A modified prognostic index based upon nutritional measurements.
This paper describes a formula which, on solution, derives a prognostic index (PI) for predicting surgical complications using an anthropometric measurement and serum protein levels which may be obtained easily and rapidly. The formula was applied to three groups of patients, firstly 106 patients undergoing major surgical resection, secondly to 16 patients admitted for minor surgery to assess a normal range, and thirdly 10 patients undergoing total parenteral nutrition. In patients undergoing major surgical resection the prognostic index was significantly greater in those patients developing complications than in the control group and a good predictor of the risk of complications. The index uses nutritional measurements to predict complications rather than being a measurement of nutritional status and is therefore a poor monitor of the efficacy of nutritional therapy.


Distal-less and spalt are distal organisers of pierid wing patterns.
Two genes, Distal-less (Dll) and spalt (sal), are known to be involved in establishing nymphalid butterfly wing patterns. They function in several ways: in the differentiation of the eyespot's central signalling cells, or foci; in the differentiation of the surrounding black disc; in overall scale melanisation (Dll); and in elaborating marginal patterns, such as parafocal elements. However, little is known about the functions of these genes in the development of wing patterns in other butterfly families. Here, we study the expression and function of Dll and sal in the development of spots and other melanic wing patterns of the Indian cabbage white, Pieris canidia, a pierid butterfly. In P. canidia, both Dll and Sal proteins are expressed in the scale-building cells at the wing tips, in chevron patterns along the pupal wing margins, and in areas of future scale melanisation. Additionally, Sal alone is expressed in the future black spots. CRISPR knockouts of Dll and sal showed that each gene is required for the development of melanic wing pattern elements, and repressing pteridine granule formation, in the areas where they are expressed. We conclude that both genes likely play ancestral roles in organising distal butterfly wing patterns, across pierid and nymphalid butterflies, but are unlikely to be differentiating signalling centres in pierids black spots. The genetic and developmental mechanisms that set up the location of spots and eyespots are likely distinct in each lineage.


A framework for effective collaboration between specialist and broad-spectrum groups for delivering priority Cochrane reviews.
We aimed to develop and pilot a process for joint working between Cochrane Review Groups (specialist-area groups responsible for producing Cochrane reviews) and Cochrane Fields (broad-spectrum interest groups), for identifying high priority review topics and enhancing quality and dissemination of priority reviews. We developed and piloted a framework for collaboration between a Cochrane Review Group (specializing in musculoskeletal injuries) and a Cochrane Field (focusing on health care of older people) for identifying, delivering, and disseminating priority Cochrane intervention reviews using hip fracture rehabilitation as an exemplar. The processes adopted included consultation of members of both the entities, mapping of trials from the Review Group's Specialized Register, jointly establishing criteria for topic prioritization, identification of researchers, and facilitating provision of expert peer review from the field. A framework for effective collaboration between a Cochrane Review Group and Cochrane Field for identifying and delivering priority Cochrane Reviews was devised and piloted. Additionally, two new Cochrane reviews, preceded by protocols, were published. The project demonstrated the feasibility and potential benefits of a structured collaboration between a Cochrane Review Group and a Cochrane Field for the identification and production of Cochrane reviews on priority topics.


Random Access Addressing of MEMS Electrostatic Shutter Array for Multi-Object Astronomical Spectroscopy.
An extended version of cross-bar type addressing technique is developed for three-port electrostatic micro shutters arranged in an arrayed format. A microelectromechanical systems (MEMS) shutter blade suspended by a pair of torsion beams works as a movable electrode that is either attracted upwards to the cover plate to close the aperture or retracted downwards into the through-hole to open it. Tri-state positioning of the shutter-i.e., open, rest, and close-is controlled by the hysteresis loop of the electrostatic pull-in and release behavior using the combination of the voltages applied to the shutter, the cover, and the substrate. Random access addressing of the shutters is demonstrated by a control system composed of MATLAB-coded Arduino electronics. The shutter array developed in this work is for a sub-cluster of a reconfigurable shutter array under development for a multi-object galactic astronomy.


Quantitative analysis of adsorption and desorption behavior of individual cellulase components during the hydrolysis of lignocellulosic biomass with the addition of lysozyme.
The effect of non-catalytic protein addition on the adsorption/desorption behavior of individual cellulase components on/from substrates during the hydrolysis of microcrystalline cellulose and steam exploded sugarcane bagasse (SEB) were investigated. The addition of non-catalytic protein enhanced the enzymatic hydrolysis of SEB, but did not enhance the hydrolysis of microcrystalline cellulose. During the hydrolysis of SEB, adsorption of beta-glucosidase (BGL) was prevented in the presence of non-catalytic protein. Cellobiohydrolase I (CBH I) and endoglucanase I (EG I) desorbed from the substrate after temporary adsorption in the presence of non-catalytic protein during SEB hydrolysis. This suggested that reduction of the non-specific adsorption of cellulase components, CBH I, EG I, and BGL, on lignin in SEB led to the improving of enzymatic hydrolysis.


BDNF serum concentrations in first psychotic episode drug-naïve schizophrenic patients: associations with personality and BDNF Val66Met polymorphism.
To investigate the relationship among brain derived neurotrophic factor (BDNF) serum concentrations, BDNF Val66Met polymorphism and personality profile in drug-naïve schizophrenic patients with first-episode psychosis (FEP) and healthy participants. This cross-sectional study included fifty FEP patients and fifty healthy participants who served as controls. To study their personality profile the standardized Greek version of the Alternative Five-Factor Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) was administered. Serum BDNF levels were measured and genotyping of BDNF Val66Met polymorphism was performed in patients and healthy subjects. FEP patients presented lower BDNF serum concentrations (P=0.002) and higher scores in ZKPQ Neuroticism (P=0.001) and Aggression-Hostility (P=0.002) scales while lower scores in the ZKPQ Sociability scale (P<0.001) than healthy participants. Multivariate analysis revealed that the odds of being assessed with FEP were 0.4 times lower in those with higher BDNF values (P<0.001) and 1.8 times greater in those with higher Neuroticism scores (P<0.001). There were no significant differences with respect to the Val66Met polymorphism between patients and healthy participants. Reduced BDNF serum concentrations along with higher Neuroticism scores might be associated with FEP. A complex interplay between BDNF serum concentrations, personality traits, BDNF Val66Met polymorphism, and psychotic symptomatology has been arisen but further investigation is needed to better clarify the observed associations.


Polarity establishment requires localized activation of Cdc42.
Establishment of cell polarity in animal and fungal cells involves localization of the conserved Rho-family guanosine triphosphatase, Cdc42, to the cortical region destined to become the "front" of the cell. The high local concentration of active Cdc42 promotes cytoskeletal polarization through various effectors. Cdc42 accumulation at the front is thought to involve positive feedback, and studies in the budding yeast Saccharomyces cerevisiae have suggested distinct positive feedback mechanisms. One class of mechanisms involves localized activation of Cdc42 at the front, whereas another class involves localized delivery of Cdc42 to the front. Here we show that Cdc42 activation must be localized for successful polarity establishment, supporting local activation rather than local delivery as the dominant mechanism in this system.


Study of the Development of Placental Microvascularity by Doppler SMI (Superb Microvascular Imaging): A Reality Today.
Our objective was to evaluate the development of placental vascularization in normal gestation by using Doppler superb microvascular imaging (SMI). The fetal and maternal parameters of 20 pregnant women without pathology were evaluated at weeks 12, 16, 20-22, 24-26, 28-30, 32-34, 36-38 and 40-42. Doppler SMI was used to evaluate the placental vascularization (pulsatile index and peak systolic velocity) of the primary, secondary and tertiary (third) villi, and qualitative placental descriptions and anatomic-pathologic studies of these placentas were performed. The number of cotyledons identified by Doppler SMI increased from two between weeks 16 and 18 to 24 between weeks 28 and 38. The secondary and tertiary villi began developing at 20 wk of gestation. The pulsatile index of the primary villi remained constant (0.8-0.9 in all pregnancies). The pulsatile index of the secondary and tertiary villi increased from 1.1 to 1.53 and from 1.4 to 1.68, respectively. The peak systolic velocity underwent a significant increase throughout gestation in the secondary and tertiary villi (9.2 to 34.9 cm/s and 7.5 to 52.9 cm/s, respectively). We evaluated the development of placental microvascularization using Doppler SMI in pregnancies without pathology and describe normal placental Doppler SMI findings.


Interferon triggers experimental synovitis and may potentiate auto-immune disease in humans.
From these data it appears that IFN is capable of stimulating prostaglandin E and hyaluronic acid production by human synovial fibroblasts in vitro and of initiating an inflammatory reaction in animal joints. In chronic arthritis its production may result from persisting viral or other antigenic stimulation. IFN may enhance the immune response and mediate the inflammatory process in the joint. Its role in the pathogenesis of rheumatic and various other autoimmune diseases is undergoing further study.


SKF 38393 reverses cocaine-conditioned place preference in mice.
Cocaine is a psychotropic drug with a high potential for abuse due to its euphoric effects. Efforts to develop medications for the treatment of cocaine dependence have not been clinically successful. Some studies using animal models have shown positive effects of dopaminergic agents such as partial agonists of the dopamine D1 receptor. Thus, this study aimed to examine the effect of the dopamine D1 receptor partial agonist SKF 38393 on cocaine craving. Adult male C57BL/6J mice were injected with cocaine for 10 days in a conditioned place preference apparatus using a biased procedure and subsequently treated for three consecutive days with SKF 38393. The results showed that SKF 38393 was able to block the preference of cocaine-conditioned animals for the compartment paired with the drug without showing effects on locomotor activity. The results of this study suggest that partial activation of D1 dopamine receptors may be necessary for the development of pharmacotherapies for cocaine addiction.


