Liquid-Phase Exfoliation of Phosphorene: Design Rules from Molecular Dynamics Simulations.
The liquid-phase exfoliation of phosphorene, the two-dimensional derivative of black phosphorus, in the solvents dimethyl sulfoxide (DMSO), dimethylformamide (DMF), isopropyl alcohol, N-methyl-2-pyrrolidone, and N-cyclohexyl-2-pyrrolidone is investigated using three molecular-scale "computer experiments". We modeled solvent-phosphorene interactions using an atomistic force field, based on ab initio calculations and lattice dynamics, that accurately reproduces experimental mechanical properties. We probed solvent molecule ordering at phosphorene/solvent interfaces and discovered that planar molecules such as N-methyl-2-pyrrolidone preferentially orient parallel to the interface. We subsequently measured the energy required to peel a single phosphorene monolayer from a stack of black phosphorus and analyzed the role of "wedges" of solvent molecules intercalating between phosphorene sheets in initiating exfoliation. The exfoliation efficacy of a solvent is enhanced when either molecular planarity "sharpens" this molecular wedge or strong phosphorene-solvent adhesion stabilizes the newly exposed phosphorene surfaces. Finally, we examined the colloidal stability of exfoliated flakes by simulating their aggregation and showed that dispersion is favored when the cohesive energy between the molecules in the solvent monolayer confined between the phosphorene sheets is high (as with DMSO) and is hindered when the adhesion between these molecules and phosphorene is strong; the molecular planarity in solvents like DMF enhances the cohesive energy. Our results are consistent with, and provide a molecular context for, experimental exfoliation studies of phosphorene and other layered solids, and our molecular insights into the significant role of solvent molecular geometry and ordering should complement prevalent solubility-parameter-based approaches in establishing design rules for effective nanomaterial exfoliation media.


Opposing roles for reactive astrocytes following traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Current medical therapies exhibit limited efficacy in reducing neurological injury and the prognosis for patients remains poor. While most research is focused on the direct protection of neuronal cells, non-neuronal cells, such as astrocytes, may exert an active role in the pathogenesis of TBI. Astrocytes, the predominant cell type in the human brain, are traditionally associated with providing only structural support within the CNS. However, recent work suggests astrocytes may regulate brain homeostasis and limit brain injury. In contrast, reactive astrocytes may also contribute to increased neuroinflammation, the development of cerebral edema, and elevated intracranial pressure, suggesting possible roles in exacerbating secondary brain injury following neurotrauma. The multiple, opposing roles for astrocytes following neurotrauma may have important implications for the design of directed therapeutics to limit neurological injury. As such, a primary focus of this review is to summarize the emerging evidence suggesting reactive astrocytes influence the response of the brain to TBI.


[Antisepsis and disinfection].
Among the complications derived from the use of venous catheters, the infections related to the insertion and the maintenance of these catheters are the most serious and most frequent ones. The author describes measures which can be taken to minimize these complications.


Morbidity and mortality of short bowel syndrome in infancy and childhood.
This report concerns 59 infants and children with short bowel syndrome, most commonly caused by necrotizing enterocolitis in this study. Resection of atretic or gangrenous bowel was performed in 53 patients, tapering enteroplasty and primary anastomosis was performed in 13 patients, and temporary enterostomies were performed in 40 patients. Second-look laparotomy was useful in two of four cases of questionable bowel viability. The ileocecal valve was resected in 32 patients and remained intact in 27. The mean length of the remaining bowel was 58.4 cm. All patients received total parenteral nutrition and early enteral feedings. Home hyperalimentation was attempted when 50 per cent of the calorie intake was enteral. Intestinal adaptation required from 3 to 14 months. Frequent setbacks were related to catheter sepsis, rotavirus infection, carbohydrate intolerance, and liver dysfunction. The overall survival rate was 80 per cent with mortality due to sepsis associated with total parenteral nutrition and liver failure.


Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway.
Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1's prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.


A non-randomized pilot study to test the feasibility of treating chronic pain and opioid prescription use in rural areas with acceptance and commitment therapy (T-PACT).
Chronic non-cancer pain (CNCP) involves one-third of the US population, and prescription opioids contribute to the opioid epidemic. The Centers for Disease Control and Prevention emphasizes maximizing non-opioid treatment, but many rural populations cannot access alternative therapies. Clinical and Translational Science Award hubs across four rural states performed a multi-site, single-arm intervention feasibility study testing methods and procedures of implementing a behavioral intervention, acceptance and commitment therapy, in primary care CNCP patients on chronic opioids. Using the CONSORT extension for feasibility studies, we describe lessons learned in recruiting/retaining participants, intervention implementation, data measurement, and multi-site procedures. Results inform a future definitive trial and potentially others conducting rural trials.


Binocular responses in the superior colliculus of the albino rat.
The retinotopic map for the contralateral eye is similar to that found in the pigmented rats and in other rodents. Cells which had ipsilateral responses were recorded in a fairly large area in the rostral portion of the tectum. Their receptive fields lay from about 40 degrees in the contralateral hemifield to about 40 degrees in the ipsilateral hemifield. The ipsilateral response of a binocular cell is similar in almost every respect to its counterpart in the opposite eye except being very weak and that the receptive field is usually smaller. Most binocular cells are distributed in the Stratum griseum superficiale (SGS) and the Stratum opticum (SO). Less binocular cells recorded in the Stratum griseum intermediale (SGI) have more scattered distribution both in the size and in the position of the receptive field.


Cognitive remediation in schizophrenia: current status and future perspectives.
Objectives. This study is aimed to review the current scientific literature on cognitive remediation in schizophrenia. In particular, the main structured protocols of cognitive remediation developed for schizophrenia are presented and the main results reported in recent meta-analyses are summarized. Possible benefits of cognitive remediation in the early course of schizophrenia and in subjects at risk for psychosis are also discussed. Methods. Electronic search of the relevant studies which appeared in the PubMed database until April 2013 has been performed and all the meta-analyses and review articles on cognitive remediation in schizophrenia have been also taken into account. Results. Numerous intervention programs have been designed, applied, and evaluated, with the objective of improving cognition and social functioning in schizophrenia. Several quantitative reviews have established that cognitive remediation is effective in reducing cognitive deficits and in improving functional outcome of the disorder. Furthermore, the studies available support the usefulness of cognitive remediation when applied in the early course of schizophrenia and even in subjects at risk of the disease. Conclusions. Cognitive remediation is a promising approach to improve real-world functioning in schizophrenia and should be considered a key strategy for early intervention in the psychoses.


[Fiber fasciotomy in Dupuytren's contracture].
42 patients with hand Dupuytren's contracture were operated. Transection of each finger scar cords was performed in transverse direction through 3-8 skin punctures from proximal portion to distal segment in the zone of middle phalanx base. In addition, complete finger extension was achieved on operating table. There were no recurrences in follow-up of 13 years.


Can changes to improve person-centred maternity care be spread across public health facilities in Uttar Pradesh, India?
Poor quality person-centred maternity care (PCMC) leads to delays in care and adverse maternal and newborn outcomes. This study describes the impact of spreading a Change Package, or interventions that other health facilities had previously piloted and identified as successful, to improve PCMC in public health facilities in Uttar Pradesh, India. A quasi-experimental design was used including matched control-intervention facilities and pre-post data collection. This study took place in Uttar Pradesh, India in 2018-2019. Six large public health facilities participated in the evaluation of the spread study, including three intervention and three control facilities. Intervention facilities were introduced to a quality improvement (QI) Change Package to improve PCMC. In total, 1200 women participated in the study, including 600 women at baseline and 600 women at endline. Difference-in-difference estimators are used to examine the impact of spreading a QI Change Package across spread sites vs. control sites and at baseline and endline using a validated PCMC scale. Out of a 100-point scale, a 24.93 point improvement was observed in overall PCMC scores among spread facilities compared to control facilities from baseline to endline (95% CI: 22.29, 27.56). For the eight PCMC indicators that the Change Package targeted, spread facilities increased 33.86 points (95% CI: 30.91, 36.81) relative to control facilities across survey rounds. Findings suggest that spread of a PCMC Change Package results in improved experiences of care for women as well as secondary outcomes, including clinical quality, nurse and doctor visits, and decreases in delivery problems.Trial registration: ClinicalTrials.gov identifier: NCT04208841..


Axillary breast tissue: clinical presentation and surgical treatment.
Aberrant breast tissue is usually present along the milk line above or below the normal breast location. Occasionally, it is found in unusual locations, such as the axilla, scapula, thigh, and labia majora. Accessory axillary breast tissue is present in approximately 2% to 6% of women. Although this finding has been reported in a variety of clinical journals, such as Radiology and Human Pathology, it has received little attention in the plastic surgery literature. Axillary breast tissue, presenting as palpable thickenings in the axilla, can undergo monthly premenstrual changes, such as tenderness and swelling, difficulty with shoulder range of motion, and irritation from clothing. These symptoms may be exacerbated and become more apparent during puberty and pregnancy. In addition, it is cosmetically unsightful, and consequently, patients often desire surgery for improvement. We present a study of 28 patients who underwent surgical removal of their axillary breast tissue. From these successful reports, we recommend that axillary breast tissue should be surgically removed.


