NMR assignments and secondary structure of the retinoid X receptor alpha DNA-binding domain. Evidence for the novel C-terminal helix.
The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and has recently been shown to function in a variety of hormonal signaling pathways by virtue of its ability to heterodimerize with other nuclear hormone receptors. Here we describe resonance assignments, the secondary structural elements and the global folding pattern of the DNA-binding domain (residues 130-223) of human RXR alpha, as determined by multidimensional nuclear magnetic resonance spectroscopy. Its overall structure is similar to those reported for the glucocorticoid, estrogen, and retinoic acid receptors, in that the two zinc fingers of RXR fold to form a single structural domain containing two helices, which are located at the carboxy terminal of the two zinc fingers. There is also a short antiparallel beta-sheet formed between two residues in the amino-terminal base of the first finger and two residues in the carboxy terminal of that same finger just before the first helix. However, in contrast to the other nuclear hormone receptor DNA-binding domains, the RXR domain contains a third helix immediately after the conserved Gly-Met sequence that signals the termination of the second helix. The second and third helices lie orthogonal to and wrap around the first helix, generating an extended hydrophobic core. Since helices two and three are separated by only two residues, the backbone flexibility afforded by the presence of the conserved glycine residue between them may be crucial for the proper positioning of the third helix relative to the first helix. A 12-amino-acid region termed the 'T-box', which includes this third helix, was recently shown to be required for homodimeric binding of RXR to its cognate response element [Wilson, T. E., Paulsen, R. E., Padgett, K. A. & Milbrandt, J. (1992) Science 256, 107-110].


Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry MSE-based untargeted milk metabolomics in dairy cows with subclinical or clinical mastitis.
In this study, a novel metabolomics technique based on ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry in the MSE mode was used to investigate the milk metabolomics of healthy, subclinical, and clinical mastitis cows, which were classified based on somatic cell count and presentation of clinical symptoms. Meanwhile, univariate and multivariate statistical analyses were performed to identify the significant differences across the 3 groups. Compared with healthy milk samples, less glucose, d-glycerol-1-phosphate, 4-hydroxyphenyllactate, l-carnitine, sn-glycero-3-phosphocholine, citrate, and hippurate were detected in the clinical mastitic milk samples, whereas less d-glycerol-1-phosphate, benzoic acid, l-carnitine, and cis-aconitate were found in the subclinical mastitic milk samples. Meanwhile, the milk concentration of arginine and Leu-Leu increased in both the clinical and subclinical mastitis groups. Besides, less 4-hydroxyphenyllactate, cis-aconitate, lactose, and oxoglutarate were detected in the clinical than the subclinical mastitic milk samples, whereas the abundance of some oligopeptides (Leu-Ala, Phe-Pro-Ile, Asn-Arg-Ala-Ile, and Val-Phe-Val-Tyr) increased by over 7.95-fold. Our results suggest that significant variations exist across healthy and mastitis cows. The current metabolomics approach will help in better understanding the pathobiology of mastitis, although clinical validation will be required before field application.


Effects of amygdala lesions on male mouse ultrasonic vocalizations and copulatory behaviour.
Mice produce ultrasonic vocalizations (USVs) in several behavioural contexts. In particular, male mice articulate a long series of various sounds to females during courtship behaviour. To determine the relationships between this kind of vocal behaviour and emotion, we examined the lesion effects of the amygdala, an important neural module in emotional behaviour, on USVs. We recorded USVs from mice in the lesion and the control (sham operation) groups upon presentation of females and compared USVs before and after surgery. We found that the mean syllable duration of the USVs shortened and the appearance rate of longer syllables decreased after the surgery. The main reasons for these alterations could be explained by the altered courtship behaviour. As reported previously, the mounting behaviour of the lesion group after surgery was markedly less than that of the control group. Therefore, the appearance rate of those longer syllables would decrease logically because longer syllables primarily appear during mounting and intromission. However, we can hypothesize another scenario for the alterations to vocal behaviour: effects on the direct amygdala-periaqueductal grey (PAG) projection might be involved in the increase in the appearance rate of shorter syllables owing to lesion-induced loss of emotions, such as vigilance. Overall, the results suggested two possible mechanisms of the amygdala lesions on the alteration of the vocal behaviour.


3,beta-Hydroxy-5agr-cholestan-6-one: A Possible Precursor of agr-Ecdysone Biosynthesis.
The conversion of cholesterol into 3beta-hydroxy-5alpha-cholestan-6-one has been demonstrated to occur in prothoracic glands of last instar larvae of the silkworm, Bombyx mori. Incubation of glands containing radiolabeled 3beta-hydroxy-5alpha-cholestan-6-one results in the disappearance of this sterol from the glands and the concomitant appearance of radiolabeled alpha-ecdysone in the medium. The observations suggest that the sterol is an intermediate in the synthesis of alpha-ecdysone.


High prevalence of congenital hypothyroidism in Isfahan: Do familial components have a role?
Despite elimination of iodine deficiency, the rates of both permanent and transient congenital hypothyroidism (CH) in our study were higher than the comparable worldwide rates, which emphasize the major role of genetic factors in the pathogenesis of CH and many studies in this regard confirm this possibility. In this review, we report all studies that established during CH screening program regarding familial and genetic component of the disease. Although we could not entirely ignore the possible role of environmental and autoimmune factors in the development and function of thyroid gland, our findings strongly suggest the role of genetic factors as dominant etiologic factor in CH. The studies support the existence of a familial component of CH involving dominant genetic predisposition factors with a low penetrance. Considering the polygenic/multifactorial basis of CH, they suggest the possible involvement of other unknown genes in the pathogenesis of the disease, which may also follow non-Mendelian pattern of inheritance.


Principal opium alkaloids as possible biochemical markers for the source identification of Indian opium.
A total of 124 opium samples originating from different licit opium growing divisions of India were analyzed for their principal alkaloid (thebaine, codeine, morphine, papaverine, and narcotine) content by capillary zone electrophoresis (CZE) without derivatization or purification. Absence of papaverine in Bareilly, Tilhar, and most of the samples originating from Kota is a significant observation in relation to the source of Indian opium. Multiple discriminant analysis was applied to the quantitative principal alkaloid data to determine an optimal classifier in order to evaluate the source of Indian opium. The predictive value based on the discriminant analysis was found to be 85% in relation to the source of opium and the study also revealed that all the principal alkaloids have to be analyzed for source identification of Indian opium. Chemometrics performed with principal alkaloids analytical data was used successfully in discriminating the licit opium growing divisions of India into three major groups, viz., group I, II, and III. The methodology developed may find wide forensic application in identifying the source of licit or illicit opium originating from India, and to differentiate it from opium originating from other opium producing countries.


The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy-An immunological perspective.
During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy.


Volunteer work in the church among older Mexican Americans.
The purpose of this study is to identify the factors that influence the amount of volunteer work that older Mexican Americans perform in the place where they worship. The relationship between religion and volunteering is viewed from a social identity perspective. Data from a nationally representative sample of older Mexican Americans suggest that Evangelical/Pentecostal church members spend more time performing volunteer work at church than older Mexican Americans who affiliate with other denominations. Moreover, the findings indicate that the difference in the amount of volunteering between the two groups can largely be explained by differences in the nature of the spiritual support that Evangelical/Pentecostal receive from their fellow church members as well as depth of their commitment to their faith.


Polymerization and gelation of whey protein isolates at low pH using transglutaminase enzyme.
Dynamic and steady shear rheology is used to examine the synthesis of low-pH (approximately 4) whey protein gels obtained through a two-step process. The first step involves cross-linking of whey proteins at pH 8 and 50 degrees C using transglutaminase enzyme, while the second step entails cold-set acidification of the resulting solution using glucono-delta-lactone (GDL) acid. During the first step, the sample undergoes enzyme-catalyzed epsilon-(gamma-glutamyl)lysine bond formation with a substantial increase in viscosity. Acidification in the second step using GDL acid leads to a rapid decrease in pH with a concomitant increase in the elastic (G') and viscous (G' ') moduli and formation of a gelled network. We examine the large strain behavior of the gel samples using a relatively new approach that entails plotting the product of elastic modulus and strain (G'gamma) as a function of increasing dynamic strain and looking for a maximum, which corresponds to the yield or fracture point. We find the enzyme-catalyzed gels to have significantly higher yield/fracture stress and strain compared to cold-set gels prepared without enzyme or conventional heat-set gels. In addition, the elastic modulus of the enzyme-catalyzed gel is also higher than its non-enzyme-treated counterpart. These results are discussed in terms of the gel microstructure and the role played by the enzyme-induced cross-links.


GM-CSF activates regenerative epidermal growth and stimulates keratinocyte proliferation in human skin in vivo.
Granulocyte/macrophage-colony-stimulating factor (GM-CSF), an immunomodulator of hematopoietic cells, has also been shown to stimulate human keratinocyte proliferation in vitro and speed healing of wounds in the skin of lepromatous leprosy patients. In this study we have examined the in vivo effects of recombinant human GM-CSF on epidermal keratinocyte proliferation and on expression of proteins marking regenerative epidermal growth. Skin biopsies from GM-CSF injected cutaneous sites were obtained between 1 and 6 d following administration of 7.5 or 15 micrograms of the growth factor. Activation of keratinocyte proliferation, quantified as the expression of the Ki67+ nuclear antigen, was noted 1 d following GM-CSF administration. A regenerative epidermal phenotype, demonstrated by immunohistochemical staining of cellular proteins involucrin, filaggrin, and keratin 16, was similarly noted as early as 1 d following GM-CSF injection. This phenotype persisted as late as 6 d post-injection. These results suggest that GM-CSF injection into human skin induces keratinocyte proliferation as well as regenerative differentiation of the epidermis. To date no other cytokine has been shown to be mitogenic for human keratinocytes both in vivo and in vitro or to alter keratinocyte differentiation along the "alternate" or regenerative pathway.


