Longevity of Sm-p80-specific antibody responses following vaccination with Sm-p80 vaccine in mice and baboons and transplacental transfer of Sm-p80-specific antibodies in a baboon.
Based on data obtained using vaccine efficacy studies in mice, hamsters, and baboons, the credentials of Sm-p80 as a first tier vaccine candidate for schistosomiasis have been well established. Sm-p80-based vaccine formulation(s) have consistently exhibited potent prophylactic efficacy in reducing adult worm burden following cercarial challenge and induce killing of established adult worms in chronic infection. This vaccine is protective against both intestinal and urinary schistosomiasis. In this study, the longevity of Sm-p80-specific antibody responses was studied in mice and in baboons. Robust antibody titers were detected in mice for up to 60 weeks following vaccination with Sm-p80 recombinant vaccine (Sm-p80 + GLA-SE). In the follow-up experiments to our published studies, Sm-p80-specific IgG was also detected in baboons 5-8 years following the initial vaccination with an Sm-p80 DNA vaccine. In one baboon, transfer of Sm-p80-specific antibody was detected in umbilical cord blood and in the baby. These long-lasting humoral immune response data coupled with the vaccine efficacy data in rodents and nonhuman primates further strengthens the case for Sm-p80 to be moved forward through development leading to human clinical trials.


Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer.
The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations.


Intrathecal morphine in mice: a new technique.
A simple, rapid technique for intrathecal injections by lumbar puncture in unanesthetized mice is described. Intrathecal [3H]morphine base was not found in significant quantities in either the midbrain or forebrain. Submicrogram quantities of morphine sulfate induced Straub tail response and tail-flick analgesia. These effects were dose related and antagonized by subcutaneous naloxone.


Catecholamines block the antimitogenic effect of estradiol on human glomerular mesangial cells.
Local sequential conversion of estradiol to hydroxyestradiols and methoxyestradiols by CYP450 and catechol-O-methyltransferase, respectively, contributes to the antimitogenic effects of estradiol on glomerular mesangial cell growth via estrogen receptor-independent mechanisms. Catecholamines are also substrates for catechol-O-methyltransferase and therefore, might abrogate the renoprotective effects of estradiol by inhibiting formation of methoxyestradiols. To test this hypothesis, we investigated the antimitogenic effects of estradiol on human glomerular mesangial cell proliferation and collagen synthesis in the presence and absence of catecholamines. Norepinephrine, epinephrine, and isoproterenol abrogated the inhibitory effects of estradiol on cell number, DNA synthesis, and collagen synthesis. For example, serum-induced DNA synthesis was inhibited from 100% to 62+/-1.9% by 0.1 micromol/L estradiol, and these inhibitory effects were reversed to 91+/-1.9% by 1 micromol/L epinephrine, 90.7+/-3.3% by 1 micromol/L isoproterenol, 87.5+/-2.8% by 10 micromol/L norepinephrine, and 92+/-1% by 10 micromol/L OR486 (catechol-O-methyltransferase inhibitor). The interaction of catecholamines with estradiol was not affected by phentolamine or propanolol, alpha- and beta-adrenoceptor antagonists, respectively. Similar to estradiol, the antimitogenic effects of 2-hydroxyestradiol were abrogated by epinephrine, isoproterenol, and OR486. In contrast to estradiol and 2-hydroxyestradiol, the antimitogenic effects of 2-methoxyestradiol were not attenuated by epinephrine, isoproterenol, or OR486. Norepinephrine, epinephrine, and isoproterenol inhibited the conversion of both estradiol and 2-hydroxyestradiol to 2-methoxyestradiol. Our findings suggest that catecholamines within the glomeruli might abrogate the antimitogenic effects of estradiol by blocking the conversion of 2-hydroxyestradiol to 2-methoxyestradiol.


Cystic tuberculosis of a metacarpal. An unusual presentation of primary lung disease.
A white woman of thirty-two years presented with tuberculous osteitis of the third metacarpal head, secondary to previously undetected active pulmonary disease. The problems of diagnosis are illustrated by review of her history, and the literature is discussed.


Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants.
Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19. Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients >7 days to <1 year old hospitalized with symptomatic acute COVID-19. We report 232 infants >7 days to <1 year of age hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients >7 days to <18 years old, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and <1% died. Infants accounted for over a fifth of children <18 years of age hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were <6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant.


Neuropsychiatric symptoms in patients with possible vascular cognitive impairment, does sex matter?
Neuropsychiatric symptoms (NPS) are common in patients with vascular cognitive impairment (VCI). We aimed to establish sex differences in the manifestation of NPS in memory clinic patients with possible VCI and identify which NPS are determinants of clinical progression in women and men separately. We included 718 memory clinic patients (age 68 ± 8; 45% women) with cognitive complaints and vascular brain lesions on MRI (i.e. possible VCI). NPS were measured using the 12-item Neuropsychiatric Inventory. Clinical progression after two years (women 18%, men 14%) was defined as increase in CDR ≥1 or institutionalization (available n = 589 without advanced dementia at baseline). The association between NPS and clinical progression was assessed with Cox proportional hazard models stratified by sex, adjusted for age and clinical diagnosis and in a second model additionally for manifestations of vascular brain lesions. Men more often presented with agitation (29% versus 17%, p<.05) and irritability (58% versus 45%, p<.05), the other 10 NPS (delusions, hallucinations, depression, anxiety, euphoria, apathy, disinhibition, aberrant motor behavior, nighttime disturbances and appetite & eating abnormalities) did not differ between sexes. In women the presence of apathy (HR 2.1[1.1;4.3]) was associated with higher risk of clinical progression. In men the presence of depression (HR 2.7[1.4;5.1]) and aberrant motor behavior (HR 2.1[1.1;3.8]) were associated with increased risk of clinical progression. Manifestations of NPS in patients with possible VCI differ by sex. Different NPS are associated with future clinical progression in men and women. Management strategies of NPS could benefit from sex-specific approaches.


Brain volumes and surface morphology in monozygotic twins.
Because healthy monozygotic twins share an identical genetic complement, they provide a unique opportunity to explore the genetic and environmental determinants of brain development. The purpose of this study was to evaluate the similarities between measures of cerebral and subcortical volumes and surface morphology in monozygotic twins compared with a matched control sample. Combinations of automated and manual methods were used to evaluate total brain volume, gray matter, white matter, ventricles and volumes of the frontal, temporal, parietal and occipital lobes. An artificial neural network algorithm was used to measure the cerebellum, thalamus, caudate and putamen. Measures of surface morphology included an index of gyral and sulcal curvature, surface area and cortical depth. The cerebral volume regions, including the gray matter, white matter and lobar volumes, were highly correlated within monozygotic twin pairs, with nearly all correlation coefficients >0.90. The cerebellum was also highly correlated (r = 0.99). Reasonably high correlations were found for the cortical depth (r = 0.84), caudate (r = 0.84), thalamus (r = 0.75) and putamen (r = 0.75). The surface measures, however, demonstrated the least correlation within twin pairs and thus are more prone to environmental influences. The high to moderate correlations between MZ twins compared with the matched controls highlights the role of heredity in both prenatal and postnatal neurodevelopment.


Evaluation of pharyngeal airway space amongst different skeletal patterns.
The aim of the present study was to evaluate the dimensions of the pharyngeal airway space (PAS) in awake, upright children with different anteroposterior skeletal patterns using cone beam computed tomography (CBCT). The volume, area, minimum axial area and seven linear measurements of PAS were obtained from the CBCT images of 50 children (mean age 9.16 years). The patients were divided in two groups according to the ANB angle (group I 2° ≤ ANB ≤ 5°; group II ANB > 5°). Means and standard deviations of each variable were compared and correlated using independent t-test and Pearson's correlation test. There were statistically significant differences in the following parameters: angle formed by the intersection between NA and NB lines (p<0.001), angle formed by the intersection between SN and NB lines (p<0.05), Minimal pharyngeal airway space between the uvula and the posterior pharyngeal wall (p<0.05), airway volume (p<0.01), airway area (p<0.01) and minimum axial area (p<0.05). The anteroposterior cephalometric variable SNB had positive correlation with the variables PAS-UP (p<0.01), Minimal pharyngeal airway space between the uvula tip and the posterior pharyngeal wall (p<0.05), Pharyngeal airway space on mandibular line (p<0.05), Minimal pharyngeal airway space between the back of the tongue and the posterior pharyngeal wall (p<0.05), volume airway (p<0.05), airway area (p<0.05) and minimum axial area (p<0.05). The vertical cephalometric variables angle formed by the intersection between SN and GoGn lines (p<0.05) and angle formed by the intersection between FH and mandible plane (p<0.05) showed negative correlation with PAS-UT. These results showed that PAS was statistically larger in group I than group II, indicating that the dimensions of the PAS are affected by different anteroposterior skeletal patterns.


ACR Appropriateness Criteria® Headache.
Headache is one of the most common human afflictions. In most cases, headaches are benign and idiopathic, and resolve spontaneously or with minor therapeutic measures. Imaging is not required for many types of headaches. However, patients presenting with headaches in the setting of "red flags" such as head trauma, cancer, immunocompromised state, pregnancy, patients 50 years or older, related to activity or position, or with a corresponding neurological deficit, may benefit from CT, MRI, or noninvasive vascular imaging to identify a treatable cause. This publication addresses the initial imaging strategies for headaches associated with the following features: severe and sudden onset, optic disc edema, "red flags," migraine or tension-type, trigeminal autonomic origin, and chronic headaches with and without new or progressive features. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


"Rapid and reversible alteration in corneal contour and power associated with Netarsudil/Latanoprost".
To describe a previously unreported case of reversible myopic shift with corresponding changes in corneal contour in a patient treated with netarsudil/latanoprost. A 72-year-old male with history of primary open angle glaucoma, prior cataract surgery, and remote radial keratotomy surgery was treated with fixed-dose combination of netarsudil/latanoprost. Despite no prior history of refractive shift in the twenty years since radial keratotomy surgery, on one month follow-up, he reported reduced visual acuity and presented with approximately 1.50 D shift in both eyes. There were associated corneal contour changes. No corneal epithelial bullae or edema were appreciated. Netarsudil/latanoprost was discontinued and timolol was initiated. One month later, both refractive error and corneal contour returned to prior levels. Netarsudil is a rho-kinase and norepinephrine transporter inhibitor that may be effective in the treatment of primary open angle glaucoma resistant to other topical treatments. In addition to corneal epithelial bullous edema previously reported, this drug may induce reversible changes in corneal contour in patients with prior corneal or refractive surgery.