Enigmatic role of lipoprotein(a) in cardiovascular disease.
Lipoprotein (a), [Lp(a)] has many properties in common with low-density lipoprotein, (LDL) but contains a unique protein apolipoprotein(a), linked to apolipoprotein B-100 by a single disulfide bond. There is a substantial size heterogeneity of apo(a), and generally smaller apo(a) sizes tend to correspond to higher plasma Lp(a) levels, but this relation is far from linear, underscoring the importance to assess allele-specific apo(a) levels. The presence of apo(a), a highly charged, carbohydrate-rich, hydrophilic protein may obscure key features of the LDL moiety and offer opportunities for binding to vessel wall elements. Recently, interest in Lp(a) has increased because studies over the past decade have confirmed and more robustly demonstrated a risk factor role of Lp(a) for cardiovascular disease. In particular, levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with coronary artery disease (CAD). Other studies suggest that proinflammatory conditions may modulate risk factor properties of Lp(a). Further, Lp(a) may act as a preferential acceptor for proinflammatory oxidized phospholipids transferred from tissues or from other lipoproteins. However, at present only a limited number of agents (e.g., nicotinic acid and estrogen) has proven efficacy in lowering Lp(a) levels. Although Lp(a) has not been definitely established as a cardiovascular risk factor and no guidelines presently recommend intervention, Lp(a)-lowering therapy might offer benefits in subgroups of patients with high Lp(a) levels.


Dietary shift of an invasive predator: rats, seabirds and sea turtles.
Rats have reached about 80% of the world's islands and are among the most successful invasive mammals. Rats are opportunistic predators that are notorious for their impact on a variety of animal and plant species. However, little documented evidence on the complexities of these interactions is available.In our study, we assessed the impact of black rats Rattus rattus introduced on a small uninhabited island with a relatively simple ecosystem, Surprise Island, New Caledonia. We also compared the diet of R. rattus in the presence and absence of breeding seabirds, assessing the dietary compensation for this potentially important food source. From 2002 to 2005, we used live trapping studies combined with stable isotope analysis and conventional diet analyses (direct observations, gut and faecal contents) to characterize the diet of rats.Our results suggest a heavy predatory impact on seabirds, which could constitute as much as 24% of the rat diet. Moreover, in the absence of birds, rats compensated marginally by preying more heavily on other components of their diet but mostly acquired a new resource. They shifted their diet by preying heavily upon another endangered species, the hatchlings of sea turtles Chelonia mydas, which could constitute the main resource in the diet of R. rattus in those periods. Abundance, body condition and distribution of the rats were consistent with heavy predation upon this additional resource.Synthesis and applications. In island ecosystems invasive rats prey mainly upon seabird eggs and chicks, thereby threatening their populations. Although rats are certainly capable of surviving on terrestrial foods outside the seabird nesting season, their ability to prey upon ephemeral but abundant resources, such as hatchling sea turtles, may contribute to maintaining their populations. This may explain their success on Surprise Island, an ecosystem of extreme conditions, and suggests that biologists and managers working with threatened species should be aware of the possibility of temporary diet shifts by introduced rodents that may cause unexpected heavy predation on these species. This dietary shift from one endangered taxa to another has major implications for the conservation of seabirds and sea turtles world-wide and more generally for the biodiversity of invaded insular communities.


Dephasing Catastrophe in 4-ε Dimensions: A Possible Instability of the Ergodic (Many-Body-Delocalized) Phase.
In two dimensions, dephasing by a bath cuts off Anderson localization that would otherwise occur at any energy density for fermions with disorder. For an isolated system with short-range interactions, the system can be its own bath, exhibiting diffusive (non-Markovian) thermal density fluctuations. We recast the dephasing of weak localization due to a diffusive bath as a self-interacting polymer loop. We investigate the critical behavior of the loop in d=4-ε dimensions, and find a nontrivial fixed point corresponding to a temperature T^{*}∼ε>0 where the dephasing time diverges. Assuming that this fixed point survives to ε=2, we associate it with a possible instability of the ergodic phase. Our approach may open a new line of attack against the problem of the ergodic to many-body-localized phase transition in d>1 spatial dimensions.


Evidence in favour of a role for peripheral-type benzodiazepine receptor ligands in amplification of neuronal apoptosis.
The mitochondrial peripheral benzodiazepine receptor (PBR) is involved in a functional structure designated as the mitochondrial permeability transition (MPT) pore, which controls apoptosis. PBR expression in nervous system has been reported in glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand fluo-FGIN-1-27 in mitochondria of rat cerebellar granule cells (CGCs). Additionally, the effect of PBR ligands on colchicine-induced apoptosis was investigated. Colchicine-induced neurotoxicity in CGCs was measured at 24 h. We show that, in vitro, PBR ligands 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4- benzodiazepin-2-one (Ro5-4864) and diazepam (25- 50 microM) enhanced apoptosis induced by colchicine, as demonstrated by viability experiments, flow cytometry and nuclear chromatin condensation. Enhancement of colchicine-induced apoptosis was characterized by an increase in mitochondrial release of cytochrome c and AIF proteins and an enhanced activation of caspase-3, suggesting mitochondrion dependent mechanism that is involved in apoptotic process. Our results indicate that exposure of neural cells to PBR ligands generates an amplification of apoptotic process induced by colchicine and that the MPT pore may be involved in this process.


An open trial of prazosin in the treatment of hypertension.
An open trial of prazosin has been conducted among 18 males aged 18-68 years (mean 42.7) and 22 females aged 23-70 years (mean 47.5) seen at the Lagos University Teaching Hospital Hypertension Clinic. 3 suffered from mild to moderate hypertension and 9 suffered from severe hypertension. The dose employed ranged from 2 to 60 mg per day in 2 or 3 divided doses. All 6 patients whose placebo diastolic pressure was below 100 mm Hg gave excellent response. 19(76%) of the 25 patients whose placebo diastolic pressure ranged from 100 to 114 mm Hg gave excellent response. Only 3 to 9 patients whose placebo diastolic pressure ranged from 115 to 129 mm Hg gave excellent response. There was improved response when polythiazide 2 mg daily was added to the treatment. The total number giving excellent response increased from 28 (70%) to 36 (90%). In 3 cases (7.5%), the response was fair and one case (2.5%) remained poor. In most cases there was slight increase in pulse rate. The side effects encountered included palpitation in 8 patients 3 of whom also had postural hypotension. There were no biochemical or haematological abnormalities caused by prazosin but on continued therapy 16 patients developed tolerance to its effect. Thus prazusin has been found to be useful addition to the antihypertensive arm amentarium.


Differences of Craniofacial Characteristics in Oral Breathing and Pediatric Obstructive Sleep Apnea.
Oral breathing (OB) was considered associated with specific craniofacial structures and same for pediatric obstructive sleep apnea (OSA). This study aimed to investigate the differences of craniofacial structures between OB and OSA. In this retrospective study, 317 children under age 18 years were recruited and divided into OB group, OSA group, and control group. OSA group (15 boys, 4 girls) were referred from qualified sleep center and diagnosed as pediatric OSA with full-night polysomnography. OB group (10 boys, 10 girls) were mostly referral from pediatric or ENT department, some of whom undertook polysomnography and were not OSA. Control group consisted of orthodontic patients within the same period. Lateral cephalograms were obtained in all groups and their parameters were compared with Chinese normal values and each other. R-PNS of OB group (18.04 ± 2.49 mm) was greater than OSA group (14.27 ± 4.36 mm) and even control group (16.22 ± 3.91 mm) (P < 0.01). U1-NA was also the greatest in OB group (7.15 ± 2.92 mm), followed by OSA group (4.88 ± 2.66 mm), while control group was the smallest (5.71 ± 2.94 mm) (P < 0.05). In addition, OB group presented the smallest adenoids and tonsils among three groups. Bony nasopharynx development, mandibular length and growth direction of mandible of OB group were all better than OSA group. Despite of oral breathing, anatomical morphology (well-developed dentoalveolar structures; mild adenotonsillar hypertrophy) might protect children from developing OSA.


Novel G-protein-coupled receptor-like proteins in the plant pathogenic fungus Magnaporthe grisea.
The G-protein-coupled receptors (GPCRs) are one of the largest protein families in human and other animal genomes, but no more than 10 GPCRs have been characterized in fungi. Do fungi contain only this handful or are there more receptors to be discovered? We asked this question using the recently sequenced genome of the fungal plant pathogen Magnaporthe grisea. Proteins with significant similarity to fungus-specific and other eukaryotic GPCRs were identified in M. grisea. These included homologs of known fungal GPCRs, the cAMP receptors from Dictyostelium, and a steroid receptor mPR. We also identified a novel class of receptors typified by PTH11, a cell-surface integral membrane protein required for pathogenicity. PTH11 has seven transmembrane regions and an amino-terminal extracellular cysteine-rich EGF-like domain (CFEM domain), a characteristic also seen in human GPCRs. Sixty-one PTH11-related proteins were identified in M. grisea that shared a common domain with homologs in Neurospora crassa and other fungi belonging to this subphylum of the Ascomycota (the Pezizomycotina). None was detected in other fungal groups (Basidiomycota or other Ascomycota subphyla, including yeasts) or any other eukaryote. The subclass of PTH11 containing the CFEM domain is highly represented in M. grisea. In M. grisea we identified homologs of known GPCRs and a novel class of GPCR-like receptors specific to filamentous ascomycetes. A member of this new class, PTH11, is required for pathogenesis, thus suggesting roles in pathogenicity for other members. The identified classes constitute the largest number of GPCR-like proteins reported in fungi to date.