In vitro and in vivo antiarrhythmic effects of prazosin in the rat.
The possible antiarrhythmic action of prazosin was studied on two experimental models: a focus of ectopic automaticity in the rat isolated right ventricle and arrhythmias induced by i.v. CaCl2 in anaesthetized animals. In vitro, prazosin at 10(-5)M abolished the ectopic automaticity focus in 83% of cases (10/12). The effects of prazosin were not modified by reserpine pretreatment. In vivo, prazosin modified the range of CaCl2 arrhythmias, reduced the mean control sinus rate (by 21.7% at 1 mg/kg), reduced incidence and mortality by ventricular fibrillation and lengthened survival time of animals that eventually died. The results indicate that antagonism of postsynaptic alpha 1-adrenoreceptors may partly explain the efficacy of prazosin against some experimental cardiac arrhythmias.


Fumonisin B(1): a neurotoxic mycotoxin.
Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB(1) is the most abundant and toxicologically the most significant one. FB(1) has a wide range of toxic effects, depending on animal species. In horses FB(1) causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB(1) is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB(1)-contaminated maize-based food. However, possible involvement of FB(1) in the development of human diseases is not clear. Nevertheless, the International Agency for Research on Cancer (IARC) has classified FB(1) as a possible carcinogen to humans (group 2B). FB(1) is a causative agent of ELEM, a brain disorder in equines, indicating that brain is a target organ of FB(1) toxicity. Several studies on experimental animals or on cell cultures of neural origin have established that FB(1) has a neurodegenerative potential, although the mechanism of its neurotoxicity is still vague. The aim of this article is to give an overview of available literature on FB(1) neurotoxicity and involved mechanisms, and to offer a new perspective for future studies.


Dysbiosis of Gut Microbiota Is an Independent Risk Factor of Stroke-Associated Pneumonia: A Chinese Pilot Study.
Identifying risks of stroke-associated pneumonia (SAP) is important for clinical management. We aimed to evaluate the association between gut microbiome composition and SAP in patients with acute ischemic stroke (AIS). A prospective observational study was conducted, and 188 AIS patients were enrolled as the training cohort. Fecal and serum samples were collected at admission. SAP was diagnosed by specialized physicians, and disease severity scores were recorded. Fecal samples were subjected to 16S rRNA V4 tag sequencing and analysed with QIIME and LEfSe. Associations between the most relevant taxa and SAP were analysed and validated with an independent cohort. Fecal short-chain fatty acid (SCFA), serum D-lactate (D-LA), intestinal fatty acid-binding protein (iFABP) and lipopolysaccharide binding protein (LBP) levels were measured. Overall, 52 patients (27.7%) had SAP in the training cohort. The gut microbiome differed between SAP and non-SAP patients; specifically, Roseburia depletion and opportunistic pathogen enrichment were noted in SAP patients, as confirmed in the validation cohort (n=144, 28 SAP [19.4%]). Based on multivariate analysis, Roseburia was identified as a protective factor against SAP in both cohorts (training, aOR 0.52; 95% CI, 0.30-0.90; validation, aOR 0.44; 95% CI, 0.23-0.85). The combination of these taxa into a microbial dysbiosis index (MDI) revealed that dysbiosis increased nearly 2 times risk of SAP (training, aOR 1.95; 95% CI, 1.19-3.20; validation, aOR 2.22; 95% CI, 1.15-4.26). Lower fecal SCFA levels and higher serum D-LA levels were observed in SAP patients. Furthermore, SAP was an independent risk factor of 30-day death and 90-day unfavorable outcome. We demonstrate that a microbial community with depleted Roseburia and enriched opportunistic pathogens is associated with increased risk of SAP among AIS patients. Gut microbiota screening might be useful for identifying patients at high risk for SAP and provide clues for stroke treatment.


Volatile Signals From Guava Plants Prime Defense Signaling and Increase Jasmonate-Dependent Herbivore Resistance in Neighboring Citrus Plants.
Intercropping can reduce agricultural pest incidence and represents an important sustainable alternative to conventional pest control methods. Citrus intercropped with guava (Psidium guajava L.) has a lower incidence of Asian citrus psyllid (ACP, Diaphorina citri Kuwayama) and huanglongbing disease (HLB), but the mechanisms are still unknown. In this study, we tested whether volatile organic compounds (VOCs) emitted by guava plants play a role in plant-plant communications and trigger defense responses in sweet orange (Citrus sinensis L. Osbeck) in the laboratory. The results showed that the behavioral preference and developmental performance of ACP on citrus plants that were exposed to guava VOCs were suppressed. The expression of defense-related pathways involved in early signaling, jasmonate (JA) biosynthesis, protease inhibitor (PI), terpenoid, phenylpropanoid, and flavonoid biosynthesis was induced in guava VOC-exposed citrus plants. Headspace analysis revealed that guava plants constitutively emit high levels of (E)-β-caryophyllene and (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), which can induce the accumulation of JA and promote stronger defense responses of citrus to ACP feeding. In addition, exposure to guava VOCs also increased the indirect defense of citrus by attracting the parasitic wasp Tamarixia radiata. Together, our findings indicate that citrus plants can eavesdrop on the VOC cues emitted by neighboring intact guava plants to boost their JA-dependent anti-herbivore activities. The knowledge gained from this study will provide mechanisms underlying citrus-guava intercropping for the ecological management of insect pests.


[Not Available].
The organization of the Russian army medical services at the Pleven area during the Liberation war (1877-78) is analyzed. Assessment is made from the viewpoint of the international character of the war, the peculiarities of conducting the fighting activities in the Balkan battlefields, the forms of fighting employed in this war, the strategical position of Pleven and the structure of the anticipated medical casualties at that time. The experience gained from the study of medical assistance of the Russian army is stressed; according to the author it continues to be valid.


Rapid selective screening and determination of ephedrine alkaloids using GC-MS footnote mark.
Ephedra (ma huang) has been widely used as an herb or herbal extract in both traditional Chinese medicine and Western world dietary supplements. The effects of Ephedra have been attributed to a series of six ephedrine alkaloids including ephedrine and pseudoephedrine. A GC-MS method for the ephedrine alkaloids is described which couples ammoniacal chloroform as the extraction solvent with a two-stage derivatisation scheme. This scheme produces the O-trimethylsilyl, N-trifluoracetyl derivatives (O-TMS, N-TFA) for the primary and secondary amine alkaloids, and the O-TMS derivatives for the tertiary amine alkaloids. Relatively clean extracts are obtained from complex matrices, and the six ephedrine alkaloids are effectively separated and identified. This approach was also evaluated for quantitative analysis, and was shown to provide quantitative results for ephedrine and pseudoephedrine, and good estimates for the four minor alkaloids. Figures of merit are presented for linearity, detection limits, precision and accuracy. We have applied this approach to the rapid screening and profiling of the ephedrine alkaloids in whole Ephedra plants, liquid plant extracts, dried powder plant extracts and a variety of Ephedra-containing dietary supplements.


Synthesis, receptor potency, and selectivity of halogenated diphenylpiperidines as serotonin 5-HT2A ligands for PET or SPECT brain imaging.
A series of 4'-substituted phenyl-4-piperidinylmethanol and benzoyl-4-piperidine derivatives was synthesized as potential novel serotonin 5-HT2A receptor ligands that can be radiolabeled for in vivo brain imaging. Compounds were prepared by alkylation of 4-substituted benzoyl-4-piperidine with an iodo- or fluoro-substituted phenylalkyl halide followed by reduction with sodium borohydride. Potency of novel compounds was determined by in vitro radioreceptor affinity assays selective for serotonin 5-HT2A receptors. Potent compounds were further evaluated for selectivity at serotonin-2A versus 2C, 6, and 7, as well as dopamine D2 and adrenergic alpha1 and alpha2 receptors. The novel compound (4-fluorophenyl)-(1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl])methanol was particularly promising with high 5-HT2A potency (K(i) = 1.63 nM) and >300-fold selectivity over other 5-HT receptor types.


Low-sensitivity FDG-PET studies: less common lung neoplasms.
Computed tomography (CT) and positron emission tomography (PET) using the radiopharmaceutical 18F-2-deoxy-d-glucose (FDG) play an important role in the diagnosis and tumor node metastasis staging of patients with non-small cell lung cancer (NSCLC). CT is the optimal modality for evaluating the primary tumor, whereas PET is useful in improving the accuracy of staging by detecting occult nodal and distant metastases. However, both modalities have limitations in the evaluation of the primary tumor and in the detection of metastases. With regard to FDG-PET, these limitations are amplified in primary adenocarcinoma of the lung that manifests as a subsolid nodule and in primary carcinoid tumors of the lung, as these malignancies commonly have low levels of FDG avidity. Because the misinterpretation of CT and PET studies can alter the diagnosis and staging when evaluating subsolid nodules and carcinoid tumors, awareness and knowledge of these limitations are required for appropriate patient management. This article reviews the use of PET in patients with these uncommon lung neoplasms as well as radiotracers that have been developed to interrogate different metabolic pathways, receptors, and targets to overcome the potential limitations of FDG-PET in the diagnosis, staging, as well as early response evaluation and monitoring of response to targeted therapies.


Comparative responses to dobutamine and nitroprusside in patients with chronic low output cardiac failure.
The acute hemodynamic effects of dobutamine and nitroprusside were compared in 19 patients with low output cardiac failure. At dosage levels yielding similar increases in cardiac index (12 patients), nitroprusside resulted in significantly lower arterial systolic and wedge pressures and did not increase heart rate suggesting advantages over dobutamine when reduction in myocardial oxygen requirement or pulmonary congestion is a major goal. Systemic arterial mean and diastolic pressures were minimally changed with dobutamine, but fell significantly with nitroprusside suggesting advantages of dobutamine over nitroprusside in patients where hypotension could limit coronary blood flow or perfusion of other vital organs. Reduction in pulmonary arteriolar resistance occurred only with nitroprusside. Arterial hypoxemia developed in three patients during nitroprusside infusion suggesting the possibility of increased right-to-left intrapulmonary shunting resulting from a direct vasodilating effect of nitroprusside on pulmonary arteriole smooth muscle. Although both inotropic and vasodilator drugs can result in hemodynamic improvement when administered to patients with chronic low output cardiac failure, significant differences of potential clinical importance exist between these two modes of therapy.