Re-appreciating the why of cognition: 35 years after marr and poggio.
Marr and Poggio's levels of description are one of the most well-known theoretical constructs of twentieth century cognitive science. It entails that behavior can and should be considered at three different levels: computation, algorithm, and implementation. In this contribution focus is on the computational level of description, the level that describes the "why" of cognition. I argue that the computational level should be taken as a starting point in devising experiments in cognitive (neuro)science. Instead, the starting point in empirical practice often is a focus on the stimulus or on some capacity of the cognitive system. The "why" of cognition tends to be ignored when designing research, and is not considered in subsequent inference from experimental results. The overall aim of this manuscript is to show how re-appreciation of the computational level of description as a starting point for experiments can lead to more informative experimentation.


Decrease in neuron size in docosahexaenoic acid-deficient brain.
Docosahexaenoic acid is an important fatty acid for neuronal function because its deficiency leads to many behavioral and functional deficits. In a previous study, we reported that docosahexaenoic acid deficiency caused a reduction in the size of neurons of the CA1 region in the hippocampus. To extend these results to other regions of the brain, the present study entailed a morphologic analysis of neuronal size in hippocampus, hypothalamus, piriform cortex, and parietal cortex in rats that were raised on docosahexaenoic acid-deficient and supplemented diets for three generations. Neuron size in these regions was measured both at weaning (21 days) and maturity (68 days), and docosahexaenoic acid content in the brain was measured on a separate set of sibling rats using fatty acid analysis. Neuron size in hippocampus, hypothalamus, and parietal cortex decreased in weanling and in piriform cortex in mature rats raised on the docosahexaenoic acid-deficient diet. The brains of these rats exhibited a nearly 90% decrease of docosahexaenoic acid. Decrease of neuron size has been linked to a loss of optimal function in neurons. In the United States, human infant-milk formulas use vegetable oils as fat sources that lack docosahexaenoic acid. If docosahexaenoic acid deficiency reduces neuron size, then human infants raised on these formulas may also have smaller neurons relative to breast-fed infants.


SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel.
Maintenance of a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. Activation of a ubiquitous volume-regulated anion channel (VRAC) plays a key role in this process; however, its molecular identity in vertebrates remains unknown. Here, we used a cell-based fluorescence assay and performed a genome-wide RNAi screen to find components of VRAC. We identified SWELL1 (LRRC8A), a member of a four-transmembrane protein family with unknown function, as essential for hypotonicity-induced iodide influx. SWELL1 is localized to the plasma membrane, and its knockdown dramatically reduces endogenous VRAC currents and regulatory cell volume decrease in various cell types. Furthermore, point mutations in SWELL1 cause a significant change in VRAC anion selectivity, demonstrating that SWELL1 is an essential VRAC component. These findings enable further molecular characterization of the VRAC channel complex and genetic studies for understanding the function of VRAC in normal physiology and disease.


Interesting case of an abdominal wall Merkel cell carcinoma highlighting the importance of developing an Australian clinical practice guideline.
A 66-year-old Australian male farmer was referred for management of an asymptomatic, rapidly expanding, anterior abdominal wall mass. It was firm and well circumscribed. There were no overlying skin changes, constitutional symptoms or weight loss. His medical history included small bowel obstruction and resection from a Meckel's diverticulitis and a 40-pack-year smoking history. Core biopsy was suggestive of a neuroendocrine tumour and Gallium-68-Dodecane-Tetraacetic-Acid (68GaTate) positron emission tomography revealed an avid solitary lesion confined to the subcutaneous space in the left anterior abdominal wall. Wide local excision was performed, and histopathology revealed Merkel cell carcinoma (MCC). Although classically regarded as a primary cutaneous neuroendocrine tumour, MCC may originate from the subcutaneous fat without obvious skin involvement. Older patients with asymptomatic, rapidly enlarging lesions, particularly if immunosuppressed, with significant ultraviolet sunlight exposure, should raise a high index of suspicion for MCC. Like melanoma, non-metastatic MCC should be treated aggressively for best prognosis.


Validation of an Oscillation Test for the Sonographic Assessment of Fetal-Type Posterior Cerebral Artery Variants in Migraine Patients with Visual Aura.
Anatomic variants of the posterior circle of Willis, including the fetal-type posterior cerebral artery (FPCA), may contribute to the formation of visual aura in migraine. We sought to validate an oscillation test to investigate FPCA frequency in migraine using transcranial color-coded duplex ultrasonography (TCCS). First, the diagnostic accuracy of the oscillation test used to identify FPCA variants by TCCS was assessed in stroke patients with available computed tomography angiography (CTA) as the set gold standard. Second, in a cross-sectional study, patients with migraine with visual aura (MWVA) and migraine without aura (MWOA), as well as healthy controls, were prospectively recruited for sonographic assessment of FPCA variants. We compared FPCA frequency between migraine patients and controls using χ2-testing and performed logistic regression analysis to investigate a potential association between MWVA and the presence of FPCA variants. Specificity, sensitivity and positive and negative predictive values for sonographic identification of FPCA with CTA as the set gold standard were 93%, 77%, 63% and 96% (partial FPCA) and 99%, 78%, 88% and 98% (complete FPCA), respectively. One hundred forty-two migraine patients (39 ± 12 y, 90 MWVA and 52 MWOA) and 49 healthy controls (31 ± 12 y) were recruited. The χ2 testing did not reveal significant differences in FPCA frequency as assessed by TCCS (unilateral or bilateral, partial and/or complete) between migraine patients and controls (MWVA: 40/90 or 44.4%, MWOA: 22/52 or 42.3%, controls: 24/49 or 49%, p = 0.79). Similarly, the frequencies of partial FPCA (p = 0.61) and complete FPCA (p = 0.27) did not vary significantly among groups. Logistic regression analysis revealed no interaction effect between migraine diagnosis and FPCA prevalence (any FPCA), when adjusted for age and sex. The sonographic oscillation test can be used as a non-invasive method to identify partial and complete FPCA variants with high specificity and reasonable sensitivity. Our findings suggest that FPCA variants do not contribute to the formation of visual migraine aura.


Designing poly(gamma-aminobutyric acid)-based nanoparticles for the treatment of major depressive disorders.
Major depressive disorder (MDD) is a worldwide concern owing to its negative impact on the quality of life. Gamma-aminobutyric acid (GABA), an essential neurotransmitter in the brain, is important for regulating the enteric nervous system and gut-brain dual communication (gut-brain axis), thus providing gastrointestinal GABA and GABA-related pathways with possible targets for MDD treatment. However, the use of GABA for this disease remains limited due to its poor pharmacokinetic properties, including the low permeability through the blood-brain barrier, and the rapid clearance from the gastrointestinal tract. Since poly(amino acid)s are advantageous for improving the beneficial bioactivities of conventional amino acids, poly(gamma-aminobutyric acid) (poly(GABA)) is a potential candidate for MDD therapy. Nevertheless, the non-water-soluble and non-dispersible characteristics of poly(GABA) render difficulty in administering its conventional forms in vitro/in vivo, thereby hindering its therapeutic applications. Therefore, this study proposes a new design for poly(GABA) in nanoparticle form, which is composed of the amphiphilic diblock copolymers of poly(GABA) and poly(ethylene glycol), providing a suitable formulation for medication applications. Herein, we report on a new orally deliverable poly(GABA)-based nanoparticles (NanoGABA) in aqueous media and their efficacy on mouse depression models. NanoGABA treatment efficiently attenuated depression-like symptoms as evidenced by behavioral tests (forced swimming tests and tail suspension tests) and stress biomarkers (corticosterone). These findings suggest that the newly designed poly(GABA)-based nanoparticles are a promising candidate for the treatment of depression. STATEMENT OF SIGNIFICANCE: This research is the first to report the preparation of poly(GABA)-based nanoparticles in aqueous conditions with beneficial physical properties to open the gate for medical and pharmaceutical applications of poly (GABA). It is also a pioneer in using poly(GABA)-based materials for major depressive disorder therapeutics in vivo. Oral administration of NanoGABA attenuates depressive-like symptoms by targeting the enteric nervous system possibly through modulation of the gut-brain axis pathways with negligible toxicity, suggesting that NanoGABA is a promising therapeutic agent for major depressive disorders.


Animal models of alcoholic neuropathy: morphologic, electrophysiologic, and biochemical findings.
A chronic high alcohol intake was induced in rats through the use of two procedures: the schedule-induced polydipsia technique and the liquid diet technique. Rats consumed 11-12 g of ethanol per kilogram body weight per day for 16 to 18 weeks. Morphologic evidence of a mild distal axonal neuropathy in the ventral caudal nerve was proposed. The red blood cell transketolase levels were normal, indicating that the rats were not deficient in thiamine and suggesting that the axonal degeneration was due to the direct toxic effect of alcohol. Axonal transport studies demonstrated a significant increase in the amount of acetylcholinesterase transported in an orthograde direction in the sciatic nerves of alcohol-exposed rats, and indicated no change in the transport of choline acetyltransferase or in the specific binding of colchicine by neurotubulin.


