Organ-specific small non-coding RNA responses in domestic (Sudani) ducks experimentally infected with highly pathogenic avian influenza virus (H5N1).
The duck represents an important reservoir of influenza viruses for transmission to other avian and mammalian hosts, including humans. The increased pathogenicity of the recently emerging clades of highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype in ducks features systemic viral spread and organ-to-organ variation in viral transcription and tissue damage. We previously reported that experimental infection of Sudani ducks (Cairina moschata) with an Egyptian HPAI (H5N1) virus (clade 18.104.22.168) features high viral replication and severe tissue damage in lung, but lower viral replication and only mild histological changes in brain. Little is known about the involvement of miRNA in organ-specific responses to H5N1 viruses in ducks, and involvement of the other classes of small noncoding RNA (sncRNA) has not been investigated so far. Following RNA sequencing, we have annotated the duck sncRNome and compared global expression changes of the four major sncRNA classes (miRNAs, piRNAs, snoRNAs, snRNAs) between duck lung and brain during a 120 h time course of infection with this HPAI strain. We find major organ-specific differences in miRNA, piRNA and snoRNA populations even before infection and substantial reprogramming of all sncRNA classes throughout infection, which was less pronounced in brain. Pathway prediction analysis of miRNA targets revealed enrichment of inflammation-, infection- and apoptosis-related pathways in lung, but enrichment of metabolism-related pathways (including tryptophan metabolism) in brain. Thus, organ-specific differences in sncRNA responses may contribute to differences in viral replication and organ damage in ducks infected with isolates from this emerging HPAI clade, and likely other strains.


Is K-O Tab 1-2-3((R)) long lasting on non-polyester mosquito nets?
Many societies use locally sourced mosquito nets made from a variety of materials. For protecting against malaria these require regular re-treatment with insecticide. K-O Tab 1-2-3 is a 'dip-it-yourself' long-lasting formulation with time-limited interim recommendation from WHO for treatment of washed white and coloured polyester nets for up to 15 washes. To determine wash-resistance on different fabrics, nets made of polyester, polyethylene, cotton or nylon were treated with K-O Tab 1-2-3 and washed up to 20 times using standard WHO washing procedures. Efficacy was assessed using cone and cylinder bioassays and tunnel tests, and deltamethrin content using high-pressure liquid chromatography. Polyethylene and cotton nets treated with K-O Tab 1-2-3 and washed 20 times achieved the WHO threshold of >80% mortality in tunnel tests. Polyethylene matched the performance of polyester in all bioassays in contrast to cotton and nylon which produced low mortality and knock-down in cone and cylinder bioassays. After 20 washes 16.5% of the loading dose of deltamethrin remained on the polyester nets compared with 28.7% on polyethylene, 38.9% on cotton and 2.2% on nylon. Cotton nets retained a high concentration of insecticide but the relatively poor performance in terms of knock-down and mortality suggest most insecticide is bound within the cotton fibres rather than on the surface. K-O Tab 1-2-3 renders insecticide wash fast on polyethylene nets, less so on cotton and nylon. Nets made from polyethylene can be treated in the home to render the insecticide long lasting.


The novel approach to enhance seed security: dual anti-counterfeiting methods applied on tobacco pelleted seeds.
Seed security is of prime importance for agriculture. To protect true seeds from being faked, more secure dual anti-counterfeiting technologies for tobacco (Nicotiana tabacum L.) pelleted seed were developed in this paper. Fluorescein (FR), rhodamine B (RB), and magnetic powder (MP) were used as anti-counterfeiting labels. According to their different properties and the special seed pelleting process, four dual-labeling treatments were conducted for two tobacco varieties, MS Yunyan85 (MSYY85) and Honghua Dajinyuan (HHDJY). Then the seed germination and seedling growth status were investigated, and the fluorescence in cracked pellets and developing seedlings was observed under different excitation lights. The results showed that FR, RB, and MP had no negative effects on the germination, seedling growth, and MDA content of the pelleted seeds, and even some treatments significantly enhanced seedling dry weight, vigor index, and shoot height in MS YY85, and increased SOD activity and chlorophyll content in HHDJY as compared to the control. In addition, the cotyledon tip of seedlings treated with FR and MP together represented bright green fluorescence under illumination of blue light (478 nm). And the seedling cotyledon vein treated with RB and MP together showed red fluorescence under green light (546 nm). All seeds pelleted with magnetic powder of proper concentration could be attracted by a magnet. Thus, it indicated that those new dual-labeling methods that fluorescent compound and magnetic powder simultaneously applied in the same seed pellets definitely improved anti-counterfeiting technology and enhanced the seed security. This technology will ensure that high quality seed will be used in the crop production.


[Iron-sulfur respiratory chain centers, ribonucleotide reductase activity and biosynthesis of macromolecules in the spleen of mice during acute radiation injury].
The functional status of iron-sulphur centers (ISC) of mitochondrial electron transport chain, ribonucleotide reductase (RR) activity and macromolecule biosynthesis in mouse spleen were studied during acute radiation sickness induced by whole-body gamma-irradiation of mice with a dose of 6 Gy. The ESR signal of active RR was registered in the spleen; the RR activity dynamics during acute radiation sickness was described. The RR activity was inhibited at early post-irradiation times (from 30 min to 12 h). Drastic inhibition of DNA biosynthesis and stimulation of transcription were registered. The increase in the RR activity and ISC content, which occurred 1-3 days following irradiation, was associated with the increase in the rate of protein biosynthesis.


Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke.
Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer's disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown. Adult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery. Choroid plexus tissues were collected and analyzed for Vcam1, Madcam1, Cx3cl1, Ccl2, Nt5e, and Ifnγ expression at different timepoints after stroke using qPCR. Changes of MDMs in CP and cerebrospinal fluid (CSF) at 1 day and 3 days after stroke were analyzed using flow cytometry. Infiltration of MDMs into CP and CSF were validated using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. CD115+ monocytes were isolated using a magnetic cell separation system from bone marrow of Cx3cr1-GFP or wild-type C57BL/6 donor mice. The freshly isolated monocytes or M2-like MDMs primed in vitro with IL4 and IL13 were stereotaxically injected into the lateral ventricle of stroke-affected mice to trace for their migration into ischemic hemisphere or to assess their effect on post-stroke recovery using open field, corridor, and active avoidance behavioral tests. We found that CP responded to cortical stroke by upregulation of gene expression for several possible mediators of MDM trafficking and, concomitantly, MDMs increased in CP and cerebrospinal fluid (CSF). We then confirmed that MDMs infiltrated from blood into CP and CSF after the insult using β-actin-GFP chimeric mice and Fgd5-CreERT2 x Lox-stop-lox-Tomato mice. When MDMs were directly administered into CSF following stroke, they homed to the ischemic hemisphere. If they had been primed in vitro prior to their administration to become M2-like macrophages, they promoted post-stroke recovery of motor and cognitive function without influencing infarct volume. Our findings suggest the possibility that autologous transplantation of M2-like MDMs into CSF might be developed into a new strategy for promoting recovery also in patients with stroke.


Sustained attention across toddlerhood: The roles of language and sleep.
The present study examined individual differences in the development of sustained attention across toddlerhood, as well as how these individual differences related to the development of language and sleep. Toddlers (N = 314; 54% male) were assessed at 30, 36, and 42 months using multiple measures of attention, a standardized language assessment, and actigraphic measures of sleep. Toddlers were 80% White. Family socioeconomic status (SES) was calculated using the Hollingshead Four Factor Index and ranged from 13 to 66 (M = 47.59, SD = 14.13). Aims were (a) to examine associations between measures of attention across situations, informants, and time; (b) to consider the independent and interactive effects of language and sleep on attention; and (c) to test potential bidirectional associations between sleep and attention. Findings showed attention measures were stable across time but were only weakly linked with each other at 42 months. Attention was consistently linked with language. More variable sleep and longer naps were associated with less growth in sustained attention across time. Nighttime sleep duration interacted with language in that sleep duration was positively associated with attention scores among toddlers with less advanced language, even when SES was controlled. The findings describe an understudied aspect of how sustained attention develops, involving the main effect of consistent sleep schedules and the interaction effect of amount of sleep and child language development. These findings are relevant to understanding early childhood risk for developing attention problems and to exploring a potential prevention target in family sleep practices. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


The influence of single molar crown placement on the smoothness of masticatory movement.
The jerk-cost is an index that can quantify the smoothness of various movements including human body movements. A previous study reported the usefulness of jerk-cost in the evaluation of masticatory movement, and proposed that the masticatory movement of subjects with good occlusion could be explained as a maximum smooth movement. The purpose of this study was to investigate the influence of a single prosthetic molar restoration on the smoothness of masticatory movement. Fourteen adults who visited this hospital seeking a single prosthetic restoration on a molar were selected. Each subject chewed a piece of chewing gum on the molars of the treated side before and after crown placement. Movement trajectory was recorded using the Sirognathograph Analyzing System. Normalized jerk-cost (NJC) was calculated on the closing phase of each chewing cycle and was compared before and after the crown placement. After the prosthetic restoration, NJC significantly decreased (P < 0.05) in seven subjects with a crown placed on a lower molar, whereas significant changes were not observed in seven subjects with a crown placed on an upper molar. These results suggest that restoring a crown on a lower molar could significantly improve the smoothness of masticatory movement on the same side.


