Psychometric properties of the Caring Efficacy Scale among personal care attendants working in residential aged care settings.
This study assessed the psychometric properties of the Caring Efficacy Scale (CES) among personal care attendants providing care to older residents in residential aged care settings. This cross-sectional study was completed in Australia in 2020-2021. Confirmatory factor analysis (CFA) of the 30-item original CES (Model 1) and 28-item CES validated in registered nurses (Model 2) was conducted to assess the goodness of fit of these models in our study population. Due to unsatisfactory fit indices for both models, exploratory factor analysis (EFA) was conducted to examine the dimensionality and underlying structure of the original CES among personal care attendants. Internal consistency of the final scale and subscales identified was examined using item-total correlations and Cronbach's alpha coefficients. Two hundred and eighty personal care attendants participated in the study. The model fit indices such as Comparative Fit Index and Tucker Lewis Index of both models were less than 0.90, while the Standardised Root Mean Square Residual and Root Mean Square of Approximation values were greater than or equal to 0.08 and 0.06, respectively. The EFA identified a two-factor structure, and 22 items of the 30 in the original scale were retained. Item-total correlations amongst items retained in the scale and subscales were greater than 0.3. Cronbach's alpha for the abbreviated scale was 0.85, with 0.83 and 0.79, respectively, for the two subscales. The modified CES can be used as a robust tool to assess the self-efficacy of personal care attendants in providing care to older residents in residential aged care settings.


Clinical factors associated with safety and efficacy in patients receiving direct oral anticoagulants for non-valvular atrial fibrillation.
Although patients suffering from atrial fibrillation have increased worldwide, detailed information about factors associated with bleeding during direct oral anticoagulant therapy remains insufficient. We studied 1086 patients for whom direct oral anticoagulants were initiated for non-valvular atrial fibrillation between April 2011 and June 2017. Endpoints were clinically relevant bleeding or major adverse cardiac and cerebrovascular events until the end of December 2018. Incidences of bleeding and thrombosis were 4.5 per 100 person-years and 4.7 per 100 person-years, respectively. Most bleeding events represented gastrointestinal bleeding. Multivariate analysis revealed initiation of anticoagulants at ≥ 85 years old as significantly associated with bleeding, particularly gastrointestinal bleeding, but not major cardiac and cerebrovascular events. Other significant factors included chronic kidney disease, low-dose aspirin and nonsteroidal anti-inflammatory drugs. For gastrointestinal bleeding alone, histories of gastrointestinal bleeding and malignancy also showed positive correlations, in addition to the above-mentioned factors. Clinicians should pay greater attention to the risk of gastrointestinal bleeding when considering prescription of anticoagulants to patients ≥ 85 years old with atrial fibrillation.


A taxonomy of driving errors and violations: Evidence from the naturalistic driving study.
Driving errors and violations are identified as contributing factors in most crash events. To examine the role of human factors and improve crash investigations, a systematic taxonomy of driver errors and violations (TDEV) is developed. The TDEV classifies driver errors and violations based on their occurrence during the theoretically based perception-reaction process and analyzes their contributions in safety critical events. To empirically explore errors and violations, made by drivers of instrumented vehicles, in diverse built environments, this study harnesses unique and highly detailed pre-crash sensor data collected in the Naturalistic Driving Study (NDS), containing 673 crashes, 1,331 near-crashes and 7,589 baselines (no-event). Human factors are categorized into recognition errors, decision errors, performance errors, and errors due to the drivers' physical condition or their lack of contextual experience/familiarity, and intentional violations. In the NDS data, built environments (measured by roadway localities) are classified based on roadway functional classification and land uses, e.g., residential areas, school zones, and church zones. Based on the crash percentage to baseline percentage in a specific locality, interstates and open country/open residential (rural and semi-rural settings) may pose lower risks, while urban, business/industrial, and school zone locations showed higher crash risk. Human errors and violations by instrumented vehicle drivers contributed to 93% of the observed crashes, while roadway factors contributed to 17%, vehicle factors contributed in 1%, and 4% of crashes contained unknown factors. The most common human errors were recognition and decision errors, which occurred in 39% and 34% of crashes, respectively. These two error types occurred more frequently (each contributing to nearly 39% of crashes) in business or industrial land use environments (but not in dense urban localities). The findings of this study reveal continued prevalence of human factors in crashes. The distribution of driving errors and violations across different roadway environments can aid in the implementation of driver assistance systems and place-based interventions that can potentially reduce these driving errors and violations.


What causes residual dual-task interference after practice?
Practice can dramatically reduce dual-task interference, but typically does not eliminate interference entirely. Residual interference after practice is especially large with certain non-preferred modality pairings (e.g., auditory-manual and visual-vocal). Does this residual interference imply the existence of a persistent central-processing bottleneck? To address this question, we transferred participants with previous dual-task practice to a psychological refractory period design. Although we observed residual dual-task costs in all four experiments, there was no evidence for a bottleneck, even with non-preferred modality pairings. We conclude that practice can eliminate the bottleneck limitation, but performance is still subject to other sources of interference, such as competition between central codes of the two tasks.