The influence of early sexual debut and pubertal timing on psychological distress among Taiwanese adolescents.
This study examined the relative influence of early sexual debut (ESD) and pubertal timing on psychological distress from adolescence to young adulthood in Taiwan, a non-Western society with a distinct cultural and family context. Data were from a cohort sample of 15-year-olds (N = 2595) first interviewed in 2000, with four follow-ups during a 7-year period. Psychological distress was assessed by a reduced form of the Symptom Checklist-90 Revised. ESD was defined by first intercourse at age 15 or younger. Multivariate analyses via growth curve modeling found a greater increase in psychological distress over time in adolescents with ESD (β = .28, p < .05). Early-pubertal adolescents were at greater risk for the onset of psychological distress (β = .46, p < .05). Further, early pubertal adolescents with an ESD appeared to be especially likely to be distressed (β = 3.39, p < .05). In addition, analyses showed a non-linear trajectory of psychological distress between the ages of 15 and 22, with distress escalating (β = .45, p < .001) as age increased before tapering off as adolescents became young adults (β = -.03, p < .001). Results suggest the contributing influence of both ESD and pubertal timing on distress trajectories, independent of parental and family characteristics.


DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature.
The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described. A BFC derived from the DATA ligand (2,2'-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe1][Tyr3]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68Ga derived via four different 68Ge/68Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2-4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68Ga-DATATOC was calculated as logP = -3.2 ± 0.3, with a HPLC retention time (tR = 10.4 min) similar to 68Ga-DOTATOC (logP = -2.9 ± 0.4, tR = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C. The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The speed, reliability, ease, flexibility and simplicity with which 68Ga-DATATOC can be prepared makes it a very attractive alternative to current standards.


Visualizing Localized Reentry With Ultra-High Density Mapping in Iatrogenic Atrial Tachycardia: Beware Pseudo-Reentry.
The activation pattern of localized reentry (LR) in atrial tachycardia remains incompletely understood. We used the ultra-high density Rhythmia mapping system to study activation patterns in LR. LR was suggested by small rotatory activations (carousels) containing the full spectrum of the color-coded map. Twenty-three left-sided atrial tachycardias were mapped in 15 patients (age: 64±11 years). 16 253±9192 points were displayed per map, collected over 26±14 minutes. A total of 50 carousels were identified (median 2; quartiles 1-3 per map), although this represented LR in only n=7 out of 50 (14%): here, rotation occurred around a small area of scar (<0.03 mV; 12±6 mm diameter). In LR, electrograms along the carousel encompassed the full tachycardia cycle length, and surrounding activation moved away from the carousel in all directions. Ablating fractionated electrograms (117±18 ms; 44±13% of tachycardia cycle length) within the carousel interrupted the tachycardia in every LR case. All remaining carousels were pseudo-reentrant (n=43/50 [86%]) occurring in areas of wavefront collision (n=21; median 0.5; quartiles 0-2 per map) or as artifact because of annotation of noise or interpolation in areas of incomplete mapping (n=22; median 1, quartiles 0-2 per map). Pseudo-reentrant carousels were incorrectly ablated in 5 cases having been misinterpreted as LR. The activation pattern of LR is of small stable rotational activations (carousels), and this drove 30% (7/23) of our postablation atrial tachycardias. However, this appearance is most often pseudo-reentrant and must be differentiated by interpretation of electrograms in the candidate circuit and activation in the wider surrounding region.


Impact of photonic crystal boundary shape on the existence of one-way edge mode.
The band structure of a two-dimensional photonic crystal (PhC) formed by a triangular lattice of air columns in a gyromagnetic material is investigated in the case when an external dc magnetic field is applied to it. It is shown that large magnetic-field-induced (MFI) bandgap is obtainable by optimizing the parameters of the PhC. The interface between a PhC with MFI bandgap and air may support unidirectional or bidirectional propagating edge modes, or even no mode, closely depending on the boundary shape of the truncated PhC. The transmission property of one-way mode sustained by the gyromagnetic PhC boundary is discussed through numerical simulation.


Asymmetry of vertical optokinetic nystagmus and afternystagmus.
The sensorimotor mechanism to stabilize the visual field in upright posture is not the same in earth-horizontal plane and vertical plane, because gravity possesses a directionality which is sensed by gravity-receptors. In this communication, asymmetric behavior of the vertical optokinetic nystagmus and afternystagmus is discussed, in conjunction with lesion placements within the peripheral and central neuro-networks (macula sacculi and cerebellar uvula and nodulus) in squirrel monkeys.


Thin, High-Flux, Self-Standing, Graphene Oxide Membranes for Efficient Hydrogen Separation from Gas Mixtures.
The preparation and gas-separation performance of self-standing, high-flux, graphene oxide (GO) membranes is reported. Defect-free, 15-20 μm thick, mechanically stable, unsupported GO membranes exhibited outstanding gas-separation performance towards H2 /CO2 that far exceeded the corresponding 2008 Robeson upper bound. Remarkable separation efficiency of GO membranes for H2 and bulky C3 or C4 hydrocarbons was achieved with high flux and good selectivity at the same time. On the contrary, N2 and CH4 molecules, with larger kinetic diameter and simultaneously lower molecular weight, relative to that of CO2 , remained far from the corresponding H2 /N2 or H2 /CH4 upper bounds. Pore size distribution analysis revealed that the most abundant pores in GO material were those with an effective pore diameter of 4 nm; therefore, gas transport is not exclusively governed by size sieving and/or Knudsen diffusion, but in the case of CO2 was supplemented by specific interactions through 1) hydrogen bonding with carboxyl or hydroxyl functional groups and 2) the quadrupole moment. The self-standing GO membranes presented herein demonstrate a promising route towards the large-scale fabrication of high-flux, hydrogen-selective gas membranes intended for the separation of H2 /CO2 or H2 /alkanes.


CSF 5-HIAA, cortisol and DHEAS levels in suicide attempters.
The serotonin system and the hypothalamic-pituitary-adrenal (HPA) axis are involved in the biological vulnerability to suicidal behaviour. Altered levels of dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS have been reported in neuropsychiatric conditions. The aim of this study was to investigate CSF levels of 5-Hydroxyindoleacetic acid (5-HIAA) and CSF and plasma levels of cortisol and DHEAS in 28 medication free suicide attempters and 19 healthy volunteers. Another aim was to investigate the relationship between neuroendocrine measures and childhood trauma in suicide attempters. As the study design includes a longitudinal part, we investigated whether CSF cortisol, 5-HIAA or DHEAS would predict subsequent suicide. We hypothesized higher cortisol levels in suicide attempters and lower CSF 5-HIAA levels and higher cortisol levels in suicide victims. Suicide attempters had higher CSF and plasma cortisol levels compared to healthy volunteers. Male suicide attempters had higher CSF DHEAS levels and female suicide attempters had lower CSF 5-HIAA levels compared to male and female healthy volunteers respectively. Exposure to interpersonal violence as a child showed a negative correlation with CSF cortisol/DHEAS ratio adjusted for age, gender and depression severity in a regression analysis. Suicide victims tended to have low CSF 5-HIAA and high CSF cortisol. Abused suicide victims had higher CSF cortisol compared to suicide victims with low exposure to interpersonal violence as a child. The results underlie the important role of the serotonergic system and HPA axis in suicidal behaviour and suggest that CSF DHEAS may be elevated in male suicide attempters.


A unique pulmonary venous abnormality: with associated pulmonary arterial anomaly and arteriovenous malformation.
A man aged 29 was first seen at the age of 11, when he was found to have a congenital anomaly of the pulmonary veins which follow an abnormal course to the hilum. On the left side, two large veins descend peripherally before turning medially towards the left atrium; on the right, several smaller veins follow a similar circuitous route from the periphery, before uniting into two main veins which enter the left atrium. The proximal pulmonary arteries are normal in their pattern of branching and distribution but are dilated and tortous and taper abruptly: the left lower lobe artery is abnormally large almost down to the diaphragm. There is also a systemic arterio/pulmonary venous fistula. There is no haemodynamic disturbance, but gas transfer is slightly impaired, and there is slight arterial desaturation. The congenital anomaly is unique. Reported cases described as having pulmonary venous varices are a heterogeneous group, but one patient described as such shows resemblances to our case.


Biodegradation of organics in landfill leachate by immobilized white rot fungi, Trametes versicolor BCC 8725.
Immobilized Trametes versicolor BCC 8725 was evaluated for the biodegradation of the organic components of four different types of landfill leachate collected at different time periods and locations from the Nonthaburi landfill site of Thailand in batch treatment. The effects of carbon source, ammonia and organic loading on colour, biochemical oxygen demand (BOD) and chemical oxygen demand (COD) removal, and the reuse of immobilized fungi were investigated. It was found that fungi can remove 78% of colour, reduce BOD by 68% and reduce COD by 57% in leachate within 15 days at optimum conditions. Organic loading and ammonia were the factors that affected the biodegradation. When immobilized T versicolor on polyurethane foam (PUF) was subjected to repeated use for treatment over the course of three cycles, the decolourization efficiency of the first and the second cycle was very similar, whereas the third cycle was about 20% lower than the first cycle under similar conditions. The obtained removal of colour, BOD and COD indicates the effectiveness of fungi for leachate treatment with high organic loading and varied leachate characteristics.