The influence of propranolol and glucagon on the pharmacokinetics of antipyrine and sodium salicylate.
Propranolol (1) decreases hepatic blood flow and glucagon (2) exerts an opposite effect on hepatic circulation. The effects of these drugs on the pharmacokinetics of phenazone (3; antipyrine)-a compound with low coefficient of hepatic extraction, and sodium salicylate (4) that is highly extracted by liver, were studied on rabbits. It was shown that changes in the pharmacokinetics of 3 and 4 in the presence of 1 or 2, seemed to be interactions between these drugs in the haemodynamic phase.


[Accuracy of references in eight nursing journals in Korea].
This study was to investigate the reference accuracy in major nursing journals in Korea. The references in articles from eight nursing journals from 2006 were compared with PubMed for authors, year, title, journal, volume, and page accuracy. Four hundred sixty-six references were reviewed. Errors were classified as major or minor and categorized by bibliographic headings (author, title, journal, year, volume and page). Of the 466 references, 223(47.9%) had citation errors. The reference error rates ranged from 28.6% to 58.7%. Most errors occurred in the author element (37.9%), followed by title (20.9%), journal (19.0%), page (13.9%), volume (5.9%), and year (2.4%). This study identified a considerable error rate in the references of nursing journals. Inaccuracy of references is a reflection on scholarly work of authors and journals. Authors and Editorial committees are responsible for the accuracy of references.


Evolutional and developmental anatomical architecture of the left inferior frontal gyrus.
The left inferior frontal gyrus (IFG) including Broca's area is involved in the processing of many language subdomains, and thus, research on the evolutional and human developmental characteristics of the left IFG will shed light on how language emerges and maturates. In this study, we used diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (fMRI) to investigate the evolutional and developmental patterns of the left IFG in humans (age 6-8, age 11-13, and age 16-18 years) and macaques. Tractography-based parcellation was used to define the subcomponents of left IFG and consistently identified four subregions in both humans and macaques. This parcellation scheme for left IFG in human was supported by specific coactivation patterns and functional characterization for each subregion. During evolution and development, we found increased functional balance, amplitude of low frequency fluctuations, functional integration, and functional couplings. We also observed higher fractional anisotropy values, i.e. better myelination of dorsal and ventral white matter language pathways during evolution and development. We assume that the resting-state functional connectivity and task-related coactivation mapping are associated with hierarchical language processing. Our findings have shown the evolutional and human developmental patterns of left IFG, and will contribute to the understanding of how the human language evolves and how atypical language developmental disorders may occur.


Surface and elemental alterations of dental alloys induced by electro discharge machining (EDM).
To evaluate the surface and elemental alterations induced by electro discharge machining (EDM) on the surface of dental cast alloys used for the fabrication of implant retained meso- and super-structures. A completed cast model of an arch that received dental implants was used for the preparation of six wax patterns which were divided into three groups (Au, Co and Ti). The wax patterns of the Au and Co groups were invested with conventional phosphate-bonded silica-based investment material and the Ti group with magnesia-based investment material. The investment rings of the Au and Co groups were cast with an Au-Ag alloy (Stabilor G) and a Co-Cr base alloy (Okta C), respectively, while the investment rings of group Ti were cast with cp Ti (Biotan). One casting of each group was subjected to electro discharge machining (EDM); the other was conventionally ground and polished. The surface morphology and the elemental compositions of conventionally and EDM-finished surfaces were studied by SEM/X-ray EDS analysis. Six spectra were collected from each surface employing the area scan mode and the mean value of each element between conventionally and EDM-finished surfaces was statistically analyzed by t-test (a=0.05). Then the specimens of each group were cut perpendicular to their longitudinal axis and after metallographic grinding and polishing the cross-sections studied under the SEM. The EDM surfaces showed a significant increase in C due to the decomposition of the dielectric fluid during spark erosion. Moreover, a significant Cu uptake was noted on these surfaces from the decomposition of the Cu electrodes used for EDM. Cross-sectional analysis showed that all alloys developed a superficial zone (recast layer) varying from 2 microm for Au-Ag to 10 microm for Co-Cr alloy. The elemental composition of dental alloy surfaces is significantly altered after EDM treatment.


[Endometrial-smear cytology using an intrauterine pessary for the early recognition of corpus uteri carcinoma].
An additional way for screening of the carcinoma of the endometrium was described reporting about 340 patients with IUD. --The cytology of the endometrium taken from the IUD was compared with the histology of the endometrium. It is reported about conclusions for practical work.


Last-come, best served? Mosquito biting order and Plasmodium transmission.
A pervasive characteristic of parasite infections is their tendency to be overdispersed. Understanding the mechanisms underlying this overdispersed distribution is of key importance as it may impact the transmission dynamics of the pathogen. Although multiple factors ranging from environmental stochasticity to inter-individual heterogeneity may explain parasite overdispersion, parasite infection is also overdispersed in an inbred host population maintained under laboratory conditions, suggesting that other mechanisms are at play. Here, we show that the aggregated distribution of malaria parasites within mosquito vectors is partially explained by a temporal heterogeneity in parasite infectivity triggered by the bites of mosquitoes. Parasite transmission tripled between the mosquito's first and last blood feed in a period of only 3 h. Surprisingly, the increase in transmission is not associated with an increase in parasite investment in production of the transmissible stage. Overall, we highlight that Plasmodium is capable of responding to the bites of mosquitoes to increase its own transmission at a much faster pace than initially thought and that this is partly responsible for overdispersed distribution of infection. We discuss the underlying mechanisms as well as the broader implications of this plastic response for the epidemiology of malaria.


[Analysis of clinicopathological features and prognosis between alpha-fetoprotein negative and positive hepatocellular carcinoma patients after R0 radical hepatectomy].
To investigate the differences between clinicopathological features and prognosis of alpha-fetoprotein (AFP) negative (AFP < 20 ng/ml) and positive (AFP ≥ 20 ng/ml) hepatocellular carcinoma (HCC) patients. Clinicopathological data of 142 AFP-negative and 109 AFP-positive HCC patients who underwent RO radical hepatectomy in the Cancer Hospital of Chinese Academy of Medical Sciences between January 2006 and December 2011 were retrospectively reviewed and analyzed in this study. Compared with the AFP-negative patients, a higher female to male sex ratio, the later Barcelona Clinic Liver Cancer ( BCLC) stage, more liver capsule invasion and poorer Edmondson-Steiner grade were in the AFP-positive cases (P < 0.05 for all). Furthermore, the 1-, 3-, and 5- year overall survival rates were 94.4%, 82.4% and 61.0% in the AFP-negative group and 87.2%, 61.1% and 40.2%, respectively, in the AFP-positive group (P < 0.001). The multivariate analysis with Cox's proportional hazards model showed that AFP status, tumor size and Edmondson-Steiner grade are independent risk factors for survival of all the patients (P < 0.05) , and large tumor and Edmondson-Steiner grades III/IV are independent risk factors for worse survival in AFP-negative patients (P < 0.05). However, large tumor diameter was proved to be an independent risk factor leading to poor prognosis of AFP-positive cases (P < 0.05). High levels of AFP indicate that the tumors are more malignant and with unfavorable prognosis.


[Detection of Aichi virus in stool samples from children in Lanzhou].
To identification and analysis Aichi virus from diarrhea and normal children in Lanzhou, and discuss the relationship between Aichi virus and Infant Diarrhea. According to the literature published data, Using RT-PCR method to amplified Aichi virus 3CD fragment and the positive products were sequenced and determined, and made the alignment analysis between the nucleotide sequences of the amplified fragment with the known sequence of this virus. There was 1 case detection of Aichi virus in the 46 hospitalized children with diarrhea and 299 children with diarrhea out-patients specifically, Overall detection rate was 0.06%, and there was no Aichi virus was detected in normal control children. 2 viral 3CD gene and the known reference strains of nucleotide sequences were 97%, while phylogenetic analysis showed that genotype of 2 viral belongs to the B. There existed B Genotype of Aichi virus in China, and more research is needed to clarified the etiology and epidemiology of Aichi virus characteristics.


Correlates of and Disparities in Cancellations or Delays of Prenatal Visits During the Covid-19 Pandemic: Emphasis on Racial/Ethnic Minorities and Persons with Low Socioeconomic Status.
To investigate barriers and disparities in prenatal visits across population subgroups. This pooled cross-sectional study was conducted using Pregnancy Risk Assessment Monitoring System for 2020 through 2021. Women who reported their experiences of cancellation or delay in prenatal visits were included. A multivariable regression analysis estimated adjusted prevalence ratios (aPR) for cancellations or delays in prenatal care. Of a total of 11,427, one-third had cancelled or delayed care. Hispanics, compared to their white counterparts, were 22% likelier to have cancelled or delayed care. Women covered by Medicaid and those with depression had 17% and 34% greater likelihoods of cancellation or delay, respectively. Cancellations or delays were comparable for the years 2020 and 2021 across reasons, except for facility closures, which were more common in 2020 than in 2021. Hispanics tended to cancel or delay prenatal visits more often than whites for reasons, such as facility closures, COVID-19-related reasons, a lack of transportation, and loss of insurance, while transportation and insurance issues were greater barriers for blacks. Women with less than a high school diploma were more likely to report cancellations or delays due to transportation issues (aPR 2.86, 95%CI 1.47-5.57; p = 0.002) and loss of insurance (aPR 4.82, 95%CI 1.64-14.23; P = 0.004). While a large proportion of women experienced disruptions in prenatal care, subsets of the population, including racial/ethnic minorities and the low socioeconomically disadvantaged, faced disproportionate challenges. The current findings provide practical implications for a tailored approach to reducing barriers and disparities in prenatal care.


Heterochromatin protein 1 binds transgene arrays.
Heterochromatin protein 1 (HP1) of Drosophila and its homologs in vertebrates are key components of constitutive heterochromatin. Here we provide cytological evidence for the presence of heterochromatin within a euchromatic chromosome arm by immunolocalization of HP1 to the site of a silenced transgene repeat array. The amount of HP1 associated with arrays in polytene chromosomes is correlated with the array size. Inverted transposons within an array or increased proximity of an array to blocks of naturally occurring heterochromatin may increase transgene silencing without increasing HP1 labeling. Less dense anti-HP1 labeling is found at transposon arrays in which there is no transgene silencing. The results indicate that HP1 targets the chromatin of transposon insertions and binds more densely at a site with repeated sequences susceptible to heterochromatin formation.


