Divergent mRNA transcription in the chloroplast psbB operon.
The genes psbB, psbH, petB and petD for the components in photosystem II and the cytochrome b6/f complex are clustered and co-transcribed in liverwort Marchantia polymorpha chloroplasts. On the opposite DNA strand in the spacer region between the genes psbB and psbH, we deduced an open reading frame consisting of 43 sense codons, and designated it as the ORF43 gene. The ORF43 gene was actively transcribed in liverwort chloroplasts. The ORF43 transcripts were entirely complementary to a part of the primary transcripts of the psbB operon. Heterogeneous Northern hybridization showed that the mRNA transcripts for the ORF43 gene increased with greening in pea seedlings. This is the first demonstration of divergent overlapping transcription in chloroplasts.


"I can't kill myself": Local narratives and meanings that foster absenteeism in Nigerian primary health centres.
Absenteeism in the health sector is increasingly seen as a form of harmful rule-breaking, with health workers receiving a salary although they are not present to provide care. It is a barrier to achieving universal health coverage yet remains widespread in primary health centres (PHCs) in Nigeria and many other low-resource settings. Traditional approaches to combatting absenteeism have relied on anti-corruption measures such as promoting accountability and transparency. However, more needs to be understood about the social and cultural realities, including perceptions and norms enabling or constraining the application of such measures in Nigeria and in similar contexts. We conducted 34 in-depth interviews (IDIs) with frontline health workers and their managers/supervisors and two focus group discussions (FDGs) with service users (n = 22) in Enugu State, South Eastern Nigeria. We discussed their experiences and views about absenteeism, allowing the respondents' framings to emerge. We adopted a mixed approach of narrative analysis and phenomenology to examine respondents' narratives - identifying the concepts and social constructs within the narratives that manifested through the language used. Stakeholders acknowledged the problem of absenteeism but had differing perspectives on its dynamics. Health workers distinguished two forms of absenteeism: one as a mundane, everyday response to the poorly funded health system; and the other, brazen and often politically enabled absenteeism, where health workers whom powerful politicians protect are absent without facing consequences. There is a general feeling of powerlessness among both health service providers and service users confronted by politically backed absentees as the power dynamics in the health sector resonate with experiences in other spheres of life in Nigeria. Health workers rationalised mundane, technical absenteeism, adjusted to it and felt it should be accommodated in the health system. Service users are often unsure about who is absent and why, but when they notice absenteeism, they often ascribe it to wider system malpractices that characterise public services. Interventions to tackle absenteeism and other forms of health sector corruption should be sensitive to socio-cultural and political contexts that shape everyday lives in specific contexts. Challenging narratives/beliefs that normalise absenteeism should be part of reform plans.


Novel Application of Point-of-Care Ocular Ultrasound in a Left Central Retinal Artery Occlusion.
Central retinal artery occlusion represents a vision-threatening entity in those presenting with monocular painless vision loss, especially in the elderly and those with cardiovascular comorbidities. While confirmation of this diagnosis requires consultation with an ophthalmologist, prompt recognition is the crucial action of the emergency physician to help reverse retinal ischemia and save vision. Here we describe the case of a central retinal artery occlusion identified on point-of-care ocular ultrasound and confirmed by fluorescein angiography.


Update on botulinum toxin use in facial plastic and head and neck surgery.
The purpose of this review is to discuss current trends in the medicinal use of botulinum toxin in head and neck and facial plastic surgery. The basic science of botulinum toxin is presented along with a comparison of the subtypes currently available on the market. Site-specific applications of botulinum toxin in the head and neck region are presented. The use of botulinum toxin continues to expand, both in volume and in number of applications. The main application of botulinum toxin in facial plastic surgery is in the effacement of dynamic or hyperkinetic facial lines. The granting of US Food and Drug Administration approval for the use of Botulinum Toxin type A in the treatment of glabella lines marks a major milestone for the more widespread usage of this product in cosmetic settings. Additional cosmetic applications include crow's feet, marionette lines, and platysma banding. Noncosmetic applications in the head and neck include dystonias (including torticollis), facial and generalized muscle spasms, migraine headaches, hyperhidrosis, spasmodic dysphonia, sialorrhea, gustatory sweating, and involuntary movement disorders. The use of botulinum toxin in the treatment of hyperkinetic conditions and disorders of excessive salivation is well established and enjoys an excellent safety profile. The cosmetic use of botulinum toxin continues to expand. The chronic use of botulinum toxin specifically for cosmetic purposes is worthy of additional study.


Palliative endoscopic electrocautery of esophageal cancer.
Six patients with obstructing esophageal carcinoma who were poor candidates for surgery were treated by endoscopic electrocautery. All of them were able to swallow well after 3 sessions of treatment. Endoscopic electrocautery is effective in palliative management of esophageal carcinoma, inexpensive and can be done with acceptable complications.


Description and comparative study of physico-chemical parameters of the teleost fish skin mucus.
The study of mucosal surfaces, and in particular the fish skin and its secreted mucus, has been of great interest recently among immunologists. Measurement of the viscosity and other physico-chemical parameters (protein concentration, pH, conductivity, redox potential, osmolality and density) of the skin mucus can help to understand its biological functions. We have used five marine species of teleost: gilthead seabream (Sparus aurata L.), European sea bass (Dicentrarchus labrax L.), shi drum (Umbrina cirrosa L.), common dentex (Dentex dentex L.) and dusky grouper (Epinephelus marginatus L.), all of them with commercial interest in the aquaculture of the Mediterranean area. Mucus showed a direct shear- and temperature-dependent viscosity, with a non-Newtonian behavior, which differed however between two groups: one with higher viscosity (D. labrax, U. cirrosa, D. dentex) and the other with lower viscosity (S. aurata, E. marginatus). In addition, there was a clear interrelation between density and osmolality, as well as between density and temperature. Taking into account that high values of viscosity should improve the barrier effect against pathogens but low values of viscosity are needed for good locomotion characteristics, our results may help elucidate the relationship between physico-chemical and biological parameters of skin mucus, and disease susceptibility.


M2-polarized tumor-associated macrophage infiltration of regional lymph nodes is associated with nodal lymphangiogenesis and occult nodal involvement in pN0 pancreatic cancer.
Tumor-associated macrophages (TAMs) are reportedly involved in lymphangiogenesis in primary tumors, playing a crucial role in lymphatic metastasis. Furthermore, nodal lymphangiogenesis precedes and promotes regional lymph node (RLN) metastasis. We investigated the relationship of M2-polarized TAM infiltration of the RLNs, nodal lymphangiogenesis, and occult nodal involvement in pN0 pancreatic cancer. Hematoxylin-eosin-stained primary tumor and regional LN specimens from 40 patients diagnosed with pN0 pancreatic cancer according to the pathological TNM classification were assessed. To evaluate lymphangiogenesis, lymphatic vessel density was measured by using D2-40 antibody. CD163 and cytokeratin AE1/AE3 antibodies were used to detect M2-polarized TAMs and isolated tumor cells in the RLNs, respectively. The nodal lymphatic vessel density had a strong association with the M2-polarized TAM density in the RLNs (P < 0.0001). Most of these TAMs expressed vascular endothelial growth factor C. Furthermore, in the RLNs, the M2-polarized TAM density was significantly associated with the incidence of isolated tumor cells (P = 0.0477). M2-polarized TAM infiltration of RLNs is significantly associated with nodal lymphangiogenesis and occult nodal involvement in pN0 pancreatic cancer. Node-infiltrating M2-polarized TAMs may facilitate nodal lymphangiogenesis via the production of vascular endothelial growth factor C and thus promote RLN metastasis.


Phenotypic spectrum of interstitial 7p duplication in mosaic and non-mosaic forms.
The phenotypes of a mother and child with a duplication of 7p15-7p22 are described. The mother is mosaic for the cytogenetic abnormality, whereas all cells are affected in her son. Fewer than 5 patients with interstitial 7p duplications are described in the world literature whereas over 30 phenotypic descriptions of individuals with terminal 7p duplication can be found. Authors have suggested that the associated phenotype amounts to a recognizable syndrome. The current cases give further insights into the phenotype that results from pure 7p duplication, both in its mosaic and in its full form. Comparisons are made with previous cases, in the light of the shorter segment involved in the current patients, whose duplication does not extend to pter. This case description will be useful in counseling patients with duplications of 7p and lends support to the existence of characteristic craniofacial features and congenital malformations in this chromosome rearrangement. In addition, as earlier case reports all describe the phenotype associated with non-mosaic partial 7p trisomy, the current observations amount to clear evidence that mosaicism attenuates the phenotype of this rearrangement.


Memory for vocal tempo and pitch.
Two experiments examined the ability to remember the vocal tempo and pitch of different individuals, and the way this information is encoded into the cognitive system. In both studies, participants engaged in an initial familiarisation phase while attending was systematically directed towards different aspects of speakers' voices. Afterwards, they received a tempo or pitch recognition task. Experiment 1 showed that tempo and pitch are both incidentally encoded into memory at levels comparable to intentional learning, and no performance deficit occurs with divided attending. Experiment 2 examined the ability to recognise pitch or tempo when the two dimensions co-varied and found that the presence of one influenced the other: performance was best when both dimensions were positively correlated with one another. As a set, these findings indicate that pitch and tempo are automatically processed in a holistic, integral fashion [Garner, W. R. (1974). The processing of information and structure. Potomac, MD: Erlbaum.] which has a number of cognitive implications.


