Cell-to-cell communication and vascular dementia.
VaD is the second-most common form of dementia, second only to that caused by AD. As the name indicates, VaD is predominantly considered a disease caused by vascular phenomena. In this invited review, we introduce the reader to recent developments in defining VaD as a unique form of dementia by reviewing the current pertinent literature. We discuss the clinical and experimental evidence that supports the notion that the microcirculation, specifically cell-to-cell communication, likely contributes to the development of VaD. Through exploration of the concept of the NVU, we elucidate the extensive cerebrovascular communication that exists and highlight models that may help test the contribution(s) of cell-to-cell communication at the microvascular level to the development and progression of VaD. Lastly, we explore the possibility that some dementia, generally considered to be purely neurodegenerative, may actually have a vascular component at the neurovascular level. This latter recognition potentially broadens the critical involvement of microvascular events that contribute to the numerous dementias affecting an increasingly larger sector of the adult population.


Effect of the menstrual cycle on the optic nerve head in diabetes: analysis by confocal scanning laser ophthalmoscopy.
The purpose of this study was to examine and compare menstrual-cycle-dependent topographic changes in the optic nerve head of normally menstruating women with different grades of type 2 diabetes mellitus. We studied the right eyes of 123 normally menstruating women (36 with severe nonproliferative diabetic retinopathy [NPDR], 42 with mild NPDR and 45 healthy subjects). All subjects underwent a complete ocular examination at baseline. At 4 hormonally distinct phases of the menstrual cycle (early follicular, late follicular, mid-luteal and late luteal), we analysed the topography of the optic nerve head, using a confocal scanning laser ophthalmoscope, and measured the serum levels of estradiol, progesterone and luteinizing hormone. We excluded from analysis the data for 8 patients with severe NPDR, 10 patients with mild NPDR and 15 control subjects who were lost to follow-up examinations during the menstrual cycle. The mean age and optic disc area did not differ significantly among the 3 groups. The duration of diabetes was significantly longer in the patients with severe NPDR than in those with mild NPDR (p < 0.05). The women with severe NPDR had a significantly increased neuroretinal rim area and a significantly decreased cup-shape measure, linear cup/disc ratio, cup/disc area ratio and cup area in the late luteal phase compared with the other phases of the menstrual cycle (p < 0.05). Those with mild NPDR or a normal retina had no significant topographic changes in the optic nerve head during the menstrual cycle. Severe NPDR is associated with significant topographic changes in the rim and cup of the optic nerve head during the menstrual cycle. This must be considered in the evaluation of women with both diabetes and glaucoma. The normal fluctuations in serum sex hormone levels during the menstrual cycle of diabetic women seem to affect the optic nerve head more when the disease is advanced.


Rabies virus immunity in genetically selected high- and low-responder lines of mice.
The antibody responsiveness to and the specific vaccination effect of rabies virus infection were investigated in high- and low-responder lines of mice produced by two-way selective breedings for quantitative production of antibodies to flagellar (H/f and L/f lines) or somatic (H/s and L/s lines) antigens of salmonellae. After specific immunization, both high lines were more resistant to rabies virus infection than were the low lines, and the protector effect was related to the level of antibody produced, as demonstrated by neutralizing serum activity. The present findings confirm the nonspecific genetic modification of the general antibody responsiveness induced in high- and low-responder lines selected for quantitative antibody production.


[Gallium scintigraphy of gynecologic neoplasms].
67Gallium whole body scintigraphy was applied in 16 patients with gynecological malignomas and 2 patients with suspicion on a recurrent tumour as a supplement to usual diagnostic procedure. Aim of this study was the detection of metastases earlier than with the usual methods. Scintigraphy results have been interpreted average of 5 years after examination. Additional clinical informations were necessary in 6 cases. 3 out of these 6 cases have been shown in detail.


Molecular pathogenesis of chronic myeloid leukaemia.
The abnormal haemopoietic precursor cells of chronic myeloid leukaemia (CML) carry the cytogenetic abnormality [t(9;22)(q34;q11)]--a reciprocal translocation that results in the expression of a chimaeric protein derived from the fused BCR and ABL genes. This Bcr-Abl protein tyrosine kinase mediates an array of effects on signal transduction pathways affecting cell survival, proliferation, adhesion and genetic stability. The end-result of these abnormal signalling processes is a bi- or triphasic clinical disease. Initially, CML is characterised by the presence of an excess of myeloid progenitor cells and their mature progeny. This chronic phase of CML is followed, either directly or with an intervening 'accelerated phase', by a stage where primitive blast cells predominate (acute transformation). This review discusses the role of Bcr-Abl-mediated signalling events in cellular transformation, genetic instability and disease progression in CML, and describes current developments in CML treatment using a Bcr-Abl inhibitor.


Assessment of beat-by-beat control of heart rate by the autonomic nervous system: molecular biology technique are necessary, but not sufficient.
Vagus nerve activity can change heart rate substantially within one cardiac cycle, and the chronotropic effects decay almost completely within one cardiac cycle after cessation of vagal activity. The ability of the vagus nerves to regulate heart rate beat by beat can be explained in large part by the speed at which the neural signal is transduced to a cardiac response and by the rapidity of the processes that restore the basal heart rate when vagal activity ceases. Currently, the question of whether the cardiac cells can transduce the sympathetic neural signals rapidly enough to implement beatwise regulation is controversial. Emphasis on the speed of the processes that initiate the responses may, however, be misplaced. Instead, the processes that terminate the responses to autonomic neural activity (especially those processes that remove the released neurotransmitters) are probably the main determinants of the ability of the vagal and sympathetic systems to affect beatwise control. The norepinephrine (NE) released from the sympathetic nerve endings is removed from the cardiac tissues much more slowly than is the acetylcholine that is released from the vagal terminals. As a consequence of the potential deleterious effects associated with the slow removal of NE, the cardiac neural control system has evolved such that the sympathetic nerves ordinarily release NE at a slow rate. Hence, changes in sympathetic neural activity can alter cardiac behavior only slightly from beat to beat. Hence, beatwise control of cardiac function would be negligible, regardless of how swiftly the sympathetic nerve impulse is transduced to a change in cardiac performance.


ECG patterns confounding the ECG diagnosis of acute coronary syndrome: left bundle branch block, right ventricular paced rhythms, and left ventricular hypertrophy.
The ECG has limitations in the evaluation of the chest-pain patient, including the presence of confounding ECG patterns; the ECG patterns that confound the diagnosis of acute myocardial infarction(AMI) include left bundle branch block (LBBB), ventricular paced rhythms (VPR), and left ventricular hypertrophy (LVH). These patterns produce new ST-segment/T-wave abnormalities, which are the new normal findings in these patients and may lead the clinician astray in two distinct instances: (1) diagnosing ECG change related to acute coronary syndromes (ACS) when the abnormality results solely from the confounding pattern; and (2) not acknowledging the confounding nature of these ECG patterns in the evaluation of potential ACS, thereby placing excessive diagnostic confidence in the ECG. This article highlights the diagnostic dilemma encountered in these confounding ECG patterns; the discussion focuses on the expected ECG abnormalities in these patients and the findings seen in ACS.


Size distribution of barrel-stave aggregates of membrane peptides: influence of the bilayer lateral pressure profile.
Some membrane peptides, such as Alamethicin, form barrel-stave aggregates with a broad probability distribution of size (number of peptides in the aggregate). This distribution has been shown to depend on the characteristics of the lipid bilayer. A mechanism for this influence is suggested, in analogy to earlier work on the effects of changes in bilayer composition on conformational equilibria in membrane proteins, that is based on coupling of shifts in the distribution of lateral pressures in the bilayer to depth-dependent changes in the lateral excluded area that accompanies the formation of an aggregate. Thermodynamic analysis is coupled with a simple geometric model of aggregates of kinked cylindrical peptides and with results of previously calculated lateral pressure distributions to predict the effects of changes in bilayer characteristics on aggregate size distributions, in qualitative agreement with experimental results.


PURLs: "Go low" or say "No" to aggressive systolic BP goals?
The SPRINT trial demonstrated the benefits--and risks--of reaching a systolic target <120 mm Hg in non-diabetic patients at high risk for CV events. Here's who might benefit.


Experimental transmission of Hepatozoon americanum Vincent-Johnson et al., 1997 to dogs by the Gulf Coast tick, Amblyomma maculatum Koch.
Experimental transmission of Hepatozoon americanum to dogs was attempted with four ixodid ticks, viz., Rhipicephalus sanguineus, Amblyomma americanum, Amblyomma maculatum and Dermacentor variabilis. Ticks that dogs ingested included some that were laboratory-reared and experimentally fed as nymphs on a dog with naturally occurring hepatozoonosis; other ticks were collected as replete or partially engorged larvae, nymphs and adults from dogs that had hepatozoonosis and natural infestations of ticks. Whole ticks used to expose susceptible dogs orally were partially dissected to help release oocysts. Among eight dogs exposed, only the three that were fed A. maculatum adults experimentally acquisition fed as nymphs became infected. Dogs developed elevated body temperature and other evidence of clinical disease starting 4 weeks after exposure. 'Cysts' typical of H. americanum were found in skeletal muscle when samples were first examined 5 weeks after dogs ingested ticks, and parasites were also observed in peripheral blood smears at approximately the same time. Our study demonstrates that A. maculatum nymphs can acquire H. americanum by feeding on a parasitemic dog and that transstadial transmission of the protozoan occurs, with dogs acquiring infection when they ingest newly molted adult ticks.


Enhanced co-production of S-adenosylmethionine and glutathione by an ATP-oriented amino acid addition strategy.
Effects of amino acids on co-production of S-adenosylmethionine (SAM) and glutathione (GSH) with Candida utilis CCTCC M 209298 were investigated. Both methionine and cysteine showed positive effects on improving intracellular SAM and GSH content simultaneously. Batch fermentative co-production of SAM and GSH was conducted in a 5L stirred fermentor, where the co-production of SAM and GSH was enhanced by 71.3% and 71.5% with 6g/L methionine and 6 mmol/L cysteine, respectively. Based on these results together with intracellular ATP levels during batch cultivation of C. utilis CCTCC M 209298, a two-stage amino acid addition strategy was developed by adding 6g/L methionine at 0 h and 6 mmol/L cysteine at 21 h. Under this ATP-oriented strategy, SAM and GSH biosynthesis was further promoted, and the co-production of SAM and GSH reached 669.3mg/L, which was increased by 124.6% compared to that without amino acid addition.


