Meeting the challenge: responding to health care needs of homeless youth.
This article presents a worldview of youth who are victims of homelessness. A view of family dynamics and how they affect the emotional, psychological, social, and physical health of homeless youth is presented. Homeless youth and their families are at high risk for poor health outcomes. Those who present for health care services are least likely to return to the same site for follow-up care. Understanding the dynamics of homelessness and its effect on youth and family will facilitate efforts to engage the family and increase the likelihood for follow-up with the same provider. A patient-centered cognitive approach when managing these youth and their family will improve communication, potentiate engagement, whet creative decision making, and facilitate continuity of care.


The impact of language barriers on documentation of informed consent at a hospital with on-site interpreter services.
Informed consent is legally and ethically required before invasive non-emergent procedures. Language barriers make obtaining informed consent more complex. Determine the impact of language barriers on documentation of informed consent among patients in a teaching hospital with on-site interpreter services. Matched retrospective chart review study. Eligible Chinese- and Spanish-speaking patients with limited English proficiency (LEP) who received a thoracentesis, paracentesis, or lumbar puncture were matched with eligible English-speaking patients by procedure, hospital service, and date of procedure. Charts were reviewed for documentation of informed consent (IC), including a procedure note documenting an IC discussion and a signed consent form. For LEP patients, full documentation of informed consent also included evidence of interpretation, or a consent form in the patient's primary language. Seventy-four procedures in LEP patients were matched with 74 procedures in English speakers. Charts of English-speaking patients were more likely than those of LEP patients to contain full documentation of informed consent (53% vs 28%; odds ratio (OR): 2.81; 95% CI, 1.42-5.56; p = 0.003). Upon multivariate analysis adjusting for patient and service factors, English speakers remained more likely than LEP patients to have full documentation of informed consent (Adj OR: 3.10; 95% CI, 1.49-6.47; p = 0.003). When examining the components of informed consent, charts of English-speaking and LEP patients were similar in the proportion documenting a consent discussion; however, charts of English speakers were more likely to contain a signed consent form in any language (85% vs 70%, p = 0.03). Despite the availability of on-site professional interpreter services, hospitalized patients who do not speak English are less likely to have documentation of informed consent for common invasive procedures. Hospital quality initiatives should consider monitoring informed consent for LEP patients.


Safety considerations of septic shock treatment.
The management of sepsis essentially relies on effective resuscitation with fluids and vasopressors, appropriate and adequate antimicrobial therapy, and organ support. Any of these interventions can have beneficial but also harmful effects. We focus on the key hemodynamic signs of sepsis and discuss the potential safety risks associated with the management of each of them, including optimizing arterial pressure, cardiac output and oxygen delivery. We also underline the importance of the timing of interventions. Patients with septic shock are heterogeneous, making it particularly difficult to provide therapeutic recommendations that are safe and effective for all. A personalized medicine approach should be used with treatment decisions carefully considered and the risks and benefits of each intervention balanced in each individual patient.


Quantitative electroencephalography within sleep/wake states differentiates GABAA modulators eszopiclone and zolpidem from dual orexin receptor antagonists in rats.
Dual orexin receptor antagonists (DORAs) induce sleep by blocking orexin 1 and orexin 2 receptor-mediated activities responsible for regulating wakefulness. DORAs represent a potential alternative mechanism to the current standard of care that includes the γ-aminobutyric acid (GABA)A receptor-positive allosteric modulators, eszopiclone and zolpidem. This work uses an innovative method to analyze electroencephalogram (EEG) spectral frequencies within sleep/wake states to differentiate the effects of GABAA modulators from DORA-22, an analog of the DORA MK-6096, in Sprague-Dawley rats. The effects of low, intermediate, and high doses of eszopiclone, zolpidem, and DORA-22 were examined after first defining each compound's ability to promote sleep during active-phase dosing. The EEG spectral frequency power within specific sleep stages was calculated in 1-Hz intervals from 1 to 100 Hz within each sleep/wake state for the first 4 h after the dose. Eszopiclone and zolpidem produced marked, dose-responsive disruptions in sleep stage-specific EEG spectral profiles compared with vehicle treatment. In marked contrast, DORA-22 exhibited marginal changes in the spectral profile, observed only during rapid eye movement sleep, and only at the highest dose tested. Moreover, while eszopiclone- and zolpidem-induced changes were evident in the inactive period, the EEG spectral responses to DORA-22 were absent during this phase. These results suggest that DORA-22 differs from eszopiclone and zolpidem whereby DORA-22 promotes somnolence without altering the neuronal network EEG activity observed during normal sleep.


How to implement paid family and medical leave: A toolkit for practices.
Paid family and medical leave policies are increasingly popular in today's competitive labor market and provide well-documented advantages to all stakeholders. Implementing paid leave for radiologists can seem daunting due to overlapping legal and institutional policies, logistical challenges and call coverage, as well as industry-specific special considerations such as resident education and historical workplace attitudes. This toolkit can empower radiology leaders to implement written paid leave policies in their home institutions and demonstrate that equitable, compassionate institutional policies for paid leave are financially favorable, widely desirable, and increasingly achievable with the right tools in hand.


Antiphospholipid antibodies bind to rat cerebellar granule cells: the role of N-methyl-D-aspartate receptors.
IgGs from sera containing antiphospholipid antibodies (aPL), detected as antibodies to cardiolipin, or control sera were incubated with rat cerebellar granule cells in primary culture. Using a mitochondrial dehydrogenase activity assay (MTT test), aPL IgGs were shown to decrease MTT metabolism after 24 h incubation with the cells, and to cause non-toxic amounts of glutamate to become neurotoxic when added to the cells for 45 min. Acute and chronic aPL toxicity were prevented by MK-801. Sera containing aPL bound to intact cerebellar neurons, as revealed by an immunofluorescent technique. These results suggest that antiphospholipid antibodies interfere with excitatory pathways in glutamatergic cerebellar granule cells by a mechanism involving overactivation of the NMDA glutamate receptor.


Use of an abdominal rotation flap for inguinal lymph node dissection.
In order to reduce the incidence of skin edge necrosis following dissection of the inguinal lymph nodes, an abdominal rotation flap has been used to help with closure. This allows excision of the most vulnerable skin, and closure without tension. Our experience in 13 groin dissections is presented, with skin edge necrosis in one patient (7.6%). This is compared with previously reported series and the reasons for the precarious blood supply to the skin following groin dissection are discussed.


Trends of coronary heart disease among men of Japanese ancestry in Hawaii.
The 15-year prospective study of cardiovascular disease among a cohort of Japanese men in Hawaii provided an opportunity to examine the temporal trends of coronary heart disease (CHD) incidence and mortality rates and to compare them with Hawaii State CHD mortality rates. The State mortality records showed a decline in CHD mortality from 1968 to 1978 which was similar to the national trends. For more than 11,000 men of Japanese ancestry under surveillance, there was no evidence of declining rates for either CHD deaths or for total CHD incidence. There was also no change in case-fatality rates during this time. An explanation for these differences could not be provided but there was a suggestion that it involved changes in classification of some groups of cardiovascular disease and stroke.


The human per1 gene: genomic organization and promoter analysis of the first human orthologue of the Drosophila period gene.
Per genes encode components of the circadian clocks controlling metabolic and behavioural rhythms. The human Per1 cDNA, RIGUI, was previously isolated and mapped on chromosome 17p12 (Sun, Z.S., Albrecht, U., Zhuchenko, O., Bailey, J., Eichele, G., Lee, C.C., 1997. RIGUI, a putative mammalian orthologue of the Drosophila period gene. Cell 90, 1003-1011). We have now isolated the entire genomic locus containing the human Per1 gene, in a search for genes associated with CpG-rich sequences. The hPer1 gene spans 15kb of human genomic DNA and is composed of 23 exons, flanked by 5' and 3' regulatory regions. Comparison of the hPer1 genomic clone with the dbEST database revealed homologies with putative alternative transcripts. Functional mapping within the 5' CpG-rich regulatory region enabled us to locate the hPer1 promoter core in a 510bp-long sequence centred around a TATA box, which supports high levels of hPer1 transcription. A second regulatory region was formally identified in intron 1, which appears to exert a negative role in transcriptional control of hPer1. These regions may be differentially involved in tissue-specificity, and/or circadian regulation, of the human hPer1 gene transcription.


Lifestyle factors in preventing mental health disorders: an interview with Felice Jacka.
In this video Q&A, we talk to Associate Professor Felice Jacka about population health approaches to the primary prevention of mental disorders across the lifespan. These include addressing lifestyle factors, such as diet, smoking and physical activity. Latest strategies are being developed through epidemiological studies and clinical trial evidence. Challenges in preventing mental disorders in general and specifically in the workplace are discussed, together with future directions on promoting well-being.


Evaluation of Postoperative Care Protocol for Roux-en-Y Gastric Bypass Patients with Same-Day Discharge.
Same-day discharge (SDD) after bariatric surgery is increasingly being performed and is safe with careful patient selection. However, detecting early complications during the first postoperative days can be challenging. We developed a postoperative care protocol for these patients and aimed to evaluate its effectiveness in detecting complications and monitoring patient recovery. A single-center retrospective observational study was conducted with patients with who underwent Roux-en-Y Gastric Bypass (RYGB) with successful SDD. The study evaluated the effectiveness of the safety net that included simple remote monitoring with a pulsoximeter and thermometer, a phone consultation on postoperative day (POD) 1, and a physical consultation on POD 2-4. Furthermore, an analysis was performed on various factors including pain scores, painkiller usage, and incidences of nausea and vomiting on POD 1. In this study, 373 consecutive patients were included, of whom 19 (5.1%) were readmitted until POD 4. Among these, 12 patients (3.2%) reached out to the hospital themselves, while 7 (1.9%) were readmitted after phone or physical consultations. Ten of the readmitted patients had tachycardia. On POD 1, the mean numeric rating scale was 4 ± 2, and 96.6% of the patients used acetaminophen, 35.5% used naproxen, and 9.7% used oxynorm. Of the patients, 13.9% experienced nausea and 6.7% reported vomiting. A postoperative care protocol for SDD after RYGB, comprising simple remote monitoring along with a phone consultation on POD 1 and a physical checkup on POD 2-4, was effective in monitoring patient recovery and detecting all early complications.