Genetic relationships among pathogenic strains of avian Escherichia coli.
Genetic relationships among 79 strains of Escherichia coli, isolated mostly from diseased chickens, were estimated on the basis of allelic variation at 15 enzyme-encoding loci, determined by multilocus enzyme electrophoresis. All 15 loci were polymorphic, with an average of 4.1 allelic states per locus. Comparisons of the observed combinations of alleles among strains revealed 37 distinct multilocus genotypes that were used to define naturally occurring cell lineages or clones. Two-thirds of the isolates were classified into 10 clones, including a single multilocus genotype that accounted for about a third of all isolates. For isolates of these clones, there was a high concordance (76%) between identity in multilocus genotype, O:K:H serotype, and pattern of resistance to five antibiotics. Cluster analysis disclosed two major complexes of closely related clones, in which more than 50% of the isolates were associated with localized infections (airsacculitis and pericarditis). Both complexes contained isolates with serotype O2:K1, indicating that this serotype can occur on diverse chromosomal backgrounds. The results suggest that colibacillosis within avian populations is caused by a relatively limited number of pathogenic clones representing at least two distinct clone complexes.


EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
Recent experiments have demonstrated that the Polycomb group (PcG) gene EZH2 is highly expressed in metastatic prostate cancer and in lymphomas. EZH2 is a component of the PRC2 histone methyltransferase complex, which also contains EED and SUZ12 and is required for the silencing of HOX gene expression during embryonic development. Here we demonstrate that both EZH2 and EED are essential for the proliferation of both transformed and non-transformed human cells. In addition, the pRB-E2F pathway tightly regulates their expression and, consistent with this, we find that EZH2 is highly expressed in a large set of human tumors. These results raise the question whether EZH2 is a marker of proliferation or if it is actually contributing to tumor formation. Significantly, we propose that EZH2 is a bona fide oncogene, since we find that ectopic expression of EZH2 is capable of providing a proliferative advantage to primary cells and, in addition, its gene locus is specifically amplified in several primary tumors.


[Social support practices from colleagues and relatives that promote the functioning of workers living with anxious or depressive symptoms].
Anxiety and depression are among the most common mental disorders in the workplace and represent one of the leading causes of disability among workers. Symptoms related to these disorders have important repercussions for workers and organizations, such as a decrease in job satisfaction, as well as various difficulties in functioning at work (e.g., presenteeism, absenteeism). Social support from colleagues and relatives represents a promising lever to support the numerous workers living with symptoms of depression or anxiety. Objective The aim of this study was to identify the social support practices of relatives and colleagues that are perceived as being beneficial to the work functioning of individuals with anxiety or depressive symptoms. Method To do this, we conducted semi-structured interviews with workers presenting symptoms of anxiety or depression (n=25) in order to explore their experiences regarding the social support they received. A 6-step thematic analysis was then performed. Results The results of our research identified 30 social support practices and grouped them into 5 broad functions: friendship (e.g., laughing with colleagues, contacting loved ones through technology or social networks during working hours), emotional support (e.g., listening, resolving conflicts quickly), social support (e.g., sharing experiences with others), instrumental support (e.g., helping with work-related or non-work-related tasks), informational support (e.g., giving advice to help reduce anxiety or depressive symptoms), and validation (e.g., normalizing or de-dramatizing situations). Conclusion In short, this study provides a relevant portrait of the various social support practices that relatives and colleagues can put forward to promote the functioning of workers presenting symptoms of anxiety or depression.


Chemical visualization of an attractant peptide, LURE.
The pollen tube attractant peptide LUREs of Torenia fournieri are diffusible peptides that attract pollen tubes in vitro. Here, we report a method enabling the direct visualization of a LURE peptide without inhibiting its attraction activity by conjugating it with the Alexa Fluor 488 fluorescent dye. After purifying and refolding the recombinant LURE2 with a polyhistidine tag, its amino groups were targeted for conjugation with the Alexa Fluor dye. Labeling of LURE2 was confirmed by its fluorescence and mass spectrometry. In our in vitro assay using gelatin beads, Alexa Fluor 488-labeled LURE2 appeared to have the same activity as unlabeled LURE2. Using the labeled LURE2, the relationship between the spatiotemporal change of distribution and activity of LURE2 was examined. LURE2 attracted pollen tubes when embedded in gelatin beads, but hardly at all when in agarose beads. Direct visualization suggested that the significant difference between these conditions was the retention of LURE2 in the gelatin bead, which might delay diffusion of LURE2 from the bead. Direct visualization of LURE peptide may open the way to studying the spatiotemporal dynamics of LURE in pollen tube attraction.


Lactoferrin suppresses loss of corneal epithelial integrity in a rabbit short-term dry eye model.
Human tear fluid contains lactoferrin at the highest concentration. In patients with dry eye such as Sjogren's syndrome, the concentration of lactoferrin in the tears is approximately half the normal value. The present study utilizes a short-term rabbit dry eye model to evaluate if lactoferrin containing eye drops can reverse any of the damage produced by blockage of blinking with an ocular speculum. Damage was evaluated based on the extent of methylene blue staining in histological sections. After 3 h of desiccation, the amount of extractable dye recovered following sacrifice increased by more than 4-fold in the vehicle-treated eyes. However, in those rabbits treated with 1% lactoferrin, dye recovery was only 40% of the value in the vehicle-treated eyes. Between 1-3 h and over a concentration range from 0.01 to 1% lactoferrin, the decreases in staining were both time and concentration dependent. Alternatively, if 1% lactoferrin was applied during the desiccation period, there was partial restoration of corneal epithelial integrity. These results suggest that lactoferrin may be of therapeutic value in decreasing the loss of corneal epithelial integrity in dry eye.


Ultrasonographic diagnosis of incompetent cervix. A case report.
The ultrasonographic findings of an incompetent cervix, the protrusion of the lower pole of the fetal membranes through the dilated internal os, may precede physical changes in the cervix. The symptoms at that time may be nonspecific. As this case report indicates, we believe that action--either close observation, conservative treatment or surgical intervention--should follow the detection of this condition.


Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14-16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4 ± 1.3 mM) than in CON rodents (6.3 ± 0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8 ± 0.2 mM) and CON animals (1.6 ± 0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.


Exploring HIV risk behavior and sexual/gender identities among transgender women and their sexual partners in Peru using respondent-driven sampling.
HIV prevalence is high among transgender women, but little is known about cisgender men who have sex with transgender women (MSTW). The objective of this study was to investigate characteristics and behavior of MSTW compared to transgender women and men who have sex with men (MSM) using a modified respondent-driven sampling design. Seed participants completed a survey and invited up to three sex partners. Forward recruitment continued in waves through the referral of sex partners. Cross-sectional data were assessed using mixed effects models. From February to July 2018, 479 participants in Lima, Peru enrolled (n = 199 transgender women, n = 196 MSTW, and n = 45 MSM). MSTW behavior and identity differed significantly from that of transgender women and MSM. MSTW primarily identified as bisexual (69%) or heterosexual (15%) and only 6% reported male partners. Insertive condomless anal intercourse was reported by 61% of MSTW; 46% did not know their HIV serostatus. Compared to MSTW without male partners, those with recent male partners were more likely to sell sex (OR 15.7, 95% CI 4.1-60.5), and report condomless receptive anal intercourse (OR 89.0, 95% CI 19.1-414.8). This evidence suggests that MSTW are a distinct population from MSM, and highlights the critical need to include MSTW in HIV research and interventions.


Rehabilitation staff nurses' job satisfaction.
The issue of job satisfaction among rehabilitation nurses has not been addressed frequently in the literature. This qualitative study was designed to assess rehabilitation nurses' concerns and suggestions for improving the program in a 38-bed acute rehabilitation unit. The study's results indicate that the role of the rehabilitation nurse remains a rewarding one when communication with staff is high and the patient is the focus.


Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells.
Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship with MSCs is not clear. Here, we have isolated from primary human neuroblastoma tumors a population of αFAP- and FSP-1-expressing CAFs that share phenotypic and functional characteristics with bone marrow-derived MSCs (BM-MSC). Analysis of human neuroblastoma tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages. These cells (designated CAF-MSCs) enhanced in vitro neuroblastoma cell proliferation, survival, and resistance to chemotherapy and stimulated neuroblastoma tumor engraftment and growth in immunodeficient mice, indicating an effect independent of the immune system. The protumorigenic activity of MSCs in vitro and in xenografted mice was dependent on the coactivation of JAK2/STAT3 and MEK/ERK1/2 in neuroblastoma cells. In a mouse model of orthotopically implanted neuroblastoma cells, inhibition of JAK2/STAT3 and MEK/ERK/1/2 by ruxolitinib and trametinib potentiated tumor response to etoposide and increased overall survival. These data point to a new type of protumorigenic CAF in the tumor microenvironment of neuroblastoma and to STAT3 and ERK1/2 as mediators of their activity. Cancer Res; 77(18); 5142-57. ©2017 AACR.


Curvature-driven morphing of non-Euclidean shells.
We investigate how thin structures change their shape in response to non-mechanical stimuli that can be interpreted as variations in the structure's natural curvature. Starting from the theory of non-Euclidean plates and shells, we derive an effective model that reduces a three-dimensional stimulus to the natural fundamental forms of the mid-surface of the structure, incorporating expansion, or growth, in the thickness. Then, we apply the model to a variety of thin bodies, from flat plates to spherical shells, obtaining excellent agreement between theory and numerics. We show how cylinders and cones can either bend more or unroll, and eventually snap and rotate. We also study the nearly isometric deformations of a spherical shell and describe how this shape change is ruled by the geometry of a spindle. As the derived results stem from a purely geometrical model, they are general and scalable.


Nitrogen-Doped Carbon Cages Encapsulating CuZn Alloy for Enhanced CO2 Reduction.
CuZn alloy, regarded as the active sites, shows excellent catalytic activity for the reverse water gas shift reaction, whereas the incorporation of N atoms, especially pyridinic N, can greatly improve its catalytic properties because of the strong promotion capacity for adsorption and activation of CO2 molecules. Herein, the synthesis strategy involving Cu-doped Zn-based metal-organic frameworks is utilized to prepare CuZn alloy coated in an N-doped carbon shell. The excellent catalytic ability for CO2 transformation originates from the synergistic catalytic effect between CuZn alloy and pyridinic N. The strong adsorption and activation capacity for CO2 of pyridinic N is ascribed to the lone pair of electrons on the N atom and the high electron density in its vicinity.