Fournier's gangrene after missed acute perforated appendicitis: A case report.
Fournier's gangrene (FG) is a rare progressive necrotizing fasciitis (NF) with high mortality rate. This case report describes a young patient with FG with no known history of disease or invasive therapeutic interventions.


CoCoNat: a novel method based on deep learning for coiled-coil prediction.
Coiled-coil domains (CCD) are widespread in all organisms and perform several crucial functions. Given their relevance, the computational detection of CCD is very important for protein functional annotation. State-of-the-art prediction methods include the precise identification of CCD boundaries, the annotation of the typical heptad repeat pattern along the coiled-coil helices as well as the prediction of the oligomerization state. In this article, we describe CoCoNat, a novel method for predicting coiled-coil helix boundaries, residue-level register annotation, and oligomerization state. Our method encodes sequences with the combination of two state-of-the-art protein language models and implements a three-step deep learning procedure concatenated with a Grammatical-Restrained Hidden Conditional Random Field for CCD identification and refinement. A final neural network predicts the oligomerization state. When tested on a blind test set routinely adopted, CoCoNat obtains a performance superior to the current state-of-the-art both for residue-level and segment-level CCD. CoCoNat significantly outperforms the most recent state-of-the-art methods on register annotation and prediction of oligomerization states. CoCoNat web server is available at https://coconat.biocomp.unibo.it. Standalone version is available on GitHub at https://github.com/BolognaBiocomp/coconat.


Biological mechanisms for the loss of the differentiated phenotype by non-terminally differentiated adipocytes.
The differentiation of 3T3 T proadipocyte stem cells is controlled at two related yet distinct states in the G1 phase of the cell cycle. They are designated GD and GD'. GD is the G1 state at which cells must growth arrest prior to differentiation, and GD' is the G1 state at which non-terminal differentiation occurs. Cells arrested at the GD and GD' states have distinct characteristics; yet cells at both states can mediate the integrated control of cellular proliferation and differentiation. In this paper we report on studies designed to further characterize the relationship of these two states, specifically to determine whether non-terminally differentiated GD'-arrested cells can be induced to lose the adipocyte phenotype and revert to the GD state. We report that retinoic acid (RA) and methyl isobutyl xanthine (MIX) can induce non-terminally differentiated GD'-arrested cells to lose the adipocyte phenotype without undergoing DNA synthesis. Such cells that have lost the adipocyte phenotype are also shown to remain in the G1 phase of the cell cycle and to reacquire most of the characteristics of GD-arrested cells. Most importantly, they demonstrate the capacity to redifferentiate without DNA synthesis. We therefore conclude that when non-terminally differentiated GD'-arrested cells are induced to lose the adipocyte phenotype they do indeed revert to the GD state and they thereby become more responsive to environmental influences which can further regulate the integrated control of cellular proliferation and differentiation.


Therapeutic elastic tape reduces morbidity after wisdom teeth removal--a clinical trial.
Although the extraction of an impacted third molar (3M) is a routine procedure, postoperative morbidities typically include swelling, pain, and trismus. The aim of the present study was to investigate whether the application of kinesiologic tape can improve the postoperative morbidities associated with 3M surgery, thereby improving the postoperative well-being of patients. Forty patients assigned for prospective 3M removal were randomized into two treatment groups (with/without kinesiologic tape). Facial swelling was quantified using a five-line measurement at six specific time points. Pain scores were assessed using a visual analog scale, and mouth opening range was assessed by means of standard calipers. In addition, all patients were asked to evaluate overall satisfaction and swelling (both groups) and the effect of the tape on movement and comfort (taped group only). The postoperational application of kinesiologic tape reduced significantly all investigated parameters: swelling, pain, and trismus. Furthermore, patients with kinesiologic tape reported a significantly lower morbidity rate. The application of kinesiologic tape following a 3M surgery is a simple and economical, yet medically relevant approach. Kinesiologic tape offers patients a less traumatic postoperational experience and therefore holds promise to enhance the quality of life of a large cohort of the population.


Epithelial-mesenchymal transition interaction with CD8+ T cell, dendritic cell and immune checkpoints in the development of melanoma.
Melanoma is fatal cancer originating from melanocytes, whose high metastatic potential leads to an extremely poor prognosis. This study aimed to reveal the relationship among EMT, TIICs, and immune checkpoints in melanoma. Gene expression data and clinical data of melanoma were downloaded from TCGA, UCSC Xena and GEO databases. EMT-related DEGs were detected for risk score calculation. "ESTIMATE" and "xCell" were used for estimating TIICs and obtaining 64 immune cell subtypes, respectively. Moreover, we evaluated the relationship between the risk score and immune cell subtypes and immune checkpoints. Seven EMT-related genes were selected to establish a risk scoring system because of their integrated prognostic relevance. The results of GSEA revealed that most of the gene sets focused on immune-related pathways in the low-risk score group. The risk score was significantly correlated with the xCell score of some TIICs, which significantly affected the prognosis of melanoma. Patients with a low-risk score may be associated with a better response to ICI therapy. The individualized risk score could effectively conduct risk stratification, overall survival prediction, ICI therapy prediction, and TME judgment for patients with melanoma, which would be conducive to patients' precise treatment.


Analysis of the Leaves and Cones of Lithuanian Hops (Humulus lupulus L.) Varieties by Chromatographic and Spectrophotometric Methods.
This work involves a comprehensive chemical composition analysis of leaf and cone samples of Lithuanian hop varieties. This study aimed to determine the chemometric properties of the leaves and cones of five Lithuanian hop varieties. Determined properties were the following: (a) xanthohumol content, (b) phenolic compounds, (c) flavonoids, (d) radical scavenging activity, and (e) the qualitative composition of volatile compounds. The total content of phenolic compounds in aqueous 75% methanolic extracts varied between 31.4-78.2 mg of rutin equivalents (RE)/g, and the concentration of flavonoids was between 11.0-23.3 mg RE/g. Radical scavenging activity varied between 34.4-87.2 mg RE/g. A QUENCHER analysis procedure showed 91.7-168.5 mg RE/g of the total phenolic compound content, 12.7-21.4 mg RE/g of flavonoids, and 48.4-121.0 mg RE/g of radical scavenging activity. 'Fredos taurieji' and 'Fredos derlingieji' varieties have shown maximum values of phenolic compounds and radical scavenging activity both in leaf and cone suspensions. These varieties accumulated a higher amount of xanthohumol in leaves. The concentration of xanthohumol in the samples varied between 0.0014-0.2136% of dry mass, with the highest concentration in the cones of 'Kauno gražieji'. We identified 19 volatile compounds in leaves, and in cones, we identified 32. In both of them, α-humulene and β caryophyllene dominated. 'Raudoniai' leaves were exceptional in their aroma due to dominating compound nagina ketone (Kovats index 1306). The QUENCHER procedure has shown a great potential for the unextractable residue of hop raw material. Further investigation and valorization of different hop biomass components, not only cones, are essential.


The effect of vitamin B supplementation on homocysteine metabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid.
To investigate the influence of vitamin B supplementation on the plasma total homocysteine (p-tHcy), serum folate (s-FA), serum B12 (s-B12), and clinical state of patients with chronic epilepsy. Beck Depression Inventory (BDI) scores and p-tHcy, s-B12, and s-FA levels were assessed at baseline, after 1 year of supplementation (G1), and before and after 1 year of VPA or CBZ therapy (G2). Eighty-one patients participated in the study: 51 patients with chronic epilepsy (G1) treated with carbamazepine (CBZ) or valproic acid (VPA), and 30 patients with newly diagnosed epilepsy (G2). At baseline, mean p-tHcy level was significantly higher in G1 than G2 (p=0.0001) with no significant differences in s-FA or s-B12 levels. p-tHcy level significantly decreased in CBZ-treated G1 patients (p=0.00002) after 1 year of supplementation and increased in G2 after 1 year of anti-epileptic drug (AED) therapy without supplementation. BDI scores in G1 decreased significantly after 1 year of supplementation (p=0.0001) and increased significantly in VPA-treated G2 patients after 1 year of AED therapy (p=0.02). The number of hyperhomocysteinemic patients significantly decreased in G1 after vitamin B supplementation (p=0.01) and increased in G2 (p=0.002). We also observed improved BDI scores and reduced seizure frequency in patients with chronic epilepsy. These data support the hypothesis that AEDs play a major role in hyperhomocysteinemia development in patients with epilepsy. Adding folate and vitamin B12 to AED therapy is a safe and inexpensive way to reduce the risk of hyperhomocysteinemia.


System Support Mapping: A Novel Systems Thinking Tool Applied to Assess the Needs of Maternal and Child Health Title V Professionals and Their Partners.
The Maternal and Child Health (MCH) workforce aims to improve health outcomes for women, children, and families. The work requires coordination and partnerships that span disciplines and service systems. As such, workforce needs assessment requires an approach that is broad, flexible, and "systems-aware." To illustrate the use of System Support Mapping, a novel systems thinking tool that was used to guide participants through a structured assessment of their discrete responsibilities, key needs, and specific resources required for each. Thirty-four Title V MCH professionals and partners from 15 states or jurisdictions. Description and frequency of Title V MCH professionals' coded roles, responsibilities, needs, resources, and wishes. An aggregated map illustrating interconnections between identified codes is presented. State- and local-level MCH professionals reported a range of roles, responsibilities, needs, resources, and wishes. The most and least frequently reported roles, responsibilities, needs, resources, and wishes by state- and local-level MCH professionals are listed, as well as the most frequent connections between those responses. The most frequent responsibility reported in local maps was "link to or provide care or resources" (82%), whereas the most frequent responsibility reported in state maps was "system management" (65%). System management was indirectly connected to 3 wishes: "access to data or information," "funding or resources," and "collaboration, coordination, or support from community or other external organizations." System Support Mapping can be used to support needs assessment with MCH professionals. System Support Maps show not only the most and least frequently reported roles, responsibilities, needs, resources, and wishes of participants but also how those responses are connected and potentially interdependent. System Support Maps may be useful for MCH leaders determining how best to organize their teams to take on complex public health challenges and prioritize improvements that will better support their work.


