Manual cleaning of hospital mattresses: an observational study comparing high- and low-resource settings.
Hospital-associated infections (HAIs) are more frequently encountered in low- than in high-resource settings. There is a need to identify and implement feasible and sustainable approaches to strengthen HAI prevention in low-resource settings. To evaluate the biological contamination of routinely cleaned mattresses in both high- and low-resource settings. In this two-stage observational study, routine manual bed cleaning was evaluated at two university hospitals using adenosine triphosphate (ATP). Standardized training of cleaning personnel was achieved in both high- and low-resource settings. Qualitative analysis of the cleaning process was performed to identify predictors of cleaning outcome in low-resource settings. Mattresses in low-resource settings were highly contaminated prior to cleaning. Cleaning significantly reduced biological contamination of mattresses in low-resource settings (P < 0.0001). After training, the contamination observed after cleaning in both the high- and low-resource settings seemed comparable. Cleaning with appropriate type of cleaning materials reduced the contamination of mattresses adequately. Predictors for mattresses that remained contaminated in a low-resource setting included: type of product used, type of ward, training, and the level of contamination prior to cleaning. In low-resource settings mattresses were highly contaminated as noted by ATP levels. Routine manual cleaning by trained staff can be as effective in a low-resource setting as in a high-resource setting. We recommend a multi-modal cleaning strategy that consists of training of domestic services staff, availability of adequate time to clean beds between patients, and application of the correct type of cleaning products.


Isolation of an ompC-like outer membrane protein gene from Salmonella typhi.
We have isolated the structural gene for an outer membrane protein of Salmonella typhi, from a genomic library constructed in bacteriophage lambda 1059, using the Escherichia coli ompC gene as a heterologous probe. E. coli ompC codes for an outer membrane pore protein (porin) that is induced preferentially at high osmolarity and high temperature. The S. typhi ompC-like gene was subcloned in pBR322 and introduced into E. coli HB101 and into P678-54, a minicell-producing strain. In both strains it expressed a 38.5-kDa protein, which was incorporated into the outer membrane envelope and comigrated with an S. typhi outer membrane protein which was expressed both at low and high osmolarity in vivo.


Trans-jugular transcutaneous closure of atrial septal defects with an adjustable curved sheath under echocardiography guidance.
Traditional transcatheter closure of atrial septal defect (ASD) via the femoral vein carries risk of radiation damage. Transcutaneous closure of ASD under echocardiography guidance avoids radiation exposure and can be gradually applied. An alternative is to transcutaneous closure of ASD trans-jugular with an adjustable curved sheath under echocardiography guidance. We retrospectively studied all cases of trans-jugular transcutaneous closure of ASD with an adjustable curved sheath under echocardiography guidance in the Heart Center of Henan Province People's Hospital between 2016 and December 2022. A total of 156 patients were included, 74 males and 82 females. Mean age was 6.9 ± 7.4 years and weight 23.7 ± 14.6 kg. Mean sizes of the ASD and occluder were (9.7 ± 4.7) mm and (14.1 ± 5.7) mm. The mean operation time was (49.6 ± 29.2) min. No complications such as atrioventricular block, reoperation, or pericardial effusion occurred. There are 3 patients had a residual shunt. All patients were followed-up for (38.7 ± 11.0) months. The three patients with residual shunt had self-closed at the 3-6-12 months follow-up. There was no complication at follow-up. Trans-jugular transcutaneous closure of ASD with adjustable curved sheath under echocardiography guidance is safe, effective and minimally invasive.


Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage.
To describe the characteristics of thrombophilia in women with idiopathic pregnancy loss. Prospective observational study. Tertiary referral center in a teaching academic hospital. One hundred forty-five patients with repeated pregnancy loss and 145 matched controls. Prospective assessment of thrombophilia in patients and controls. Prevalence of activated protein C (APC) resistance, protein C, protein S, and antithrombin III deficiencies, antiphospholipid antibodies, factor V Leiden, factor II G20210A, and MTHFR C677T mutations. At least one thrombophilic defect was found in 66% of study group patients compared with 28% in control group patients. Combined thrombophilic defects were documented in 21% of women with pregnancy loss compared with 5.5% of control patients. Late pregnancy wastage occurred more frequently in women with thrombophilia compared with women without thrombophilia (160/429 [37%] vs. 39/162 [24%], respectively). APC resistance was documented in 39% of women with pregnancy loss compared with 3% of the control patients. APC resistance without factor V Leiden mutation was documented in 18% of women with pregnancy loss compared with none of the controls. While factor V Leiden mutation was more common in women with pregnancy loss (25% vs. 7.6%), factor II G20210A and homozygosity for MTHFR C677T contributed to pregnancy loss only in the presence of other thrombophilia. Thrombophilia was found in the majority (66%) of women with idiopathic pregnancy loss. APC resistance with or without factor V Leiden mutation is the most common thrombophilic defect, and combined thrombophilia is a frequent finding in women with pregnancy loss. Thrombophilia is associated with increased frequency of late pregnancy wastage.


Assessing uncertainty in reference intervals via tolerance intervals: application to a mixed model describing HIV infection.
We define the reference interval as the range between the 2.5th and 97.5th percentiles of a random variable. We use reference intervals to compare characteristics of a marker of disease progression between affected populations. We use a tolerance interval to assess uncertainty in the reference interval. Unlike the tolerance interval, the estimated reference interval does not contains the true reference interval with specified confidence (or credibility). The tolerance interval is easy to understand, communicate and visualize. We derive estimates of the reference interval and its tolerance interval for markers defined by features of a linear mixed model. Examples considered are reference intervals for time trends in HIV viral load, and CD4 per cent, in HIV-infected haemophiliac children and homosexual men. We estimate the intervals with likelihood methods and also develop a Bayesian model in which the parameters are estimated via Markov-chain Monte Carlo. The Bayesian formulation naturally overcomes some important limitations of the likelihood model.


ADAM15 protein amplifies focal adhesion kinase phosphorylation under genotoxic stress conditions.
ADAM15, a disintegrin and metalloproteinase, is capable of counteracting genotoxic stress-induced apoptosis by the suppression of caspase-3 activation. A cell line expressing the membrane-bound ADAM15 without its cytoplasmic tail, however, lost this anti-apoptotic property, suggesting a crucial role of the intracellular domain as a scaffold for recruitment of survival signal-transducing kinases. Accordingly, an enhanced phosphorylation of FAK at Tyr-397, Tyr-576, and Tyr-861 was detected upon genotoxic stress by camptothecin in ADAM15-transfected T/C28a4 cells, but not in transfectants expressing an ADAM15 mutant without the cytoplasmic tail. Accordingly, a specific binding of the cytoplasmic ADAM15 domain to the C terminus of FAK could be shown by mammalian two-hybrid, pulldown, and far Western studies. In cells expressing full-length ADAM15, a concomitant activation of Src at Tyr-416 was detected upon camptothecin exposure. Cells transfected with a chimeric construct consisting of the extracellular IL-2 receptor α-chain and the cytoplasmic ADAM15 domain were IL-2-stimulated to prove that the ADAM15 tail can transduce a percepted extracellular signal to enhance FAK and Src phosphorylation. Our studies further demonstrate Src binding to FAK but not a direct Src interaction with ADAM15, suggesting FAK as a critical intracellular adaptor for ADAM15-dependent enhancement of FAK/Src activation. Moreover, the apoptosis induction elicited by specific inhibitors (PP2, FAK 14 inhibitor) of FAK/Src signaling was significantly reduced by ADAM15 expression. The newly uncovered counter-regulatory response to genotoxic stress in a chondrocytic survival pathway is potentially also relevant to apoptosis resistance in neoplastic growth.


Exclusive breastfeeding reduces asthma in a group of children from the Caguas municipality of Puerto Rico.
Breast-feeding is the preferred method of infant nutrition. Its role in preventing childhood asthma is controversial. Determine whether breastfeeding protects against the development of bronchial asthma in children. A survey was answered by parents of children less than 18 years of age attending a Pediatric clinic at Cidra, Puerto Rico from July to December 2008. A group of 175 mothers were included in the study. The mean age was 28 years (range 14-50). The mean age of the children was 5 years. There was family history of asthma in 64% of the families. The prevalence of asthma in these children was 50%. Sixty-six percent of the mother's breastfed but only 27% did it exclusively. Children who were exclusively breastfed had a lower prevalence of asthma and milk protein allergy. This study correlates with literature reports linking exclusive breastfeeding to a reduction in asthma and other allergic diseases.


Analysis by liquid chromatography-mass spectrometry of sterols and oxysterols in brain of the newborn Dhcr7(Δ3-5/T93M) mouse: a model of Smith-Lemli-Opitz syndrome.
In this study the sterol and oxysterol profile of newborn brain from the Dhcr7(Δ3-5/T93M) mouse model of Smith-Lemli-Opitz syndrome (SLOS) has been investigated. This is a viable mouse model which is compound heterozygous containing one null allele and one T93M mutation on Dhcr7. We find the SLOS mouse has reduced levels of cholesterol and desmosterol and increased levels of 7- and 8-dehydrocholesterol and of 7- and 8-dehydrodesmosterol in brain compared to the wild type. The profile of enzymatically formed oxysterols in the SLOS mouse resembles that in the wild type but the level of 24S-hydroxycholesterol, the dominating cholesterol metabolite, is reduced in a similar proportion to that of cholesterol. A number of oxysterols abundant in the SLOS mouse are probably derived from 7-dehydrocholesterol, however, the mechanism of their formation is unclear.