Quantitation of pyridylhydroxybutyl-DNA adducts in liver and lung of F-344 rats treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen in rats and is believed to be one cause of lung cancer in smokers. NNK is metabolized to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also a strong lung carcinogen in rats and has a chiral center at its 1-carbon. Previous studies have demonstrated that cytochrome P450-catalyzed alpha-hydroxylation of NNK in the lung leading to the formation of methyl and pyridyloxobutyl (POB)-DNA adducts is critical for its carcinogenicity. alpha-Hydroxylation of NNAL would similarly produce pyridylhydroxybutyl (PHB)-DNA adducts, but these have not been previously investigated in vivo. POB- and PHB-DNA adduct levels can indicate the amounts of pyridyloxobutylating and pyridylhydroxybutylating agents present in tissues of NNK- or NNAL-treated rats at any given point. Therefore, in this study, we developed a sensitive and quantitative liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring method to determine levels of the PHB-DNA adducts O(6)-[4-(3-pyridyl)-4-hydroxybut-1-yl]-2'-deoxyguanosine (O(6)-PHB-dGuo, 10b), O(2)-[4-(3-pyridyl)-4-hydroxybut-1-yl]thymidine (O(2)-PHB-dThd, 11b), and 7-[4-(3-pyridyl)-4-hydroxybut-1-yl]-2'-deoxyguanosine (7-PHB-dGuo, 12b), the latter as the corresponding base 7-[4-(3-pyridyl)-4-hydroxybut-1-yl]-Gua (7-PHB-Gua, 14b) in DNA isolated from liver and lung of rats treated with 10 ppm NNK, (S)-NNAL, or (R)-NNAL in the drinking water for 20 weeks and sacrificed at 1, 2, 5, 10, 16, and 20 weeks. PHB-DNA adduct levels were higher in lung than in liver at each time point, consistent with previous studies of POB-DNA adducts in rats treated with NNK and NNAL in the drinking water. The results showed that NNK and (S)-NNAL behaved in a similar fashion, while (R)-NNAL was strikingly different. In the rats treated with NNK or (S)-NNAL, levels of each adduct at each time point were remarkably similar in lung, and levels of O(2)-PHB-dThd were generally greater than 7-PHB-Gua > O(6)-PHB-dGuo. The highest PHB-DNA adduct levels were found in lung and liver of rats treated with (R)-NNAL, suggesting that there are cytochrome P450s that efficiently catalyze the alpha-methyl hydroxylation of this compound. The results of this study provide further support for our hypothesis that (S)-NNAL is rapidly formed from NNK, sequestered at an unknown site in the lung, and then released and reoxidized to NNK with consequent DNA adduct formation resulting in lung carcinogenicity.


Serological differences between the multiple amine oxidases of yeasts and comparison of the specificities of the purified enzymes from Candida utilis and Pichia pastoris.
1. Antiserum to purified methylamine oxidase of Candida boidinii formed precipitin lines (with spurs) in double-diffusion tests with crude extracts of methylamine-grown cells of the following yeast species: Candida nagoyaensis, Candida nemodendra, Hansenula minuta, Hansenula polymorpha and Pichia pinus. No cross-reaction was observed with extracts of Candida lipolytica, Candida steatolytica, Candida tropicalis, Candida utilis, Pichia pastoris, Sporobolomyces albo-rubescens, Sporopachydermia cereana or Trigonopsis variabilis. Quantitative enzyme assays enabled the relative titre of antiserum against the various methylamine oxidases to be determined. 2. The amine oxidases from two non-cross-reacting species, C. utilis and P. pastoris, were purified to near homogeneity. 3. The methylamine oxidases, despite their serological non-similarity, showed very similar catalytic properties to methylamine oxidase from C. boidinii. Their heat-stability, pH optima, molecular weights, substrate specificities and sensitivity to inhibitors are reported. 4. The benzylamine oxidases of C. utilis and P. pastoris both oxidized putrescine, and the latter enzyme failed to show any cross-reaction with antibody to C. boidinii methylamine oxidase. Benzylamine oxidase from C. boidinii itself also did not cross-react with antibody to methylamine oxidase. The heat-stability, molecular weights, substrate specificities and sensitivity to inhibitors of the benzylamine/putrescine oxidases are reported. 5. The benzylamine/putrescine oxidase of C. utilis differed only slightly from that of C. boidinii. 6. Benzylamine/putrescine oxidase from P. pastoris differed from the Candida enzymes in heat-stability, subunit molecular weight and substrate specificity. In particular it catalysed the oxidation of the primary amino groups of spermine, spermidine, lysine, ornithine and 1,2-diaminoethane, which are not substrates for either of the Candida benzylamine oxidases that have been purified. 7. Spermine and spermidine were oxidized at both primary amino groups; in the case of spermidine this is a different specificity from that of plasma amine oxidase. 8. Under appropriate conditions, P. pastoris benzylamine/putrescine oxidase (which is very easy to purify) can be a useful analytical tool in measuring polyamines.


Fatal diphenhydramine intoxication in infants.
Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.


A novel variant in CDKN1C is associated with intrauterine growth restriction, short stature, and early-adulthood-onset diabetes.
CDKN1C, a cyclin-dependent kinase inhibitor and negative regulator of cellular proliferation, is paternally imprinted and has been shown to regulate β-cell proliferation. CDKN1C mutations are associated with growth disorders, including Beckwith-Wiedemann syndrome and IMAGe syndrome. To investigate the genetic basis for a familial disorder characterized by intrauterine growth restriction, short stature, and early-adulthood-onset diabetes. Genomic DNA samples (15 affected and 26 unaffected from a six-generation pedigree) were analyzed by genome-wide single nucleotide polymorphism arrays, whole exome and Sanger sequencing, and multiplex ligation-dependent probe amplification. Subjects were assessed for height, weight, adrenal gland size, ACTH, diabetes status, and testis volume. Linkage and sequence analyses were performed, and the identified genetic variant was functionally evaluated in reconstitution studies. The pedigree followed a paternally imprinted pattern of inheritance, and genetic linkage analysis identified a single significant 2.6-megabase locus on chromosome 11p15, within the imprinting center region 2. Multiplex ligation-dependent probe amplification did not detect copy number variants or methylation abnormalities. Whole exome sequencing revealed a single novel variant in the proliferating cell nuclear antigen-binding region of CDKN1C (c.842G>T, p.R281I) that co-segregated with affected status and, unlike variants found in IMAGe, did not entirely abrogate proliferating cell nuclear antigen binding. Clinical assessments revealed that affected individuals had low testicular volume but normal adrenal function. We report a novel CDKN1C mutation associated with features of IMAGe syndrome, but without adrenal insufficiency or metaphyseal dysplasia, and characterized by early-adulthood-onset diabetes. Our data expand the range of phenotypes observed with CDKN1C defects and suggest that CDKN1C mutations may represent a novel monogenic form of diabetes.


Neighborhoods and obesity in New York City.
Recent studies reveal disparities in neighborhood access to food and fitness facilities, particularly in US cities; but few studies assess the effects of multiple neighborhood factors on obesity. This study measured the multilevel relations between neighborhood food availability, opportunities and barriers for physical activity, income and racial composition with obesity (BMI> or =30 kg/m(2)) in New York City, controlling for individual-level factors. Obesity rates varied widely between neighborhoods, ranging from 6.8% to 31.7%. Obesity was significantly (p<0.01) associated with neighborhood-level factors, particularly the availability of supermarkets and food stores, fitness facilities, percent of commercial land use and area income. These findings are consistent with the growing literature showing that area income and availability of food and physical activity resources are related to obesity.


Toward the restoration of hand use to a paralyzed monkey: brain-controlled functional electrical stimulation of forearm muscles.
Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES) of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord.


Compositional genomes: prebiotic information transfer in mutually catalytic noncovalent assemblies.
Mutually catalytic sets of simple organic molecules have been suggested to be capable of self-replication and rudimentary chemical evolution. Previous models for the behavior of such sets have analyzed the global properties of short biopolymer ensembles by using graph theory and a mean field approach. In parallel, experimental studies with the autocatalytic formation of amphiphilic assemblies (e.g., lipid vesicles or micelles) demonstrated self-replication properties resembling those of living cells. Combining these approaches, we analyze here the kinetic behavior of small heterogeneous assemblies of spontaneously aggregating molecules, of the type that could form readily under prebiotic conditions. A statistical formalism for mutual rate enhancement is used to numerically simulate the detailed chemical kinetics within such assemblies. We demonstrate that a straightforward set of assumptions about kinetically enhanced recruitment of simple amphiphilic molecules, as well as about the spontaneous growth and splitting of assemblies, results in a complex population behavior. The assemblies manifest a significant degree of homeostasis, resembling the previously predicted quasi-stationary states of biopolymer ensembles (Dyson, F. J. (1982) J. Mol. Evol. 18, 344-350). Such emergent catalysis-driven, compositionally biased entities may be viewed as having rudimentary "compositional genomes." Our analysis addresses the question of how mutually catalytic metabolic networks, devoid of sequence-based biopolymers, could exhibit transfer of chemical information and might undergo selection and evolution. This computed behavior may constitute a demonstration of natural selection in populations of molecules without genetic apparatus, suggesting a pathway from random molecular assemblies to a minimal protocell.