Synergistic potentiation of 5-hydroxytryptamine secretion by platelet agonists and phorbol myristate acetate despite inhibition of agonist-induced arachidonate/thromboxane and beta-thromboglobulin release and Ca2+ mobilization by phorbol myristate acetate.
Previous studies have demonstrated an inhibition of agonist-induced inositol phospholipid breakdown and intracellular Ca2+ ([Ca2+]i) mobilization by phorbol esters in platelets. In this study, we have examined the effect of phorbol 12-myristate 13-acetate (PMA) on agonist-induced granule secretion and correlated it with agonist-induced [Ca2+]i mobilization, arachidonate and thromboxane (Tx) release in human platelets. With increasing times of incubation with PMA (10 s-5 min), the rise in [Ca2+]i induced by thrombin and the TxA2 mimetic, U46619, was increasingly inhibited (90-100% with 5 min incubation) and, correlating with this, thrombin-induced [3H]arachidonate, TxB2 and beta-thromboglobulin (beta TG) release were also inhibited. In addition, the conversion of exogenously added arachidonate to TxB2 was inhibited (50-80%) by a 10 s-5 min pretreatment with PMA. However, secretion of 5-hydroxy[14C]tryptamine (5HT) induced by thrombin or U46619 was not inhibited by 10 s-2 min incubations with PMA and, on the contrary, with low agonist concentrations, was potentiated by PMA in the absence of a significant rise in [Ca2+]i or endogenous Tx formation, to levels significantly greater than or equal to the sum of that obtained when agonist and PMA were added separately. With longer times of incubation with PMA (5 min), these synergistic effects became less pronounced as inhibitory effects of PMA on agonist-induced [14C]5HT secretion became apparent. The results indicate that, while PMA may cause an inhibition of agonist-induced [Ca2+]i mobilization resulting in an inhibition of agonist-induced arachidonate, TxB2 and beta TG release, its effects on agonist-induced 5HT secretion may be complicated by [Ca2+]i-independent synergistic effects of agonist and PMA.


Effects of Metabolic Syndrome and its components on the postoperative recurrence in Chronic Rhinosinusitis with Nasal Polyps' patients.
Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (p < 0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (p < 0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (p < 0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (p < 0.05). Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. Level 4.


Preoperative Treatment of Obstructive Sleep Apnea With Positive Airway Pressure is Associated With Decreased Incidence of Atrial Fibrillation After Cardiac Surgery.
Based on clinical studies in the nonsurgical population that positive airway pressure (PAP) therapy for patients with obstructive sleep apnea (OSA) provides benefits for those with atrial fibrillation, the authors tested the hypothesis that PAP in patients with OSA reduces the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery. Retrospective analysis. Single-center university hospital. The study comprised 192 patients in sinus rhythm preoperatively who were undergoing nontransplantation or ventricular assist device implantation cardiac surgery requiring cardiopulmonary bypass but not requiring systemic circulatory arrest, with documented PAP adherence from January 2008 to October 2015. Retrospective review of medical records. POAF was defined as atrial fibrillation requiring therapeutic intervention. Of the 192 patients with OSA, 104 (54%) were documented to be PAP-adherent and 88 (46%) were reported to be PAP-nonadherent. Among PAP users, 49 (47%) developed POAF; among PAP nonusers, 59 (66%) developed POAF. The adjusted hazard ratio was 0.59 (95% confidence interval 0.40-0.86, p<0.01). No differences were observed in intensive care unit length of stay (4.0±3.4 days for PAP-adherent group v 5.0±6.2 days for PAP-nonadherent group; p = 0.22) or hospital length of stay (10.7±6.6 days for PAP-adherent group v 10.9±7.3 days for PAP nonadherent group; p = 0.56). A lower median postoperative creatinine rise was observed in PAP-adherent patients (18.2% [8.3%-37.5%) v 31.3% [13.3%-50%]; p< 0.01). Preoperative PAP use in patients with OSA was associated with a decreased rate of POAF after cardiac surgery.


Improving the image quality of 3D FLAIR with a spiral MRI technique.
Fluid-attenuated inversion recovery (FLAIR) nulls the CSF signal and is widely used in neuro MRI exams. A 3D scan can provide high SNR, contiguous coverage, and reduced sensitivity to through-plane CSF flow. In this work, a 3D spiral FLAIR technique is proposed to improve the image quality of conventional 3D Cartesian FLAIR. The 3D spiral FLAIR sequence incorporated a spiral-in/out readout to preserve higher scan efficiency and eliminate off resonance-induced artifacts observed with a commonly implemented spiral-out readout, a compensation approach to minimize phase errors due to the concomitant fields accompanying the spiral gradient, and an adapted variable flip angle scheme to preserve scan efficiency and maintain a long and stable echo train. 3D Cartesian and spiral FLAIR (~6 min each) were acquired on a 3 Tesla scanner from 6 subjects (age range: 31-64 years; mean: 39.5). Two neuroradiologists rated the images in a blinded fashion on a 5-point scale. The noise performance was assessed quantitatively. Compared to 3D Cartesian FLAIR, 3D spiral FLAIR exhibits greater reduction of artifacts from CSF, especially anterior to the brain stem (rated better in 4 cases), artifacts attributed to blood/flow in the deep brain (better or much better in all 6 cases), and superior overall image quality (much better in 5 cases) despite residual susceptibility artifacts near the nasal cavity. Quantitative assessment demonstrates ~1.5× higher average SNR than Cartesian data. 3D spiral FLAIR achieves higher SNR, reduced CSF, and blood/flow artifacts, providing an alternative to 3D Cartesian FLAIR for neurological exams.


[Fibromyalgia, or whole body pain].
Fibromyalgia is a rheumatic syndrome which is being recognized and diagnosed more often all the time. Its symptoms include a general state of pain not localized in the joints, combined with tremendous tiredness and sleep alterations. Although its exact etiology is still unknown, medical professionals speculate on the existence of multiple cause factors. Therefore, an integrated therapeutic treatment having the coordinated participation of medical professionals from different fields of expertise is necessary. Mental health professionals play an important role since it is proven the existence of psychological and socio-psychological factors at the start, during the duration of and in the evolution of this syndrome.


Built environment and the metropolitan pandemic: Analysis of the COVID-19 spread in Hong Kong.
The COVID-19 reported initially in December 2019 led to thousands and millions of people infections, deaths at a rapid scale, and a global scale. Metropolitans suffered serious pandemic problems as the built environments of metropolitans contain a large number of people in a relatively small area and allow frequent contacts to let virus spread through people's contacting with each other. The spread inside a metropolitan is heterogeneous, and we propose that the spatial variation of built environments has a measurable association with the spread of COVID-19. This paper is the pioneering work to investigate the missing link between the built environment and the spread of the COVID-19. In particular, we intend to examine two research questions: (1) What are the association of the built environment with the risk of being infected by the COVID-19? (2) What are the association of the built environment with the duration of suffering from COVID-19? Using the Hong Kong census data, confirmed cases of COVID-19 between January to August 2020 and large size of built environment sample data from the Hong Kong government, our analysis are carried out. The data is divided into two phases before (Phase 1) and during the social distancing measure was relaxed (Phase 2). Through survival analysis, ordinary least squares analysis, and count data analysis, we find that (1) In Phase 1, clinics and restaurants are more likely to influence the prevalence of COVID-19. In Phase 2, public transportation (i.e. MTR), public market, and the clinics influence the prevalence of COVID-19. (2) In Phase 1, the areas of tertiary planning units (i.e., TPU) with more restaurants are found to be positively associated with the period of the prevalence of COVID-19. In Phase 2, restaurants and public markets induce long time occurrence of the COVID-19. (3) In Phase 1, restaurant and public markets are the two built environments that influence the number of COVID-19 confirmed cases. In Phase 2, the number of restaurants is positively related to the number of COVID-19 reported cases. It is suggested that governments should not be too optimistic to relax the necessary measures. In other words, the social distancing measure should remain in force until the signals of the COVID-19 dies out.


Charcot's neuroarthropathy of the hand in a patient with diabetes mellitus.
Charcot's neuroarthropathy (CNA) is a destructive disease associated with a reduced proprioceptive sensation. Diabetes mellitus (DM) is one of the most common etiological factor for CNA which typically affects ankles and small joints of feet. Neuroarthropathy seen in upper extremity in patients with DM is a rare clinical condition. In this report, we presented a case of CNA with hand involvement who had type-II DM. Neuroarthropathy was rapidly progressed and destructive changes were observed in right hand joints after a minor trauma in current case. Charcot's neuroarthropathy may rarely occur in the joints of hand in patients with DM. Early diagnosis of CNA is important in order to protect joints and avoid further disability.


Rap1 activation is required for Fc gamma receptor-dependent phagocytosis.
Phagocytosis of IgG-opsonized microbes via the Fc gamma receptor (Fc gammaR) requires the precise coordination of a number of signaling molecules, including the low-molecular mass GTPases. Little is known about the Ras-family GTPase Rap1 in this process. We therefore investigated its importance in mediating Fc gammaR-dependent phagocytosis in NR8383 rat alveolar macrophages. Pulldown of active Rap1 and fluorescence microscopic analysis of GFP-RalGDS (Ral guanine dissociation stimulator)-transfected macrophages revealed that Rap1 is indeed activated by Fc gammaR crosslinking. Inhibition of Rap1 activity, both by Rap1GAP (GTPase-activating protein) expression and liposome-delivered blocking Ab, severely impaired the ability of cells to ingest IgG-opsonized targets. Fc gammaR-induced Rap1 activation was found to be independent of both cAMP and Ca(2+), suggesting a role for the second messenger-independent guanosine exchange factor, C3G. This was supported by the facts that 1) liposome-delivered blocking Ab against C3G inhibited both Fc gammaR-dependent phagocytosis and Rap1 activation, and 2) both active Rap1GTP and C3G were found to translocate to the phagosome. Taken together, our data demonstrate a novel role for Rap1 and its exchange factor C3G in mediating Fc gammaR-dependent phagocytosis.