A pilot-study of a minimally invasive technique to elevate the sinus floor membrane and place graft for augmentation using high hydraulic pressure: 18-month follow-up of 20 cases.
To evaluate medical efficacy and safety of crestal, minimally invasive sinus floor augmentation (MISFA) using an innovative method based on high hydraulic pressure. Twenty MISFA using the novel Jeder-System were performed in 18 patients at 2 study sites in Vienna, Austria. The Jeder-System consists of the Jeder-drill, the Jeder-pump, and a connecting tube-set. The pump generates high hydraulic pressure (1.5 bar) pushing back the sinus membrane from the drill at the first perforation. The pump also monitors the whole procedure by constantly measuring pressure and volume. Five percent membrane perforation rate (1/20) only detected in the postoperative computed tomography scan and without implication for implant placement. Height gain of 9.2 ± 1.7 mm achieved (from 4.6 ± 1.4 mm to 13.8 ± 2.3 mm). Average patient satisfaction was 9.82 on scale from 1 to 10 (10 = very satisfied). Mean duration of sick leave was 0.19 days. 18-month survival rate was 95% (1/20 implant lost). Within the limits of a prospective open cohort study with 20 cases, our data demonstrate the safety and medical efficacy of the novel method.


Epilithic biofilms in Saint Callixtus Catacombs (Rome) harbour a broad spectrum of Acidobacteria.
The phylum Acidobacteria is broadly represented in a variety of environments as reported during microbial molecular surveys. This study represents the first attempt to analyze the diversity of Acidobacteria in Roman Catacombs (Rome, Italy). Both 16S and 23S rRNA gene sequences were used to confirm the affiliation within different acidobacterial subgroups. The results showed Acidobacteria belonging to subgroups 3, 4, 6, 9, and 10 in the analyzed samples. The presence of acidobacterial sequences in biodeteriorating biofilms in Roman Catacombs suggest they could participate in this negative process, most likely in cooperation with other microbial groups.


Engineering Pseudomonas for phenazine biosynthesis, regulation, and biotechnological applications: a review.
Pseudomonas strains are increasingly attracting considerable attention as a valuable bacterial host both for basic and applied research. It has been considered as a promising candidate to produce a variety of bioactive secondary metabolites, particularly phenazines. Apart from the biotechnological perspective, these aromatic compounds have the notable potential to inhibit plant-pathogenic fungi and thus are useful in controlling plant diseases. Nevertheless, phenazines production is quite low by the wild-type strains that necessitated its yield improvement for large-scale agricultural applications. Metabolic engineering approaches with the advent of plentiful information provided by systems-level genomic and transcriptomic analyses enabled the development of new biological agents functioning as potential cell factories for producing the desired level of value-added bioproducts. This study presents an up-to-date overview of recombinant Pseudomonas strains as the preferred choice of host organisms for the biosynthesis of natural phenazines. The biosynthetic pathway and regulatory mechanism involved in the phenazine biosynthesis are comprehensively discussed. Finally, a summary of biological functionalities and biotechnological applications of the phenazines is also provided.


Effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine in glial and neuroblastoma cells.
Cultured glial cells (clones NN and I6) and neuroblastoma cells (clones M1 and M1NN) were used to study the effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine. Treatment of NN cells with a mixture of dBcAMP and BrcGMP for one or two days resulted in a more than 3-fold increase in the Vmax of L-glutamate high affinity uptake. Similar but smaller change was observed in a related glial clone (I6). Effects of cyclic nucleotide derivatives on high affinity uptake of L-glutamate by neuroblastoma cells (clones M1 and M1NN) or of taurine by both glial or neuroblastoma cells were either smaller or absent. Some differences were found in kinetic parameters of uptake of L-glutamate and taurine by original and re-isolated cellls, respectively. It is possible that these differences resulted from co-cultivation of glial and neuronal cells. However, since some values reported in this paper differ to some extent from those published previously, some other factors, such as subcloning, may have been responsible.


Diffusion distances of known iron complexes in model systems.
Diffusion distances (abbreviated d's), the distances between the sites of generation of presumed hydroxyl radicals (*OH) by low molecular weight forms of Fe and the site of their reaction with substrate, were measured for three model systems for cellular DNA of varying degrees of complexity. Two d's for Fe complexed with each of ethylene diamminetetraaccetic acid (FeEDTA) and nitrilotriacetic acid (FeNTA) were measured for generation of malondialdehyde-type products (MDA) from deoxyribose and of single-strand breaks (SSBs) in the plasmid pBR322. The closer d's for pBR322 SSB generation (5-6 nm) were considerably greater than the d's for MDA generation in the deoxyribose assay (2-3 nm). This is consistent with charge-charge interactions playing an important role in defining d. The d's for FeNTA, FeEDTA, and other Fe species generating SSBs in isolated Ehrlich ascites tumor cell nuclei ranged from 2.1 to 14 nm. Charge-charge interactions, Fe-ligand-specific interactions, and binding to nuclear components were concluded to be important factors affecting d in isolated nuclei. Other factors related to nuclear structure may also play a role.


Nonstandard finite difference method for solving complex-order fractional Burgers' equations.
The aim of this work is to present numerical treatments to a complex order fractional nonlinear one-dimensional problem of Burgers' equations. A new parameter σ t is presented in order to be consistent with the physical model problem. This parameter characterizes the existence of fractional structures in the equations. A relation between the parameter σ t and the time derivative complex order is derived. An unconditionally stable numerical scheme using a kind of weighted average nonstandard finite-difference discretization is presented. Stability analysis of this method is studied. Numerical simulations are given to confirm the reliability of the proposed method.


Reducing graphene oxide carbon skeleton supported P-N heterostructure of bimetallic sulfide CoS-MoS2 nanorods for high-performance lithium storage.
Constructing bimetallic sulfide components are considered to be a promising and efficient lithium storage materials. Nonetheless, preparation routes of rational structures that have abundant hierarchical interfaces or phase boundaries bimetallic sulfide are still a problem to over come. In this work, a novel hierarchical nanostructure of bimetal sulfide CoS-MoS2 nanorods are synthesized successfully by in-situ self-growth means at the hydrothermal conditions. Subsequently, we loaded it to the carbon matrix (CoS-MoS2@rGO) forming a three-dimensional structures with the help of freeze drying technology. This well-designed hierarchical structure could created a stable heterogeneous contact surface, which guarantees rapid Li+ ions diffusion and facilitates charge transfer at the heterointerface. Which can maintain capacity of 776 mAh/g over 800 cycles at 1 A/g. On the other hand, it shows an excellent rate capability of 464 mAg h-1 at 5 A/g. From the perspective of electrochemical kinetics, we analyze and explore the reason about the improved lithium storage performance. Furthermore, to insight into the relationship between matter and phase conversion, the in-situ X-ray diffraction characterization is executed. The strategy of rationally designing hierarchical heterostructures will shed light on outstanding electrochemical performance in energy storage applications.


Ambulatory treatment of psoriasis: combined use of occlusive dressings with locacorten tar at night and 'open' treatment with locasalen during the day.
Fifty patients with refractory psoriasis were treated with a combined method consisting in the application of occlusive dressings with Locacorten Tar ointment at night and of 'open' treatment (without occlusive dressings) with Locasalen ointment during the day. The aim of this trial was to obtain the benefit of the occlusive-dressing method without having to hospitalize the patients. The mean time required for the eradication of psoriatic scales was 3.46 days, while that needed for complete recovery was 14 days. The results clearly indicated that this combined approach has all the advantages of occlusives dressings but allows the patient greater freedom during the day. The very good effect of the treatment is also attributable to the triple action obtained with this combination: the anti-epidermoplastic effect of flumethasone pivalate, the squamolytic effect of salicylic acid, and the keratoplastic action of the tar compound.


Genomic Approaches for the Study of Flower Development in Floriculture Crops.
The advances in genomics and bioinformatics have made possible the study in non-model plants of phenotypes associated to flower development. Floriculture crops are an interesting source of traits associated to flower development such as the transition between zygomorphic and actinomorphic flowers or the production of flowers with double and triple corollas. In this chapter, we summarize the material and methods for the use of floriculture crops to study flower development using genomic tools, from the sequencing and assembly of a reference genome to QTL and RNA-Seq analysis to search candidate genes associated to specific traits.


Multiple cavernous hemangiomas of the orbits.
Intraocular tumors were detected in both orbits simultaneously by computed tomography scanning in a 45-year-old woman complaining of proptosis of the right eye, decreased visual acuity, and diplopia. The tumor in the right orbit was resected by the subfrontal extradural approach, and that in the left orbit by the Krönlein-Berke method. The right tumor was found on the side of the external ear of the muscle cone and the left tumor was located inferiorly on the side of the external ear of the muscle cone. Both tumors were cavernous hemangiomas with identical macroscopic and histologic features.


Achieving Exemplary Attributes With AccrualNet.
The AccrualNet Web site is a helpful compilation of resources for sites aspiring to improve trial accrual.


Using word processor text files as an active bibliography.
Data base systems for microcomputers are generally available. Most are reasonable priced and easy to use. Their disadvantages are restrictions placed on the amount of data stored in a single field, and the output format--usually tabular or label in style. This article describes the use of word processor text files as a data base allowing search and retrieval, with special reference to abstracting and storage of literature citations. Size of text entry and ultimate output format are extremely flexible using this method.


Positively Charged Gold Quantum Dots: An Nanozymatic "Off-On" Sensor for Thiocyanate Detection.
The concentration of thiocyanate (SCN-) in bodily fluids is a good indicator of potential and severe health issues such as nasal bleeding, goiters, vertigo, unconsciousness, several inflammatory diseases, and cystic fibrosis. Herein, a visual SCN- sensing method has been developed using the enzyme-like nature of positively charged gold quantum dots (Au QDs) mixed with 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2). This research also reports a new method of synthesizing positively charged Au QDs directly from gold nanoparticles through a hydrothermal process. Microscopic imaging has showed that the Au QDs were 3-5 nm in size, and the emission wavelength was at 438 nm. Au QDs did not display any enzyme-like nature while mixed up with TMB and H2O2. However, the nanozymatic activity of Au QDs appeared when SCN- was included, leading to a very low detection limit (LOD) of 8 nM and 99-105% recovery in complex media. The steady-state kinetic reaction of Au QDs showed that Au QDs had a lower Michaelis-Menten constant (Km) toward H2O2 and TMB, which indicates that the Au QDs had a higher affinity for H2O2 and TMB than horseradish peroxidase (HRP). A mechanism study has revealed that the scavenging ability of hydroxyl (•OH) radicals by the SCN- group plays an important role in enhancing the sensitivity in this study. The proposed nanozymatic "Off-On" SCN- sensor was also successfully validated in commercial milk samples.