Measuring Myocardial Energetics with Cardiovascular Magnetic Resonance Spectroscopy.
The heart has the highest energy demands per gram of any organ in the body and energy metabolism fuels normal contractile function. Metabolic inflexibility and impairment of myocardial energetics occur with several common cardiac diseases, including ischemia and heart failure. This review explores several decades of innovation in cardiac magnetic resonance spectroscopy modalities and their use to noninvasively identify and quantify metabolic derangements in the normal, failing, and diseased heart. The implications of this noninvasive modality for predicting significant clinical outcomes and guiding future investigation and therapies to improve patient care are discussed.


Multi-factorial retainer design analysis of posterior resin-bonded fixed partial dentures: a finite element study.
Biomechanical aspects related to prosthesis design of RBFPD have been proposed as the predominant contributor to unpredictable clinical retention. The aim of this study was to investigate the biomechanics of multiple posterior retainer designs and their interactions using three-dimensional finite element analysis. To understand the interactions among the retainer design factors, three values of retainer thicknesses (1.2, 0.8 and 0.4mm), heights (100, 75 and 50% of the distance from 2mm above the CEJ to the occlusal surface) and angle of the axial surface extensions (150, 180 and 210 degrees ) were selected as the design parameters. Twenty-seven RBFPD FE models with three retainer-design parameters were created by image processing, contour stacking, and mapping mesh procedures. The maximum principal and von Mises stresses in remaining tooth and prosthesis, respectively, were recorded in 54 FE analyses (27 FE models with axial and lateral occlusal loadings). The simulated results showed that the averaged stress values of the remaining tooth and prosthesis decreased with greater retainer thickness and height as a result of increasing prosthesis stiffness and maximizing of the bonding area between the enamel and the retainer, respectively. However, no significant stress differences were found according to the angle of the retainer extension because stress transmission was concentrated at the connectors. The stress elevation rate (termed as VSR-stress elevation by decreasing one unit volume of the remaining tooth) addresses that the height was the most influential factor for the remaining tooth structure, followed by retainer thickness and extension angle.


The spatiotemporal response of China's vegetation greenness to human socio-economic activities.
Climate change and human socioeconomic activities both strongly impact long-term vegetation greenness. It is more a challenge to evaluate the impacts of socioeconomic activities on vegetative greenness than climate change, partially due to the lack of appropriate quantitative indicators of the former. Here we examined the relationship between the remote sensing nighttime light (NTL) data and the Normalized Difference Vegetation Index (NDVI), which in this study are used as the proxies of socioeconomic activities and vegetation greenness, respectively. We first eliminated the vegetation greenness changes in response to climate change and calculated the human-activities-induced NDVI (HNDVI). After explored the spatiotemporal patterns of the HNDVI and NTL data across China from 1998 to 2018, we studied the relationship between the HNDVI and NTL at the grid and county levels, respectively. Our results show that the mean adjusted DN values of the NTL data (NTLI) continuously increase (+0.2938) across our study area from 1998 to 2018, whereas the HNDVI values fluctuate with a general upward trend (+0.0018). Most grids (91.2%) with increased HNDVI were found in rural areas, particularly in the Northeast forest shelterbelt and the Loess Plateau. By contrast, the HNDVI values in rapidly urbanized areas in Chinese major urban agglomerations mainly show a downward trend, especially in the Yangtze River Delta (YRD) urban agglomeration. The relationships between the NTLI and HNDVI are inconsistent over time and across space, which could be attributed to land use conditions, afforestation projects in rural areas, and greening activities in urban areas over different periods and regions.


Plekhh1, a partner of myosin 1 and an effector of EphB2, controls the cortical actin network during cell repulsion.
EphB2-ephrinB signalling, which plays a major role in cell segregation during embryonic development and tissue homeostasis, induces an important reorganization of the cortical actin network. We have previously reported that myosin 1b contributes to reorganization of the cortical actin network upon EphB2 signalling. In this report, we identify Plekhh1 as a new partner of members of the myosin 1 family and EphB2 receptors. Plekhh1 interacts with myosin 1b via its N-terminal domain and with EphB2 via its C-terminal domain. Furthermore, Plekhh1 is tyrosine phosphorylated, and this depends on EphB2 kinase activity. Similar to the effects of manipulating levels of myosin 1b and myosin 1c, manipulation of Plekhh1 expression levels alters the formation of filopodia, the length of focal adhesions and the formation of blebs. Furthermore, binding of the Plekhh1 interacting domain to myosin 1b increases the motor activity of myosin 1b in vitro. Taken together, our data show that Plekhh1 is an effector of EphB2 and suggest that Plekhh1 regulates the cortical actin network via the interaction of its N-terminal domain with myosin 1 upon EphB2-ephrinB signalling.


Pneumatic retinopexy: A critical reappraisal.
Pneumatic retinopexy (PR) has been widely advocated for treatment of selected rhegmatogenous retinal detachments: those with small, anterior, superior, retinal breaks and little or no proliferative vitreoretinopathy. It has been suggested that PR is underused and is advantageous because it is an outpatient clinic or office procedure, short in duration, nonincisional, and cost saving - with reduced perioperative morbidity, faster postoperative recovery, better and faster visual recovery, a low rate of complications and a high rate of overall success compared with scleral buckling or pars plana vitrectomy. We reevaluated these advantages to substantiate the effectiveness and efficiency of PR and critically define its role in the treatment of rhegmatogenous retinal detachment. We found that PR has a much higher rate of subsequent reoperation and proliferative vitreoretinopathy than scleral buckling or pars plana vitrectomy for simple, good prognosis rhegmatogenous retinal detachments. PR often involves multiple procedures that largely negates its potential cost savings and subjects the patient to prolonged stress and disability. Scleral buckling rather than PR is ideally suited for simple, good prognosis rhegmatogenous retinal detachments for surgeons who feel comfortable with the technique; alternatively, pars plana vitrectomy is indicated.


Deriving allowable daily intakes for systemic toxicants lacking chronic toxicity data.
The lack of human toxicological data for most chemical compounds makes it difficult to quickly assess health risks associated with exposure to contaminants at hazardous waste sites. It would therefore be advantageous to have a technique for estimating acceptable daily intakes (ADIs) of potentially toxic substances based on more widely available animal toxicity data. This article focuses on the use of LD50 data to derive provisional ADIs, and it suggests multiplying oral LD50 values (expressed in mg/kg of body wt) by a factor in the range of 5 X 10(-6) to 1 X 10(-5) day-1 to convert them to such ADIs. It is emphasized that these interim ADI values are no substitute for toxicity testing, but that such testing would most likely result in higher ADI estimates.


A randomized controlled trial comparing two ways of providing evidence-based drug information to GPs.
To investigate whether tailored evidence-based drug information (EBDI) to general practitioners (GPs) can change the proportion of ACE inhibitor prescriptions more effectively than EBDI provided as usual three and six months after the intervention. Randomized controlled trial. GPs in southern Sweden working at primary health care centres (PHCCs) in seven drug and therapeutic committee areas. EBDI tailored to motivational interviewing (MI) technique and focused on the benefit aspect was compared with EBDI provided as usual. There were 408 GPs in the intervention group and 583 GPs in the control group. Change in proportion of ACE inhibitor prescriptions relative to the sum of ACE inhibitors and angiotensin receptor blockers, three and six months after the intervention. The GPs' average proportions of prescribed ACE inhibitors increased in both groups. No statistically significant differences in the change of proportions were found between intervention and control groups. Information was provided to 29% of GPs in both groups. This study could not prove that specially tailored EBDI using MI implements guidelines more effectively than EBDI provided as usual.


[Decreased lipid levels in arteriosclerotic plaques of the human aorta after LDL-apheresis (an in vitro study)].
A comparative study of the effects of LDLP-apheresis on lipids in short-lived organ culture and primary cell culture of human atherosclerotic aorta demonstrated that a fall in free cholesterol, triglycerides, phospholipids and cholesterol esters was largely due to reduced concentration of extracellular lipids.


Withdrawal of longterm antihyperuricemic therapy in tophaceous gout.
After longterm treatment (mean duration 7.2 years) with antihyperuricemic drugs, ten tophaceous gouty patients requested withdrawal of the medication because they had not felt any arthritic pains for years, the tophi had disappeared, and they disliked the idea of taking the medicine daily for the rest of their lives. Five patients (Group I) had no recurrence of either arthritis or tophi during follow-up for 18 to 52 months (average duration 33 months). Five patients (Group II) had a recurrence of arthritis 5 to 29 months (average 15.8 months) after cessation of therapy and two of them developed tophi again at 29 months and resumed treatment. Group II patients tended toward obesity, more severe hyperuricemia and an earlier age onset of gout, as compared with Group I patients. The creatinine concentration determined before, during, and after treatment showed no change. On the basis of the present findings it seems justified to withdraw medication in cases of tophaceous gout in remission when aggravating factors such as obesity and severe hyperuricemia are absent. Attacks of gout and tophi are likely to recur, but so far in our series the duration of the symptom-free period without medication is almost three years for Group I patients, who are now considered as "asymptomatic hyperuricemics".


Autologous tissue reconstruction after mastectomy-A cross-sectional survey of 110 hospitals in China.
Autologous reconstruction after mastectomy became more and more popular, so this study aimed to obtain up-to-date and comprehensive data on autologous reconstruction in China. An electronic questionnaire was sent to 110 hospitals, which were chosen depending on geographical distribution and hospital types. The questionnaire investigated the demographics, characteristics, breast cancer treatment and reconstruction situation of these hospitals through different modules. We only focused on the autologous breast reconstruction module data. 96 hospitals have performed breast reconstruction surgery. The proportion of the hospital performing latissimus dorsi flap (LDF, N = 91), pedicle transverse rectus abdominis myocutaneous flap (pTRAM, N = 62), free abdominal flap (N = 43) and other kinds of flap decreased in sequence. Of the overall reconstruction cases, only 34.3% were autologous reconstruction and LDF was still the most popular option for autologous reconstruction. Related factors of hospital performing different procedures included years of performing breast reconstruction, breast surgical volume, and establishment of an independent plastic surgery department. Compared with LDF, abdominal breast reconstruction was associated with a higher flap necrosis rate. This cross-sectional survey offers real-life autologous reconstruction information on a large population and covers the national surgical landscape in China. Autologous reconstruction is still an important part of breast reconstruction. Nevertheless, its low proportion and lower proportion of abdominal flap reconstruction in each institution, demonstrates that special training should be developed for breast surgeons and multidisciplinary cooperation would be promoted in the future.