Practice status of specialized agencies for occupational health management of small- to medium-size enterprises and the factors improving their performance: a cross-sectional survey study.
We examined the current status of specialized agencies for occupational health management (SAs) and their workforce. Furthermore, we aimed to clarify the current practice status of SA healthcare professionals and factors that influence their performance. To examine the current SA workforce, we analyzed data from the 2014 Survey of Current Status of SA and their Workforce from the Ministry of Employment and Labor (MOEL). Furthermore, we mailed out an original questionnaire to SA professionals to determine their current health management status and factors that affect their performance. Data from the respondents (N = 384) were analyzed. In 2014, the workforce performing health management in SAs comprised 232 physicians, 507 nurses, and 312 occupational hygienists, with no significant regional differences in the distribution of physicians and nurses. According to the findings of the questionnaire, the average daily number of worker consultations by physicians and nurses was 22.8, while the average time taken for health management ranged from 74.3 to 104.3 min, depending on the size of the firm. Most of the respondents (41.5%) answered that they were following-up on more than 80% of individuals with illnesses. Among health management tasks, performance scores of "consultations for general diseases" and "consultations for lifestyle habits" were relatively high, whereas health promotion activities at workplaces were relatively low. There was a significant correlation between the utilization of general and special health examination results and task performance. Among health management tasks, follow-up management of individuals with illnesses and consultations for disease/lifestyle habits were relatively well performed, whereas health promotion activities at workplaces were not performed well. Among factors that positively influenced SA performance at workplaces, only the utilization of health examination results had significant effects. Therefore, to accomplish health management goals and perform effective health management at workplaces, there is a need to establish a comprehensive system of occupational health service outsourcing integrating health examinations and health management services. Furthermore, the current task system, which focuses on follow-up management, should be expanded to incorporate preventive and health promotion functions-the fundamental functions of occupational health services (OHS).


Differentiation of postpartum Graves' thyrotoxicosis from postpartum destructive thyrotoxicosis using antithyrotropin receptor antibodies and thyroid blood flow.
Postpartum thyroid dysfunction occurs in approximately 5-10% of women in the general population within one year of delivery. Differentiation of postpartum Graves' thyrotoxicosis (PPGr) from postpartum destructive thyrotoxicosis (PPDT) is essential because of the difference in treatment measures between the two. However, it is sometimes difficult because radioactive iodine uptake is contraindicated when patients are lactating. We examined the usefulness of determining the time of onset postpartum and measurement of antithyrotropin (anti-TSH) receptor antibodies and thyroid blood flow. Forty-two patients with newly developed thyrotoxicosis after delivery were examined: 18 had Graves' disease and 24 had destructive thyrotoxicosis. Serum free thyroxine (fT4), free triiodothyronine (fT3), and TSH were measured by chemiluminescent immunoassays. Anti-TSH receptor antibodies (TRAb), antithyroglobulin antibodies (TgAb), and antithyroid peroxidase antibodies (TPOAb) were measured by the Elecsys electrochemiluminescence immunoassay. Thyroid volume and blood flow (TBF) were measured quantitatively by color flow Doppler ultrasonography. Onset of thyrotoxicosis was distributed from 2 to 12 months postpartum. Twelve (85.7%) of 14 patients who developed thyrotoxicosis at three months or earlier after delivery had PPDT. On the other hand, all 11 patients who developed thyrotoxicosis at 6.5 months or later had PPGr. All patients with PPGr had positive TRAb (14.9±14.9 IU/L, mean±standard deviation (SD)) and all patients with PPDT had negative TRAb (0.1±0.3 IU/L, p<0.0001). Fifteen (83.3%) of 18 PPGr patients had high TBF of more than 4.0% (8.9±4.4), and all PPDT patients had low TBF of <4.0% (1.6±1.0, p<0.0001). The fT3/fT4 ratio was higher in PPGr (64.0±23.9) than in PPDT (38.9±13.1, p<0.0002), but absolute values overlapped between the two. Early onset of thyrotoxicosis postpartum was associated mainly with PPDT, and a late onset was suggestive of PPGr. Positive TRAb and high TBF >4.0% are indicators of postpartum onset of Graves' disease.


General psychopathology factor and borderline personality disorder: Evidence for substantial overlap from two nationally representative surveys of U.S. adults.
A general psychopathology factor reflects an underlying liability for a wide range of mental disorders. There is suggestive evidence that borderline personality disorder (BPD) may be strongly associated with the general psychopathology factor, but there are no detailed data on the degree of overlap between the general psychopathology factor and BPD or its individual symptoms. This study examined the overlap between the general psychopathology factor and BPD using cross-sectional survey data from two nationally representative samples of U.S. adults, the National Comorbidity Survey Replication (N = 5,692) and the National Comorbidity Survey follow-up (N = 5,001). Structural equation modeling was used to fit a bifactor general psychopathology model and to examine the general psychopathology factor's associations with (a) a series of Clusters A, B, and C personality disorder symptoms including BPD symptoms and (b) a latent BPD. Results showed that the shared variance between the general psychopathology factor and a latent BPD was 56% in the National Comorbidity Survey Replication and 71% in the National Comorbidity Survey follow-up. The correlation between the general factor and BPD could be set to unity without worsening model fit, suggesting that BPD closely reflects a general liability to psychopathology. The affective features of BPD were particularly strongly associated with the general psychopathology factor. Findings are discussed with respect to the nosology of BPD and the treatment of mental disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Paraneoplastic manifestations of lymphoma.
Paraneoplastic syndromes are manifestations of malignancies that have produced effects that are distant from the primary tumor or metastases. Paraneoplastic syndromes are not caused by local effects of compression or infiltration into tissues, but are generally due to ectopic hormone production, autoimmune phenomena, or overproduction of cytokines. Paraneoplasia may be the presenting symptom of underlying malignancy and can affect almost any organ system, such as the neurologic syndromes associated with small-cell lung cancer or hypercalcemia associated with squamous cell carcinomas. Lymphoproliferative disorders are also associated with many paraneoplastic disorders; however, to date, most published information has been in the form of case reports and series of small numbers of patients. In this review, the most common paraneoplastic syndromes associated with non-Hodgkin's lymphoma and Hodgkin's disease will be discussed.


Efficient Killing of Planktonic and Biofilm-Embedded Coagulase-Negative Staphylococci by Bactericidal Protein P128.
Coagulase-negative staphylococci (CoNS) are the major causative agents of foreign-body-related infections, including catheter-related bloodstream infections. Because of the involvement of biofilms, foreign-body-related infections are difficult to treat. P128, a chimeric recombinant phage-derived ectolysin, has been shown to possess bactericidal activity on strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). We tested the killing potential of P128 on three clinically significant species of CoNS, S. epidermidis, S. haemolyticus, and S. lugdunensis, under a variety of physiological conditions representing growing and nongrowing states. The MIC90 and minimum bactericidal concentration at which 90% of strains tested are killed (MBC90) of P128 on 62 clinical strains of CoNS were found to be 16 and 32 μg/ml (0.58 and 1.16 μM), respectively, demonstrating the bactericidal nature of P128 on CoNS strains. Serum showed a potentiating effect on P128 inhibition, as indicated by 4- to 32-fold lower MIC values observed in serum. P128 caused a rapid loss of viability in all CoNS strains tested. Persisters of CoNS that were enriched in the presence of vancomycin or daptomycin were killed by P128 at 1× the MIC in a rapid manner. Low concentrations of P128 caused a 2- to 5-log reduction in CFU in stationary-phase or poorly metabolizing CoNS cultures. P128 at low concentrations eliminated CoNS biofilms in microtiter plates and on the surface of catheters. Combinations of P128 and standard-of-care (SoC) antibiotics were highly synergistic in inhibiting growth in preformed biofilms. Potent activity on planktonic cells, persisters, and biofilms of CoNS suggests that P128 is a promising candidate for the clinical development of treatments for foreign-body-related and other CoNS infections.


Laser-Aided Directed Energy Deposition of Steel Powder over Flat Surfaces and Edges.
In the framework of Additive Manufacturing of metals, Directed Energy Deposition of steel powder over flat surfaces and edges has been investigated in this paper. The aims are the repair and overhaul of actual, worn-out, high price sensitive metal components. A full-factorial experimental plan has been arranged, the results have been discussed in terms of geometry, microhardness and thermal affection as functions of the main governing parameters, laser power, scanning speed and mass flow rate; dilution and catching efficiency have been evaluated as well to compare quality and effectiveness of the process under conditions of both flat and edge depositions. Convincing results are presented to give grounds for shifting the process to actual applications: namely, no cracks or pores have been found in random cross-sections of the samples in the processing window. Interestingly an effect of the scanning conditions has been proven on the resulting hardness in the fusion zone; therefore, the mechanical characteristics are expected to depend on the processing parameters.


Pharmacological features of the coronary, renal, mesenteric, and femoral vascular beds of rats revealed by intra-arterial administration of drugs.
We investigated the effects of 42 drugs on the circulation in the isolated, blood-perfused heart, kidney, small intestine, and hindlimb of rats and compared them with previously reported results in dogs. Single intra-arterial injections of drugs were made into the perfusion system of the coronary, renal, mesenteric, or femoral vascular bed. The most striking qualitative differences between rats and dogs were observed in vascular responses to nicotine, dipyridamole, 5-hydroxytryptamine (5-HT), lobeline, tetraethylammonium (TEA), and procaine. Nicotine constricted all vascular beds except the coronary bed in dogs, but dilated all four vascular beds in rats. Dipyridamole produced a dilatation in all vascular beds of rats, while it specifically constricted the renal vasculature of dogs. 5-HT constricted all vascular beds of rats, but dilated the coronary vasculature of dogs. Lobeline, TEA, and procaine constricted only the renal vascular bed in dogs, but elicited constriction of all vascular beds of rats.