Clinical trial of safety and efficacy of INH-A21 for the prevention of nosocomial staphylococcal bloodstream infection in premature infants.
To determine if INH-A21, an intravenous immune globulin (IGIV) derived from donors with high titers of antibody to surface adhesins of Staphylococcus epidermidis and S. aureus prevents late-onset sepsis (LOS) in very low birth weight (VLBW) infants. In this double-blind, placebo-controlled study, infants with birth weights 500 to 1250 g were randomized to receive up to four doses of INH-A21 (Veronate) or placebo. The primary objective was to determine the safety and efficacy of INH-A21 versus placebo for prevention of S. aureus LOS in VLBW infants. A total of 1983 infants from 95 neonatal intensive care units were randomized, and received at least one dose of study drug. S. aureus LOS developed in 50 of 989 (5%) and 60 of 994 (6%) infants who received placebo or INH-A21, respectively (P = .34). No differences were found in the frequencies of LOS caused by coagulase-negative staphylococci (CoNS), Candida spp, or overall mortality. No adverse events were statistically significantly associated with INH-A21 infusions compared with placebo. INH-A21 failed to reduce the incidence of staphylococcal LOS or candidemia in premature infants.


Vieussens' ring coronary collateral circulation: a natural bypass history.
"Vieussens' ring" or "arterial circle of Vieussens" is a crucial hetero-coronaric pathway, bridging proximal right coronary artery (RCA) and left anterior descending artery (LAD) when a hemodynamically stenosis is established in the either of the vessel. In detail such coronary collateral circulation is usually supplied by branches of the conus artery. We present a case of a 62-year-old man who was admitted to our emergency department complaining of chest pain. Coronary angiography showed LAD occlusion at the mid tract with delayed and slight opacification of its distal segment sustained by Vieussens' ring. Coronary computed tomography angiography (CCTA) was subsequently performed which confirmed the presence of such natural bypass and evaluated its relationship with adjacent structures. Imaging, particularly CCTAoffers a valid tool in assessing the hetero-coronaric collateral vessel. Due to its high spatial resolution it may provide many information about the coronary anatomy by delineating their origin, course and termination.


Elucidation of the coumarin degradation by Pseudomonas sp. strain NyZ480.
As a phytotoxin and synthetic chemical, coumarin (COU) is known for its hepatotoxicity and carcinogenicity. However, no thorough characterization of its microbial degradation has been reported. Here, Pseudomonas sp. strain NyZ480 was isolated for its capability of utilizing COU as the sole carbon source. Studies on its growth and degradation efficiency of COU under various conditions suggested that strain NyZ480 performed the optimum degradation at 30 ℃, pH 7, and 0.5 mM COU was completely removed within 4 h with 1% inoculum. HPLC and LC-MS analyses indicated that dihydrocoumarin (DHC), melilotic acid (MA) and 3-(2,3-dihydroxyphenyl)propionate (DHPP) were the upstream biotransformation intermediates of COU. Enzyme assay established that the initial reaction transforming COU to DHC required an NAD(P)H-dependent reductase, followed by the hydrolysis of DHC to generate MA, and the third reaction catalyzing the monooxygenation of MA to DHPP utilized a strict NADH-dependent hydroxylase. Combining genomics and transcriptomics, we proposed that the COU downstream degradation (from DHPP) was catalyzed by enzymes encoded by a gene cluster homologous to the mhp cluster for 3(3-hydroxyphenyl)propionate degradation via DHPP in E. coli. This study thoroughly identified the intermediates from the COU catabolism, providing essential insights into the molecular evidences of its biodegradation pathway.


The plausibility of RNA-templated peptides: simultaneous RNA affinity for adjacent peptide side chains.
According to the RNA world hypothesis, coded peptide synthesis (translation) must have been first catalyzed by RNAs. Here, we show that small RNA sequences can simultaneously bind the dissimilar amino acids His and Phe in peptide linkage. We used in vitro counterselection/selection to isolate a pool of RNAs that bind the dipeptide NH(2)-His-Phe-COOH with K (D) ranging from 36 to 480 μM. These sites contact both side chains, usually including the protonated imidazole of His, but bind-free L: -His and L: -Phe with much lower, sometimes undetectable, affinities. The most frequent His-Phe sites do not usually contain previously isolated sites for individual amino acids, and are only ≈35 % larger than previously known separate His and Phe sites. Nonetheless, His-Phe sites appear enriched in His anticodons, as previous L: -His sites also were. Accordingly, these data add to existing experimental evidence for a stereochemical genetic code. In these peptide sites, bound amino acids approach each other to a proximity that allows a covalent peptide linkage. Isolation of several RNAs embracing two amino acids with a linking peptide bond supports the idea that a direct-RNA-template could encode primordial peptides, though crucial experiments remain.


Characterization of yeasts with high L[+]-lactic acid production: lactic acid specific soft-agar overlay (LASSO) and TAFE-patterns.
Only few yeast strains are known for the high level production of L[+]-lactate. We report indications for the conspecifity of Kluyveromyces thermotolerans (formerly Saccharomyces veronae) strain CBS 4728 with Stamm 42 (formerly Saccharomyces pretoriensis, RADLER 1984). We suggest that Stamm 42 has little, if any relationship to Saccharomyces cerevisiae. Furthermore, we have optimized the method of Subden et al. (1982) for the detection of lactate producing microorganisms. Using this method in a screening with 100 yeast strains of our institute collection, we could not find additional strains with high L[+]-lactate production. This method may provide a useful tool for the molecular cloning of the unique yeast L[+]-LDH1) gene (s).


Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics.
Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models. The method utilizes the steady-state diffusion kinetics of a fluorescent dye to establish a gradient along the radial axis of disease models. Classification of sample layers based on dye accessibility enables dissociated and sorted cells to be characterized by transcriptomic and regional identities. Using SEEP, we analyze spheroid, organoid, and in vivo tumor models of high-grade serous ovarian cancer (HGSOC). The results validate long-standing beliefs about the relationship between cell state and position while revealing new concepts regarding how spatially unique microenvironments influence the identity of individual cells within tumors.


Anterior segment changes with age and during accommodation measured with partial coherence interferometry.
To evaluate anterior segment alterations with age and during accommodation in different age groups. Department of Ophthalmology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. Fifty-three subjects (101 normal eyes) were enrolled in this study and divided into 3 age groups: younger than 30 years (Group 1), between 31 years and 44 years (Group 2), and older than 45 years (Group 3). The total amplitude of accommodation was determined with a defocusing technique, and anterior segment measurements were performed by partial coherence interferometry. Group 1 comprised 32 eyes; Group 2, 37 eyes; and Group 3, 32 eyes. The total amplitude of accommodation decreased with age (P<.0001). With the target position at infinity, the lens thickness (LT) and anterior segment length (ASL) increased and the anterior chamber depth (ACD) decreased significantly with age (P<.0001). During accommodation in the youngest group, the mean change in LT was 36.3 mum/diopter (D) and in ACD, -26.7 mum/D. The mean accommodation-induced ACD change was -0.08 mm +/- 0.06 (SD) in Group 1, -0.064 +/- 0.087 mm in Group 2, and -0.03 +/- 0.06 mm in Group 3 (P = .0004). The mean LT change during near fixation was 0.109 +/- 0.063 mm in Group 1, 0.103 +/- 0.136 mm in Group 2, and 0.006 +/- 0.05 mm in Group 3 (P<.0001). The mean ASL change during accommodation was 0.029 +/- 0.037 mm, 0.039 +/- 0.114 mm, and -0.023 +/- 0.051, respectively (P<.0001). In addition to forward movement of the anterior lens surface with age, the posterior surface moved backward. Alterations in LT and ACD sufficient for a unit of refractive power change during accommodation might be smaller than previously thought. Anterior shifting of the lens may also participate in the accommodative response.


A touch-based multimodal and cryptographic bio-human-machine interface.
The awareness of individuals' biological status is critical for creating interactive and adaptive environments that can actively assist the users to achieve optimal outcomes. Accordingly, specialized human–machine interfaces—equipped with bioperception and interpretation capabilities—are required. To this end, we devised a multimodal cryptographic bio-human–machine interface (CB-HMI), which seamlessly translates the user's touch-based entries into encrypted biochemical, biophysical, and biometric indices. As its central component, the CB-HMI features thin hydrogel-coated chemical sensors and inference algorithms to noninvasively and inconspicuously acquire biochemical indices such as circulating molecules that partition onto the skin (here, ethanol and acetaminophen). Additionally, the CB-HMI hosts physical sensors and associated algorithms to simultaneously acquire the user's heart rate, blood oxygen level, and fingerprint minutiae pattern. Supported by human subject studies, we demonstrated the CB-HMI's capability in terms of acquiring physiologically relevant readouts of target bioindices, as well as user-identifying and biometrically encrypting/decrypting these indices in situ (leveraging the fingerprint feature). By upgrading the common surrounding objects with the CB-HMI, we created interactive solutions for driving safety and medication use. Specifically, we demonstrated a vehicle-activation system and a medication-dispensing system, where the integrated CB-HMI uniquely enabled user bioauthentication (on the basis of the user's biological state and identity) prior to rendering the intended services. Harnessing the levels of bioperception achieved by the CB-HMI and other intelligent HMIs, we can equip our surroundings with a comprehensive and deep awareness of individuals' psychophysiological state and needs.


Case report: splenic infarct in sickle cell disease.
It is well recognized that patients with sickle cell disease are susceptible to splenic infection and infarction. A case of total splenic infarction is presented in which the ultrasound and CT features are atypical.


Crystal clear structural evidence for electron delocalization in 1,2-dihydro-1,2-azaborines.
The first examples of "pre-aromatic" 1,2-dihydro-1,2-azaborine heterocycles have been structurally characterized, enabling the direct comparison of delocalized bonds of 1,2-dihydro-1,2-azaborines to their corresponding formal double and single bonds in nonaromatic systems. The crystallographic data provide an unprecedented look into the structural changes that occur in six-membered BN-heterocycles on their road to aromaticity, and they establish with little ambiguity that 1,2-dihydro-1,2-azaborines possess delocalized structures consistent with aromaticity.