Molecular phylogeny and biogeography of caecilians from Southeast Asia (Amphibia, Gymnophiona, Ichthyophiidae), with special reference to high cryptic species diversity in Sundaland.
We investigated the phylogenetic relationships and estimated the history of species diversification and character evolution in two ichthyophiid genera: Caudacaecilia and Ichthyophis. We estimated the phylogenetic relationships of 67 samples from 33 localities in Southeast Asia from 3840-bp sequences of the mitochondrial 12S rRNA, 16S rRNA, and cyt b genes using Bayesian inference, maximum likelihood, and maximum parsimony methods. The Southeast Asian samples formed a well-supported clade differentiated from a South Asian sample. The Southeast Asian clade was divided into two subclades, one containing samples from South China, Indochina, Malay Peninsula, and Java. The other consisted of samples from Borneo and the Philippines. Neither Caudacaecilia nor Ichthyophis was monophyletic, nor did samples with or without light stripes lateral to the body form clades. We found several distinct sympatric lineages and undescribed species, especially from Sundaland.


Review on Selected Aggression Causes and the Role of Neurocognitive Science in the Diagnosis.
Aggression as a behavior is not always desirable, often ends in abandonment and/or euthanasia. However, it is possible to prevent the occurrence of unwanted aggression in domestic dogs. Aggression is not a fully understood phenomenon. In recent years, many studies have focused on the influence of diet and physiology (including the endocrine system) on the emergence of behavioral disorders. In particular, the emphasis was put on nutritional additives such as fatty acids, amino acids, and probiotics. In addition, the possibility of using neurocognition in the observation of abnormal behavior in dogs has also been discussed, which may allow for a more detailed determination of the basis of aggressive behavior in dogs. In this review, the concepts related to aggression and its potential causes have been gathered. In addition, the possible influence of diet and hormones on aggression in dogs has been discussed, as well as the application of neurocognition in the possibility of its diagnosis.


Prospective study of the effect of rectopexy on colonic motility in patients with rectal prolapse.
Patients with rectal prolapse have abnormal hindgut motility. This study examined the effect of rectal prolapse surgery on colonic motility. Twelve patients undergoing sutured rectopexy were studied before and 6 months after surgery by colonic manometry, colonic transit study and clinical assessment of bowel function. The results were compared with those from seven control subjects. Before surgery colonic pressure was greater in patients than controls (P < 0.050). Controls responded to a meal stimulus by increasing colonic pressure; this increase was absent in patients. After rectopexy, colonic pressure reduced towards control values and patients' colonic pressure response to a meal returned. High-amplitude propagated contractions (HAPCs) were seen in all controls but in only three patients before and two patients after surgery. Three patients had prolonged colonic transit before and eight after rectopexy. Patients with rectal prolapse have abnormal colonic motility associated with reduced HAPC activity. Rectopexy reduces colonic pressure but fails to restore HAPCs, reduce constipation or improve colonic transit. These observations help explain the pathophysiology of constipation associated with rectal prolapse.


Enhancing involvement in NICE guideline development.
This article examines professional stakeholders' involvement in the development of National Institute for Health and Clinical Excellence (NICE) clinical guidelines. NICE produces guidance on the appropriate treatment and care of people with specific diseases and conditions in the NHS in England and Wales.


One-step synthesis of AgCl concave cubes by preferential overgrowth along <111> and <110> directions.
A new class of AgCl microstructures, concave cubes, with preferential overgrowth along <110> and <111> directions, has been prepared in a monodisperse fashion by a wet chemical oxidization method. With high-index facets exposed, the concave cubic AgCl exhibits higher photocatalytic activity in O(2) evolution than cubic ones.


Effect of peripheral nerve section and nerve crush on spinal cord neuropeptides in the rat; increased VIP and PHI in the dorsal horn.
An increase in vasoactive intestinal polypeptide (VIP) immunoreactivity in the dorsal lumbar hemisegment L4 of the spinal cord was observed by both radioimmunoassay and immunocytochemistry following sciatic nerve section or crush. Compared to the contralateral control hemisegment there was 125% and 35% more VIP immunoreactivity in the L4 hemisegment ipsilateral to the lesion 14 days following nerve section and crush respectively. The contralateral control hemisegment contained levels similar to L4 hemisegments from unoperated control rats. This increase appeared by immunocytochemistry to be confined to the substantia gelatinosa, in the region of termination of the majority of unmyelinated sciatic nerve afferents. Similar increases to VIP were observed for the peptide PHI, which is closely related to VIP. However, spinal cord substance P and somatostatin immunoreactivities were reduced following nerve section and unchanged following nerve crush whilst neurotensin and bombesin immunoreactivities were not affected following either lesion. Previous studies have shown that peripheral nerve injury produces a number of electrophysiological and biochemical changes in the dorsal horn of the spinal cord, including depletion of substance P in primary afferent neurones. The location of the cell bodies of fibres showing increased immunoreactivity remains to be established. Further studies are required to elucidate how these peptide changes are related to the adaptive processes which occur centrally following peripheral nerve injury.


Developmental changes in the variability of tongue and lip movements during speech from childhood to adulthood: an EMA study.
This study investigated the developmental variability of lip and tongue movement in 48 children and adults. Motion of the tongue-tip, tongue-body and lower lip was recorded using electromagnetic articulography during productions of sentences containing /t/, /s/, /l/, /k/ and /p/. Four groups of speakers participated in the study: (1) aged 6-7 years; (2) 8-11 years; (3) 12-17 years; and (4) adults. The variation in distance, duration, speed, acceleration and deceleration of the articulators during single open-close speech movements was analysed, and the stability of multiple movement sequences was examined using the spatiotemporal index. The experimental findings revealed a gradual developmental progression from 6 years to adulthood. At adolescence, speakers continued to exhibit significantly more variable speech motor output compared to adult speakers. The observed developmental pattern suggests that attenuated, but important, changes in the speech motor system occurs from mid-childhood, through adolescence, to adulthood.


Regulation of glutamate receptors by cations.
Current evidence suggests that glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS); particularly, glutamate excites most neurones in the CNS. Until recently this effect was widely used to study glutamate receptors and to distinguish them from those of other excitatory amino acids. The development of ligand binding studies for many neurotransmitters has facilitated the study of receptors at the molecular level and using these methods we recently reported the existence in hippocampal membranes of pharmacologically distinct sodium-dependent and sodium-independent glutamate binding sites, the former related to high-affinity uptake and the latter exhibiting several characteristics of postsynaptic receptor sites. We now report that, as with other neurotransmitters, several ions regulate the Na-independent binding of glutamate; the monovalent cations induce a decreased binding while certain divalent cations enhance this Na-independent binding. Additionally, since some of these effects appear to be irreversible, we propose that the regulation of glutamate binding by cations might account for the extremely long-lasting potentiation of synaptic responses found in the hippocampus following bursts of repetitive electrical stimulation (see ref. 9 for a review).


[Between red tape and scalpel : Urological literature, denazification and censorship in East Germany in the early postwar period].
This paper addresses the question of how the urological disciplinary culture and urological knowledge were reformed during the early postwar period under conditions of the allied policy of denazification and demilitarization in East Germany. This article deals with the urological textbook as a central medium of disciplinary communication and explores how urological knowledge was processed in complex negotiation processes between authors, publishers and censorship authorities of the Soviet occupation zone. The focus is on mechanisms of medial control to which medical knowledge cycles have been subjected, and thus the archival holdings of censorship authorities that have not yet been evaluated. The evaluation results are presented here with a focus on urology and illustrated with selected case studies.


Fusarium toxins in different food samples.
Samples of wheat for human nutrition, wheat flour, bread and noodles were analysed for different trichothecenes and partly for zearalenone (ZEA). The toxin contents for deoxynivalenol (DON) and ZEA were compared with the maximum tolerated levels recently discussed for foodstuffs in Germany. The limits for DON were exceeded in 20, 15, 5 and 9% of the samples of wheat, wheat flour, bread and noodles respectively, the limits for ZEA in 4 and 0% for wheat and wheat flour respectively.ZUSAMMENFASSUNG: Proben von Weizen für die menschliche Ernährung, Weizenmehl, Brot und Nudeln wurden auf verschiedene Trichothecene und z. T. auf Zearalenon (ZEA) untersucht und die ermittelten Gehalte an Deoxynivalenol (DON) und ZEA mit den in Deutschland zur Diskussion stehenden Höchstgehalten verglichen. Diese Werte wurden für DON in 20, 15, 5 und 9% der Weizen, Weizenmehl, Brot bzw. Nudelproben überschritten, für ZEA in 4% der Weizenproben und in 0% der Weizenmehlproben.


Unmasking materialistic depression as a mental health problem: its effect on depression and materialism in an African-United States undergraduate sample.
Misdiagnosis of African-U.S. persons is argued to be a built-in characteristic of Western-based assessment requiring augmentation with culture-focused input where possible. Regarding depression, materialistic depression is explained as an African-centered African-U.S. culture-focused construct of masked depression. Materialistic depression symptomatology is presented. Materialism orientation is postulated to necessarily be associated with materialistic depression. 144 undergraduates, 37 male (25.7%) and 107 female (74.3%), average age of 21 completed the Zung Self-rating Depression Scale, the depression subscale of the Symptom Checklist 90-R, the materialism subscale of the Cultural Misorientation Scale, and the Materialistic Depression Quiz. Contrasting high versus lower scoring MDQ groups on both depression scores produced reliable t-tests (p<.017). One-way ANOVA on materialism scores with high, medium, low MDQ groups was reliable (p<.017). The sample precluded generalization to clinically depressed and non-college African-U.S. populations. Using the Materialistic Depression Quiz, high scorers versus medium and low scorers had greater depression scores on two depression measures and greater materialism scores. Materialistic depression appears a masked form of depression not to be overlooked.