The Relationship between Exosomes and Cancer: Implications for Diagnostics and Therapeutics.
Exosomes are very small extracellular vesicles secreted by cells to local and distant tissues. These mini signal transporters elicit acute and chronic effects on recipient cells. Studies regarding exosomes and their relationship to disease, as well as healthy functions, are eliciting extraordinary excitement as data pours in from groups around the world. Reporting of exosome biogenesis, selective loading of cargo, directed release, and resulting changes in adjacent and distal cells are providing information that is changing the way we view cancer progression and treatment. As a result, the properties of exosomes are being exploited for diagnostic, prognostic, and therapeutic applications. First, by referring to the signaling molecules carried by exosomes, they are being tested as indicators of the presence of transformed cells in early stages of cancer. Secondly, the cargo of exosomes secreted from tumors have been linked to prognostic factors and metastatic properties. Thirdly, exosome-based therapies are being developed which utilize the inherent properties of these mini-transporters to affect and interfere with cancer. Exosome creation, loading, and release plays an important role in cancer formation, progression and organotropic metastasis. The developed and developing therapies should be considered with understanding of their advantages and pitfalls, as well as the various roles exosomes play in normal and pathogenic processes. The combination of previously discovered attributes of exosomes with new discoveries occurring daily provide valuable and additive relevant factors to be considered as we embark on the continued discovery of exosomes and their relationship to cancer diagnostics and therapeutics.


Expression of helminth genes in Leishmania: an experimental transfection system to test immunological function.
Functional analysis of genes from parasitic helminths requires, at the present time, heterologous expression. We have adapted the well-characterized system of transfection in Leishmania protozoal parasites, as a means of analysing the effect of single filarial genes on the mammalian immune system. For example, testing the function of the Brugia malayi abundant larval transcript (ALT) gene-transfected Leishmania mexicana were found to be significantly more virulent in macrophages in vitro. The course of infection in vivo is also aggravated by expression of the ALT gene. Examples are also given of transgenes which reduced in vitro growth within macrophages, as well as others which exert no effect on the protozoal parasitism. Thus, Leishmania transfection provides a tractable system to analyse helminth gene function within the context of the host immune system.


The cytotoxic, mutagenic and clastogenic effects of chromium-containing compounds on mammalian cells in culture.
Examples of chromic and chromate salts have been examined for their effects on a cultured Chinese hamster cell line. The responses studied were cytotoxicity, mutagenesis and clastogenesis. Chromate (hexavalent chromium) salts of both high and medium water solubility were active in producing all three classes of response, whereas an insoluble chromate salt and a soluble chromic (trivalent chromium) salt were inactive. In addition to illustrating the value of using mammalian cells in culture for screening chemicals for biological activity, the results of this study reinforce current views regarding the genotoxic properties of chromates.


Learning Curve of Endoscopic Retrograde Cholangiopancreatography Using Single-Balloon Enteroscopy.
Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically difficult. Extensive training is required to develop the ability to perform this procedure. To investigate the learning curve of single-balloon-assisted enteroscopy ERCP (SBE-ERCP). We conducted a retrospective, observational case series at a single center. We evaluated the SBE-ERCP procedures between April 2011 and February 2021. The main outcomes were the rate of reaching the target site and the success rate of the entire procedure. These parameters were additionally expressed as a learning curve. A total of 687 SBE-ERCP procedures were analyzed. The learning curve was analyzed in blocks of 10 cases. In this study, seven endoscopists, experts in conventional ERCP, were included. The overall SBE-ERCP procedural success rate was 92.2% (634/687 cases). Combining all data from individual endoscopists' evaluation periods, the insertion and success rates of the SBE-ERCP procedures gradually increased with increased experience performing SBE-ERCP. The insertion success rates for the number of SBE-ERCP cases (< 20, 21-30, > 30) were 82.9%, 92.9%, and 94.3%, respectively; the procedure success rates were 74.3%, 81.4%, and 92.9%, respectively. The endoscopists who had performed > 30 SBE-ERCP cases had a success rate of ≥ 90%. Our results suggest that performing > 30 cases is one of the targets for conventional ERCP experts to become competent in performing SBE-ERCP in patients with a surgically altered anatomy.


Fabrication and characterization of nanostructured lipid carriers (NLC) using a plant-based emulsifier: Quillaja saponin.
Nanostructured lipid carriers (NLCs) are a type of colloidal delivery system that was developed in the pharmaceutical industry to combine the advantages and eliminate the shortcomings of oil-in-water (O/W) nanoemulsions and solid lipid nanoparticles (SLNs). The hydrophobic core of the particles within NLCs consists of a solidified fat phase with a partially disorganized structure, which inhibits morphological changes and bioactive expulsion. In the present study, we formulated NLCs using a hot-homogenization approach using fully hydrogenated soybean oil (HSO) as the lipid phase and quillaja saponins as a natural surfactant. The NLCs formed had a low viscosity and milky white appearance similar to that of O/W nanoemulsions. The fabrication conditions were optimized, including the number of passes through the microfluidizer, stirring conditions, cooling rate, and emulsifier level. Unlike bulk HSO, the emulsified form had to be supercooled substantially to promote crystallization of the lipid droplets, which was attributed to differences in nucleation behavior. The crystallization temperature decreased with increasing saponin concentration, which was probably because smaller droplets were formed at higher emulsifier levels. For instance, at 3, 6, 9, and 12 wt% saponin, the degree of supercooling was 10, 15, 18, and 18 °C, while the mean particle diameter was 0.82, 0.53, 0.41, and 0.44 μm, respectively. The melting and crystallization behavior of the NLCs was characterized using an optical microscope and differential scanning calorimetry (DSC), while the morphology of the NLCs was characterized using transmission electron microscopy (TEM). This analysis showed that the NLCs contained spherical particles with a crystallization temperature around 31 °C. This information may be useful for formulating NLC from natural ingredients for application in the food and beverage industry.


Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.
This article is a review of the use of quantitative (and qualitative) structure-activity relationships (QSARs and SARs) by regulatory agencies and authorities to predict acute toxicity, mutagenicity, carcinogenicity, and other health effects. A number of SAR and QSAR applications, by regulatory agencies and authorities, are reviewed. These include the use of simple QSAR analyses, as well as the use of multivariate QSARs, and a number of different expert system approaches.


Early partial systolic closure of the pulmonic valve relates to severity of pulmonary hypertension.
Ultrasound studies in pulmonary hypertension often show systolic partial closure of the pulmonic valve and early peaking of Doppler pulmonary flow velocity, but these findings are poorly understood. Our initial observations of earlier systolic partial closure with higher pulmonary pressures suggested that this phenomenon might relate to pressure. In 30 patients with documented pulmonary hypertension, the timing of systolic partial closure and the corresponding decrease in Doppler flow velocity related inversely to pulmonary artery pressure at catheterization. Peak flow preceded the systolic velocity decrease and also related inversely to pressure. Since changing flow velocity might reflect a changing driving force across the valve, we examined simultaneous high-fidelity catheter pressure tracings from the right ventricle and pulmonary artery from 24 patients with and without pulmonary hypertension. In 30 studies, a positive right ventricular to pulmonary artery pressure gradient was present early in systole, but the gradient decreased to a minimum value in mid-to-late systole. The timing of this minimum also related inversely to pressure. We conjectured that forces opposing ejection occur earlier in pulmonary hypertension, thereby decreasing the forward driving force and allowing earlier partial systolic closure.


The unresolved role of the neurologist in providing dietary advice to people with multiple sclerosis.
People with MS often make dietary changes after diagnosis with the aim of slowing disease progression. Although people with MS commonly use the internet for information on diet and MS, neurologists are their preferred source of information. However, little is known about what dietary advice is provided by neurologists. To explore the perceptions of neurologists about diet and MS, and to identify the type of dietary advice they provide to their patients with MS. In this exploratory qualitative study, 11 semi-structured interviews were conducted with neurologists in Western Australia. Audio files were transcribed verbatim, and transcripts were thematically analysed using a general inductive approach. Four themes emerged: 1) juggling the evidence on the role of diet in MS; 2) acknowledging the risks and benefits of specific diets; 3) distancing from the diet 'gurus'; and 4) the unresolved role of the neurologist in providing dietary advice. Neurologists could meet their patients' expectations by providing evidence-based dietary advice, such as promoting the benefits of diets that adhere to national dietary guidelines, and being prepared to explain potential risks of restrictive diets. Information about healthy eating needs to be targeted to people with MS.


Hemostatic changes in human adoptive immunotherapy with activated blood monocytes or derived macrophages.
Human blood monocytes (Mo) and monocyte-derived macrophages (M psi) possess cytotoxic effects against tumor cell lines when appropriately stimulated by various biological response modifiers, e.g., gamma interferon (gamma IFN) and muramyltripeptide (MTP). Activated Mo/M psi represent a new tool for the treatment of human malignancies, termed "adoptive cellular immunotherapy". Activated Mo/M psi express tissue factor procoagulant activity (PCA), which is a physiological trigger of blood coagulation. PCA was evaluated in vitro using a modification of the one-stage recalcification clotting time, and hemostatic changes were studied in vivo in cancer patients. Nine patients with peritoneal carcinomatosis were injected intraperitoneally with activated Mo and 11 patients with non-small cell lung carcinomas were infused intravenously with activated M psi. Hemostatic changes were followed using activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen level, antithrombin III (ATIII) and protein C (PC) activities. Fibrinolytic activity was estimated by euglobulin lysis time and assays for plasminogen and fibrin/fibrinogen degradation products (FDP). These assays were performed before and after each autologous infusion and on days 2 and 3. Activated Mo and M psi expressed potent PCA (85.5 +/- 7.5 U/ml for MTP activated Mo and 50 +/- 5.3 U/ml for gamma IFN activated M psi suspensions). In both groups of patients, APTT, PT, and TT underwent no significant variations. There was no significant consumption of ATIII or PC, and fibrinolysis was not activated during the study period. In the group injected intraperitoneally with MTP-activated Mo, fibrinogen showed a significant and progressive increase in relation to the development of an inflammatory reaction, reaching a maximum average value of 6.1 g/l at the end of the therapy with a concomitant increase in FDP levels. This increase was not observed after intravenous therapy with gamma IFN-activated M psi. No patient suffered from hemorrhagic or thrombotic events. In our experience, repeated injections of activated Mo or M psi expressing potent tissue factor PCA did not induce significant in vivo activation of the coagulation system in cancer patients.