Protein kinase CK2 regulates the dimerization of histone deacetylase 1 (HDAC1) and HDAC2 during mitosis.
Histone deacetylase 1 (HDAC1) and HDAC2 are components of corepressor complexes that are involved in chromatin remodeling and regulation of gene expression by regulating dynamic protein acetylation. HDAC1 and -2 form homo- and heterodimers, and their activity is dependent upon dimer formation. Phosphorylation of HDAC1 and/or HDAC2 in interphase cells is required for the formation of HDAC corepressor complexes. In this study, we show that during mitosis, HDAC2 and, to a lesser extent, HDAC1 phosphorylation levels dramatically increase. When HDAC1 and -2 are displaced from the chromosome during metaphase, they dissociate from each other, but each enzyme remains in association with components of the HDAC corepressor complexes Sin3, NuRD, and CoREST as homodimers. Enzyme inhibition studies and mutational analyses demonstrated that protein kinase CK2-catalyzed phosphorylation of HDAC1 and -2 is crucial for the dissociation of these two enzymes. These results suggest that corepressor complexes, including HDAC1 or HDAC2 homodimers, might target different cellular proteins during mitosis.


The essential cysteines in the CIPC motif of the thioredoxin-like Trypanosoma brucei MICOS subunit TbMic20 do not form an intramolecular disulfide bridge in vivo.
The mitochondrial protein import machinery of trypanosomatids is highly divergent from that of the well-studied models such as baker's yeast. A notable example is that the central catalyst of the mitochondrial intermembrane space import and assembly pathway (MIA), named Mia40, is missing in trypanosomatids. Mia40 works in a two-step process. First it recognizes by direct binding reduced MIA substrate proteins and then catalyzes their oxidative folding to produce intramolecular disulfide bridges. It was recently proposed that a thioredoxin-like subunit of the trypanosomal mitochondrial contact site and cristae organizing system (MICOS) called TbMic20 may be the Mia40 replacement. Our study performed on procyclic stage of the parasite revealed that each of the two cysteines in TbMic20's active site is essential for the stability of MIA substrate proteins although they do not form a disulfide bridge in vivo. The two cysteines of Mia40's active site form an intramolecular disulfide bridge at steady state, which is a prerequisite for its oxidative folding of MIA substrates. Thus, we conclude that TbMic20 is unlikely to represent a bona fide Mia40 replacement and plays a still unresolved role in the stability and/or import of MIA substrates in trypanosomatids. Despite this, the effect of TbMic20 depletion and mutation indicates that the trypanosomal MICOS complex still plays a vital role in the maturation and/or stability of proteins imported by the MIA pathway.


Application of alternative spatiotemporal metrics of ambient air pollution exposure in a time-series epidemiological study in Atlanta.
Exposure error in studies of ambient air pollution and health that use city-wide measures of exposure may be substantial for pollutants that exhibit spatiotemporal variability. Alternative spatiotemporal metrics of exposure for traffic-related and regional pollutants were applied in a time-series study of ambient air pollution and cardiorespiratory emergency department visits in Atlanta, GA, USA. Exposure metrics included daily central site monitoring for particles and gases; daily spatially refined ambient concentrations obtained from regional background monitors, local-scale dispersion, and hybrid air quality models; and spatially refined ambient exposures from population exposure models. Health risk estimates from Poisson models using the different exposure metrics were compared. We observed stronger associations, particularly for traffic-related pollutants, when using spatially refined ambient concentrations compared with a conventional central site exposure assignment approach. For some relationships, estimates of spatially refined ambient population exposures showed slightly stronger associations than corresponding spatially refined ambient concentrations. Using spatially refined pollutant metrics, we identified socioeconomic disparities in concentration-response functions that were not observed when using central site data. In some cases, spatially refined pollutant metrics identified associations with health that were not observed using measurements from the central site. Complexity and challenges in incorporating modeled pollutant estimates in time-series studies are discussed.


Short-chain fatty acids regulate B cells differentiation via the FFA2 receptor to alleviate rheumatoid arthritis.
Short-chain fatty acids (SCFAs) are metabolites from gut microbes involved in the host's inflammatory response and immunity. The aim of this study was to investigate the role of SCFAs in rheumatoid arthritis (RA) and possible mechanisms. Gut microbiota diversity in mice was analysed by 16S rDNA sequencing. SCFAs levels were analysed by gas chromatography mass spectrometry. T and B cells were analysed by flow cytometry. Bone damage was analysed by micro-CT and X-ray. Histopathological status was analysed by HE staining. Proteins in tissues were analysed by immunohistochemistry and PCR. Mice with CD19+ B cells deficient in FFA2 receptors were used to explore the molecular mechanisms involved. Levels of acetate, propionate, butyrate, and valerate were decreased in RA patients, and the first three correlated positively with the frequency of Bregs but not Tregs in peripheral blood. Administration of the three SCFAs prior to the onset of collagen-induced arthritis in mice improved arthritic symptoms, increased the Bregs frequency, and decreased transitional B and follicular B cell frequency. However, the preceding phenomena could not be observed in mice with CD19+ B cells deficient in FFA2 receptors. The effects of the three SCFAs in RA were dependent on FFA2 receptors but were independent of the other five B cell receptors (FFA3 receptor, HCA2 receptor, PPARγ, Olfr-78, and AhR). SCFAs regulate B cells differentiation via FFA2 receptors to alleviate RA. This provides new insights into the treatment of RA from an immunological and microbiological perspective.


[The principle of an occupational approach in expert evaluation of carbon monoxide poisoning during the investigation of aviation accidents].
In case of expert evaluation of poisonings (CO in particular) violation of occupational duties under the influence of toxic substances should be considered as these violations in some cases may result in erroneous actions of a man-operator, which may cause the development or aggravation of accident situation and in the end, death of aircrew and passengers of an aircraft.


Dual-energy computed tomography for evaluation of breast cancer: value of virtual monoenergetic images reconstructed with a noise-reduced monoenergetic reconstruction algorithm.
To evaluate the image quality and lesion visibility of virtual monoenergetic images (VMIs) reconstructed using a new monoenergetic reconstruction algorithm (nMERA) for evaluation of breast cancer. Forty-two patients with 46 breast cancers who underwent 4-phasic breast contrast-enhanced computed tomography (CT) using dual-energy CT (DECT) were enrolled. We selected the peak enhancement phase of the lesion in each patient. The selected phase images were generated by 120-kVp-equivalent linear blended (M120) and monoenergetic reconstructions from 40 to 80 keV using the standard reconstruction algorithm (sMERA: 40, 50, 60, 70, 80) and nMERA (40 +, 50 +, 60 +, 70 +, 80 +). The contrast-to-noise ratio (CNR) was calculated and objectively analyzed. Two independent readers subjectively scored tumor visibility and image quality each on a 5-point scale. The CNR at 40 + and tumor visibility scores at 40 + and 50 + were significantly higher than those on M120. The CNR at 50 + was not significantly different from that on M120. However, the overall image quality score at 40 + was significantly lower than that at 50 + and on M120 (40 + vs M120, P < 0.0001 and 40 + vs 50 +, P = 0.0001). VMI reconstructed with nMERA at 50 keV is preferable for evaluation of patients with breast cancer.


Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells.
The expression vector containing the full-length cDNA of human aromatic L-amino acid decarboxylase (EC 126.96.36.199) was transfected in COS cells by a modified calcium phosphate coprecipitation method. The cells transfected with plasmids that had a true direction of the cDNA gave a major immunoreactive band at 50 kDa. This expressed enzyme catalyzed the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA), L-5-hydroxytryptophan (L-5-HTP) and L-threo-3,4-dihydroxyphenylserine. The optimal pH of the enzyme activity with L-DOPA as a substrate was 6.5, whereas the enzyme had a broad pH optimum when L-5-HTP was used as a substrate. Addition of pyridoxal phosphate to the incubation mixture greatly enhanced the activity for both L-DOPA and L-5-HTP.


Simultaneous determination of six antibiotics belonging to four different classes in chicken meat BY HPLC/DAD and verification BY LC-MS/MS.
The hypothesis of this study was to develop an extraction method allowing side-by-side extraction of six antibiotics belonging to four different classes and an HPLC/DAD method for the determination of their residues in chicken breast meat. The validation data showed that this hypothesis was achieved. The results were then confirmed by LC-MS/MS method. Sample preparation was based on the classical solid-liquid extraction with methanolic citric acid. The average recoveries were satisfactory and ranged from 75.68 to 101.3%. The linearity of the developed HPLC/DAD method was very high in the concentration range studied (R2 > 0.9969). The accuracy and precision of the analytical method were between -10.8 and 12.0% relative error and 0.82 to 10.1% relative standard deviation, respectively. The LODs for five antibiotics ranged from 0.6 to 2.7 µg kg-1 and LOQs ranged from 2.0 to 8.9 µg kg-1. For penicillin G, the LOD was 0.16 and LOQ was 0.52 mg kg-1.


Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator.
We have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biological tools for the study of sirtuin function as well as their potential therapeutic interest.