All-Cause and Cause-Specific Mortality Among Individuals With Hypochondriasis.
Hypochondriasis, also known as health anxiety disorder, is a prevalent, yet underdiagnosed psychiatric disorder characterized by persistent preoccupation about having serious and progressive physical disorders. The risk of mortality among individuals with hypochondriasis is unknown. To investigate all-cause and cause-specific mortality among a large cohort of individuals with hypochondriasis. This Swedish nationwide matched-cohort study included 4129 individuals with a validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of hypochondriasis assigned between January 1, 1997, and December 31, 2020, and 41 290 demographically matched individuals without hypochondriasis. Individuals with diagnoses of dysmorphophobia (body dysmorphic disorder) assigned during the same period were excluded from the cohort. Statistical analyses were conducted between May 5 and September 27, 2023. Validated ICD-10 diagnoses of hypochondriasis in the National Patient Register. All-cause and cause-specific mortality in the Cause of Death Register. Covariates included birth year, sex, county of residence, country of birth (Sweden vs abroad), latest recorded education, civil status, family income, and lifetime psychiatric comorbidities. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs of all-cause and cause-specific mortality. Of the 4129 individuals with hypochondriasis (2342 women [56.7%]; median age at first diagnosis, 34.5 years [IQR, 26.3-46.1 years]) and 41 290 demographically matched individuals without hypochondriasis (23 420 women [56.7%]; median age at matching, 34.5 years [IQR, 26.4-46.2 years]) in the study, 268 individuals with hypochondriasis and 1761 individuals without hypochondriasis died during the study period, corresponding to crude mortality rates of 8.5 and 5.5 per 1000 person-years, respectively. In models adjusted for sociodemographic variables, an increased rate of all-cause mortality was observed among individuals with hypochondriasis compared with individuals without hypochondriasis (HR, 1.69; 95% CI, 1.47-1.93). An increased rate was observed for both natural (HR, 1.60; 95% CI, 1.38-1.85) and unnatural (HR, 2.43; 95% CI, 1.61-3.68) causes of death. Most deaths from unnatural causes were attributed to suicide (HR, 4.14; 95% CI, 2.44-7.03). The results were generally robust to additional adjustment for lifetime psychiatric disorders. This cohort study suggests that individuals with hypochondriasis have an increased risk of death from both natural and unnatural causes, particularly suicide, compared with individuals from the general population without hypochondriasis. Improved detection and access to evidence-based care should be prioritized.


Modernity and postmodernity in the genesis of transhumanism-posthumanism.
There are various authors who, within the realm of bioethics, propose as a model of the human being, a man who is enhanced, transhuman or even posthuman. The philosophical roots of these bioethical thinkers have not been sufficiently analysed. In this article our aim is to demonstrate the connection of this movement with the evolution of philosophy over the past several decades. Therefore, and keeping in mind that the transhumanist-posthumanist proposals appeared in the last decades of the 20th century, a time when important philosophical change was afoot, with a movement from the modern age to the postmodern, we begin our article by identifying the philosophical characteristics of both periods, as well as the relationship that exists between them. We will analyse synthetically the conception of the human being, of ethics and of empirical science in both periods, coming to the conclusion that the postmodern era is the result of the radicalization of ideas that were already latent in modernity. Afterwards, and following a brief summary of the postulates of transhumanism-posthumanism, we study the links that this current of thought has with modern and postmodern perspectives regarding the human person, ethics and technoscientific activity. We conclude that even though transhumanist-posthumanist thought has roots in modernity, its objectives and their theoretical bases reveal a strong dependence on postmodern thought. And further, since this latter current of thought is, at base, antihumanist it is logical that transhumanism-posthumanism, influenced by postmodernity, would reveal a strong tendency not merely to negate what the human being is, but even to forget what it is out of a desire to construct something different from the human in the future.


[Application of Ilizarov's external fixator on the basis of biology].
Ilizarov's biology includes that, in the presence of tension and stress, both regeneration of bone and soft tissues with cellular proliferation and their biological synthesis become vigorous. The Ilizarov's external fixator has five functions namely: compression, distraction, de-angulation, derotation and translocation. The principles of this procedure include: corticotomy instead of conventional osteotomy, placement of 4-5 sets of 1.5 mm wires transfixed in the bones at different levels under tension of 70-110 kg on the circular rings without acute diastasis until the 5 th to 7th day, and then, callotasis-callus distraction. The quality and quantity of the regenerated bone within the widening distraction gap are closely related to the maximum preservation of bone marrow and periosseous blood supply, and a distraction of 1 mm per day and preferably done by 4 times 0.25 mm each time should be emphasized. Experiences in 17 cases of pseudarthrosis and unequal length of leg treated with Ilizarov's technique are presented.


[Changes in the nutritive physiological value of proteins modified by dialdehyde starch].
The reaction of dialdehyde starch with the proteins of certain model protein texturates produces changes in the nutrition physiological quality of the proteins. Under the experimental conditions chosen, these changes were barely or not at all detectable by amino-acid analysis. On using the technique of aminoacid liberation under in vitro conditions, these changes were evidenced only for lysine and arginine. The determination of the lysine availability, however, testifies to a reversible or irreversible change of lysine which reduces significantly the PER values (animal experiments) of protein texturates treated with 100% oxidized dialdehyde starch. The differences between the NPU values were but insignificant. In spite of the detectable change in protein quality, the quality of the model protein texturates tested still satisfies the criteria for proteins with a composition which is favourable from the viewpoint of nutrition physiology.


The effects of soy protein in women and men with elevated plasma lipids.
Fifty four postmenopausal women with elevated cholesterol were recruited for a randomised, double-blind controlled trial of soy protein containing isoflavones. (ISP+) or a soy protein with a low isoflavone content (ISP-), taken daily for 12 weeks. There was an overall reduction after 12 weeks in total cholesterol (TC), LDL cholesterol (LDL-C), sex hormone binding globulin (SHBG), and luteinizing hormone (LH). There were no significant differences between treatment groups. In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks. In this male study there was a significant increase in HDL cholesterol (HDL-C) and SHBG. Soy protein has a cholesterol lowering effect in both women and men. These studies suggest that this effect is independent of isoflavones. Soy protein also reduces SHBG levels in both sexes.


Highly elevated serum CA 125 in a lady with ascites and retroperitoneal mass--a diagnostic dilemma.
Cancer antigen 125 (CA 125), a widely used tumor marker for monitoring epithelial ovarian cancer, is also found to be raised in non-gynecological tumors and non malignant disease involving peritoneum. We report a case of non-Hodgkin's lymphoma who presented with peritoneal and pleural effusions with a very high level of serum CA 125. Fifty four years female presented with gross ascitis, bilateral moderate pleural effusions, right retroperitoneal mass and a very high serum CA 125 level (4462.60 u/ml). She was initially evaluated to rule out ovarian malignancy but her biopsy from retroperitoneal mass came out to be diffuse large B cell non-Hodgkin's lymphoma. In a female patient with ascitis with high serum CA 125 level, a differential diagnosis of lymphoma should not be overlooked unless cytology comes positive for epithelial carcinoma cells.


Topography of fibers in the human corpus callosum mediating interhemispheric inhibition between the motor cortices.
In 1 split-brain patient and 13 patients with circumscript surgical lesions within different parts of the corpus callosum (CC), the topography of fibers within the CC mediating an interhemispheric inhibition between the motor cortices was investigated in the phase of a stable disconnection syndrome. The aim of the study was to characterize the system of callosal fibers activated by transcranial magnetic brain stimulation in more detail as a basis for a diagnostic application of this technique. The locations and areas of the lesions were measured on sagittal magnetic resonance (MR) slices and attributed to five segments of the CC, because the borders of the anatomic subdivisions of the CC are not clearly defined. Transcallosal inhibition (TI) of tonic electromyographical hand muscle activity was elicited by focal transcranial magnetic stimulation over the primary motor cortex. In a reference group of normal subjects, TI started after 35.8+/-3.6 msec had a duration of 24.8+/-2.7 msec and an estimated transcallosal conduction time of 15.5+/-3.0 msec (range, 10.2-20.0 msec, n = 24 hands). No significant differences were found for the TI originating from the right and left motor cortices. From the absence and presence of TI in patients with lesions in different parts of the CC it can be concluded that most of the fibers mediating TI pass through the posterior third and anterior fourth segment of the CC, that is, through the posterior half of the trunk of the CC. The clinical findings suggest a role for TI in the performance of fast and complex hand motor tasks.


Perceptuo-motor interactions during prehension movements.
Adaptive behavior relies on the integration of perceptual and motor processes. In this study, we aimed at characterizing the cerebral processes underlying perceptuo-motor interactions evoked during prehension movements in healthy humans, as measured by means of functional magnetic resonance imaging. We manipulated the viewing conditions (binocular or monocular) during planning of a prehension movement, while parametrically varying the slant of the grasped object. This design manipulates the relative relevance and availability of different depth cues necessary for accurate planning of the prehension movement, biasing visual information processing toward either the dorsal visual stream (binocular vision) or the ventral visual stream (monocular vision). Two critical nodes of the dorsomedial visuomotor stream [V6A (anterior visual area 6) and PMd (dorsal premotor cortex)] increased their activity with increasing object slant, regardless of viewing conditions. In contrast, areas in both the dorsolateral visuomotor stream [anterior intraparietal area (AIP) and ventral premotor cortex (PMv)] and in the ventral visual stream [lateral-occipital tactile-visual area (LOtv)] showed differential slant-related responses, with activity increasing when monocular viewing conditions and increasing slant required the processing of pictorial depth cues. These conditions also increased the functional coupling of AIP with both LOtv and PMv. These findings support the view that the dorsomedial stream is automatically involved in processing visuospatial parameters for grasping, regardless of viewing conditions or object characteristics. In contrast, the dorsolateral stream appears to adapt motor behavior to the current conditions by integrating perceptual information processed in the ventral stream into the prehension plan.


Congenital anorectal malformations. Harbingers of sacrococcygeal teratomas.
Since 1973, seven infants treated at the University of Florida, Gainesville, for congenital anorectal anomalies have been found to have concomitant sacrococcygeal teratomas. As anorectal anomalies occur in approximately one in every 5,000 live births and sacrococcygeal teratomas are noted in one in every 40,000 live births, this presentation would suggest a prevalence that precludes a random association. The presence of significant anorectal strictures in these patients resulted in a delay in the diagnosis of the presacral teratomas. As the frequency of malignant change in sacrococcygeal teratomas has been documented to increase proportionately with age, early diagnosis and excision of these lesions is essential. Our experience with these children suggests that the presence of congenital anorectal malformations in infancy should raise the physician's index of suspicion for associated sacrococcygeal teratomas.