The pyruvate dehydrogenase complex of Mycoplasma hyopneumoniae contains a novel lipoyl domain arrangement.
The genes encoding the pyruvate dehydrogenase (PDH) complex (pdhA, pdhB, pdhC and pdhD) from Mycoplasma hyopneumoniae have been cloned and sequenced. The genes are arranged into two operons, designated pdhAB and pdhCD, which are not found together in the chromosome. The pdhA, pdhB, pdhC and pdhD genes encode proteins of predicted molecular masses of 44.2 kDa (pyruvate dehydrogenase major subunit; E1alpha), 36.6 kDa (pyruvate dehydrogenase minor subunit; E1beta), 33.1 kDa (dihydrolipoyl acetyltransferase; E2) and 66.3 kDa (dihydrolipoyl dehydrogenase; E3), respectively. Sequence analysis of the pdhCD operon revealed the presence of a lipoyl-binding domain in pdhD but not in pdhC. The lipoyl domain is believed to act as a "swinging arm" that spans the gaps between the catalytic domains of each of the subunits. Portions of the N-terminal regions of pdhA and pdhD were expressed as 6xHis-tag fusion proteins in Escherichia coli and purified by nickel affinity chromatography. The purified proteins were used to raise antibodies in rabbits, and Western blot analysis was performed with the polyclonal rabbit antiserum. Both the pdhA and pdhD genes were expressed among various strains of M. hyopneumoniae as well as the porcine mycoplasmas, Mycoplasma hyorhinis and Mycoplasma flocculare. Southern hybridisation analysis using probes from pdhA and pdhD detected one copy of each gene in the chromosome of M. hyopneumoniae. Since previous studies have shown pyruvate dehydrogenase activity in M. hyopneumoniae [J. Gen. Microbiol. 134 (1988) 791], it appears likely that a functional lipoyl-binding domain in the N terminus of PdhC is not an absolute prerequisite for pyruvate dehydrogenase enzyme activity. We hypothesise that the lipoyl-binding domain of PdhD is performing the enzymatic function normally attributed to the PdhC lipoyl-binding domain in other organisms. Searches of pyruvate dehydrogenase gene sequences derived from other Mycoplasma species showed that a putative lipoyl domain was absent in the pdhC gene from Mycoplasma pulmonis. However, like other bacterial species, pdhC gene sequences from Mycoplasma capricolum, Mycoplasma genitalium and Mycoplasma pneumoniae contain a putative lipoyl domain.


Performance Testing of a Homemade Aerosol Generator for Pulmonary Administration of Dry Powder Formulations to Mice.
A challenge in the development of dry powder formulations for inhalation is the poor reproducibility of their administration to small laboratory animals. The currently used devices for the pulmonary administration of dry powder formulations to small rodents often function sub-optimally as they use the same puff of air for both powder dispersion and aerosol delivery. As a result, either the air volume and flow rate are too low for complete powder deagglomeration or they are too high for effective aerosol delivery to the lungs of the animal. Therefore, novel and better devices are desired. We here present an aerosol generator designed to administer a pre-generated aerosol to the lungs of mice. By mapping the complex relationship between the airflow rate, delivery time and emitted dose, we were able to control the amount of powder being delivered from the aerosol generator. The emitted aerosol had a size range favorable for lung deposition and could be measured reproducibly. Nevertheless, in vivo fluorescent imaging still revealed considerable differences between the mice in terms of the dose deposited and the distribution of powder over the lungs, suggesting that a certain biological variation in lung deposition is inevitable.


[What does a hospital building tell?].
Hospital architecture may be seen as an artistic expression and interpreted as such. In general, architecture is more dependent than other form of art on external forces: The requested function of the building normally puts important constraints on the implementation of architectural ideas. In addition, buildings are often rebuilt and altered in ways that make a retrospective analysis of the basic ideas behind them difficult. Hospital buildings usually reflect the state of the art of medicine at the time of construction or reconstruction, and their architecture should be interpreted in the light of the medical setting of the time. Other elements and influences, such as general views on health and sickness, religion, economy, style etc. should also be taken into consideration. This article discusses examples that show some of the possible pitfalls when we attempt to give a cultural interpretation of hospital buildings. The conflict between charity and rationality seems to be a basic problem in modern hospitals, an example is given where this conflict is reflected in the architecture.


[Electroencephalography and cerebrospinal fluid glutamine in portal-systemic encephalopathies].
A group of patients with portal-systemic encephalopathy were studied. The conscious disturbances, eletroencephalographic findings and the spinal fluid glutamine levels were analyzed. Based on the results the authors concluded that the eletrencephalogram can be utilized for determination of the degree of hepatic coma and also for its prognostic valuation. In addition they found that monitorization of spinal fluid glutamine levels is the most important test for characterization of the degree of hepatic encephalopathy.


Elucidating Potential Energy Surfaces for Singlet O2 Reactions with Protonated, Deprotonated, and Di-Deprotonated Cystine Using a Combination of Approximately Spin-Projected Density Functional Theory and Guided-Ion-Beam Mass Spectrometry.
The reactivity of cystine toward electronically excited singlet O2 (a1Δg) has been long debated, despite the fact that most organic disulfides are susceptible to oxidation by singlet O2. We report a combined experimental and computational study on reactions of singlet O2 with gas-phase cystine at different ionization and hydration states, aimed to determine reaction outcomes, mechanisms, and potential energy surfaces (PESs). Ion-molecule collisions of protonated and di-deprotonated cystine ions with singlet O2, in both the absence and the presence of a water ligand, were measured over a center-of-mass collision energy (Ecol) range from 0.1 to 1.0 eV, using a guided-ion-beam scattering tandem mass spectrometer. No oxidation was observed for these reactant ions except collision-induced dissociation at high energies. Guided by density functional theory (DFT)-calculated PESs, reaction coordinates were established to unravel the origin of the nonreactivity of cystine ions toward singlet O2. To account for mixed open- and closed-shell characters, singlet O2 and critical structures along reaction coordinates were evaluated using broken-symmetry, open-shell DFT with spin contamination errors removed by an approximate spin-projection method. It was found that collision of protonated cystine with singlet O2 follows a repulsive potential surface and possesses no chemically significant interaction and that collision-induced dissociation of protonated cystine is dominated by loss of water and CO. Collision of di-deprotonated cystine with singlet O2, on the other hand, forms a short-lived electrostatically bonded precursor complex at low Ecol. The latter may evolve to a covalently bonded persulfoxide, but the conversion is blocked by an activation barrier lying 0.39 eV above reactants. At high Ecol, C-S bond cleavage dominates the collision-induced dissociation of di-deprotonated cystine, leading to charge-separated fragmentation. Cross section for the ensuing fragment ion H2NCH(CO2-)CH2SS• was measured as a function of Ecol, and the mechanism of charge-separated fragmentation was discussed. It was also found that the reaction of deprotonated cystine with singlet O2 follows a similar mechanism as that of di-deprotonated cystine, but with an even higher activation barrier (0.72 eV).


[Radioimmunoscintigraphy of colorectal cancer using the anti-CEA monoclonal antibody BW 431/26. Final results].
The anti-carcinoembryonic antigen (CEA) antibody, BW 431/26 (Scintimun CEA, Behringwerke, Marburg, Germany ) labeled with technetium pertechnectate (99mTc), is an intact immunoglobulin G1, monoclonal antibody that has been used to image colorectal cancer. Planar and SPECT images of chest, abdomen and pelvis were performed at 10 minutes, 4-6 and 18-24 hours after the intravenous antibody injection. 44 patients were studied and the pathological antibody concentration localization by radioimmunoimaging (RI) were correlated with surgical, clinical and other imaging modality findings to validate the RI. The RI was positive in 29 patients and negative in the other 15 patients. The CEA and CA 19.9 were elevated in the serum of some patients with primary tumors or recurrence. The HAMA were determined in all the patients before and after the RI.


The control of CTP:choline-phosphate cytidylyltransferase activity in pea (Pisum sativum L.).
Several possible control mechanisms for CTP:choline-phosphate cytidylyltransferase (EC 188.8.131.52) activity in pea (Pisum sativum L.) stems were investigated. Indol-3-ylacetic acid (IAA) treatment of the pea stems decreased total cytidylyltransferase activity but did not affect its subcellular distribution. Oleate (2 mM) caused some stimulation of enzyme activity by release of activity from the microsomal fraction into the cytosol, but neither phosphatidylglycerol nor monoacyl phosphatidylethanolamine had an effect on activity or subcellular distribution. A decrease in soluble cytidylyltransferase protein concentrations was found in IAA-treated pea stems, but this was not sufficient to account for all of the decrease in cytidylyltransferase activity. A 50% inhibition of enzyme activity could be obtained with 0.2 mM-CMP, which indicated possible allosteric regulation. Similar inhibition was obtained with 1.5 mM-ATP, but other nucleotides had no effect. The cytidylyltransferase enzyme protein was not directly phosphorylated, and the inhibition with 1.5 mM-ATP occurred with the purified enzyme, thus excluding an obligatory mediation via a modulator protein. The results indicate that the cytosolic form of cytidylyltransferase is the most important in pea stem tissue and that the decrease in cytidylyltransferase activity in IAA-treated material appears to be brought about by several methods.