"Bunch of grapes" in complete hydatidiform mole.
Complete hydatidiform mole is a common cause of gestational bleeding of the first trimester, commonly assessed by ultrasound. It represents an abnormal proliferation of trophoblastic tissue, with no fetal formation, just hydropic villi. These abnormal villi seen in ultrasound are compared to a "bunch of grapes," a classic description of this disease.


Hepatic Venous Outflow Obstruction in Adult Deceased Donor Liver Transplantation: Classic Piggyback Implantation Versus a Modified Technique that Widens the Ostium of the Recipient's Left and Middle Hepatic Veins.
The classic piggyback technique uses the union of the 3 hepatic veins to perform the cavo-caval anastomosis. However, due to the lateral localization of the right hepatic vein, the partial clamping of the vena cava in this technique significantly reduces the venous return to the right atrium. To avoid this, we adopted in 2015 a modified piggyback technique, in which we use the common trunk of the middle and left hepatic veins and also perform a lateral incision toward the right in the anterior wall of the vena cava in order to widen the final ostium of the cavo-caval anastomosis. The aim of the study was to analyze the incidence of hepatic venous outflow obstruction between those 2 techniques. Retrospective study of liver transplant recipients undergoing venography for suspected hepatic venous outflow obstruction from January 2009 to June 2021. Patients undergoing transplantation with living donors or split grafts and pediatric cases were excluded from the study. From January 2009 to December 2014 and from January 2015 to June 2021, 587 (group 1) and 730 (group 2) deceased-donor liver transplants were performed with the classic and the modified piggyback techniques, respectively. The incidence of cases with suspected hepatic venous outflow obstruction in groups 1 and 2 were 1.87% (n = 11) and 0.95% (n = 7), respectively (P = 0,15). The number of confirmed patients with outflow blockage that required endovascular treatment during venography in groups 1 and 2 were 4 (0.68%) and 5 (0.68%), respectively (P = 0,31). This modified piggyback technique did not increase the incidence of hepatic venous outflow obstruction at our service.


Predictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastases.
Despite progress in resection for colorectal liver metastases (CLM), the majority of patients experience recurrence. We aimed to evaluate factors influencing time to recurrence (TTR), treatment and post-recurrence survival (PRS) related to site of recurrence. This is a retrospective population-based cohort study (1998-2012) of consecutive patients without extrahepatic disease treated with resection for CLM in a referral centre. A total of 311 patients underwent resection for CLM. After a median follow-up of 4.2 years (range 1.2-15.2), 209 (67.4 %) patients developed recurrence, hepatic 90, extrahepatic 59 and both 60. Median TTR was 14.0 months, and 5-year recurrence-free status was 25.7 %. Five- and 10-year overall survival (OS) was 38.8 and 22.0 %, respectively. Median OS was 45 months. A multivariate analysis displayed synchronous disease (hazard ratio (HR) 1.50), American Society of Anaesthesiologists (ASA) score (HR 1.40), increasing number (HR 1.24) and size of metastases (HR 1.08) to shorten TTR (all p < 0.05). Perioperative chemotherapy (n = 59) increased overall TTR (HR 0.63) and overall survival (OS; HR 0.55). Hepatic TTR was correlated to synchronous disease (HR 2.07), number of lesions (HR 1.20), R1 resection (HR 2.00) and ASA score (HR 1.69), whereas extrahepatic TTR was correlated to N stage of the primary (HR 1.79), number (HR 1.27) and size of metastases (HR 1.16). Single-site recurrence was most common (135 of 209, 64.5 %), while 58 patients had double- and 16 triple-site relapses. Median PRS was 24.3 months. There was a difference in median PRS (months) according to site of relapse: liver 30.5, lung 32.3, abdominal 22.0, liver and lung 14.3, others 14.8 (p = 0.002). Repeated liver resections were performed in n = 57 patients resulting in 40.6 months median OS and 36.8 % 5-year OS. An adverse overall TTR was correlated to number and size of metastases, ASA score and synchronous disease. Perioperative chemotherapy increased TTR and OS after surgery for CLM. Patients with solitary post-resection relapse in the liver or lungs had the potential for longevity due to multimodal treatment.


[A comparative study of the occupational disease list between Taiwan region and the mainland].
To provide technical reference for the revision of the list of occupational diseases of China, the list of occupational diseases between the Taiwan district and the Mainland China have been analyzed and compared. Focus on the system of occupational diseases list between the Taiwan district and the Mainland China, the literature analysis and comparative methods were commonly used, and to explore the similarities and differences of the list of occupational diseases between the mainland and Taiwan. The list of occupational diseases between the mainland and Taiwan shows uniformity in the legislative process, the status and role, classification, but exists difference in the enumeration mode, the legal basis of the development, the institutions to develop the list, classification and coverage et al. To revise the National List of Occupational Diseases, the socio-economic development requirements should be based on, combined with social security capacity, gradually expand the coverage of occupational diseases, to adapt to the needs of the occupational disease prevention.


Acute dislocation of the trapeziometacarpal joint in a child.
An acute dorsal dislocation of the trapeziometacarpal joint in a child is presented. The mechanisms of injury and controversies of treatment are discussed. The achievement of a stable reduction acutely is emphasized. After healing, joint stability is confirmed by obtaining stress radiographs to identify whether joint subluxation is present before degenerative changes occur.


Haemoperitoneum--a complication of acute cholecystitis in a patient on anticoagulant therapy. A case report.
A case of haemoperitoneum in a patient taking warfarin sodium, originating in the wall of a perforated, inflamed gallbladder, is presented. To the best of our knowledge such a case has not been reported previously. Diagnostic and therapeutic aspects are briefly discussed.


Total syntheses of both enantiomers of amphirionin 4: A chemoenzymatic based strategy for functionalized tetrahydrofurans.
The total syntheses of (-)-amphirionin-4 and (+)-amphirionin-4 have been achieved in a convergent and enantioselective manner. The tetrahydrofuranol cores of amphirionin-4 were constructed in optically active form by enzymatic resolution of racemic cis-3-hydroxy-5-methyldihydrofuran-2(3H)-one. The polyene side chain was efficiently synthesized using Stille coupling. The remote C8-stereocenter was constructed using the Nozaki-Hiyama-Kishi coupling reaction. A detailed 1H-NMR studies of Mosher esters of (-)-amphirionin-4 and (+)-amphirionin-4 were carried out to support the assignment of the absolute configurations of C-4 and C-8 asymmetric centers of amphirionin-4.


Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study.
Prolonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population. This was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin. Of the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 - 149.95, p < 0.05). The majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.


Characteristics of successful competitors: an evaluation of potential growth rate in two cold desert tussock grasses.
Within the first few weeks after seedling emergence, Agropyron desertorum, a more competitive tussock grass, had a much higher mean relative growth rate (RGR) than Agropyron spicatum, a very similar, but less competitive species. However, beyond the early seedling stage, the two grasses had a remarkably similar whole-plant RGR in hydroponic culture and aboveground RGR in glasshouse soil, if root temperatures were above approximately 12°C. At soil temperatures between 5 and 12°C, A. desertorum exhibited a 66% greater aboveground RGR than A. spicatum (P<0.05). Both species responded similarly to warming soil temperatures. In the field, however, tiller growth rates were generally similar. Neither species showed marked tiller elongation until a couple of weeks after snowmelt, by which time soil temperatures, at least to a depth of 10 cm, were above 12°C for a significant portion of the day. Aboveground biomass accumulation over a three-year period indicated that both grasses had similar potential growth rates whereas Artemisia tridentata ssp. vaseyana, a common neighbor planted in the same plots, had a much greater potential growth rate. The greater competitive ability of adult A. desertorum, as compared to A. spicatum, cannot be attributed to appreciable differences in potential growth rates.


Effects of diversity and pattern on relative yields of four michigan first year fallow field plant species.
1. A study was designed to investigate the effects of intra and inter-specific competition on the productivity of single and multi-species stands of plants normally dominant in first year old-field communities of mid-Michigan. The four species used were Amaranthus retroflexus, Chenopodium album, Panicum capillare and Setaria viridis. 2. Specifically, we tested (1) the relationship between diversity and productivity, (2) the effect of arrangement (pattern) of individuals within an array of old-field dominants on yield and (3) the expression of dominance and resultant allocation of yields within mixture arrays of different plant species. In direct contrast to many earlier studies, our experiments were completed in the field under natural conditions. 3. Mean yield of the highest yielding monoculture, Amaranthus, was greater than any of the yields of the mixture plots. 4. Changing the pattern within mixtures had no significant effect on the yields of the mixture plots. Distribution of biomass among the component species followed a geometric pattern similar to that predicted by the niche pre-emption hypothesis (Whittaker, 1965, 1969). Using yield as a criterion, dominance was clearly expressed in the mixture plots. Amaranthus contributed more than 50% of the yield in all of the mixture plots. 5. A relative competitive ability index (RCA) was developed to demonstrate more clearly the intra and interspecific relationships among the species in mixture plots and to "equalize" the inherent weight differential among species. Relative Competitive Ability, from highest to lowest, was Amaranthus, Chenopodium, Setaria and Panicum. 6. The paired species experiment demonstrated that the performance of species in multi-species arrays cannot be predicted from paired competition experiments. 7. In the diversity-yield experiment and the paired-species competitive ability experiment, dicotyledons were clearly superior to monocotyledons.


The V108M mutation decreases the structural stability of catechol O-methyltransferase.
The human gene for catechol O-methyltransferase has a common single-nucleotide polymorphism that results in substitution of methionine (M) for valine (V) 108 in the soluble form of the enzyme (s-COMT). 108M s-COMT loses enzymatic activity more rapidly than 108V s-COMT at physiological temperature, and the 108M allele has been associated with increased risk of breast cancer and several neuropsychiatric disorders. We used circular dichroism (CD), dynamic light scattering, and fluorescence spectroscopy to examine how the 108V/M polymorphism affects the stability of the purified, recombinant protein to heat and guanidine hydrochloride (GuHCl). COMT contains two tryptophan residues, W143 and W38Y, which are located in loops that border the S-adenosylmethionine (SAM) and catechol binding sites. We therefore also studied the single-tryptophan mutants W38Y and W143Y in order to dissect the contributions of the individual tryptophans to the fluorescence signals. The 108V and 108M proteins differed in the stability of both the tertiary structure surrounding the active site, as probed by the fluorescence yields and emission spectra, and their global secondary structure as reflected by CD. With either probe, the midpoint of the thermal transition of 108M s-COMT was 5 to 7 degrees C lower than that of 108V s-COMT, and the free energy of unfolding at 25 degrees C was smaller by about 0.4 kcal/mol. 108M s-COMT also was more prone to aggregation or partial unfolding to a form with an increased radius of hydration at 37 degrees C. The co-substrate SAM stabilized the secondary structure of both 108V and 108M s-COMT. W143 dominates the tryptophan fluorescence of the folded protein and accounts for most of the decrease in fluorescence that accompanies unfolding by GuHCl. While replacing either tryptophan by tyrosine was mildly destabilizing, the lower stability of the 108M variant was retained in all cases.