An ataxia telangiectasia model: inefficient cell differentiation and possible reversal by serine protease inhibitors, tumor necrosis factor inhibitors, dexamethasone, and glutathione enhancers.
Ataxia telangiectasia (AT) is a rare genetic disorder. Symptoms of the disease include cerebellar ataxia, depressed immunoresponsiveness, increased sensitivity to radiation, and leukemias. Various kinds of AT cells show reduced efficiency of differentiation. The ataxia telangiectasia gene (ATM) may reduce differentiation by suppressing cell responsivity to insulin. Insulin sensitivity seems lower in AT. Tumor necrosis factor may overactivate NF-kappa B in AT, and this increases the radiosensitivity of AT cells. Intracellular reduced glutathione may also become depleted. The reduced levels of glutathione may further alter differentiation of AT cells. Serine protease inhibitors may counteract the effects of tumor necrosis factor. Glutathione enhancers may also prove valuable as therapy.


Investigation of the inhibitory effect and mechanism of epigallocatechin-3-gallate against Streptococcus suis sortase A.
Streptococcus suis seriously harms people and animals, and importantly, causes great economic losses in the pig industry. Similar to most Gram-positive pathogenic bacteria, sortase A (SrtA) of S. suis can mediate the anchoring of a variety of virulence factors that contain specific sorting sequences to the surface of the bacterial cell wall envelope and participate in pathogenicity. The purpose of this study is to clarify the molecular mechanism of epigallocatechin-3-gallate (EGCG) inhibiting S. suis SrtA and provide more evidence for the development of novel anti-S. suis infections drugs. Through the SrtA substrate cleavage experiment, we found that the main component of green tea, EGCG, can effectively inhibit the enzyme activity of S. suis SrtA. Further, molecular docking and molecular dynamics simulation were used to clarify the molecular mechanism of its inhibitory effect, demonstrating that EGCG mainly interacts with amino acids at 113 and 115 to exert its inhibitory function. It was previously found that EGCG can inhibit the growth of S. suis and reduce the activity of suilysin and inhibit its expression. Our research reveals a new function of EGCG in S. suis infection. Our research proves that EGCG can effectively inhibit the transpeptidase activity of SrtA. We also clarify the accompanying molecular mechanism, providing more sufficient evidence for the use of EGCG as a potential lead compound against S. suis infection.


Determinants of drug utilisation in a Swedish municipality.
The cost for pharmaceuticals is rapidly increasing in most countries. Identification of the characteristics of the population that determine drug utilisation appears essential for the appropriate allocation of resources to caregivers. The primary aim of this study was to identify sociodemographic factors and measures of well-being and disease that were independently related to the use of drugs, including herbal, and self-care products in Håbo, a Swedish primary health care district. Another aim was to evaluate combinations of such factors that may improve the prediction of drug utilisation. A postal questionnaire was sent to a representative age-stratified population sample from Håbo. Out of 1312 subjects in the population sample, 827 (63%) answered the questionnaire. The questionnaire contained questions on sociodemographic variables, well-being and symptoms and use of drugs, herbal and self-care products. Chronic disease was the most important of several factors that identified users of drugs. Other important factors were female sex, poor perceived health, sick-leave or disability pension and a high number of symptoms (complaint score). When combined, these variables could explain 18% of the use of prescribed pharmaceuticals using the logistic regression model. Several sociodemographic characteristics as well as perceived health, complaint score and chronic disease were independently related to the use of drugs and self-care products. The likelihood of using prescribed drugs was very high in subjects with a certain profile. Eighteen per cent of the use could be attributed to this profile.


Identification of predominant lactic acid bacteria isolated from traditionally fermented vegetable products of the Eastern Himalayas.
Gundruk, sinki and khalpi are lactic-fermented vegetable products of Sikkim in India, and inziangsang is a fermented leafy vegetable product of Nagaland and Manipur in India. A total of 65 samples of gundruk (25), sinki (12), khalpi (25) and inziangsang (3) were analysed for microbial counts. The population of lactic acid bacteria (LAB) as well as aerobic mesophilic counts were at the level of 10(7) cfu g(-1). Yeasts were detected only in few samples of sinki and khalpi. No moulds were detected. In order to identify the predominating organisms, a total of 269 strains of LAB were isolated from gundruk, sinki, khalpi and inziangsang samples. The phenotypic characteristics of these strains were determined followed by genotyping using RAPD-PCR, repetitive element PCR and species-specific PCR techniques. The major representatives of the LAB involved in these fermentations were identified as Lactobacillus brevis, Lactobacillus plantarum, Pediococcus pentosaceus, Pediococcus acidilactici and Leuconostoc fallax.


An electrophysiology report-generating system with data base capabilities.
This article describes the Electrophysiology Report-Generating system (EPREG) which produces reports of clinical cardiac electrophysiologic studies. Reports generated by EPREG are permanently stored on floppy disk media. Selected information from the reports is used to generate an on-line data base upon which selective searches may be made. Use of the system saves an estimated 2 to 3 hours per week compared to an equivalent manual approach. The system has been implemented on a programmable word processor (Wang OIS-140) which is also used for other activities within our medical division.


A horseradish peroxidase labeling technique for correlation of motoneuron metabolic activity with muscle fiber types.
Modifications in the tetramethylbenzidine technique by Mesulam et al. (1980) for demonstration of retrogradely transported horseradish peroxidase (HRP) in alpha-motoneurons have been made. The methodology was designed to permit use of quantitative enzyme histochemical techniques on sections serial to those used for demonstration of HRP. Injections of HRP into different muscles on contralateral limbs, each of which are composed almost exclusively of one muscle fiber type, have allowed us to determine relative enzyme activities in the motoneurons innervating specific muscle fiber types. The modifications should be useful to others using HRP as a peripheral or central nervous system tracer since significant time and chemical costs are saved, the slide-mounted sections are easier to handle, and the sensitivity is superior to currently available methods.


Modification of cardiac Ca2+ release channel gating by DIDS.
The effects of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) on individual cardiac sarcoplasmic reticulum Ca2+ release channels have been examined in planar lipid bilayers. A sudden step-like increase in open probability (Po) induced by DIDS was observed. At zero holding potential it proceeded with an apparent time constant of 84 s and Po was increased 15 times in the steady state. Independent of membrane voltage, DIDS induced a long-lived open state with tau o = 15 ms at 0 mV and tau o = 5 ms at -50 mV (cis (cytoplasmic) side negative). While at 0 mV the modified channel spent most of the time in this long-lived state, at -50 mV the occupancy of the long-lived state was very low and most openings occurred to the short and medium open state, leading to deactivation of the channel to only 2-3 times of control. Voltage-induced changes in the activity of modified channels were reversible and proceeded with time constants of 14 s for deactivation and 12 s for activation, that is, faster than onset of activation by DIDS. As no changes in single channel conductance of the channel were observed in the presence of DIDS and its abrupt activating action could not be removed, a covalent modification of an amino group residing in the gating structure of the channel by DIDS can be considered.


Functional autoantibodies, a new paradigm in autoimmunity?
The recent detection of stimulatory autoantibodies as a characteristic feature of systemic sclerosis (scleroderma), established the presence of such autoantibodies as a characteristic pathophysiologic finding in a second classical autoimmune disease after autoimmune thyroid disease. This observation raises the possibility of a new paradigm in abnormal autoimmune function, the presence of stimulatory (and suppressive), functional autoantibodies as characteristic features of abnormal autoimmune function. The assumption of such a paradigm opens interesting new research avenues within rheumatology and in other medical specialty areas. Within reproductive medicine, and akin to the concept of hypo- and hyperthyroidism, the possible juxtaposition of polycystic ovarian syndrome (PCOS) and premature ovarian aging (POA), as opposite abnormalities of adrenal function, under control of autoimmune adrenal antibodies, deserves further investigation.


Spectral peaking in an ultrashort-pulse fiber laser oscillator with a molecular gas cell.
Here we report the demonstration of a spectral peaking phenomenon in a fiber laser oscillator. An HCN gas cell was inserted in an ultrashort-pulse Er-doped fiber laser with single-wall carbon nanotubes. Sech2-shaped ultrashort pulses with intense multiple sharp spectral peaks were stably generated. When the generated pulses were coupled into highly nonlinear fiber, enhanced multiple spectral peaks were generated by periodical spectral peaking in the optical fiber. The characteristics and physical mechanism of spectral peaking in the fiber laser were investigated via numerical simulations. As the magnitude of absorption was increased, the magnitude of the generated spectral peaks increased almost exponentially. It was clarified that the spectral peaks were generated through the accumulation of filtering components generated in each round trip.


Impact of urologic resident training on patient pain and morbidity associated with office-based cystoscopy.
To determine whether pain and morbidity experienced by patients undergoing cystoscopy were affected by whether a staff urologist or resident was the primary surgeon. Patients scheduled to undergo cystoscopy were assigned to either the staff urologist or a resident as the primary surgeon. After cystoscopy, patients were given a visual analogue scale (VAS, 0 to 100 mm) to assess pain. A two-part model was fit to investigate the effect that staff or resident had on pain scores. Confounding factors, such as age, gender, viewing of the procedure on video, and resident training year, were accounted for with multivariable regression techniques. There was no statistically significant difference between the VAS scores for patients undergoing cystoscopy regardless of whether staff or resident performed the procedure. Further comparisons indicated no statistically significant differences in the effect that resident training year had on pain scores. Office-based cystoscopy can be performed by residents under staff supervision, with pain and morbidity comparable to when a staff urologist performs the procedure. The impact of urologic resident training on patient care is an area that is relatively unexplored in the literature.


Allowance for effects of thermodynamic nonideality in sedimentation equilibrium distributions reflecting protein dimerization.
This reexamination of a high-speed sedimentation equilibrium distribution for α-chymotrypsin under slightly acidic conditions (pH 4.1, I(M) 0.05) has provided experimental support for the adequacy of nearest-neighbor considerations in the allowance for effects of thermodynamic nonideality in the characterization of protein self-association over a moderate concentration range (up to 8 mg/mL). A widely held but previously untested notion about allowance for thermodynamic nonideality effects is thereby verified experimentally. However, it has also been shown that a greater obstacle to better characterization of protein self-association is likely to be the lack of a reliable estimate of monomer net charge, a parameter that has a far more profound effect on the magnitude of the measured equilibrium constant than any deficiency in current procedures for incorporating the effects of thermodynamic nonideality into the analysis of sedimentation equilibrium distributions reflecting reversible protein self-association.