A comprehensive genotype-phenotype evaluation of eight Chinese probands with Waardenburg syndrome.
Waardenburg syndrome (WS) is the most common form of syndromic deafness with phenotypic and genetic heterogeneity in the Chinese population. This study aimed to clarify the clinical characteristics and the genetic cause in eight Chinese WS families (including three familial and five sporadic cases). Further genotype-phenotype relationships were also investigated. All probands underwent screening for the known WS-related genes including PAX3, SOX10, MITF, EDNRB, EDN3, and SNAI2 using next-generation sequencing to identify disease-causing genes. Further validation using Sanger sequencing was performed. Relevant findings for the associated genotype-phenotype from previous literature were retrospectively analyzed. Disease-causing variants were detected in all eight probands by molecular genetic analysis of the WS genes (SOX10(NM_006941.4): c.544_557del, c.553 C > T, c.762delA, c.336G > A; MITF(NM_000248.3): c.626 A > T; PAX3(NM_181459.4): c.838delG, c.452-2 A > G, c.214 A > G). Six mutations (SOX10:c.553 C > T, c.544_557del, c.762delA; PAX3: c.838delG, c.214 A > G; MITF:c.626 A > T) were first reported. Clinical evaluation revealed prominent phenotypic variability in these WS patients. Twelve WS1 cases and five WS2 cases were diagnosed in total. Two probands with SOX10 mutations developed progressive changes in iris color with age, returning from pale blue at birth to normal tan. Additionally, one proband had a renal malformation (horseshoe kidneys).All cases were first described as WS cases. Congenital inner ear malformations were more common, and semicircular malformations were exclusively observed in probands with SOX10 mutations. Unilateral hearing loss occurred more often in cases with PAX3 mutations. Our findings helped illuminate the phenotypic and genotypic spectrum of WS in Chinese populations and could contribute to better genetic counseling of WS.


Clinical outcome in recurrent and/or metastatic head and neck cancer patients after discontinuation of nivolumab monotherapy due to immune-related adverse events.
Significant immune-related adverse events (irAEs) requiring therapy discontinuation sometimes occur. The influence of discontinuation on disease control after an irAE is unclear. The aim of this study was to investigate whether or not patients continued to show a response or durable disease control even after stopping therapy following an irAE. The response after nivolumab monotherapy discontinuation was examined for 14 patients in whom therapy was stopped without progression. The best response was CR in 5 (36%) patients, PR in 8 (57%) patients and SD in 1 (7%) patient. The estimated 1-year overall and progression-free survival rates were 92.9% and 78.6%, respectively. The best response during nivolumab therapy in patients who developed PD was CR in 0 of 5 patients (0%), PR in 3 of 8 patients (38%) and SD in 1 patient (100%). Patients obtaining CR tended to have a lower risk of PD than those with PR or SD. Patients with CR status may continue to show a response or durable disease control even after stopping therapy due to an irAE.


Effects of calmodulin inhibitor on histamine release from rat peritoneal mast cells induced by concanavalin A and ionophore A23187.
The involvement of calmodulin in stimulus-secretion coupling of histamine release from rat mast cells was examined using a specific calmodulin inhibitor, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide]. W-7 at low concentrations inhibited histamine release induced by either concanavalin A or ionophore A23187 and at high concentrations enhanced the release. But its congener, W-5 [N-(6-aminohexyl)-1-naphthalenesulfonamide], which has virtually no calmodulin-inhibiting activity, did not affect the release. It is concluded that W-7 modulates histamine release by inhibiting some functions of calmodulin in the cells.


The historical and current research progress on jujube-a superfruit for the future.
Jujube (Ziziphus jujuba Mill.), or Chinese date, is the most important species of Rhamnaceae, a large cosmopolitan family, and is one of the oldest cultivated fruit trees in the world. It originates from the middle and lower reaches of the Yellow River, the 'mother river' of the Chinese people. It is distributed in at least 48 countries on all continents except Antarctica and is becoming increasingly important, especially in arid and semiarid marginal lands. Based on a systematic analysis of the unique characteristics of jujube, we suggest that it deserves to be recognized as a superfruit. We summarized historical research achievements from the past 3000 years and reviewed recent research advances since 1949 in seven fields, including genome sequencing and application, germplasm resources and systematic taxonomy, breeding and genetics, cultivation theory and techniques, pest control, postharvest physiology and techniques, and nutrition and processing. Based on the challenges facing the jujube industry, we discuss eight research aspects to be focused on in the future.


Oral versus intra-vaginal imidazole and triazole anti-fungal agents for the treatment of uncomplicated vulvovaginal candidiasis (thrush): a systematic review.
To compare the relative effectiveness, cost effectiveness and safety of oral versus intra-vaginal anti-fungal treatments for uncomplicated vulvovaginal candidiasis (thrush) and establish patient preference for the route of anti-fungal administration. A systematic review of studies comparing oral and intra-vaginal anti-fungal treatments for uncomplicated vulvovaginal candidiasis. Standard Cochrane Collaboration methods were used. The following sources were searched: the Cochrane Controlled Trials Register; the Cochrane Sexually Transmitted Disease review group Specialised Register of Controlled Trials; EMBASE (January 1980 to January 2000); and MEDLINE (January 1985 to May 2000). The reference list of each trial was checked for additional references. The manufacturers of anti-fungal treatments in the UK were asked for information on trials fulfilling the inclusion criteria. There was duplicate, independent examination and selection of the electronic search results followed by duplicate data abstraction. Disagreements regarding inclusion status and data abstraction were resolved by discussion between reviewers and the editor of the Cochrane Sexually Transmitted Disease group. Randomised controlled trials conducted worldwide and published in any language were included. The primary outcome measure was clinical cure. Mycological cure, patient preference and safety were secondary outcome measures. Seventeen trials were included in the review, reporting 19 oral versus intra-vaginal anti-fungal treatment comparisons. No statistically significant differences were shown between oral and intra-vaginal anti-fungal treatment for clinical or mycological cure. All 10 trials that reported a preference favoured oral treatment (compared with intra-vaginal or no preference). No trials presented cost data. There is no difference between the relativeeffectiveness of oral and intra-vaginal anti-fungal treatment for thrush.


When Two Become One: Conformational Changes in FXR/RXR Heterodimers Bound to Steroidal Antagonists.
Farnesoid X receptor (FXR) is a nuclear receptor with an essential role in regulating bile acid synthesis and cholesterol homeostasis. FXR activation by agonists is explained by an αAF-2-trapping mechanism; however, antagonism mechanisms are diverse. We discuss microsecond molecular dynamics (MD) simulations investigating our recently reported FXR antagonists 2a and 2 h. We study the antagonist-induced conformational changes in the FXR ligand-binding domain, when compared to the synthetic (GW4064) or steroidal (chenodeoxycholic acid, CDCA) FXR agonists in the FXR monomer or FXR/RXR heterodimer r, and in the presence and absence of the coactivator. Our MD data suggest ligand-specific influence on conformations of different FXR-LBD regions, including the α5/α6 region, αAF-2, and α9-11. Changes in the heterodimerization interface induced by antagonists seem to be associated with αAF-2 destabilization, which prevents both co-activator and co-repressor recruitment. Our results provide new insights into the conformational behaviour of FXR, suggesting that FXR antagonism/agonism shift requires a deeper assessment than originally proposed by crystal structures.


Characteristics and degradation of carbon and phosphorus from aquatic macrophytes in lakes: Insights from solid-state (13)C NMR and solution (31)P NMR spectroscopy.
Water extractable organic matter (WEOM) derived from macrophytes plays an important role in biogeochemical cycling of nutrients, including carbon (C), nitrogen (N) and phosphorus (P) in lakes. However, reports of their composition and degradation in natural waters are scarce. Therefore, compositions and degradation of WEOM derived from six aquatic macrophytes species of Tai Lake, China, were investigated by use of solid-state (13)C NMR and solution (31)P NMR spectroscopy. Carbohydrates were the predominant constituents of WEOM fractions, followed by carboxylic acid. Orthophosphate (ortho-P) was the dominant form of P (78.7% of total dissolved P) in the water extracts, followed by monoester P (mono-P) (20.6%) and little diester P (0.65%). The proportion of mono-P in total P species increased with the percentage of O-alkyl and O-C-O increasing in the WEOM, which is likely due to degradation and dissolution of biological membranes and RNA from aquatic plants. Whereas the proportion of mono-P decreased with alkyl-C, NCH/OCH3 and COO/N-C=O increasing, which may be owing to the insoluble compounds including C functional groups of alkyl-C, NCH/OCH3 and COO/N-C=O, such as aliphatic biopolymers, lignin and peptides. Based on the results of this study and information in the literature about water column and sediment, we propose that WEOM, dominated by polysaccharides, are the most labile and bioavailable component in debris of macrophytes. Additionally, these WEOMs would also be a potential source for bioavailable organic P (e.g., RNA, DNA and phytate) for lakes.


Candidacy for kidney transplantation of older adults.
To develop a prediction model for kidney transplantation (KT) outcomes specific to older adults with end-stage renal disease (ESRD) and to use this model to estimate the number of excellent older KT candidates who lack access to KT. Secondary analysis of data collected by the United Network for Organ Sharing and U.S. Renal Disease System. Retrospective analysis of national registry data. Model development: Medicare-primary older recipients (aged ≥ 65) of a first KT between 1999 and 2006 (N = 6,988). Model application: incident Medicare-primary older adults with ESRD between 1999 and 2006 without an absolute or relative contraindication to transplantation (N = 128,850). Comorbid conditions were extracted from U.S. Renal Disease System Form 2728 data and Medicare claims. The prediction model used 19 variables to estimate post-KT outcome and showed good calibration (Hosmer-Lemeshow P = .44) and better prediction than previous population-average models (P < .001). Application of the model to the population with incident ESRD identified 11,756 excellent older transplant candidates (defined as >87% predicted 3-year post-KT survival, corresponding to the top 20% of transplanted older adults used in model development), of whom 76.3% (n = 8,966) lacked access. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for KT. A risk-prediction model specific to older adults can identify excellent KT candidates. Appropriate referral could result in significantly greater rates of KT in older adults.