Saliva antiviral antibody levels are detectable but correlate poorly with serum antibody levels following SARS-CoV-2 infection and/or vaccination.
The importance of salivary SARS-CoV-2 antibodies, following infection and vaccination, has not been fully established. 875 healthcare workers were sampled during the first wave in 2020 and 66 longitudinally in response to Pfizer BioNTech 162b2 vaccination. We measured SARS-CoV-2 total IgGAM and individual IgG, IgA and IgM antibodies. IgGAM seroprevalence was 39.9%; however, only 34.1% of seropositive individuals also had salivary antibodies. Infection generated serum IgG antibodies in 51.4% and IgA antibodies in 34.1% of individuals. In contrast, the salivary antibody responses were dominated by IgA (30.9% and 12% generating IgA and IgG antibodies, respectively). Post 2nd vaccination dose, in serum, 100% of infection naïve individuals had IgG and 82.8% had IgA responses; in saliva, 65.5% exhibited IgG and 55.2% IgA antibodies. Prior infection enhanced the vaccine antibody response in serum but no such difference was observed in saliva. Strong neutralisation responses were seen for serum 6 months post 2nd-vaccination dose (median 87.1%) compared to low neutralisation responses in saliva (median 1%). Intramuscular vaccination induces significant serum antibodies and to a lesser extent, salivary antibodies; however, salivary antibodies are typically non-neutralising. This study provides further evidence for the need of mucosal vaccines to elicit nasopharyngeal/oral protection. Although saliva is an attractive non-invasive sero-surveillance tool, due to distinct differences between systemic and oral antibody responses, it cannot be used as a proxy for serum antibody measurement.


Plasticity of fruit and oil traits in olive among different environments.
Olive is a long-living perennial species with a wide geographical distribution, showing a large genetic and phenotypic variation in its growing area. There is an urgent need to uncover how olive phenotypic traits and plasticity can change regardless of the genetic background. A two-year study was conducted, based on the analysis of fruit and oil traits of 113 cultivars from five germplasm collections established in Mediterranean Basin countries and Argentina. Fruit and oil traits plasticity, broad-sense heritability and genotype by environment interaction were estimated. From variance and heritability analyses, it was shown that fruit fresh weight was mainly under genetic control, whereas oleic/(palmitic + linoleic) acids ratio was regulated by the environment and genotype by environment interaction had the major effect on oil content. Among the studied cultivars, different level of stability was observed, which allowed ranking the cultivars based on their plasticity for oil traits. High thermal amplitude, the difference of low and high year values of temperature, negatively affected the oil content and the oleic acid percentage. Information derived from this work will help to direct the selection of cultivars with the highest global fitness averaged over the environments rather than the highest fitness in each environment separately.


Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially.
The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case-control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18-59 years; controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma; sibling profile (number; dates of birth); and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11; 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68; 95% CI: 0·49, 0·95) but not asthma (OR = 1·47; 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative 'sibling effect'.


Quantifying periodic activity in central pattern generators: the crayfish swimmeret.
Experimental recordings from neurons are generally difficult to quantify. Spike patterns and membrane potential cycles are often compared qualitatively and are hence limited by human resolution and judgement. This paper describes a statistical method for quantifying individual spike patterns and membrane potential fluctuations in oscillating systems, allowing quantification of successive 'individual' bursts. The neuronal activities of the network can therefore be subject to more extensive analyses and comparisons. Principal-component analysis was used to extract the principal components from a sequence of bursts recorded in vitro from the crayfish (Pacifasticus leniusculus) swimmeret. The principal component coefficients were correlated with intuitive biological concepts such as burst displacement, number of spikes in a burst, and burst width. The bursting of both interneurones and motor neurones were found to be modulated by some unidentified oscillator that displaced the bursts in time. The amplitude of the time displacements was significant, i.e., of the order of the bursting period (1.5 s), and the period of the oscillation was approximately 200 bursts. The strength of the method is that this feature was detected without any prior suspicion of its existence.


Incidence, outcomes and prognostic factors during 25 years of treatment of chondrosarcomas.
There are few studies detailing the incidence, patient outcomes and prognostic factors for chondrosarcomas (CS). Those that do exist have small sample sizes and/or use older datasets. The purpose of this study was to determine the incidence, overall survival (OS) and prognostic factors for OS of CS patients, as well as investigate the efficacy of curettage. We analyzed data of 2186 patients diagnosed with chondrosarcomas between '89-'13 from the Netherlands Cancer Registry. The effect of risk factors on OS was assessed with a multivariate Cox regression. Median Follow-up was determined with reversed Kaplan-Meier. OS was estimated using Kaplan-Meier method. The relative incidence of CS was 2.88 per million citizens between '89-'96, 4.15 between '96-'04 and 8.78 between '05-'13. Most of the increase in incidence came from atypical cartilaginous tumours/grade I chondrosarcoma (ACT/CS I). The 3-, 5- and 10-years survival were, respectively, 96%, 93% and 88% for ACT/CS I, 82%, 74% and 62% for grade II CS and 38%, 31% and 26% for grade III CS. Prognostics factors significantly associated with OS were age, histological grade, year of diagnosis, tumour location and size. The incidence of CS, and especially ACT/CS I, has increased over time, which could be driven by both an ageing population and increased diagnostic imaging. With the increased number of diagnosed ACT/CS I, the number of preventative curettages of this tumour has also increased. Despite the supposed preventative character of this treatment, the incidence of high-grade CS did not decrease.


Cardiac contractility modulation electrical signals improve myocardial gene expression in patients with heart failure.
The objective of this study was to test whether cardiac contractility modulation (CCM) electric signals induce reverse molecular remodeling in myocardium of patients with heart failure. Heart failure is associated with up-regulation of myocardial fetal and stretch response genes and down-regulation of Ca(2+) cycling genes. Treatment with CCM signals has been associated with improved symptoms and exercise tolerance in heart failure patients. We tested the impact of CCM signals on myocardial gene expression in 11 patients. Endomyocardial biopsies were obtained at baseline and 3 and 6 months thereafter. The CCM signals were delivered in random order of ON for 3 months and OFF for 3 months. Messenger ribonucleic acid expression was analyzed in the core lab by investigators blinded to treatment sequence. Expression of A- and B-type natriuretic peptides and alpha-myosin heavy chain (MHC), the sarcoplasmic reticulum genes SERCA-2a, phospholamban and ryanodine receptors, and the stretch response genes p38 mitogen activated protein kinase and p21 Ras were measured using reverse transcription-polymerase chain reaction and bands quantified in densitometric units. The 3-month therapy OFF phase was associated with increased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase, and p21 Ras and decreased expression of alpha-MHC, SERCA-2a, phospholamban, and ryanodine receptors. In contrast, the 3-month ON therapy phase resulted in decreased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase and p21 Ras and increased expression of alpha-MHC, SERCA-2a, phospholamban, and ryanodine receptors. The CCM signal treatment reverses the cardiac maladaptive fetal gene program and normalizes expression of key sarcoplasmic reticulum Ca(2+) cycling and stretch response genes. These changes may contribute to the clinical effects of CCM.


Infantile Bullous Pemphigoid Following Vaccination.
Post-vaccination infantile bullous pemphigod is a rare presentation. A 2-month-old girl presented with widespread bullae, erosions, necrotic and targetoid lesions over body and mucosae after vaccination. Histology and direct immunofluorescence (DIF) were consistent with bullous pemphigoid. Clinical remission with oral steroids and no recurrence with subsequent vaccination. Continuation of vaccination may not be contraindicated in infants where bullous pemphigoid onset occurs after vaccination.


Comparative transcriptome profiling analysis provides insight into the mechanisms for sugar change in Chinese jujube (Ziziphus jujuba Mill.) under rain-proof cultivation.
Chinese jujube (Ziziphus jujuba Mill.) is a globally popular and economically important fruit that is rich in bioactive compounds with strong anti-cancer effects. Rain-proof cultivation is widely used to cultivate Chinese jujube, as it helps avoid rainfall damage during fruit harvest. Although the sugar content of jujube fruits differs between rain-proof and open-field cultivation, the underlying molecular mechanisms are unknown. Here, we analyzed the levels of sugar content, sugar accumulation pattern, and transcriptome profiles of jujube fruits at five developmental stages grown under rain-proof and open-field cultivation modes. The sugar content of jujube fruits was significantly higher under rain-proof cultivation than under open-field cultivation, although the sugar composition and sugar accumulation patterns were comparable. Comparative analysis of transcriptomic profiles showed that rain-proof cultivation enhanced the intrinsic metabolic activity of fruit development. Gene expression and correlation analyses suggested that ZjSPS, ZjSS, ZjHXK, and ZjINV regulate the development-related changes in sugar content in jujube fruits grown under rain-proof cultivation. Temperature, humidity, and moisture conditions were key climatic factors affecting sugar accumulation. Our results provide insights into the molecular mechanisms regulating sugar content and sugar accumulation in Chinese jujube fruits grown under rain-proof cultivation, and we provide genetic resources for studying the development mechanism of Chinese jujube fruit.