A prospective study of burns trauma in children in the University of Calabar Teaching Hospital, Calabar, south-south Nigeria.
Burns are among the most devastating injuries seen in the emergency units. The epidemiology varies from one part of the world to another. This communication is a 3-year report of burns in children in an attempt to provide information on the current epidemiology of burns in this centre. Children admitted into the University of Calabar Teaching Hospital, Calabar with burns were prospectively studied from February 2005 and January 2008. There were 56 patients (28 males and 28 females). The ages ranged from 9 days and 14 years (mean 3.5 years) and 19 (73.1%) were preschool children. There were 39 (69.6%) who sustained scald injuries while 17 (30.4%) suffered flame injuries. Twenty-six (46.4%) patients sustained burns with total burn surface area above 10%. Education of the public on burns prevention based on the factors highlighted, establishment of burns support groups dedicated to publicity on prevention and provision of financial aid would sustain strategies when adopted.


Effect of enhanced proteolysis on formation of biogenic amines by lactobacilli during Gouda cheese ripening.
The effect of enhanced proteolysis on amine formation by amino acid decarboxylase positive Lactobacillus sp. during Gouda cheese ripening was examined. A commercial proteolytic enzyme preparation was added to pasteurized milk prior to cheese preparation. The effect of this manipulation on the formation of putrescine, histamine and tyramine was investigated in the presence and absence of amino acid decarboxylase-positive strains during a 12-week ripening period. Four batches were supplemented with a proteolytic enzyme. Batch I contained the proteolytic enzyme only, whereas batches II-IV were additionally supplemented with Lactobacillus delbrueckii LTH 1260 (batch II), Lactobacillus buchneri LTH 1388 (batch III) or Lactobacillus brevis LTH 2560 (batch IV). In batch I putrescine was detected with 4 mg/kg, in batch II, 42 mg/kg putrescine, 238 mg/kg histamine and 636 mg/kg tyramine were found. Batch III contained 13 mg/kg putrescine and 418 mg/kg histamine, whereas in batch IV, 26 mg/kg putrescine and 776 mg/kg tyramine were present. Batch V was supplemented with all three lactobacilli but did not contain the proteolytic enzyme. In this experiment, 4 mg/kg putrescine, 179 mg/kg histamine and 337 mg/kg tyramine were detected. A control cheese batch (VI) without addition of amine forming lactobacilli or a proteolytic enzyme was produced and only 4 mg/kg putrescine were detected. An increase in amine concentration during cheese ripening under conditions of enhanced proteolysis in the presence of starter and spoilage lactobacilli was evident from the experiments.


Elastic stockings in the control of hand oedema.
Elastic support and compression in the form of an elastic finger stall or glove seems to be a simple and comfortable way to obviate and reduce oedema of the hand and fingers after surgery or trauma. It may also prove useful in inflammatory conditions such as rheumatoid arthritis, though the authors have not used it as yet for that condition.


Association of daunomycin to membrane domains studied by fluorescence resonance energy transfer.
1,6-Diphenyl-1,3,5-hexatriene and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene are fluorophores used to explore different hydrophobic domains of membrane bilayers (Andrich, M.P. and Vanderkooi, J.M. (1976) Biochemistry 15, 1257-1265; Prendergast, F.G., Haugland, R.P. and Callahan, P.J. (1981) Biochemistry 20, 7333-7338). Fluorescence resonance energy transfer between these fluorophores, acting as energy donors, and the anthracycline, daunomycin, as the acceptor, was used to analyze the interaction of the drug with natural membranes, and its relative location within the membrane bilayer. The transfer process was demonstrated by: (1) emission fluorescence of the acceptor when the samples were excited at the excitation maximum of the donor (360 nm); and (2) progressive quenching of the energy donor (at 428 nm) when in the presence of increasing acceptor concentration. Also, the disruption of the energy transfer by solubilization of the membrane with Triton X-100 evidences a role for the membrane in providing the appropriate site(s) for energy transfer to occur. At moderately low daunomycin/membrane lipid ratios, the different efficiencies of resonance energy transfer between the two donors and daunomycin predicts a preferential, but not exclusive, location of the drug at membrane 'surface' domains, i.e., those regions of the bilayer explored by the 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene probe. In support of this observation, a large fraction (approx. 75%) of membrane-associated daunomycin was rapidly sequestered away from the membrane upon addition of excess DNA, which forms high-affinity complexes with daunomycin (Chaires, J.B., Dattagupta, n. and Crothers, D.M. (1982) Biochemistry 21, 3927-3932), thus acting as a drug 'sink'. Also, a large fraction of drug was accessible to fluorescence quenching by iodide, a collisional water-soluble quencher. On the other hand, a smaller population of the membrane-associated daunomycin was characterized by slow sequestering by the added DNA and inaccessibility to quenching by iodide. We conclude that the daunomycin, which is only slowly sequestered, is located deep within the hydrophobic domains of the bilayer, likely to be those probed by 1,6-diphenyl-1,3,5-hexatriene.


Proteins from toad's parotoid macroglands: do they play a role in gland functioning and chemical defence?
Parotoid gland secretion of bufonid toads is a rich source of toxic molecules that are used against predators, parasites and pathogens. Bufadienolides and biogenic amines are the principal compounds responsible for toxicity of parotoid secretion. Many toxicological and pharmacological analyses of parotoid secretions have been performed, but little is known about the processes related to poison production and secretion. Therefore, our aim was to investigate protein content in parotoids of the common toad, Bufo bufo, to understand the processes that regulate synthesis and excretion of toxins as well as functioning of parotoid macroglands. Applying a proteomic approach we identified 162 proteins in the extract from toad's parotoids that were classified into 11 categories of biological functions. One-third (34.6%) of the identified molecules, including acyl-CoA-binding protein, actin, catalase, calmodulin, and enolases, were involved in cell metabolism. We found many proteins related to cell division and cell cycle regulation (12.0%; e.g. histone and tubulin), cell structure maintenance (8.4%; e.g. thymosin beta-4, tubulin), intra- and extracellular transport (8.4%), cell aging and apoptosis (7.3%; e.g. catalase and pyruvate kinase) as well as immune (7.0%; e.g. interleukin-24 and UV excision repair protein) and stress (6.3%; including heat shock proteins, peroxiredoxin-6 and superoxide dismutase) response. We also identified two proteins, phosphomevalonate kinase and isopentenyl-diphosphate delta-isomerase 1, that are involved in synthesis of cholesterol which is a precursor for bufadienolides biosynthesis. STRING protein-protein interaction network predicted for identified proteins showed that most proteins are related to metabolic processes, particularly glycolysis, stress response and DNA repair and replication. The results of GO enrichment and KEGG analyses are also consistent with these findings. This finding indicates that cholesterol may be synthesized in parotoids, and not only in the liver from which is then transferred through the bloodstream to the parotoid macroglands. Presence of proteins that regulate cell cycle, cell division, aging and apoptosis may indicate a high epithelial cell turnover in parotoids. Proteins protecting skin cells from DNA damage may help to minimize the harmful effects of UV radiation. Thus, our work extends our knowledge with new and important functions of parotoids, major glands involved in the bufonid chemical defence.


[The characteristics of the mechanism of action in the joint use of solutions of brine and mud extracts with galvanization and ultrasonic exposure. 2].
Radionuclide tracing has demonstrated that intraperitoneal introduction of natural brine and mud solutions to intact rats followed by ultrasound versus galvanization provides more intensive delivery of chemical elements to the target organs and tissues. These differences should be taken into account when planning rehabilitation schemes with various physiotherapeutic modalities.


Trisomy 7p due to a mosaic normal/dir dup(7)(p13----p22). Syndrome delineation, critical segment assignment, and a comment on duplications.
A 4 4/12 year-old girl with a peculiar phenotype due to a 46,XX/46,XX, dir dup(7)(p1300----p2200) karyotype is described. The comparison with about ten similar cases permitted a better delineation of the 7p trisomy syndrome and the assignment of the band 7p21 as the critical one. Mechanisms for the origin of homogeneous and mosaic duplications, including one model based on a meiotic half chromatid duplication, are discussed.


Sputtered anti-reflection layer on transparent polyimide - substrate improves adhesion strength to - copper layer: effects of layer thickness and sputtering power.
In order to shield the electronic circuits on a transparent polyimide (PI) substrate, an anti-reflection (AR) layer was deposited on a PI film via DC reactive magnetron sputtering. The effects of sputtering power and thickness of AR layer on the optical property and adhesion strength of the PI were investigated. The composition of the AR layer influences the bonding between layers. Sufficient thickness of the AR layer is essential to strengthen the adhesion between the PI and copper (Cu) layers. The sputtered AR layer on the PI also improves the barrier property for water vapor. The AR layer-sputtered PI substrates remain transparent and exhibit high peel strength to the Cu layer, suggesting their potential applications as reliable transparent substrates for modern electronic devices.


Surface modeling of soil antibiotics.
Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1 μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0 μg/kg, 102.8 μg/kg, 106.3 μg/kg and 108.7 μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2 μg/kg (88.6 μg/kg, 20.4 μg/kg and 39.2 μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints.