Comparative immunocompetence and interspecies transmission of avian orthoavulavirus-1 in feral birds originating from rural and urban settings.
Feral birds residing close to urban settings exhibit higher immunocompetence against environmental pathogens than their counterparts in rural areas. In this study, we comprehensively evaluated the immunocompetence of five specific feral bird species and investigated the potential for interspecies transmission and pathogenicity of Avian orthoavulavirus-1 (AOAV-1) originating from the Anseriformes order. The immunocompetence assessment involved administering the phytohemagglutinin (PHA) test to individual groups of birds from rural and urban settings, measuring patagium thickness at specific time intervals (12, 24, 36, 48, and 60 h) following the administration of 0.1 mL (1 mg/mL) of PHA. Urban birds displayed significantly enhanced mean swelling responses, particularly urban pigeons, which exhibited a significant difference in patagium thickness at all-time intervals except for 24 h (p = 0.000, p = 0.12). Similarly, rural and urban quails and crows showed substantial differences in patagium thickness at all-time intervals except for 12 h (p = 0.542, p = 0.29). For the assessment of interspecies transmission potential and pathogenicity, each feral bird group was separately housed with naive broiler birds (n = 10 each) and challenged with a velogenic strain of AOAV-1 isolate (Mallard-II/UVAS/Pak/2016) at a dose of 1 mL (108 EID50/mL). Urban birds demonstrated higher resistance to the virus compared to their rural counterparts. These findings highlight the specific immunocompetence of feral bird species and their potential contributions to AOAV-1 transmission and pathogenicity. Continuous monitoring, surveillance, and strict implementation of biosafety and biosecurity measures are crucial for effectively controlling AOAV-1 spillover to the environment and wild bird populations in resource-limited settings, particularly Pakistan.


Pembrolizumab for Treatment of Patients with Advanced or Unresectable Melanoma.
From Coley's toxin to combination immune checkpoint inhibition, strategies to activate the immune system and generate anticancer immunity have been ongoing for well over a century. Over the past decade, the so-called immune checkpoint inhibitors, generally monoclonal antibodies that target key regulators of T-cell activation, emerged as the most effective immune-targeted agents. Pembrolizumab is the first anti-programmed death 1 (PD-1) antibody approved by the FDA for the treatment of metastatic melanoma. With responses seen in 25% to 40% of patients, depending on dose and setting (i.e., before or after ipilimumab), pembrolizumab specifically and anti-PD-1 antibodies generally are revolutionizing the treatment of melanoma. However, in the setting of other recent advances in the field, a number of practical issues are emerging that need to be addressed to optimize the care of patients with melanoma. First, the optimal sequencing of therapy (first-line immunotherapy over molecular targeted therapy, ipilimumab versus pembrolizumab as initial immune checkpoint inhibitor) is unknown and must be evaluated through randomized trials. Second, there is a strong rationale to combine immune checkpoint inhibitors (i.e., anti-PD-1 with ipilimumab) and to combine immune therapies with targeted therapy agents, so determining whether combination therapy is better than direct sequencing is another critical issue that needs to be addressed in carefully carried out studies.


Marine protected area improves yield without disadvantaging fishers.
Potential fishery benefits of Marine Protected Areas (MPAs) are widely acknowledged, yet seldom demonstrated, as fishery data series that straddle MPA establishment are seldom available. Here we postulate, based on a 15-year time series of nation-wide, spatially referenced catch and effort data, that the establishment of the Goukamma MPA (18 km alongshore; 40 km²) benefited the adjacent fishery for roman (Chrysoblephus laticeps), a South African endemic seabream. Roman-directed catch-per-unit-effort (CPUE) in the vicinity of the new MPA immediately increased, contradicting trends across this species' distribution. The increase continued after 5 years, the time lag expected for larval export, effectively doubling the pre-MPA CPUE after 10 years. We find no indication that establishing the MPA caused a systematic drop in total catch or increased travel distances for the fleet. Our results provide rare empirical evidence of rapidly increasing catch rates after MPA implementation without measurable disadvantages for fishers.


The relation between serum MDA and cystatin C levels in chronic spinal cord injury patients.
The assessment of renal function is particularly important in patients with spinal cord injury (SCI). Creatinine (Cr) is known to be unsuitable as a marker of renal function in SCI because of muscle wasting. Although cystatin C (cys-C) is more reliable than Cr, its expression may be affected by oxidative stress accompanying SCI. The aim of the study was to estimate the cys-C levels in SCI patients with normal functioning kidneys. The prooxidant/antioxidant state in plasma of the patients and controls was measured, and any correlations between these parameters and cys-C were determined. Blood samples from 41 chronic SCI patients and 13 controls were obtained. Serum Cr was assayed by the Cobas Integra 400 autoanalyzer and cys-C by particle-enhanced immunoturbidimetry. Heparinized plasma was used for biochemical determinations of vitamin E, total antioxidant status (TAS) and malondialdehyde (MDA). Cr, TAS and MDA levels were significantly lower in SCI patients compared to the controls (P = 0.007, P = 0.019, P = 0.000, respectively), whereas no difference was seen in cys-C and vit E concentrations. Body mass indices (BMI) of SCI patients were less than those of the controls (P = 0.03). No correlation existed between cys-C and MDA in SCI patients and controls. Cys-C levels were independent from the body mass indices of subjects. In our study, although BMI and MDA were both affected in SCI patients, cys-C levels were unchanged. Therefore, the measurement of cys-C appeared to be of value for the follow-up of renal function in SCI. The low MDA levels observed in these patients suggest that various adaptation mechanisms may be relevant for subjects undergoing prolonged stress situations.


A novel approach for N-glycosylation studies using detergent extracted microsomes.
Recently, it has become apparent that asparagine-linked (N-linked) oligosaccharide at an early stage of processing can play an important role in quality control of the secretory pathway. Here, we have developed a system for better understanding of the N-glycosylation machinery and its involvement in quality control in the endoplasmic reticulum (ER). Rough microsomes (RM) treated with 0.18% Tx-100 (TxRM) preserved translocation activities to a similar extent detected in RM. TxRM were depleted of many soluble proteins including glucosidase II, BiP and Erp72, but maintained approximately 80% of calnexin, a membrane protein. More importantly, TxRM revealed insufficient glycosylation of T cell receptor-alpha (TCR-alpha), suggesting that a factor or factors extracted with 0.18% Tx-100 is responsible for facilitating the transfer of oligosaccharides to the protein. In addition, the top band of TCR-alpha translated in TxRM migrated slower than that in RM, but faster than that in RM treated with castanospermine (CST), an inhibitor of glucosidase I/II. This suggests that the trimming of the inner two glucose sugars is impaired by the loss of glucosidase II. Furthermore, we demonstrated that TCR-alpha coprecipitated with calnexin migrated between unglucosylated and diglucosylated forms on SDS-PAGE. Thus, the treatment of RM with low concentration of detergent is a very powerful method for elucidating not only N-glycosylation processes but also other biological functions such as quality control in the ER.