Balancing harms and benefits of service mammography screening programs: a cohort study.
The use of screening mammography is still under debate within the medical community. The aim of this study is to define a balance sheet of benefits (breast cancer mortality reduction) and harms (overdiagnosis) for mammography screening programs. We compared breast cancer incidence and mortality in two cohorts of women, defined as 'attenders' or 'non-attenders' on the basis of the individual attitudes towards screening, who were invited to the first round of the Florentine screening program. The effects of screening exposure on breast cancer incidence and mortality were evaluated by fitting Poisson regression models adjusted for age at entry, marital status and deprivation index. We performed a sensitivity analysis excluding 34 women not responding to the invitation with a breast cancer diagnosis in the following six months. In total, we included 51,096 women aged 50 to 69 years invited at the first screening round (1991 to 1993) and followed-up for breast cancer incidence and mortality until 31 December 2007 and 31 December 2008, respectively The estimate of mortality reduction varies from 45% among 50 to 59 year-old women up to 51% among 60 to 69 year-old women. The estimate of overdiagnosis, according to the cumulative-incidence method, is an additional 10% of all breast cancer cases among 60 to 69 year-old women screened. Comparing the breast cancer mortality and breast cancer incidence between attenders and non-attenders, we have determined that the overall cost to save one life corresponds to no more than one over-diagnosed tumor (from 0.6 to 1 depending on the selection criteria of the cohort), even if a residual self-selection bias cannot be excluded.


Role of H1 and H2 receptors in increased small airways resistance in the dog.
The relative importance of H1 and H2 receptors to central and peripheral airways resistance in the anesthetized intact dog lung were determined through the use of pharmacologically specific antagonists during graded intravenous infusions of histamine. The indirect effects of infused histamine were also tested via alpha and beta adrenergic blockade (alpha + beta blk) and post-ganglionic parasympathetic blockade (vagal blk). We measured pulmonary resistance (RL), dynamic compliance (Cdyn), thoracic gas volume (Vtg), and partitioned oscillatory pulmonary resistance (RLosc) into a peripheral (Rp) and central component with an intrabronchial catheter. Infused histamine caused a significant increase in RL, primarily the result of the increase in Rp, with substantial dose-dependent reductions in Cdyn, and increases in Vtg. These effects were not altered by vagal blk, were increased by alpha + beta blk, and were completely prevented by H1 receptor blockade, but not by H2 receptor blockade. We conclude that histamine infusion causes bronchoconstriction in the canine lung, primarily in peripheral airways (less than 3 mm diameter), by its direct action on H1-type receptors.


Low levels of pro-resolving lipid mediators lipoxin-A4, resolvin-D1 and resolvin-E1 in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is a disease in which joint inflammation is at the forefront but the whole body is affected, and prevention of inflammation is the main treatment approach. Lipoxins (LXs) and resolvins (Rvs) are critical molecules in the resolution of inflammation. In this study, we aimed to investigate the role of LXs and Rvs in the RA pathogenesis. To this end, we measured the LXA 4, RvD 1, RvE 1 levels, and inflammatory cytokines and chemokines IL-6, IL-8, IL-10, IL-17a, IL-22 and MCP-1 in patients with RA and healthy individuals. We found that the LXA4, RvD1, RvE1 levels of the active RA cases were significantly lower than in remission RA and healthy individuals, but the levels of inflammatory cytokines and chemokines were significantly higher. The decreases in LXs and Rvs were independent of disease activity, suggesting that there might be an impairment of LX and Rvs synthesis or catabolism in patients with RA.


Anesthesia outcomes of pregnant women with spinal diseases: a single-center case-series study.
Neuraxial anesthesia is widely used as the most effective and standard method in obstetric anesthesia. However, there is a concern that neuraxial anesthesia may be technically difficult or ineffective in pregnant women with spinal disease. Therefore, this study aimed to investigate the implementation rate of neuraxial anesthesia among pregnant women with spinal diseases and their success rate at our institution. The subjects of this study were pregnant patients who delivered at Juntendo University Nerima Hospital between April 2017 and December 2020. After obtaining ethics committee approval, data were collected from patients' medical records. Of the 2682 pregnant women who delivered, 1550 underwent preanesthetic evaluation. There were 42 deliveries in 39 pregnant women with spinal diseases (1.7% of all pregnant women and 2.7% of those who underwent preanesthetic evaluation). The diagnoses included adolescent idiopathic scoliosis (51.3%), lumbar disc herniation (23.1%), and others. The mode of delivery was the elective cesarean section in 5 cases, emergent cesarean section in 8 cases, and vaginal delivery in 29 cases. Only one case required general anesthesia. Of the 38 cases of labor analgesia, the neuraxial block was inadequate in 3 cases (7.9%) and technically difficult in 3 cases (7.9%). However, the patients complained of no lower extremity neuropathy, infection, or inadvertent dural puncture. Neuraxial anesthesia was an option in most cases, even in pregnant women complicated with spinal disease, if an anesthesiologist's plan before delivery after careful preanesthetic evaluation.


Quantitative comparison of zero-loss and conventional electron diffraction from two-dimensional and thin three-dimensional protein crystals.
The scattering cross-section of atoms in biological macromolecules for both elastically and inelastically scattered electrons is approximately 100,000 times larger than that for x-ray. Therefore, much smaller (<1 microm) and thinner (<0.01 microm) protein crystals than those used for x-ray crystallography can be used to analyze the molecular structures by electron crystallography. But, inelastic scattering is a serious problem. We examined electron diffraction data from thin three-dimensional (3-D) crystals (600-750 A thick) and two-dimensional (2-D) crystals (approximately 60 A thick), both at 93 K, with an energy filtering electron microscope operated at an accelerating voltage of 200 kV. Removal of inelastically scattered electrons significantly improved intensity data statistics and R(Friedel) factor in every resolution range up to 3-A resolution. The effect of energy filtering was more prominent for thicker crystals but was significant even for thin crystals. These filtered data sets showed better intensity statistics even in comparison with data sets collected at 4 K and an accelerating voltage of 300 kV without energy filtering. Thus, the energy filter will be an effective and important tool in the structure analysis of thin 3-D and 2-D crystals, particularly when data are collected at high tilt angle.


Recruitment and retention of rural general practitioners: a marketing approach reveals new possibilities.
This paper repositions the challenge of attracting and retaining rural GPs in a marketing context as a new focus for future research and policy development. Case study with mixed design of surveys of GPs and medical students and depth interviews with GPs, medical students, regional-division administrators and GP recruitment agents. GP recruitment and retention in the Limestone Coast region of South Australia. Twenty-seven Limestone Coast (LC) GPs; random sample of medical students from Adelaide University, Adelaide University Rural Health Society and Flinders University; snowball sampling two adjacent rural regions (20 GPs); and administrators from LC and adjacent regions and GP recruitment agencies in Adelaide. Drawing from marketing theory, creative suggestion of 'promotion of the practice and not the region' offers a means of GP recruitment and retention for structured succession planning for rural general practices. Structural attempts to broaden the GP market with overseas recruitment have done little for improving full-time equivalent GP levels. Market segmentation and market orientation offer a new emphasis on value exchange between the corporation (the practice), customer (GPs) and competition (all practices) to influence future mobility. A marketing orientation to the GP challenge emphasises individual's perceptions of value, GP expectations and practice offerings. Failure to acknowledge benefits of this marketing approach means that solutions such as those developed in the Limestone Coast region are unlikely. Research is now required to define GP satisfaction and value for long-term viability of general practices.


Primary lymphoma of bone: the use of MRI in pretreatment evaluation.
Primary lymphoma of bone (PLB) is an uncommon neoplasm representing only 5% of all extranodal non-Hodgkin's lymphomas. The precise role of magnetic resonance imaging (MRI) scanning is unknown. A review of the literature and a recent case treated at the University of Alabama at Birmingham in which MRI unveiled other foci of disease undetected by routine staging studies is presented.


Inhibitory effects of sanguinarine on human liver cytochrome P450 enzymes.
Sanguinarine (SAG) has been recognized as an anticancer drug candidate. However, the drug-drug interactions (DDI) potential for SAG via the inhibition against human cytochrome P450 (CYP) enzymes remains unclear. In the present study, the inhibitory effects of SAG on seven major human CYP isoforms 1A2, 2A6, 2E1, 2D6, 2C8, 2C9 and 3A4 were investigated with human liver microsomes (HLM). The results showed that SAG was a potent noncompetitive inhibitor of CYP2C8 activity (Ki=8.9 μM), and competitive inhibitor of CYP1A2, CYP2C9 and CYP3A4 activities (Ki=2.7, 3.8 and 2.0 μM, respectively). Furthermore, SAG exhibited time- and NADPH-dependent inhibition towards CYP1A2 and CYP3A4 with KI/kinact values of 13.3/0.087 and 5.58/0.029 min(-1) μM(-1), respectively. Weak inhibition of SAG against CYP2E1, CYP2D6 and CYP2A6 was also observed. In vitro-in vivo extrapolation (IV-IVE) from HLM data showed that more than 35.9% of CYP1A2, CYP2C9, CYP2C8 and CYP3A4 activities in vivo could be inhibited by SAG, suggesting that harmful DDIs could occur when SAG or its medical preparations are co-administered with drugs primarily cleared by these CYP isoforms. Further in vivo studies are needed to evaluate the clinical significance of the data presented herein.


Retracted: Influence Mechanism of Educational Leadership on Environmental Accounting Based on Big Data Algorithm.
[This retracts the article DOI: 10.1155/2022/5690230.].


Determination of fluorine in tea using high-resolution molecular absorption spectrometry with electrothermal vaporization of the calcium mono-fluoride CaF.
High-resolution continuum source molecular absorption of the calcium mono-fluoride molecule CaF in a graphite furnace has been used to determine fluorine in tea after acid digestion, alkaline solubilization and preparation of a conventional aqueous infusion. The strongest absorption 'line' of the CaF molecule is at 606.440 nm, which is part of the rotational fine structure of the X(2)Σ(+)-A(2)Π electronic transition; it has a bond dissociation energy of 529 kJ mol(-1), which is comparable with other molecules used for fluorine determination. One advantage of using Ca as the molecule-forming reagent is that spectral interferences are extremely unlikely in the spectral range of its strongest absorption. Another advantage is that Ca acts both as molecule forming reagent and chemical modifier, so that no other reagent has to be added, making the method very simple. The only disadvantage is that Ca has a somewhat negative influence on the graphite tube lifetime. The limit of detection was found to be 0.16 mg L(-1) F, corresponding to 1.6 ng F absolute, and the calibration curve was linear in the range between 0.5 and 25 mg L(-1) with a correlation coefficient of R=0.9994. The results obtained for a certified tea reference material were in agreement with the certified value on a 95% confidence level. There was also no difference between the results obtained after an acid digestion and an alkaline solubilization for 10 tea samples, based on a paired t-test. The values found in the 10 samples ranged between 42 μg g(-1) and 87 μg g(-1) F; the tea infusions contained between 21 μg g(-1) and 56 μg g(-1) F, with an extraction rate between 48% and 74%.