Alarmin-induced cell migration.
Alarmins are endogenous, constitutively available, damage-associated molecular patterns that upon release can mobilize and activate various leukocytes for the induction of innate and adaptive immune responses. For our immune system to function appropriately, it relies on navigating various leukocytes to distinct places at the right time. The direction of cell migration is determined by chemotactic factors that include classical chemoattractants, chemokines, certain growth factors, and alarmins. This viewpoint provides an overview of alarmin-induced cell migration. Alarmins are capable of inducing the migration of diverse types of leukocytes and nonleukocytes either directly by triggering specific receptors or indirectly by inducing production of chemokines through the activation of various leukocytes via pattern recognition receptors. The receptors used by alarmins to directly induce cell migration can either be Gαi protein-coupled receptors or receptors such as the receptor for advanced glycation end products; however, the intracellular signaling events responsible for the direct chemotactic activities of alarmins are, to date, only partially elucidated. Given that alarmins act in concert with chemokines to regulate the recruitment and trafficking of leukocytes, these damage-associated molecular patterns are potentially involved in diverse biological processes as discussed in this viewpoint.


Breast Cancer Screening and Prevention.
This issue provides a clinical overview of breast cancer screening and prevention, focusing on risk assessment, screening, prevention, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.


Structure of the liganded T state of haemoglobin identifies the origin of cooperative oxygen binding.
A molecular description of haemoglobin's cooperative oxygen binding and release was founded on the X-ray crystal structures of the deoxy-T and oxy-R states. Since the R state's oxygen affinity is close to that of an isolated subunit, the crucial allosteric phenomena are (1) the reduced affinity of the T state and (2) the kinetic pathway between the two quaternary structures. To investigate these phenomena directly, we have determined at high resolution (dmin = 2.1 A) the crystal structures of two liganded T-state haemoglobins. In the liganded T-state alpha subunit, both the tight packing of the haem and the intersubunit contacts inhibit a conformational change between the F helix and FG corner which would allow the haem to become planar and the iron to assume symmetrical R-like coordination. In the beta subunit, by contrast, we find no strain on the proximal side, but the intersubunit contacts prevent the haem from tilting about an axis parallel to the F helix which would open up the binding site to oxygen. In both subunits, ligand binding in the T state induces structural changes towards the tertiary conformation of the R state.


Mixed-type inhibition of bovine lung angiotensin converting enzyme by lisinopril and its dansyl derivative.
The steady-state inhibition of bovine lung angiotensin converting enzyme (ACE; EC 188.8.131.52) by the slow-binding inhibitor lisinopril and its dansyl derivative conformed to a linear mixed inhibition model with inhibitor binding to ES as well as to E. Studied at pH8, 35 degrees, and using N-(3-[2-furyl]-acryloyl)phe-gly-gly as substrate, the approach to steady-state activity at different substrate concentrations pointed to slow isomerizations in both EI and EIS. While an inhibitory scheme involving a single I-binding site adequately accounts for the data presented, information relating to the primary structure of ACE brings up a two-site alternative which remains to be tested.


Impact on psychosocial outcomes of a nationally available weight management program tailored for individuals with type 2 diabetes: Results of a randomized controlled trial.
Type 2 diabetes mellitus (T2DM) can substantially decrease quality of life (QOL). This study examined the effects on QOL-relevant psychosocial measures of a widely available commercial weight loss program enhanced for individuals with T2DM. A year-long multi-site randomized clinical trial compared the Weight Watchers (WW) approach, supplemented with phone and email counseling with a certified diabetes educator (CDE), to brief standard diabetes nutrition counseling and education (Standard Care; SC). Participants were 400 women and 163 men (N=279 WW; 284 SC) with T2DM [mean (±SD) HbA1c 8.32±1%; BMI=37.1±5.7kg/m2; age=55.1 ± 9.1years]. Psychosocial outcomes were assessed at baseline, month 6, and month 12 using a diabetes specific psychosocial measure (Diabetes Distress Scale [DDS]), Impact of Weight on Quality of Life-Lite scale (IWQOL), a generic QOL measure (SF-36), and a depression screen (PHQ-9). WW participants showed significantly greater improvements than did SC participants on all DDS subscales and total score and on IWQOL total score and physical function, sex life and work domains (all ps<.05). There was no significant treatment effect on SF-36 scores or PHQ-9. WW enhanced for individuals with T2DM was superior to SC in improving psychosocial outcomes most specific to T2DM and obesity. Available commercial WL programs, combined with scalable complementary program-specific diabetes counseling, may have benefits that extend to diabetes-related distress and weight-relevant QOL.


A phase I study of the safety and efficacy of talimogene laherparepvec in Japanese patients with advanced melanoma.
Talimogene laherparepvec (T-VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open-label, dose de-escalation study evaluated the safety and efficacy of T-VEC in Japanese patients with unresectable stage IIIB-IV melanoma. Eligible adult patients had histologically confirmed stage IIIB-IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T-VEC was injected intralesionally (first dose, ≤4.0 ml of 106 PFU/ml; after 3 weeks and then every 2 weeks thereafter, ≤4.0 ml of 108 PFU/ml). Primary endpoints were dose-limiting toxicities (DLTs) and durable response rate (DRR). Of 18 enrolled patients (72.2% female), 16 had received ≥1 prior line of therapy. Ten patients discontinued T-VEC due to disease progression. Median (range) follow-up was 20.0 (4-37) months. No DLTs were observed; 17 (94.4%) patients had treatment-emergent adverse events (AEs). Fourteen (77.8%) patients had treatment-related AEs; the most frequent were pyrexia (44.4%), malaise (16.7%), chills, decreased appetite, pruritus, and skin ulcer (11.1% each). The primary efficacy endpoint was met: 2 (11.1%) patients had a durable partial response ≥6 months. The DRR was consistent with that observed in a phase III trial of T-VEC in non-Asian patients. The safety profile was consistent with the patients' underlying disease and the known safety profile of T-VEC.


Pharmacokinetics of high-dose etoposide.
The pharmacokinetics of etoposide at doses of 1 gm/m2 to 3 gm/m2 were studied in patients with hematologic malignancies. The noncompartmental systemic clearance, mean residence time, steady-state volume of distribution, and elimination half-life were independent of the dose of etoposide, whereas the AUC was proportional to the dose. Comparison of these results with those reported previously indicates that etoposide exhibits linear pharmacokinetics over a thirtyfold range in doses (0.1 to 3 gm/m2).


Prospective of mycorrhiza and Beauvaria bassiana silica nanoparticles on Gossypium hirsutum L. plants as biocontrol agent against cotton leafworm, Spodoptera littoralis.
Plant-herbivorous insects are a severe danger to the world's agricultural production of various crops. Insecticides used indiscriminately resulted in habitat destruction due to their high toxicity, as well as disease resistance. In this respect, the development of a sustainable approach to supreme crop production with the least damage is a crucially prerequisite. As a result, the current study was carried out to understand the potential effect of arbuscular mycorrhizal (AM) fungi along with Beauvaria bassiana silica nanoparticles (Si NPs) as a new approach to increase cotton (Gossypium hirsutum L. Merr.) defense against an insect herbivore, Spodoptera littoralis. AM and non-AM cotton plants were infested with S. littoralis and then sprayed with a biopesticide [B. bassiana Si NPs] or a chemical insecticide (Chlorpyrifos). The gas chromatography-mass spectrometry (GC-MS) analysis of B. bassiana Si NPs fungal extract showed that the major constituents identified were Oleyl alcohol, trifluoroacetate, 11-Dodecen-1-AL and 13-Octadecenal, (Z)-(CAS). Besides, results revealed a highly significant decrease in growth parameters in S. littoralis infested plants, however, with AM fungal inoculation a substantial improvement in growth traits and biochemical parameters such as protein and carbohydrates contents was observed. In addition, stimulation in proline and antioxidant enzymes activity and a decrease in malondialdehyde content were observed after AM inoculation. AM fungi mitigate the harmful effects of herbivorous insects by strengthening the cotton plant's health via enhancing both morphological and biochemical traits that can partially or completely replace the application of chemical insecticides.


Efficacy of Temozolomide Therapy in Patients With Aggressive Pituitary Adenomas and Carcinomas-A German Survey.
Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.


New prognostic factors in melanoma: mRNA tumour markers.
Circulating tumour cells in the peripheral blood may be important for haematogenous spread of malignant disease. Monitoring these cells may therefore be of prognostic value. Reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays to detect occult neoplastic cells offer the highest sensitivity for the study of tumour dissemination and minimal residual disease. This review summarises technical considerations and clinical investigations in melanoma patients of various disease stages. The clinical data are promising, but to clearly define the clinical usefulness of messenger RNA (mRNA) tumour markers, methodological issues must be resolved and the clinical value must be assessed prospectively in sufficiently large patient cohorts.


Intramolecular reactions of 2-indolylacyl radicals: access to 1,2-fused ring indole derivatives.
The generation of 2-indolylacyl radicals from the corresponding phenyl selenoesters under reductive conditions and their behavior in intramolecular addition reactions to carbon-carbon double bonds located at the indole nitrogen have been studied. [reaction: see text]


Amphetamine discrimination as a test for anti-parkinsonism drugs.
Rats were trained and tested on a two-lever discrimination task based upon the presence or absence of 0.8 mg/kg d-amphetamine. After 80% criterion performance was attained, dopaminergic drugs reported to be effective in the treatment of Parkinson's disease were tested to investigate their ability to produce d-amphetamine-like responding. Amantidine (50 mg/kg), apomorphine (2.5 mg/kg), n-propylnoraporphine (0.1, 0.2 and 1.0 mg/kg), and piribedil (25 mg/kg) were all observed to produce d-amphetamine-appropriate responding. These results indicate that discriminative behavior controlled by d-amphetamine is mediated by central dopaminergic systems and the use of this technique in the evaluation of potential anti-Parkinsonism drugs is discussed.