An inexpensive strain gage amplifier and signal conditioner for biological applications.
The design and operation of a strain gage signal conditioning amplifier is described. The complete amplifier is based on the Analog Devices 2B30 module and features adjustable gain, bridge excitation voltage, bridge balance, d.c. offset and low-pass filtering. The ease of construction and low cost of this amplifier make it ideal for applications requiring a large number of signal channels.


[Changes in the reflex discharges and electrotonic potentials of spinal nerve roots in the rat upon exposure to biologically active substances].
The ionic nature of neuronal postsynaptic responses to monoamines, aminoacids and the substance P was studied in the newborn rat isolated spinal cord. The responses of motoneurons to GABA, glycine, noradrenaline and dopamine appeared to be Cl-dependent. The depolarization of motoneurons induced by L-glutamate and 5-hydroxytryptamine was Na-dependent whereas the same response to the substance P was Cl-dependent. Primary afferent depolarization with GABA is Cl-dependent whereas if induced by glycine and 5-hydroxytryptamine it is Na-dependent. Neurochemical and ionic profiles of mono- and polysynaptic ventral and dorsal root potentials are discussed.


Morphology of postcoital spermatozoa in the cervical secretion and its clinical significance.
Morphologic analysis of spermatozoa recovered 10 hours postcoitally from the human female genital tract and its correlation to the clinical situation have shown that (1) spermatozoa in the vagina are equivalent to those in the semen sample; (2) spermatozoa within the cervical secretion exhibit significantly better morphology than do those of the semen sample, indicating the presence of a barrier against abnormal spermatozoa at the level of the external os; (3) this barrier is significantly more effective in cases where conceptions later occur than in cases of persistent, unexplained infertility; and (4) the barrier is particularly active against spermatozoa with abnormal heads.


Scanning electron microscopy of human ossicles.
Human middle ear ossicles removed from cadavers and during surgical procedures have been examined with scanning electron microscope (SEM). Two kinds of bone tissue compose ossicles: periosteal and endochrondral bone. Periosteal bone occurs in the form of external covering on the ossicles. In the middle of the ossicles there is endochrondral bone which shows various spatial arrangement of collagen bundles. Lamellar bone occurs also in this bone around vascular channels but rarely in the form of typical osteons. Surface appearance of periosteal, coarse-fibred bone and lamellar, fine-fibred bone is almost the same. Lamellar bone is composed of coarse collagen bundles arranged tightly in the rows. The space between the rows is filled by fine fibres which link the coarse bundles.


Using reflexology to manage stress in the workplace: a preliminary study.
Work stress is a major occupational problem in the UK. Few studies have examined the role of complementary therapies in reducing stress in the workplace. To help determine the usefulness of reflexology in managing stress a preliminary study was conducted in an occupational setting. To explore the use of reflexology in managing stress in the workplace. In a single-subjects experimental design, four employees from a single organisation received reflexology treatments. A range of outcome measures, including the GHQ-12 and the MYMOP2, were used to monitor psychological health and well-being, symptoms and quality of life. Measures were taken at baseline, intervention and follow-up. The data suggested some trends towards improvement in perceived health and well-being following reflexology intervention. Improvements varied by participant and across the different measures. This study was limited by the size of the sample and the nature of the design, which cannot demonstrate cause and effect. The trends towards improvement associated with reflexology suggested that further research may be warranted.


Cloning, expression and enzyme activity delineation of two novel CANT1 mutations: the disappearance of dimerization may indicate the change of protein conformation and even function.
Desbuquois dysplasia (DBQD) was a rare autosomal recessive skeletal dysplasia. Calcium activated nucleotidase 1 (CANT1) mutation was identified as a common pathogenic change for DBQD type 1 and Kim variant but not for DBQD type 2. To our knowledge, all patients with DBQD type 1 currently found could be explained by mutations in the CANT1 gene, but mutations in the CANT1 gene might not be directly diagnosed as DBQD type 1. We have identified two novel CANT1 mutations (mut1: c.594G > A [p.Trp198*], mut2: c.734C > T [p.Pro245Leu]) in three children from a family of Chinese origin for the first time. Two of the three children could be diagnosed as typical DBQD type 1 and one child could not be diagnosed as DBQD type 1 based on the clinical data we had. To further clarify the effect of the two mutations of the CANT1 gene, we studied the CANT1 gene expression and detected the protein secretion and nucleotide enzyme activity through cDNA cloning and expression vectors construction for wild and mutant types. The mut1 was a nonsense mutation which could lead to premature termination and produced the truncated bodies; The CANT1 dimer of mut2 was significantly reduced and even undetectable. The extracellular secretion of mut1 was extremely high while mut2 was significantly reduced compared with the wild type. And mut1 and mut2 also could result in a significant reduction in the activity of CANT1 nucleotidease. From the results we could deduce that the two mutations of the CANT1 gene were the causes of the two cases in this study. Regarding the particularity of the cases reported in this study, the pathogenesis of CANT1 might be more complicated. The genetic and phenotype of three children with the same genetic background need to be further studied. Larger cohort of patients was needed to establish genotype-phenotype correlations in DBQD.


Tissue inhibitor of metalloproteinases: serum levels during pregnancy and labor, term and preterm.
To determine the levels in serum of tissue inhibitor of metalloproteinases (TIMP) in pregnancy and to examine the possibility of a time course in relation to parturition, both term and preterm. Serum tissue inhibitor of metalloproteinases was measured using an enzyme-linked immunosorbent assay. A cross-sectional study was conducted in 333 women during pregnancy, labor, and the postpartum period and in 27 nonpregnant volunteers. Longitudinal data were obtained from 22 women who provided a sample at term, during labor, and in the postpartum period. In uncomplicated pregnancies, serum TIMP levels were low from the onset of pregnancy until 37 weeks' gestation, in comparison to levels in nonpregnant women (P < .001). During the final weeks of pregnancy, levels rose and at 37-42 weeks were similar to nonpregnant levels. The levels did not change with the onset of labor. Serum concentrations of TIMP obtained during preterm labor were elevated compared to a control group of patients at a similar gestation who subsequently delivered at term (P < .01). Serum TIMP levels were significantly higher during the postpartum period than at all other times (P < .001). Changes in serum TIMP levels during and after pregnancy may parallel the remodeling of the extracellular matrix that takes place throughout this period. Further work is necessary to evaluate the prognostic value of TIMP for preterm labor.


Adverse impact of renin-angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study.
The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. This retrospective cohort study was performed in all hospitalized patients with COVID-19 in tertiary hospitals in Daegu, Korea. Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. The analysis of the primary outcome, in-hospital mortality, was performed using the Cox proportional hazards regression model. Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10-4.38; P = 0.025). ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02-6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15-8.15; P = 0.026). Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P < 0.05). ACE-I or ARB therapy in patients with severe COVID-19 was associated with the occurrence of severe complications and increased in-hospital mortality. The potentially harmful effect of ACE-I or ARB therapy may be higher in patients who received high doses.


A simple motif for protein recognition in DNA secondary structures.
DNA in a single-stranded form (ssDNA) exists transiently within the cell and comprises the telomeres of linear chromosomes and the genomes of some DNA viruses. As with RNA, in the single-stranded state, some DNA sequences are able to fold into complex secondary and tertiary structures that may be recognized by proteins and participate in gene regulation. To better understand how such DNA elements might fold and interact with proteins, and to compare recognition features to those of a structured RNA, we used in vitro selection to identify ssDNAs that bind an RNA-binding peptide from the HIV Rev protein with high affinity and specificity. The large majority of selected binders contain a non-Watson-Crick G.T base-pair and an adjacent C:G base-pair and both are essential for binding. This GT motif can be presented in different DNA contexts, including a nearly perfect duplex and a branched three-helix structure, and appears to be recognized in large part by arginine residues separated by one turn of an alpha-helix. Interestingly, a very similar GT motif is necessary also for protein binding and function of a well-characterized model ssDNA regulatory element from the proenkephalin promoter.


Ring chromosome 21 and SOD activity of blood cells.
A female infant was found to have an abnormal karyotype with mosaicism: 45,XX,-21/46,XX,r(21) (p11.2 q22.3). She showed a slightly decreased level of superoxide dismutase (SOD) activity in erythrocytes, polymorphonuclear and mononuclear leukocytes. The cuprozinc SOD (SOD-1) activity of leukocytes was 70-80% of normal level, while their manganese SOD (SOD-2) activity was within the normal range. The relationship between the chromosomal aberration and the SOD activity is discussed in relation to the gene dosage effect.