Progenitor cells from brown adipose tissue undergo neurogenic differentiation.
Multipotent cells derived from white adipose tissue have been shown to differentiate into multiple lineages including neurogenic lineages. However, the high innervation of brown adipose tissue by the sympathetic nervous system suggest it might be a better source of neural precursor cells. To investigate potential differences between white and brown progenitors, we cultured white and brown dedifferentiated fat (wDFAT and brDFAT) cells from mouse and human adipose tissue and compared marker expression of neural precursors, and neuronal and glial cells, using fluorescence-activated cell sorting, bright-field imaging, immunofluorescence, and RNA analysis by qPCR. The results showed that both wDFAT and brDFAT cells had the capacity to generate neuronal and glial-like cells under neurogenic conditions. However, the brDFAT cells exhibited enhanced propensity for neurogenic differentiation. The neurogenic cells were at least in part derived from Adiponectin-expressing cells. TdTomato-expressing cells derived from Adiponectin (Adipoq) Cre ERT2 -tdTomato flox/flox mice gave rise to individual cells and cell clusters with neurogenic characteristics. Moreover, human brDFAT cells demonstrated a similar ability to undergo neurogenic differentiation after treatment with neurogenic medium, as assessed by immunofluorescence and qPCR. Together, our results support that brDFAT cells have ability to undergo neurogenic differentiation.


Persistent undeveloped mesonephric duct (a case report).
The mesonephric duct may fail to develop, resulting in congenital absence of the kidney and ureter. A unique case of persistence of the mesonephric duct without development into the kidney and ureter is presented.


Synchronous ovarian metastases at the time of laparotomy for colon cancer.
The aim of the study was to identify clinical features, define prognostic factors and optimize treatment in patients with colorectal cancer with synchronous ovarian metastases at the time of initial diagnosis. A retrospective analysis of patients treated by the gynecologic oncology service at Barnes Jewish Hospital between 1990 and 2001 was performed. Twenty-eight patients with colorectal carcinomas with synchronous ovarian metastases at the time of diagnosis were identified. Clinical and pathological characteristics were evaluated, and survival was analyzed by the method of Kaplan and Meier. Abdominal pain was the most common symptom at presentation. Only 14% of the patients presented with gastrointestinal bleeding. Fifty-four percent of patients who underwent barium enema had intrinsic colonic lesions, while 40% of patients who had endoscopies performed had their colonic tumors identified. Preoperatively colon cancer was considered in the differential diagnosis of 71% of the patients. At exploration, the ovarian metastases were significantly larger than the primary colon tumors. Overall, 68% of patients had intraperitoneal nodal metastasis and 86% had transmural extension of their tumors. The only pathological variable associated with survival was tumor grade. The median disease-free survival was 10.3 months while the median overall survival was 18.4 months. Most patients with colon cancer with synchronous ovarian metastases present with vague symptoms. At exploration, locally advanced tumors and other distant metastases such as in the liver are common. Surgical management should include extirpation of the primary tumor and any bulky ovarian metastases. Cytoreduction may be considered in highly selected patients.


A sliding-window weighted linkage disequilibrium test.
Multilocus linkage disequilibrium (LD) tests that consider inter-marker (LD) are more powerful than single-locus tests when disease etiology is contributed simultaneously by several linked and correlated loci. However, inclusion of redundant non-informative markers may result in reduced testing power and/or inflated false-positive rate, therefore selection of proper marker sets is important in such tests. We introduce a unified LD test based on a convenient marker-selection procedure (sliding window) combined with an adjustment approach (marker weighting) to dilute the impact of nuisance markers on tests. The proposed procedure includes several conventional p-value combination methods as its special cases. Simulation studies were performed to evaluate the impact of inclusion of nuisance markers and performance of the procedure. The results showed that testing power was often inversely proportional to the quantity of nuisance markers. Among a class of p-value combination methods, the product p-value method had the highest testing power. P-value truncation somewhat reduced the testing power but controlled the false-positive rate well. Compared with conventional unweighted approaches, the weighted strategy alleviated the false-positive rate and/or increased testing power when nuisance markers were included. Analyses of two authentic data sets for psoriasis and Alzheimer's disease using our proposed method confirmed previous findings.


Dissociation of implicit and explicit memory tests: effect of age and divided attention on category exemplar generation and cued recall.
In this article, we report an experiment that provides further evidence concerning the differences between explicit and implicit measures of memory. The effects of age and divided attention on the implicit conceptual test of category exemplar generation (CEG) were compared with their effects on the explicit test of cued, recall, where the category names served as cues in both tasks. Four age groups (20-35, 40-55, 60-75, and 76-90) were compared. Half of the subjects were also required to carry out a secondary letter-detection task during the learning phase. Cued recall performance was significantly impaired by increased age and imposition of the secondary task. In contrast, the CEG task was unaffected by these two factors. These results suggest that implicit conceptual tasks and explicit memory tasks are mediated by different processes. This conclusion opposes those of previous studies that showed that experimental manipulations (level of processing, generation, organization) influenced these two kinds of memory tests in a similar way.


Comparative Morphology of the Digestive Tract of African Bush Fish (Ctenopoma acutirostre) and Paradise Fish (Macropodus opercularis) Inhabiting Asian and African Freshwaters.
Anabantidae is a large and diverse group of fish cultured both under aquaculture conditions and as a hobby. These fish share a common structural feature in the form of an additional respiratory organ. Despite the enormous availability of these fish worldwide, little is known about their feeding preferences in husbandry and their influence on homeostasis under both industrial and domestic conditions. This study describes, for the first time, the structure of the digestive tracts of two Anabantoidei fishes: African bush fish (Ctenopoma acutirostre) and paradise fish (Macropodus opercularis). The overall structure of the digestive tract and its histological structure were analyzed and compared in both fish species. Physiological predispositions indicated a predominance of omnivorous fish traits in M. opercularis in contrast to C. acutirostre, which has several morphological traits indicating greater adaptation to carnivory, particularly ichthyophagy. The results obtained will allow further research to be conducted in the future to optimize the nutrition and feeding of these fish and to develop appropriate dietary recommendations.


[The Foot in Language, Symbols, and Myths].
In the history of evolution, the human foot is the youngest part of our skeleton and allows plane bipedal walking due to development of a longitudinal and transverse arch of the foot, with a stable, parallel first ray, but sacrificing the ability to grasp. Due to the loss of grasping, the hominoid mothers had to lay down their babies while working. To prevent babies from crying in dangerous surroundings with wild animals, mothers had to calm them with sounds and singing that likely led to language. A third somehow synchronous step was growth of the telencephalon and the development of specialised hands that could produce tools for fishing and hunting. As these elementary changes allowed upright walking and the discovery of new worlds, the foot is really deeply anchored in our speech and has become a symbol for life itself, for the human being as a "pars pro toto", for freedom, power and subjection. According to many myths, metaphors and symbols for the foot also represent life-spending fertility, eroticism, and sexuality. But nevertheless the foot is also a symbol of respect, reverence, and subservience, feet washing and anointing is an act of humility and love. At least we know nowadays that the foot is a subconscious ambassador of our emotions in non-verbal communication. With the help of our feet, we can hunt each other or approach each other, not only symbolically, but also in fact.


A prospective evaluation of neonatal hypoglycaemia in infants of women with gestational diabetes mellitus.
To analyse first-day-of-life glucose levels in infants of women with gestational diabetes (GDM) and the influence of maternal, gestational and peripartum factors on the development of neonatal hypoglycaemia. Prospective cohort study including newborns of GDM mothers. Capillary blood glucose (CBG) was measured serially on the first day of life. CBG values were defined as normal (≥ 2.5 mmol/l), mild hypoglycaemia (2.2-2.4 mmol/l), moderate hypoglycaemia (1.6-2.1 mmol/l) and severe hypoglycaemia (<1.6 mmol/l). One hundred and ninety infants were included: 23 (12.1%) presented mild, 20 (10.5%) moderate and only 5 (2.6%) severe hypoglycaemia. Hypoglycaemic infants were more frequently large-for-gestational-age (29.3% vs 11.3%, p=0.003), had lower umbilical cord pH (7.28 vs 7.31, p=0.03) and their mothers had more frequently been hyperglycaemic during labour (18.8% vs 8.5%, p=0.04). In multivariate analysis Pakistani origin (OR: 2.94; 95% CI: 1.14-7.55) and umbilical cord venous pH (OR: 0.04, 95% CI: 0.261-0.99) were significantly and independently associated with hypoglycaemia. Mild and moderate neonatal hypoglycaemias were common although severe episodes were unusual in infants of women with GDM. Hypoglycaemia is mainly influenced by ethnicity and cord blood pH, although maternal peripartum glycaemic control and large-for-gestational-age condition may also play a role.


The developmental psychobiology of behavioural plasticity in mice: the role of social experiences in the family unit.
Small perturbations of young animals' sensory experience or hormonal milieu have been shown to alter ontogenetic pathways and to potentially produce huge effects on CNS functioning and behaviour later in life. From a social point of view, variables such as the expression of affiliative bonding and of playful interactions among littermates, the quantity/quality of maternal care, or episodes of maternal or sibling deprivation during critical phases in development, seem to interfere as epigenetic factors with the rigidly ordered temporal sequences of events that occur during the ontogenesis of CNS. This leads to the onset of adaptive neurodevelopmental changes, which are observable within a continuum that encompasses both "normal" individual variability and potential behavioural disorganisation, which in turn will probably be related to profound alteration in the establishment of adult social competence. The present review summarises the more recent work in mice dealing with short-term, as well as long-term modifications, in naturally occurring species-typical social and non-social responses as a function of the early manipulation of social characteristics of the family unit (such as litter gender composition and time of weaning). These analyses were carried out on infant animals, i.e. during the ontogenetic stage of the establishment of social bonding, as well as on pre-pubertal and adult mice and on lactating adult females. Critical issues, such as the respective roles of sibling-sibling and dam-offspring interactions in the shaping of "sibling effects", are also addressed. Overall, these studies indicate that, within their natural range of variation, early patterns of social stimulation are powerful determinants of subsequent behaviour of developing altricial rodents, and confirm that early social life events warrant attention because they can strongly affect neurobehavioural development. Evidence of a relationship between social events occurring during early rearing (i.e. when dramatic transitions in neuroendocrine and neurochemical CNS systems occur) and individual behavioural variability in the infant and adult response to the effects of psychostimulants abused by humans is presented. A better understanding of the mechanisms that mediate such remarkable plasticity might have great psychobiological as well as clinical importance, especially when considering the issue of vulnerability to drug abuse.