Anti-inflammatory efficacy of dexamethasone and Nrf2 activators in the CNS using brain slices as a model of acute injury.
Limiting excessive production of inflammatory mediators is an effective therapeutic strategy for many diseases. It's also a promising remedy for neurodegenerative diseases and central nervous system (CNS) injuries. Glucocorticoids are valuable anti-inflammatory agents, but their use is constrained by adverse side-effects. Activators of NF-E2-related factor-2 (Nrf2) signaling represent an attractive anti-inflammatory alternative. In this study, dexamethasone, a synthetic glucocorticoid, and several molecular activators of Nrf2 were evaluated for efficacy in slices of cerebral cortex derived from adult SJL/J mice. Cortical explants increased expression of IL-1β and TNF-α mRNAs in culture within 5 h of sectioning. This expression was inhibited with dexamethasone in the explant medium or injected systemically in mice before sectioning. Semi-synthetic triterpenoid (SST) derivatives, potent activators of the Nrf2 pathway, demonstrated fast-acting anti-inflammatory activity in microglia cultures, but not in the cortical slice system. Quercetin, luteolin, and dimethyl fumarate were also evaluated as molecular activators of Nrf2. While expression of inflammatory mediators in microglia cultures was inhibited, these compounds did not demonstrate anti-inflammatory efficacy in cortical slices. In conclusion, brain slices were amenable to pharmacological modification as demonstrated by anti-inflammatory activity with dexamethasone. The utilization of Nrf2 activators to limit inflammatory mediators within the CNS requires further investigation. Inactivity in CNS tissue, however, suggests their safe use without neurological side-effects in treating non-CNS disorders. Short-term CNS explants may provide a more accurate model of in vivo conditions than microglia cultures since the complex tissue microenvironment is maintained.


Differences in the prevalence of diagnosis of overweight-obesity in Spanish children according to the diagnostic criteria set used.
To examine relevant differences in the prevalence of overweight and obesity in children aged 2-15 years according to different sets of criteria (Orbegozo Foundation, International Obesity Task Force and World Health Organization), and how their use affects the trends in obesity recorded for both sexes between 1995 and 2011 in Spain. Cross-sectional study, a population between 2 and 15 years. Three diagnosis criteria of overweight and obesity were be used. The boys according to the three criteria, showed higher values of overweight and obesity compared to the girls. The lowest levels of overweight and obesity were observed using the Orbegozo tables. The prevalence of overweight and obesity varies significantly according to the criteria used to define overweight and obesity. The percentiles of the Foundation Orbegozo gave the lowest estimates and the standards of growth of the World Health Organization were higher.


Management of migraine in children and adolescents in the emergency department and inpatient setting.
Migraine is a chronic disorder that can be debilitating, especially when the attacks are severe and frequent. Children and adolescents are significantly affected. The prevalence of migraine in this age group is higher than predicted due to more recognition of the disease in this population throughout the past century. Severe chronic migraine can cause failure in academic work and may lead to depression. Multiple medications are used to break an acute attack. Most approaches are based on outpatient treatments and include the use of over-the-counter medications and triptans and narcotics. This manuscript reviews most of the available therapies for acute treatment of primary headache that did not respond to outpatient management.


Predicting Glioblastoma Cellular Motility from In Vivo MRI with a Radiomics Based Regression Model.
Characterizing the motile properties of glioblastoma tumor cells could provide a useful way to predict the spread of tumors and to tailor the therapeutic approach. Radiomics has emerged as a diagnostic tool in the classification of tumor grade, stage, and prognosis. The purpose of this work is to examine the potential of radiomics to predict the motility of glioblastoma cells. Tissue specimens were obtained from 31 patients undergoing surgical resection of glioblastoma. Mean tumor cell motility was calculated from time-lapse videos of specimen cells. Manual segmentation was used to define the border of the enhancing tumor T1-weighted MR images, and 107 radiomics features were extracted from the normalized image volumes. Model parameter coefficients were estimated using the adaptive lasso technique validated with leave-one-out cross validation (LOOCV) and permutation tests. The R-squared value for the predictive model was 0.60 with p-values for each individual parameter estimate less than 0.0001. Permutation test models trained with scrambled motility failed to produce a model that out-performed the model trained on the true data. The results of this work suggest that it is possible for a quantitative MRI feature-based regression model to non-invasively predict the cellular motility of glioblastomas.


Supra-molecular hydrogen-bonding patterns in the N(9)-H protonated and N(7)-H tautomeric form of an N(6) -benzoyl-adenine salt: N (6)-benzoyl-adeninium nitrate.
In the title molecular salt, C12H10N5O(+)·NO3 (-), the adenine unit has an N (9)-protonated N(7)-H tautomeric form with non-protonated N(1) and N(3) atoms. The dihedral angle between the adenine ring system and the phenyl ring is 51.10 (10)°. The typical intra-molecular N(7)-H⋯O hydrogen bond with an S(7) graph-set motif is also present. The benzoyl-adeninium cations also form base pairs through N-H⋯O and C-H⋯N hydrogen bonds involving the Watson-Crick face of the adenine ring and the C and O atoms of the benzoyl ring of an adjacent cation, forming a supra-molecular ribbon with R 2 (2)(9) rings. Benzoyl-adeninum cations are also bridged by one of the oxygen atoms of the nitrate anion, which acts as a double acceptor, forming a pair of N-H⋯O hydrogen bonds to generate a second ribbon motif. These ribbons together with π-π stacking inter-actions between the phenyl ring and the five- and six-membered adenine rings of adjacent mol-ecules generate a three-dimensional supra-molecular architecture.


Variation of soil organic carbon and physical properties in relation to land uses in the Yellow River Delta, China.
Soil physical properties and soil organic carbon (SOC) are considered as important factors of soil quality. Arable land, grassland, and forest land coexist in the saline-alkali reclamation area of the Yellow River Delta (YRD), China. Such different land uses strongly influence the services of ecosystem to induce soil degradation and carbon loss. The objective of this study is to evaluate the variation of soil texture, aggregates stability, and soil carbon affected by land uses. For each land use unit, we collected soil samples from five replicated plots from "S" shape soil profiles to the depth of 50 cm (0-5, 5-10, 10-20, 20-30, and 30-50 cm). The results showed that the grassland had the lowest overall sand content of 39.98-59.34% in the top 50 cm soil profile. The content of soil aggregates > 0.25 mm (R0.25), mean weight diameter and geometric mean diameter were significantly higher in grassland than those of the arable and forest land. R0.25, aggregate stability in arable land in the top 30 cm were higher than that of forest land, but lower in the soil profile below 20 cm, likely due to different root distribution and agricultural practices. The carbon management index (CMI) was considered as the most effective indicator of soil quality. The overall SOC content and CMI in arable land were almost the lowest among three land use types. In combination with SOC, CMI and soil physical properties, we argued that alfalfa grassland had the advantage to promote soil quality compared with arable land and forest land. This result shed light on the variations of soil properties influenced by land uses and the importance to conduct proper land use for the long-term sustainability of the saline-alkali reclamation region.


Chondroitin sulfate proteoglycans down-regulate spine formation in cortical neurons by targeting tropomyosin-related kinase B (TrkB) protein.
Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix that inhibit axonal sprouting and experience-dependent plasticity. Although protein-tyrosine phosphatase σ (PTPσ) has been proven to be a receptor for CSPGs, its downstream signaling has remained a mystery. Here, we show that CSPGs target and dephosphorylate tropomyosin-related kinase B, the receptor of brain-derived neurotrophic factor (BDNF), via PTPσ in embryonic cortical neurons in vitro. Whereas BDNF promoted dendritic spine formation in embryonic cortical neurons, CSPGs abolished the effects of BDNF and eliminated existing dendritic spines when BDNF was present. The latter effect was dependent on the p75 receptor, presumably because BDNF binding to the p75 receptor elicits elimination of dendritic spines. These results suggest that the inhibitory activity of CSPGs on dendritic spine formation operates through the targeting of neurotrophins at the receptor level.


Zexie decoction reduce glucose-dependent lipid accumulation and oxidative stress in Caenorhabditis elegans.
Obesity has become a global public health problem. Zexie decoction (ZXT) is a classic formula from Synopsis of the Golden Chamber. However, the long-term effect of ZXT in lipid accumulation remain unclear. This study aims to investigate the effect of ZXT on aging, lipid metabolism and oxidative stress. Different concentration of ZXT was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or the high glucose nematode growth media (GNGM). The lifespan, heat stress resistance, lipid accumulation and related mRNA expression of the worms were examined. Oil Red staining and triglyceride were used to evaluated the lipid accumulation. Nhr-49, fat-5/fat-7, fat-5/fat-6 or skn-1 knockout mutants were used to clarify the effect on lipid metabolism of ZXT. GFP-binding mutants were used to observe the changes in protein expression. ZXT improved the survival rate of C. elegans in lifespan test and heat stress test. ZXT also reduced lipid accumulation in C. elegans and significantly changed the expression of fatty acid synthesis related genes and lipid metabolism related genes. In addition, ZXT-treated C. elegans showed a higher expression of anti-oxidative protein, and reduced the expression of oxidative stress and mitochondrial dysfunction marker. However, when skn-1 was knockdown, ZXT no longer had the effect of maintaining the mitochondria membrane potential and lipid lowering but still effectively decreased the O2·- induced by high glucose. ZXT reduced fat accumulation by regulating lipid metabolism via multiple targets and enhanced stress resistance by its antioxidant effect in C. elegans.