Luminescence enhancement from silica-coated gold nanoparticle agglomerates following multi-photon excitation.
Multi-photon absorption induced luminescence (MAIL) from bare gold nanoparticles, silica-coated particles, as well as silica-coated agglomerated gold nanoparticles suspended in aqueous solution was studied by using time-resolved and steady-state luminescence spectroscopy. The nanoparticles were excited by femtosecond pulses of wavelengths ranging from 630 nm to 900 nm. The luminescence from the particles exhibits a broad spectrum in the UV and VIS region. The time-resolved measurements indicate a luminescence lifetime of a few ps, limited by the response of the experimental system. The studied dependence of the MAIL efficiency on the excitation wavelength showed that the luminescence from silica-coated agglomerates was enhanced over the whole range of excitation wavelengths, when compared to the luminescence from individual gold nanoparticles. The agglomerates show an almost excitation wavelength independent efficiency of the MAIL, while for individual nanoparticles a rapid decrease of the MAIL efficiency was observed with increasing excitation wavelength. The observed enhancement of the MAIL from the agglomerated nanostructures can be attributed to the presence of localized surface plasmon resonances in the spectral region corresponding to the excitation wavelengths. The high MAIL efficiency from the agglomerated nanoparticle structures in the near-infrared could be an advantage in the expanding field of luminescence-based-imaging, as well as in biosensor technology.


Effects of pulsed versus conventional radiofrequency current on rabbit dorsal root ganglion morphology.
Lesioning using radiofrequency (RF) current has been increasingly used in clinical practice for the treatment of pain syndromes. Although formation of heat causing "thermocoagulation" of the nervous tissues is thought to be responsible of the clinical outcome, a more recent modality of RF application named pulsed radiofrequency (PRF) delivers the RF current without producing destructive levels of heat. In our study, we compared the effects of conventional RF (CRF) and PRF on rabbit dorsal root ganglion (DRG) morphology, including also control and sham operated groups. The setting of the experiment and the RF parameters used were similar to those used in current clinical practice. The specimens were analyzed both with light microscopy and electron microscopy, two weeks after the procedure. At the light microscopic level, all groups had preserved the normal DRG morphology and no differences were observed between them. In the electron microscopic analysis there were no pathological findings in the control and sham operated groups. But the ganglion cells in the RF groups had enlarged endoplasmic reticulum cisterns and increased number of cytoplasmic vacuoles which were more evident in the CRF group. Some of the ganglion cells in the CRF group had mitochondrial degeneration, nuclear membrane disorders or loss of nuclear membrane and neurolemma integrity. The myelinated and unmyelinated nerve fibers were of normal morphology in all groups. Our results suggest that PRF application is less destructive of cellular morphology than CRF at clinically used "doses". Before making certain judgements, more experimental and clinical studies should be planned.


Cyberlindnera xishuangbannaensis f.a., sp. nov., a yeast isolated from rotting wood.
Three strains representing a novel species of yeast were isolated from samples of rotting wood collected from Xishuangbanna Tropical Rainforest in Yunnan Province, PR China. Phylogenetic analysis based on the concatenated sequences of the internal transcribed spacer (ITS) region and the D1/D2 domains of the large subunit (LSU) rRNA gene revealed that the novel species is a member of the genus Cyberlindnera, although the formation of ascospores was not observed. The novel species was related most closely to the type strain of the species Candida pattaniensis, but they had a 0.5 % sequence divergence (3 substitutions, 0 gap) in the D1/D2 domain and a 5.4 % sequence divergence (21 substitutions, 10 gaps) in the ITS region. The novel species could also be differentiated from the closely related species by some biochemical and physiological characteristics. The species name Cyberlindnera xishuangbannaensis f.a., sp. nov. is proposed to accommodate these strains, with NYNU 16752T (=CICC 33163T=CBS 14692T) designated as the type strain. The MycoBank number is MB 822199.


Survey response rates in health sciences education research: A 10-year meta-analysis.
Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta-analysis evaluated survey trends over one decade (2011-2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta-analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9-69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.


Preliminary seroepidemiological studies on the human syncytial virus.
The seroepidemiology of the human syncytial virus was investigated by means of an indirect immunofluorescence test on 241 sera from Kenya, Tunisia, Singapore and Britain. These included sera from patients with nasopharyngeal carcinoma, other tumours of the oro-nasopharynx, tumours of other parts of the body, and from normal donors. In this study, the virus was found to infect only Kenyan Africans and all but one of these seropositive subjects had tumours, particularly of the oro-nasopharyngeal spaces. The significance of these findings is discussed.


Red-shifted aequorin-based bioluminescent reporters for in vivo imaging of Ca2 signaling.
Real-time visualization of calcium (Ca(2+)) dynamics in the whole animal will enable important advances in understanding the complexities of cellular function. The genetically encoded bioluminescent Ca(2+) reporter green fluorescent protein-aequorin (GA) allows noninvasive detection of intracellular Ca(2+) signaling in freely moving mice. However, the emission spectrum of GA is not optimal for detection of activity from deep tissues in the whole animal. To overcome this limitation, two new reporter genes were constructed by fusing the yellow fluorescent protein (Venus) and the monomeric red fluorescent protein (mRFP1) to aequorin. Transfer of aequorin chemiluminescence energy to Venus (VA) is highly efficient and produces a 58 nm red shift in the peak emission spectrum of aequorin. This substantially improves photon transmission through tissue, such as the skin and thoracic cage. Although the Ca(2+)-induced bioluminescence spectrum of mRFP1-aequorin (RA) is similar to that of aequorin, there is also a small peak above 600 nm corresponding to the peak emission of mRFP1. Small amounts of energy transfer between aequorin and mRFP1 yield an emission spectrum with the highest percentage of total light above 600 nm compared with GA and VA. Accordingly, RA is also detected with higher sensitivity from brain areas. VA and RA will therefore improve optical access to Ca(2+) signaling events in deeper tissues, such as the heart and brain, and offer insight for engineering new hybrid molecules.


Block versus random amphiphilic copolymers as antibacterial agents.
We examined the antibacterial and hemolytic activities in a series of amphiphilic block and random copolymers of poly(vinyl ether) derivatives prepared by base-assisting living cationic polymerization. Block and random amphiphilic copolymers with similar monomer compositions showed the same level of activity against Escherichia coli . However, the block copolymers are much less hemolytic compared to the highly hemolytic random copolymers. These results indicate that the amphiphilic copolymer structure is a key determinant of activity. Furthermore, the block copolymers induced dye leakage from lipid vesicles consisting of E. coli -type lipids, but not mammalian lipids, while the random copolymers disrupted both types of vesicles. In addition, both copolymers displayed bactericidal and hemolytic activities at concentrations 1 or 2 orders of magnitude lower than their critical (intermolecular) aggregation concentrations (CACs), as determined by light scattering measurements. This suggests that polymer aggregation or macromolecular assembly is not a requisite for the antibacterial activity and selectivity against bacteria over human red blood cells (RBCs). We speculate that different single-chain conformations between the block and random copolymers play an important role in the antibacterial action and underlying antibacterial mechanisms.


Absolute fracture risk reporting in clinical practice: a physician-centered survey.
Non-expert clinical practitioners who had received bone density reports based on 10-year absolute fracture risk were surveyed to determine their response to this new system. Absolute fracture risk reporting was well received and was strongly preferred to traditional T-score-based reporting. Non-specialist physicians were particularly supportive of risk-based bone mineral density (BMD) reporting. Absolute risk estimation is preferable to risk categorization based upon BMD alone. The objective of this study was to specifically assess the response of non-expert clinical practitioners to this approach. In January 2006, the Province of Manitoba, Canada, started reporting 10-year osteoporotic fracture risks for patients aged 50 years and older based on the hip T-score, gender, age, and multiple clinical risk factors. In May 2006 and October 2006, a brief anonymous survey was sent to all physicians who had requested a BMD test during 2005 and 206 responses were received. When asked whether the report contained the information needed to manage patients, the mean score for the absolute fracture risk report was higher than for the T-score-based report (p<0.0001). When asked whether the report was easy to understand, the mean score for the absolute fracture risk report was again higher than for the T-score-based report (p<0.0001). Non-specialists gave a higher ranking than specialists to the absolute fracture risk information (p<0.05). Absolute fracture risk reporting is well-received by physicians and is strongly preferred to traditional T-score-based reporting. Non-specialist physicians are particularly supportive of risk-based BMD reporting.


Extended-release lipid-foam encapsulated epidural morphine: clinical efficacy and safety precautions.
DepoDur is a unique delivery system that has a Food and Drug Administration-approved recommended close of 15 mg for orthopedic lower extremity surgery and a 10- to 15-mg dose for lower abdominal or pelvic surgery. Some patients may benefit from a 20-mg dose, but the incidence of serious adverse respiratory events has been close related in clinical trials. For cesarean section, the recommended dose is 10 mg. Most patients will require supplemental analgesics during the 48 hours post surgical procedure as well as routine monitoring similar to present continuous epidural monitoring procedures. The unique delivery system requires additional safety and storage precautions. The clinical studies to date do not show DepoDur administration to have any lower adverse reaction profile compared to standard epidural morphine.