Palladium-Catalyzed para-Selective Allylation of 1-(Cyanomethyl)arenes with Allyl Acetates.
The Pd/PMe3-catalyzed allylation of 1-(cyanomethyl)naphthalenes with allyl acetates proved to be para- rather than α-regioselective. This reaction is thought to proceed through ligand attack of the para-carbon in the arenes, electronically enriched by a cyano-stabilized α-carbanion, to the (π-allyl)palladium and a 1,5-hydrogen shift of the para-hydrogen from the dearomatized intermediate.


Salary and power: How occupational status affects children's occupational aspirations.
In many countries, labor markets are still highly gender segregated, with very few men working in communal occupations such as nursing. Because occupational aspirations start to develop during early childhood, it seems crucial to foster our understanding of which factors affect occupational aspirations during this period. Earlier correlational research showed that the status of occupations seems to be one important factor. Therefore, in the current work, we experimentally tested the effect of two dimensions of status (i.e., salary and power) on children's occupational aspirations and examined its interaction with child gender. We also tested the relationship among gender, self-perceptions, and occupational values. Using a 2 (Salary: high vs. low) × 2 (Power: high vs. low) within-participants design (N = 127 [59 boys and 68 girls], Mage = 9.37 years, SD = 0.50) with child gender as a between-participants factor, we show positive main effects of both salary and power on children's occupational aspirations but no interaction with gender. Correlational analyses show preliminary evidence for the mediating role of agentic self-perceptions in the relationship between gender and occupational values related to status. Thus, we provide evidence for the causal effect of occupational status on children's occupational aspirations but show experimentally that this is independent of child gender. Interestingly, the correlational analyses indicate that gender norms might play a role given that boys in trend reported stronger agentic self-perceptions, which then were associated with a stronger desire to pursue high-status occupations. Implications for early interventions to reduce occupational gender segregation are discussed.


[Study on the assignment method of intensity modulated radiotherapy plan for nasopharyngeal carcinoma based on MR images].
Objective: To discuss the influence of different computed tomography (CT) value assignment methods on dose calculation of intensity modulated radiotherapy (IMRT) plan which designed for nasopharyngeal carcinoma (NPC) and the value assignment methods of IMRT plan for NPC based on magnetic resonance (MR) images. Methods: Simulation CT and MR image of 32 NPC patients in Shandong Cancer Hospital from March 2018 to November 2018 were selected for this study. Populate CT values were obtained by contouring and analyzing the simulation CT of patients' tissue, including bone, air, brain, eyeball, optic-nerve, lens, parotid, masseter, skin. Pseudo-CT were generated by different CT value assignment methods: CT1: CT value of all tissues was set to 0HU; CT2: CT value of air cavity was set to populate CT value based on CT1; CT3: CT value of Bone was set to populate CT value based on CT2; CT4: CT value of each soft tissue were set to populate CT value based on CT3. The IMRT plan for NPC as Plan0 was designed base on simulation CT. Then Plan0 was transplanted to four pseudo-CT to recalculate the dose and obtain Plan1, Plan2, Plan3 and Plan4, the differences of dosimetric parameters were compared with Plan0. NPC-IMRT plan was designed base on MR images by using the assignment method with CT value of each tissue were set to populate CT value. Results: In the head and neck CT images, the average populate CT values of bone and cavity were 621 HU and -720 HU, respectively. The populate CT values of other soft tissue ranges from -20 HU to 70 HU. The differences of dosimetric indexes of Plan1, Plan2, Plan3, Plan4 decreased sequentially compare to Plan0, the difference of the dosimetry parameters of Plan4 and Plan0 was the smallest. The differences of PTV D(99), PTV D(95), isocenter dose, D(mean) of all tissues, D(max) of bilateral eye balls, D(max) of bilateral lens, D(max) of bilateral optic nerves, D(mean) of bilateral parotid, V(20) of bilateral parotid, D(50) of bilateral parotid, D(max) of spinal cord, D(max) of brainstem, D(5) of brainstem between Plan4 and Plan0 were all less than 1%. The difference of V(30) in bilateral parotid between Plan4 and Plan0 was less than 1.5%. In the comparison of the pixel dose distribution, the regions of dose distribution difference greater than 1% mainly distributed in the air cavity, bone periphery and the skin. The target area of the IMRT plan for NPC based on MR images met 95% of the prescribed dose, and the dose of each organ at risk was within the dose limit. Conclusions: The assignment method of each tissue and organs set to populate CT value compared with other methods has the least influence on the dose calculation of NPC-IMRT plan, which could meet the clinical requirements. Therefore, it should be the first choice of assignment method when designing NPC-IMRT plan based on MR image.


[Autoimmune pemphigus combined with alpha 1-antitrypsin deficiency].
It has been demonstrated experimentally that the bullae observed in autoimmune pemphigus are due to the action of proteases. So far, no case of pemphigus associated with deficiency in antiprotease has been reported. We present a case of pemphigus associated with familial deficiency in alpha 1-antitrypsin (alpha 1-AT), a major human body antiprotease. A 35-year old man presented with pemphigus preceded during 18 months, and accompanied by pruritus. The lesions were polymorphous, being made of solitary bullae, circinate vesiculobullae and squamous scabie plaques. Histopathological examination showed an intraepidermal bulla with acantholysis, a very spongiosis. The diagnosis of autoimmune pemphigus was confirmed by fluorescence of the epidermis in IgG and C3 and by the presence of antibodies directed against the intracellular substance. The initial treatment, which consisted of prednisolone 10 mg/kg/day and 10 plasma exchanges, was rapidly successful, but several relapses occurred thereafter. Two years after the pemphigus was diagnosed, a panlobular emphysema was discovered which made it possible to demonstrate a severe familial deficiency in alpha 1-AT of the Pi phenotype. This is the first published case of alpha 1-AT deficiency associated with autoimmune pemphigus. In our patient the skin disease presented as herpetiform pemphigus (initial features of dermatitis herpetiformis, followed by misleading polymorphous lesions, rare acantholytic cells, good response to corticosteroids), but there was no eosinophilic spongiosis. The frequency of alpha1-AT deficiency (estimated at 1 in 1,000 in northern Europe) and the lack of published cases with such an association may suggest a pure coincidence.(ABSTRACT TRUNCATED AT 250 WORDS)


The cost of an upper gastroduodenal endoscopy: an activity-based approach.
The cost of medical procedures is often unknown, but is nevertheless crucial for setting reimbursement and health care policies. The cost of an upper gastroduodenal endoscopy was investigated in ambulatory adults in a large academic hospital in the province of Quebec, from the perspective of the hospital. An activity-based costing methodology was used to break down the procedure into a number of priory tasks, to which resources used at the department level (labour, equipment, materials) were allocated. The direct cost of performing an endoscopy ranged from $62 for an unsedated, unbiopsied patient to $89 for a sedated, biopsied patient. Not included in this amount were separate reimbursement fees of $15 for biopsy analysis and the $50 professional fee for the performing physician, which are charged directly to the Ministry of Health. Incorporating overall, general hospital fixed overhead costs raises the cost of the procedure substantially, by $41, as does the use of nonreusable biopsy forceps, which adds about $63 to the total cost of the procedure. Given the high proportion of overall, hospital-wide, overhead costs in the total cost of the procedure, allocation methods of these overhead costs in current hospital accounting systems should be improved to obtain a more precise estimate of the full cost of upper gastroduodenal endoscopy.


A comparison of underwater hearing sensitivity in bottlenose dolphins (Tursiops truncatus) determined by electrophysiological and behavioral methods.
Variable stimulus presentation methods are used in auditory evoked potential (AEP) estimates of cetacean hearing sensitivity, each of which might affect stimulus reception and hearing threshold estimates. This study quantifies differences in underwater hearing thresholds obtained by AEP and behavioral means. For AEP estimates, a transducer embedded in a suction cup (jawphone) was coupled to the dolphin's lower jaw for stimulus presentation. Underwater AEP thresholds were obtained for three dolphins in San Diego Bay and for one dolphin in a quiet pool. Thresholds were estimated from the envelope following response at carrier frequencies ranging from 10 to 150 kHz. One animal, with an atypical audiogram, demonstrated significantly greater hearing loss in the right ear than in the left. Across test conditions, the range and average difference between AEP and behavioral threshold estimates were consistent with published comparisons between underwater behavioral and in-air AEP thresholds. AEP thresholds for one animal obtained in-air and in a quiet pool demonstrated a range of differences of -10 to 9 dB (mean = 3 dB). Results suggest that for the frequencies tested, the presentation of sound stimuli through a jawphone, underwater and in-air, results in acceptable differences to AEP threshold estimates.


Outpatient dermatology consultation impacts the diagnosis and management of pediatric oncology patients: A retrospective study.
The impact of dermatology consultation on the care of children with oncologic conditions is unknown. To review outpatient dermatology visits and the resulting impact on diagnosis and management of pediatric oncology patients. Retrospective review of pediatric oncology patients with outpatient dermatology visits at a tertiary care center from 2008 to 2015. The most common dermatologic diagnoses in 516 patients were skin infections (21.3%) and nonmalignant skin eruptions (33.4%). A diagnosis of significant impact (ie, malignancy, adverse cutaneous drug reaction, graft-versus-host disease, varicella-zoster virus, or herpes simplex virus infection), was made at the dermatology clinic in 14.7% of visits. Consultation resulted in a change in diagnosis in 59.8% of patients, change in dermatologic management in 72.4% of patients, and change in management of noncutaneous issues in 12.4% of patients. The use of electronic medical records, the nongeneralizable study population, and the retrospective design represent potential limitations. Outpatient dermatology consultation can affect the care of pediatric oncology patients with respect to diagnosis and treatment of skin conditions and management of nondermatologic issues.