Vertical ground reaction forces in patients after calcaneal trauma surgery.
Vertical ground reaction forces (VGRFs) are altered in patients after foot trauma. It is not known if this correlates with ankle kinematics. The aim of this study was to analyze VGRFs in patients after calcaneal trauma and correlate them to patient-reported outcome measures (PROMs), radiographic findings and kinematic analysis, using a multi-segment foot model. In addition, we determined the predictive value of VGRFs to identify patients with altered foot kinematics. Thirteen patients (13 feet) with displaced intra-articular calcaneal fractures, were included an average of two years after trauma surgery. PROMs, radiographic findings on postoperative computed tomography scans, gait analysis using the Oxford foot model and VGRFs were analysed during gait. Results were compared with those of 11 healthy subjects (20 feet). Speed was equal in both groups, with healthy subjects walking at self-selected slow speed (0.94±0.18m/s) and patients after surgery walking at self-selected normal speed (0.94±0.29m/s). ROC curves were used to determine the predictive value. Patients after calcaneal surgery showed a lower minimum force during midstance (p=0.004) and a lower maximum force during toe-off (p=0.011). This parameter correlated significantly with the range of motion in the sagittal plane during the push-off phase (r 0.523, p=0.002), as well as with PROMs and with postoperative residual step-off (r 0.423, p=0.016). Combining these two parameters yielded a cut-off value of 193% (p<0.001), area under the curve 0.93 (95%confidence interval 0.84-1.00). Patients after calcaneal fracture showed lower minimum force during midstance and lower maximum force during toe-off compared to healthy subjects. This lower maximum force during push-off correlated significantly with PROMs, range of motion in the sagittal plane during push-off and radiographic postoperative residual step-off in the posterior facet of the calcaneal bone. VGRFs are a valuable screening tool for identifying patients with altered gait patterns.


Glycophorins, Blood Groups, and Protection from Severe Malaria.
In Malaŵi, Malungo alibe odi is a saying that translates as: 'Malaria does not ask permission before coming in'. The recent finding of a new severe malaria resistance locus next to a cluster of glycophorin genes involved in Plasmodium falciparum erythrocyte invasion seems to suggest otherwise: that evolutionary pressure is enabling erythrocytes to lock the door to keep malaria out.


Applications of a simple theory of the acoustic motion of fibrous networks in viscous media.
The rupture of blood capillaries in the spinal chords of rats by pulsed ultrasound and the motion of fibrils in the corneal stroma are analysed in detail in terms of a simple theory of wave propagation in a fibrous network permeated by a viscous medium. The advantages of inelastic light scattering experiments in connection with studies of ultrasound are emphasized.


Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system.
Porous hollow hydroxyapatite microspheres (PHHMs) are the promising biomaterials, owing to their excellent biocompatibility, biodegradability and bioactivity. PHHMs have been used as drug controlled carriers due to their advantages such as large drug loading capacity, nanochannels for drug loading and release and high specific surface area. In this study, PHHMs were prepared successfully in Na2HPO4 solution by an anion-exchange process using vaterite CaCO3 through a hydrothermal method. The previous vaterite CaCO3 was synthesized by a polymer-templated method in the poly(styrene sulfonic acid) sodium salt (PSS) aqueous solutions. The PHHMs have a size distribution from 0.8 to 2.0 μm, with an average pore size of about 24.3 nm. The wall of PHHMs is constructed with building units of hydroxyapatite nanofibers with an average length of 300 nm and an average width of 20 nm. The PHHMs displayed a high drug loading capacity and pH-responsive sustained-controlled drug release behavior when we used doxorubicin hydrochloride (DOX) as a loading drug. Moreover, the controlled drug release system showed a high ability to kill cancer cells and less damage to normal cells. These results indicated that PHHMs are promising for applications in various biomedical fields such as drug delivery system and oncotherapy.


Metabolic implications of distal atrophy. Carbohydrate metabolism in centronuclear myopathy.
Centronuclear myopathy, like myotonic dystrophy, is characterized by muscle wasting and type 1 fiber atrophy. To determine whether this disorder might include a derangement in carbohydrate metabolism similar to that in myotonic dystrophy, 3 comparably wasted patients with centronuclear myopathy, myotonic dystrophy, and neurogenic atrophy were investigated. The patient with centronuclear myopathy had mild glucose intolerance and hypoinsulinemia after oral glucose ingestion in bold contrast to the normal glucose tolerance and hyperinsulinemia observed in the myotonic dystrophy patient. No abnormality was seen in oral glucose tolerance in the patient with neurogenic atrophy, and all 3 patients had normal insulin tolerance. Forearm insulin infusion demonstrated normal stimulation of muscle glucose uptake in the patients with centronuclear myopathy and neurogenic atrophy in contrast to the markedly diminished response to insulin seen in the patient with myotonic dystrophy. These data indicate that neither distal wasting or type 1 fiber atrophy are responsible for the abnormalities in carbohydrate metabolism in myotonic dystrophy.


Primary angiosarcoma of the ovary: a case report of Stage I disease.
There are 20 documented cases of primary ovarian angiosarcoma. Most patients present with metastatic disease and respond poorly to chemotherapy. There is little information available to counsel early-staged patients on the need for or efficacy of adjuvant chemotherapy. We present a case of Stage Ic primary ovarian angiosarcoma treated with 3 cycles of adjuvant MAID chemotherapy. The patient is without evidence of disease 10 months post-operatively. A review of the literature indicates a potential role for MAID chemotherapy in the treatment of ovarian angiosarcomas. Detection of Stage I disease appears to confer a better prognosis regardless of the utilization of adjuvant chemotherapy.


Regulating NETosis: An emerging facet of statin pleiotropy.
NETosis has emerged as a new player in the pathogenesis of several diseases including atherosclerotic cardiovascular disease. There is accumulating evidence suggesting that NETosis is regulated by statins, thereby justifying an important lipid-independent pleiotropic action of statin drugs in reducing the risk of atherothrombosis as well as other pathologies.


Fetal echocardiography: retrospective review of clinical experience and an evaluation of indications.
To assess the indications, use, and yield of fetal echocardiography. We reviewed our 8-year experience with fetal echocardiography at a large health maintenance organization in northern California to assess the yield of abnormal findings for each indication and the accuracy of prenatal cardiac diagnosis. The study included 915 fetuses undergoing fetal echocardiography between 18-38 weeks' gestation because of accepted indications. All live-born infants had the presence or absence of congenital heart disease (CHD) confirmed postnatally. Family history of CHD led to 34% of all fetal echocardiography studies, with a detection rate of 0.7%. Maternal diabetes mellitus accounted for 28% of all studies, with a detection rate of 1.2%. Exposure of mothers to a potential teratogen led to 48 studies, but no abnormalities were detected. Only 4% of fetal echocardiograms were obtained because of a suspected heart defect noted on a screening obstetric sonogram; this indication had a detection rate of 68% and yielded by far the most cases of severe CHD. Based on the expected occurrence rate of severe CHD in our closed referral system, only about 15% were referred for fetal echocardiography and detected prenatally. Basing fetal echocardiography referral on risk factors misses most clinically significant detectable CHD.


Tuberculous meningitis in adults: MRI contribution to the diagnosis in 29 patients.
Tuberculous meningitis (TBM) is a life-threatening disease and is difficult to diagnose. We aim to promote the role of magnetic resonance imaging (MRI) in TBM diagnosis and survey. This was a retrospective study undertaken between 1996 and 2003 in which we reviewed all cases of TBM that had undergone cerebral computed tomography (CT) and MRI performed with and without contrast. We reviewed 29 patients; all had had subacute lymphocytic meningitis. Diagnosis was definite in only 11 cases and presumptive in 18 cases. MRI was performed showing one or more abnormalities in 26 cases. The use of MRI allowed the detection of CNS lesions in both brain and spine. Cerebrospinal MRI performed when TBM is suspected aids in its diagnosis and is also a useful means of monitoring the course of the disease under treatment.


Methylene Blue-Mediated Photodynamic Inactivation Followed by Low-Laser Therapy versus Miconazole Gel in the Treatment of Denture Stomatitis.
Photodynamic therapy (PDT) appears to be an effective method for the in vitro and in vivo inactivation of Candida spp., but no clinical trials in this context have yet been conducted. The aim of this study was to compare the effect of oral miconazole gel to PDT combined with low-power laser (LPL) therapy in the treatment of denture stomatitis. Forty participants with clinical and microbiological diagnoses of type II denture stomatitis were randomly allocated to two treatment groups (PDT and miconazole gel), each with 20 individuals. The PDT group was submitted to one session of methylene blue-mediated PDT plus two sessions of low-laser therapy twice a week for 15 days. The miconazole group was submitted to the drug four times a day for 15 days. Forty percent of the patients achieved clinical and microbiological resolution of denture stomatitis after methylene blue-mediated photodynamic inactivation followed by low-laser therapy. The cure rate associated with miconazole was 80% (p < 0.05). Fifteen days after the end of treatment, the recurrence rate was 25% in patients treated with PDT combined with LPL therapy and 12.5% in patients treated with miconazole. Miconazole gel provides better results than a protocol combining methylene blue-mediated PDT and LPL therapy in the treatment of type II denture stomatitis.


Lymphoedema of the eyelids in the yellow nail syndrome.
The nails are frequently deformed or otherwise affected in a very large number of systemic diseases or as part of the general picture in many syndromes of congenital origin. One of the latter is the yellow nail syndrome (Samman and White, 1964) an example of which we present in this paper.