Predictability-mediated pain modulation in context of multiple cues: An event-related fMRI study.
When the pain intensity of an impending stimulus is highly unpredictable, the uncertain expectation of pain may exacerbate the perceived pain intensity of the stimulus, compared to the same stimulus delivered with certain expectation. Here, we address how the perception of physically identical stimuli delivered with different predictability of the pain intensity is influenced by learning. We hypothesized that the difference in perceived pain intensity following high and low predictable cues could be explained by: (1) uncertainty-driven hyperalgesia associated with hippocampal activity; (2) certainty-driven hypoalgesia associated with activity in the periaqueductal gray (PAG) and the rostral anterior cingulate cortex (rACC); and (3) a mixed model of both. To test this hypothesis, two sessions of a delayed conditioning paradigm was employed in conjunction with event-related functional magnetic resonance imaging and trial-by-trial rating of the pain intensity. Participants had to simultaneously learn the outcome association of two cues. One cue was always delivered at the same intensity while the other cue was delivered either at a matched or a substantially higher intensity. As expected, the uncertain condition resulted in higher perceived pain intensity than the certain condition. However, this effect occurred only in the second session and was driven by decreased perceived pain in the certain condition. Furthermore, this effect was associated with decreased activity in the PAG but not the rACC. The changing pain ratings and PAG activity across sessions reflect a dynamic learning process that may mirror decreased perceived threat of and/or decreased attention to pain in the certain condition.


Applications of DNA-nanozyme-based sensors.
Since the discovery of the enzyme-like activities of nanomaterials, the study of nanozymes has become one of the most popular research frontiers of diverse areas including biosensors. DNA also plays a very important role in the construction of biosensors. Thus, the idea of combined applications of nanozymes with DNA (DNA-nanozyme) is very attractive for the development of nanozyme-based biosensors, which has attracted considerable interest of researchers. To date, many sensors based on DNA-functionalized or templated nanozymes have been reported for the detection of various targets and highly accelerated the development of nanozyme-based sensors. In this review, we summarize the main applications and advances of DNA-nanozyme-based sensors. Additionally, perspectives and challenges are also discussed at the end of the review.


Hydraulically-vulnerable trees survive on deep-water access during droughts in a tropical forest.
Deep-water access is arguably the most effective, but under-studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep-water access may delay plant dehydration. Here, we tested the role of deep-water access in enabling survival within a diverse tropical forest community in Panama using a novel data-model approach. We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990-2015) to vapor pressure deficit, water potentials in the whole-soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water-access depths. Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35 years (1981-2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress-related mortality risk through deep-water access. The role of deep-water access in mitigating mortality of hydraulically-vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates.


[Seizures following Billroth II gastrectomy].
A 64-year old somnolent man was admitted to the emergency department with a reported seizure half an hour earlier. Due to similar episodes the patient had been treated with antiepileptics in the past. The patient s past history revealed a partial gastrectomy (Billroth II) more than ten years ago. At the time of admission blood glucose was 31 mg/dl. Other routine laboratory analyses and the clinical examination were normal. In addition, a detailed neurological examination and a cranial CT-scan were normal. Due to the hypoglycemia a dumping syndrome was suspected. A three hour oral glucose tolerance test (OGTT) resulted in a late hypoglycemia, establishing the diagnosis of late dumping. After adaptation of the patient's diet no further hypoglycemic episodes occurred. Manifestation of a dumping syndrome may occur even years after gastrectomy. Therefore, in patients presenting with hypoglycemia and a history of gut surgery, a dumping syndrome should be suspected. Furthermore, seizures due to hypoglycemia may be the only manifestation of late dumping.


Phylogeny of putative cholinergic visual pathways through the pretectum to the hypothalamus in teleost fish.
Three patterns of pretectal organization can be discerned morphologically in teleosts. The taxonomic distribution of these pretectal patterns suggests that the intermediately complex pattern (seen in most teleost groups) has given rise to both the elaborate pattern (seen in percomorphs) and the simple pattern (seen in cyprinids). Two pretectal patterns (intermediately complex and elaborate) form part of similar, homologous visual pathways to the hypothalamus; the third pattern is involved in a nonhomologous pathway to the hypothalamus. Acetylcholinesterase (AChE) histochemistry was used in the present study in order to characterize these pretectal patterns further. It is demonstrated that AChE is a highly selective and reliable interspecific marker for all divisions of the superficial pretectum, the nucleus corticalis, the posterior pretectal nucleus (or nucleus glomerulosus) and portions of the inferior lobe. Therefore, the histochemical data support the hypothesis of a homology between the three patterns of pretectal organization in teleosts. Furthermore, the present data provide a basis for more specific investigations regarding the involvement of acetylcholine as a neurotransmitter within the visual pathways to the hypothalamus in teleosts.


Reliable, scalable functional genetics in bloodstream-form Trypanosoma congolense in vitro and in vivo.
Animal African trypanosomiasis (AAT) is a severe, wasting disease of domestic livestock and diverse wildlife species. The disease in cattle kills millions of animals each year and inflicts a major economic cost on agriculture in sub-Saharan Africa. Cattle AAT is caused predominantly by the protozoan parasites Trypanosoma congolense and T. vivax, but laboratory research on the pathogenic stages of these organisms is severely inhibited by difficulties in making even minor genetic modifications. As a result, many of the important basic questions about the biology of these parasites cannot be addressed. Here we demonstrate that an in vitro culture of the T. congolense genomic reference strain can be modified directly in the bloodstream form reliably and at high efficiency. We describe a parental single marker line that expresses T. congolense-optimized T7 RNA polymerase and Tet repressor and show that minichromosome loci can be used as sites for stable, regulatable transgene expression with low background in non-induced cells. Using these tools, we describe organism-specific constructs for inducible RNA-interference (RNAi) and demonstrate knockdown of multiple essential and non-essential genes. We also show that a minichromosomal site can be exploited to create a stable bloodstream-form line that robustly provides >40,000 independent stable clones per transfection-enabling the production of high-complexity libraries of genome-scale. Finally, we show that modified forms of T. congolense are still infectious, create stable high-bioluminescence lines that can be used in models of AAT, and follow the course of infections in mice by in vivo imaging. These experiments establish a base set of tools to change T. congolense from a technically challenging organism to a routine model for functional genetics and allow us to begin to address some of the fundamental questions about the biology of this important parasite.


The Effects of Transcranial Direct Current Stimulation Versus Electroacupuncture on Working Memory in Healthy Subjects.
Objective: Working memory (WM) can influence human thought processes through interactions with perception, long-term memory, and behavior. In recent years, transcranial direct current stimulation (tDCS) and electric acupuncture have been used to improve the performance of WM. Therefore, due to the n-back task as a continuous performance task that is commonly used to measure WM, the aim of this study is to investigate the differences in short-term efficacy between tDCS and electroacupuncture on WM under n-back task paradigm in healthy subjects. Methods: Forty-four college students (age: 23.70 ± 1.52 years; education: 16.93 ± 2.24 years) were recruited as experimental subjects and randomly divided into two groups by a random double-blind two-stage crossover experiment design. Group A received a tDCS intervention followed by at least 1 week of washout period and then the electroacupuncture intervention. Group B had the opposite sequence of interventions. The WM test under the n-back task paradigm was conducted before and after each intervention, and the changes in the accuracy (number of correct responses) and correct response time (RT) before and after the interventions were detected. The data were statistically analyzed using SPSS 24.0 to compare the short-term efficacy of tDCS and electroacupuncture on WM under different tasks. Results: In the 0-back task and 1-back tasks, there was no significant difference in the accuracy or RT before and after the interventions between tDCS and electroacupuncture stimulation. In the 2-back task, there was no significant difference in the accuracy before and after interventions between tDCS and electroacupuncture stimulation. However, there was a significant difference in RT (p < 0.05), which was lower after tDCS than after electroacupuncture in the 2-back task. Conclusion: The results show that tDCS with anodal stimulation on the left dorsolateral prefrontal cortex could increase the RT of the 2-back task performance in comparison with electroacupuncture stimulation of the Baihui (GV20) and Shenting (DU24) acupoints. The present results indicate that tDCS may have greater impact on WM in healthy subjects than electroacupuncture stimulation.


Image computing for fibre-bundle endomicroscopy: A review.
Endomicroscopy is an emerging imaging modality, that facilitates the acquisition of in vivo, in situ optical biopsies, assisting diagnostic and potentially therapeutic interventions. While there is a diverse and constantly expanding range of commercial and experimental optical biopsy platforms available, fibre-bundle endomicroscopy is currently the most widely used platform and is approved for clinical use in a range of clinical indications. Miniaturised, flexible fibre-bundles, guided through the working channel of endoscopes, needles and catheters, enable high-resolution imaging across a variety of organ systems. Yet, the nature of image acquisition though a fibre-bundle gives rise to several inherent characteristics and limitations necessitating novel and effective image pre- and post-processing algorithms, ranging from image formation, enhancement and mosaicing to pathology detection and quantification. This paper introduces the underlying technology and most prevalent clinical applications of fibre-bundle endomicroscopy, and provides a comprehensive, up-to-date, review of relevant image reconstruction, analysis and understanding/inference methodologies. Furthermore, current limitations as well as future challenges and opportunities in fibre-bundle endomicroscopy computing are identified and discussed.


Optimal generation scheduling based on AHP/ANP.
This paper proposes an application of the analytic hierarchy process (AHP) and analytic network process (ANP) for enhancing the selection of generating power units for appropriate price allocation in a competitive power environment. The scheme addresses adequate ranking, prioritizing, and scheduling of units before optimizing the pricing of generation units to meet a given demand. In the deregulated environment, the classical optimization techniques will be insufficient for the above-mentioned purpose. Hence, by incorporating the interaction of factors such as load demand, generating cost curve, bid/sale price, unit up/down cost, and the relative importance of different generation units, the scheme can be implemented to address the technical and nontechnical constraints in unit commitment problems. This information is easily augmented with the optimization scheme for an effective optimal decision. The scheme proposed is tested using the IEEE 39-bus test system.