Oral and dental findings in a child with growth hormone insensitivity syndrome.
Growth hormone insensitivity syndrome, also known as Laron syndrome, is an autosomal recessive disorder caused by defects the of growth hormone receptor gene and may lead to increased growth hormone levels. This syndrome's main clinical features are: dwarfism; acromicria; organomicria; cervical spinal stenosis; early osteoarthritic changes of the atlantoaxial joint; small oropharynx; decreased growth velocity; insulin resistance; hypoglycemia; delayed skeletal maturation and osteoporosis; and muscular and central nervous tissue underdevelopment. The facial bones, especially sphenoid and mandibular, are also underdeveloped. No reports of the incidence of growth hormone insensitivity syndrome in the population are available in the literature. The purpose this case report was to describe oral findings and particularities of dental treatment in a child with growth hormone insensitivity syndrome.


Pregnancy outcome in women with pre-existing lupus nephritis.
The aim of the present study was to assess the fetal and maternal outcome in a cohort of patients with lupus nephritis. Twenty-four pregnancies in 22 women with lupus nephritis occurring between 1991 and 2000 were analysed retrospectively. Lupus nephritis was biopsy proven before pregnancy in all cases. Women were followed from the beginning of pregnancy up to 6 months postpartum. Close fetal-maternal monitoring and frequent laboratory investigations were applied routinely to all patients. All women were prescribed steroid therapy from the beginning of the pregnancy. There were 18 live births, four spontaneous abortions and two stillbirths. Of the 18 live births, 14 were premature and four were term deliveries, representing a 25% fetal loss rate and 58% prematurity rate. There were two fetuses with congenital heart block. We recorded hypertension in 42%, proteinuria in 50% and pre-eclampsia in 25% of our patients. Proteinuria was irreversible in four cases. No maternal deaths or postpartum exacerbation of the disease were recorded in the study period. All renal flares were reversed postpartum. Patients positive for antiphospholipid antibodies had a worse perinatal outcome. Hypertension, proteinuria and antiphospholipid antibodies appear to be associated with adverse perinatal outcome and pregnancy complications. Pregnancy is not contraindicated in women with lupus nephritis, but is associated with significant fetal and maternal risks.


A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L.
Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC. The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%-53%; P = 0.031). The median PFS was 7.5 (6.2-12.3) months, while OS did not reach the median value. Major adverse event was grade 3-4 neutropenia in 34 patients (87%). There was no treatment-related death. In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.


Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway.
On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the KATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake.


Metabolic syndrome and its components associated with chronic kidney disease.
There is limited information on the relationship between metabolic syndrome (MetS) and chronic kidney disease (CKD) in the Iranian population, a group that has a high prevalence of CKD and obesity. The aim of present study was to determine the relationship between MetS and CKD in West of Iran. A total of 800 subjects aged more than 35 years admitted from 2011 to 2013 were enrolled in the study. MetS was defined based on the Adult Treatment Panel III criteria, and CKD was defined from the Kidney Disease Outcomes Quality Initiative practice guidelines. Waist circumference and body mass index were calculated, as well, blood samples were taken and lipid profile, plasma glucose levels, and serum creatinine were measured. Data were analyzed with SPSS version 17 (SPSS Inc., Chicago, IL, USA). CKD was seen in 14.8% patients with MetS and 8.3% individuals without MetS. MetS was associated with an increased odds ratio (OR) for a glomerular filtration rate <60 ml/min/1.73 m(2) (OR: 1.91; 95% confidence interval [CI]: 1.22-2.99; P = 0.004). Individuals with 2, 3, 4, and 5 components of the MetS had an increased OR for CKD: 2.19 (95% CI: 0.95-3.62), 2.65 (95% CI: 1.03-4.71), 2.86 (95% CI: 1.08-5.53), and 5.03 (95% CI: 1.80-8.57), respectively, compared with individuals with none of the components. We found a high prevalence of CKD in patients with MetS compared with the subject without MetS. Our observations raised major clinical and public health concerns in Iran, where both the MetS and kidney diseases are becoming common.


Content-based image retrieval in radiology: current status and future directions.
Diagnostic radiology requires accurate interpretation of complex signals in medical images. Content-based image retrieval (CBIR) techniques could be valuable to radiologists in assessing medical images by identifying similar images in large archives that could assist with decision support. Many advances have occurred in CBIR, and a variety of systems have appeared in nonmedical domains; however, permeation of these methods into radiology has been limited. Our goal in this review is to survey CBIR methods and systems from the perspective of application to radiology and to identify approaches developed in nonmedical applications that could be translated to radiology. Radiology images pose specific challenges compared with images in the consumer domain; they contain varied, rich, and often subtle features that need to be recognized in assessing image similarity. Radiology images also provide rich opportunities for CBIR: rich metadata about image semantics are provided by radiologists, and this information is not yet being used to its fullest advantage in CBIR systems. By integrating pixel-based and metadata-based image feature analysis, substantial advances of CBIR in medicine could ensue, with CBIR systems becoming an important tool in radiology practice.


The somatotype of medium class Italian basketball players.
The aim of this observational study was to determine the somatotype of average basketball players (BP) and to compare them with the values found in relevant literature. Thirty-eight Italian members of "B" and "C" BP league teams were measured according to the Health/Carter anthropometric somatotype method. Since our group was, on average, made up of mesomorphic-ectomorphs (2.2-3.2-3.8), it appeared to be quite well suited to the sporting activity undertaken. However, the comparison carried out for the anthropometric variables and the somatotype scores found for higher level athletes, show that their physique lacks some of the characteristics needed to excel.


Prostate adenocarcinoma presenting as a large supraclavicular mass.
Metastatic prostate cancer is classically associated with bony or pelvic lymphatic metastasis. This case review represents an unusual case of prostate cancer presenting with a large left supraclavicular neck mass.


EARLY DETECTION OF RETINAL HEMANGIOBLASTOMAS IN VON HIPPEL-LINDAU DISEASE USING ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY.
To study the use of ultra-widefield fluorescein angiography (UWF FA) in the detection and management of retinal capillary hemangioblastomas in patients with von Hippel-Lindau disease. This is a retrospective study of patients with von Hippel-Lindau disease who underwent UWF FA using the Optos camera at a single center from June 2009 to May 2015. The clinical use of UWF FA was reviewed, and the number of hemangioblastomas identified on UWF FA was compared with ophthalmoscopy and a simulated seven standard field (7SF) FA montage. Twenty eyes of 10 patients were identified. Only 33% of lesions seen on UWF FA were also found on ophthalmoscopy, and 88% of lesions visualized on UWF FA were located outside the 7SF overlay. In 5 eyes that had gaze steering, 18% of lesions could be visualized only on gaze-steered images. For the 14 eyes with data available, 6 had procedures recommended and 8 eyes observed based on data from UWF FA. One of 20 eyes had a lesion on ophthalmoscopy that was missed by imaging. Ultra-widefield FA using the Optos camera is helpful for the evaluation and management of patients with von Hippel-Lindau disease. The UWF FA with gaze steering appears to detect more hemangioblastomas than ophthalmoscopy and conventional angiography.


Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle.
Immune checkpoint blockade therapy has shifted the paradigm for cancer treatment. However, the majority of patients lack effective responses due to insufficient T cell infiltration in tumors. Here we show that expression of mitochondrial uncoupling protein 2 (UCP2) in tumor cells determines the immunostimulatory feature of the tumor microenvironment (TME) and is positively associated with prolonged survival. UCP2 reprograms the immune state of the TME by altering its cytokine milieu in an interferon regulatory factor 5-dependent manner. Consequently, UCP2 boosts the conventional type 1 dendritic cell- and CD8+ T cell-dependent anti-tumor immune cycle and normalizes the tumor vasculature. Finally we show, using either a genetic or pharmacological approach, that induction of UCP2 sensitizes melanomas to programmed cell death protein-1 blockade treatment and elicits effective anti-tumor responses. Together, this study demonstrates that targeting the UCP2 pathway is a potent strategy for alleviating the immunosuppressive TME and overcoming the primary resistance of programmed cell death protein-1 blockade.


Jak2 tyrosine kinase mediates angiotensin II-dependent inactivation of ERK2 via induction of mitogen-activated protein kinase phosphatase 1.
Previous work has shown that inhibition of Jak2 via the pharmacological compound AG490 blocks the angiotensin II (Ang II)-dependent activation of ERK2, thereby suggesting an essential role of Jak2 in ERK activation. However, recent studies have thrown into question the specificity of AG490 and therefore the role of Jak2 in ERK activation. To address this, we reconstituted an Ang II signaling system in a Jak2-/-cell line and measured the ability of Ang II to activate ERK2 in these cells. Controls for this study were the same cells expressing Jak2 via the addition of a Jak2 expression plasmid. In the cells expressing Jak2, Ang II induced a marked increase in ERK2 activity as measured by Western blot analysis and in vitro kinase assays. ERK2 activity returned to basal levels within 30 min. However, in the cells lacking Jak2, Ang II treatment resulted in ERK2 activation that did not return to basal levels until 120 min after ligand addition. Analysis of phosphatase gene expression revealed that Ang II induced mitogen-activated protein kinase phosphatase 1 (MKP-1) expression in cells expressing Jak2 but failed to induce MKP-1 expression in cells lacking Jak2. Therefore, our results suggest that Jak2 is not required for Ang II-induced ERK2 activation. Rather Jak2 is required for Ang II-induced ERK2 inactivation via induction of MKP-1 gene expression.