A Randomized Pilot Study of a Group-Delivered HIV Risk Reduction Intervention for At-Risk Urban Men Who Have Sex with Men Who Regularly Attend Private Sex Events.
Across HIV prevention studies, as many as 25% of men who have sex with men (MSM) report meeting male partners at private sex events and attendance is associated with increased number of sexual partners, condomless anal sex (CAS), and HIV infection. Despite the need for effective HIV prevention interventions, no risk reduction interventions have been tested to reduce HIV sexual risk of MSM that regularly engage in sexual risk at private sex events. This randomized pilot study assessed the feasibility and acceptability of an HIV risk reduction intervention to reduce CAS among urban MSM (N = 14) reporting risk at a private sex event in the prior 12 months. The intervention arm received four group sessions (2 h/session) focusing on HIV risk reduction education and skills building. Both the intervention (n = 8) and control (n = 6) conditions received HIV testing and pre- and posttest risk reduction counseling and completed a sexual risk and psychosocial assessment visit at baseline and 3 months post-intervention. In addition, intervention participants completed a brief exit interview post-intervention. Mean age was 37 years, and 57% were racial/ethnic minorities. At follow-up, the intervention group reported greater reductions in sexual risk behavior in the past 3 months including number of CAS episodes, number of partners at private sex events, and CAS episodes at private sex events. The intervention group also reported reduced sexual compulsivity, increases in HIV disclosure, and reduced drug use at private sex events over study follow-up. Exit interviews revealed that participants found the intervention to be highly acceptable. Findings demonstrate feasibility of procedures, participant acceptability, and initial promise of a group-delivered HIV risk reduction intervention for MSM who attend and engage in CAS at private sex events. Further testing of this intervention in a larger pilot randomized controlled trial is warranted.


Study of the mutagenicity of metal derivatives with Salmonella typhimurium TA102.
The mutagenic potential of 16 metal derivatives was studied with a new mutant of Salmonella typhimurium, the strain TA102 (Levin et al., 1983). Some of these compounds are known as carcinogens (As, Cr VI, Cd, Ni) or suspected carcinogens in man (Pb, Hg), others are known as non-carcinogens (Cr III, Al, Cu, Mn, Fe). Among these 16 derivatives, only the two Cr(VI) compounds are strong mutagens (K2Cr2O7 or K2CrO4).


In vivo evaluation of chondroitin sulfate-glycyl-prednisolone for anti-arthritic effectiveness and pharmacokinetic characteristics.
A conjugate between chondroitin sulfate (CS) and glycyl-prednisolone (GP), named CS-GP, was prepared as a delivery system for the treatment of rheumatoid arthritis by referring to the previous report. CS-GP conjugates with different prednisolone (PD) contents of 1.4, 2.0 and 4.3% (w/w) were obtained, and their conversion characteristics were investigated at 37 °C under pH 6 and 7.4. Release profiles were similar among the conjugates, being slow at pH 6 (24 h: 9-14%), and fairly fast at pH 7.4 (7 h: 46-58%). CS-GP, PD, CS and the PD/CS mixture were investigated for anti-inflammatory effects by i.v. administration to rats with adjuvant-induced arthritis. At 2.5mg PD equiv./kg×2 d, CS-GP significantly suppressed swelling of both hind paws, while other preparations were less effective. CS-GP (2.5mg PD equiv./kg×2 d) tended to be more effective than PD (5 mg/kg×2 d). Change in body weight indicated that CS-GP was not toxic. After i.v. injection in normal rats, CS-GP showed much higher plasma levels than PD alone, and organ accumulation of CS-GP was not observed. CS-GP was suggested to be possibly useful for the treatment of rheumatoid arthritis.


Effects of recombinant bovine somatotropin (rbST) and season on plasma and milk insulin-like growth factors I (IGF-I) and II (IGF-II) in lactating dairy cows.
During two studies, effects of recombinant bovine somatotropin (rbST) on plasma and milk IGF's in cows adapted to summer (S; 12 cows) or winter (W; 12 cows) conditions were evaluated. Each study consisted of on-farm periods (30 days) followed by climatology chamber periods (CC; 30 days). Cows were given daily injections of rbST, Sometribove, USAN (25mg/day; 6 cows each study) or saline (control; 6 cows each study). During on-farm periods, blood and milk (am and pm) samples were collected once weekly. During CC periods, blood samples were collected every 2 days and milk samples (am and pm) were collected daily. Plasma IGF-I and IGF-II were increased in cows treated with rbST. A pronounced seasonal pattern in basal and rbST-stimulated plasma IGF-I but not IGF-II was detected. Higher basal and rbST-stimulated plasma IGF-I concentrations in S occurred despite large decreases in feed intake and energy balance. Milk IGF-I and IGF-II was not affected by rbST treatment or season. Although milk IGF-I and IGF-II concentrations were unaffected by rbST treatment, total IGF-output increased due to increased milk yield. The observed seasonal patterns in plasma IGF-I may be indicative of seasonal differences in the coupling of the somatotropin-IGF axis. In particular, we failed to detect an uncoupling of the somatotropin-IGF-I axis in S despite an induced negative energy balance during thermal stress.


A two-step deep learning method for 3DCT-2DUS kidney registration during breathing.
This work proposed KidneyRegNet, a novel deep registration pipeline for 3D CT and 2D U/S kidney scans of free breathing, which comprises a feature network, and a 3D-2D CNN-based registration network. The feature network has handcrafted texture feature layers to reduce the semantic gap. The registration network is an encoder-decoder structure with loss of feature-image-motion (FIM), which enables hierarchical regression at decoder layers and avoids multiple network concatenation. It was first pretrained with a retrospective dataset cum training data generation strategy and then adapted to specific patient data under unsupervised one-cycle transfer learning in onsite applications. The experiment was performed on 132 U/S sequences, 39 multiple-phase CT and 210 public single-phase CT images, and 25 pairs of CT and U/S sequences. This resulted in a mean contour distance (MCD) of 0.94 mm between kidneys on CT and U/S images and MCD of 1.15 mm on CT and reference CT images. Datasets with small transformations resulted in MCDs of 0.82 and 1.02 mm, respectively. Large transformations resulted in MCDs of 1.10 and 1.28 mm, respectively. This work addressed difficulties in 3DCT-2DUS kidney registration during free breathing via novel network structures and training strategies.


Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma.
The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% (P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols.


T2-weighted and T1-weighted dynamic superparamagnetic iron oxide (ferucarbotran) enhanced MRI of hepatocellular carcinoma and hyperplastic nodules.
Iron oxide contrast medium (ferucarbotran) shortens both T1 and T2 relaxation time. We used the T2- and the T1-weighted dynamic ferucarbotran-enhanced magnetic resonance (MR) imaging to predict the histologic grade of hepatocellular carcinoma (HCC) and to distinguish HCC from hyperplastic nodules. Forty-three patients with 48 representative hepatic lesions (13 well differentiated HCC, 19 moderately differentiated HCC, 4 poorly differentiated HCC, 12 hyperplastic nodules) were included in the study. T1-weighted image, T2-weighted turbo spin echo, and T2*EPI (echo-planar) images were obtained before and after ferucarbotran injection. The percentage T2 signal intensity loss (T2 PSIL) of the tumors was calculated at 5 minutes and 25 minutes after contrast injection. The enhancement in dynamic T1 images was interpreted by two independent radiologists. The T2 PSIL of well differentiated HCC was 39.5 +/- 8.23%, moderately differentiated HCC was 26.4 +/- 13.78%, poorly differentiated HCC was 4.4 +/- 9.42%, and hyperplastic nodules was 44.3 +/- 11.04%. Comparison of T2 PSIL showed significant differences in the three histologically graded HCCs (p < 0.001), but not between the well differentiated HCCs and hyperplastic nodules (p > 0.05). Delayed post-contrast (25 minutes) T2-weighted images were not necessary and shortened the examination time. In the post contrast dynamic T1 study, no significant differences between all the groups was seen. Ferucarbotran MR images help in differentiating the different histologic grades of HCC but T2 PSIL could not differentiate hyperplastic nodules from well differentiated HCC. Dynamic post contrast T1-weighted images provide no additional information.


Immunological detection of high molecular weight proteins by gel and blot overlay.
The sensitivity and specificity of the gel overlay and western blot methods of immunodetection are compared for spectrins, typical high molecular weight proteins. The gel overlay method is more sensitive and specific for the immunodetection of brain spectrin (240/235) and rbc spectrin. As the western blot technique will remain the method of choice for many applications because of its relative speed, we discuss methods for optimizing its sensitivity and selectivity.


Association between physical activity and immunogenicity of an inactivated virus vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases.
To investigate whether physical activity is associated with enhanced immunogenicity of a SARS-CoV-2 inactivated vaccine (Coronavac) in patients with autoimmune rheumatic diseases (ARD) (n = 898) and in non-ARD (n = 197) individuals without pre-existing immunogenicity to SARS-CoV-2. This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial. Immunogenicity was assessed after vaccination by measuring seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity. Physical activity (active being defined as ≥ 150 min/week) and sedentary behavior (>8h/day) were assessed by questionnaire. Physically active ARD patients (n = 494) were younger and less frequently used prednisone/biologics than inactive patients (n = 404). After controlling for covariates, active patients exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary vs. inactive/sedentary ARD patients. A dose-response was observed, with greater benefits for the group of patients performing ≥ 350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively) vs. the least active group (≤30 min/week). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised patients. Clinicaltrials.gov #NCT04754698.


Clinical characteristics, HIV status, and molecular biomarkers in squamous cell carcinoma of the conjunctiva in Ghana.
Conjunctival squamous cell carcinoma (CSCC) varies in incidence geographically from 0 to 1 case per 100 000 per year globally. Additionally, the incidence of CSCC is known to increase 49% for every 10° decrease in latitude. Since the onset of the AIDS epidemic, there has been a trend of increasing incidence of CSCC in Africa, and despite relatively stable levels of ultraviolet (UV) exposure, there is an observed 12 times greater risk of developing CSCC when individuals are infected with HIV. In this study, we aim to analyze the clinical characteristics and biomarkers of CSCC in Ghana. In this study, a registry review of patients from January 2011 to May 2016 with CSCC at Komfo-Anokye Teaching Hospital in Kumasi, Ghana, was performed (n = 64). Tumor blocks of the CSCC were analyzed for the expression of various biomarkers. In this study, the median age of onset of CSCC is 46.5 years old (range of 20-90 y old). Fifty one and a half percent (n = 33) of the cohort is female. There is a low rate of smoking and alcohol use in our CSCC cohort. Thirty-nine percent (n = 12) of Ghanaian men with CSCC are HIV-, while only 12% (n = 4) of women are HIV-. Fifteen patients had metastasis to lymph nodes or other tissues, and we observed a statistically significant relationship between HIV infection and metastasis (P = 0.027, chi-squared test). We observed no statistically significant relationship between known prognostic CSCC biomarkers and HIV status, age, or tumor stage. Better characterization of CSCC could have a profound impact on the prevention, early identification, and treatment of CSCC in Africa. A retrospective chart analysis and collection of tumor samples can be challenging in this region due to methods of record keeping and stigma attached to clinical data such as HIV testing and smoking and alcohol use. As a result, in this study, data were often incomplete leading to inconclusive results and analysis that should be interpreted with caution. Future studies should consider a prospective study design that gathers clinical data in a standardized format and ensures fresh tissue from CSCC tumors.