Determinants of the relation between systolic pressure and duration of isovolumic relaxation in the right ventricle.
Previous studies have suggested that right ventricular systolic pressure can be predicted from noninvasive estimates of the interval between pulmonary valve closure and tricuspid valve opening. To determine the basis for this relation, phonocardiograms and high fidelity right atrial and ventricular pressures were recorded in 29 patients with a right ventricular systolic pressure ranging from 20 to 149 mm Hg. In 22 patients with normal right atrial pressure (less than or equal to 8 mm Hg), both the time interval and the magnitude of pressure decrease from pulmonary valve closure to tricuspid valve opening were linearly related to systolic pressure (r = 0.89 and 0.96, respectively). Early pulmonary valve closure (decreased "hang-out" time) contributed to the greater magnitude of isovolumic pressure decrease at high systolic pressures, but correction for hang-out time did not eliminate the relation between systolic pressure and the pulmonary valve closure-tricuspid valve opening interval (n = 10). When patients with documented right coronary artery disease were excluded, the time constant for isovolumic pressure decrease also increased as a function of systolic pressure (r = 0.67, p less than 0.01, n = 24), suggesting impaired relaxation at high systolic pressures. However, the mean rate of pressure decrease (mean negative dP/dt) still was greater in patients with a high pressure because of the exponential nature of the isovolumic pressure-time relation.(ABSTRACT TRUNCATED AT 250 WORDS)


Decreased c-Jun expression correlates with impaired spinal motoneuron regeneration in aged mice following sciatic nerve crush.
Post-injury nerve regeneration of the peripheral nervous system declines with age, but the mechanisms underlying the weakened axonal regeneration are not well understood. Increased synthesis and activity of the AP-1 transcription factor c-Jun have been implicated in efficient motor axonal regeneration. In the present study, we evaluated the hypothesis that the impaired regenerative capacity in the aged is associated with impaired induction of c-Jun. In non-manipulated young adult or aged mice, no c-Jun and its phosphorylated form were detected in the ventral horn of the spinal cord. Following nerve crush, significant c-Jun and phosphorylated c-Jun occurred in the injured motoneurons of young adult mice, but not in aged animals. In accord with the immunohistochemistry, Western blots also showed that sciatic nerve crush induced c-Jun and its phosphorylation expression in the ventral horn of young adult but not in aged mice. Changes in c-Jun mRNA level detected by in situ hybridization are congruent with that in c-Jun protein content, showing an increase at 5 days after crush in young adult but not aged. Moreover, compared with young adult mice, aged mice showed impaired motor axonal regeneration. These results demonstrate that the impaired motor axonal regeneration seen in aged mice is correlated with impaired c-Jun expression and phosphorylation following injury. These data provide a neurobiological explanation for the poor outcome associated with nerve repair in the aged.


Effect of natural curcuminoids-intercalated layered double hydroxide nanohybrid against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis: A bactericidal, antibiofilm, and mechanistic study.
The study aimed to determine the antibacterial/antibiofilm effect and mechanism of interaction of curcuminoids-intercalated Mg/Al layered double hydroxide (curcuminoids-LDH) against three different bacteria. Antimicrobial effect of curcuminoids-LDH nanohybrid was investigated against P. aeruginosa, S. aureus, and E. faecalis (for both standard strains and clinical isolates), using agar well diffusion method. Minimum inhibitory concentrations (MIC) of planktonic bacteria were determined using the broth microdilution method. MIC of biofilms (MBIC50 ) and killing time for 48 hr matured biofilms were determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Scanning electron microscopy (SEM) was used to determine pre- and postexposure architecture of biofilms. The mechanism of the antibiofilm activity of curcuminoids-LDH was determined using UV-visible spectroscopy. All tested bacteria had given a zone of inhibition in the presence of curcuminoids-LDH. The MIC values were 0.200 g/ml for P. aeruginosa, 0.025 g/ml for S. aureus, and 0.100 g/ml for E. faecalis. The 48 hr matured biofilms were reduced by curcuminoids-LDH with an MBIC50 of 0.100 g/ml. The minimum time to achieve MBIC50 was 3 hr, and the reduction was constant until 48 hr. SEM images showed a significant reduction of biofilm cell density and exopolymer matrics for all biofilms in the presence of curcuminoids-LDH. UV-visible studies revealed the antibiofilm activity of curcuminoids-LDH as due to the auto-oxidation of curcuminoids. The oxidation products are more limited in both product concentration per unit time and the variety of products, compared to pure curcuminoids, resulting in sharper UV-visible peaks than in the case of the latter. Curcuminoids-LDH has a potential antibacterial activity against P. aeruginosa, S. aureus, and E. faecalis. An antibiofilm activity has been achieved within 3 hr of the treatment. Curcuminoids released from the LDH showed the antibacterial activity due to oxidation products interfering with bacterial cell functions, and also encapsulation in the LDH causes curcuminoids to exhibit the activity in a persistent manner compared to pure curcuminoids.


An Extremely Stable Interprotein Tetrahedral Hg(Cys)4 Core Forms in the Zinc Hook Domain of Rad50 Protein at Physiological pH.
Invited for the cover of this issue is the group of Artur Krężel at the University of Wrocław in collaboration with Lars Hemmingsen at The University of Copenhagen and Eva Freisinger at the University of Zürich. The image depicts the outcomes of HgII interactions with Rad50 protein. Read the full text of the article at 10.1002/chem.202202738.


Critically ill septic patients have elevated oxidative stress biomarkers: lack of attenuation by parenteral vitamin C.
Patients with septic shock are under an intense inflammatory burden, which is closely associated with increased oxidative stress and depletion of antioxidants such as vitamin C. We hypothesized that patients with septic shock would present with elevated oxidative stress (assessed as F2-isoprostanes) and that administration of parenteral vitamin C to these patients would attenuate F2-isoprostane concentrations. We recruited 40 critically ill patients with septic shock into a randomized placebo-controlled trial and assessed the effect of short-term (4-day) parenteral vitamin C administration (100 mg/kg/d) on 8-isoprostane F2α concentrations, which were measured using enzyme-linked immunosorbent assays. Sources of sepsis and intensive care unit severity scores were recorded. Smokers (n = 20) and nonsmoking controls (n = 50) were assessed for comparison. The median baseline 8-isoprostane F2α concentration in the septic patients was 3.95 (interquartile range [Q1, Q3] 2.1, 6.63) ng/mg creatinine; this was higher than smokers 1.61 [1.25, 2.82] P = .007 ng/mg creatinine; P = .005) and nonsmoking controls 1.12 [0.76, 1.57] ng/mg creatinine; P < .0001). The 8-isoprostane F2α concentrations in the placebo group did not vary significantly over the duration of the study. Although parenteral vitamin C administration significantly increased the vitamin C status of the patients within 24 hours, this did not affect their 8-isoprostane F2α concentrations. In conclusion, patients with septic shock have elevated 8-isoprostane F2α excretion, which short-term parenteral vitamin C administration is unable to attenuate. If vitamin C is to work by antioxidant mechanisms, then early administration, before the development of shock, may be required. This trial was registered at anzctr.org.au (ACTRN12617001184369).


Erratum: Correction of Text in the Article "Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI".
This corrects the article on p. 304 in vol. 52, PMID: 35129316.


Labelled-replica techniques: post-shadow labelling of intramembrane particles in freeze-fracture replicas.
Three methods are described for direct post-fracture, post-shadow labelling of individual classes of intramembrane particles (IMPs) in freeze-fracture replicas of biological membranes. The P-face IMPs corresponding to the acetylcholine receptor complexes (AChRs) of vertebrate neuroeffector junctions are identified by post-replication labelling with ferritin-antibody complexes and with neurotoxin-biotin-avidin-colloidal gold affinity ligands. (The freeze-etch nomenclature of Branton et al., 1975, is used in this report.) These post-shadow labelling techniques resemble conventional en bloc labelling techniques except that the labelling reagents must penetrate a thin but discontinuous layer of platinum superimposed on the molecules of interest. In the 'sectioned labelled-replica technique', the replicated and labelled tissues are stained, embedded in plastic and sectioned parallel to the replica-tissue interfaces. In the direct 'labelled-replica techniques', the replicated and labelled samples are freeze-dried or critical point dried, the labelled surfaces are stabilized by carbon coating, and the underlying tissues are dissolved, allowing the labelled-replicas to be examined as conventional freeze-fracture replicas. The unshadowed side of each AChR IMP is shown to retain sufficient biochemical information to permit both immunospecific and neurotoxin specific labelling despite formaldehyde fixation, freezing, fracturing, platinum shadowing, and thawing in aqueous media. A new mixed ferricyanide-osmium staining method reveals electron opaque structures spanning the membrane bilayer in the same size, number and distribution as the labelled IMPs. These experiments demonstrate the feasibility of identifying individual IMPs in freeze-fracture replicas and may allow the identification of specific membrane lesions in human disease.


Tantalum in type IV and V Paprosky periprosthetic acetabular fractures surgery in Paprosky type IV and V periprosthetic acetabular fractures surgery.
Periprosthetic acetabular fractures represent a growing and serious complication of total hip arthroplasty (THA). The purpose of the study is to report our experience in the use of tantalum for the treatment of Paprosky type IV and V periprosthetic acetabular fractures. We analyzed 24 patients with type IV and V periprosthetic acetabular fractures. Patients were treated with a revision surgery using tantalum components, in some cases in association with posterior plating. Outcomes were evaluated using VAS, Harris hip score and considering the average time of integration of the acetabulum and the number of complications. The endpoint evaluation was established at 24 months. Results show that the average time of integration of the neoacetabulum in tantalum was 12.3 months (range 6-18 months). The average VAS pain is 8.7/10 cm at time 0 and gradually returns to basic pre-injury values in the following months. The average value of HHS at time 0 is 13.5 points. This value tends to increase progressively until reaching a mean score of 89.3 points at 24 months, higher than the average pre-trauma value of 84.3 points. Periprosthetic fractures of the acetabulum with bone loss are a rare but potentially disastrous complication of total hip prostheses. Their management and therapeutic choice will test the ability of the orthopedic surgeon. It is important to determine the type of fracture and characteristics in order to pursue an adequate therapeutic strategy. The modern biomaterials, such as porous tantalum, offer a greater potential in replacing bone loss, promoting bone regrowth and obtaining a stable implant.