N-Hydroxy peptides: solid-phase synthesis and β-sheet propensity.
Peptide backbone amide substitution can dramatically alter the conformational and physiochemical properties of native sequences. Although uncommon relative to N-alkyl substituents, peptides harboring main-chain N-hydroxy groups exhibit unique conformational preferences and biological activities. Here, we describe a versatile method to prepare N-hydroxy peptide on solid support and evaluate the impact of backbone N-hydroxylation on secondary structure stability. Based on previous work demonstrating the β-sheet-stabilizing effect of α-hydrazino acids, we carried out an analogous study with N-hydroxy-α-amino acids using a model β-hairpin fold. In contrast to N-methyl substituents, backbone N-hydroxy groups are accommodated in the β-strand region of the hairpin without energetic penalty. An enhancement in β-hairpin stability was observed for a di-N-hydroxylated variant. Our results facilitate access to this class of peptide derivatives and inform the use of backbone N-hydroxylation as a tool in the design of constrained peptidomimetics.


Routine Intraoperative Inhaled Milrinone and Iloprost Reduces Inotrope Use in Patients Undergoing Cardiac Surgery: A Retrospective Cohort Pilot Study.
Catecholamine inotropes are frequently used after cardiopulmonary bypass (CPB) but may have undesirable effects. The aim was to identify whether the routine use of inhaled pulmonary vasodilators might reduce the requirement for inotrope drugs after cardiac surgery. Retrospective cohort study of sequential patients undergoing cardiac surgery at the Royal Melbourne Hospital performed by a single surgeon and anesthesia care team, within 14 months before and after routine implementation of inhaled pulmonary vasodilators, August 2017. Milrinone 4 mg and iloprost 20 µg were inhaled using a vibrating mesh nebulizer (Aerogen) before initiation of CPB and at chest closure. Other aspects of clinical management were unaltered over the time period. Two investigators blinded to each other extracted data from electronic and written medical records. The primary outcome was any use of inotropes in the perioperative period; a Fisher exact test was used to analyze any differences between the 2 groups. Demographic data, hemodynamic data, and use of inotropes and vasopressors were collected from induction of anesthesia to 36 hours postoperative in the intensive care unit (ICU). Hospital and ICU length of stay, cost, and complications were collected. Any use of inotropes was significantly lower with inhaled pulmonary dilators (62.5% vs 86.8%, odds ratio [95% confidence interval {CI}], 0.253 (0.083-0.764); P = .011), including intraoperative inotrope use (37.5% vs 86.8%, odds ratio [95% CI], 0.091 (0.03-0.275); P < .001). ICU length of stay was significantly lower with inhaled pulmonary dilators (45 hours, interquartile range [IQR], 27-65 vs 50 hours, IQR, 45-74; P = .026). There were no significant differences among major postoperative complications or costs between groups. Routine use of inhaled milrinone 4 mg and iloprost 20 µg before and after CPB is associated with reduced postoperative inotrope use.


Correlates of individual participation in boundary patrols by male chimpanzees.
Group territory defence poses a collective action problem: individuals can free-ride, benefiting without paying the costs. Individual heterogeneity has been proposed to solve such problems, as individuals high in reproductive success, rank, fighting ability or motivation may benefit from defending territories even if others free-ride. To test this hypothesis, we analysed 30 years of data from chimpanzees (Pan troglodytes) in the Kasekela community, Gombe National Park, Tanzania (1978-2007). We examined the extent to which individual participation in patrols varied according to correlates of reproductive success (mating rate, rank, age), fighting ability (hunting), motivation (scores from personality ratings), costs of defecting (the number of adult males in the community) and gregariousness (sighting frequency). By contrast to expectations from collective action theory, males participated in patrols at consistently high rates (mean ± s.d. = 74.5 ± 11.1% of patrols, n = 23 males). The best predictors of patrol participation were sighting frequency, age and hunting participation. Current and former alpha males did not participate at a higher rate than males that never achieved alpha status. These findings suggest that the temptation to free-ride is low, and that a mutualistic mechanism such as group augmentation may better explain individual participation in group territorial behaviour. This article is part of the theme issue 'Intergroup conflict across taxa'.


The Biology and Evolution of Mammalian Y Chromosomes.
Mammals have the oldest sex chromosome system known: the mammalian X and Y chromosomes evolved from ordinary autosomes beginning at least 180 million years ago. Despite their shared ancestry, mammalian Y chromosomes display enormous variation among species in size, gene content, and structural complexity. Several unique features of the Y chromosome--its lack of a homologous partner for crossing over, its functional specialization for spermatogenesis, and its high degree of sequence amplification--contribute to this extreme variation. However, amid this evolutionary turmoil many commonalities have been revealed that have contributed to our understanding of the selective pressures driving the evolution and biology of the Y chromosome. Two biological themes have defined Y-chromosome research over the past six decades: testis determination and spermatogenesis. A third biological theme begins to emerge from recent insights into the Y chromosome's roles beyond the reproductive tract--a theme that promises to broaden the reach of Y-chromosome research by shedding light on fundamental sex differences in human health and disease.


RT 3D TEE: Characteristics of Mitral Valve in Ischemic Mitral Regurgitation Evaluated by MVQ Program.
To assess the changes of mitral valve (MV) in ischemic mitral regurgitation (IMR) using Mitral Valve Quantification (MVQ) program. We examined 46 patients (18 women) with IMR aged 45-86 and a control group of 33 healthy individuals (14 women) aged 18-88. Following parameters were assessed: Area of minimal surface spanning annulus (A3), annulus height (h), tenting height (Th), exposed area of anterior (AL), posterior (PL) and both leaflets (BL), ejection fraction of the left ventricle (LV EF), regurgitation volume (RV) and BL/A3, AL/A3, PL/A3 ratios. The normal range of BL/A3 ratio was defined as the average ± 2SD of control group. The study group was separated into subgroup 1 with BL/A3 ratio within normal values and subgroup 2 with pathological BL/A3 ratio. Corresponding parameters of IMR group were compared to the controls and both subgroups were compared to each other using Student t-test. In IMR group, as compared to the controls, A3, AL, PL, BL as well as BL/A3, AL/A3, PL/A3 ratios and Th were significantly increased, conversely, h and LV EF was significantly decreased. In the subgroup 2 as compared to the subgroup 1 there was significant increase of Th, BL, AL and PL, while EF LV was significantly decreased. There was no significant difference between these subgroups in A3, h and RV. In ischemic MV remodeling two stages were identified without relation to the severity of IMR. The first stage was mainly influenced by the LV dilatation while LV remodeling was more important in the second stage.


Broadly Reactive Anti-Respiratory Syncytial Virus G Antibodies from Exposed Individuals Effectively Inhibit Infection of Primary Airway Epithelial Cells.
Respiratory syncytial virus (RSV) causes severe respiratory disease in young children. Antibodies specific for the RSV prefusion F protein have guided RSV vaccine research, and in human serum, these antibodies contribute to >90% of the neutralization response; however, detailed insight into the composition of the human B cell repertoire against RSV is still largely unknown. In order to study the B cell repertoire of three healthy donors for specificity against RSV, CD27+ memory B cells were isolated and immortalized using BCL6 and Bcl-xL. Of the circulating memory B cells, 0.35% recognized RSV-A2-infected cells, of which 59% were IgA-expressing cells and 41% were IgG-expressing cells. When we generated monoclonal B cells selected for high binding to RSV-infected cells, 44.5% of IgG-expressing B cells and 56% of IgA-expressing B cells reacted to the F protein, while, unexpectedly, 41.5% of IgG-expressing B cells and 44% of IgA expressing B cells reacted to the G protein. Analysis of the G-specific antibodies revealed that 4 different domains on the G protein were recognized. These epitopes predicted cross-reactivity between RSV strain A (RSV-A) and RSV-B and matched the potency of antibodies to neutralize RSV in HEp-2 cells and in primary epithelial cell cultures. G-specific antibodies were also able to induce antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis of RSV-A2-infected cells. However, these processes did not seem to depend on a specific epitope. In conclusion, healthy adults harbor a diverse repertoire of RSV glycoprotein-specific antibodies with a broad range of effector functions that likely play an important role in antiviral immunity.IMPORTANCE Human RSV remains the most common cause of severe lower respiratory tract disease in premature babies, young infants, the elderly, and immunocompromised patients and plays an important role in asthma exacerbations. In developing countries, RSV lower respiratory tract disease has a high mortality. Without an effective vaccine, only passive immunization with palivizumab is approved for prophylactic treatment. However, highly potent RSV-specific monoclonal antibodies could potentially serve as a therapeutic treatment and contribute to disease control and mortality reduction. In addition, these antibodies could guide further vaccine development. In this study, we isolated and characterized several novel antibodies directed at the RSV G protein. This information can add to our understanding and treatment of RSV disease.


Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats.
Inflammation is a crucial step for the wound healing process. The effect of linoleic and oleic acids on the inflammatory response of the skin during the healing process and on the release of pro-inflammatory cytokines by rat neutrophils in vitro was investigated. A wound in the dorsal surface of adult rats was performed and fatty acids were then topically administered. Both oleic and linoleic acids increased the wound healing tissue mass. The total protein and DNA contents of the wounds were increased by the treatment with linoleic acid. The treatments with oleic and linoleic acids did not affect vascular permeability. However, the number of neutrophils in the wounded area and air pouches was increased and the thickness of the necrotic cell layer edge around the wound was decreased. A dose-dependent increase in vascular endothelial growth factor-alpha (VEGF-alpha) and interleukin-1beta (IL-1beta) by neutrophils incubated in the presence of oleic and linoleic acid was observed. Oleic acid was able to stimulate also the production of cytokine-induced neutrophil chemoattractant in inflammation 2 alpha/beta (CINC-2alpha/beta). This pro-inflammatory effect of oleic and linoleic acids may speed up the wound healing process.