Interaction of glutathione peroxidase-1 and selenium in endemic dilated cardiomyopathy.
Keshan disease (KD) is a fatal dilated cardiomyopathy with unknown etiology. We studied the gene-environment interaction in the pathogenesis of KD by assessing the association of low blood selenium and polymorphisms in glutathione peroxidase-1 (GPx-1) gene. The concentration of blood selenium and the activity and polymorphisms of GPx-1 in 71KD patients and 290 controls were measured. The functions of rat neonatal cardiomyocytes resulting from overexpression of 2 variants of GPx-1 were studied. Blood concentration of selenium and GPx-1 activity were lower in patients than in controls. Genetic analysis revealed a single nucleotide polymorphism (Pro198Leu) in GPx-1 gene associated with selenium deficiency as well as impaired GPx-1 activity. Gene-environment interaction analysis revealed a synergistic-multiplicative interaction between polymorphism of GPx-1 and selenium deficiency. Overexpression of the GPx-1 leucine-containing allele in cultured cardiomyocytes caused a 30% reduction in selenium-induced GPx-1 activity and increased serum starvation induced apoptosis as compared with that of the wild-type variant 198Pro. Selenium deficiency in carriers with the GPx-1 leucine-containing allele is associated with low GPx-1 enzyme activity, which may, in turn, increase the incidence of KD. Results from this unique disease may have broad implications for a gene-environment reaction in the etiology of other diseases.


Reducing short- and long-term cocaine craving with voluntary exercise in male rats.
In a previous study in female rats, voluntary wheel running attenuated incubation of cocaine craving after 30 but not 3 days (Zlebnik and Carroll Zlebnik and Carroll, Psychopharmacology 232:3507-3413, 2015). The present study in male rats, using the same procedure, showed that wheel running reduced incubated craving after both 30 and 3 days of abstinence. Male rats self-administered i.v. cocaine (0.4 mg/kg) during 6-h sessions for 10 days. They were then moved from the operant chamber to a home cage with an attached running wheel or stationary wheel, for 6 h daily for a 3- or 30-day period when cocaine craving was hypothesized to incubate. Rats were then returned to the operant chamber for a 30-min test of cocaine seeking, or "craving," indicated by responses on the former "drug" lever was formerly associated with drug stimulus lights and responses (vs. no drug stimuli), and lever responding was compared to responses on the "inactive" that was illuminated and counted lever pressing. Mean wheel revolutions were similar across the 3- and 30-day incubation groups, when both groups of rats were given access to wheel running vs. access to a stationary wheel in controls. Subsequently, when rats were tested in the operant chamber for "relapse" responding (drug-lever responding) on the lever formerly associated with drug access, cocaine craving was reduced by recent running wheel access (vs. stationary wheel access) in both the 3- and 30-day wheel exposure groups. Voluntary, self-initiated, and self-sustained physical exercise reduced cocaine craving after short- (3 days) and long-term (30 days) abstinence periods in male rats that previously self-administered cocaine. This was contrasted with reduction of cocaine seeking in females after 30-day, but not 3-day, incubation periods under the wheel running vs. stationary wheel conditions in a previous study (Zlebnik and Carroll Zlebnik and Carroll, Psychopharmacology 232:3507-3413, 2015). These initial findings suggest males may be more sensitive to incubated craving for cocaine than females.


mTORC1 maintains metabolic balance.
Anticancer therapeutics aimed at the inhibition of mTORC1 activity shift metabolism to favor the degradation of extracellular proteins. Recently Thompson and colleagues demonstrated a novel regulatory mechanism whereby mTORC1 plays a distinct role as a key regulator of metabolism depending on the environmental nutrient status.


Lupinus albus gamma-tubulin: mRNA and protein accumulation during development and in response to darkness.
We have isolated a genomic DNA fragment encoding a gamma-tubulin in white lupin ( Lupinus albus L.). The predicted polypeptide encoded by the La-TubG1 gene possesses between 91 and 95% identity with other higher-plant gamma-tubulins. The mRNA and protein level of lupin gamma-tubulin is highly correlated with beta-tubulin as well as with the growth rate of the tissue. Both La-TubG1 transcript and gamma-tubulin protein expression levels are down-regulated in the embryonic axis of dry seeds as compared with the embryonic axis of germinated seeds. In 7-day-old seedlings, the La-TubG1 gene is ubiquitously expressed, with the highest level found in immature leaves. In contrast, La-TubG1 gene expression is down-regulated in mature leaves. The gamma-tubulin protein level follows a similar age-dependent accumulation, decreasing during leaf development. The expression of the gamma-tubulin gene in the hypocotyl is down-regulated by light. Nevertheless, the protein levels were not significantly altered by light, suggesting that gamma-tubulin accumulation might be controlled at both transcriptional and protein levels. Immunocytochemistry studies showed that lupin gamma-tubulin displays the localization observed in most plant microtubule arrays, corroborating a functional conservation in different species.


Association between genetic polymorphisms of leptin receptor and preeclampsia in Chinese women.
Leptin signaling plays an important role in regulating metabolism and reproduction. In the present study, we investigated the relationship between polymorphisms of leptin receptor (LEPR) gene A223G and A668G and preeclampsia (PE) and evaluated influences of genotypes on clinical, metabolic, and oxidative stress indices in Chinese women. This is a case-control study including 322 patients with PE and 1295 healthy pregnant women. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragments length polymorphism method. Clinical and biochemical parameters were analyzed. The frequencies of the AA + AG genotypes (28.6% vs. 36.1%) and A allele (14.9% vs. 19.8%) of LEPR A223G polymorphism, and those of the AA + AG genotypes (17.7% vs. 24.6%) and A allele (9.0% vs. 12.9%) of LEPR A668G polymorphism were significantly lower in the PE group than those in the control group. The 223A and 668A alleles were protective factors against PE in the regression model, which included age and delivery body mass index as covariates (OR = 0.684, 95% CI: 0.506-0.926, p = .014; OR = 0.650, 95% CI: 0.456-0.927, p = .017, respectively). When the 668GG/223GG combined genotype served as the reference category, the 668A/223A combined allele had further enhanced the protective effect on PE (OR = 0.558, 95% CI: 0.374-0.833, p = .004). Patients possessing the LEPR 223A allele had higher total antioxidant capacity and lower oxidative stress index (p < .05), while those with the LEPR 668A allele had higher high-density lipoprotein cholesterol levels (p = .045) compared with those carrying the corresponding GG genotype. The 223A and 668A alleles of LEPR polymorphisms are genetic protective factors for PE in Chinese women. The two alleles may exert a beneficial effect on oxidative stress and lipid metabolism in patients.


Acute Kidney Injury After Pulmonary Thromboendarterectomy: Associated Factors and Impact.
Acute kidney injury (AKI) is a common complication after pulmonary thromboendarterectomy (PTE) that has been shown to be associated with worse outcomes. Our study assesses factors associated with the development of postoperative AKI after PTE and its impact on clinical outcomes. We retrospectively analyzed 247 patients who underwent PTE at our institution between June 2009 and December 2020. Baseline characteristics, risk factors, and outcomes were compared between patients with and without postoperative AKI. The primary endpoint was development of postoperative AKI using the Kidney Disease Improving Global Outcomes definition, and secondary endpoints were length of hospital stay, hospital mortality, and 5-year mortality. The overall incidence of postoperative AKI in our study population was 49%. One hundred twenty-three patients (50.8%) did not develop AKI postoperatively, 87 patients (35.9%) developed stage 1 AKI postoperatively, 21 patients (8.7%) developed stage 2 AKI postoperatively, and 11 (4.5%) developed stage 3 AKI postoperatively. Patients who developed AKI postoperatively had longer hospital stays, higher in-hospital mortality rates, and higher 5-year mortality rates than patients who did not develop postoperative AKI. Higher body mass index, older age, low preoperative hemoglobin, low ejection fraction, and low creatinine were shown to be associated with postoperative AKI development. Patients who developed AKI after PTE had worse mortality and morbidity. Clinicians should have a lower threshold for suspecting AKI and consider implementing Kidney Disease Improving Global Outcomes-based AKI prevention bundles for patients with factors associated with development of AKI.


COVID-19 among healthcare workers in a specialist infectious diseases setting in Naples, Southern Italy: results of a cross-sectional surveillance study.
A coronavirus disease 2019 (COVID-19) surveillance study was performed in March-April 2020 among asymptomatic healthcare workers (HCWs) at a specialist infectious diseases hospital in Naples, Italy. All HCWs underwent two rounds of molecular and serological testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). One hundred and fifteen HCWs were tested; of these, two cases of infection were identified by reverse transcriptase polymerase chain reaction and two HCWs were SARS-CoV-2 immunoglobulin G seropositive. The overall prevalence of current or probable previous infection was 3.4%. The infection rate among HCWs was reasonably low. Most of the infected HCWs had been asymptomatic for the preceding 30 days, which supports the need for periodic screening of HCWs for COVID-19.


Salmonella and Campylobacter contamination of broiler chicken carcasses and scald tank water: the influence of water pH.
Scalding at 50 degrees +/- 0.5 degrees C, in water maintained at pH 9.0 +/- 0.2 by the addition of sodium hydroxide, had no effect on the incidence of salmonella or campylobacter contamination of chicken carcasses. There were significant reductions, however, in the numbers of these organisms in the water itself.