Sea buckthorn seed oil reduces blood cholesterol and modulates gut microbiota.
Sea buckthorn seed oil (SBSO) has been used as a functional food in the prevention of heart diseases. The present study investigates the effects of SBSO on blood cholesterol and the gut microbiota in hypercholesterolemia hamsters. Four groups of hamsters (n = 8 each) were given one of four diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD) containing 0.1% cholesterol, and an HCD diet with sea buckthorn seed oil replacing 50% lard (SL) or replacing 100% lard (SH). Feeding SL and SH diets could reduce blood total cholesterol by 20-22%. This was accompanied by the down-regulation of the gene expression of acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporter8 (ABCG8). SBSO supplementation also increased the production of intestinal short-chain fatty acids and fecal outputs of neutral sterols. Metagenomic analysis demonstrated that feeding SL and SH diets could favorably modulate the relative abundance of Bacteroidales_S24-7_group, Ruminococcaceae, and Eubacteriaceae. It was therefore concluded that SBSO was effective in reducing blood cholesterol in hypercholesterolemic hamsters via increasing intestinal cholesterol excretion and promoting the growth of SCFA-producing bacteria.


Corticotropin-releasing activity of alpha-melanotropin.
Synthetic alpha-melanotropin stimulated the release of immunoreactive adrenocorticotropin from primary cultures of rat anterior pituitary cells. The effect of the alpha-melanotropin was dose-dependent. Cells incubated with synthetic arginine-vasopressin and alpha-melanotropin simultaneously produced an amount of adrenocorticotropin that was greater than the sum of the amount that the cells produced in response to each peptide added separately. Other peptides structurally similar to alpha-melanotropin, such as, beta-, gamma 1-, gamma 2-, and gamma 3-melanotropin, were also tested for adrenocorticotropin-releasing activity. Only the gamma 3-melanotropin demonstrated a statistically significant effect. A vasopressin preparation (Pitressin, Parke-Davis) purified from posterior pituitaries and previously shown to contain some alpha-melanotropin was much more potent in releasing adrenocorticotropin than the synthetic vasopressin.


Evaluating coral trophic strategies using fatty acid composition and indices.
The ecological success of shallow water reef-building corals has been linked to the symbiosis between the coral host and its dinoflagellate symbionts (herein 'symbionts'). As mixotrophs, symbiotic corals depend on nutrients 1) transferred from their photosynthetic symbionts (autotrophy) and 2) acquired by host feeding on particulate organic resources (heterotrophy). However, coral species differ in the extent to which they depend on heterotrophy for nutrition and these differences are typically poorly defined. Here, a multi-tracer fatty acid approach was used to evaluate the trophic strategies of three species of common reef-building coral (Galaxea fascicularis, Pachyseris speciosa, and Pocillopora verrucosa) whose trophic strategies had previously been identified using carbon stable isotopes. The composition and various indices of fatty acids were compared to examine the relative contribution of symbiont autotrophy and host heterotrophy in coral energy acquisition. A linear discriminant analysis (LDA) was used to estimate the contribution of polyunsaturated fatty acids (PUFA) derived from various potential sources to the coral hosts. The total fatty acid composition and fatty acid indices revealed differences between the more heterotrophic (P. verrucosa) and more autotrophic (P. speciosa) coral hosts, with the coral host G. fascicularis showing overlap with the other two species and greater variability overall. For the more heterotrophic P. verrucosa, the fatty acid indices and LDA results both indicated a greater proportion of copepod-derived fatty acids compared to the other coral species. Overall, the LDA estimated that PUFA derived from particulate resources (e.g., copepods and diatoms) comprised a greater proportion of coral host PUFA in contrast to the lower proportion of symbiont-derived PUFA. These estimates provide insight into the importance of heterotrophy in coral nutrition, especially in productive reef systems. The study supports carbon stable isotope results and demonstrates the utility of fatty acid analyses for exploring the trophic strategies of reef-building corals.


Measuring the surface dynamics of glassy polymers.
The motion of polymer chain segments cooled below the glass transition temperature slows markedly; with sufficient cooling, segmental motion becomes completely arrested. There is debate as to whether the chain segments near the free surface, or in thin films, are affected in the same way as the bulk material. By partially embedding and then removing gold nanospheres, we produced a high surface coverage of well-defined nanodeformations on a polystyrene surface; to probe the surface dynamics, we measured the time-dependent relaxation of these surface deformations as a function of temperature from 277 to 369 kelvin. Surface relaxation was observed at all temperatures, providing strong direct evidence for enhanced surface mobility relative to the bulk. The deviation from bulk alpha relaxation became more pronounced as the temperature was decreased below the bulk glass transition temperature. The temperature dependence of the relaxation time was much weaker than that of the bulk alpha relaxation of polystyrene, and the process exhibited no discernible temperature dependence between 277 and 307 kelvin.


Prevalence of gastroesophageal reflux in a Tunisian primary care population determined by patient interview.
Although gastresophageal reflux disease (GERD) is highly prevalent in Western countries, we have very little data about it in African countries. The aim of the study is to determine the prevalence and severity of GERD symptoms among Tunisian subjects and report its characteristics, consultation rate, management modes, as well as patients' satisfaction. Five hundred subjects living in Tunisia were interviewed face to face. The study was conducted at seven centers of primary care at Monastir's department by six interviewer doctors. The questionnaire consisted of 30 questions relating to subject attributes, lifestyle factors, medical history, reflux-related symptom characteristics, consultation behavior, previous treatments for GERD, and description of the last episode. Symptoms were defined as 'frequent' if they occurred at least weekly and 'occasional' if they occurred less frequently during the last year. The mean age was 42.3 ± 17.3 years and 75.6% were females. Over the previous year, 60% of the respondents reported suffering any GERD symptom. The prevalence of frequent GERD is 24%. Female gender (odds ratio [OR]: 1.97[1.15-3.37]) and body mass index ≥ 25 (OR: 1.54[1.042-2.29]) were associated with increased risk of GERD symptom. Only 22.3%, sought medical advice about GERD symptoms in the last year. In the univariate and multivariate analysis, work status, frequency and intensity of symptoms, duration of symptom, and association of atypical symptoms were associated with a higher frequency of medical consultation for GERD symptoms. Among the subjects complaining about heartburn, 34% took medications. GERD symptoms are common among Tunisian subjects. Few heartburn sufferers seek medical attention, and most do not take medications for symptomatic control.


Digital image processing, a potential noninvasive technique in the diagnosis of diseased intervertebral discs.
The detection of the posterior edge of the L4-L5 intervertebral disc has been accomplished by applying digital image processing techniques on conventional lateral radiograms of the spine, and the method is described. The results of this study have shown that there can be substantial absorption at the site of the disc if the radiogram is properly taken; the existing information on the radiogram can be processed so that an improvement in the diagnostic quality of the radiogram can be achieved; and the edge of the posterior portion of the disc can be determined. This study, although a preliminary one, opens new possibilities for a safer and probably more accurate way of diagnosing herniated discs.


[Phlebotominae (Diptera: Psychodidae) of Lagoas, a city of Buriticupu, Amazonia of Maranhão. I. The richness and relative abundance of the species in an area of recent colonization].
In this study the diversity of the species and relative abundance of the sand flies in the Amazonian community of Lagoas, in Buriticupu, Maranhão State, was determined. The study consisted of adult sandflies captured with CD light-traps, Shannon-trap and manual aspiration tube, between 18 PM and 6 AM, once a month, from December/95 to January/97, in a forest fragment and in the domestic environment (peri and intra). In all, 9,393 specimens were captured (4,302 males and 5,140 females) distributed among 38 species (1 Brumptomyia and 37 Lutzomyia). The diversity and abundance of species was higher in the forest, followed by the peri and intra. The predominance in the wild ambient is a consequence of the potentialities found in the remaining fragments of the forest which have survived the lumber yard exploitation and agricultural activities. In the forest environment Lutzomyia whitmani (64.9%), L. migonei (27%) and L. serrana (3.6%) were the most frequent species. In the peri and intra domicile L. evandroi predominated (55.4% and 97.9%). The species, L. whitmani (33.4%) and L. migonei (6.4%), were important in the peri domicile. The peridomestic habit of 7.7% of the sand flies showed the greatest epidemiologic importance, due to the existence of patients with leishmaniasis ulcers, who believe they were infected near their habitations.


[Monoaminergic structures of the hypothalamus in chronic stress].
Falk's histochemical fluorescent method was used to study monoamine (MA)-containing structures in isolated hypothalamus nuclei and in the neurohemal region of the medial eminence (ME) in 40 male rats under the conditions of a long-term stress (6 months) which was caused by a repeated weak electrodermal stimulation. A statistically significant decrease in the intensity of MA fluorescence in the early period of the experiment, particularly significant in the fibers of the paraventricular nucleus and in the ME, was replaced by an increase in the intensity of MA fluorescence in the fibers and perikaryons in the arcuate paraventricular nuclei and in the ME on the 100th day. On the 180th day of the experiment MA fluorescence in the hypothalamus structures of the experimental and control rats did not differ significantly. Thus MA in the hypothalamus nuclei and ME were involved in adaptation processes of the body to chronic stress action. Changes of the MA content were particularly marked in the paraventricular nucleus, associated with cortical RH and vasopressin production as well as in the arcuate nucleus and in the ME associated with the entry of these hormones in the hypophysial portal vessels to regulate ACTH secretion.