Care of infants with esophageal atresia, tracheoesophageal fistula, and associated anomalies.
One hundred consecutive patients with esophageal atresia or tracheoesophageal fistula, or both, were treated at The Children's Mercy Hospital during the past 14 years. Each patient was evaluated and a plan for therapy was formulated depending on the type and urgency of concomitant disease. Healthy patients were treated by primary repair. Those with respiratory disease were treated before repair by gastrostomy, upper pouch suction, and antibiotics. In the small premature infant and the patient with major associated anomalies, repair of the esophageal atresia and tracheoesophageal fistula was postponed by gastrostomy, upper pouch suction, and parenteral nutrition while the concomitant disease was treated. Fifteen patients with life-threatening associated anomalies required operation before esophageal repair and 13 of them survived. During the initial hospitalization two deaths related to esophageal atresia occurred, whereas three prerepair and two late (2 1/2 and 3 months) postrepair deaths related to associated anomalies occurred. Thus, 93 of the 100 patients left the hospital alive. The increased survival is due not only to improved care of esophageal atresia and tracheoesophageal fistula, but also to a more aggressive approach to the treatment of the serious associated anomalies.


Single agent maintenance therapy for advanced stage non-small cell lung cancer: a meta-analysis.
Maintenance therapy is a new treatment paradigm for advanced non-small cell lung cancer (NSCLC). We conducted a meta-analysis of randomized studies with single agent maintenance therapy. An electronic literature search of public databases (MEDLINE, EMBASE, Cochrane library) and manual search of relevant conference proceedings was performed. A formal meta-analysis was conducted using Comprehensive Meta Analysis software (Version 2.0). Outcome data were pooled and reported as hazard ratio (HR). The primary outcome of interest was overall survival (OS) and secondary outcome was progression free survival (PFS). Twelve studies were included (5 meeting abstracts, 7 full manuscripts) with a total of 4286 patients (maintenance arm/control arm - 2449/1837, median age 61 years, males - 69%). The OS (HR 0.86, 95% confidence intervals [CI] 0.80-0.92; P=0.0003) and PFS (HR 0.80, 95% CI 0.77-0.84; P<0.0001) were superior with maintenance therapy. 'Switch' maintenance was associated with significant OS and PFS improvement (OS HR 0.84, 95% CI 0.77-0.91; P=0.00026; PFS HR 0.62, 95% CI 0.57-0.67; P<0.0001). Despite a modest improvement in PFS (HR 0.90, 95%CI 0.85-0.95; P=0.007), "continuation" maintenance was not associated with survival benefit (HR 0.927, 95%CI 0.78-1.09; P=0.33). Improvements in OS and PFS were observed with both EGFR-targeted agents (HR 0.83, 95% CI 0.74-0.92; P=0.004; HR 0.64, 95% CI 0.58-0.71 P<0.0001) and cytotoxic agents (HR 0.89, 95% CI 0.80-0.98; P=0.018; HR 0.85, 95% CI 0.80-0.89; P<0.0001). Single agent maintenance therapy improves overall survival, though statistical significance was only noted with 'switch' maintenance.


From Debt to Dollars: Assessing a General Surgeon's Career Value.
Surgical residents make decisions that may have a dramatic impact on career earnings based off conceptions regarding future income potential. This study examines the effect of debt burden, repayment plan, and practice setting on a general surgeon's career value. Debt levels, repayment plans, and practice setting were considered to model a surgeon's career value using net present value (NPV) across 35 scenarios. The NPV was calculated using salary, education debt, yearly spending, and a discount rate of 5%. Salary data were obtained from the Medical Group Management Association, student debt information from the Association of American Medical Colleges, and tax and household spending data from U.S. government records. Assumptions included no gaps in training, no prior debt, single-person household, and career duration of 35 y. A general surgeon's salary adequately repays debt burdens from $100,000-$300,000 over 10-25 y, regardless of repayment plan or practice setting. Practice setting decreased career value for academic surgeons when debt burden and repayment plan were held constant: the NPV for an academic surgeon was $382,000 compared to $500,000 for a nonacademic surgeon with the same debt and repayment plan. Debt burden repaid through unsubsidized and income-based repayment plans reduced NPV for all surgeons, while subsidized plans increased NPV. The projected NPV for all scenarios ranged $2.35M-$2.87 M. Though the modeled scenarios do not account for prior debt burden, major expenditures, or increases in yearly household spending beyond national averages, surgery residents should be aware that general surgery remains a financially feasible career.


Microscopic Epididymal Sperm Aspiration (MESA) Should be Employed Over Testicular Sperm Extraction (TESE) Sperm Retrieval Surgery for Obstructive Azoospermia (OA).
Testicular sperm extraction (TESE) has been widely used as a sperm extraction surgery for azoospermia even for obstructive azoospermia (OA) because it does not require surgical skill. However, there are postoperative pain issues, and subsequent testicular atrophy and decreased testosterone levels may occur with TESE. This study examines the usefulness of microscopic epididymal sperm aspiration (MESA) for OA. We studied 108 patients diagnosed with OA and treated with MESA at our institute between April 2004 and December 2021. The MESA was performed using a micropipette with a micropuncture technique under an operative microscope. When no sperm were present or motility was not observed, additional punctures to the epididymal tubule were performed. Motile sperm were recovered in all cases (108 cases). Of these, intracytoplasmic sperm injection (ICSI) using frozen-thawed sperm was performed in 101 cases and the normal fertilization rate was 76.2%. A total of 436 embryo transfer (ET) cycles were performed. The implantation rate per transfer cycle was 47.9%, the clinical pregnancy rate was 41.0%, and the live birth rate was 23.7%. The per-case live birth rate was 84.8%. MESA-ICSI has a very good fertilization rate, clinical pregnancy rate, and delivery rate. Furthermore, the patient's postoperative pain is less, the number of sperm collected is larger, the burden on the embryologist who processes the collected sperm is less, and ICSI can be easily attempted after frozen-thawed sperm. MESA rather than TESE should be employed for the OA subjects.