Early predictors of outcomes in pediatric lupus nephritis: focus on proliferative lesions.
Studies regarding the clinical features and outcomes of pediatric lupus nephritis are limited, and risk factors of poor outcome in the more severe form of renal involvement, proliferative lupus nephritis (PLN), are poorly understood. This study analyzed the data from a large prospective cohort of childhood systemic lupus erythematosus to determine such risk factors. Subjects younger than 18 years at onset with biopsy-proven lupus nephritis were enrolled. Data on baseline presentations and laboratory values, response to treatment, and outcomes were collected. Primary outcome measures were death or end-stage renal disease (ESRD). Survival analysis was done and predictors were approached. One hundred four patients with mean age of 12.4 ± 2.5 years (range, 4.0-17.2 years) and the female-to-male ratio of 5.94:1 were included. Among them, 81 patients had PLN and 23 had non-proliferative lupus nephritis. Those with PLN had significantly lower GFR, more proteinuria, more urine sediment, more hypertension, and poor early response to treatment (within 6 months). There was no significant difference in extra-renal manifestations. All poor outcomes happened in the PLN group. The prognostic factors were high baseline SLEDAI-2k >20 (HR, 6.76; p = 0.002), baseline GFR <60ml/min/m² (HR, 3.88; p = 0.022), and early responder (HR, 0.19; p = 0.013). Patients with pediatric lupus nephritis and high risk factor can be identified early by concomitantly considering their baseline features and early response, which provides a novel hint in decision for management decisions.


Oxidative stress induced by self-adhesive resin cements affects gene expression, cellular proliferation and mineralization potential of the MDPC-23 odontoblast-like cells.
Clinical issues have been raised about problems related to cytotoxic effects caused when applying self-adhesive cement. It was hypothesized that byproducts eluted from self-adhesive cements modulate oxidative stress response, the gene expression of signaling pathways of inflammatory process/transcriptional activators, and the expression and activity of interstitial collagenases, and modify the phenotypic characteristics of cellular proliferation and mineral deposition in odontoblastic-like cells. Cements (MaxCem Elite [MAX] and RelyX U200 [U200)]) were mixed, dispensed into moulds, and photoactivated according to the manufacturers' instructions. Immortalized rat odontoblast-like cells (MDPC-23) were cultured and exposed to polymerized specimens of cements for 4 h. Reactive oxidative specimen production and quantification of gene expression were evaluated. Cell proliferation assay and alizarin red staining were also performed to evaluate the disturbance induced by the cements on cellular proliferation and mineralization. Despite their cytotoxic effects, both self-adhesive cements influenced the metabolism in the odontoblast cells on different scales. MAX induced significantly higher oxidative stress in odontoblast cells than U200. Gene expression varied as a function of exposure to self-adhesive cements; MAX induced the expression of pro-inflammatory cytokines such as TNF-α, whereas U200 downregulated, virtually depleted TNF-α expression, also inducing overexpression of the transcriptional factor Runx2. Overexpression of heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TRXR1) occurred after exposure to both cements, antioxidant genes that are downstream of Keap1-Nrf2-ARE system. MAX significantly induced the overexpression of collagenase MMP-1, and U200 induced the expression of gelatinase MMP-2. MAX significantly inhibited cell proliferation whereas U200 significantly activated cell proliferation. Alizarin red staining revealed significantly decreased mineral deposition especially when exposed to MAX. These results support the hypothesis that byproducts of different self-adhesive cements play important roles in the highly orchestrated process which ultimately affect the cellular proliferation and the mineral deposition in odontoblastic-like cells, possibly delaying the reparative dentin formation after cementation of indirect restorations, especially on recently exposed dentin preparations.


Matrisome AnalyzeR - a suite of tools to annotate and quantify ECM molecules in big datasets across organisms.
The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays crucial roles in all aspects of life - from orchestrating cell migration during development, to supporting tissue repair. It also plays critical roles in the etiology or progression of diseases. To study this compartment, we have previously defined the compendium of all genes encoding ECM and ECM-associated proteins for multiple organisms. We termed this compendium the 'matrisome' and further classified matrisome components into different structural or functional categories. This nomenclature is now largely adopted by the research community to annotate '-omics' datasets and has contributed to advance both fundamental and translational ECM research. Here, we report the development of Matrisome AnalyzeR, a suite of tools including a web-based application and an R package. The web application can be used by anyone interested in annotating, classifying and tabulating matrisome molecules in large datasets without requiring programming knowledge. The companion R package is available to more experienced users, interested in processing larger datasets or in additional data visualization options.


Author Correction: A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Advances in optical gastrointestinal endoscopy: a technical review.
Optical endoscopy is the primary diagnostic and therapeutic tool for management of gastrointestinal (GI) malignancies. Most GI neoplasms arise from precancerous lesions; thus, technical innovations to improve detection and diagnosis of precancerous lesions and early cancers play a pivotal role in improving outcomes. Over the last few decades, the field of GI endoscopy has witnessed enormous and focused efforts to develop and translate accurate, user-friendly, and minimally invasive optical imaging modalities. From a technical point of view, a wide range of novel optical techniques is now available to probe different aspects of light-tissue interaction at macroscopic and microscopic scales, complementing white light endoscopy. Most of these new modalities have been successfully validated and translated to routine clinical practice. Herein, we provide a technical review of the current status of existing and promising new optical endoscopic imaging technologies for GI cancer screening and surveillance. We summarize the underlying principles of light-tissue interaction, the imaging performance at different scales, and highlight what is known about clinical applicability and effectiveness. Furthermore, we discuss recent discovery and translation of novel molecular probes that have shown promise to augment endoscopists' ability to diagnose GI lesions with high specificity. We also review and discuss the role and potential clinical integration of artificial intelligence-based algorithms to provide decision support in real time. Finally, we provide perspectives on future technology development and its potential to transform endoscopic GI cancer detection and diagnosis.


Understanding persuasion contexts in health gamification: A systematic analysis of gamified health behavior change support systems literature.
Gamification is increasingly used as a design strategy when developing behavior change support systems in the healthcare domain. It is commonly agreed that understanding the contextual factors is critical for successful gamification, but systematic analyses of the persuasive contexts have been lacking so far within gamified health intervention studies. Through a persuasion context analysis of the gamified health behavior change support systems (hBCSSs) literature, we inspect how the contextual factors have been addressed in the prior gamified health BCSS studies. The implications of this study are to provide the practitioners and researchers examples of how to conduct a systematic analysis to help guide the design and research on gamified health BCSSs. The ideas derived from the analysis of the included studies will help identify potential pitfalls and shortcomings in both the research and implementations of gamified health behavior change support systems. We systematically analyzed the persuasion contexts of 15 gamified health intervention studies. According to our results, gamified hBCSSs are implemented under different facets of lifestyle change and treatments compliance, and use a multitude of technologies and methods. We present a set of ideas and concepts to help improve endeavors in studying gamified health intervention through comprehensive understanding of the persuasive contextual factors. Future research on gamified hBCSSs should systematically compare the different combinations of contextual factors, related theories, chosen gamification strategies, and the study of outcomes to help understand how to achieve the most efficient use of gamification on the different aspects of healthcare. Analyzing the persuasion context is essential to achieve this. With the attained knowledge, those planning health interventions can choose the 'tried-and-tested' approaches for each particular situation, rather than develop solutions in an ad-hoc manner.


Breath analysis of smokers, non-smokers, and e-cigarette users.
Solid phase micro extraction-Gas Chromatography/Mass Spectrometry (SPME-GC/MS) analysis was performed in exhaled breath samples of 48 healthy volunteers: 20 non-smokers, 10 smokers and 18 e-cigarette (EC, vape) users. Each volunteer provided 1 L of exhaled breath in a pre-cleaned Tedlar bag, in which an SPME fiber was exposed to absorb the emitted breath volatile organic compounds (VOCs). The acquired data were processed using multivariate data analysis (MDA) methods in order to identify the characteristic chemicals of the three groups. The results revealed that the breath of non-smokers demonstrated inverse correlation with a variety of molecules related to the breath from smokers including furan, toluene, 2-butanone and other organic substances. Vapers were distinguished from smokers by the chemical speciation of the e-liquids, such as that of esters (e.g. ethyl acetate), terpenes (e.g. α-pinene, β-pinene, d-limonene, p-cymene, etc.) and oxygenated compounds (e.g. 3-hexen-1-ol, benzaldehyde, hexanal, decanal, etc). Two classification models were developed (a) using principal component analysis (PCA) with hierarchical cluster analysis (HCA) and (b) using partial least squares-discriminant analysis (PLS-DA). Both models were validated using 8 new samples (4 vapers and 4 smokers), collected in addition to the 48 samples of the calibration set. The combination of GC/MS breath analysis and MDA contributed successfully in classifying the volunteers into their respective groups and highlighted the relevant characteristic VOCs. The respective dynamic combination (SPME-GC/MS and MDA) provides a means for long term non-invasive monitoring of the population's health status for early detection purposes.


Doxorubicin: a fluorescent neurotoxin retrogradely transported in the central nervous system.
Doxorubicin, a fluorescent cytotoxic antibiotic, was found to be both a retrograde neuron pathway tracer and neurotoxin to cells retrogradely labeled with it. Doxorubicin was injected into rat caudate-putamen and within 4 h the nuclei in the ipsilateral substantia nigra zona compacta (SNc) and ventral tegmental area (VTA) were stained with red fluorescent doxorubicin. After 2 weeks, portions, but not all of the ipsilateral SNc and VTA were depleted of neurons. Retrograde neurotoxicity was obvious following injections of 20%, 10%, 6%, 5% or 4% doxorubicin but not after 1% or 2%. Five months following doxorubicin treatment, the ipsilateral SNc and VTA were shrunken, distorted and nearly absent; the injected caudate was shrunken and replaced by ventricle. The ipsilateral thalamic parafasicular center median nucleus, a complex nucleus also known to project to the caudate, was depleted of large neurons 2 weeks following caudate injection. Doxorubicin can be transported over relatively long distances; lumbar spinal cord injections labeled cortical pyramidal neurons 3 days later. Doxorubicin's unique pathway-specific neurotoxicity may be useful in future neuroscientific studies.