Proliferin transport and binding in the mouse fetus.
Proliferin (PLF), a member of the PRL/GH family secreted by the placenta, can be detected in both the maternal and fetal compartments. We now show that PLF immunoreactivity can be detected in association with the yolk sac, consistent with the transport of PLF across this structure into the amniotic fluid. Furthermore, PLF is transported across the extraembryonic membranes in isolated conceptuses that are placed in culture, and specific binding sites for PLF are detected in these embryos. The major binding sites for PLF in the cultured conceptus correspond to sites at which endogenous PLF localizes in the fetus, including developing vertebral and vascular structures. Similar binding patterns were also detected for PLF that was incubated with fetal sections. Competition and comparative binding studies indicate that the insulin-like growth factor II/mannose 6-phosphate receptor is involved in PLF binding to specific cells in the fetus. These results suggest that in addition to the effects of PLF in the placenta on neovascularization and in the maternal uterus on cell proliferation, PLF may also act at specific sites in the developing fetus.


Successful Implementation of Integrated Care in Slovenian Primary Care.
For the purpose of celebrating the 40th anniversary of Alma Ata declaration, the WHO published a successful model of integrated patient care being performed in Slovenia. After two years, the WHO experts evaluated the success in practise during a visit to the Slovenian primary care environment. This report showed that Slovenia was a notable exception regarding developing effective primary care systems. The country has an impressive primary care which performs very well.


Postoperative delirium and postoperative cognitive dysfunction: updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives.
Postoperative delirium, the onset of confusion/delirium during the early postoperative phase, is the most common postoperative complication in older adults and represents a medical emergency that requires immediate assessment and treatment. On the other hand, the term postoperative cognitive decline or dysfunction refers to a wide spectrum of clinical conditions featuring a decline in a variety of neuropsychological domains including memory, executive functioning, and speed of processing emerging week to months after anesthesia and surgery. Postoperative delirium and postoperative cognitive decline represent two distinct clinical entities along the continuum of cognitive impairment after anesthesia and surgery. All patients experiencing delirium does however not develop postoperative dysfunction and likewise all patients showing various degree of postoperative decline have not explicitly exhibited postoperative delirium. Although neuroinflammation seems to be main cause, the exact pathophysiology of both phenomena is very difficult to ascertain because it involves the crossroads of many mechanisms. This paper aimed to provide an update in the pathophysiology of these conditions with special attention to the roles of the neuroinflammation, the microglia activation, the surgical stress response, the impairment of neurotransmitter systems, and the direct neurotoxic effect of general anesthetic drugs. Potential translational approaches to clinical practice and further research perspectives are also given.


[Occupational activity and prevalence of osteomuscular pain among dentists in Belo Horizonte, Minas Gerais State, Brazil: a contribution to the debate on work-related musculoskeletal disorders].
The objective was to determine the prevalence of upper-limb and back pain among dentists (n = 358) and factors associated with these symptoms. Dentists were interviewed using a self-administered questionnaire containing data on sociodemographic, occupational, lifestyle, and psychosocial factors and presence, site, and characteristics of pain. Participation rate was 92.3%. 58% reported upper limb pain, with 22, 21, 20, and 17% for the arm, back, neck, and shoulder, respectively. 26% reported daily frequency and 40% classified pain as moderate or severe. In the multivariate analysis (multiple logistic regression), the factors associated with pain were: neck: anxiety/depression (OR = 2.3; CI95%: 1.2-4.5), compressor in the office (OR = 2.1; CI95%: 1.2-3.7), job satisfaction (OR = 0.3; CI95%: 0.1-0.9), and use of indirect vision (OR = 0.5; CI95%: 0.3-0.9); shoulder: income > 20 minimum wage (OR = 2.9; CI95%: 1.2-6.7), greater productivity (OR = 3.3; CI95%: 1.3-8.4), height > or = 160cm (OR = 0.3; CI95%: 0.2-0.7), and age 30-49 years (OR = 0.3; CI95%: 0.1-0.8); back: anxiety/depression (OR = 2.3; CI95%: 1.2-4.5), manual activity (OR = 0.4; CI95%: 0.2-0.9), and being married (OR = 0.5; CI95%: 0.3-0.9); arms: manual activity (OR = 1.8; CI95%: 1.0-3.2).


Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer.
Epithelial-mesenchymal transition (EMT) is an essential developmental program that becomes reactivated in adult tissues to promote the progression of cancer. EMT has been largely studied by examining the beginning epithelial state or the ending mesenchymal state without studying the intermediate stages. Recent studies using trophoblast stem (TS) cells paused in EMT have defined the molecular and epigenetic mechanisms responsible for modulating the intermediate "metastable" stages of EMT. Targeted inactivation of MAP3K4, knockdown of CBP, or overexpression of SNAI1 in TS cells induced similar metastable phenotypes. These TS cells exhibited epigenetic changes in the histone acetylation landscape that cause loss of epithelial maintenance while preserving self-renewal and multipotency. A similar phenotype was found in claudin-low breast cancer cells with properties of EMT and stemness. This intersection between EMT and stemness in TS cells and claudin-low metastatic breast cancer demonstrates the usefulness of developmental EMT systems to understand EMT in cancer.


Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes.
Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4 degree of freedom) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-β. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.


The reliability of the results of ultrasound detection of fluid collections in the early postceliotomy period.
The results of this prospective clinical study have demonstrated a low rate of false-positive abdominal sonographic findings in patients undergoing routine studies the seventh day after abdominal surgical procedures. It is concluded that any intraperitoneal fluid collection detected by ultrasound examination in a patient postoperatively demonstrating signs and symptoms of abdominal sepsis (fever, leukocytosis, pain, tenderness, persistent ileus, excessive drainage, wound changes and so on), should be considered as the source, as abdominal fluid collections do not persist as a "normal" part of the healing process one week after extensive biliary tract or colonic operations. Sonography is a highly specific procedure for the detection of abdominal abscesses after the seventh postoperative day. The type of procedure, type of incision, type of closure, presence of drains, history of prior intraperitoneal surgical procedures and operative blood loss did not affect the accuracy of the test. Postoperative ultrasonography is a specific, sensitive and accurate test and is widely applicable to almost all groups of patients.


What investigation after an anaphylactic reaction during anaesthesia?
Anaphylactic reactions occurring during anaesthesia may be life threatening. Lethal issues may be involved in up to 3-10% of the cases. The allergological assessment (including biochemical tests and skin tests) is the key to the management of these reactions. The scope of this review is to focus on the allergological assessment required to prove the immune mechanism, to identify the culprit drug or substance and the cross-reactive molecules, especially for neuromuscular blocking agents, allowing preventive measures for future anaesthetic procedures. To describe the allergological assessment (including biochemical tests and skin tests performed according to the current guidelines) in order to prove the immune mechanism as the responsibility of the culprit allergen. The most frequent and less frequent drugs involved are described. The different biological tools available are detailed. To ensure an accurate diagnosis, the interpretation of the allergological assessment should be linked to the description of the clinical events as their time onset following the injection/administration of the suspected drug(s)/substance. To describe the different tools (biochemical tests and skin tests) available in order to prove the diagnosis of an anaphylactic reaction occurring during anaesthesia.


A dense SNP-based linkage map for Atlantic salmon (Salmo salar) reveals extended chromosome homeologies and striking differences in sex-specific recombination patterns.
The Atlantic salmon genome is in the process of returning to a diploid state after undergoing a whole genome duplication (WGD) event between 25 and100 million years ago. Existing data on the proportion of paralogous sequence variants (PSVs), multisite variants (MSVs) and other types of complex sequence variation suggest that the rediplodization phase is far from over. The aims of this study were to construct a high density linkage map for Atlantic salmon, to characterize the extent of rediploidization and to improve our understanding of genetic differences between sexes in this species. A linkage map for Atlantic salmon comprising 29 chromosomes and 5650 single nucleotide polymorphisms (SNPs) was constructed using genotyping data from 3297 fish belonging to 143 families. Of these, 2696 SNPs were generated from ESTs or other gene associated sequences. Homeologous chromosomal regions were identified through the mapping of duplicated SNPs and through the investigation of syntenic relationships between Atlantic salmon and the reference genome sequence of the threespine stickleback (Gasterosteus aculeatus). The sex-specific linkage maps spanned a total of 2402.3 cM in females and 1746.2 cM in males, highlighting a difference in sex specific recombination rate (1.38:1) which is much lower than previously reported in Atlantic salmon. The sexes, however, displayed striking differences in the distribution of recombination sites within linkage groups, with males showing recombination strongly localized to telomeres. The map presented here represents a valuable resource for addressing important questions of interest to evolution (the process of re-diploidization), aquaculture and salmonid life history biology and not least as a resource to aid the assembly of the forthcoming Atlantic salmon reference genome sequence.


High levels of recombinant CYP3A4 expression in Chinese hamster ovary cells are modulated by coexpressed human P450 reductase and hemin supplementation.
Expression of recombinant cytochrome P450s (P450s) in mammalian cells has been used as a powerful tool to study these enzymes. However, the activity of CYP3A4 expressed in several stable mammalian cell lines was much lower than native enzyme in human liver. The low level of recombinant CYP3A4 may have been due to the low copy number of the cDNA. In addition, the low activity is caused by the low level of P450 reductase in these cells. To achieve high levels of CYP3A4 expression, we employed gene amplification of the CYP3A4 cDNA in Chinese hamster ovary (CHO) cells followed by transfection of the P450 reductase cDNA. Using this strategy, we have obtained a cell line, designated D3A4, with high levels of recombinant CYP3A4. The content of spectrally active P450 was 14 pmol/mg total cellular protein. Hemin treatment increased the P450 content 2-fold. Upon coexpression of P450 reductase in DHR/3A4 cells, enzyme activity of CYP3A4 was stimulated 15-fold, despite a 40% decrease in spectrally active P450. Interestingly, the latter effect was not due to a decrease in CYP3A4 mRNA. Treatment of these cells with hemin, however, counteracted the P450 reductase-mediated decrease of spectrally active P450. These data demonstrate that P450 reductase has a strong influence on the levels of recombinant P450 holoenzyme, possibly by modulating the level of heme in CHO cells. Concomitantly our results show that the gene amplification strategy provides a powerful approach to obtain a high level of functional recombinant P450.