Genetic Characteristics of Coronaviruses from Korean Bats in 2016.
Bats have increasingly been recognized as the natural reservoir of severe acute respiratory syndrome (SARS), coronavirus, and other coronaviruses found in mammals. However, little research has been conducted on bat coronaviruses in South Korea. In this study, bat samples (332 oral swabs, 245 fecal samples, 38 urine samples, and 57 bat carcasses) were collected at 33 natural bat habitat sites in South Korea. RT-PCR and sequencing were performed for specific coronavirus genes to identify the bat coronaviruses in different bat samples. Coronaviruses were detected in 2.7% (18/672) of the samples: 13 oral swabs from one species of the family Rhinolophidae, and four fecal samples and one carcass (intestine) from three species of the family Vespertiliodae. To determine the genetic relationships of the 18 sequences obtained in this study and previously known coronaviruses, the nucleotide sequences of a 392-nt region of the RNA-dependent RNA polymerase (RdRp) gene were analyzed phylogenetically. Thirteen sequences belonging to SARS-like betacoronaviruses showed the highest nucleotide identity (97.1-99.7%) with Bat-CoV-JTMC15 reported in China. The other five sequences were most similar to MERS-like betacoronaviruses. Four nucleotide sequences displayed the highest identity (94.1-95.1%) with Bat-CoV-HKU5 from Hong Kong. The one sequence from a carcass showed the highest nucleotide identity (99%) with Bat-CoV-SC2013 from China. These results suggest that careful surveillance of coronaviruses from bats should be continued, because animal and human infections may result from the genetic variants present in bat coronavirus reservoirs.


A COMBINATION OF HERPES VIRUS INFECTION (HSV-1, HHV-6) AND MULTI-RESISTANT BACTERIAL INFECTION IN A SEVERELY BURNED PEDIATRIC PATIENT - A CASE REPORT.
Serious burn trauma is associated with changes of the immune system, and immunosuppression induced by burn trauma can lead to reactivation of latent infections. Herpetic viruses are known for their lifelong persistence after primary infection and ability to reactivate. Their reactivation in the setting of burn trauma or primary infection can cause serious complications for a weakened burn patient. Presented is a case of a toddler who sustained second-degree scald burns over 20% of his body surface area. The injury was complicated by a multi-resistant bacterial infection in addition to reactivation of a latent HHV-6 infection concurrently with a primary HSV-1 infection. Described further are basic diagnostics, local and systemic treatment strategies, and other complications due to disseminated herpetic infections. To date, HHV-6 reactivation has not been described in conjunction with burn injury.


Application of Queueing Theory to the Analysis of Changes in Outpatients' Waiting Times in Hospitals Introducing EMR.
This research used queueing theory to analyze changes in outpatients' waiting times before and after the introduction of Electronic Medical Record (EMR) systems. We focused on the exact drawing of two fundamental parameters for queueing analysis, arrival rate (λ) and service rate (µ), from digital data to apply queueing theory to the analysis of outpatients' waiting times. We used outpatients' reception times and consultation finish times to calculate the arrival and service rates, respectively. Using queueing theory, we could calculate waiting time excluding distorted values from the digital data and distortion factors, such as arrival before the hospital open time, which occurs frequently in the initial stage of a queueing system. We analyzed changes in outpatients' waiting times before and after the introduction of EMR using the methodology proposed in this paper, and found that the outpatients' waiting time decreases after the introduction of EMR. More specifically, the outpatients' waiting times in the target public hospitals have decreased by rates in the range between 44% and 78%. It is possible to analyze waiting times while minimizing input errors and limitations influencing consultation procedures if we use digital data and apply the queueing theory. Our results verify that the introduction of EMR contributes to the improvement of patient services by decreasing outpatients' waiting time, or by increasing efficiency. It is also expected that our methodology or its expansion could contribute to the improvement of hospital service by assisting the identification and resolution of bottlenecks in the outpatient consultation process.


Prevalence and influencing factors of muscle mass loss in adults with diabetes and a high body fat percentage: A cross-sectional study.
In adults with type 2 diabetes (T2DM), sarcopenia and obesity are two common body composition issues. We investigated the associated influencing factors of muscle mass loss in obese adults with T2DM, to provide a theoretical basis for the prevention of sarcopenic obesity in patients with T2DM. We recruited 315 participants in this study. The participants underwent body composition assessment and clinical information was collected. Dual-energy X-ray absorptiometry was used to verify the accuracy of the body composition data. Based on their body fat percentage, 189 patients with T2DM were classified as obese. Patients with T2DM and obesity were grouped into the muscle mass loss group and non-muscle mass loss group based on gender. We collected demographic and clinical information about patients with T2DM who were obese, including their age, gender, body mass index (BMI), appendicular skeletal muscle index (ASMI), and body fat percentage (PBF). Among the participants who were obese and had T2DM, 56.61% (107/189) experienced muscle mass loss, with a detection rate of 43.42% (33/76) among females and 65.49% (74/113) among males. Body mass index, fat index, Android fat, Gynoid fat, limb fat, trunk fat, and total body bone mineral content were all lower in the muscle mass loss group compared to the non-muscle mass loss group, regardless of gender (all P< 0.001). Muscle mass loss in obese adults with T2DM was affected by BMI, body fat index, and limb fat. Muscle mass loss is more prevalent in adults with T2DM and a high PBF. Body mass index, body fat index, and limb fat are the protective factors of muscle mass loss in adult patients with T2DM and obesity.


Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection.
Clostridioides difficile infection (CDI) can result in severe disease and death, with no accurate models that allow for early prediction of adverse outcomes. To address this need, we sought to develop serum-based biomarker models to predict CDI outcomes. We prospectively collected sera ≤48 h after diagnosis of CDI in two cohorts. Biomarkers were measured with a custom multiplex bead array assay. Patients were classified using IDSA severity criteria and the development of disease-related complications (DRCs), which were defined as ICU admission, colectomy, and/or death attributed to CDI. Unadjusted and adjusted models were built using logistic and elastic net modeling. The best model for severity included procalcitonin (PCT) and hepatocyte growth factor (HGF) with an area (AUC) under the receiver operating characteristic (ROC) curve of 0.74 (95% confidence interval, 0.67 to 0.81). The best model for 30-day mortality included interleukin-8 (IL-8), PCT, CXCL-5, IP-10, and IL-2Rα with an AUC of 0.89 (0.84 to 0.95). The best model for DRCs included IL-8, procalcitonin, HGF, and IL-2Rα with an AUC of 0.84 (0.73 to 0.94). To validate our models, we employed experimental infection of mice with C. difficile Antibiotic-treated mice were challenged with C. difficile and a similar panel of serum biomarkers was measured. Applying each model to the mouse cohort of severe and nonsevere CDI revealed AUCs of 0.59 (0.44 to 0.74), 0.96 (0.90 to 1.0), and 0.89 (0.81 to 0.97). In both human and murine CDI, models based on serum biomarkers predicted adverse CDI outcomes. Our results support the use of serum-based biomarker panels to inform Clostridioides difficile infection treatment.IMPORTANCE Each year in the United States, Clostridioides difficile causes nearly 500,000 gastrointestinal infections that range from mild diarrhea to severe colitis and death. The ability to identify patients at increased risk for severe disease or mortality at the time of diagnosis of C. difficile infection (CDI) would allow clinicians to effectively allocate disease modifying therapies. In this study, we developed models consisting of only a small number of serum biomarkers that are capable of predicting both 30-day all-cause mortality and adverse outcomes of patients at time of CDI diagnosis. We were able to validate these models through experimental mouse infection. This provides evidence that the biomarkers reflect the underlying pathophysiology and that our mouse model of CDI reflects the pathogenesis of human infection. Predictive models can not only assist clinicians in identifying patients at risk for severe CDI but also be utilized for targeted enrollment in clinical trials aimed at reduction of adverse outcomes from severe CDI.


Genome-wide profiling of micro-RNA expression in gefitinib-resistant human lung adenocarcinoma using microarray for the identification of miR-149-5p modulation.
To understand the mechanism involved in gefitinib resistance, we established gefitinib-resistant human HCC827/GR-8-1 cell line from the parental HCC827 cell line. We compared the micro-RNA expression profiles of the HCC827 cells HCC827/GR-8-1 using Agilent micro-RNA microarrays. The micro-RNAs, such as the miR-149-5p, were up- or downregulated and associated with acquired gefitinib resistance. Quantitative real-time polymerase chain reaction was then performed to verify the expression patterns of different micro-RNAs. The result showed that miR-149-5p was upregulated in the HCC827/GR-8-1 cell line. To investigate the biological function of miR-149-5p in non-small cell lung cancer cells acquired gefitinib resistance, we examined cell proliferation using a cell counting kit-8 assay. Cell viability was evaluated after the miR-149-5p mimics, inhibitors, and negative control were separately transfected into the non-small cell lung cancer cells. The results showed that the non-small cell lung cancer cells transfected with miR-149-5p mimics exhibited reduced cell motility. The drug-sensitivity assay results revealed that the overexpression of miR-149-5p effectively evaluates the half maximal inhibitory concentration values of the cell in response to gefitinib, and the downregulation of miR-149-5p can attenuate the half maximal inhibitory concentration values of the cell lines in response to gefitinib. Furthermore, the levels of miR-149-5p in the HCC827 and HCC827/GR-8-1 cells were inversely correlated with caspase-3 expression. In conclusion, this study revealed that miR-149-5p is upregulated in the HCC827/GR-8-1 cells and involved in the acquired gefitinib resistance.


Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment.
Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.


Modeling and numerical computation of drug transport in laminates: model case evaluation of transdermal delivery system.
This study reports on the modeling and numerical computation of drug transport from a laminated system into the skin. The model is based on the diffusion equation, on partitioning of the drug between individual layers of the device, and on continuity conditions for diffusive flux across the material interfaces of the system. Numerical computation of concentration profiles across the system was performed using a sophisticated software package designed for a general class of kinetics-diffusion problems, including time variable diffusion coefficients and interface conditions in case of nonhomogeneous media. This program is demonstrated by a model case evaluation of a transdermal delivery system for nitroglycerin and applies previous data on drug diffusion and partitioning in this system. The layers involved in drug transport are: a polymer film to carry the drug depot; a microporous membrane, the pores of which are filled with nonpolar liquids and solids; an adhesive layer; and a final layer representing the skin. Transport kinetics in the delivery system and the skin are being followed by plots of concentration profiles as a function of application time. Major concentration gradients indicate sites of release control. For practical purposes, the package is intended to serve for preformulation studies of laminated drug delivery systems.


Liquid-crystal NMR structure of HIV TAR RNA bound to its SELEX RNA aptamer reveals the origins of the high stability of the complex.
Transactivation-response element (TAR) is a stable stem-loop structure of HIV RNA, which plays a crucial role during the life cycle of the virus. The apical loop of TAR acts as a binding site for essential cellular cofactors required for the replication of HIV. High-affinity aptamers directed against the apical loop of TAR have been identified by the SELEX approach. The RNA aptamers with the highest affinity for TAR fold as hairpins and form kissing complexes with the targeted RNA through loop-loop interactions. The aptamers with the strongest binding properties all possess a GA base pair combination at the loop-closing position. Using liquid-crystal NMR methodology, we have obtained a structural model in solution of a TAR-aptamer kissing complex with an unprecedented accuracy. This high-resolution structure reveals that the GA base pair is unilaterally shifted toward the 5' strand and is stabilized by a network of intersugar hydrogen bonds. This specific conformation of the GA base pair allows for the formation of two supplementary stable base-pair interactions. By systematic permutations of the loop-closing base pair, we establish that the identified atomic interactions, which form the basis for the high stability of the complex, are maintained in several other kissing complexes. This study rationalizes the stabilizing role of the loop-closing GA base pairs in kissing complexes and may help the development or improvement of drugs against RNA loops of viruses or pathogens as well as the conception of biochemical tools targeting RNA hairpins involved in important biological functions.


Antigenic and structural relationships of the surface antigens of hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis virus.
The surface antigens of human hepatitis B (HBsAg), ground squirrel hepatitis (GSHsAg), and woodchuck hepatitis (WHsAg) viruses were compared serologically, and their major polypeptides were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping. Results showed that both GSHsAg and WHsAg are antigenically cross-reactive, that their major pairs of polypeptides have identical mobilities on sodium dodecyl sulfate gels, and that the major polypeptides of GSHsAg and WHsAg migrate faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than do the corresponding bands of HBsAg. The peptide maps of the major (P-22) surface antigen polypeptides of GSHsAg and WHsAg showed that they shared over half of their spots. Peptide mapping of HBsAg subtypes indicated a close relationship between the major polypeptides (P-24) of adw and adr and a more distal relationship to ayw. Only about 25% of the spots shared by the combined HBsAg subtypes were also found in the peptide maps of GSHsAg and WHsAg, indicating at least some structural homology among the major polypeptides of the human and animal virus surface antigen particles. This is also reflected in the serological cross-reactivity among HBsAg, GSHsAg, and WHsAg. Further, the detection of ground squirrel and woodchuck antigens by Ausria II radioimmunoassay, combined with peptide mapping data indicating the common origin of these viruses, suggests that the common a determinant is shared by each and is restricted to approximately 25% of the sequences in their major polypeptides.


The midgut microbiota plays an essential role in sand fly vector competence for Leishmania major.
For many arthropod vectors, the diverse bacteria and fungi that inhabit the gut can negatively impact pathogen colonization. Our attempts to exploit antibiotic treatment of colonized Phlebotomus duboscqi sand flies in order to improve their vector competency for Leishmania major resulted instead in flies that were refractory to the development of transmissible infections due to the inability of the parasite to survive and to colonize the anterior midgut with infective, metacyclic stage promastigotes. The parasite survival and development defect could be overcome by feeding the flies on different symbiont bacteria but not by feeding them on bacterial supernatants or replete medium. The inhibitory effect of the dysbiosis was moderated by lowering the concentration of sucrose (<30% w/v) used in the sugar feeds to maintain the colony. Exposure of promastigotes to 30% sucrose was lethal to the parasite in vitro. Confocal imaging revealed that the killing in vivo was confined to promastigotes that had migrated to the anterior plug region, corresponding to the highest concentrations of sucrose. The data suggest that sucrose utilization by the microbiota is essential to promote the appropriate osmotic conditions required for the survival of infective stage promastigotes in vivo.


[Latrodectism in Madagascar].
Data concerning lactrodectism in Madagascar is scarce. Two spider species of the Latrodectus genus are found on the Grand Isle: the black widow Latrodectus mactans mena vody and the brown widow Latrodectus geometricus. From March 1991 through July 1992, 10 cases of envenomation by these spiders were treated in the Intensive Care Unit of Antananarivo Hospital. Symptomatology was remarkable with regard to severity (one fatality due to cardiovascular failure, one gangrene of the foot) as well as clinical manifestations (immediate local pain, kidney dysfunction, arterial hypertension). In two cases, the spider was captured and identified. Both were female brown widows (Latrodectus geometricus), which might explain the differences observed in comparison with the classic features of latrodectism that have been established from American and European black widow bites. Since antivenom was unavailable, only symptomatic treatment was administered, including intravenous calcium that proved effective for pain relief.


Three Arterial Ruptures in a Patient with Neurofibromatosis Type 1.
Neurofibromatosis type 1 (NF-1) is a rare disease known to cause vascular fragility. A case of a 59-year-old man with NF who had ruptures in three different arteries within a month is presented. The first rupture occurred in the right renal artery and was treated using a stent graft and embolization coils. The second and third ruptures occurred in an artery that had been compressed by a hematoma formed during the first bleed; both were embolized. In patients with NF-1, blood vessel fragility must be considered in treatment selection, especially when performing surgery or other invasive procedures near the great vessels.


Kaempferol Protects Against Cerebral Ischemia Reperfusion Injury Through Intervening Oxidative and Inflammatory Stress Induced Apoptosis.
The aim of this research is to investigate the potential neuro-protective effect of kaempferol which with anti-oxidant, anti-inflammatory, and immune modulatory properties, and understand the effect of kaempferol on reducing cerebral ischemia reperfusion (I/R) injury in vivo. Male adult Sprague Dawley (SD) rats were pretreated with kaempferol for one week via gavage before cerebral I/R injury operation. We found that kaempferol treatment can reduce the cerebral infarct volume and neurological score after cerebral I/R. Rats were sacrificed after 24 h reperfusion. We observed that kaempferol improved the arrangement, distribution, and morphological structure of neurons, as well as attenuated cell apoptosis in brain tissue via hematoxylin and eosin (H&E) staining, Nissl staining and TUNEL staining. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH) kit analysis, enzyme-linked immunosorbent (ELISA) assay, real-time PCR, Western blot, and immunohistochemical examination indicated that kaempferol mitigated oxidative and inflammatory stress via regulating the expression of proteins, p-Akt, p-GSK-3β, nuclear factor erythroid2-related factor 2 (Nrf-2), and p-NF-κB during cerebral I/R, thus increasing the activity of SOD and GSH, meanwhile decreasing the content of MDA in serum and brain tissue, as well as restoring the expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in vivo. Taken together, this study suggested that kaempferol protects against cerebral I/R induced brain damage. The possible mechanism is related with inhibiting oxidative and inflammatory stress induced apoptosis.


Introduction: Reappraising Paul Feyerabend.
This volume is devoted to a reappraisal of the philosophy of Paul Feyerabend. It has four aims. The first is to reassess his already well-known work from the 1960s and 1970s in light of contemporary developments in the history and philosophy of science. The second is to explore themes in his neglected later work, including recently published and previously unavailable writings. The third is to assess the contributions that Feyerabend can make to contemporary debate, on topics such as perspectivism, realism, and political philosophy of science. The fourth and final aim is to reconsider Feyerabend's place within the history of philosophy of science in the light of new scholarship.


Different Measures of Auditory and Visual Stroop Interference and Their Relationship to Speech Intelligibility in Noise.
Inhibition-the ability to suppress goal-irrelevant information-is thought to be an important cognitive skill in many situations, including speech-in-noise (SiN) perception. One way to measure inhibition is by means of Stroop tasks, in which one stimulus dimension must be named while a second, more prepotent dimension is ignored. The to-be-ignored dimension may be relevant or irrelevant to the target dimension, and the inhibition measure-Stroop interference (SI)-is calculated as the reaction time difference between the relevant and irrelevant conditions. Both SiN perception and inhibition are suggested to worsen with age, yet attempts to connect age-related declines in these two abilities have produced mixed results. We suggest that the inconsistencies between studies may be due to methodological issues surrounding the use of Stroop tasks. First, the relationship between SI and SiN perception may differ depending on the modality of the Stroop task; second, the traditional SI measure may not account for generalized slowing or sensory declines, and thus may not provide a pure interference measure. We investigated both claims in a group of 50 older adults, who performed two Stroop tasks (visual and auditory) and two SiN perception tasks. For each Stroop task, we calculated interference scores using both the traditional difference measure and methods designed to address its various problems, and compared the ability of these different scoring methods to predict SiN performance, alone and in combination with hearing sensitivity. Results from the two Stroop tasks were uncorrelated and had different relationships to SiN perception. Changing the scoring method altered the nature of the predictive relationship between Stroop scores and SiN perception, which was additionally influenced by hearing sensitivity. These findings raise questions about the extent to which different Stroop tasks and/or scoring methods measure the same aspect of cognition. They also highlight the importance of considering additional variables such as hearing ability when analyzing cognitive variables.