Drug-related HIV risk behaviors and cocaine preference among injection drug users in Los Angeles.
Based on a 1988-91 sample of 422 drug-using arrestees in Los Angeles, this study compares the drug-related risk behavior of users whose preferred injection drug is cocaine and users with a preference for heroin or no preference between the two drugs. Cocaine preference is unrelated to the likelihood of needle sharing overall, needle sharing with strangers, needle sharing at shooting galleries, and failure to use bleach as a needle disinfectant. In analyses restricted to users who reported needle sharing, the frequency of sharing is no more closely related to heroin injection frequency than to cocaine injection frequency. These results suggest that local preventive education programs do not need to address distinctive patterns of drug-related risk behavior among injection cocaine users and injection heroin users in Los Angeles.


An assay method for the measurement of urinary inhibitors of calcium phosphate formation.
An assay method has been developed for studying quantitatively the formation of calcium phosphate. The method will detect both substances which affect the solubility of calcium phosphate and substances which affect the crystal growth of the material. It is sensitive as or more sensitive than other methods described in the literature for detecting such compounds.


Identification of novel immunoreactive proteins and delineation of a specific epitope of Anaplasma phagocytophilum.
Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum. Because of nonspecific clinical manifestations, diagnosis of HGA highly depends on laboratory tests. Identification of immunoreactive proteins is prerequisite for development of specific and sensitive immunoassays for HGA. In this study, we identified novel immunoreactive proteins of A. phagocytophilum. Previous studies indicated that secreted proteins of A. phagocytophilum and other bacteria can be immunoreactive antigens. Here we in silico screened A. phagocytophilum genome for encoding proteins which bear features of type IV secretion system substrates. Among seventy seven predicted proteins, fourteen proteins were determined for antigenicity and nine proteins were showed to be immunoreactive antigens. In addition, an APH1384 peptide harboring a B cell epitope predicted by bioinformatics was found specifically reacting with anti-A. phagocytophilum sera. Hereby, we identified novel immunoreactive proteins and delineated a specific epitope of A. phagocytophilum, which might be employed for HGA diagnosis.


The human glutathione S-transferase. Studies on the kinetic, stability and inhibition characteristics of the erythrocyte enzyme.
Bromosulphophthalein and N-ethylmaleimide, inhibitors of glutathione S-transferase (EC 188.8.131.52 RX: glutathione R. transferase), have been used to identify variant forms of the erythrocyte enzyme. One 'atypical' sample was detected and was shown to have appreciably different kinetic and stability properties. These inhibitors may be useful in surveys of variation in this group of enzymes.


Peptide nucleic acid-dependent artifact can lead to false-positive triplex gene editing signals.
Triplex gene editing relies on binding a stable peptide nucleic acid (PNA) sequence to a chromosomal target, which alters the helical structure of DNA to stimulate site-specific recombination with a single-strand DNA (ssDNA) donor template and elicits gene correction. Here, we assessed whether the codelivery of PNA and donor template encapsulated in Poly Lactic-co-Glycolic Acid (PLGA)-based nanoparticles can correct sickle cell disease and x-linked severe combined immunodeficiency. However, through this process we have identified a false-positive PCR artifact due to the intrinsic capability of PNAs to aggregate with ssDNA donor templates. Here, we show that the combination of PNA and donor templates but not either agent alone results in different degrees of aggregation that result in varying but highly reproducible levels of false-positive signal. We have identified this phenomenon in vitro and confirmed that the PNA sequences producing the highest supposed correction in vitro are not active in vivo in both disease models, which highlights the importance of interrogating and eliminating carryover of ssDNA donor templates in assessing various gene editing technologies such as PNA-mediated gene editing.


Evidence of Fluconazole-Resistant Candida Species in Tortoises and Sea Turtles.
The aim of this study was to evaluate the antifungal susceptibility of Candida spp. recovered from tortoises (Chelonoidis spp.) and sea turtles (Chelonia mydas, Caretta caretta, Lepidochelys olivacea, Eretmochelys imbricata). For this purpose, material from the oral cavity and cloaca of 77 animals (60 tortoises and 17 sea turtles) was collected. The collected specimens were seeded on 2% Sabouraud dextrose agar with chloramphenicol, and the identification was carried out by morphological and biochemical methods. Sixty-six isolates were recovered from tortoises, out of which 27 were C. tropicalis, 27 C. famata, 7 C. albicans, 4 C. guilliermondii and 1 C. intermedia, whereas 12 strains were obtained from sea turtles, which were identified as Candida parapsilosis (n = 4), Candida guilliermondii (n = 4), Candida tropicalis (n = 2), Candida albicans (n = 1) and Candida intermedia (n = 1). The minimum inhibitory concentrations for amphotericin B, itraconazole and fluconazole ranged from 0.03125 to 0.5, 0.03125 to >16 and 0.125 to >64, respectively. Overall, 19 azole-resistant strains (14 C. tropicalis and 5 C. albicans) were found. Thus, this study shows that Testudines carry azole-resistant Candida spp.


Assessment of unscheduled DNA synthesis in a cultured line of renal epithelial cells exposed to cysteine S-conjugates of haloalkenes and haloalkanes.
The ability of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC), S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine (PCBC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFEC) and S-(2-chloroethyl)-L-cysteine (CEC) to induce DNA repair was investigated in LLC-PK1, a cultured line of porcine kidney tubular epithelial cells. DNA repair due to exposure of the cells to the S-conjugates was determined as unscheduled DNA synthesis (UDS) after inhibition of replicative DNA synthesis in confluent LLC-PK1 monolayers. DCVC, TCVC and PCBC induced dose-dependent UDS in LLC-PK1 at concentrations which did not impair the viability of the cells compared to untreated controls; higher concentrations were cytotoxic, resulting in lactate dehydrogenase leakage into the medium. Cell death was also induced by CTFEC, which failed to exert genotoxicity. CEC induced the highest response among these cysteine conjugates without impairing cell viability. Inhibition of cysteine conjugate beta-lyase with aminooxyacetic acid abolished the effects of DCVC, TCVC, PCBC and CTFEC but did not influence the genotoxicity of CEC.


Production of N-acetylglucosamine with Vibrio alginolyticus FA2, an emerging platform for economical unsterile open fermentation.
Members of the Vibrionaceae family are predominantly fast-growing and halophilic microorganisms that have captured the attention of researchers owing to their potential applications in rapid biotechnology. Among them, Vibrio alginolyticus FA2 is a particularly noteworthy halophilic bacterium that exhibits superior growth capability. It has the potential to serve as a biotechnological platform for sustainable and eco-friendly open fermentation with seawater. To evaluate this hypothesis, we integrated the N-acetylglucosamine (GlcNAc) pathway into V. alginolyticus FA2. Seven nag genes were knocked out to obstruct the utilization of GlcNAc, and then 16 exogenous gna1s co-expressing with EcglmS were introduced to strengthen the flux of GlcNAc pathway, respectively. To further enhance GlcNAc production, we fine-tuned promoter strength of the two genes and inactivated two genes alsS and alsD to prevent the production of acetoin. Furthermore, unsterile open fermentation was carried out using simulated seawater and a chemically defined medium, resulting in the production of 9.2 g/L GlcNAc in 14 h. This is the first report for de-novo synthesizing GlcNAc with a Vibrio strain, facilitated by an unsterile open fermentation process employing seawater as a substitute for fresh water. This development establishes a basis for production of diverse valuable chemicals using Vibrio strains and provides insights into biomanufacture.


Peripheral tears of the meniscus. The effect of open versus arthroscopic repair on intraarticular contact stresses in the human knee.
The mechanical properties of the repaired meniscus may affect its ability to heal and to protect the articular surface against degenerative changes. We compared the immediate biomechanical consequences of open versus arthroscopic repair in the human cadaver knee. Additionally, having measured postoperative stresses at various degrees of knee flexion, we have addressed the effect of tethering of the meniscus, a question relevant to both meniscus repair and replacement. Peak stresses were measured by the Pressensor system. Fresh human cadaver knees were subjected to loading in an Instron unit, on an unconstrained base. Instantaneous loads were applied with the knee in 0 degree, 30 degrees, or 60 degrees of flexion, and stress distributions were measured after repair of a 2 cm peripheral tear, by an open or arthroscopic approach. The results of loading experiments on five knees revealed no statistically significant differences between stresses after the two repairs. Similarly, there was no statistically significant difference between the normal and repaired menisci. In our model, this suggests that the immediate biomechanical consequences of open and arthroscopic repair are equivalent and that the "tethered" meniscus distributes loads as well as the normal meniscus.


[Conservative local therapy of inflammation of joints: local invasive forms of therapy].
Local invasive procedures represent possibilities for the treatment of arthritic swollen joints without surgical interventions, when general measures alone are not successful and intra-articular injections are of utmost importance in this context. The differences between degenerative and rheumatologic diseases must be considered as well as possible specific adverse reactions, side effects and contraindications. The technical intervention is performed according to the guidelines of scientific societies such as the Scientific Medical Profession Society (AWMF). Cortisone and radiosynoviorthesis/chemosynoviorthesis are suitable for activated rheumatic and degenerative joints, low-grade radiation therapy or infiltration of hyaluronic acid is recommended for relief in cases of arthritic inflammation. The combination of arthroscopic synovectomy and subsequent radiosynoviorthesis in the early stages of rheumatically swollen joints show the best results with respect to regression prophylaxis and slowing the process of rapidly progressing destruction of chondral surfaces and distension of the capsules and ligaments.