Longitudinal study of multidimensional factors influencing maternal and offspring health outcomes: a study protocol.
Reducing preventable adverse maternal and offspring outcomes is a global priority. The causes of adverse maternal and fetal outcomes are complex with multidimensional influencing factors. In addition, the Covid-19 epidemic has had a significant psychological and physical impact on people. China is now stepping into the post-epidemic era. We are curious about the psychological and physical situation of maternity in China at this stage. Therefore, we plan to initiate a prospective longitudinal study to investigate the multidimensional influences and mechanisms that affect maternal and offspring health. We will recruit eligible pregnant women at Renmin Hospital of Hubei Province, China. The expected sample size is 1490. We will assess socio-demographics, Covid-19 related information, social capital, sleep, mental health and medical records, including clinical examination and biochemical tests. Eligible pregnant women will be enrolled in the study with less than 14 weeks of gestation. Participants will receive a total of nine follow-up visits between mid-pregnancy and one year postpartum. The offspring will be followed up at birth, 6 weeks, 3 months, 6 months and one year. In addition, a qualitative study will be conducted to understand the underlying causes that affect maternal and offspring health outcomes. This is the first longitudinal study of maternity in Wuhan, Hubei Province which integrates physical, psychological and social capital dimensions. Wuhan is the first city to be affected by Covid-19 in China. As China moves into the post-epidemic era, this study will provide us with a better understanding of the long-term impact of the epidemic on maternal and offspring health outcomes. We will implement a range of rigorous measures to enhance participants' retention rate and ensure the quality of data. The study will provide empirical results for maternal health in the post-epidemic era.


Effects of Maillard-type caseinate glycation on the preventive action of caseinate digests in acrylamide-induced intestinal barrier dysfunction in IEC-6 cells.
Dietary acrylamide has attracted widespread concern due to its toxic effects; however, its adverse impact on the intestines is less assessed. Protein glycation of the Maillard-type is widely used for property modification, but its potential effect on preventive efficacy of protein digest against the acrylamide-induced intestinal barrier dysfunction is quite unknown. Caseinate was thus glycated with lactose. Two tryptic digests from the glycated caseinate and untreated caseinate (namely GCN digest and CN digest) were then assessed for their protective effects against acrylamide-induced intestinal barrier dysfunction in the IEC-6 cell model. The results showed that acrylamide at 1.25-10 mmol L-1 dose-dependently had cytotoxic effects on IEC-6 cells, leading to decreased cell viability and increased lactate dehydrogenase release. Acrylamide also brought about barrier dysfunction, including decreased trans-epithelial electrical resistance (TEER) value and increased epithelial permeability. However, the two digests at 12.5-100 μg mL-1 could alleviate this dysfunction via enhancing cell viability by 70.2-83.9%, partly restoring TEER values, and decreasing epithelial permeability from 100% to 76.6-94.1%. The two digests at 25 μg mL-1 strengthened the tight junctions via increasing tight junction proteins ZO-1, occludin, and claudin-1 expression by 11.5-68.6%. However, the results also suggested that the GCN digest always showed lower protective efficacy than the CN digest in the cells. It is concluded that Maillard-type caseinate glycation with lactose endows the resultant tryptic digest with impaired preventive effect against acrylamide-induced intestinal barrier dysfunction, highlighting another adverse effect of the Maillard reaction on food proteins.


Blood, balloons, and blades: State of the art trauma resuscitation.
Traumatic injury remains the leading cause of death in patients 45 and younger. State of the art trauma care requires rapid interventions to provide hemodynamic support en route to definitive hemostasis. This article will review three critical elements in management of the bleeding trauma patient: blood products, resuscitative endovascular balloon occlusion of the aorta (REBOA), and the trauma hybrid operating room (THOR).


Comparison between radiolabelled and endogenous dopamine release from rat striatal slices: effects of electrical field stimulation and regulation by D2-autoreceptors.
Direct comparisons have been made between the release of radiolabelled and endogenous dopamine from superfused rat striatal slices prelabelled with 3H-dopamine. Both spontaneous release and release evoked by electrical field stimulation (3 Hz, 2 min) were measured using a high-sensitivity HPLC system with electrochemical (coulometric) detection, plus scintillation counting of chromatographically separated superfusate fractions. Two periods of electrical stimulation released similar amounts of endogenous dopamine, but the second stimulation released much less 3H-dopamine than did the first, although the levels of spontaneous release immediately before the two stimuli were similar. Substantial increases in endogenous 3,4-dihydroxy phenyl acetic acid (DOPAC) release but only minor increases in 3H-DOPAC release occurred following the two stimuli. The dopamine agonist pergolide (1 microM) reduced the electrically-stimulated release of both 3H-dopamine and endogenous dopamine to a similar extent, whilst the D2-selective antagonist sulpiride (1 microM) produced large increases in both 3H-dopamine and endogenous dopamine electrically-stimulated release. In addition, spontaneous release of both 3H-dopamine and endogenous dopamine were decreased by pergolide and increased by sulpiride. Co-addition of sulpiride and pergolide produced lesser increases than those seen with sulpiride alone. These studies indicate that, despite major differences between 3H-dopamine and endogenous dopamine release in response to various stimuli, their regulation by D2-autoreceptors appears similar; a novel finding being the modulation of spontaneous 3H-dopamine release by autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamics of microbial growth and metabolic activity and their control by aeration.
The optimization of fermentation processes depends to a large extent on the modelling of microbial activity under complex environmental conditions where aeration is an important limiting and control factor. Simple relationships are used to establish the sensitivity of cultures to oxygen stress. Specific limitation coefficients which can be determined in laboratory reactors allow a projection to industrial operation and the definition of appropriate aeration and agitation profiles. Optimum control can be assured on the basis of directly measurable process parameters. This is shown for the case of ethanol production using S. cerevisiae at high cell dry weight concentrations.


C-type lectin receptor-induced NF-κB activation in innate immune and inflammatory responses.
The C-type lectin receptors (CLRs) belong to a large family of proteins that contain a carbohydrate recognition domain (CRD) and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors (PRRs) recognizing carbohydrate ligands from infected microorganisms. Upon ligand binding, these CLRs induce multiple signal transduction cascades through their own immunoreceptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ. Emerging evidence indicate that CLR-induced signaling cascades lead to the activation of nuclear factor kappaB (NF-κB) family of transcriptional factors through a Syk- and CARD9-dependent pathway(s). The activation of NF-κB plays a critical role in the induction of innate immune and inflammatory responses following microbial infection and tissue damages. In this review, we will summarize the recent progress on the signal transduction pathways induced by CLRs, and how these CLRs activate NF-κB and contribute to innate immune and inflammatory responses.


Selective hydrogenation of α,β-unsaturated aldehydes catalyzed by amine-capped platinum-cobalt nanocrystals.
More Greasy, more selective: amine-capped Pt(3)Co nanocatalysts were synthesized and used for the hydrogenation of cinnamaldehyde (CAL). Capping the catalysts with amines that contain long carbon chains results in an ordered surface "array", in which high selectivity towards C=O hydrogenation can be achieved because the C=C bond in CAL does not interact with the surface. The longer the carbon chains in the amine, the higher the selectivity.


Cancer complementary and alternative medicine research at the US National Cancer Institute.
The United States National Cancer Institute (NCI) supports complementary and alternative medicine (CAM) research which includes different methods and practices (such as nutrition therapies) and other medical systems (such as Chinese medicine). In recent years, NCI has spent around $120 million each year on various CAM-related research projects on cancer prevention, treatment, symptom/side effect management and epidemiology. The categories of CAM research involved include nutritional therapeutics, pharmacological and biological treatments, mind-body interventions, manipulative and body based methods, alternative medical systems, exercise therapies, spiritual therapies and energy therapies on a range of types of cancer. The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) supports various intramural and extramural cancer CAM research projects. Examples of these cancer CAM projects are presented and discussed. In addition, OCCAM also supports international research projects.


The screening of visual impairment among preschool children in an urban population in Malaysia; the Kuching pediatric eye study: a cross sectional study.
To screen for visual impairment in Malaysian preschool children. Visual screening was conducted in 400 preschool children aged 4 to 6 years. The screening involved two basic procedures; the distant visual acuity test using the Sheridan Gardiner chart and the depth perception test using the Langs stereoacuity test. Criteria for referral were a visual acuity of 6/12 or less in the better eye or a fail in the depth perception test. The prevalence of visual impairment was 5% (95% confidence interval [CI] = 3.3, 7.6). Of the 400 preschool children screened, 20 of them failed the distant visual acuity test or the stereopsis test. Refractive errors were the most common cause of visual impairment (95%, 95% CI = 76.2, 98.8); myopic astigmatism was the commonest type of refractive error (63.2%, 95% CI = 40.8, 80.9). The study is a small but important step in the effort to understand the problem of visual impairment among our preschool children. Our study showed that it is feasible to measure distant visual acuity and stereopsis in this age group.


Role of Decompressive Craniectomy in Traumatic Brain Injury - A Meta-analysis of Randomized Controlled Trials.
Several studies have indicated that decompressive craniectomy (DC) for traumatic brain injury (TBI) is lifesaving. However, there is lack of level 1 evidence to define the role of DC in TBI. We performed a meta-analysis of all the randomized controlled trials (RCTs) published so far on the role of DC in adult patients with TBI. A systematic literature search was performed for articles published until September of 2016 for RCTs of DC in adult patients with TBI. The primary end-point was mortality at six-months. We also evaluated the overall adverse outcomes at six months. Assessment of risk of bias of the RCTs was also performed. Three trials evaluating adult population satisfied the eligibility criteria. Pooled analysis involved 285 and 288 patients in DC group and control groups respectively. Patients undergoing DC for TBI had a lower mortality association of nearly 50 percent. However, patients surviving DC were more likely to have a poor neurological outcome compared to patients undergoing medical management. Based on the available RCTs on DC in TBI, the results of our meta-analysis show that there is a mortality benefit of performing a DC over the best medical management in adult patients. Furthermore, surviving following DC, a greater incidence of a poor neurological outcome is noted. In the event of small number of high-quality RCTs, our results must be interpreted with caution.


Internal adaptation, marginal accuracy and microleakage of a pressable versus a machinable ceramic laminate veneers.
The aim of this study was to evaluate the internal adaptation and marginal properties of ceramic laminate veneers fabricated using pressable and machinable CAD/CAM techniques. 40 ceramic laminate veneers were fabricated by either milling ceramic blocks using a CAD/CAM system (group 1 n=20) or press-on veneering using lost wax technique (group 2 n=20). The veneers were acid etched using hydrofluoric acid, silanated, and cemented on their corresponding prepared teeth. All specimens were stored under water (37 °C) for 60 days, then received thermocycling (15,000 cycles between 5 and 55 °C and dwell time of 90 s) followed by cyclic loading (100,000 cycles between 50 and 100 N) before immersion in basic fuchsine dye for 24 h. Half of the specimens in each group were sectioned in labio-lingual direction and the rest were horizontally sectioned using precision cutting machine (n=10). Dye penetration, internal cement film thickness, and vertical and horizontal marginal gaps at the incisal and cervical regions were measured (α=0.05). Pressable ceramic veneers demonstrated significantly lower (F=8.916, P<0.005) vertical and horizontal marginal gaps at the cervical and incisal margins and lower cement film thickness (F=50.921, P<0.001) compared to machinable ceramic veneers. The inferior marginal properties of machinable ceramic veneers were associated with significantly higher microleakage values. Pressable ceramic laminate veneers produced higher marginal adaptation, homogenous and thinner cement film thickness, and improved resistance to microleakage compared to machinable ceramic veneers. The manufacturing process influences internal and marginal fit of ceramic veneers. Therefore, dentist and laboratory technicians should choose a manufacturing process with careful consideration.