Impairment of taste and olfaction in patients with cirrhosis: the role of vitamin A.
Taste and olfaction sensory modalities and the response to vitamin A replenishment were studied in 37 vitamin A deficient patients (determined by low serum levels and abnormal dark adaptation) with stable alcoholic cirrhosis. Among this group of patients, 11 also had low serum zinc levels which ranged from 45 to 63 micrograms/dl. Initial taste and olfaction mean detection thresholds for all test substances were significantly higher (less sensitive) in all patients as compared to 21 sex-matched healthy subjects of the same age range (P less than 0.05). Twenty-seven patients including the 11 patients with low serum zinc were treated with oral vitamin A (10 000 micrograms/d) for 4 weeks. Among the vitamin a deficient patients there was significant improvement following vitamin A treatment in the mean detection and mean recognition thresholds for bitter and salty taste (P less than 0.01) and for pyridine olfaction (P less than 0.05) regardless of zinc status. Improvement in taste and olfaction correlated with a reversal of serum vitamin A levels and dark adaptation toward normal. The mechanism whereby vitamin A affects specific taste and smell (ie salty and bitter taste; pyridine smell) modalities is at present unknown.


[Analgesic effect of intra-artcular fentanyl in knee arthroscopy to treat patellofemoral lateral hyperpressure syndrome].
During arthroscopy for the treatment of patellofemoral lateral hyper-pressure syndrome (LHS), intra-articular morphine or its derivatives (fentanyl) may reduce postoperative pain when combined with anesthetics. We therefore decided to determine whether adding fentanyl to epinephrine and bupivacaine produced an increased analgesia. We randomly distributed 40 patients into two groups. The experimental group (n=20) was given 0.5% bupivacaine (2 mg/kg), epinephrine (100 microg) and fentanyl (2.5 microg/kg). The control group (n=20) received 0.5% bupivacaine (2 mg/kg) and epinephrine (100 microg). Patients underwent chondroplasty and retinacular release, and we assessed pain, time of analgesia and postoperative range of motion at postoperative hours 6 and 24. The age and the grade of patellofemoral chondromalacia (PFC) were similar in both groups (p > 0.05). No differences were found in pain and ranges of motion intraoperatively and at postoperative hours 6 and 24 (p > 0.05) between both groups. The postoperative analgesia time was similar (p > 0.05). Adding intra-articular fentanyl to the combination of epinephrine plus bupivacaine did not decrease pain, and did not increase neither the analgesia time nor the range of motion in patients with LHS undergoing knee arthroscopy.


Toward improved adherence: a text message intervention in an human immunodeficiency virus pediatric clinic in Guatemala City.
As access to human immunodeficiency virus treatment expands in Low to Middle Income Countries, it becomes critical to develop and test strategies to improve adherence and ensure efficacy. Text messaging improves adherence to antiretroviral treatment antiretroviral treatment in some patient populations, but data surrounding the use of these tools is sparse in pediatric and adolescent patients in low to middle income countries. We evaluated if a text message intervention can improve antiretroviral treatment adherence while accounting for cell phone access, patterns of use, and willingness to receive text messages.We carried out a cross sectional study to understand willingness of receiving text message reminders, followed by a randomized controlled trial to assess effectiveness of text message intervention.Enrolled participants were randomized to receive standard care with regular clinic visits, or standard care plus short message service reminders. Adherence was measured 3 times during the study period using a 4-day Recall Questionnaire. Outcome was measured based on differences in the average adherence between the intervention and control group at each time point (baseline, 3 months, 6 months).Most respondents were willing to receive text message adherence reminders (81.1%, n = 53). Respondent literacy, travel time to clinic, cell phone access, and patterns of use were significantly associated with willingness. In the randomized trial the intervention group (n = 50) experienced a small but significant mean improvement in adherence over the six-month period (4%, P < .01) whereas the control group (n = 50) did not (mean improvement: 0.8%, P = .64).Text message interventions effectively support antiretroviral adherence in pediatric patients living with human immunodeficiency virus. Studies designed to assess the impact of text messaging interventions must examine local context for cellular phone infrastructure and use and must account for potential loss to follow up when patients miss appointments and study assessments.


Stochastic Simulation of Dopamine Neuromodulation for Implementation of Fluorescent Neurochemical Probes in the Striatal Extracellular Space.
Imaging the dynamic behavior of neuromodulatory neurotransmitters in the extracelluar space that arise from individual quantal release events would constitute a major advance in neurochemical imaging. Spatial and temporal resolution of these highly stochastic neuromodulatory events requires concurrent advances in the chemical development of optical nanosensors selective for neuromodulators in concert with advances in imaging methodologies to capture millisecond neurotransmitter release. Herein, we develop and implement a stochastic model to describe dopamine dynamics in the extracellular space (ECS) of the brain dorsal striatum to guide the design and implementation of fluorescent neurochemical probes that record neurotransmitter dynamics in the ECS. Our model is developed from first-principles and simulates release, diffusion, and reuptake of dopamine in a 3D simulation volume of striatal tissue. We find that in vivo imaging of neuromodulation requires simultaneous optimization of dopamine nanosensor reversibility and sensitivity: dopamine imaging in the striatum or nucleus accumbens requires nanosensors with an optimal dopamine dissociation constant (Kd) of 1 μM, whereas Kds above 10 μM are required for dopamine imaging in the prefrontal cortex. Furthermore, as a result of the probabilistic nature of dopamine terminal activity in the striatum, our model reveals that imaging frame rates of 20 Hz are optimal for recording temporally resolved dopamine release events. Our work provides a modeling platform to probe how complex neuromodulatory processes can be studied with fluorescent nanosensors and enables direct evaluation of nanosensor chemistry and imaging hardware parameters. Our stochastic model is generic for evaluating fluorescent neurotransmission probes, and is broadly applicable to the design of other neurotransmitter fluorophores and their optimization for implementation in vivo.


Analysis of karyotype variation following carcinogen treatment of Chinese hamster primary cell lines.
Chinese hamster primary fibroblasts derived from several embryos were treated with the carcinogens benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine. Karyotype analysis, sister chromatid exchange frequency, evidence of transformation by growth in agar, cell morphology and reaction to cytocholasin B were tested at regular intervals over many culture passages. Carcinogen treatment was found to shorten the time period before onset of permanent karyotypically changed stem and side lines and in vitro transformation. Chromosomes X, 6 and 10 were more frequently involved in all cultures in these karyotype changes which were usually preceded by a period of chromosome variation. Spontaneous chromatid aberrations and aneuploidy increased in frequency with time in culture and generally appeared prior to the expression of transformation. No specific chromosomes were involved with the different carcinogens. There was no correlation between in vitro transformation and karyotype evolution and the criteria for transformation were present independently of one another. It is suggested that the lack of correlation between the parameters tested indicates that the expression of in vitro transformation is a result of selection for growth advantage from a cell population expressing an increasing degree of genetic instability and variation with time in culture.


Time to initiation of antenatal care visit and its predictors among reproductive age women in Ethiopia: Gompertz inverse Gaussian shared frailty model.
Early initiation of antenatal care (ANC) is essential for the early detection of pregnancy-related problems and unfavorable pregnancy outcomes. However, a significant number of mothers do not initiate ANC at the recommended time. Therefore, this study aimed to determine the median time of ANC initiation and its predictors among reproductive-age women in Ethiopia. We used the Ethiopian Demographic and Health Survey (EDHS) 2016 data set. The proportional hazard assumption was assessed using Schoenfeld residual test and log-log plot. A life table was used to determine the median survival time (time of ANC initiation). The Gompertz inverse Gaussian shared frailty model was the best-fitting model for identifying the predictors for the early initiation of ANC booking. Finally, the adjusted hazard ratio (AHR) with a 95% confidence interval (CI) was used to determine the significance of predictors. A total of 7,501 reproductive-aged women gave recent birth in the last 5 years preceding the survey. Nearly three in five women [61.95% (95% CI: 60.85-63.04%)] booked their first ANC visit with a median time of 4.4 months. Women who attended primary education (AHR = 1.10, 95% CI: 1.01-1.20), secondary and above (AHR = 1.26, 95% CI: 1.11-1.44), media exposure (AHR = 1.07, 95% CI: 1.00-1.16), rich wealthy (AHR = 1.17, 95% CI: 1.06-1.30), grand multiparous (AHR = 0.82, 95% CI: 0.72-0.93), unwanted pregnancy (AHR = 0.88, 95% CI: 0.81-0.96), small periphery region (AHR = 0.58, 95% CI: 0.51-0.67), and rural residence (AHR = 0.86, 95% CI: 0.75-0.99) were significantly associated with first ANC visit. According to this study, a significant number of women missed their first ANC visit. The education status of women, place of residence, region, wealth index, media exposure, unintended pregnancy, and multi-parity were significantly associated with the time of initiation of the first ANC visit. Therefore, policymakers should focus on improving the socioeconomic status (education, media coverage, and wealth) of reproductive-aged women by prioritizing women who live in small periphery regions and rural residences to improve the early initiation of ANC.