Rapid ultrasensitive detection platform for antimicrobial susceptibility testing.
Rapid detection and phenotyping of pathogenic microbes is critical for administration of effective antibiotic therapies and for impeding the spread of antibiotic resistance. Here, we present a novel platform, rapid ultrasensitive detector (RUSD), that utilizes the high reflectance coefficient at high incidence angles when light travels from low- to high-refractive-index media. RUSD leverages a principle that does not require complex manufacturing, labeling, or processing steps. Utilizing RUSD, we can detect extremely low cell densities (optical density [OD] ≥ 5 × 10-7) that correspond to approximately 20 bacterial cells or a single fungal cell in the detection volume, which is nearly 4 orders of magnitude more sensitive than standard OD methods. RUSD can measure minimum inhibitory concentrations (MICs) of commonly used antibiotics against gram-negative and gram-positive bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, within 2 to 4 h. Here, we demonstrate that antibiotic susceptibility tests for several pathogens can rapidly be performed with RUSD using both small inoculum sizes (500 cells/mL) and larger inoculum sizes (5 × 105 cells/mL) used in standard antibiotic susceptibility tests. We anticipate that the RUSD system will be particularly useful for the cases in which antibiotic susceptibility tests have to be done with a limited number of bacterial cells that are available. Its compatibility with standard antibiotic susceptibility tests, simplicity, and low cost can make RUSD a viable and rapidly deployed diagnostic tool.


A critical review of typing methods for Candida albicans and their applications.
During the 1980s, a large number of typing methods for the strain differentiation of Candida albicans were described in the literature. Although these methods have been based on a variety of physiological and genetic markers, none is ideal. This review discusses the characteristics of an ideal typing method in terms of its typability, reproducibility, and discriminatory power. Ways of determining these characteristics are presented so that the available typing methods for Candida albicans can be objectively compared. Available typing methods for C. albicans include serotyping, morphotyping, resistotyping, biotyping, and killer yeast typing. Electrophoretic methods include immunoblotting, isoenzyme analysis, analysis of DNA restriction fragment length polymorphism, karyotyping, and the use of DNA probes. The application of these methods to epidemiological research, the investigation of outbreaks of disease, and the study of virulence is described. The potential impact of the phenomenon of phenotypic switching on the reproducibility of these typing methods is discussed. It is concluded that many of the available typing methods have not been adequately assessed by their developers and that several have only poor discriminatory power or reproducibility.


Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides.
The inheritance of the apolipoprotein E (apoE) epsilon4 allele is a prevailing risk factor for sporadic and familial Alzheimer's disease (AD). ApoE isoforms bind directly to Alzheimer's amyloid beta (Abeta) peptides both in vitro and in vivo. Recent studies suggest that association of apoE with lipids may modulate its interaction with Abeta. We examined the binding of lipid-associated and delipidated apoE3 and apoE4 isoforms to Abeta utilizing a solid-phase binding assay and estimated the dissociation constants for the interaction of various apoE and Abeta species. Using native apoE isoforms from stably transfected RAW 264 and human embryonic kidney 293 cells, apoE3 had greater affinity than apoE4 for both Abeta1-40 and Abeta1-42. Delipidation of apoE decreased its affinity for Abeta peptides by 5-10-fold and abolished the isoform-specificity. Conversely, incorporation of apoE isoforms produced by baculovirus-infected Sf9 cells into reconstituted human high-density-lipoprotein lipoparticles restored the affinity values for Abeta peptides and resulted in preferential binding of apoE3. The data demonstrate that native lipid-associated apoE3 binds to Abeta peptides with 2-3-fold higher affinity than lipid-associated apoE4. Since the isoforms' binding efficiency correlate inversely with the risk of developing late-onset AD, the results suggest a possible involvement of apoE3 in the clearance or routing out of Abeta from the central nervous system as one of the mechanisms underlying the pathology of the disease.


CGRP and its receptors provide new insights into migraine pathophysiology.
Over the past 300 years, the migraine field has been dominated by two main theories-the vascular theory and the central neuronal theory. The success of vasoconstrictors such as ergotamine and the triptans in treating acute migraine bolstered the vascular theory, but evidence is now emerging that vasodilatation is neither necessary nor sufficient to induce a migraine attack. Attention is now turning to the core migraine circuits in the brain, which include the trigeminal ganglia, trigeminal nucleus, medullary modulatory regions, pons, periaqueductal gray matter, hypothalamus and thalamus. Migraine triggers are likely to reflect a disturbance in overall balance of the circuits involved in the modulation of sensory activity, particularly those with relevance to the head. In this Review, we consider the evidence pointing towards a neuronal mechanism in migraine development, highlighting the role of calcitonin gene-related peptide (CGRP), which is found in small to medium-sized neurons in the trigeminal ganglion. CGRP is released during migraine attacks and can trigger migraine in patients, and CGRP receptor antagonists can abort migraine. We also examine whether other drugs, such as triptans, might exert their antimigraine effects via their actions on the neuronal circuit as opposed to the intracranial vasculature.


Design principles for electronic charge transport in solution-processed vertically stacked 2D perovskite quantum wells.
State-of-the-art quantum-well-based devices such as photovoltaics, photodetectors, and light-emission devices are enabled by understanding the nature and the exact mechanism of electronic charge transport. Ruddlesden-Popper phase halide perovskites are two-dimensional solution-processed quantum wells and have recently emerged as highly efficient semiconductors for solar cell approaching 14% in power conversion efficiency. However, further improvements will require an understanding of the charge transport mechanisms, which are currently unknown and further complicated by the presence of strongly bound excitons. Here, we unambiguously determine that dominant photocurrent collection is through electric field-assisted electron-hole pair separation and transport across the potential barriers. This is revealed by in-depth device characterization, coupled with comprehensive device modeling, which can self-consistently reproduce our experimental findings. These findings establish the fundamental guidelines for the molecular and device design for layered 2D perovskite-based photovoltaics and optoelectronic devices, and are relevant for other similar quantum-confined systems.


Presence of human papilloma virus, herpes simplex virus and Epstein-Barr virus DNA in oral biopsies from Sudanese patients with regard to toombak use.
Using PCR/DNA sequencing, we investigated the prevalence of human papillomavirus (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) DNA in brush biopsies obtained from 150 users of Sudanese snuff (toombak) and 25 non-users of toombak in formalin-fixed paraffin-embedded tissue samples obtained from 31 patients with oral dysplasias (25 toombak users and 6 non-users), and from 217 patients with oral cancers (145 toombak users and 72 non-users). In the brush tissue samples from toombak users, HPV was detected in 60 (40%), HSV in 44 (29%) and EBV in 97 (65%) of the samples. The corresponding figures for the 25 samples from non-users were 17 (68%) positive for HPV, 6 (24%) positive for HSV and 21 (84%) for EBV. The formalin-fixed samples with oral dysplasias were all negative for HPV. In the 145 oral cancer samples from toombak users, HPV was detected in 39 (27%), HSV in 15 (10%) and EBV in 53 (37%) of the samples. The corresponding figures for the samples from non-users were 15 (21%) positive for HPV, 5 (7%) for HSV and 16 (22%) for EBV. These findings illustrate that prevalence of HSV, HPV and EBV infections are common and may influence oral health and cancer development. It is not obvious that cancer risk is increased in infected toombak users. These observations warrant further studies involving toombak-associated oral lesions, to uncover the possible mechanisms of these viral infections in the development of oral cancer, and the influence of toombak on these viruses.


Plasmonic nanoparticle simulations and inverse design using machine learning.
Collective oscillation of quasi-free electrons on the surface of metallic plasmonic nanoparticles (NPs) in the ultraviolet to near-infrared (NIR) region induces a strong electromagnetic enhancement around the NPs, which leads to numerous important applications. These interesting far- and near-field optical characteristics of the plasmonic NPs can be typically obtained from numerical simulations for theoretical guidance of NP design. However, traditional numerical simulations encounter irreconcilable conflicts between the accuracy and speed due to the high demand of computing power. In this work, we utilized the machine learning method, specifically the deep neural network (DNN), to establish mapping between the far-field spectra/near-field distribution and dimensional parameters of three types of plasmonic NPs including nanospheres, nanorods, and dimers. After the training process, both the forward prediction of far-field optical properties and the inverse prediction of on-demand dimensional parameters of NPs can be accomplished accurately and efficiently with the DNN. More importantly, we have achieved for the first time ultrafast and accurate prediction of two-dimensional on-resonance electromagnetic enhancement distributions around NPs by greatly reducing the amount of electromagnetic data via screening and resampling methods. These near-field predictions can be realized typically in less than 10-2 seconds on a laptop, which is 6 orders faster than typical numerical simulations implemented on a server. Therefore, we demonstrate that the DNN is an ultrafast, highly efficient, and computing resource-saving tool to investigate the far- and near-field optical properties of plasmonic NPs, especially for a number of important nano-optical applications such as surface-enhanced Raman spectroscopy, photocatalysis, solar cells, and metamaterials.


Synthesis of marine polycyclic polyethers via endo-selective epoxide-opening cascades.
The proposed biosynthetic pathways to ladder polyethers of polyketide origin and oxasqualenoids of terpenoid origin share a dramatic epoxide-opening cascade as a key step. Polycyclic structures generated in these biosynthetic pathways display biological effects ranging from potentially therapeutic properties to extreme lethality. Much of the structural complexity of ladder polyether and oxasqualenoid natural products can be traced to these hypothesized cascades. In this review we summarize how such epoxide-opening cascade reactions have been used in the synthesis of ladder polyethers and oxasqualenoid natural products.


Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia.
Myopia, or nearsightedness, is the most common eye disorder, resulting primarily from excess elongation of the eye. The etiology of myopia, although known to be complex, is poorly understood. Here we report the largest ever genome-wide association study (45,771 participants) on myopia in Europeans. We performed a survival analysis on age of myopia onset and identified 22 significant associations ([Formula: see text]), two of which are replications of earlier associations with refractive error. Ten of the 20 novel associations identified replicate in a separate cohort of 8,323 participants who reported if they had developed myopia before age 10. These 22 associations in total explain 2.9% of the variance in myopia age of onset and point toward a number of different mechanisms behind the development of myopia. One association is in the gene PRSS56, which has previously been linked to abnormally small eyes; one is in a gene that forms part of the extracellular matrix (LAMA2); two are in or near genes involved in the regeneration of 11-cis-retinal (RGR and RDH5); two are near genes known to be involved in the growth and guidance of retinal ganglion cells (ZIC2, SFRP1); and five are in or near genes involved in neuronal signaling or development. These novel findings point toward multiple genetic factors involved in the development of myopia and suggest that complex interactions between extracellular matrix remodeling, neuronal development, and visual signals from the retina may underlie the development of myopia in humans.


VALIDATION OF A HEMATOLOGY ANALYZER IN DONKEY MEDICINE.
Asinina de Miranda is a protected donkey sub-species from the Mirandês plateau in northeastern of Portugal. Donkeys are animals that have substantially lost their place as working animals in modern society, this had led to a decrease in their population numbers. A need to preserve native species has led to the foundation of organizations like Associação para o Estudo e Proteção do Gado Asinino (AEPGA) and the development of studies regarding breed welfare, such as hematology. The IDEXX ProCyte Dx is a veterinary hematology analyzer validated for several species, but not for donkeys. The aim of this study was to validate the ProCyte Dx for Asinina de Miranda donkeys. The validation requires a controlled study of precision, carryover, linearity and comparison between the equipment and the manually obtained values for the leukocyte differential count and hematocrit. Results indicated coefficient of variation was good (below 5%) for both the intra-assay and the inter-assay precision, except for basophils. Carryover was 0% for all the parameters except platelets (5.88%). Linearity showed a very high Pearson correlation coefficient, above 0.99, for erythrocytes, hematocrit, hemoglobin, leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, platelets and plateletcrit. Comparison demonstrated excellent agreement for hematocrit (rs=0.96) and good Spearman rank correlation for neutrophils (rs=0.84) and lymphocytes (rs=0.90). Accuracy for total leukocyte count and platelets could not be determined. In conclusion, the ProCyte Dx seems appropriate to be used in Asinina de Miranda hematology.


Cellular proton dynamics in Elodea canadensis leaves induced by cadmium.
Our earlier investigations showed that Elodea canadensis shoots, grown in the presence of cadmium (Cd), caused basification of the surrounding medium. The present study was aimed to examine the proton dynamics of the apoplastic, cytosolic and vacuolar regions of E. canadensis leaves upon Cd exposure and to establish possible linkage between cellular pH changes and the medium basification. The changes in cytosolic calcium [Ca(2+)]cyt was also investigated as the [Ca(2+)]cyt and [pH]cyt homeostasis are closely linked. The cellular H(+) and Ca(2+) concentrations were monitored by fluorescence microscopy and ion-specific fluorescent dyes. Cadmium concentration of leaf-cell walls was measured after plant cultivation at different fixed levels of starting pH. The protoplasts from E. canadensis leaves were isolated by use of a newly developed enzymatic method. Upon Cd addition, both cytosolic and vacuolar pH of leaf protoplasts increased with a concomitant rise in the cytosolic Ca(2+) concentration. Time course studies revealed that changes in [Ca(2+)]cyt and [pH]cyt followed similar dynamics. Cadmium (0.5 μM) exposure decreased the apoplastic pH by 0.85 units. The maximum cell wall bound Cd-contents were obtained in plants grown at low starting pH. It is concluded that Cd treatment causes apoplastic acidosis in E. canadensis leaves associated with enhanced Cd binding to the cell walls and, consequently, reduced Cd influx into the cytosol.


Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.
Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation.


Seizure characteristics and prognostic factors of gliomas.
Epilepsy in neuroepithelial tumors is highly prevalent. Neurogliomas (dysembryoplastic neuroepitheliomas [DNETs] and gangliogliomas) have a seizure incidence of 80-100%, low-grade gliomas of 60-85%, and glioblastoma of 30-60%. With each type, the appearance of seizures is usually the presenting clinical symptom, and with neuroglial tumors often the only clinical sign. Tumor locations in the temporal and insular cortex are associated with a higher risk of developing epilepsy in both neuroglial tumors and low-grade gliomas. Focal seizures with or without alteration of consciousness and/or secondary generalization are common. Focal seizures with altered consciousness are present in 50-70% of neuroglial tumors, and secondarily generalized seizures in 70% of low-grade gliomas. Surgical treatment, particularly gross tumor resection, contributes strongly to seizure freedom, especially in neuroglial tumors. Refractory epilepsy is more common in low-grade gliomas, occurring in 30-35%. Recurrence or worsening of seizures is often associated with tumor recurrence in glioblastomas. Translational studies have revealed a strong prevalence of IDH1 enzyme mutation together with the presence of seizures and long-term survival in low-grade gliomas. Disturbances of glutamate metabolism occur both in low-grade tumors and glioblastomas, and provide insight into mutual cellular pathway abnormalities contributing to both seizure development and tumor growth. Likewise, the recent clinical observations on antitumor activity of the anticonvulsant valproic acid in glioblastoma now provide promising outlooks on single therapies that target both seizures and gliomas.


Lymphocyte-rich gastric cancer: associations with Epstein-Barr virus, microsatellite instability, histology, and survival.
Lymphocyte-rich gastric carcinomas may have a better prognosis than cancers without a pronounced host inflammatory response. Two subsets of gastric cancer-Epstein-Barr virus-positive and microsatellite instability high-have been associated with a lymphocyte-rich phenotype. We assessed relationships between tumor-infiltrating lymphocytes, Epstein-Barr virus status, microsatellite instability status, and cancer-specific survival in 110 resected gastric cancers. Seven patients had Epstein-Barr virus-positive cancer, including 4 (3.7%) of 107 consecutive patients. Tumors from 17 patients (16%) were designated microsatellite instability high on the basis of negative immunohistochemical staining for MLH1; all tumors had intact expression of MSH2 and MSH6. Epstein-Barr virus-positive cancers had increased tumor-infiltrating lymphocytes compared with Epstein-Barr virus-negative cancers (median 450/10 HPF versus 21/10 HPF, P <.001). Microsatellite instability-high cancers also had increased tumor-infiltrating lymphocytes compared with non-microsatellite instability-high cancers (median 150/10 HPF versus 20/HPF, P <.001). Microsatellite instability-high cancers affected older patients and were more likely to be intestinal in the Lauren classification and expanding in the Ming classification. By univariate analysis, decreased risk of death from gastric cancer was significantly associated with low tumor stage, expanding growth pattern, increasing tumor-infiltrating lymphocyte count, and microsatellite instability-high status. High tumor-infiltrating lymphocyte count and microsatellite instability-high status retained statistical significance as favorable prognostic factors after adjustment for tumor stage in multivariate analysis. Tumor-infiltrating lymphocyte count retained statistical significance as a favorable prognostic factor after adjustment for microsatellite instability-high status; but microsatellite instability-high status did not remain a significant independent prognosticator after adjustment for tumor-infiltrating lymphocyte count. The association between microsatellite instability-high cancers and high tumor-infiltrating lymphocyte counts may account for the association of microsatellite instability-high gastric cancers with improved survival.


Childhood emotional abuse and neglect as predictors of psychological and physical symptoms in women presenting to a primary care practice.
There were two aims to this study: first to examine whether emotional abuse and neglect are significant predictors of psychological and somatic symptoms, and lifetime trauma exposure in women presenting to a primary care practice, and second to examine the strength of these relationships after controlling for the effects of other types of childhood abuse and trauma. Two-hundred and five women completed the Childhood Trauma Questionnaire (Bernstein et al., 1994), Trauma History Questionnaire (Green, 1996), the Symptom Checklist-revised (Derogatis, 1997), and the Revised Civilian Mississippi Scale for posttraumatic stress disorder (Norris & Perilla, 1996) when presenting to their primary care physician for a visit. Hierarchical multiple regression analyses were conducted to examine unique contributions of emotional abuse and neglect variables on symptom measures while controlling for childhood sexual and physical abuse and lifetime trauma exposure. A history of emotional abuse and neglect was associated with increased anxiety, depression, posttraumatic stress and physical symptoms, as well as lifetime trauma exposure. Physical and sexual abuse and lifetime trauma were also significant predictors of physical and psychological symptoms. Hierarchical multiple regressions demonstrated that emotional abuse and neglect predicted symptomatology in these women even when controlling for other types of abuse and lifetime trauma exposure. Long-standing behavioral consequences may arise as a result of childhood emotional abuse and neglect, specifically, poorer emotional and physical functioning, and vulnerability to further trauma exposure.


Self-recognition deficits in schizophrenia patients with auditory hallucinations: a meta-analysis of the literature.
Theories about auditory hallucinations in schizophrenia suggest that these experiences occur because patients fail to recognize thoughts and mental events as self-generated. Different theoretical models have been proposed about the cognitive mechanisms underlying auditory hallucinations. Regardless of the cognitive model being tested, however, experimental designs are almost identical in that they require a judgment regarding whether an action was self-originated or not. The aim of the current study was to integrate all available literature for a meta-analysis on this topic and reach conclusions about self-recognition performance in (1) patients with schizophrenia compared with healthy controls and (2) patients with auditory hallucinations compared with patients without these symptoms. A comprehensive literature review identified 23 studies that contrasted the performance of schizophrenia patients with healthy controls (1370 participants) and 9 studies that directly compared patients with and without auditory hallucinations (315 participants). We found significantly reduced self-recognition performance in schizophrenia patients, which was more pronounced in patients with auditory hallucinations compared with patients without. In patients with hallucinations, this pattern of performance was specific to self-recognition processes and not to the recognition of new external information. A striking finding was the homogeneity in results across studies regardless of the action modality, timing delay, and design used to measure self-recognition. In summary, this review of studies from the last 30 years substantiates the view that self-recognition is impaired in patients with schizophrenia and particularly those with auditory hallucinations. This suggests an association, perhaps a causal one, between such deficit and hallucinatory experiences in schizophrenia.