The impact of price transparency and competition on hospital costs: a research on all-payer claims databases.
Public reporting has been considered effective in reducing health care costs by mitigating information asymmetry in the market as payers have incorporated publicly available information mandates into pay-for-performance programs and value-based purchasing. Therefore, hospitals have faced increasing pressures to provide price transparency. Despite the widespread promotion of healthcare transparency, the effectiveness of public reporting has not yet been sufficiently understood. This study analyzed the impact of transparency policy and competition on hospital costs by taking the state operations of all-payer claims databases (APCDs) as a case of interest. We employed a fixed-effects regression, which allows the generation of hospital-specific effects, in accordance with the suggestion by the Hausman test. The study samples comprise nonprofit and for-profit general acute care hospitals in the United States for 2011-2017. The finalized dataset ranges from 3547 observations in 2011 to 3405 observations in 2015 after removing missing values. We found that hospitals in the states with APCDs tend to bear higher average operating expenses than those without APCDs, which may indicate that states maintaining higher healthcare expenditures are more attentive to a price transparency initiative and tend to adopt APCDs. With regard to competition, the results showed that weak market competition is significantly associated with higher operating costs, supporting the traditional competition theory. However, the combined effect of APCDs and competition did not indicate a significant association with operating expenses. Further investigation showed a continued tendency for a weak intensity of competition to be linked to lower hospital operating costs in states without APCDs. For those located in non-APCD adopted states, market consolidation helped hospitals coordinate care more effectively, economize operating costs, and enjoy economies of scale due to their large size. Similar trends did not appear in APCD-adopted states except for in 2015. This study observed limited evidence of the impact of APCDs and market competition. Our findings suggest that states need to make multifaceted efforts to contain hospital costs, not solely depending on the rollout of cost information or market competition. Market concentration may lead to coordinated care or cost economization in some cases. Still, the existing literature also demonstrates some potentially harmful impacts of increased concentration in the healthcare market, such as inefficient use of resources, unilateral market power, and deterrence of innovation. The introduction of a price transparency tool may require additional policy actions that take market competition into consideration.


A circular network of purine metabolism as coregulators of dilated cardiomyopathy.
The crosstalk of purine biosynthesis and metabolism exists to balance the cell energy production, proliferation, survival and cytoplasmic environment stability, but disorganized mechanics of with respect to developing heart failure (HF) is currently unknown. We conducted a multi-omics wide analysis, including microarray-based transcriptomes, and full spectrum metabolomics with respect to chronic HF. Based on expression profiling by array, we applied a bioinformatics platform of quantifiable metabolic pathway changes based on gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Shapley Additive Explanations (SHAP), and Xtreme Gradient Boosting (XGBoost) algorithms to comprehensively analyze the dynamic changes of metabolic pathways and circular network in the HF development. Additionally, left ventricular tissue from patients undergoing myocardial biopsy and transplantation were collected to perform the protein and full spectrum metabolic mass spectrometry. Systematic bioinformatics analysis showed the purine metabolism reprogramming was significantly detected in dilated cardiomyopathy. In addition, this result was also demonstrated in metabolomic mass spectrometry. And the differentially expressed metabolites analysis showing the guanine, urea, and xanthine were significantly detected. Hub markers, includes IMPDH1, ENTPD2, AK7, AK2, and CANT1, also significantly identified based on XGBoost, SHAP model and PPI network. The crosstalk in the reactions involved in purine metabolism may involving in DCM metabolism reprogramming, and as coregulators of development of HF, which may identify as potential therapeutic targets. And the markers of IMPDH1, ENTPD2, AK7, AK2, and CANT1, and metabolites involved in purine metabolism shown an important role.


Catalytic reduction of NO with decomposed methanol on alumina-supported Mn-Ce catalysts.
A series of manganese-ceria supported on alumina catalysts with various Mn/Ce ratios are investigated in both methanol decomposition to CO and hydrogen and SCR of NO(x) with CO. The study is aimed at the potential application of both reactions in integrated devices, where NO(x) is reduced with the products of the decomposed methanol. The samples are characterized by nitrogen physisorption, XRD, TEM, XPS, UV-Vis, and TPR. It was established that manganese-ceria supported on alumina catalysts are perspective in both methanol decomposition and NO reduction at temperatures above 723 K, which are typical for exhausted gases from the vehicles and some stationary stations. The best catalytic activity and selectivity to the desired products under these conditions was found for the samples with Mn/Mn+Ce ratio of 0.5 and 0.7. This superior catalytic performance is related to the formation of mixed valence Mn(3+)/Ce(4+) and Mn(4+)/Ce(3+) active sites.


Naturally occurring regulatory T cells: markers, mechanisms, and manipulation.
Naturally occurring CD4(+)CD25(high) forkhead box protein 3 (FOXP3)(+) regulatory T cells (nTregs) are key mediators of immunity, which orchestrate and maintain tolerance to self and foreign antigens. In the recent 1.5 decades, a multitude of studies have aimed to define the phenotype and function of nTregs and to assess their therapeutic potential for modulating immune mediated disorders such as autoimmunity, allergy, and episodes of transplant rejection. In this review, we summarize the current knowledge on the biology of nTregs. We address the exact definition of nTregs by specific markers and combinations thereof, which is a prerequisite for the state-of-the-art isolation of defined nTreg populations. Furthermore, we discuss the mechanism by which nTregs mediate immunosuppression and how this knowledge might translate into novel therapeutic modalities. With first clinical studies of nTreg-based therapies being finished, questions concerning the reliable sources of nTregs are becoming more and more eminent. Consequently, approaches allowing conversion of CD4(+) T cells into nTregs by coculture with antigen-presenting cells, cytokines, and/or pharmacological agents are discussed. In addition, genetic engineering approaches for the generation of antigen-specific nTregs are described.


Avoidance conditioning in bamboo sharks (Chiloscyllium griseum and C. punctatum): behavioral and neuroanatomical aspects.
Animals face different threats; to survive, they have to anticipate how to react or how to avoid these. It has already been shown in teleosts that selected regions in the telencephalon, i.e., the medial pallium, are involved in avoidance learning strategies. No such study exists for any chondrichthyan. In nature, an avoidance reaction may vary, ranging from a 'freeze' reaction to a startling response and quick escape. This study investigated whether elasmobranchs (Chiloscylliumgriseum and C. punctatum) can be conditioned in an aversive classical conditioning paradigm. Upon successful conditioning, the dorsal, medial and lateral pallium were removed (group 1) and performance tested again. In a second group, the same operation was performed prior to training. While conditioning was successful in individuals of both groups, no escape responses were observed. Post-operative performance was assessed and compared between individual and groups to reveal if the neural substrates governing avoidance behavior or tasks learned in a classical conditioning paradigm are located within the telencephalon, as has been shown for teleosts such as goldfish.


30° inclination in handles of plastic boxes can reduce postural and muscular workload during handling.
The handling of materials, which occurs in the industrial sector, is associated with lesions on the lumbar spine and in the upper limbs. Inserting handles in industrial boxes is a way to reduce work-related risks. Although the position and angle of the handles are significant factors in comfort and safety during handling, these factors have rarely been studied objectively. To compare the handling of a commercial box and prototypes with handles and to evaluate the effects on upper limb posture, muscle electrical activity, and perceived acceptability using different grips while handling materials from different heights. Thirty-seven healthy volunteers evaluated the handles of prototypes that allowed for changes in position (top and bottom) and angle (0°, 15°, and 30°). Wrist, elbow, and shoulder movements were evaluated using electrogoniometry and inclinometry. The muscle electrical activity in the wrist extensors, biceps brachii, and the upper portion of the trapezius was measured using a portable electromyographer. The recorded data on muscle movements and electrical activity were synchronized. Subjective evaluations of acceptability were evaluated using a visual analog scale. The prototypes with handles at a 30° angle produced the highest acceptability ratings, more neutral wrist positions, lower levels of electromyographic activity for the upper trapezius, and lower elevation angles for the arms. The different measurement methods were complementary in evaluating the upper limbs during handling.


Bleeding and stenosis caused by reflux esophagitis was not common in emergency endoscopic examinations: a retrospective patient chart review at a single institution in Japan.
Bleeding and stenosis are serious complications of reflux esophagitis, although few studies have been performed in Japan regarding these complications. This study aimed to indicate the characteristics of reflux esophagitis observed during emergency endoscopic examination in Japan. All subjects who had emergency endoscopic examination performed between 1990 and 2004 at Saga Medical School Hospital were evaluated. Patients with endoscopic reflux esophagitis were evaluated with a retrospective patient chart review. A total of 1621 subjects underwent emergency endoscopy; 1420 of the endoscopies were because of hematemesis or melena. Endoscopic examination revealed that 19 cases with bleeding were caused by reflux esophagitis (19/1621, 1.2%). The 19 patients with bleeding and the four patients with stenosis (0.2%) had emergency endoscopy performed for complications of reflux esophagitis. The Los Angeles classification of these 23 cases showed that most were severe esophagitis (grade A, 0; B, 2; C, 8; and D, 13). The frequency of comorbidity with diabetes mellitus and collagen disease and the proportion of heavy drinkers were higher in patients who received emergency endoscopy because of reflux esophagitis than in those diagnosed with reflux esophagitis but who received emergency endoscopy because of other diseases. Relatively small numbers of patients with reflux esophagitis undergo emergency endoscopy in Japan, and most such patients have underlying diseases, including diabetes mellitus and collagen disease. This finding is supported by a previous report that severe esophagitis is not common in Japan.


Histamine receptor assays.
This unit describes three standard in vitro bioassays for studying histamine H₁, H₂ and H₃ receptors in isolated intact tissues removed from the guinea pig. Both the H₁ and H₃ receptor assays are based on preparations of the ileum, whereas the spontaneously beating right atrium assay is used for the H₂-receptor.This unit describes three standard in vitro bioassays for studying histamine H₁, H₂ and H₃ receptors in isolated intact tissue.


The pectoralis major myocutaneous flap. Experience in 100 consecutive cases.
The authors have made a study of 100 consecutive cases in whom a pectoralis major myocutaneous flap was employed for reconstruction after surgical ablation of advanced malignant tumours in the head and neck. The results obtained show that primary healing took place in 74% of cases with a relatively low incidence of complications. The authors therefore confirm the reliability of the pectoralis major myocutaneous flap, which, owing to its rich blood supply, offers the possibility of providing large cutaneous islands, and its proximity to the site of ablation provides a simple and reliable method which may be used in the majority of cases of immediate or delayed reconstruction of the cervico-maxillo-facial area.