A flow cytometric method for measuring and isolating mammary epithelial cells from bovine milk.
Sampling frequent time points of mammary signaling pathways is not possible with tissue biopsies. We have validated a flow cytometry and cell sorting procedure for isolating live bovine mammary epithelial cells from somatic cell populations in milk using butyrophilin 1A1 as a marker for mammary epithelial cells and CD45 as a marker for hematopoietic cells. Hoechst 33342 staining and propidium iodide exclusion were used to select for nucleated live cells. Positive selection of butyrophilin (BTN)-expressing cells was performed by fluorescence-activated cell sorting. Quantitative real-time PCR performed on mRNA isolated from these cells showed a 226-fold increase in κ-casein (CSN3) mRNA expression in BTN single-positive cells compared with unsorted cells, whereas CD45 single-positive cells showed a significant decrease. A negative selection strategy for cells not expressing the hematopoietic cell marker CD45 also resulted in a cell population with a 196-fold increase in CSN3 mRNA expression compared with unsorted cells. We found no enrichment of CSN3 mRNA expression after sorting cells using cytokeratin antibodies. The noninvasive assays described here allow for daily or more frequent sampling time points for measurement of mammary epithelial cells during the course of lactation.


Cortical activity in multiple motor areas during sequential finger movements: an application of independent component analysis.
Multiple cortical regions such as the supplementary motor area (SMA), premotor cortex (PM), and primary motor cortex (M1) are involved in the sequential execution of hand movements, but it is unclear how these areas collaborate in the preparation and execution of ipsilateral and contralateral hand movements. In this study, we used right-handed subjects to examine the spatial distribution and temporal profiles of motor-related activity during visually cued sequential finger movements by applying independent component analysis (ICA) to event-related functional magnetic resonance imaging (fMRI) signals. The particular merit of the ICA method is that it allows brain activity in individual subjects to be elucidated without making a priori assumptions about the anatomical areas that are activated or the temporal profile of activity. By applying ICA, we found that (1) the SMA contributed to both the preparation and execution of movements of the right and left hand; (2) the left M1 and dorsal premotor cortex (PMd) contributed to both the preparation and execution of movements of the right and left hand, whereas the right M1 and PMd contributed mainly to the execution of movements of the left hand; (3) pre-SMA areas were activated in some subjects in concert with the posterior parietal and prefrontal cortex; and (4) fMRI signals over superficial cortical draining veins could be distinguished from cortical activation. We suggest that ICA is useful for categorizing distributed task-related activities in individual subjects into several spatially independent activities that represent functional units in motor control.


Urinary incontinence.
Accurate diagnosis and successful management depend on knowledge of the anatomy and regulatory physiology of micturition. Incontinence is classified according to its mechanisms--passive incontinence, active incontinence with or without complete emptying, and overflow incontinence. Approaches to management include pharmacotherapy, surgical procedures and important steps in supportive care. This is a problem of any age. Educating the patient is essential.


A dynamic view to the modulation of phosphorylation and O-GlcNAcylation by inhibition of O-GlcNAcase.
Protein phosphorylation and O-GlcNAcylation are reciprocally regulated. As hyperphosphorylation is implicated in tau pathology, approaches have been exploited to reduce the magnitude of tau phosphorylation by increasing the level of tau O-GlcNAcylation. With mathematic models constructed to describe different kinetic scenarios, we analyzed the temporal change of an O-GlcNAcylated protein in contrast to that of the phosphorylated form upon inhibition of O-GlcNAcase (OGA). The analyses indicate that when degradation of the modified protein is negligible relative to the naked one, the magnitude of O-GlcNAcylated protein increase is proportional to the level of inhibition, while the extent of phosphorylated protein decline varies due to other factors. Furthermore, the increase of O-GlcNAcylated protein parallels with the decrease of phosphorylated form upon acute or short-term inhibition of OGA, as observed in many in vitro and short term in vivo studies. However, phosphorylated protein is predicted to return to its initial level while O-GlcNAcylated protein to achieve a higher steady level under sustained inhibition. This simulated result is in line with a recent report on long-term inhibition of OGA in transgenic mice. Noticeably, inhibition withdrawal is anticipated to cause a transient rise of phosphorylated protein. If degradation of modified proteins proceeds in addition to the naked one, the characteristic temporal profiles of each form in response to OGA inhibition would depend on the relative importance of individual degradation pathways. The models described herein may serve as a useful investigational tool that will provide insight into pharmacological intervention for tauopathies in particular and for reciprocally modulated reactions in general.


Arthroscopy-Assisted Scapholunate Reconstruction With Internal Brace Augmentation.
Various surgical techniques exist to repair or reconstruct complete scapholunate (SL) interosseous ligament tears, including capsulodesis, static or dynamic tenodesis, ligament reconstruction with tendon graft, bone-retinaculum-bone reconstruction, and the reduction and association of the scaphoid and lunate (RASL) procedure. The choice of surgical technique depends on arthroscopic assessment using the Geissler classification and European Wrist Arthroscopy Society staging of SL injury. This article describes arthroscopy-assisted extracapsular SL reconstruction using free tendon graft and internal brace augmentation for the treatment of unrepairable complete SL interosseous ligament tears.


Identifying brain regions for integrative sensorimotor processing with ankle movements.
The objective of this study was to define cortical and subcortical structures activated during both active and passive movements of the ankle, which have a fundamental role in the physiology of locomotion, to improve our understanding of brain sensorimotor integration. Sixteen healthy subjects, all right-foot dominant, performed a dorsi-plantar flexion task of the foot using a custom-made wooden manipulandum, which enabled measurements of the movement amplitude. All subjects underwent a training session, which included surface electromyography, and were able to relax completely during passive movements. Patterns of activation during active and passive movements and differences between functional MRI (fMRI) responses for the two types of movement were assessed. Regions of common activation during the active and passive movements were identified by conjunction analysis. We found that passive movements activated cortical regions that were usually similar in location to those activated by active movements, although the extent of the activations was more limited with passive movements. Active movements of both feet generated greater activation than passive movements in some regions (such as the ipsilateral primary motor cortex) identified in previous studies as being important for motor planning. Common activations during active and passive movements were found not only in the contralateral primary motor and sensory cortices, but also in the premotor cortical regions (such as the bilateral rolandic operculum and contralateral supplementary motor area), and in the subcortical regions (such as the ipsilateral cerebellum and contralateral putamen), suggesting that these regions participate in sensorimotor integration for ankle movements. In future, similar fMRI studies using passive movements have potential to elucidate abnormalities of sensorimotor integration in central nervous system diseases that affect motor function.


Erythroid stem cells in Friend-virus infected mice.
The erythropoietic stem cell compartment was studied in Friend-virus (polycythemic strain, FV-P) infected DBA/2 and NMRI mice with the CFUE and BFUE technique. Early after infection there was a depression in CFUE number in bone marrow and spleen, followed by an increase of the CFUE concentration, earlier and more pronounced in the spleen than in the marrow. Three days after FV-P infection an erythropoietin (Ep) independent CFUE population started to grow and replaced the normal Ep-dependent population within 8 to 12 days. The shift to Ep independency was not gradual. CFUE colonies of FV-P infected bone marrow cells were two to three times larger than control colonies after three days in vitro incubation. BFUE colonies increased in number during the first days of infection, but were totally lost after more than ten days. After velocity sedimentation of bone marrow cells of FV-P infected animals, however, the BFUE containing fractions showed normal BFUE colony growth and normal Ep sensitivity. In unfractionated bone marrow cell cultures BFUE colony growth could be observed later than ten days post infection when the cultures were refed with medium. It was therefore concluded that the loss of BFUE colony growth after FV-P infection was an in vitro artefact due to inadequate culture conditions.


Light intensity alters the effects of light-induced circadian disruption on glucose and lipid metabolism in mice.
Circadian disruption induced by rotating light cycles has been linked to metabolic disorders. However, how the interaction of light intensity and light cycle affects metabolism under different diets remains to be explored. Eighty mice were first randomly stratified into the low-fat diet (LFD, n = 40) or high-fat diet (HFD, n = 40) groups. Each group was further randomly subdivided into four groups (n = 8-12 per group) in terms of different light intensities [lower (LI, 78 lx) or higher intensity (HI, 169 lx)] and light cycles [12-h light:12-h dark cycle or circadian-disrupting (CD) light cycle consisting of repeated 6-h light phase advancement]. Body weight was measured weekly. At the end of the 16-wk experiment, mice were euthanized for serum and pathological analysis. Glucose and insulin tolerance tests were performed during the last 2 wk. The CD cycle increased body weight gain, adipocyte area, glucose intolerance, and insulin resistance of LFD as well as HFD mice under HI but not LI condition. Moreover, the serum and hepatic triglyceride levels increased with LFD-HI treatment, regardless of light cycle. In addition, the CD cycle improved lipid and glucose metabolism under HFD-LI condition. In summary, the detrimental effects of the CD cycle on metabolism were alleviated under LI condition, especially in HFD mice. These results indicate that modulating light intensity is a potential strategy to prevent the negative metabolic consequences associated with jet lag or shift work.NEW & NOTEWORTHY Glucose and lipid homeostasis is altered by the CD cycles in a light-intensity-dependent manner. Lower-intensity light reverses the negative metabolic effects of the CD cycles, especially under HFD feeding. The interaction of light intensity and light cycle on metabolism is independent of energy intake and eating pattern. Glucose metabolic disorders caused by rotating light cycles occur along with compensatory β-cell mass expansion.


Deep whole-genome resequencing sheds light on the distribution and effect of amphioxus SNPs.
Amphioxus is a model organism for vertebrate evolutionary research. The significant contrast between morphological phenotypic similarity and high-level genetic polymorphism among amphioxus populations has aroused scientists' attention. Here we resequenced 21 amphioxus genomes to over 100X depth and mapped them to a haploid reference. More than 11.5 million common SNPs were detected in the amphioxus population, which mainly affect genes enriched in ion transport, signal transduction and cell adhesion, while protein structure analysis via AlphaFold2 revealed that these SNPs fail to bring effective structural variants. Our work provides explanation for "amphioxus polymorphism paradox" in a micro view, and generates an enhanced genomic dataset for amphioxus research.