Effects of intra-aortic balloon pump on in-hospital outcomes and 1-year mortality in patients with acute myocardial infarction complicated by cardiogenic shock.
The role of intra-aortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction (AMI) is still a subject of intense debate. In this study, we aim to investigate the effect of IABP on the clinical outcomes of patients with AMI complicated by cardiogenic shock undergoing percutaneous coronary intervention (PCI). From the Medical Information Mart for Intensive Care (MIMIC)-IV 2.2, 6017 AMI patients were subtracted, and 250 patients with AMI complicated by cardiogenic shock undergoing PCI were analyzed. In-hospital outcomes (death, 24-hour urine volumes, length of ICU stays, and length of hospital stays) and 1-year mortality were compared between IABP and control during the hospital course and 12-month follow-up. An IABP was implanted in 30.8% (77/250) of patients with infarct-related cardiogenic shock undergoing PCI. IABP patients had higher levels of Troponin T (3.94 [0.73-11.85] ng/ml vs. 1.99 [0.55-5.75] ng/ml, p-value = 0.02). IABP patients have a longer length of ICU and hospital stays (124 [63-212] hours vs. 83 [43-163] hours, p-value = 0.005; 250 [128-435] hours vs. 170 [86-294] hours, p-value = 0.009). IABP use was not associated with lower in-hospital mortality (33.8% vs. 33.0%, p-value = 0.90) and increased 24-hour urine volumes (2100 [1455-3208] ml vs. 1915 [1110-2815] ml, p-value = 0.25). In addition, 1-year mortality was not different between the IABP and the control group (48.1% vs. 48.0%; hazard ratio 1.04, 95% CI 0.70-1.54, p-value = 0.851). IABP may be associated with longer ICU and hospital stays but not better short-and long-term clinical prognosis.


Opiate antagonist--receptor interaction unchanged by acute or chronic opiate treatment.
The apparent pA2 of naloxone, a measure of the apparent receptor affinity for the antagonist, was estimated in naive rats, in rats after acute and various schedules of chronic morphine pretreatment, and in rats during abrupt withdrawal. The results were adjusted to compensate for the amount of pretreatment drug in the rat brains as, otherwise, such a drug could have inflated the apparent pA2 values (see appendix). After this adjustment, a tendency of the apparent pA2 values to be increased after chronic pretreatment disappeared. The apparent pA2 of naloxone in acutely pretreated rats was also unchanged from that in naive rats, while the results in abruptly withdrawn rats were ambiguous. Thus, no change in the affinity of the antagonist for opiate receptors was found and theories suggesting that a conformational change takes place in the opiate receptor during the development of tolerance/dependence could not be supported.


Examining the impact of ADHD polygenic risk scores on ADHD and associated outcomes: A systematic review and meta-analysis.
Early identification of attention-deficit/hyperactivity disorder (ADHD) is critical for mitigating the many negative functional outcomes associated with its diagnosis. Because of the strong genetic basis of ADHD, the use of polygenic risk scores (PRS) could potentially aid in the early identification of ADHD and associated outcomes. Therefore, a systematic search of the literature on the association between ADHD and PRS in pediatric populations was conducted. All articles were screened for a priori inclusion and exclusion criteria, and, after careful review, 33 studies were included in our systematic review and 16 studies with extractable data were included in our meta-analysis. The results of the review were categorized into three common themes: the associations between ADHD-PRS with 1) the diagnosis of ADHD and ADHD symptoms 2) comorbid psychopathology and 3) cognitive and educational outcomes. Higher ADHD-PRS were associated with increased odds of having a diagnosis (OR = 1.37; p<0.001) and more symptoms of ADHD (β = 0.06; p<0.001). While ADHD-PRS were associated with a persistent diagnostic trajectory over time in the systematic review, the meta-analysis did not confirm these findings (OR = 1.09; p = 0.62). Findings showed that ADHD-PRS were associated with increased odds for comorbid psychopathology such as anxiety/depression (OR = 1.16; p<0.001) and irritability/emotional dysregulation (OR = 1.14; p<0.001). Finally, while the systematic review showed that ADHD-PRS were associated with a variety of negative cognitive outcomes, the meta-analysis showed no significant association (β = 0.08; p = 0.07). Our review of the available literature suggests that ADHD-PRS, together with risk factors, may contribute to the early identification of children with suspected ADHD and associated disorders.


Advances in the epigenetics of fibroblast biology and fibrotic diseases.
Fibroblasts have a central role in tissue fibrosis and fibrotic diseases. Fibroblast activation is regulated by several mechanisms including epigenetic modifications; histone modifications, DNA methylation and non-coding RNAs. Although research has significantly contributed to our basic understanding of fibrotic diseases over the last decade, cooperative activity of epigenetic mechanisms demonstrates the complexity of fibrogenesis. This review will summarise the latest epigenetic advances in fibroproliferative diseases. Current studies investigating biological implications of epigenetic modifiers, inhibitors of DNA methylation/histone modifying enzymes are promising. Given that ncRNA-based or CRISPR-based epigenetic-editing have shown therapeutic potential in the preclinical models; we consider epigenetic mechanisms represent a potential tool with clinical utility.


Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphisms: association with early coronary disease.
To examine the association between coronary artery disease and polymorphisms at the angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) genes. A total of 181 patients younger than 50 years and 240 controls from the same homogeneous Caucasian population (Asturias, Northern Spain) were genotyped (using polymerase chain reaction) for the ACE insertion/deletion (ACE-I/D) and the AT1R A/C transversion (AT1R-A/C) (3-untranslated region) polymorphisms. The DD-genotype was at a non-significant higher frequency among patients (50%) than in controls (41%). No difference between the two groups was found for the AT1R-genotypes. Distribution of ACE-genotypes according to AT1R-genotypes showed a significant association between ACE-DD and AT1R-CC and early coronary disease. Among the CC patients 58% were DD, compared to 21% among the controls (p = 0.02; OR = 5.32, 95% CI = 1.45, 19.51). We determined the distribution of these genotypes among the hypertensive and non-hypertensive patients. Frequencies of ACE- or AT1R-genotypes did not differ between the two groups. However, we found an interaction between the DD- and CC-genotypes in the group of normotensives. Among the CC patients, 13% of the hypertensives and 75% of the normotensives were DD (p = 0.014). Our results indicate a synergistic contribution of ACE and AT1R polymorphisms to the risk of coronary artery disease. This gene-gene interaction could have clinical implications. Approximately 2% of individuals in our population are CC + DD, and the genotyping of both polymorphisms could identify those with a high relative risk for coronary artery disease.


Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up.
Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. Twenty eight AN of median age of 26.5 (20-31.50) years and disease duration of 3 (0.7-5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98-1296) ng/mg which fell significantly to 62.69 (28.04-502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5-46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00-1550.43) µg/ml to 338.52 (211.35-525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.


Plasma human chorionic somatomammotropin deficiency in a normal pregnancy is the consequence of low concentration of messenger RNA coding for human chorionic somatomammotropin.
Human chorionic somatomammotropin (hCS) is important in the hormonal monitoring of human pregnancies. Presented is the case of a clinically normal pregnancy in which a very low plasma level of hCS was detected. The concentration of messenger ribonucleic acid (mRNA) coding for hCS was evaluated to determine the level on which the deficiency occurred.


Surgical outcomes for pulmonary metastases from hepatocellular carcinoma.
Although favourable prognosis following aggressive treatment of extrahepatic metastases from hepatocellular carcinoma (HCC) has been reported, surgical outcomes for pulmonary metastases are unclear. Sixty-one patients (2.6%) of 2297 registered with the Metastatic Lung Tumor Study Group of Japan between 1990 and 2006, who underwent surgery for pulmonary metastases from HCC, were retrospectively reviewed from the registry. The overall 5-year survival rate was 32.2%. The prognosis was significantly better for < or =2 lesions than for > or =3 lesions (p=0.046), for < or =3 lesions than for > or =4 lesions (p=0.0070), and for < or =4 lesions than for > or =5 lesions (p=0.029). No other factors that influence outcomes were identified. A stepwise regression analysis showed three or less pulmonary metastases to be an independent factor for better prognosis (p=0.048). With careful patient selection, comparatively good outcomes can be expected following surgical resection of pulmonary HCC metastases. Among them, patients with multiple metastases, if number of metastases is small such as four or less, can be expected to survive long after surgery.


Retracted: Identification and Validation of an Inflammatory Response-Related Polygenic Risk Score as a Prognostic Marker in Hepatocellular Carcinoma.
[This retracts the article DOI: 10.1155/2022/1739995.].


Optimal hash arrangement of tentacles in jellyfish.
At first glance, the trailing tentacles of a jellyfish appear to be randomly arranged. However, close examination of medusae has revealed that the arrangement and developmental order of the tentacles obey a mathematical rule. Here, we show that medusa jellyfish adopt the best strategy to achieve the most uniform distribution of a variable number of tentacles. The observed order of tentacles is a real-world example of an optimal hashing algorithm known as Fibonacci hashing in computer science.


Paradoxical metastatic progression following 3 months of neo-adjuvant androgen suppression in the TROG 96.01 trial for men with locally advanced prostate cancer.
In the TROG 96.01 trial 6 month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared to RT alone, but 3 months did not. We ask why? Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0 month NAS) to 66 Gy, 3 months or 6 months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology. In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6 month NAS, respectively. Compared with 0 month, significant reductions in PSA doubling time in subjects with DP occurred following 3 month NAS (p=0.01), but a significant reduction (p=0.01) and a near significant delay in DPs (p=0.06) occurred after 6 month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4 years. The data are consistent with the failure of 3 month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment.


The over-expression of ERbeta modifies estradiol effects on mitochondrial dynamics in breast cancer cell line.
Mitochondrial biogenesis and function are under the control of 17β-estradiol, which acts through two distinct estrogen receptors (alpha or beta), and the estrogen receptors ratio can determine the final effect of 17β-estradiol on mitochondria. Our aim was to study the effects of 17β-estradiol on mitochondrial biogenesis, dynamics and function in breast cancer cell lines with different estrogen receptors ratios. Mitochondrial biogenesis was increased in MDA-MB-231 (with only estrogen receptor beta expression), T47D (normal estrogen receptors ratio) and MCF-7 (highest estrogen receptors ratio) breast cancer cell lines, in response to different mitochondrial and cellular status. In fact, mitochondria of the MDA-MB-231 and T47D cell lines maintained their functionality, although, the MCF-7 cell line did suffer an important decrease in mitochondrial function. Thus, mitochondrial biogenesis increased in MCF-7 with the aim of mitigating these defective mitochondria. In normal conditions, mitophagic processes remove defective mitochondria to refresh the mitochondrial pool. Mitochondrial dynamics were also under control by 17β-estradiol, and showed modifications in the fusion/fission processes and the modulation of mitochondrial removal. In fact, cells with only estrogen receptor beta or with a low estrogen receptors ratio, such as MDA-MB-231 and T47D, showed an increase in fusion processes. However, the MCF-7 cell line, with more estrogen receptor alpha, also showed an increase in fusion processes, even though the fission processes were diminished and led to an accumulation of unfunctional mitochondria. Finally, the importance of estrogen receptor beta in mitochondrial biogenesis, function, as well as in mitochondrial dynamics was examined. Using the T47D-estrogen receptor beta tetracycline-inducible cell line, the results confirmed that when the overexpression of estrogen receptor beta was inhibited, there was an increase in mitochondrial biogenesis, although these mitochondria were less functional, and with fewer fission events, although there was an increase in fusion processes.


