose (3-OMG) is a nonmetabolizable structural analog of glucose that offers potential to be used as a CEST-contrast agent for tumor detection. Here, we explore it for CEST-detection of malignant brain tumors and compare it with D-glucose. Glioma xenografts of a U87-MG cell line were implanted in five mice. Dynamic 3-OMG weighted images were collected using CEST-MRI at 11.7 T at a single offset of 1.2 ppm, showing the effect of accumulation of the contrast agent in the tumor, following an intravenous injection of 3-OMG (3 g/kg). Tumor regions showed higher enhancement as compared to contralateral brain. The CEST contrast enhancement in the tumor region ranged from 2.5-5.0%, while it was 1.5-3.5% in contralateral brain. Previous D-glucose studies of the same tumor model showed an enhancement of 1.5-3.0% and 0.5-1.5% in tumor and contralateral brain, respectively. The signal gradually stabilized to a value that persisted for the length of the scan. 3-OMG shows a CEST contrast enhancement that is approximately twice as much as that of D-glucose for a similar tumor line. In view of its suggested low toxicity and transport properties across the BBB, 3-OMG provides an option to be used as a nonmetallic contrast agent for evaluating brain tumors.


Identification and characterization of the fibrinogen-like domain of fibrinogen-related proteins in the mosquito, Anopheles gambiae, and the fruitfly, Drosophila melanogaster, genomes.
The fibrinogen-like (FBG) domain, which consists of approximately 200 amino acid residues, has high sequence similarity to the C-terminal halves of fibrinogen beta and gamma chains. Fibrinogen-related proteins (FREPs), which contain FBG domains in their C-terminal region, are found universally in vertebrates and invertebrates. In invertebrates, FREPs are involved in immune responses and other aspects of physiology. To understand the complexity of this family in insects, we analyzed FREPs in the mosquito genome and made comparisons to FREPs in the fruitfly genome. By using the genome data of the mosquito, Anopheles gambiae, 53 FREPs were identified, whereas only 20 members were found in the Drosophila melanogaster genome. Using sequence profile analysis, we found that FBG domains have high sequence similarity and are highly conserved throughout the FBG domain region. By secondary structure analysis and comparison, the FBG domains of FREPs are predicted to function in recognition of carbohydrates and their derivatives on the surface of microorganisms in innate immunity. Detailed sequence and structural analysis discloses that the FREP family contains FBG domains that have high sequence similarity in the A. gambiae genome. Expansion of the FREP family in mosquitoes during evolutionary history is mainly accounted for by a major expansion of the FBG domain architecture. The characterization of the FBG domains in the FREP family is likely to aid in the experimental analysis of the ability of mosquitoes to recognize parasites in innate immunity and physiologies associated with blood feeding.


Clinical Applications of Single-Stranded Oligonucleotides: Current Landscape of Approved and In-Development Therapeutics.
Single-stranded oligonucleotides have been explored as a therapeutic modality for more than 20 years. Only during the last 5 years have single-stranded oligonucleotides become a modality of choice in the fields of precision medicine and targeted therapeutics. Recently, there have been a number of development efforts involving this modality that have led to treatments for genetic diseases that were once untreatable. This review highlights key applications of single-stranded oligonucleotides that function in a sequence-dependent manner when applied to modulate precursor (pre-)mRNA splicing, gene expression, and immune pathways. These applications have been used to address diseases that range from neurological to muscular to metabolic, as well as to develop vaccines. The wide range of applications denotes the versatility of single-stranded oligonucleotides as a robust therapeutic platform. The focus of this review is centered on approved single-stranded oligonucleotide therapies and the evolution of oligonucleotide therapeutics into novel applications currently in clinical development.


Feasibility study of MEMS-based stenosis detection using a prototypical catheter design with intravascular scanning probes (IVSPs).
X-ray coronary angiography (XRA) is a standard clinical method for diagnosing coronary artery disease (CAD). However, despite continuous improvements in XRA technology, it has limitations that include being visible only in color contrast, and the information it provides on coronary artery plaques is not comprehensive due to its low signal-to-noise ratio and limited resolution. In this study, we propose a novel diagnostic tool, a MEMS-based smart catheter with an intravascular scanning probe (IVSP), to complement XRA and verify its effectiveness and feasibility. The IVSP catheter uses Pt strain gauges embedded on the probe to examine the characteristics of a blood vessel, such as the degree of stenosis and morphological structures of the vessel walls, through physical contact. The feasibility test results showed that the output signals of the IVSP catheter reflected the morphological structure of the phantom glass vessel that mimicked stenosis. In particular, the IVSP catheter successfully assessed the morphology of the stenosis, which was only 17% of the cross-sectional diameter obstructed. In addition, the strain distribution on the probe surface was studied using finite element analysis (FEA), and a correlation between the experimental and FEA results was derived.


Escherichia coli cell division.
Recent progress in the molecular analysis of bacterial septation and chromosome partitioning suggests that these processes may involve cytoskeletal elements previously thought to be present only in eukaryotic cells. The continued biochemical and genetic analysis of key proteins, such as the tubulin-like FtsZ, should lead to further unravelling of the regulation and mechanism of bacterial cell division.