Cutaneous toxicities of epidermal growth factor receptor inhibitors: A prospective study in 60 Asian patients.
Several prospective studies have been conducted in epidermal growth factor receptor (EGFR) inhibitor-related cutaneous reactions in Caucasian patients, but prospective studies in Asian populations are scarce. To investigate the cutaneous side effects of EGFR inhibitors in Asian cancer patients and to assess tumor response to dermatologic manifestations. Sixty patients with lung or colorectal cancer who were receiving EGFR inhibitors were prospectively followed for at least one year by oncologists and dermatologists. Of 60 patients (33 males, 27 females), 46 lung cancer patients received erlotinib (n=29) and gefitinib (n=17). Cetuximab was prescribed in 14 colorectal cancer patients. Fifty-eight patients (58/60, 96.7%) developed cutaneous reactions. The most common reactions were xerosis (82.8%), acne (79.3%), and skin desquamation (62.1%). Most reactions were mild and well-tolerated. Of 14 patients who had severe reactions, temporary treatment interruption was necessary in 3 patients and a decreasing dose was required in another 3 patients. There were no statistically significant differences in type, severity, or number of cutaneous reactions between responders (29/58) and non-responders (29/58) to EGFR inhibitors. At median follow-up time of 11.92±1.08 months, no patient died from cutaneous toxicities. Nine patients died from cancer and 11 patients lost to follow-up. In this Asian population, almost all patients (96.7%) developed cutaneous toxicities of EGFR inhibitors. Xerosis, acne, and desquamation were common in Asian cancer patients. Most reactions were mild and well tolerated. Due to limited number of patients, this study did not show significant associations between cutaneous toxicities and tumor response.


Origin of and therapeutic approach to cardiac syndrome X: results of the proton pump inhibitor therapy for angina-like lingering pain trial (PITFALL trial).
To investigate the frequency of gastroenterological diseases in the etiology and the efficacy of proton pump inhibitors (PPIs) in the treatment of cardiac syndrome X (CSX) as a subform of non-cardiac chest pain (NCCP). We investigated 114 patients with CSX using symptom questionnaires. A subgroup of these patients were investigated regarding upper gastrointestinal disorders (GIs) and treated with PPI. Patients not willing to participate in investigation and treatment served as control group. Thirty-six patients denied any residual symptoms and were not further evaluated. After informed consent in 27 of the remaining 78 patients, we determined the prevalence of disorders of the upper GI tract and quantified the effect of treatment with pantoprazole. We found a high prevalence of gastroenterological pathologies (26/27 patients, 97%) with gastritis, gastroesophageal reflux disease (GERD) and acid reflux as the most common associated disorders. If treated according to the study protocol, these patients showed a significant improvement in the symptom score. Patients treated by primary care physicians, not according to the study protocol had a minor response to treatment (n = 19, -43%), while patients not treated at all (n = 26) had no improvement of symptoms (-0%). Disorders of the upper GI tract are a frequent origin of CSX in a German population and can be treated with pantoprazole if given for a longer period.


Clinical management and algorithms in osteoporosis.
The aim of management in osteoporosis is to reduce the risk of fractures. Case-finding strategies are currently recommended to identify subjects at high risk of future fracture who will benefit most from therapy. This article reviews these approaches and discusses the current and future treatment options that are available for patients with osteoporosis.


Motives of the human animal: comprehending, managing, and sharing inner states.
We propose that four fundamental developments of the human animal together produce distinct human motives: (a) social consciousness or awareness that the outcomes or significance of a person's action (self or other) depend upon how another person (self or other) reacts to it; (b) recognizing that people's inner states can mediate their outward behaviors; (c) relating the present to both the past and the future (mental time travel); and (d) sharing reality with other people. We review a typology of four categories of concern for these motivational developments: thoughts, feelings/attitudes, competencies, and reference values (goals and standards). We then review the recent research on three specific areas related to these motivational concerns: imagining future-self inner states, managing how others comprehend us, and sharing knowledge about the world.


Arsenic trioxide, a potent inhibitor of NF-kappaB, abrogates allergen-induced airway hyperresponsiveness and inflammation.
Overactivation of nuclear factor kappaB (NF-kappaB) orchestrates airway eosinophilia, but does not dampen airway hyperresponsiveness in asthma. NF-kappaB repression by arsenic trioxide (As2O3) contributes to apoptosis of eosinophils (EOS) in airways. Here we provide evidence that As2O3 abrogates allergen (OVA)-induced airway eosinophilia by modulating the expression of IkappaBalpha, an NF-kappaB inhibitory protein, and decreases the airway hyperresponsiveness. Using a murine model of asthma, the airway hyperresponsiveness was conducted by barometric whole-body plethysmography. Airway eosinophilia, OVA-specific IgE in serum, and chemokine eotaxin and RANTES (regulated upon activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid were measured by lung histology, Diff-Quick staining, and ELISA. Chemokine-induced EOS chemotactic activity was evaluated using EOS chemotaxis assay. Electrophoretic mobility shift assay and Western blot analysis were performed to assess pulmonary NF-kappaB activation and IkappaBalpha expression, respectively. As2O3 attenuated the allergen-induced serum IgE, chemokine expression of eotaxin and RANTES, and the EOS recruitment in bronchoalveolar lavage fluid, which is associated with an increased IkappaBalpha expression as well as a decreased NF-kappaB activation. Also, As2O3 suppressed the chemotaxis of EOS dose-dependently in vitro. Additionally, As2O3 significantly ameliorated the allergen-driven airway hyperresponsiveness, the cardinal feature underlying asthma. These findings demonstrate an essential role of NF-kappaB in airway eosinophilia, and illustrate a potential dissociation between airway inflammation and hyperresponsiveness. As2O3 likely exerts its broad anti-inflammatory effects by suppression of NF-kappaB activation through augmentation of IkappaBalpha expression in asthma.


Comparing government (school) vs. private (non-school) dental laboratories in marginal adaptation of single porcelain-fused-to-metal crowns.
The purpose of this study was to compare school and non-school dental laboratories in marginal adaptation of single Porcelain-Fused-to-Metal (PFM) crowns. Six dental laboratories (three school- and three non-school laboratories) participated in this study. Each dental laboratory was requested to fabricate PFM crowns for three different ivorine teeth on different typodont jaw models (n=18). The crowns received from the laboratories and fitted in their abutments using fit-checker under uniform pressure. We examined 162 sites viewed under a scanning electron microscope to measure the vertical and horizontal marginal discrepancy. The mean vertical marginal discrepancy for school dental laboratories was 208.9 µm, while for non-school dental laboratories was 182.8 µm. For the horizontal marginal discrepancy, the median values were 48.5 µm for school dental laboratories and 50 µm for non-school dental laboratories. There was no statistically significant difference in the mean vertical and median horizontal values between school and non-school dental laboratories. However, a significant difference was observed within the non-school laboratories.


Action of Bacillus subtilis alpha-amylase on native wheat starch.
Native starch granules from wheat have been subjected to enzymatic depolymerization with an alpha-amylase from Bacillus subtilis. Crystallites made from short-chain amylose and residues from mild acid hydrolysis have been also tested. Electron microscopy, particle size analysis, DSC, and x-ray diffractometry reveal that enzymatic degradation occurs granule by granule. Gel permeation chromatography shows off the macromolecular nature of the remaining material. In contrast, acid erodes simultaneously all the granules, leading to a splitting into small particles. Crystalline fractions are completely degraded by alpha-amylase. These results support evidence for an active disentanglement of chains, carried out by the different subsites of alpha-amylase molecules. A simple mathematical treatment is proposed to explain the results of the kinetics.


Month of birth and mortality in Sweden: a nation-wide population-based cohort study.
Month of birth--an indicator for a variety of prenatal and early postnatal exposures--has been associated with life expectancy in adulthood. On the northern hemisphere, people born in the autumn live longer than those born during the spring. Only one study has followed a population longitudinally and no study has investigated the relation between month of birth and mortality risk below 50 years. In this nation-wide Swedish study, we included 6,194,745 subjects, using data from population-based health and administrative registries. The relation between month of birth (January-December) and mortality risk was assessed by fitting Cox proportional hazard regression models using attained age as the underlying time scale. Analyses were made for ages >30, >30 to 50, >50 to 80 and >80 years. Month of birth was a significant predictor of mortality in the age-spans >30, >50 to 80, and >80 years. In models adjusted for gender and education for ages >30 and >50 to 80 years, the lowest mortality was seen for people born in November and the highest mortality in those born in the spring/summer, peaking in May for mortality >30 years (25‰ excess hazard ratio compared to November, [95% confidence interval = 16-34 ]) and in April for mortality >50 to 80 years (42‰ excess hazard ratio compared to November, [95% confidence interval = 30-55]). In the ages >80 years the pattern was similar but the differences in mortality between birth months were smaller. For mortality within the age-span >30 to 50 years, results were inconclusive. Month of birth is associated to risk of mortality in ages above 50 years in Sweden. Further studies should aim at clarifying the mechanisms behind this association.


Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine.
To study the feasibility of multimodal neuroimaging in mild to moderate Alzheimer disease (AD) and to estimate the size of possible treatment effects of memantine on potential functional, structural and metabolic biomarkers of disease progression. In this randomised, double-blind, placebo-controlled pilot study, 36 patients with moderate AD received 52 weeks of memantine (20 mg/day) or placebo. Patients were re-evaluated after 26 and 52 weeks to measure the change from baseline in several outcome measures including global and regional glucose metabolism, total brain and hippocampal volumes, as well as chemical shift imaging-derived global and regional N-acetylaspartate and myoinositol concentrations. In the total population, global glucose metabolism decreased by 2.3% (p<0.01), total brain volume by 2.1% (p<0.001) and hippocampal volume by 2.7% (p<0.01) after 52 weeks. Chemical shift imaging (CSI) spectra were severely affected by patient-induced artefacts and highly variable. Patients receiving memantine showed less decline in glucose metabolism in all brain areas than patients on placebo. Their loss of hippocampal volume was substantially smaller (2.4% vs 4.0%). No between-group differences were seen for changes in total brain volume. The results support the use of multimodal imaging including MRI and positron emission tomography (PET) to monitor the progression of moderate AD. CSI yielded unreliable longitudinal results. The data suggest that memantine has potentially protective effects in AD and they can be used for planning larger confirmatory studies on the cerebral effects of memantine.