Wrist and hand postures when falling and description of the upper limb falling reflex.
Falling studies, i.e. assessing what happens when an individual falls, have been conducted in controlled environments but not in field studies for ethical reasons; this potentially limits the validity and applicability of previous studies. We performed field studies on existing YouTube © videos of skateboarders falling. The aims of these studies were to measure the wrist angle at impact on videos of real unprotected falls and to study the dynamics of the upper limbs when falling. Youtube © videos of skateboarders falling were studied assessing the direction of the fall, the positions of both upper limbs and especially the wrists on impact quantitatively and qualitatively. This study would not be ethical by other means. In study one (the more quantitative study) there were 48 men and 50 falls. The mean elbow flexion was 300 (range 00 to 800) and the mean maximal wrist extension was 800 (range 500 to 1100). The second wrist extended less or the same in > 90%. The second wrist only once (of 31) extended > 900 which should minimise the risk of toppling. Falls onto only one wrist gave significantly greater maximal wrist extension. In the second more qualitative study we observed the "upper limb falling reflex" where the response to falling is for the upper limb(s) to align the upper limb with the direction of falling of the body with the elbow mostly but not fully extended. Initially the wrists extend c. 400-500 with the fingers held mildly flexed. Immediately before impact the fingers hyper-extend with some compensatory wrist flexion to c. 300 of extension. The fingertips impact the ground first followed by the hand. These studies confirm wrist extension at impact around 800 but the wrist(s) may hyper-extend risking toppling. Falls on both wrists minimise the risk of toppling. The "upper limb falling reflex" is defined; it is a rapid dynamic response leading to the fingers impacting the ground first on falling. Abnormalities with the upper limb falling reflex may indicate problems with development in young children and may increase the risk of injury in older people.


[Severe vitamin D deficiency in children from Punta Arenas, Chile: Influence of nutritional status on the response to supplementation].
There is a high risk of vitamin D (VD) deficiency in the population of southern Chile that can be treated with VD supplements. Weight excess (WE) can influence the response to supplements. To study the prevalence of VD deficiency and the effect of cholecalciferol (VD3) supplements in healthy children from Punta Arenas, Chile, and evaluate a possible association with nutritional status. Demographic and anthropometric data, as well as laboratory assessment of serum 25-hidroxyvitamin D (25OHD) and other bone metabolism parameters were evaluated. After baseline evaluation, children were supplemented with VD3 1600 IU/day for one month, after which 25OHD was retested. Of the 108 children studied, 50% were boys, and had a mean age of 9.6±0.5 years. Nutritional assessment showed that 39% had normal weight, 46% were overweight, and 15% were obese. Median 25OHD was 10.9ng/ml: 96.3% had deficiency (<20ng/ml) and 3.7% insufficiency (20-29ng/ml). Severe deficiency was found in 62% (<12ng/ml). Baseline 25OHD was not affected by nutritional status. After supplementation, median 25OHD was 17.5ng/ml: 62% had deficiency, 36% insufficiency, and 2% sufficiency (>30ng/ml). Children with WE had a significantly lower increase in 25OHD than children with normal weight (5±5.5 vs. 7.7±4.9, p=03). Children with WE may require 32% higher VD dose than normal weight children to attain the same 25OHD concentration. Chilean schoolchildren from Punta Arenas have high prevalence of WE and VD deficiency, with a majority in the range of severe VD deficiency. WE interferes in the response to VD supplementation, leading to a lower increase in 25OHD.


Physiological function and ecological aspects of fatty acid-amino acid conjugates in insects.
In tritrophic interactions, plants recognize herbivore-produced elicitors and release a blend of volatile compounds (VOCs), which work as chemical cues for parasitoids or predators to locate their hosts. From detection of elicitors to VOC emissions, plants utilize sophisticated systems that resemble the plant-microbe interaction system. Fatty acid-amino acid conjugates (FACs), a class of insect elicitors, resemble compounds synthesized by microbes in nature. Recent evidence suggests that the recognition of insect elicitors by an ancestral microbe-associated defense system may be the origin of tritrophic interactions mediated by FACs. Here we discuss our findings in light of how plants have customized this defense to be effective against insect herbivores, and how some insects have successfully adapted to these defenses.


Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial.
The primary purposes of this study were to prove the efficacy of PRP injection therapy on knee pain and functions by comparing patients with mild to moderate OA with a placebo control group, and also to understand the effectiveness of multiple doses compared to a single dose. It was hypothesized that PRP would lead to more favorable results than the placebo at 1, 3, 6, 12 and 24 months after treatment. 237 patients diagnosed with OA were randomly separated into 4 groups, who were administered the following: single dose of PRP (n: 62), single dose of sodium saline (NS) (n: 59), three doses of PRP (n: 63), and three doses of NS (n: 53). Clinical evaluations were made pre-treatment and at 1, 3, 6, 12 and 24 months post-treatment, using the Knee Injury and Osteoarthritis Result Score (KOOS), Kujala Patellofemoral Score, knee joint range of motion (ROM), measurements of knee circumference (KC), and mechanical axis angle (MAA) and a Visual Analog Scale (VAS) for the evaluation of pain. The better score values in the groups were recorded at 3 and 6 months. Patients treated with PRP maintained better scores at 3, 6 and 12 months compared to the NS groups (p < 0.05). Multiple doses of PRP were seen to be more effective than single-dose PRP at 6 and 12 months (p < 0.05). At the end of 24 months, there was no significant score difference across all the groups. The most positive change in scores was found in stage 2 OA, and the most positive change in ROM was in stage 3 OA patients. In the PRP groups, KC decreased more at 1 and 6 months (p < 0.05). Compared to other age groups, patients aged 51-65 years scored better at 6 months (p < 0.05). A negative correlation was determined with MAA scores (r = - 0.508, p < 0.001). In comparison to the placebo (NS), leukocyte-rich PRP treatment was determined to be effective in the treatment of OA. Multiple doses of PRP increase the treatment efficacy and duration. Of all the patients treated with PRP, the best results were obtained by patients aged 51-65 years, with lower MAA, and by K/L stage 2 OA patients. Randomized controlled trial; Level of evidence, 1. NCT04454164 (ClinicalTrials.gov identifier).