Water-soluble cellulose acetate from waste cotton fabrics and the aqueous processing of all-cellulose composites.
The objective of this study is to explore the possibility of using waste cotton fabrics (WCFs) as low cost feedstock for the production of value-added products. Our previous study (Tian et al., 2014) demonstrated that acidic ionic liquids (ILs) can be highly efficient catalysts for controllable synthesis of cellulose acetate (CA) due to their dual function of swelling and catalyzing. In this study, an optimized "quasi-homogeneous" process which required a small amount of acidic ILs as catalyst was developed to synthesize water-soluble CA from WCFs. The process was optimized by varying the amounts of ILs and the reaction time. The highest conversion of water-soluble CA from WCFs reached 90.8%. The structure of the obtained water-soluble CA was characterized and compared with the original WCFs. Moreover, we demonstrate for the first time that fully bio-based and transparent all-cellulose composites can be fabricated by simple aqueous blending of the obtained water-soluble CA and two kinds of nanocelluloses (cellulose nanocrystals and cellulose nanofibrils), which is attractive for the applications in disposable packaging materials, sheet coating and binders, etc.


Progesterone attenuates early brain injury after subarachnoid hemorrhage in rats.
Although the neuroprotective effects of progesterone against early brain injury (EBI) after trauma have been demonstrated in several studies, whether progesterone reduces EBI after subarachnoid hemorrhage (SAH) remains unknown. In this study, we explored the effect of progesterone on cell apoptosis, stability of the blood-brain barrier (BBB), brain edema, and mortality in male Sprague-Dawley rats subjected to subarachnoid hemorrhage-induced EBI by endovascular perforation. Rats (n=66) were randomly assigned to sham, SAH+vehicle, and SAH+progesterone groups. Progesterone (16 mg/kg) or an equal volume of vehicle was administered at 1h, 6h and 12h after SAH. Mortality within 24h, neurological scores, brain edema, Evans blue dye extravasation, cell apoptosis, and the expression of caspase-3 and matrix metalloproteinase (MMP)-9 were assayed after 24h of SAH. Progesterone treatment significantly reduced mortality, brain edema, Evans blue dye extravasation, cell apoptosis, expression of caspase-3 and MMP-9, and improved neurological scores compared with the vehicle group. Progesterone may reduce EBI after SAH by inhibiting cell apoptosis and stabilizing the BBB.


Different demographic and drinking profiles of motorcyclists and car drivers with the first-time offense of driving/riding under the influence of alcohol.
Driving/riding under the influence (DUI) of alcohol is a major public concern worldwide. Only a few studies have distinguished DUI-related variables between motorcyclists and car drivers. This study examined the differences in demographic characteristics and drinking behaviors among first-time DUI offenders operating different transportation vehicles, and risk factors for frequent DUI (fDUI) among them. We conducted an anonymous survey for 561 first-time DUI offenders who attended a mandatory educational program. Participants self-administered questionnaires concerning alcohol drinking behaviors and DUI. We defined fDUI as at least two DUI behaviors per month based on self-reported information. Demographic and drinking characteristics were compared between DUI offenders, car drivers and motorcyclists. Logistic regression analysis was used to examine risk factors for fDUI. Two-thirds of first-time DUI offenders were motorcyclists. Compared with car drivers, motorcyclists were younger and less educated, with a higher percentage of them being women and unmarried. Car drivers reported a higher rate of fDUI than motorcyclists (16.5% vs. 9.7%). Regression analysis revealed that binge drinkers had a higher fDUI risk in both groups. Regarding the drinking place prior to DUI behavior, workplace was significantly associated with fDUI in car drivers. Distinct strategies may be required for motorcyclists and car drivers for DUI recidivism prevention, and drinking place interventions should also be considered.


Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21.
Liposomes have shown promise as constituents of adjuvant formulations in vaccines to parasitic and viral diseases. A particular type of liposomal construct, referred to as Army Liposome Formulation (ALF), containing neutral and anionic saturated phospholipids, cholesterol, and monophosphoryl lipid A (MPLA), has been used as an adjuvant for many years. Here we investigated the effects of physical and chemical changes of ALF liposomes on adjuvanted immune responses to CN54 gp140, a recombinant HIV-1 envelope protein. While holding the total amounts of liposomal MPLA and the gp140 antigen constant, different liposome sizes and liposomal MPLA:phospholipid molar ratios, and the effect of adding QS21 to the liposomes were compared for inducing immune responses to the gp140. For liposomes lacking QS21, higher titers of IgG binding antibodies to gp140 were induced by small unilamellar vesicle (SUV) rather than by large multilamellar vesicle (MLV) liposomes, and the highest titers were obtained with SUV having the MPLA:phospholipid ratio of 1:5.6. ALF plus QS21 (ALFQ) liposomes induced the same maximal binding antibody titers regardless of the MPLA:phospholipid ratio. ALF MLV liposomes induced mainly IgG1 and very low IgG2a antibodies, while ALF SUV liposomes induced IgG1≥IgG2a>IgG2b antibodies. Liposomes containing QS21 induced IgG1>IgG2a>IgG2b>IgG3 antibodies. ELISPOT analysis of splenocytes from immunized mice revealed that ALF liposomes induced low levels of IFN-γ, but ALFQ induced high levels. ALF and ALFQ liposomes each induced approximately equivalent high levels of IL-4. Based on antibody subtypes and cytokine secretion, we conclude that ALF liposomes predominantly stimulate Th2, while ALFQ strongly induces both Th1 and Th2 immunity. When CN54 gp140 was adjuvanted with either ALF or ALFQ liposomes, antibodies were induced that neutralized two HIV-1 tier 1 clade C strain pseudoviruses.


Penile change following radical prostatectomy: size, smooth muscle atrophy, and curve.
Dr. Patrick Walsh's description of nerve-sparing prostatectomy was an important landmark in the surgical treatment of prostate cancer. Despite the dramatic improvement in postoperative potency rates, anecdotal reports of penile size loss were increasingly reported by patients. Experimental studies in animals revealed penile fibrosis and corporal cavernosal smooth muscle apoptosis after cavernosal nerve ablation. After an observational cross-sectional study demonstrated a time-dependent loss of penile length and circumference in men presenting with erectile dysfunction after nerve-sparing prostatectomy, several prospective studies supported the observational study. A prospective penile biopsy study before and after surgery demonstrated replacement of corporal smooth muscle with collagen and provided a possible explanation for loss of penile length. The mechanism has not yet been elucidated. This article reviews in detail the existing studies on loss of penile size after prostatectomy and possible etiologic mechanisms.


Shape determination of attached fluctuating phospholipid vesicles.
A method to determine the shapes of a thermally fluctuating phospholipid vesicle is described. The vesicle that was attached at one point to a glass plate was submitted to a flow. It was observed by an inverted optical microscope using phase contrast technique. A large number of consecutive video images were digitised at different flow velocities and stored on computer disk. They were off-line binarised using the global average value as a threshold. The vesicle outlines were determined by a contour following procedure based on the maze walking algorithm. They were described in terms of Fourier coefficients, which were calculated by the least square fitting of the contour points using normal equations and LU matrix decomposition. This method, which was the basis for the determination of the membrane bending modulus, was thoroughly tested and it proved to be robust and efficient.


Selective effects of estradiol on human corneal endothelial cells.
Fuchs endothelial corneal dystrophy (FECD) results from genetic and environmental factors triggering mitochondrial and oxidative stress in corneal endothelial cells (CEnCs) leading to CEnC death and corneal opacification. FECD is more common in women than men, but the basis for this observation is unknown. Because FECD is commonly diagnosed around the time of the menopausal transition in women when estrogen levels decrease precipitously, we studied the effects of the potent estrogen,17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of human CEnCs (HCEnCs) under conditions of physiologic 2.5% O 2 ([O 2 ] 2.5 ) and under hyperoxic stress ([O 2 ] A : room air + 5% CO 2 ). We hypothesized that E2 would counter the stresses of the hyperoxic environment in HCEnCs. HCEnCs were treated ± 10 nM E2 for 7-10 days at [O 2 ] 2.5 and [O 2 ] A followed by measurements of cell density, viability, reactive oxygen species (ROS), mitochondrial morphology, oxidative DNA damage, ATP levels, mitochondrial respiration (O 2 consumption rate [OCR]), and glycolysis (extracellular acidification rate [ECAR]). There were no significant changes in HCEnC density, viability, ROS levels, oxidative DNA damage, OCR, and ECAR in response to E2 under either O 2 condition. We found that E2 disrupted mitochondrial morphology in HCEnCs from female donors but not male donors at the [O 2 ] A condition. ATP levels were significantly higher at [O 2 ] 2.5 compared to [O 2 ] A in HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the overall resilience of primary HCEnCs against hyperoxic stress. The selective detrimental effects of hyperoxia and estradiol on HCEnCs from female but not male donors suggests mechanisms of toxicity based upon cell-sex in addition to hormonal environment.


The Potential Role of Changes in the Glucose and Lipid Metabolic Pathways in Gastrointestinal Cancer Progression: Strategy in Cancer Therapy.
Changes in cell metabolism are a well-known feature of some cancers, and this may be involved in the etiology of tumor formation and progression, as well as tumor heterogeneity. These changes may affect fatty acid metabolism and glycolysis and are required to provide the increase in energy necessary for the high rate of proliferation of cancer cells. Gastrointestinal cancers remain a difficult-to-treat cancer, particularly as they are usually diagnosed at a late stage of disease and are associated with poor outcomes. Recently, the changes in the metabolic pathways, including the expression of the rate-limiting enzymes involved, have been considered to be a potential target for therapy for gastrointestinal tumors. A combination of routine chemotherapy drugs with metabolic inhibitors may improve the effectiveness of treatment.