Using molecular network analysis to understand current HIV-1 transmission characteristics in an inland area of Yunnan, China.
HIV-1 molecular surveillance provides a new approach to explore transmission risks and targeted interventions. From January to June 2021, 663 newly reported HIV-1 cases were recruited in Zhaotong City, Yunnan Province, China. The distribution characteristics of HIV-1 subtypes and HIV-1 molecular network were analysed. Of 542 successfully subtyped samples, 12 HIV-1 strains were identified. The main strains were CRF08_BC (47.0%, 255/542), CRF01_AE (17.0%, 92/542), CRF07_BC (17.0%, 92/542), URFs (8.7%, 47/542), and CRF85_BC (6.5%, 35/542). CRF08_BC was commonly detected among Zhaotong natives, illiterates, and non-farmers and was mostly detected in Zhaoyang County. CRF01_AE was frequently detected among married and homosexual individuals and mostly detected in Weixin and Zhenxiong counties. Among the 516 pol sequences, 187 (36.2%) were clustered. Zhaotong natives, individuals aged ≥60 years, and illiterate individuals were more likely to be found in the network. Assortativity analysis showed that individuals were more likely to be genetically associated when stratified by age, education level, occupation, and reporting area. The genetic diversity of HIV-1 reflects the complexity of local HIV epidemics. Molecular network analyses revealed the subpopulations to focus on and the characteristics of the risk networks. The results will help optimise local prevention and control strategies.


Locomotor activity induced by noncompetitive NMDA receptor antagonists versus dopamine transporter inhibitors: opposite strain differences in inbred long-sleep and short-sleep mice.
The actions of ethanol in the brain involve multiple neuroreceptor systems, including glutamatergic N-methyl-D-aspartate receptor (NMDAR) channels. In a novel environment, both ethanol and the noncompetitive NMDAR antagonist MK-801 stimulate locomotor activity to a lesser extent in inbred long-sleep (ILS) mice compared with inbred short-sleep (ISS) mice. The behaviorally activating effects of noncompetitive NMDAR antagonists are thought to involve increased monoamine neurotransmission. Thus, in this study, we sought to determine whether: (1) habituation to the behavioral environment alters the differential locomotor-stimulant effects of noncompetitive NMDAR antagonists in ILS and ISS mice and (2) the differential behavioral sensitivity of ILS and ISS mice to noncompetitive NMDAR antagonists is mediated through direct inhibition of the dopamine transporter (DAT). Open field locomotor activity was measured following acute systemic injection of saline or drug. [3H]DA uptake parameters were determined in striatal synaptosomes prepared from drug-naïve mice. Habituation to the testing environment abolished the strain differences in saline-induced locomotor activity. However, ethanol- as well as MK-801-treated ILS mice still exhibited reduced locomotor activity compared with ISS mice, suggesting that a drug-environment interaction is not the primary explanation for the strain differences. The noncompetitive NMDAR antagonists phencyclidine and ketamine also induced significantly lower locomotor activity in ILS than in ISS mice. In contrast, the DAT inhibitors cocaine and GBR 12909 and the DA releaser amphetamine induced greater locomotor activity in ILS than in ISS mice, a strain difference opposite that of the noncompetitive NMDAR antagonists. Furthermore, the differential behavioral effect found with DAT inhibitors was not mediated by differences in the affinity nor number of striatal DATs between ILS and ISS mice. Our results support the conclusion that the differential locomotor-stimulant effects of ethanol and noncompetitive NMDAR antagonists in ILS and ISS mice are not mediated through direct inhibition of DAT.


Postoperative interventricular septal haematoma following tetralogy of Fallot repair and perimembranous ventricular septal defect repair.
Interventricular septal haematoma is a rare postoperative complication in congenital heart surgery. We present one case of a 6-month-old after tetralogy of Fallot repair and 1 case of a 10-month-old after ventricular septal defect repair. Both were noted to have interventricular septal haematoma on intraoperative transoesophageal and postoperative echocardiogram. Although multiple previous reports, mainly in adults, have suggested aggressive intervention, both these cases were managed conservatively, highlighting the management and evolution of a rare postoperative complication in the paediatric population.


Vasorelaxant and hypotensive effects of tilisolol hydrochloride (N-696) in isolated rat thoracic aorta and pithed rats.
Vasorelaxant and hypotensive effects of tilisolol hydrochloride (N-696) in isolated rat thoracic aorta and pithed rats were investigated. In rat thoracic aorta pre-contracted with KCl (20 mM), tilisolol (10(-5)-10(-3) M) produced concentration-related relaxation, but nadolol and atenolol did not significantly inhibit the responses to 20 mM KCl. The concentration-relaxation curve of tilisolol underwent rightward parallel shifts only to a limited extent in the presence of glibenclamide, a specific antagonist of K+ channel openers. Glibenclamide also shifted the concentration-relaxation curve of cromakalim to the right and in a parallel manner, whereas it did not change that of propranolol. In pithed rats, tilisolol (0.5-2.0 mg/kg, i.v.), but neither nadolol nor atenolol, caused a dose-dependent decrease in diastolic blood pressure and a slight increase in heart rate. Following treatment of the preparation with glibenclamide, the hypotensive effects of tilisolol and cromakalim were antagonized, while that of propranolol was not affected. These results suggest that the vasorelaxant and hypotensive actions of tilisolol involve an opening of K+ channels which can be inhibited by glibenclamide and may also involve additional relaxant mechanisms of action independent of K+ channel opening.


Taurine accelerates the synthesis of ceramides and hyaluronic acid in cultured epidermis and dermal fibroblasts.
Taurine is a sulfur-containing amino acid derivative that can be found in the majority of mammalian tissues. Taurine is also present in the skin and is involved in maintaining skin homeostasis by exerting osmoregulatory and antioxidant effects. Previous studies have indicated that taurine treatment is effective against age-, ultraviolet- or detergent-induced skin dysfunction. To determine the mechanism responsible for the beneficial actions of taurine in the skin, the present study aimed to evaluate the effects of taurine on epidermal components (ceramides and filaggrin) and on the dermal extracellular matrix, in three-dimensionally (3D) cultured epidermis and dermal fibroblasts, respectively. These cells were cultured in the presence of 3-50 mM taurine, and cells or culture medium were collected for analysis. The effects of taurine on transepidermal water loss (TEWL) in the skin and the expression of inflammatory cytokines, including IL-1α, IL-1β and IL-1 receptor antagonist, were investigated in acetone-treated 3D-cultured epidermis using a Tewameter and reverse transcription-quantitative PCR (RT-qPCR), respectively. The mRNA expression levels of MMP-1 and hyaluronic acid (HA) production were measured in skin dermal fibroblasts using RT-qPCR and ELISA, respectively. Taurine was found to suppress acetone-induced elevation in TEWL in 3D-cultured epidermis. Taurine also stimulated the mRNA expression of ceramide synthase 4 and filaggrin, a major structural protein in the stratum corneum, in 3D-cultured epidermis. In skin dermal fibroblasts, taurine inhibited the IL-1α-stimulated mRNA and protein expression of MMP-1. In addition, taurine treatment increased HA synthase-2 mRNA expression and in turn HA production. Results from the present study suggest that the protective effect of taurine on the skin is associated with the enhancement of epidermal barrier component expression and modulation of dermal extracellular matrix metabolism.


The effect of ischemic preconditioning on secondary ischemia in skin flaps.
Ischemic preconditioning is a useful manipulation to reduce the undesirable effects of ischemia. The beneficial results of this phenomenon against ischemia-reperfusion have been seen in different flap models; however, all these studies have focused on primary ischemia. In this study, we investigated the effects of ischemic preconditioning on secondary ischemia in a skin flap model. We used the 6- x 3-cm-sized epigastric skin flap in 40 Wistar rats. In all animals, primary global ischemia of 2 hours was followed by 4 hours of either arterial or venous secondary ischemia 24 hours after the primary ischemia and ischemic preconditioning (IP) was tested in this protocol. Ischemic preconditioning was performed by 2 cycles of 15 minutes of repeated ischemia/reperfusion periods. The animals were allocated into 4 groups: group 1 (n = 10 animals): primary ischemia (2 hours) + secondary arterial ischemia (4 hours); group 2 (n = 10 animals): IP + primary ischemia (2 hours) + secondary arterial ischemia (4 hours); group 3 (n = 10 animals): primary ischemia (2 hours) + secondary venous ischemia (4 hours); group 4 (n = 10 animals): IP + primary ischemia (2 hours) + secondary venous ischemia (4 hours). Flap viability was assessed 1 week after the surgical procedure, and surviving flap area was recorded as a percentage of the whole flap area. Group 1 was compared with group 2, and group 3 was compared with group 4 to evaluate the effects of ischemic preconditioning against secondary arterial and venous ischemia. t test and Mann-Whitney rank sum tests were used for statistical analysis. There were statistical differences both between groups 1 and 2 and groups 3 and 4. The results revealed that ischemic preconditioning was an effective procedure to reduce the flap necrosis as a cause of secondary ischemia in skin flaps.


Development and validation of a prognostic nomogram for open elbow arthrolysis : the Shanghai Prediction model for Elbow Stiffness Surgical Outcome.
The aim of this study was to develop and internally validate a prognostic nomogram to predict the probability of gaining a functional range of motion (ROM ≥ 120°) after open arthrolysis of the elbow in patients with post-traumatic stiffness of the elbow. We developed the Shanghai Prediction Model for Elbow Stiffness Surgical Outcome (SPESSO) based on a dataset of 551 patients who underwent open arthrolysis of the elbow in four institutions. Demographic and clinical characteristics were collected from medical records. The least absolute shrinkage and selection operator regression model was used to optimize the selection of relevant features. Multivariable logistic regression analysis was used to build the SPESSO. Its prediction performance was evaluated using the concordance index (C-index) and a calibration graph. Internal validation was conducted using bootstrapping validation. BMI, the duration of stiffness, the preoperative ROM, the preoperative intensity of pain, and grade of post-traumatic osteoarthritis of the elbow were identified as predictors of outcome and incorporated to construct the nomogram. SPESSO displayed good discrimination with a C-index of 0.73 (95% confidence interval 0.64 to 0.81). A high C-index value of 0.70 could still be reached in the interval validation. The calibration graph showed good agreement between the nomogram prediction and the outcome. The newly developed SPESSO is a valid and convenient model which can be used to predict the outcome of open arthrolysis of the elbow. It could assist clinicians in counselling patients regarding the choice and expectations of treatment. Cite this article: Bone Joint J 2022;104-B(4):486-494.