Acute inflammation stimulates a regenerative response in the neonatal mouse heart.
Cardiac injury in neonatal 1-day-old mice stimulates a regenerative response characterized by reactive cardiomyocyte proliferation, which is distinguished from the fibrotic repair process in adults. Acute inflammation occurs immediately after heart injury and has generally been believed to exert a negative effect on heart regeneration by promoting scar formation in adults; however, little is known about the role of acute inflammation in the cardiac regenerative response in neonatal mice. Here, we show that acute inflammation induced cardiomyocyte proliferation after apical intramyocardial microinjection of immunogenic zymosan A particles into the neonatal mouse heart. We also found that cardiac injury-induced regenerative response was suspended after immunosuppression in neonatal mice, and that cardiomyocytes could not be reactivated to proliferate after neonatal heart injury in the absence of interleukin-6 (IL-6). Furthermore, cardiomyocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3), the major downstream effector of IL-6 signaling, decreased reactive cardiomyocyte proliferation after apical resection. Our results indicate that acute inflammation stimulates the regenerative response in neonatal mouse heart, and suggest that modulation of inflammatory signals might have important implications in cardiac regenerative medicine.


Prevalence of Cryptosporidium oocysts and giardia cysts in the drinking water supply in Japan.
A one-year monitoring of Cryptosporidium oocysts and Giardia cysts was conducted at a water purification plant. A total of 13 samples of 50 L river source water and 26 samples of 2,000 L-filtered water, treated by coagulation flocculation, sedimentation and rapid filtration, were tested. Prior to conducting a survey of a water purification plant, we developed a method for concentrating Cryptosporidium oocysts from a large volume of raw or filtered water using a hollow fiber ultrafiltration (UF) membrane, and this procedure was adapted to survey a water purification plant. Cryptosporidium oocysts were detected in all of the 13 raw water samples. The geometric mean concentration was 40 oocysts 100 L. Giardia cysts were detected in 12 of 13 raw water samples (92%) and the geometric mean concentration was 17 cysts/100 L. Probability distributions of both Cryptosporidium oocyst and Giardia cyst concentration in raw water were nearly lognormal. In filtered water samples, Cryptosporidium oocysts were detected in 9 of the 26 samples (35%) with the geometric mean concentration of 1.2 oocysts /1,000 L and Giardia cysts in 3 samples (12%) with 0.8 cysts/1,000 L. The estimated log10 removal efficiency of Cryptosporidium oocysts and Giardia cysts by rapid-sand filtration was 2.47 and 2.53, respectively. Empty particles were removed at a higher log10 than intact oocysts and cysts. The efficiency of particle removal in the rapid sand filtration process tends to be reduced under cold-water conditions. Close management is necessary in the winter when the water temperature is low.


Alkylated purines in the DNA of various rat tissues after administration of 1,2-dimethylhydrazine.
[1,2-3H] Dimethylhydrazine (1,2-DMH) (300 mg/kg; 4 mCi/kg) was injected s.c. to BD-VI rats and the degree of DNA alkylation was measured in various tissues 3 h after the administration. The O6-methylguanine/7-methylguanine ratio was approx. 4 times higher in the colon's DNA (0.0565), the principal target organ of this carcinogen, than in the liver's DNA (0.0136). These findings are briefly discussed in relation to the organ specificity of this carcinogen.


Measurement of DNA single-strand breaks by alkaline elution and fluorometric DNA quantification.
The method presented is based on the alkaline elution procedure for the determination of DNA single-stand (ss) breaks developed by Kohn and on the principles of DNA quantification after binding with the dye Hoechst 33258. In the present study, modification of the alkaline elution procedure with regard to the elution solution volume was performed. The influences of the DNA strandedness, the ethylenediaminetetraacetate/tetraethylammonium hydroxide denaturation and elution solution presence, the DNA solution pH, the dye amount, and the incubation time for the formation of the dye-ssDNA complex on the DNA fluorometric quantification were also studied. The modified DNA alkaline elution procedure followed by the optimized fluorometric determination of the ssDNA was applied on liver tissue from both untreated and treated (N-nitroso-N-methylurea- administered) Wistar rats. The criteria for the selection of the appropriate estimator and statistical analysis of the obtained results are also presented. The method of the DNA alkaline elution followed by fluorometric determination of ssDNA as modified and evaluated is an accurate and reliable approach for the determination of in vivo induced ssDNA strand breaks.


Selegiline transdermal system: use pattern and adherence in patients with major depressive disorder.
To discern the pattern of use of selegiline transdermal system as well as the level of adherence relative to other pharmacotherapies for treatment of major depressive disorder. Deidentified patient-level data (2010-2011; N = 2,985) were abstracted from US longitudinal archives (Medicaid, Medicare, managed care) in this retrospective exploratory claims-based analysis. Major depressive disorder was defined as ICD-9-CM codes 292.2, 296.3, 300.4, or 311. Antidepressant treatment failure was defined as receipt of < 90 days of initial antidepressant. Most patients received selegiline transdermal system as a second or third treatment option following treatment failure, and only 71 patients received it as first-line therapy. Patients were more likely to receive selegiline transdermal system for 60, 90, or 180 days compared to other therapies irrespective of treatment failure (P < .05). Among patients who did not fail treatment in the first 90 days, selegiline transdermal system was associated with a greater probability of receipt compared to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors at 120 days (odds ratio [OR] = 1.21; 95% CI, 1.14-1.47) and 180 days (OR = 1.09; 95% CI, 1.01-1.28). Although limited by the small sample size of patients receiving selegiline transdermal system versus other pharmacotherapies, the results suggest that after antidepressant treatment failure, earlier use of selegiline transdermal system may be warranted.