Derivation of pre-oligodendrocytes from human endometrial stromal cells by using overexpression of microRNA 338.
MicroRNAs have a critical role in oligodendrocyte development including cell proliferation, differentiation, and myelin formation. MicroRNA 338 (miR-338) is necessary to promote oligodendrocyte differentiation by repressing negative regulators of oligodendrocyte differentiation. Oligodendrocytes (OLs) are responsible for myelin sheath synthesis around nerve fibers in the central nervous system (CNS) that form the myelin sheath of axons. Human endometrial-derived stromal cells (hEnSCs) are a new source of mesenchymal-like stem cells for cell replacement therapy. The hEnSCs, after treating with fibroblast growth factor 2/epidermal growth factor (20 ng/mL) and platelet-derived growth factor (PDGF)-AA (10 ng/mL) for 12 days, were divided in two groups: in the first group, the cells were treated by triiodothyronine (T3), and in the second group, the cells were infected by miR-338-green fluorescent protein-expressing lentiviruses. Six days after infection, the cells were collected and analyzed for the expression of stage-specific markers Nestin, microtubule-associated protein 2, neurofilament-L, oligodendrocyte lineage transcription factor, SRY-box containing gene 10, PDGF receptor alpha, 2',3'-cyclic nucleotide 3' phosphodiesterase, A2B5, O4, and myelin basic protein by immunocytochemistry and quantitative reverse transcription PCR. Result showed that in the infected cells, the expression of pre-oligodendrocyte markers was higher than that of T3-treated cells. The EnSCs can differentiate to oligodendrocyte cells by the overexpression of miR-338, and these cells can be used as a unique source for cell therapy of neurodegenerative disease.


RNA-Seq Analysis Reveals Dendrobium officinale Polysaccharides Inhibit Precancerous Lesions of Gastric Cancer through PER3 and AQP4.
There has been mounting evidence that Dendrobium officinale polysaccharides (DOP), a traditional Chinese medicine, are a potential candidate treatment for N-methyl-N'-nitro-N-nitrosoguanidine- (MNNG-) induced precancerous lesions of gastric cancer (PLGC). However, the underlying mechanisms have not been adequately addressed. We utilized RNA-Seq analysis to investigate possible molecular targets and then used Venn software to identify the differentially expressed genes (DEGs). Further, we analyzed these DEGs with core analysis, upstream analysis, and interaction network analysis by IPA software and validated the DEGs by real-time PCR and Western blot. 78 DEGs were identified from the normal control group (CON), the PLGC model group (MOD), and the DOP-treated group (DOP) by the Venn software. Further analysis of these DEGs, including core analysis, upstream analysis, and interaction network analysis, was performed by Ingenuity Pathway Analysis (IPA). The main canonical pathways involved were SPINK1 Pancreatic Cancer Pathway (-log (P value) = 4.45, ratio = 0.0667) and Circadian Rhythm Signaling (-log (P value) = 2.33, ratio = 0.0606). Circadian Rhythm Signaling was strongly upregulated in the model group versus the DOP group. CLOCK was predicted to be strongly activated (z-score = 2.236) in upstream analysis and induced the downstream PER3. In addition, the relative mRNA expression levels of seven DEGs (CD2AP, ECM1, AQP4, PER3, CMTM4, ESRRG, and KCNJ15) from RT-PCR agreed with RNA-Seq data from MOD versus CON and MOD versus DOP groups. The gene and protein expression levels of PER3 and AQP4 were significantly downregulated in the PLGC model and significantly increased by DOP treatment (9.6 g/kg). These findings not only showed DOP inhibits PLGC development by upregulating the PER3 and AQP4 gene and protein expression but also suggested that its mechanism of action involved modulating the Circadian Rhythm Signaling pathway.


Immune response to lipopolysaccharide in primary biliary cirrhosis and autoimmune diseases.
A bacteriological aetiology is suspected to be the triggering factor in primary biliary cirrhosis. We studied lipid A, the toxic and immunogenic moiety of gram-negative bacteria lipopolysaccharide, which accumulates abnormally in Kupffer cells, hepatocytes, and biliary epithelial cells in primary biliary cirrhosis patients. Anti-lipid A antibody levels from serum samples from 36 primary biliary cirrhosis patients, drawn before and after ursodeoxycholic acid treatment, were compared to those from patients with other liver diseases (n=236), non-hepatic diseases (n=249), and healthy subjects (n=75). In primary biliary cirrhosis patients, the prevalence of IgM anti-lipid A antibodies was higher before than after ursodeoxycholic acid therapy (64% vs 22%, respectively; P<0.001). Patients with anti-lipid A antibodies had significantly higher IgM levels than those without antibodies (8.7+/-1.1 g/l vs 4.4+/-0.8 g/l, P<0.02). Total IgM levels were correlated with anti-lipid A antibody levels (r=0.65, P<0.02). After therapy, the serum IgM levels decreased significantly (P<0.03). These results indicate that bacterial antigens may participate in the observed increase of serum IgM levels, and support an aetiological role of a gut-derived endotoxin antigen in the pathogenesis of primary biliary cirrhosis.


Nested oscillations and brain connectivity during sequential stages of feature-based attention.
Brain mechanisms of visual selective attention involve both local and network-level activity changes at specific oscillatory rhythms, but their interplay remains poorly explored. Here, we investigate anticipatory and reactive effects of feature-based attention using separate fMRI and EEG recordings, while participants attended to one of two spatially overlapping visual features (motion and orientation). We focused on EEG source analysis of local neuronal rhythms and nested oscillations and on graph analysis of connectivity changes in a network of fMRI-defined regions of interest, and characterized a cascade of attentional effects at multiple spatial scales. We discuss how the results may reconcile several theories of selective attention, by showing how β rhythms support anticipatory information routing through increased network efficiency, while reactive α-band desynchronization patterns and increased α-γ coupling in task-specific sensory areas mediate stimulus-evoked processing of task-relevant signals.


A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study.
The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K1 provides a significant risk factor for hip fractures. This case-cohort study aims to investigate the associations between serum vitamin K1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association. The source cohort was 21,774 men and women aged 65 to 79 years who attended Norwegian community-based health studies during 1994-2001. Hip fractures were identified through hospital registers during median follow-up of 8.2 years. Vitamins were determined in serum obtained at baseline in all hip fracture cases (n = 1090) and in a randomly selected subcohort (n = 1318). Cox proportional hazards regression with quartiles of serum vitamin K1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K1 ≥ 0.76 and 25(OH)D ≥ 50 nmol/l, II: vitamin K1 ≥ 0.76 and 25(OH)D < 50 nmol/l, III: vitamin K1 < 0.76 and 25(OH)D ≥ 50 nmol/l, and IV: vitamin K1 < 0.76 and 25(OH)D < 50 nmol/l. Age- and sex-adjusted analyses revealed an inverse association between quartiles of vitamin K1 and the risk of hip fracture. Further, a 50 % higher risk of hip fracture was observed in subjects with both low vitamin K1 and 25(OH)D compared with subjects with high vitamin K1 and 25(OH)D (HR 1.50, 95 % CI 1.18-1.90). The association remained statistically significant after adjusting for body mass index, smoking, triglycerides, and serum α-tocopherol. No increased risk was observed in the groups low in one vitamin only. Combination of low concentrations of vitamin K1 and 25(OH)D is associated with increased risk of hip fractures.


Dynamics of interrelationships between the content of lipoprotein particles, fibrinogen, and leukocyte count in the plasma from patients with coronary heart disease treated with Kwai.
The hypolipidemic effect of Kwai, a preparation based on garlic powder (Allium sativum), depended on the initial content of cholesterol and/or triglycerides. This effect was most pronounced in patients with coronary heart disease with initial cholesterol >7.0 mmol/liter and triglyceride >1.92 mmol/liter. After treatment with Kwai the correlation between triglyceride content and leukocyte count remained unchanged, the correlation between cholesterol content and leukocyte count disappeared, fibrinogen concentration decreased by 11%, and no correlation was found between fibrinogen content and leukocyte count.


Evaluation of the Antimicrobial Activity of an Extract of Lactobacillus casei-Infected Hermetia illucens Larvae Produced Using an Automatic Injection System.
In the present study, we developed an automatic mass-injection system (AMIS) to produce an extract of infected H. illucens larvae (iHIL-E) and then evaluated antimicrobial peptide (AMP) expressions and assessed the antimicrobial activity of iHIL-E against various pathogens and Lactobacillus species. AMP gene expressions were assessed by real-time quantitative polymerase chain reaction (PCR) and the antimicrobial activities of iHIL-E were estimated using a radial diffusion assay and by determining minimal inhibitory concentrations. Results showed that the antimicrobial activity of HIL extract was effectively enhanced by L. casei infection and that the gene expressions of cecropin 3 and defensin 3 (antimicrobial peptides) were up-regulated. iHIL-E also prevented the growths of Enterococcus faecalis, Streptococcus mutans, and Candida vaginitis (MICs 200, 500, and 1000 µg/100 µL, respectively) and demonstrated high protease resistance. Moreover, the growths of methicillin-resistant Staphylococcus aureus, antibiotic-resistant Pseudomonas aeruginosa and AMP-resistant bacteria, Serratia marcescens, and Pseudomons tolaasii were significantly suppressed by iHIL-E. In addition, although iHIL completely cleared Salmonella species at concentrations of >200 µg/100 µL, Lactobacillus species were unaffected by iHIL at concentrations of <1000 µg/100 µL. The present investigation shows that the devised automatic mass injection system is effective for the mass production of the extract of infected HIL and that this extract is a novel, natural, protease-resistant, antibiotic candidate with broad-spectrum antibiotic activity.