Local water sensing: water exchange in bacterial photosynthetic reaction centers embedded in a trehalose glass studied using multiresonance EPR.
Using isotope labeled water (D2O and H217O) and pulsed W-band (94 GHz) high-field multiresonance EPR spectroscopies, such as ELDOR-detected NMR and ENDOR, the biologically important question of detection and quantification of local water in proteins is addressed. A bacterial reaction center (bRC) from Rhodobacter sphaeroides R26 embedded into a trehalose glass matrix is used as a model system. The bRC hosts the two native radical cofactor ions (primary electron donor) and (primary electron acceptor) as well as an artificial nitroxide spin label site-specifically attached to the surface of the H-protein domain. The three paramagnetic reporter groups have distinctly different local environments. They serve as local probes to detect water molecules via magnetic interactions (electron-nuclear hyperfine and quadrupole) with either deuterons or 17O nuclei. bRCs were equilibrated in an atmosphere of different relative humidities allowing us to control precisely the hydration levels of the protein. We show that by using oxygen-17 labeled water quantitative conclusions can be made in contrast to using D2O which suffers from proton-deuterium exchange processes in the protein. From the experiments we also conclude that dry trehalose operates as an anhydrobiotic protein stabilizer in line with the "anchorage hypothesis" of bio-protection. It predicts selective changes in the first solvation shell of the protein upon trehalose-matrix dehydration with subsequent changes in the hydrogen-bonding network. Changes in hydrogen-bonding patterns usually have an impact on the global function of a biological system.


Generating realistic scaled complex networks.
Research on generative models plays a central role in the emerging field of network science, studying how statistical patterns found in real networks could be generated by formal rules. Output from these generative models is then the basis for designing and evaluating computational methods on networks including verification and simulation studies. During the last two decades, a variety of models has been proposed with an ultimate goal of achieving comprehensive realism for the generated networks. In this study, we (a) introduce a new generator, termed ReCoN; (b) explore how ReCoN and some existing models can be fitted to an original network to produce a structurally similar replica, (c) use ReCoN to produce networks much larger than the original exemplar, and finally (d) discuss open problems and promising research directions. In a comparative experimental study, we find that ReCoN is often superior to many other state-of-the-art network generation methods. We argue that ReCoN is a scalable and effective tool for modeling a given network while preserving important properties at both micro- and macroscopic scales, and for scaling the exemplar data by orders of magnitude in size.


Antenatal Testing for Women With Preexisting Medical Conditions Using Only the Ultrasonographic Portion of the Biophysical Profile.
To report the utility of the ultrasonographic biophysical profile, which includes all the components of a biophysical profile minus the nonstress test, in women with maternal indications for antepartum surveillance. We conducted a case series reviewing the records of all women at 32 weeks of gestation or greater with at least one indication for antenatal testing (per the American College of Obstetricians and Gynecologists) delivered by a single maternal-fetal medicine practice between 2006 and 2018. Indications included diabetes, hypertension, lupus, antiphospholipid syndrome, sickle cell disease, renal disease, heart disease, hyperthyroidism, isoimmunization, inherited thrombophilia, and prior intrauterine fetal demise. Weekly ultrasonographic biophysical profiles were initiated at 32 weeks of gestation. We calculated the test-positive rate, the percentage of women delivered for an abnormal ultrasonography biophysical profile, and the intrauterine fetal demise rate (false-negative rate). Nine hundred eighty-five women underwent 3,981 ultrasonographic biophysical profiles (four per woman; range 1-11). Sixteen women had an abnormal ultrasonographic biophysical profile, for a test positive rate of 1.6% (95% CI 1.0-2.6%) per woman, or 0.4% (95% CI 0.3-0.7%) per ultrasonographic biophysical profile. Of the 16 women with abnormal ultrasonographic biophysical profiles, 13 were delivered with good outcomes and three women had normal follow-up testing and uncomplicated deliveries at a later date. There were three women with intrauterine fetal demise (false-negative rate of 0.3%, 95% CI 0.1-0.9%). One woman with intrauterine fetal demise had a factor V Leiden mutation, fetal ventriculomegaly, and fetal growth restriction. The second woman with intrauterine fetal demise had advanced maternal age, a factor V Leiden mutation, and fetal growth restriction. The third woman with intrauterine fetal demise had class B diabetes. All three intrauterine fetal demises were diagnosed antepartum with an interval from normal ultrasonographic biophysical profile to intrauterine fetal demise of 7, 7, and 6 days, respectively. The use of ultrasonographic biophysical profile in a high-risk cohort is associated with a very low test-positive rate and a very low incidence of intrauterine fetal demise. In women with preexisting medical conditions that place them at higher risk for intrauterine fetal demise, ultrasonographic biophysical profile can be used for antenatal testing.


Nosocomial infection in an intensive care unit in a Brazilian university hospital.
This prospective study aimed to determine the nosocomial infection (NI) incidence in an Intensive Care Unit (ICU), its association with clinical characteristics and occurrence sites. It was carried out among 1.886 patients admitted in an ICU of a University Hospital, from August 2005 to January 2008. Data analysis was done using Fishers test and Relative Risk (RR). There were 383 NIs (20.3%). The infections were in the urinary tract (n=144; 37.6%), pneumonia (n=98; 25.6%), sepsis (n=58; 15.1%), surgical site (n=54; 14.1%) and others (n=29; 7.7%). Hospitalization average was 19.3 days for patients with NI and 20.2 days for those with colonization by resistant microorganisms. The mortality was 39.5% among patients with NI (RR: 4.4; 3.4-5.6). The NI was associated with patients originated from other units of the institution/emergency unit, more than 4 days of hospitalization, community infection, colonized by resistant microorganisms, using invasive procedures and deaths resulting from NI.


Association between breast milk erythropoietin and reduced risk of mother-to-child transmission of HIV.
We examined the prospective associations between breast milk concentrations of erythropoietin, a factor with trophic effects on infant gut epithelia, and the risk of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) through breast-feeding in a study of 59 MTCT cases and 116 controls nested within a cohort of antiretroviral-naive HIV-infected Tanzanian women. Controls were matched to cases on the basis of the time from birth when the breast milk sample was collected. The risk of MTCT was inversely related to breast milk erythropoietin concentration (adjusted odds ratio for highest vs lowest erythropoietin concentration tertile, 0.34 [95% confidence interval, 0.14-0.82]; P = .02). These results suggest a protective effect of breast milk erythropoietin against MTCT.


Culture, chaos, and refounding. How leaders can refound the Catholic health ministry.
Culture provides us with what we so desperately need in human life--a set of felt meanings in an orderly pattern. A group creates a culture as a way to cope with life's challenges and teach members the correct way to feel, think, and behave. No group is ever without a culture. If culture has a built-in tendency to resist change, how does change take place at all? The process of change involves separation, chaos, and reentry--the letting go of the old and familiar and the embracing of the uncertain new. The way to use chaos constructively is for people to return to the sacred time of their founding in order to identify, relive, and reown the heart of their creation mythology, liberated from the accidental and historical accretions that hold back creativity. For healthcare workers today, this means reidentifying with Christ's actions such as healing the sick or giving sight to the blind. Through this reidentification, healthcare givers can be fired up to form a new cultural integration adapted to changing needs. The chaos that our healthcare ministry is experiencing today offers us unparalleled opportunities for refounding. By acknowledging the chaos of the healthcare system, we thus lock in on the healing and reconciliatory power of God, and from this comes the energy to journey through the refounding process--the process whereby we struggle to enter collaboratively into the paschal mystery with Christ for his mission of healing; thus energized, we work to challenge systems and to create responses to the most urgent needs confronting the health of the people we serve.


Use of a surgical positioner for bone-anchored facial prostheses.
The use of osseointegrated implants to retain facial prostheses in craniofacial rehabilitation is a reliable procedure. Proper location of the implants is critical for fabrication of a prosthesis with ideal shape and contour. The use of a positioner at time of surgery can guide placement of the implants to achieve an optimum result. The positioner is also useful as a guide to the shape of the retentive element and as a quick method for obtaining a wax pattern for the prosthesis. This article describes-the fabrication and applications of a positioner.


Characterization of a doxorubicin liposome formulation by a novel in vitro release test methodology using column-switching high-performance liquid chromatography.
A novel in vitro release test methodology for a liposome formulation was developed using a column-switching high-performance liquid chromatography (HPLC) system. Doxorubicin (DXR) liposome formulations were used as a model. A DXR liposome formulation was dispersed into a release medium, and the dispersion fluid was directly injected at predetermined time points into the column-switching HPLC system. To evaluate the release profile, this system can be used for determining the released and encapsulated DXR in the liposome formulation separately. Comparison with a conventional in vitro release test methodology by dialysis revealed that the methodology developed by column-switching HPLC had no rate-limiting process of membrane permeation of the drug (which is occasionally observed in the dialysis method). The in vitro release profiles of DXR liposome formulations were well characterized using the method developed by column-switching HPLC, and different in vitro release characteristics were revealed. The developed method did not require a large amount of sample or a complicated pretreatment. In addition, the developed column-switching HPLC system was applicable for characterization of the encapsulation profile of liposome formulations.


Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet.
To investigate safety, compliance, and efficacy, on weight loss and cardiovascular risk factors of a multiphasic dietary intervention based on meal replacements, including a period of very low calorie diet (VLCD) in a population of obese patients. Anthropometric parameters, blood tests (including insulin), dual-energy-X-ray absorptiometry (DXA), and questionnaires for the assessment of safety and compliance before and after (phase I) a 30-day VLCD, 700 kcal/day, normoproteic, 50 g/day carbohydrate, four meal replacements; (phase II) a 30-day low calorie diet (LCD), 820 kcal/day, three meal replacements plus a protein plate; (phase III) 60-day LCD, 1,100 kcal/day, two meal replacements plus two protein plates and reintroduction of small amounts of carbohydrates; (phase IV) 60-day hypocaloric balanced diet (HBD), 1,200 kcal/day, one meal replacement, two protein plates and the reintroduction of carbohydrates. 24 patients (17 females, 7 males, mean BMI 33.8±3.2 kg/m2, mean age 35.1±10.2 years) completed the study. The average weight loss was 15.4±6.7%, with a significant reduction of fat mass (from 32.8±4.7 to 26.1±6.3% p<0.05) and a relative increase of lean mass (from 61.9±4.8 to 67.1±5.9% p<0.05). An improvement of metabolic parameters and no variations of the liver and kidney functions were found. A high safety profile and an excellent dietary compliance were seen. The VLCD dietary program and the replacement dietary system described here is an effective, safe, and well-tolerated treatment for weight control.


Indications for enucleation and evisceration in a tertiary eye hospital in Riyadh over a 10-year period.
Enucleation and evisceration are eye removal procedures considered as palliative treatment when all other therapeutic options are exhausted. Describe the causes and histopathological findings leading to enucleation/evisceration, and correlate the clinical findings with the histopathological findings. Retrospective, descriptive study. Tertiary care hospital, Riyadh, Saudi Arabia. The medical records of patients who underwent enucleation or evisceration from February 2005 to May 2015 were reviewed. Patients were classified into two categories based on indications of surgery: traumatic and nontraumatic. Causes of ocular injury in the traumatic group were documented, and the histopathological findings were reviewed for the nontraumatic cases. Number of enucleation and evisceration surgeries and their causes and histopathological findings. One hundred ten patients underwent evisceration (n=69, 63%) and enucleation (n=41, 37%). Causes were traumatic in 38 (35%) and nontraumatic in 72 (65%). The median age was 50 years and there were 64 men and 46 women. Postoperative endophthalmitis was the most common indication for surgery (n=24, 21.8%), followed by painful blind eye (n=22, 20%). Ocular trauma was more predominant in men (n=29, 76%) than in women (n=9, 24%), and the leading mechanism of trauma was metallic nail injuries (n=6, 15.8%). In the nontraumatic group, endophthalmitis was the most common histopathological finding (n=25, 34.7%). The majority of the eye enucleation/evisceration surgeries were due to nontraumatic causes, especially postoperative infections. However, severe eye trauma was still a main indication for this destructive procedure. Guidelines are needed to decrease the incidence/severity of work-related eye injuries and to detect and manage eye infections earlier and more promptly. Retrospective study, in one hospital in one area; therefore, results cannot be generalized.


A Shallow Water Ferrous-Hulled Shipwreck Reveals a Distinct Microbial Community.
Shipwrecks act as artificial reefs and provide a solid surface in aquatic systems for many different forms of life to attach to, especially microbial communities, making them a hotspot of biogeochemical cycling. Depending on the microbial community and surrounding environment, they may either contribute to the wreck's preservation or deterioration. Even within a single wreck, preservation and deterioration processes may vary, suggesting that the microbial community may also vary. This study aimed to identify the differences through widespread sampling of the microbial communities associated with the Pappy Lane shipwreck (NC shipwreck site #PAS0001), a shallow water ferrous-hulled shipwreck in Pamlico Sound, North Carolina to determine if there are differences across the wreck as well as from its surrounding environment. Loose shipwreck debris, drilled shipcores, surrounding sediment, and seawater samples were collected from the Pappy Lane shipwreck to characterize the microbial communities on and around the shipwreck. Results indicated that the shipwreck samples were more similar to each other than the surrounding sediment and aquatic environments suggesting they have made a specialized niche associated with the shipwreck. There were differences between the microbial community across the shipwreck, including between visibly corroded and non-corroded shipwreck debris pieces. Relative abundance estimates for neutrophilic iron-oxidizing bacteria (FeOB), an organism that may contribute to deterioration through biocorrosion, revealed they are present across the shipwreck and at highest abundance on the samples containing visible corrosion products. Zetaproteobacteria, a known class of marine iron-oxidizers, were also found in higher abundance on shipwreck samples with visible corrosion. A novel Zetaproteobacteria strain, Mariprofundus ferrooxydans O1, was isolated from one of the shipwreck pieces and its genome analyzed to elucidate the functional potential of the organism. In addition to iron oxidation pathways, the isolate has the genomic potential to perform carbon fixation in both high and low oxygen environments, as well as perform nitrogen fixation, contributing to the overall biogeochemical cycling of nutrients and metals in the shipwreck ecosystem. By understanding the microbial communities associated with shallow water ferrous-hulled shipwrecks, better management strategies and preservation plans can be put into place to preserve these artificial reefs and non-renewable cultural resources.


Anisotropic etching and nanoribbon formation in single-layer graphene.
We demonstrate anisotropic etching of single-layer graphene by thermally activated nickel nanoparticles. Using this technique, we obtain sub-10-nm nanoribbons and other graphene nanostructures with edges aligned along a single crystallographic direction. We observe a new catalytic channeling behavior, whereby etched cuts do not intersect, resulting in continuously connected geometries. Raman spectroscopy and electronic measurements show that the quality of the graphene is resilient under the etching conditions, indicating that this method may serve as a powerful technique to produce graphene nanocircuits with well-defined crystallographic edges.


Madurella mycetomatis is highly susceptible to ravuconazole.
The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between ≤ 0.002 and 0.031 µg/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma.


CNS regulation of glucose homeostasis.
The past decade has hosted a remarkable surge in research dedicated to the central control of homeostatic mechanisms. Evidence indicates that the brain, in particular the hypothalamus, directly senses hormones and nutrients to initiate behavioral and metabolic responses to control energy and nutrient homeostasis. Diabetes is chiefly characterized by hyperglycemia due to impaired glucose homeostatic regulation, and a primary therapeutic goal is to lower plasma glucose levels. As such, in this review, we highlight the role of the hypothalamus in the regulation of glucose homeostasis in particular and discuss the cellular and molecular mechanisms by which this neural pathway is orchestrated.


Identification of Mycobacterium avium complex in sarcoidosis.
Cell wall-defective bacteria which later reverted to acid-fast bacilli have been isolated from sarcoid tissue. These have not been conclusively shown to be mycobacteria. Specific PCR assays were applied to identify mycobacterial nucleic acids in these cultured isolates and in fresh specimens obtained from patients with sarcoidosis. Positive amplification and hybridization were observed with Mycobacterium avium complex- and/or Mycobacterium paratuberculosis-specific probes in five of the six cultured isolates and two fresh skin biopsy samples and one cerebrospinal fluid specimen. There was no amplification or hybridization with Mycobacterium tuberculosis or M. avium subsp. silvaticum probes, respectively. Patients' sera were also tested for antibody reactivities by immunoblotting with M. paratuberculosis recombinant clones expressing the 36,000-molecular-weight antigen (36K antigen) (p36) and the 65K heat shock protein (PTB65K). All seven sarcoidosis, four of six tuberculosis, and all six leprosy patient serum specimens showed strong reactivity with p36 antigen. In contrast, 13 of 38 controls showed only weak reactivity with p36 (P = 0.002 for controls versus sarcoidosis samples). Similarly, PTB65K reacted with high intensity with sera from 5 of 5 sarcoidosis, 5 of 6 tuberculosis, and 5 of 6 leprosy patients, compared with its low-intensity reaction with 5 of 22 controls (P = 0.001 for controls versus sarcoidosis samples). This study demonstrates the isolation and/or identification of M. paratuberculosis or a closely related M. avium complex strain from sarcoid skin lesions and cerebrospinal fluid. Furthermore, the reactivity of antibodies in sarcoid patient sera against p36 and PTB65K antigens was comparable to the reactivity of sera obtained from patients with known mycobacterial disease. Collectively, these data provide further support for the theory of the mycobacterial etiology of sarcoidosis.


[Understanding the neuropsychological symptoms associated with cortical dysfunction].
Damage to association cortices can result in a variety of cognitive and behavioral symptoms. Superficially, the relationship between lesion sites and the corresponding symptoms seems constant. However, some degree of dissociation of symptoms among patients with different etiologies appears to be the rule rather than the exception, even when the lesion locations appear similar in neuroimaging studies. Examinations of patients with primary progressive aphasia (PPA) have challenged the classic language model that is based on observations mainly made in patients with cerebrovascular diseases. The neuropsychological findings of patients with semantic variant PPA and neuroimaging evidence in healthy subjects converge to indicate that the anterior temporal lobe is an important component of language and semantic networks. Recent findings, however, have demonstrated that atrophy and dysfunction in patients with semantic variant PPA involve a number of regions in addition to the anterior temporal lobe. This indicated that specifically linking language deficits to the anterior temporal lobe is difficult. An understanding the pathophysiological processes is require to comprehend the symptoms of cortical dysfunction, especially in the association cortices.