Regulation of plasminogen activator secretion in mouse peritoneal macrophages. I. - Role of serum studied by a new spectrophotometric assay for plasminogen activators.
A chromogenic tripeptide - H-D-Val-Leu-Lys-p-nitroanilide-substrate of plasmin, can be used to follow plasminogen activation by an activator such as urokinase or the activator secreted by mouse peritoneal macrophages (thioglycolate-elicited). The acceleration of p-nitroaniline production is proportional to the initial rate of plasmin formation from plasminogen. Thus, at a given plasminogen concentration, this acceleration is proportional to the activator concentration. The acceleration can be evaluated from the spectrophotometer trace recording at 405 nm the appearance of p-nitroaniline, either by means of a computer program or by a plot of delta A405 vs.t2. The sensitivity of this assay allows detection of 0.003 CTA units of urokinase. Thioglycollate-elicited mouse peritoneal macrophages secrete plasminogen activator into the extracellular medium during in vitro cultivation only after a contact with serum.


Determinants of precancerous cervical lesion among HIV infected women on ART in Woldia comprehensive specialized hospital NorthEast Ethiopia.
Precancerous cervical lesion is a priority public health problem that jeopardizes the life of enormous women. previous studies in Ethiopia were more focused on knowledge, attitude, and practices of Cervical cancer screening. studies on the risk factors of pre-cancerous cervical lesions among the risk population (HIV infected) relative to the general population were limited. This study aimed to identify the determinants of precancerous cervical lesions among HIV Infected Women in Woldia Comprehensive Specialized Hospital in Northeast Ethiopia, 2022. Hospital-based unmatched case-control study was conducted in Woldia Comprehensive Specialized Hospital among HIV-infected women from June to August 2022. Data were collected from 104 cases and 208 controls using an interviewer-administered questionnaire and clinical data from the patient chart using Electronic Medical Record _ Anti-Retroviral Therapy Smart care database checklist. The binary logistic regression model was used to identify the determinants of the precancerous cervical lesion. An odds ratio with a 95% Confidence interval was used to measure the association and p-value < 0.05 were considered significant. Women who have two or more lifetime sexual partners (AOR = 3.21,95% CI: 1.71-6.04), history of sexually transmitted infection (AOR = 4.97, 95% CI: 2.78-8.78), early age at first sexual intercourse (< 18 years) (AOR = 4.35,95% CI: 2.48-7.67) and baseline CD4 count < 200 cells/mm3 (AOR = 1.89, 95% CI: 1-3.57) had a higher odd of developing a precancerous cervical lesion. This study confirms that having a history of sexually transmitted infection, two or more lifetime sexual Partners, the initiation of sexual intercourse before the age of 18 years, and Baseline CD4 count < 200 cells/mm3 were determinants for precancerous cervical lesions. So it should be focused on prevention through early detection and treatment of sexually transmitted infections.


Differential management of scaphocephaly.
The objective of this study was to review the outcomes of scaphocephaly management. We hypothesized that differential treatment of scaphocephaly based on age at correction and degree of severity yields consistently satisfying results while reducing the operative morbidity. Retrospective patient record review. Three cranial vault-remodeling procedures with varying levels of aggressiveness (limited-access, partial, and total cranial-vault remodeling) were performed on patients with scaphocephaly from 1995 to 2010. More-aggressive procedures were performed on older patients and patients having more-severe deformities. Patient records were reviewed for age, weight, blood loss, and length of hospital stay, and cephalic indices (CIs) were calculated from computed tomography scans and clinical photographs. Fifty-one patients underwent surgery for scaphocephaly during the study period. The average estimated blood volume fraction lost was 0.41. The average length of hospital stay was 4.49 days. Pre- and postoperative CIs were calculable for 36 patients. The average preoperative CI was 68.7. The average postoperative CI was 79.3, for an average operative change of 15%. The three procedures had statistically different values for average length of stay. A trend was suggested for estimated blood loss and volume fraction lost. There was no statistically significant difference in CI outcomes. This study supports the concept of a proportionate response in the management of scaphocephaly. Less-aggressive procedures do not yield less-desirable results when properly selected to match the clinical situation of the individual patient.


Mismatch between iodine-123 IMP and technetium-99m HM-PAO brain perfusion imaging in a patient with meningioma.
The discrepancy between three methods for cerebral perfusion imagings in the case of a man with meningioma is presented. Imaging with N-isopropyl-P-[I-123] iodoamphetamine (IMP) showed no activity in the tumor. Imaging with Tc-99m hexamethylpropyleneamine oxime (HM-PAO) and the local cerebral blood flow (LCBF) image with Xe-133 inhalation showed high tumor activity. IMP is a more accurate method for imaging the brain tissue blood flow.


[State of the blood circulation system in stabilization of blood with sodium citrate during hemosorption in patients with acute poisoning].
The time course of cardiovascular parameters in the course of citrate hemoperfusion was studied by routine noninvasive methods: tetrapolar thoracic rheoplethysmography, acceleration kineticocardiography, transesophageal diagnostic electrocardiostimulation, and electrocardiography. Hemoperfusion was carried out at a bloodstream velocity of 100 ml/min. Blood preserving agent glucigar was used for blood stabilization, with the citrate to blood ratio 1:1 maintained. Analysis of changes in the central hemodynamics and phase structure of left-ventricular systole was carried out in two groups of patients with the normo- and hypodynamic circulation. No appreciable changes in the hemo- and cardiodynamics were observed over the course of hemoperfusion with sodium citrate stabilization in patients with normodynamic circulation, nor were any adverse reactions on the part of the cardiovascular system observed in the patients with hypodynamic circulation. Reliable changes in the electrophysiological parameters were not recorded either. Moreover, hemosorption did not involve arrhythmias or conduction disorders.


Midbrain stimulation in the anesthetized rat: direct locomotor effects and modulation of locomotion produced by hypothalamic stimulation.
The midbrain contains circuits that modulate locomotion. To delineate some of the involved regions, low-level stimulation (25 microA, 10 s train of 0.5 ms pulses at 50 Hz) was applied to the midbrain during locomotor stepping. Stepping was elicited in the anesthetized (pentobarbital, 40 mg/kg) rat by stimulating the hypothalamus with 0.5 ms pulses at 40 Hz at various currents. The rat was held in a stereotaxic apparatus such that locomotor stepping movements turned a wheel. Facilitation of locomotion was produced by stimulation in the anterior ventromedial midbrain and in the posterodorsal midbrain. When presented alone, such stimulation produced locomotion. Inhibition of locomotion was produced by stimulation of the superior colliculus (ventral layers) and the ventromedial midbrain. Additional inhibitory sites were found in the central gray and the lateral tegmentum. Inhibitory collicular stimulation, when presented alone, was characterized by the absence of any hindlimb response. Inhibitory ventromedial stimulation, when presented alone, frequently produced poststimulation locomotion and when presented with hypothalamic stimulation was characterized by postinhibitory increases in locomotion. These results indicate that: (1) the locomotor effects of stimulation in midbrain and hypothalamic sites can summate: (2) multiple locomotor suppressive systems are present in the midbrain and among them are a collicular system and a ventromedial system.


Charged chelate-capillary electrophoresis of endogenous corticosteroids.
Separation of endogenous 17- or 18-hydroxylated corticosteroids (of the 21-hydroxylated 4-pregnen series) as charged chelates in capillary electrophoresis with borate as the ligand is demonstrated. Aldosterone, 18-hydroxycorticosterone, 18-hydroxy-11-deoxycorticosterone, cortisone, cortisol, and 11-deoxycortisol are separated and resolved by 400 mM borate buffer at pH 9.0. Separation characteristics of the corticosteroid charged chelates were examined by varying the separation buffer borate concentration, pH, ionic strength, and addition of organic modifiers. The borate ion [B(OH)4]- is identified as the critical buffer component. Corticosteroids chelate borate with proximal hydroxyls composed of either the 17- or 18-hydroxyl in combination with the 21-position hydroxyl. Corticosteroid/borate chelation as indicated by CE results is corroborated with 11B-nuclear magnetic resonance (11B-NMR) spectra. Chelation is a readily reversible process, with the strength of the resultant chelate, as opposed to the charge-to-mass ratio, predominantly determining analyte mobility in charged chelate - capillary electrophoresis (CC-CE).


Neuromuscular fatigue during whole body exercise.
This short review offers a general summary of the consequences of whole body exercise on neuromuscular fatigue pertaining to the locomotor musculature. Research from the past two decades have shown that whole body exercise causes considerable peripheral and central fatigue. Three determinants characteristic for locomotor exercise are discussed, namely, pulmonary system limitations, neural feedback mechanisms, and mental/psychological influences. We also discuss existing data suggesting that the impact of whole body exercise is not limited to locomotor muscles, but can also impair non-locomotor muscles, such as respiratory and cardiac muscles, and other limb muscles not directly contributing to the task.


Animal migration research takes wing.
In the beginning there was great confusion about animal migration. Aristotle, noting that the types of birds around him changed with the seasons, concluded that summer redstarts turned into robins at the onset of winter, and that garden warblers became blackcaps [1]. Others thought that birds disappear in winter because they hibernate submerged in mud. In a case of art decidedly not imitating life, a 16th century illustration accompanying the writings of Swedish Archbishop Olaus Magnus showed a fishing net filled with hibernating swallows being pulled from a lake [1]. Gradually, over centuries, these fanciful early explanations gave way to an understanding that migration is a widespread phenomenon and that Earth is alive with itinerant animals traversing continents, seas, and skies (Figure 1).


Sleep disorders in anti-NMDAR encephalitis.
To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe). Patients recovering from anti-NMDARe were invited to participate in a prospective observational single-center study including comprehensive clinical, video-polysomnography (V-PSG) sleep assessment, and neuropsychological evaluation. Age- and sex-matched healthy participants served as controls. Eighteen patients (89% female, median age 26 years, interquartile range [IQR] 21-29 years) and 21 controls (81% female, median age 23 years, IQR 18-26 years) were included. In the acute stage, 16 (89%) patients reported insomnia and 2 hypersomnia; nightmares occurred in 7. After the acute stage, 14 (78%) had hypersomnia. At study admission (median 183 days after disease onset, IQR 110-242 days), 8 patients still had hypersomnia, 1 had insomnia, and 9 had normal sleep duration. Patients had more daytime sleepiness than controls (higher Barcelona Sleepiness Index, p = 0.02, and Epworth Sleepiness Score, p = 0.04). On V-PSG, sleep efficiency was similar in both groups, but patients more frequently had multiple and longer confusional arousals in non-REM (NREM) sleep (videos provided). In addition, 13 (72%) patients had cognitive deficits; 12 (67%) had psychological, social, or occupational disability; and 33% had depression or mania. Compared with controls, patients had a higher body mass index (median 23.5 [IQR 22.3-30.2] vs 20.5 [19.1-21.1] kg/m2; p = 0.007). Between disease onset and last follow-up, 14 (78%) patients developed hyperphagia, and 6 (33%) developed hypersexuality (2 requiring hospitalization), all associated with sleep dysfunction. Sleep disturbances are frequent in anti-NMDARe. They show a temporal pattern (predominantly insomnia at onset; hypersomnia during recovery), are associated with behavioral and cognitive changes, and can occur with confusional arousals during NREM sleep.