Invasion of lumbosacral ventral roots and spinal pia mater by substance P-immunoreactive axons after sciatic nerve lesion in kittens.
An indirect immunohistochemical technique was used to identify substance P immunoreactive nerve fibers in the ventral roots and spinal pia mater in kittens previously subjected to sciatic nerve lesion. It was shown that the ipsilateral L7 ventral root and spinal pia mater was invaded by substance P immunoreactive nerve fibers after the nerve lesion.


Diabetes prevalence and outcomes in hospitalized cardiorenal-syndrome patients with and without hyponatremia.
Hyponatremia is known to be associated with a worse patient outcome in heart failure. In cardiorenal syndrome (CRS), the prognostic role of concomitant hyponatremia is unclear. We sought to evaluate potential risk factors for hyponatremia in patients with CRS presenting with or without hyponatremia on hospital admission. In a retrospective study, we investigated 262 CRS patients without sepsis admitted to the University Hospital Halle over a course of 4 years. CRS diagnosis was derived from an electronic search of concomitant diagnoses of acute or chronic (NYHA 3-4) heart failure and acute kidney injury (AKIN 1-3) or chronic kidney disease (KDIGO G3-G5nonD). A verification of CRS diagnosis was done based on patient records. Depending on the presence (Na < 135 mmol/L) or absence (Na ≥ 135 mmol/L) of hyponatremia on admission, the CRS patients were analyzed for comorbidities such as diabetes, presence of hypovolemia on admission, need for renal replacement therapy and prognostic factors such as in-hospital and one-year mortality. Two hundred sixty-two CRS patients were included in this study, thereof, 90 CRS patients (34.4%) with hyponatremia (Na < 135 mmol/L). The diabetes prevalence among CRS patients was high (> 65%) and not related to the serum sodium concentration on admission. In comparison to non-hyponatremic CRS patients, the hyponatremic patients had a lower serum osmolality, hypovolemia was more prevalent (41.1% versus 16.3%, p < 0.001). As possible causes of hypovolemia, diarrhea, a higher number of diuretic drug classes and higher diuretic dosages were found. Hyponatremic and non-hyponatremic CRS patients had a comparable need for renal-replacement therapy (36.7% versus 31.4%) during the hospital stay. However, after discharge, relatively more hyponatremic CRS patients on renal replacement therapy switched to a non-dialysis therapy regimen (50.0% versus 22.2%). Hyponatremic CRS patients showed a trend for a higher in-hospital mortality (15.6% versus 7.6%, p = 0.054), but no difference in the one-year mortality (43.3% versus 40.1%, p = 0.692). All CRS patients showed a high prevalence of diabetes mellitus and a high one-year mortality. In comparison to non-hyponatremic CRS patients, hyponatremic ones were more likely to have hypovolemia, and had a higher likelihood for temporary renal replacement therapy.


Incorporation of carbon originating from CO2 into different compounds of soil microbial biomass and soil organic matter.
In general, soils without the vegetation growing on them are regarded as sources of CO2. However, there are indications that CO2 is also fixed by soil microorganisms. Although this process is not significant from a quantitative point of view, it may change the isotopic composition of soil organic matter. Therefore, we conducted an incubation study with soil and 13C-labeled CO2 to investigate this process. We found that the label was transferred from CO2 into organic compounds in soil. At the end of a 61-day incubation period, 1.3 micromol C g(-1) soil, corresponding to approximately 0.08% of the soil organic carbon, had been fixed. CO2 may, therefore, be an additional source of soil organic carbon. Compound-specific analysis of amino sugars, amino acids, and fatty acids indicated that the label is incorporated into microbial, mainly bacterial, biomass. All groups of microorganisms were involved in the assimilation of CO2, but the relatively high enrichment of mono-unsaturated and mid-chain branched fatty acids indicates that gram negative bacteria and actinomycetes may be slightly more important in this process than other groups of microorganisms.


Tryptophan exposure in various conformational isomers of bovine prothrombin fragment 1. An acrylamide quenching study.
In order to assess the importance of a variety of environmental factors on the structure of bovine prothrombin fragment 1, we have examined acrylamide quenching of fragment 1 intrinsic fluorescence. Tryptophan exposure, determined from Stern-Volmer plots, is heterogeneous with one or more of the three fragment 1 tryptophans being exposed to solvent. In the presence of Ca2+ or Mg2+ even the most accessible tryptophan(s) are relatively buried. Only small differences in tryptophan exposure may exist between fragment 1-Ca2+ and fragment 1-Mg2+ complexes. Lowering pH, on the other hand, results in increased tryptophan exposure. Finally, structural isomers of fragment 1 which exist in the absence of metal ions have identical tryptophan exposure as determined by acrylamide quenching and fluorescence intensity.


Application of knowledge about prevention in social work education and practice.
The status of preventive social work in the United States is reviewed, as are the three knowledge sources used in the teaching and practice of prevention: public health, mental health, and social work. The integration of concepts of prevention in social work curricula and practice are discussed, and new directions for its use are projected.


No evidence of exogenous origin for the abnormal glutathione redox state in schizophrenia.
Schizophrenia has been associated with low glutathione (GSH), one of the most important substrates for natural defense against oxidative stress. This abnormality is often attributed to genetic or other pathological causes. However, low GSH in schizophrenia could also be due to insufficient antioxidant consumption or other exogenous factors. We evaluated GSH in relation to diet, smoking, and medication status in schizophrenia patients. We recruited 54 participants (29 schizophrenia patients and 25 normal controls). The Antioxidant Dietary Source Questions was used to estimate the total antioxidant capacity (TAC) from participants' diet. GSH and the oxidized form of glutathione (GSSG) were assayed. We found that GSH was significantly lower (p<0.001) while %GSSG was 2 to 5 fold higher (p = 0.023) in patients compared with controls. No evidence for lower TAC dietary intake was found in schizophrenia patients compared with controls; rather nominally higher TAC level was found in the patients diet (p = 0.02). Analysis of consumption of individual food categories also failed to find evidence of reduced dietary antioxidant intake in schizophrenia patients. Smoking and medications did not significantly predict the GSH deficit either. However, there was a significant smoking by diagnosis interaction on GSH (p = 0.026) such that smoking was associated with higher GSH level in controls while smoking in patients was not associated with this effect. Schizophrenia patients may have an impaired upregulation of GSH synthesis that normally occurs due to smoking-induced antioxidative response. Lower GSH was independently present in patients on clozapine (p = 0.005) and patients on other antipsychotics (p<0.001) compared with controls. In conclusion, none of the exogenous sources played a major role in explaining abnormalities in the glutathione pathway in patients. The state of abnormal glutathione redox may therefore be a part of schizophrenia pathophysiology.


NYU's Dental Faculty Practice: Private Practice Opportunities for Faculty, Care Options for Patients, and a Mini Residency for DDS Students.
The New York-University College of Dentistry's Dental Faculty Practice operates two clinics in Manhattan, staffed by specialists from multiple disciplines who hold teaching positions at the college. These facilities service several populations, ranging from students to patients with very complex dental conditions. The practices are managed by the school with a view to financial stability while allowing faculty members to focus on their advanced professional skills.


Urethral paraganglioma presenting as a urethral polyp.
We report the first case of paraganglioma of the urethra presenting as a pendulous urethral polyp. The pathologic criteria and usual site of presentation in the genitourinary tract are discussed.


Pristane-induced effects on cytochrome P-4501A, ornithine decarboxylase and putrescine in rats.
The effects of pristane (2,6,10,14-tetramethylpentadecane) on cytochrome P-4501A (cP4501A) activity in microsomes, as well as on ornithine decarboxylase (ODC) activity and concomitant putrescine levels were examined in Copenhagen rats. In general, pristane treatment led to increased cP4501A levels when compared to basal levels, while co-treatment with 3-methylcholanthrene (3-MC) and pristane elicited augmented cP4501A responses when compared to responses induced by 3-MC alone. Increases in both ODC activity and putrescine levels were also observed in pristane treated rats. Collectively, these results indicate that pristane influences cP4501A activity and elicits promoter-like responses as reflected in elevated ODC activity and increased amount of putrescine.


Patterns of coronary artery stenosis vasomotion: observed versus "predicted" stenosis reactivity in patients with chronic stable angina.
Patterns of constriction and dilatation of angiographically normal coronary artery segments and coronary stenoses, in response to vasoactive stimuli, remain speculative. We compared the vasomotor response of angiographically normal and stenotic coronary segments and assessed the effects of stenosis location and morphology on coronary stenosis vasomotion in 52 patients with chronic stable angina (40 men and 12 women) who underwent intracoronary ergonovine or isosorbide dinitrate administration or both. Changes in coronary diameter in response to nitrate and ergonovine were assessed by computed arteriography. The "predicted" change in stenosis diameter was calculated according to the "geometric theory" (based on the vasomotor response of angiographically normal segments adjacent to the lesion and on stenosis severity). Coronary diameter was assessed at baseline and after nitrate administration in 58 stenoses (34 concentric and 24 eccentric), of which 40 were located proximally and 18 distally, and also after ergonovine administration (23 stenoses: 14 proximal and 9 distal, 14 concentric and 9 eccentric). Significant (> or = 10% lumen diameter change) vasoconstriction was observed after ergonovine administration in 14 of the 23 stenoses (61%), and significant vasodilation was noted after nitrate administration in 29 of 58 stenoses (50%). A larger proportion of distal (89%) and eccentric (89%) compared with proximal (43%) and concentric (43%) stenoses showed a greater than 10% vasoconstriction after ergonovine administration (P < 0.05). Vasodilatation after nitrate administration was also observed in a larger proportion of distal (78%) and eccentric (67%) than in proximal (38%) and concentric (38%) stenoses (P < 0.05). On average, the "observed" changes in coronary diameter in response to nitrate and ergonovine administration were of significantly less magnitude than those "predicted" by the geometric theory in both proximal and distal stenoses and in concentric and eccentric stenoses. In only 17% of stenoses were observed and predicted vasoconstriction similar. Our results suggest that in patients with chronic stable angina, calculations based on the "geometric theory" cannot predict the actual vasomotor response of a stenosis. Factors other than severity, such as baseline coronary tone, stenosis location, and stenosis morphology, appear to modulate stenosis vasomotion in vivo.