Plasticity, elasticity, and adhesion energy of plant cell walls: nanometrology of lignin loss using atomic force microscopy.
The complex organic polymer, lignin, abundant in plants, prevents the efficient extraction of sugars from the cell walls that is required for large scale biofuel production. Because lignin removal is crucial in overcoming this challenge, the question of how the nanoscale properties of the plant cell ultrastructure correlate with delignification processes is important. Here, we report how distinct molecular domains can be identified and how physical quantities of adhesion energy, elasticity, and plasticity undergo changes, and whether such quantitative observations can be used to characterize delignification. By chemically processing biomass, and employing nanometrology, the various stages of lignin removal are shown to be distinguished through the observed morphochemical and nanomechanical variations. Such spatially resolved correlations between chemistry and nanomechanics during deconstruction not only provide a better understanding of the cell wall architecture but also is vital for devising optimum chemical treatments.


Residents' experiences of relationships with nurses in community-based supported housing - a qualitative study based on Giorgi's method of analysis and self psychology.
One of the prioritizations in the World Health Organization's (WHO) Mental Health Action Plan 2013-2020 is the provision of community mental health and social care services, such as supported housing. The ongoing process of such deinstitutionalization has raised issues concerning the impact on users' quality of life. The purpose of this study was to explore how residents in supported housing experience receiving professional help and how they perceived their relationships with nurses. The second aim was to investigate the relevance of Giorgi's method of analysis and self psychology in analyzing these experiences. Four residents were interviewed individually. The interviews were based on a semi-structured interview guide and analyzed by Giorgi's method of analysis. Relations were interpreted within self psychology. The residents reported that they not only felt safe in the community but also felt a greater awareness of wanting to appear normal. They seemed to have an easier daily life and felt that the personnel met their selfobject needs when routines allowed for it. Professional awareness of empathic attunement and selfobject roles might enhance residents' self-cohesiveness. The interviews were analyzed by Giorgi's method of analysis, and the use of clinical concepts from self psychology was chosen to achieve a more dynamic understanding of the participants' relational experiences and needs in supported housing.


Virus-like particles of a fish nodavirus display a capsid subunit domain organization different from that of insect nodaviruses.
The structure of recombinant virus-like particles of malabaricus grouper nervous necrosis virus (MGNNV), a fish nodavirus isolated from the grouper Epinephelus malabaricus, was determined by electron cryomicroscopy (cryoEM) and three-dimensional reconstruction at 23-A resolution. The cryoEM structure, sequence comparison, and protein fold recognition analysis indicate that the coat protein of MGNNV has two domains resembling those of tomato bushy stunt virus and Norwalk virus, rather than the expected single-domain coat protein of insect nodaviruses. The analysis implies that residues 83 to 216 fold as a beta-sandwich which forms the inner shell of the T=3 capsid and residues 217 to 308 form the trimeric surface protrusions observed in the cryoEM map. The structural similarities between fish nodaviruses and members of the tombusvirus and calicivirus groups provide significant new data for understanding the evolution of the nodavirus family.


Comparison of effects of sevoflurane/nitrous oxide and enflurane/nitrous oxide on myocardial contractility in humans. Load-independent and noninvasive assessment with transesophageal echocardiography.
Few studies have been reported on the direct depressive effects of sevoflurane on myocardial contractility in humans. Direct assessment of contractile state is possible by examining the slope of left ventricular end-systolic wall stress (LVESWS) versus velocity of circumferential fiber shortening with heart rate corrected (Vcfc) relationship with echocardiography. Using this contractile index, the effects of sevoflurane/nitrous oxide were compared with that of enflurane/nitrous oxide on myocardia contractility in humans. Twenty-eight subjects were studied during either sevoflurane/nitrous oxide or enflurane/nitrous oxide anesthesia. Systolic, diastolic, and mean arterial blood pressure, heart rate, and transesophageal echocardiographic data were determined at 0.9 MAC and 1.35 MAC of sevoflurane or enflurane, both with 60% N2O, and at 1.6 MAC of sevoflurane with 60% N2O. Furthermore, another 28 awake subjects were studied with transthoracic echocardiography to examine the contractile state at awake state, and echocardiograms, heart rate, and arterial blood pressure were recorded. Heart rate did not changed significantly in either group. Enflurane/nitrous oxide produced significantly greater decrease in arterial blood pressure than did sevoflurane/nitrous oxide. The Vcfc at each anesthetic dose in both anesthetic groups was significantly less than that in the awake subjects group. Sevoflurane/nitrous oxide produced no significant change in Vcfc at 1.5 MAC, whereas enflurane/nitrous oxide caused significant dose-related decrease in Vcfc. Vcfc produced by sevoflurane/nitrous oxide was significantly greater than that produced by enflurane/nitrous oxide. There was no significant difference in LVESWS (index of afterload) between the groups. With respect to the LVESWS-Vcfc relationship, myocardial contractility was significantly depressed in both the sevoflurane and the enflurane groups compared to the awake subjects group. However, myocardial contractility produced by enflurane/nitrous oxide was significantly less than that by sevoflurane/nitrous oxide at equiMAC concentration. The results of the present study suggest that sevoflurane has fewer depressant effects on cardiac function than does enflurane.


[Evaluation of intrapulmonary nodules by thoracoscopic ultrasonography].
We evaluated the usefulness of thoracoscopic ultrasonography for diagnosing intrapulmonary nodules. We studied 7 patients undergoing thoracoscopic operations. Three had benign lung tumors, one had metastatic lung tumors from a renal cell cancer, and three had primary lung cancers. During thoracoscopy three benign tumors were seen as masses protruding from the visceral pleura in to the pleural space, and two primary lung cancers were seen as pleural indentations. However, the presence of one metastatic lung tumor and one primary lung cancer could not be confirmed by thoracoscopy because of the lack of pleural changes. Furthermore, intrapulmonary spread of malignant tumors in four cases could not be seen by thoracoscopy. All tumors were seen clearly and their characteristics were identified by thoracoscopic ultrasonography. Partial lung resection during thoracoscopy was successful in all patients. We found thoracoscopic ultrasonography to be useful for confirming the presence of peripheral solid nodules, and for deciding where to make incisions for partial lung resection.


The Insular Subregions Topological Characteristics of Patients With Bipolar Depressive Disorder.
The insular cortex appears to have a crucial role in emotional processing and cognitive control in bipolar disorder (BD). However, most previous studies focused on the entire insular region of BD, neglecting the topological profile of its subregions. Our study aimed to investigate its subregion topological characteristics using the resting-state functional connectivity (rsFC) in patients with BD on depression episode. The magnetic resonance imaging (MRI) data of 28 depressed BD patients and 28 age- and gender-matched healthy controls (HCs) were acquired. We observed that compared to HCs, depressed patients with BD exhibited significantly decreased rsFC between the right ventral anterior insula (vAI) and the left middle temporal gyrus/the right angular, the right dorsal anterior insula (dAI) and the left precuneus, as well as the right posterior insula and the right lingual gyrus. Furthermore, hyperconnectivity was observed between the left dAI and the left medial frontal gyrus, as well as right dAI and left superior temporal gyrus in BD depression. However, no significant group effect was observed between aberrant FC patterns and clinical variables. These findings revealed the functional connectivity patterns of insular subregions for the depressed BD patients, suggesting the potential neural substrate of insular subregions involved in depressive episode of BD. Hence, these results may provide a neural substrate for the potential treatment target of BD on depression episode.


A 3D-Printed Portable Sterilizer to Be Used During Surgical Procedures in Spaceflight.
INTRODUCTION: During spaceflight, it is important to consider the mechanisms by which surgeries and medical procedures can be safely and efficiently conducted. Instruments used to carry out these processes need to be sterilized. Thus, we have designed and tested a three-dimensional-printed (3D-printed) portable sterilizer that implements far ultraviolet-C (Far UV-C) light radiation to disinfect bacteria and microorganisms from surgical instruments.METHODS: The sterilizer was 3D-printed with polylactic acid filament. Effectiveness was assessed through three trials at differing times of sterilization and compared against a control group of no sterilization and against Clorox wipes. Cultures were incubated on agar dishes and counted with ImageJ.RESULTS: Increasing time under Far UV-C light radiation increased the percentage of sterilization up to 100% at 10 min. The 3D-printed sterilizer was significantly better than Clorox wipes and control.DISCUSSION: As sterilization will be necessary for surgical procedures in microgravity and upmass is a significant concern, we have successfully demonstrated a 3D-printable portable sterilizer for surgical instruments that achieves 100% success in using Far UV-C light to disinfect its surface of bacteria with a 10-min sterilizing time. Further research is necessary to test this design in microgravity and with differently sized and shaped instruments.Kovalski E, Salazar L, Levin D, Kamine TH. A 3D-printed portable sterilizer to be used during surgical procedures in spaceflight. Aerosp Med Hum Perform. 2023; 94(11):857-860.


[The clinical application of warm acupuncture and penetration moxibustion by professor GAO Xiyan].
To introduce professor GAO Xiyan's clinical application of warm acupuncture and penetration moxibustion, and explain from the aspects of formation, application scope and innovation of warm acupuncture and penetration moxibustion. Professor GAO emphasized that intensive moxibustion and moxibustion sensation are the key factors to ensure the clinical curative effect. According to the different parts of the moxibustion, it can be applied to the head, abdomen, waist and knee joints, etc, which plays the role of warming the meridians, replenishing qi and fixing collaterals,dispersing cold and removing stasis, harmonizing qi and blood.And to introduce the specific application of warm acupuncture and penetration moxibustion through the typical medical case.