Pseudomediastinal fibrosis caused by massive lymphadenopathy in domestically acquired particulate lung disease.
In this report, we describe a case of domestically acquired particulate lung disease (DAPLD) or "hut lung" in a 59-year-old woman of Moroccan descent who emigrated to the Netherlands, having lived in an rural area for most her life. She presented with obstructive lung disease and with signs of mediastinal fibrosis which were shown to be caused by massive enlargement of mediastinal lymph nodes. To the best of our knowledge, this is the first case of DAPLD from Morocco and the first report of a case of DAPLD mimicking mediastinal fibrosis.


Dominance is not inevitable.
In a diploid organism, a mutant gene that results in elimination of an enzyme activity in the homozygote is almost universally found to be recessive, so that the heterozygote phenotype is virtually indistinguishable from the wild type. It has been argued (H. Kacser & J. A. Burns, Genetics 97, 639-666 (1981)) that there is no need to look to evolution for an explanation of this phenomenon, as it is an inevitable consequence of the low control coefficients for metabolic flux possessed by nearly all enzymes. However, it is possible to envisage pathways in which every enzyme is more than half-saturated, so that moderate changes in the concentration of any enzyme result in substantial changes in metabolic flux. Such behaviour can occur, for example, if the limiting rates of the enzymes decrease as one proceeds along the pathway and the precursor concentration is large compared with the Michaelis constants of all the enzymes. Consequently one does require an explanation in terms of natural selection of why such pathways are apparently not observed in nature.


Study on quality difference between Belamcanda chinensis (L.) DC and Iris tectorum Maxim. based on chemical chromatogram analysis, biological activity evaluation and in vivo distribution rule.
Belamcanda chinensis (L.) DC. (BC) and Iris tectorum Maxim. (ITM) have been widely used in recent years due to their remarkable curative effects on sore throat, cough and asthma. but they are often misused due to their similar appearance. A comprehensive comparison of the chemical composition, biological activity, pharmacokinetics and tissue distribution between the two active differential components has not been performed. Differences in their specific effects have not been fully elucidated. This work aims at differentiating between BC and ITM in terms of appearance, chemical composition, biological activity, pharmacokinetics and tissue distribution. In this study, the HPLC-FP method was used to find the differences between the chemical components of BC and ITM. The pharmacological experiments were used to compare the differences in activity, including in vitro anti-inflammatory activity with LPS-induced inflammation model of RAW 264.7 cells, inhibition of AChE activity, and the regulation of isolated small intestinal smooth muscle in mice. The pharmacokinetic and tissue distribution profiles were used to analyze the differences between the two in rats. The types of isoflavones in BC and ITM are basically the same, but their contents in ITM is much higher than that in BC. At the same doses, the release of TNF-α, NO, IL-1β and IL-6 from RAW 264.7 cells in the ITM group was lower than that of the BC group, and the in vitro anti-inflammatory activity of ITM was stronger than that of BC. Meanwhile, ITM had stronger inhibition ability to inhibit AChE activity than BC. The BC extract exhibited an inhibitory effect on the isolated small intestinal smooth muscle of mice, and the ITM extract showed stimulatory effect at low concentration and inhibitory effect at high concentration. There were significant differences in drug-time profiles, kinetic parameters and tissue distribution. There are significant differences in the multidimensional aspects of appearance, chemical composition, biological activity, pharmacokinetics, and tissue distribution between BC and ITM. This study provides a theoretical basis for the quality control, pharmacological efficacy and clinical application of the two herbs.


Tropical obstetrics and gynaecology. 3. Vesico-vaginal fistula--a tropical disease.
The predominantly obstetric origin of vesico-vaginal fistulae in the tropics is contrasted with the mainly surgical aetiology of those in Europe by analysis of 543 cases treated in Nigeria and in the United Kingdom. Reasons are given for the high incidence in tropical countries of obstructed labour and hence of vesico-vaginal fistulae. The general management of patients with obstetric fistulae is described, followed by the principles of their surgical treatment and postoperative nursing care. The importance of success at the first attempt at repair is stressed, and the small place for managing failures by urinary diversion is mentioned. It is concluded that obstetric fistulae should be preventable in the tropics, having now been effectively eliminated from industrialized countries.


Cytoimmunofluorescent localization of severin in Dictyostelium amoebae.
Severin is a 40-kDa Ca2+-activated protein from Dictyostelium that rapidly fragments and disassembles actin filaments in vitro (S.S. Brown, K. Yamamoto, and J.A. Spudich, J. Cell Biol. 93, 205-210, 1982; and K. Yamamoto, J.D. Pardee, J. Reidler, L. Stryer, and J.A. Spudich. J. Cell Biol. 95, 711-719, 1982). To determine if severin is colocalized with actin filaments in vivo, we have used the agar-overlay technique of S. Yumura, H. Mori, and Y. Fukui (J. Cell Biol. 99, 894-899, 1984) to examine the intracellular locations of severin and F-actin in vegetative Dictyostelium amoebae. In rounded cells taken from suspension culture severin colocalized with F-actin at cortical edges while maintaining an endoplasmic presence. Both severin and F-actin were present throughout nascent pseudopods of motile cells, while severin appeared concentrated at the leading edge of fully developed pseudopods. Amoebae feeding on a bacterial lawn formed large phagocytic vesicles that were surrounded by an extensive cell cortex rich in severin. Streaming cells entering aggregates during the Dictyostelium developmental cycle showed severin staining throughout the cytoplasm with F-actin at the cortex. The preferential localization of severin in cytoplasmic regions of vegetative cells undergoing extensive actin cytoskeletal rearrangement prompts consideration of a role for severin-mediated disruption of actin filament networks during pseudopod extension and phagocytosis.


Split-thickness skin graft donor site care: a quantitative synthesis of the research.
Split-thickness skin grafting (STSG) is a frequently used reconstructive technique but is associated with a large variation in practice. The purposes of this article are to integrate and synthesize the available empirical evidence regarding STSG donor site dressings, identify which dressings are associated with the best outcomes, and provide practice recommendations. This review of 33 studies found transparent film to be the best dressing for the care of STSG donor site wounds. Transparent film was associated with one of the fastest healing rates (9.47 days), a smooth epithelialized surface, a low infection rate (10 out of 394 patients or 3%), the least amount of pain (1.59 on 0 to 10 scale), and minimal cost ($.005 per square inch) when compared with other dressings.


Hyperechogenic fetal bowel: Current evidence-based prenatal diagnosis and management.
Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%-1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter-observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post-natal follow-up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause.


A Novel Tissue Preservation and Transport Solution as a Substitute for Formalin.
Formalin, a common laboratory fixative, is a type 1 carcinogen; a biohazard with risks, environmental, disposal, and legal costs; and a chemical modifier of protein epitopes in tissues. A less-toxic tissue preservation method is therefore badly needed. We have developed a novel tissue preservation medium, Amber, composed of low-potassium dextran glucose, 10% honey, and 1% coconut oil. This study investigates Amber as compared with formalin with respect to the following aspects: (1) histologic preservation, (2) epitope integrity with immunohistochemistry (IHC) and immunofluorescence (IF), and (3) integrity of tissue RNA. Rat and human lung, liver, kidney, and heart tissues were collected and stored for 24 hours at 4 °C in Amber or formalin. The tissues were evaluated with hematoxylin and eosin; IHC: thyroid transcription factor, muscle-specific actin, hepatocyte-specific antigen, and common acute lymphoblastic leukemia antigen; and IF: VE-cadherin, vimentin, and muscle-specific actin. RNA quality upon extraction was also assessed. Amber demonstrated superior and/or noninferior performance in rat and human tissue evaluation with respect to standard techniques of histology, IHC, IF, and extracted RNA quality. Amber maintains high-quality morphology without compromising the ability to perform IHC and nucleic acid extraction. As such, Amber could be a safer and superior substitute to formalin for clinical tissue preservation for contemporary pathological examination.


Chemokines in allergic airway disease.
Expression of chemokine receptors on T helper 2 cells and eosinophils has been postulated to be the mechanism by which these cells are selectively recruited to the lung during allergic inflammatory reactions. Mouse models have provided evidence to show that blocking the ligands for these receptors is successful in abrogating the pathophysiological effects of allergen challenge. However, recent studies describing the effect of genetic deletions of these chemokine receptors have not confirmed the results obtained with ligand knockouts or neutralising antibodies. Coupled with the realisation that, because of a lack of species cross-reactivity, it is not possible to test small molecule antagonists against human receptors in the original in vivo animal models, the future of chemokine receptor therapeutics is in question. However, recent advances have been made regarding the therapeutic potential of blocking the chemokine receptors CCR3, CCR4 and CCR8 in allergic airway disease.


The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors measured with (123)I-R91150 SPECT.
Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system.


Identification of plasma inactive renin as prorenin with a site-directed antibody.
A sequence-specific antibody that recognizes a portion of the prosegment of human renin precursor was raised and used to provide direct evidence that plasma inactive renin contains the prosequence of renal renin and is therefore probably prorenin rather than an inactivated form of previously active renin. The information may help not only to resolve a major controversy concerning the nature of inactive renin in human plasma but also to elucidate its exact physiological role.