Inhibition of pyrite oxidation by a phospholipid in the presence of silicate.
The influence of sodium silicate on the ability of a diacetylene-containing phospholipid (23:2 diyne PC) to inhibit the oxidation of pyrite at pH 2 and pH 6 was investigated. The phospholipid used has previously been reported to show up to 80% suppression of pyrite oxidation and to show excellent stability down to at least pH 2. Pyrite was leached with a solution containing Fe3+ but no coating agent and three different solutions or treatments: a lipid treatment, a silicate treatment, and a lipid + silicate treatment. Pyrite oxidation was based on iron (Fe3+, Fe2+) leached out of a continuous-flow porous-bed reactor system. The results show that at pH 6 the silicate and lipid both bind strongly to the pyrite surfaces, providing a barrier that inhibits the production and subsequent release of oxidation products. The lipid is superior to the silicate in suppressing pyrite oxidation at both pH 2 and pH 6. Also, the presence of silicates decreased the ability for the lipid to suppress pyrite oxidation, both at pH 2 and pH 6. The reaction mechanism for pyrite oxidation at pH 2 is first order for pyrite leached by solutions containing only ferric, ferric together with silicate, and ferric combined with silicate and lipid. The only treatment that effectively prevented pyrite oxidation at pH 2 was the lipid treatment. The Fe speciation results are supported by both SEM images and EDS calculations.


Induction effects of ritonavir: implications for drug interactions.
To review the literature on the induction effects of ritonavir on the cytochrome P450 enzyme system and glucuronyl transferase and identify resultant established and potential drug interactions. Primary literature was identified from MEDLINE (1950-April 2008), EMBASE (1988-April 2008) and International Pharmaceutical Abstracts (1970-April 2008) using the search terms ritonavir, cytochrome P450 enzyme system, enzyme induction, glucuronyl transferase, and drug interactions. Additionally, relevant conference abstracts and references of relevant articles were reviewed. All English-language articles and abstracts identified were reviewed. Ritonavir is a well-known inhibitor of the metabolism of numerous medications that are substrates of the CYP3A and CYP2D6 pathways. It also exhibits a biphasic, time-dependent effect on P-glycoprotein of inhibition followed by induction. Numerous pharmacokinetic studies suggested that ritonavir induces cytochrome P450 enzymes 3A, 1A2, 2B6, 2C9, and 2C19, as well as glucuronyl transferase. Additionally, several case reports described clinically significant subtherapeutic effects of drugs metabolized by these isoenzymes when coadministered with ritonavir. Both therapeutic and boosting doses of ritonavir appear to induce these enzymes; however, most of the studies of low-dose ritonavir involved a second protease inhibitor such as lopinavir, darunavir, or tipranavir. It is, therefore, difficult to distinguish the relative effects of additional medications unless well-designed, 3-way studies are conducted. At both therapeutic and boosting doses, ritonavir exhibits a clinically relevant induction effect on numerous drug-metabolizing enzymes. A decrease or loss of therapeutic effect may be observed when ritonavir is coadministered with medications that are substrates for these enzymes. It is important for clinicians to be aware of drugs potentially impacted by ritonavir therapy to identify and manage these interactions.


A Dual-Mechanism Based Nutrient Partitioning Nanoregulator for Enhanced Immunotherapy against Anti-PD-1 Resistant Tumors.
Competitive consumption of nutrients between rapidly proliferating cancer cells and T cells results in an immunosuppressive tumor microenvironment (TME) and nutrient deprivation of T cells, which can cause low response rate and resistance to immunotherapies. In this study, we proposed a dual-mechanism based nutrient partitioning nanoregulator (designated as DMNPN), which can simultaneously regulate the immunosuppressive TME and enhance T cell nutrient availability. DMNPN consists of a charge-reversal biodegradable mesoporous silica, encapsulating glycolysis inhibitor lonidamine, and small interfering RNA against glutaminase. Through inhibiting glycolysis to decrease the lactic acid production and downregulating glutaminase expression to reduce the uptake of glutamine by tumor cells, DMNPN enables effective remodeling of metabolism and nutrient partitioning, which alleviates the immunosuppressive TME and boosts nutrient availability for T cells with enhanced antitumor immunity. Such a nutrient partitioning nanoregulator can effectively inhibit the growth of anti-programmed death receptor 1 (anti-PD-1) resistant tumors and prevent tumor metastasis and recurrence. Overall, this dual-mechanism based nutrient reallocation strategy provides a promising approach for cancer therapy.


Emergency separation of craniopagus twins: case report.
Craniopagus is a very rare congenital anomaly that tends to affect females more often than males. It is classified as partial or total. Most affected twins are either stillborn or die during the perinatal period. Those who survive birth should undergo detailed radiological evaluations soon after their condition becomes stable so that the precise anatomy of the conjoined part can be defined and surgery can be planned in detail by a multidisciplinary team. Recommendations for decreasing the risk of unsuccessful surgery include performing surgery on an elective basis after extensive preoperative radiological evaluations as well as when the twins are at an acceptable age and weight for a complex surgical separation, generally as staged procedures. In addition, the operation should be performed by a well-equipped expert multidisciplinary team. When one of the conjoined twins dies, however, surgical separation cannot be postponed because the shared circulatory system predisposes the alive child to life-threatening complications, including coagulopathy. The authors report on the successful separation of craniopagus twins performed on an emergency basis at 32 weeks of gestational age because of the sudden death of one of them. At the time of separation surgery, the twins each weighed 1250 g. To the best of the authors' knowledge, this is the youngest age and lowest weight yet reported for successful surgical separation. The surviving twin developed a pseudomeningocele, which required a second operation and placement of a cystoperitoneal shunt 4 months after the operation. Additional surgery is planned to repair a cranial defect that resulted from the pseudomeningocele, but his general physical and mental condition was otherwise good at latest follow-up (12 months after separation surgery).


Bupivacaine-induced regeneration of rat soleus muscle: ultrastructural and immunohistochemical aspects.
The regeneration of soleus muscle injury induced by the bupivacaine model was studied ultrastructurally and immunohistochemically. Twenty-one young (age range 3-3.5 months) male Wistar rats were subjected to a single intramuscular injection of 1 mL of 0.5% Marcaine. The muscles were examined on biopsy days 1, 2, 3, 5, 7, 14, and 21. By day 1, mononuclear inflammatory cells had invaded the necrotic sarcoplasm. Degenerative morphological findings counted mainly for the hypercontracted fibers, dilation of sarcoplasmic reticulum, plasma membrane defects, mitochondrial alterations, and myofibril discontinuities. By day 2 proliferating myoblasts were seen with variety in shape, which fused on the day 3. Myotubes with multiple central nuclei and euchromatic nucleoli were formed by day 5. Asynchronous repair events were seen with bundles of myofilaments toward the core of the fibers, in contrast to the least mature distal growth cones, which had free myoblasts in proximity and formatted pseudopods. Chronologically asynchronous regeneration stages possibly suggested successive satellite cell activation profiles or heterogeneity in satellite cell population. In parallel with the electron microscopy, in light microscope immunocytochemistry, desmin- and vimentin-positive mononuclear cells were observed within the first 3 biopsy days, but as regeneration proceeded, desmin predominated over vimentin. Merosin immunoreactivity revealed preservation of the basal lamina, which is crucial for the stability and survival of myotubes. By day 21, fibers restored the overall control architecture.


Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves' disease treated using antithyroid medication.
To determine the course of thyrotropin (thyroid-stimulating hormone [TSH]) receptor antibodies (TRAbs) in children and adolescents with Graves' disease treated using antithyroid drugs (ATDs). Retrospective, cross-sectional study of 86 children and adolescents with Graves' disease treated medically for >3 years. Patients with Hashimoto's thyroiditis and idiopathic short stature (n = 30) served as controls. A second-generation enzyme-linked immunosorbent assay (ELISA) for TRAbs was used. Twenty-two out of 23 (95.7%) patients with newly diagnosed Graves' disease, but 0/30 controls, had detectable TRAbs (22.0 +/- 13.5 U/L [mean +/- SD] vs. 0.9 +/- 0.9 U/L, p < 0.0001). Mean TRAb levels decreased with duration of therapy, but even after 13-24 months, TRAbs had normalized in only 3/16 (18.8%) patients. The initial TRAb titer correlated significantly with severity of the initial hyperthyroidism, but did not predict the response to therapy as indicated by the dosage of ATD required to control the hyperthyroidism at 6 and 12 months. Unlike adults, most children and adolescents with Graves' disease require >2 years of ATD treatment before TRAbs are normalized. Although initial TRAb activity reflects disease severity, it does not predict the response to medical therapy. Recommendations as to treatment duration developed for adult patients should not be applied to the young.


Regulations and Norms for Reuse of Residual Clinical Biospecimens and Health Data.
Nurse scientists are increasingly interested in conducting secondary research using real world collections of biospecimens and health data. The purposes of this scoping review are to (a) identify federal regulations and norms that bear authority or give guidance over reuse of residual clinical biospecimens and health data, (b) summarize domain experts' interpretations of permissions of such reuse, and (c) summarize key issues for interpreting regulations and norms. Final analysis included 25 manuscripts and 23 regulations and norms. This review illustrates contextual complexity for reusing residual clinical biospecimens and health data, and explores issues such as privacy, confidentiality, and deriving genetic information from biospecimens. Inconsistencies make it difficult to interpret, which regulations or norms apply, or if applicable regulations or norms are congruent. Tools are necessary to support consistent, expert-informed consent processes and downstream reuse of residual clinical biospecimens and health data by nurse scientists.