High throughput screening of bradykinin-potentiating peptides in Bothrops moojeni snake venom using precursor ion mass spectrometry.
Snake venoms are known to be an extensive source of bioactive peptides. Bradykinin-potentiating peptides (BPPs) are inhibitors of the angiotensin-converting enzyme that have already been identified in the venom of many snake, scorpion, spider and batrachian species. Their most characteristic structural features are an invariable N-terminal pyroglutamate residue (pGlu or Z) and two consecutive proline residues at the C-terminus. Fragmentation of BPPs by collision-induced dissociation during electrospray tandem mass spectrometry analysis (ESI-MS/MS) generates a predominant signal at m/z 213.1 corresponding to the y-ion of the terminal Pro-Pro fragment. In addition, signals at m/z 226.1 and 240.1 that correspond to the b ions of the N-terminus pGlu-Asn and pGlu-Lys, respectively, can often be observed. Based on these structural determinants, the present work describes an original methodology for the discovery of BPPs in natural extracts using liquid chromatography coupled to ESI-MS/MS operated in precursor ion-scan mode. The venom of the Bothrops moojeni snake was used as a model and the methodology was applied for subsequent structural analysis of the identified precursors by tandem mass spectrometry on quadrupole-time-of-flight (Q-TOF) and matrix-assisted laser-desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS) instruments. More than 40 peptides below 2500 Da could be detected, among them 20 were shown to belong to the BPP-like family including the related tripeptides pGlu-Lys-Trp and pGlu-Asn-Trp. A total of 15 new sequences have been identified using this approach.


Concentration-dependent effects of carbon nanotubes on growth and biphenyl degradation of Dyella ginsengisoli LA-4.
To enrich the understanding on interactions between carbon nanotubes (CNTs) and microbes, the responses of a biphenyl-degrading bacterium to single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs) and carboxyl single-walled carbon nanotubes (SWCNT-COOHs) were investigated. Electron microscopy, viability test, cellular membrane integrity, and oxidative stress analyses indicated that CNT toxicity was mainly caused by physical piercing. Apart from antibacterial activities, the experimental results showed that CNTs enhanced cell growth and biphenyl degradation at certain concentrations (1.0-1.5 mg/L). The CNTs aggregated and adsorbed cells and biphenyl to form a CNTs-cells-biphenyl coexisting system, thus it created a suitable microenvironment for cell attachment and proliferation where the cells could utilize biphenyl easier for their growth. To the best of our knowledge, this is the first report about CNTs' impact on biodegradation efficacy and growth of aromatic-degrading bacterium.


Risk factors for mortality after emergency laparotomy: scoping systematic review.
Emergency laparotomy (EL) is a common procedure with high mortality leading to several efforts to record and reduce mortality. Risk scores currently used by quality improvement programmes either require intraoperative data or are not specific to EL. To be of utility to clinicians/patients, estimation of preoperative risk of mortality is important. We aimed to explore individual preoperative risk factors that might be of use in developing a preoperative mortality risk score. Two independent reviewers identified relevant articles from searches of MEDLINE, EMBASE and Cochrane databases from January 1980 to January 2018. We selected studies that evaluated only preoperative predictive factors for mortality in EL patients. The search yielded 6648 articles screened, with 22 studies included examining 157 728 patients. The combined post-operative 30-day mortality was 13%. All, but one small study, were at low risk of bias. A meta-analysis of results was not possible due to the heterogeneity of populations and outcomes. Age, American Society of Anesthesiologists, preoperative sepsis, dependency status, current cancer and comorbidities were associated with increased mortality. Acute physiological derangements seen in renal, albumin and complete blood count assays were strongly associated with mortality. Delay to surgery and diabetes did not influence mortality. Higher body mass index was protective. Preoperatively, risk factors identified can be used to develop and update risk scores specific for EL mortality. This scoping review focused on the preoperative setting which helps tailor treatment decisions. It highlights the need for further research to test the relevance of newer risk factors such as frailty and nutrition.


In vivo properties of colicin A: channel activity is voltage dependent but translocation may be voltage independent.
The kinetics of K+ efflux caused by colicin A in Escherichia coli-sensitive cells have been investigated by using a K(+)-selective electrode. The order of magnitude of the rate of K+ efflux per colicin molecule was comparable to that of ion channels. The dependence of K+ efflux upon multiplicity, pH, temperature, and membrane potential (delta psi) was determined. The translocation of colicin A from the outer membrane receptor to the inner membrane and insertion into the inner membrane required a fluid membrane, but once inserted, the channel properties showed little dependence upon the state of the lipids. At a given multiplicity, the lag time before the onset of K+ efflux was found to reflect the time required for translocation and/or insertion of colicin into the cytoplasmic membrane. Opening of the channel only occurred above a threshold value of delta psi of 85 +/- 10 and 110 +/- 5 mV at pH 6.8 and 7.8, respectively. Conditions were designed for closing and reopening of the channel in vivo. These conditions allowed us to test separately the delta psi requirements for translocation and channel opening: translocation and/or insertion did not appear to require delta psi. The channel formed in vivo featured properties similar to that of the channel in lipid planar bilayers.


Proliferation of epithelial cells of vas deferens and epididymis in young adult rabbits.
Epithelial proliferation of the vas deferens and epididymis was studied in rabbits after flash or continuous labeling with DNA precursor by autoradiography. A high proliferative capacity of the epithelium was found: after 2 days of labeling, 11% of labeled cells were found in the vas deferens and 20% in the ductus epididymidis.


Oral Anticoagulant Use in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Review of the Evidence With Recommendations for Australian Clinical Practice.
Chronic kidney disease is common in patients with atrial fibrillation (AF) and is associated with heightened risks of stroke/systemic embolisation and bleeding. In this review we outline the evidence for AF stroke prevention in kidney disease, identify current knowledge gaps, and give recommendations for anticoagulation at various stages of chronic kidney disease. Overall, anticoagulation is underused. Warfarin use becomes increasingly difficult with advancing kidney disease, with difficulty maintaining international normalised ratio (INR) in therapeutic range, increased risk of intracranial and fatal bleeding compared to non-vitamin K oral anticoagulants (NOACs), and high rates of discontinuation. Similarly, the direct thrombin inhibitor dabigatran is not recommended as it is predominantly renally excreted with consequent increased plasma levels and bleeding risk with advanced kidney disease. The Factor Xa inhibitors apixaban and rivaroxaban have less renal excretion (25-35%), modest increases in plasma levels with advancing kidney disease, and are the preferred first line choice for anticoagulation in moderate kidney disease based on strong evidence from randomised clinical trials (RCTs). In severe kidney disease there is a paucity of RCT data, but extrapolation of the pharmacokinetic and RCT data for moderate kidney disease, and observational studies, support the considered use of dose-adjusted Factor Xa inhibitors unless the bleeding risk is prohibitive. In Australia, apixaban is approved for creatinine clearance down to 25 mL/min, and rivaroxaban down to 15 mL/min. For end-stage kidney disease warfarin is the only agent approved, but we recommend against anticoagulation (except in selected cases) due to high bleeding risk, multiple co-morbidities, and questionable benefit.


The effect of remote learning on the mental health of first year university students in Japan.
We examined the effects of the coronavirus disease 2019 (COVID-19) pandemic on first-year Japanese university students' mental health by comparing current year's survey results with previous year's results. Accordingly, an online survey was conducted on first-year Gifu University students from April 20 to May 31, 2020. Study results revealed that, despite the emergence of the COVID-19 pandemic, the number of "high-risk" students and the depression level were lower among the 2020 first-year students compared to previous year's students. However, the 2020 first-year students experienced high academic distress since they had to adapt to an unfamiliar e-learning environment.


Hypercalcitoninemia in pancreatitis--evidence for immunochemical heterogeneity.
Recently in our laboratory we have demonstrated increased immunoreactive calcitonin (iCT) levels in 4 patients with acute pancreatitis and hypocalcemia. The present study consists of 17 additional patients in whom serial determinations for (iCT) were performed. Furthermore, with the use of 2 different antisera directed against human calcitonin we present evidence for immunochemical heterogeneity of this hormone in acute pancreatitis.


Caudal block vs. transversus abdominis plane block for pediatric surgery: a systematic review and meta-analysis.
The caudal block and transversus abdominis plane block (TAP) are commonly used in combination with general anesthesia for pediatric lower abdominal, inguinal, and genitourinary surgeries. There is limited data directly comparing the impact of these techniques on recovery. In this meta-analysis, we compare the duration of postoperative analgesia between these two techniques. This review examined the duration of analgesia in pediatric patients (age 0-18 years) undergoing surgery who received caudal or TAP block after induction of general anesthesia. The primary outcome was duration of analgesia, defined as the time to first rescue analgesic dose. Secondary outcomes included number of rescue analgesic doses, acetaminophen usage within 24 h postoperatively, 24 h pain score area under the curve, and postoperative nausea and vomiting. We systematically searched Pubmed, Central, EMBASE, CINAHL, Google Scholar, Web of Science citation index, the US clinical trials register, and abstracts from prominent 2020-2022 anesthesia conferences for randomized controlled trials that compared these blocks and reported analgesia duration. Twelve RCTs inclusive of 825 patients were identified. TAP block was associated with longer analgesia duration (Mean difference = 1.76 h, 95% CI: 0.70-2.81, p = 0.001) and reduced doses of rescue analgesic within 24 h (Mean difference = 0.50 doses, 95% CI: 0.02-0.98, p = 0.04). No statistically significant differences were detected in other outcomes. This meta-analysis suggests that TAP block provides greater duration of analgesia than caudal block after pediatric surgeries. TAP block was also associated with fewer rescue analgesic doses in the first 24 h without increased pain scores. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=380876, identifier: CRD42022380876.