Staphylococcus lugdunensis bacteremia and endocarditis treated with cefazolin and rifampin.
This case report describes the treatment of a rare infection caused by Staphylococcus lugdunensis with cefazolin and rifampin. A 48-year-old man with significant comorbidities was admitted to our institution with complaints of malaise, shortness of breath, and vague persistent pain. He was diagnosed with S. lugdunensis infective endocarditis and was treated with cefazolin continuous infusion for 10 days without resolution of bacteremia. As surgical intervention was deemed inappropriate, rifampin was added to the treatment regimen for its antibiofilm activity. After rifampin initiation, resolution of bacteremia was rapidly achieved. Subsequent blood cultures remained negative, and the patient was discharged home in stable condition to complete six weeks of i.v. cefazolin and rifampin therapy. The patient continued treatment, as documented by the infusion center, weekly for five weeks. The patient was rehospitalized during his sixth week of treatment due to impending respiratory failure, whereupon he was intubated and admitted to the intensive care unit. The patient's cardiac status gradually worsened over the following days, and he ultimately died. Blood cultures from days 1 and 2 of hospitalization revealed no bacterial growth at five days. Cefazolin and rifampin therapy in a hospitalized patient with bacteremia and aortic valve endocarditis caused by S. lugdunensis resulted in rapid eradication of the bacteremia. After more than five weeks of cefazolin-rifampin treatment, the patient was rehospitalized with worsening cardiac function and died. Blood cultures during the second admission were negative.


Condom-use self-efficacy as a mediator between syndemics and condomless sex in men who have sex with men (MSM).
Among men who have sex with men (MSM), HIV sexual risk and poor self-care behavior is associated with syndemics, or co-occurring psychosocial problems. Though prior research has demonstrated an additive total effect of syndemics on HIV risk behavior and infection, mostly within cross-sectional designs, it is possible that these associations are not direct but rather that syndemics disrupt relevant individual-level mediating psychological variables. One of the more common individual-level psychological variables that predicts health behavior generally, and HIV risk behavior specifically, is self-efficacy. This study sought to examine the potential effects of syndemics on condomless sex via condom-use self-efficacy as an intermediary variable. In high-risk MSM (N = 197), across 3 time points (baseline, 3 months, and 6 months) we used latent growth curve modeling to test the degree to which self-efficacy mediated the relationship between syndemics (heavy alcohol use, substance use disorder, sexual compulsivity, depression, social anxiety, intimate partner violence, childhood sexual abuse) and condomless anal sex. The baseline analyses were consistent with an indirect effect of the association between syndemics and condomless sex through self-efficacy. Prospective longitudinal mediation was partially supported, such that baseline syndemics were associated with lower baseline self-efficacy, which in turn predicted higher increases in condomless anal sex across time. These findings provide preliminary evidence (due to the partial support for the longitudinal model) that syndemics themselves may not be directly causal in their association with condomless sex, but the association may be through modifiable social-cognitive mechanisms such as condom self-efficacy. (PsycINFO Database Record


Ask dying adults about their spiritual beliefs.
Essential facts Religion should be included in the vital discussions about the care people and those close to them want to receive in the last two to three days of life, according to the National Institute for Health and Care Excellence (NICE).


Sources of sediment and phosphorus in stream flow of a highly productive dairy farmed catchment.
Both sediment and phosphorus (P) are important contaminants for surface water quality. Knowing the main sources of sediment and P loss within agricultural catchments enables mitigation practices to be better targeted. With this in mind seasonal loads of suspended sediment (SS), dissolved reactive P (DRP), total P (TP), and bioavailable P (BAP) were measured in a low gradient stream draining an intensively farmed New Zealand dairying catchment. Integrating in situ samplers were deployed to collect samples and the results merged with continuous flow data to calculate seasonal loads during 2005 through 2006. Flow rate, SS, and TP concentrations peaked in winter-spring and were lowest in summer-autumn. Concentrations of BAP in trapped sediment were greatest in autumn, contrasting with winter and spring when greater amounts of sediment were trapped, but with lower P enrichment. Analysis of (137)Cs and mixing model output showed that a major source of sediment and associated P in winter and spring was stream banks. Possible causes for this include trampling and destabilization by stock, channel straightening and sediment removal, and removal of riparian trees that stabilize banks. Modelling indicated that overland flow probably from topsoil (but could include sediment from lanes) contributed most sediment during summer and autumn. Remediation aimed at decreasing particulate P inputs to streams should focus on riparian protection measures, such as permanent stock exclusion and planting with shrubs and trees, ensuring runoff from lanes is minimized, and decreasing Olsen P to nearer optimum agronomic levels.


Chronic exposure to low levels of antigen in the periphery causes reversible functional impairment correlating with changes in CD5 levels in monoclonal CD8 T cells.
This study describes a double-transgenic model in which monoclonal CD8 F5 T cells are chronically exposed to self Ag (nucleoprotein) in the periphery, but are not affected during thymic development. Chronic exposure of CD8 T cells to their cognate Ag rendered them unable to proliferate or produce cytokines in response to antigenic stimulation in vitro. However, the cells still retained some killer function in vivo and continuously eliminated APC expressing high levels of Ag. In addition, when crossed with mice expressing Ag in the anterior pituitary gland (triple-transgenic mice), F5 T cells migrated to this site and killed growth hormone producing somatotrophs. The anergic state was reversible upon transfer into Ag-free recipients, resulting in full recovery of in vitro responsiveness to Ag. Anergic CD8 T cells express higher levels of CD5, a negative regulator of T cell signaling, whereas after transfer and residence in Ag-free hosts, CD5 levels returned to normal. This suggests that up-regulation of negative T cell regulators in peripheral T cells exposed to chronic stimulation by Ag may prevent full functionality and thus avoid overt autoreactivity.


Neurovegetative symptom subtypes in young people with major depressive disorder and their structural brain correlates.
Depression is a leading cause of burden of disease among young people. Current treatments are not uniformly effective, in part due to the heterogeneous nature of major depressive disorder (MDD). Refining MDD into more homogeneous subtypes is an important step towards identifying underlying pathophysiological mechanisms and improving treatment of young people. In adults, symptom-based subtypes of depression identified using data-driven methods mainly differed in patterns of neurovegetative symptoms (sleep and appetite/weight). These subtypes have been associated with differential biological mechanisms, including immuno-metabolic markers, genetics and brain alterations (mainly in the ventral striatum, medial orbitofrontal cortex, insular cortex, anterior cingulate cortex amygdala and hippocampus). K-means clustering was applied to individual depressive symptoms from the Quick Inventory of Depressive Symptoms (QIDS) in 275 young people (15-25 years old) with MDD to identify symptom-based subtypes, and in 244 young people from an independent dataset (a subsample of the STAR*D dataset). Cortical surface area and thickness and subcortical volume were compared between the subtypes and 100 healthy controls using structural MRI. Three subtypes were identified in the discovery dataset and replicated in the independent dataset; severe depression with increased appetite, severe depression with decreased appetite and severe insomnia, and moderate depression. The severe increased appetite subtype showed lower surface area in the anterior insula compared to both healthy controls. Our findings in young people replicate the previously identified symptom-based depression subtypes in adults. The structural alterations of the anterior insular cortex add to the existing evidence of different pathophysiological mechanisms involved in this subtype.


Significance and value of non-traded ecosystem services on farmland.
Background. Ecosystem services (ES) generated within agricultural landscapes, including field boundaries, are vital for the sustainable supply of food and fibre. However, the value of ES in agriculture has not been quantified experimentally and then extrapolated globally. Methods. We quantified the economic value of two key but contrasting ES (biological control of pests and nitrogen mineralisation) provided by non-traded non-crop species in ten organic and ten conventional arable fields in New Zealand using field experiments. The arable crops grown, same for each organic and conventional pair, were peas (Pisum sativum), beans (Phaseolus vulgaris), barley (Hordeum vulgare), and wheat (Triticum aestivum). Organic systems were chosen as comparators not because they are the only forms of sustainable agriculture, but because they are subject to easily understood standards. Results. We found that organic farming systems depended on fewer external inputs and produced outputs of energy and crop dry matter generally less than but sometimes similar to those of their conventional counterparts. The economic values of the two selected ES were greater for the organic systems in all four crops, ranging from US$ 68-200 ha(-1) yr(-1) for biological control of pests and from US$ 110-425 ha(-1)yr(-1) for N mineralisation in the organic systems versus US$ 0 ha(-1)yr(-1) for biological control of pests and from US$ 60-244 ha(-1)yr(-1) for N mineralisation in the conventional systems. The total economic value (including market and non-market components) was significantly greater in organic systems, ranging from US$ 1750-4536 ha(-1)yr(-1), with US$ 1585-2560 ha(-1)yr(-1) in the conventional systems. The non-market component of the economic value in organic fields was also significantly higher than those in conventional fields. Discussion. To illustrate the potential magnitude of these two ES to temperate farming systems and agricultural landscapes elsewhere, we then extrapolate these experimentally derived figures to the global temperate cropping area of the same arable crops. We found that the extrapolated net value of the these two services provided by non-traded species could exceed the combined current global costs of pesticide and fertiliser inputs, even if utilised on only 10% of the global arable area. This approach strengthens the case for ES-rich agricultural systems, provided by non-traded species to global agriculture.