Vitamin-D deficiency impairs CD4+T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: A longitudinal study.
We implemented a prospective study among human immunodeficiency virus (HIV)-positive adults to examine the association between vitamin-D deficiency (VDD) and insufficiency (VDI) vs sufficiency (VDS) and CD4+T-cell improvement over 18 months of highly active antiretroviral therapy (HAART). We used data from a randomized placebo-controlled micronutrient trial with 25-hydroxy vitamin-D (25(OH)D) measured at enrollment in 398 adults. CD4+T-cell count was measured repeatedly at months 0, 3, 6, 12 and 18. Linear mixed models quantified the vitamin-D-related differences in CD4+T-cell count and associated 99% confidence intervals at baseline and respective follow-up intervals. At baseline 23%, 60% and 17% of participants were VDS, VDI and VDD, respectively. Absolute CD4+T- cell counts recovered during follow-up were persistently lower for baseline VDD and VDI relative to VDS participants. The greatest deficit in absolute CD4+T-cells recovered occurred in VDD vs VDS participants with estimates ranging from a minimum deficit of 26 cells/μl (99% CI: -77, 26) to a maximum deficit of 65 cells/μl (99% CI: -125, -5.5) during follow-up. This VDD-associated lower absolute CD4+T-cell gain was strongest among patients 35 years old or younger and among participants with a baseline body mass index of less than 25 kg/m(2). VDD is associated with lower absolute CD4+T-cell count recovery in HIV-positive patients on HAART. Vitamin-D supplementation may improve CD4+T-cell recovery during HAART. However, future intervention studies are needed to definitively evaluate the effectiveness of this vitamin as an adjunct therapy during HAART.


The role of plastic surgery in reconstruction after oncological surgery.
One in three people is affected by cancer in their lifetime. Surgical treatment commonly has the greatest impact on long-term survival, so a large proportion of patients undergo major oncological resection. This is the first in a symposium of four articles describing plastic surgical reconstruction after oncological resection.


A risk assessment method for remote sensing of cyanobacterial blooms in inland waters.
The widespread occurrence of Cyanobacterial blooms (CABs) in inland waters is a typical and severe challenge for water resources management and environment protection. An accurate and spatially continuous risk assessment of CABs is critical for prediction and preparedness in advance. In this study, a multivariate integrated risk assessment (MIRA) method of CABs in inland waters was proposed. MIRA was simplified with the trophic levels, cyanobacterial and other aquatic plant condition using remote sensing indexes, including the Trophic State Index (TSI), Floating Algae Index (FAI) and Cyanobacteria and Macrophytes Index (CMI). First, the dates of risk assessment were carefully selected based on TSI. Then, we obtained the trophic levels, cyanobacterial, and other aquatic plant condition of water using TSI, CMI and FAI on the selected date, and further scored them pixel by pixel to quantify the risk value. Finally, the risk of CABs in water was accurately assessed based on the pixel risk value. Based on Landsat 8 OLI dataset, MIRA was executed and validated in three different lakes of Wuhan urban agglomeration (WUA) with different trophic states. The results demonstrated that the risk of CABs in Lake LongGan was overall higher than that in Lake LiangZi and Lake FuTou. And the risk of CABs in the east part of Lake LongGan was higher than the other parts. Seasonally, the risk level ranking in Lake LiangZi was the highest in summer, while lowest in winter. However, the seasonal risk ranking was spring, summer, autumn, and winter in Lake LongGan. Based on the comparisons with monthly water quality classification data and results of the existing study, including trophic level, ecology risk, and algal extent, the MIRA method was valuable for accurate and spatially continuous identifying the risk of CABs in inland waters with potential eutrophication trends.


Typhoid vaccine introduction: An evidence-based pilot implementation project in Nepal and Pakistan.
The World Health Organization (WHO) in 2008 recommended the use of currently licensed typhoid vaccines using a high risk or targeted approach. The epidemiology of disease and the vaccine characteristics make school-based vaccination most feasible in reducing typhoid disease burden in many settings. To assess feasibility of school-based typhoid vaccination, two districts in Kathmandu, Nepal and two towns in Karachi, Pakistan were selected for pilot program. Vaccination campaigns were conducted through the departments of health and in partnerships with not-for-profit organizations. In total 257,015 doses of Vi polysaccharide vaccine were given to students in grades 1-10 of participating schools. The vaccination coverage ranged from 39 percent (38,389/99,503) in Gulshan town in Karachi, to 81 percent (62,615/77,341) in Bhaktapur in Kathmandu valley. No serious adverse event was reported post vaccination. The coverage increased for vaccination of the second district in Pakistan as well as in Nepal. There was an initial concern of vaccine safety. However, as the campaign progressed, parents were more comfortable with vaccinating their children in schools. Supported and conducted by departments of health in Pakistan and Nepal, a school-based typhoid vaccination was found to be safe and feasible.


Injuries Due to Law Enforcement Use of Force in the United States, 2006-2015: Trends in Severity and by Race.
The purpose of the study was to assess incidence and severity of hospital reported injuries related to law enforcement Use of Force (UoF) in the US over time, and by race. Data from the National Emergency Department Sample from the Healthcare Cost and Utilization Project and the National Electronic Injury Surveillance System (NEISS-AIP) from US Consumer Product Safety Commission were queried to identify UoF injuries. Regression analysis, t-tests, and chi-square tests were used in the analysis. Between 2006-15, there were 529,259 emergency department admissions for UoF injury in the NEDS, and 870,779 admissions in the NEISS-AIP. In a model adjusting for year, sex, and age, the Injury Severity Score increased by 1.1% annually (p<0.0001). Black people were 6 times as likely to be admitted to the ED as White people or Native Americans/Alaska Natives, and 25 times as likely as Asians/Pacific Islanders. Black patients were 4 times as likely as White patients to be admitted as inpatients. Per arrest rate by race using FBI uniform crime reporting data, Black arrestees were 2.5-3.1 times as likely as any other race to be hospitalized for UoF injury. The results of the study demonstrate that US law enforcement are injuring civilians more frequently and severely over time, and that Black people are disproportionately affected.


High-Density Electroencephalography-Informed Multiband Functional Magnetic Resonance Imaging Reveals Rhythm-Specific Activations Within the Trigeminal Nociceptive Network.
The interest in exploring trigeminal pain processing has grown in recent years, mainly due to various pathologies (such as migraine) related to this system. However, research efforts have mainly focused on understanding molecular mechanisms or studying pathological states. On the contrary, non-invasive imaging studies are limited by either spatial or temporal resolution depending on the modality used. This can be overcome by using multimodal imaging techniques such as simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although this technique has already been applied to neuroscientific research areas and consequently gained insights into diverse sensory systems and pathologies, only a few studies have applied EEG-fMRI in the field of pain processing and none in the trigeminal system. Focusing on trigeminal nociception, we used a trigeminal pain paradigm, which has been well-studied in either modality. For validation, we first acquired stand-alone measures with each imaging modality before fusing them in a simultaneous session. Furthermore, we introduced a new, yet simple, non-parametric correlation technique, which exploits trial-to-trial variance of both measurement techniques with Spearman's correlations, to consolidate the results gained by the two modalities. This new technique does not presume a linear relationship and needs a few repetitions per subject. We also showed cross-validation by analyzing visual stimulations. Using these techniques, we showed that EEG power changes in the theta-band induced by trigeminal pain correlate with fMRI activation within the brainstem, whereas those of gamma-band oscillations correlate with BOLD signals in higher cortical areas.


The radioactivity of coloured rain in Thessaloniki, Greece.
The radioactivity of coloured rain precipitated over Thessaloniki, Greece, on 4-5 April 1988 was determined. The long-lived fission product radionuclides such as 137Cs, 134Cs, 144Ce, 106Ru and 125Sb were identified in dust originating from the Sahara desert which was precipitated with the rain to produce coloured rain. Caesium-137 concentrations reached 1000 Bq kg-1, resulting in a deposition of 3.03 Bq m-2, which is four orders of magnitude lower than measured on 5-6 May 1986 after the Chernobyl reactor accident.


Single-incision laparoscopic versus conventional laparoscopic surgery for Hirschsprung's disease: A comparison of medium-term outcomes.
This study aims to report medium-term outcomes of single-incision laparoscopic surgery (SILS) and compare its results with conventional laparoscopic surgery (CLS). Seventy-five patients with Hirschsprung's disease (HD) underwent operations from January 2009 to December 2012 in our institution (SILS, n=40; CLS, n=35). SILS procedure is similar to CLS, but uses a single, 1.5-cm horizontal skin incision in the umbilicus for laparoscopic access. Operative characteristics and medium-term outcomes were assessed. On average, patients in the SILS group had shorter operative times (mean±standard deviation, 226±69.4min) than those in the CLS group (268.9±83.6min) (P=0.01). Fourteen cases (35%) in the SILS group and ten cases (28.6%) in the CLS group had extended HD. Medium-term outcomes did not significantly differ between the groups, and the SILS group had better cosmetic results. SILS could be safely performed in HD patients with good medium-term outcomes. Although SILS and CLS procedures had similar medium-term outcomes, SILS has advantages such as better cosmetic results and shorter operative times.


[Pachychoroid Disease].
Pachychoroid spectrum disorders include uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularisation, focal choroidal excavation and peripapillary pachychoroid syndrome. They are characterized by a thickened and hyperpermeable choroid and thinning of the choriocapillaris. The disorders are being diagnosed with increasing frequency and differentiation due to the advancement of multimodality imaging. Current understanding of the development, course, possible complications and treatment of these diseases is growing rapidly, but not all mechanisms have yet been elucidated. A correct diagnosis is important, especially the differentiation between the presence of active neovascularisation or a purely exudative stage, in order to initiate a therapy. It is also not yet clear why patients have a thickened choroid and why some of these patients develop pathological changes such as subretinal fluid, RPE changes or neovascularisation.