Research on the promotion of new energy vehicles based on multi-source heterogeneous data: consumer and manufacturer perspectives.
Under the background of green development, new energy vehicles, as an important strategic emerging industry, play a crucial role in energy conservation and emission reduction. In the post-epidemic era, steadily promoting the promotion of new energy vehicles will be a hot topic. Based on multi-source heterogeneous data, combined with the latent Dirichlet allocation topic model, social network analysis, and econometric methods, this paper explores whether individual purchase decisions and company-level cooperative research and development will promote the promotion of new energy vehicles. The results show that whether it is battery electric vehicles, hybrid electric vehicles or plug-in hybrid electric vehicles, users are more concerned about space dimension, power performance, and design style. Patent collaboration network analysis indicates that new energy vehicle enterprises are establishing close partnerships, which will urge the promotion of new energy vehicles. An interesting test result found that for short-term innovation, new energy vehicles enterprises should invest more patent research and development in battery electric vehicles and hybrid electric vehicles models to better accelerate the promotion of new energy vehicles.


Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort.
Hazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. In-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. Mean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 μg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 μg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 μg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. Prenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.


Mental health status and stressful life events among postgraduate nursing students in Cyprus: a cross-sectional descriptive correlational study.
Despite prior evidence supporting the association between stressful life events and mental health status, there are limited data on the number and severity of stressful life events and their effects on university students' mental health status. Therefore, the present study aimed to: (a) examine mental health status and subsequent predictors of clinically significant mental distress symptoms, (b) estimate the number and severity of stressful life events, and (c) explore the associations between mental health status, stressful life events (number and severity) and sociodemographic characteristics. This study was descriptive, cross-sectional, and correlational with internal comparisons. A convenience sample of 90 Master of Science in nursing and midwifery students, participated in the study. Participants with a General Health Questionnaire-28 (GHQ-28) total score ≥ 24 were considered to have clinically significant mental distress symptoms. Descriptive and inferential statistics were evaluated, and Pearson's chi-square test for group differences was used to analyse the data. Analysis of variance and t-tests were used for comparisons between two or more groups, and regression analyses were employed to identify the predictors of GHQ-28 scores and clinical mental distress symptoms. The final sample comprised 90 students (response rate: 97.8%), 33 (36.7%) of whom reported clinically significant symptoms of mental distress. Students with divorced parents [29.92 (± 10.62), p < .05] scored high on the GHQ-28. Participants who had low/no satisfaction with the education system posted higher scores than participants who had high/very high satisfaction [24.82 (± 11.68) vs. 17.93 (± 9.78), p < .05]. In the subscale measuring depressive symptoms, there was a statistically significant gender difference, with men reporting higher scores than females. [3.0± (3.69) vs. 1.60 (± 2.42), p = .034]. In multiple analyses of sociodemographic characteristics and those who scored higher on the Life Events Scale for Students (LESS) scale (≥ 340), the loss of parent/s was associated with the total GHQ-28 score (B=-17.046, p < .001). In multiple analyses, chronic physical disorders or disabilities and numerous stressful life events among students (≥ 8 events) were correlated with higher overall GHQ-28 scores (B = 15.232, p < .005). The high frequency of clinical symptoms of mental distress among postgraduate university nursing students and their correlation with stressful life events highlights the need for university counselling services to provide psychological support strategies to students.


Early emergence of increased fearful behavior in prenatally stressed rats.
We have been studying the mildly prenatally stressed (PS) rat as a potentially useful animal model of anxiety disorders. Previously we have demonstrated that there are anatomical and biochemical alterations in the amygdalas of adult PS offspring and that these offspring show increased fearful behaviors. However, human data indicate that anxiety disorders often present first in early childhood and then persist throughout adolescence and adulthood. To determine if PS rats also model this characteristic of human anxiety disorders, here we asked whether behavioral indices of increased fear would be detectable at an early age. We tested the hypotheses that young PS rats would show increased behavioral fearfulness in response to an acute stressor and that this would increase with age. A mild prenatal stressor, consisting of removal of the dam from the home cage and administration of a subcutaneous injection of 0.1 ml of 0.9% saline daily, was administered during the last week of pregnancy. Offspring were tested in the defensive-withdrawal apparatus before and after exposure to restraint stress at 25, 45 and 60 days of age. PS animals showed increased defensive-withdrawal behavior following the stressor and were more fearful following restraint when compared to controls (CON). This was significant at P45 and increased to P60. Hence, fearful behaviors in PS rats emerge prior to sexual maturation and increase in magnitude thereafter, further validating our model as a means to investigate the underpinnings of anxiety disorders.


Structure reactivity relationship in the reaction of DNA guanyl radicals with hydroxybenzoates.
In DNA, guanine bases are the sites from which electrons are most easily removed. As a result of hole migration to this stable location on guanine, guanyl radicals are major intermediates in DNA damage produced by the direct effect of ionizing radiation (ionization of the DNA itself and not through the intermediacy of water radicals). We have modeled this process by employing gamma irradiation in the presence of thiocyanate ions, a method which also produces single electron oxidized guanyl radicals in plasmid DNA in aqueous solution. The stable products formed in DNA from these radicals are detected as strand breaks after incubation with the FPG protein. When a phenolic compound is present in solution during gamma irradiation, the formation of guanyl radical species is decreased by electron donation from the phenol to the guanyl radical. We have quantified the rate of this reaction for four different phenolic compounds bearing carboxylate substituents as proton acceptors. A comparison of the rates of these reactions with the redox strengths of the phenolic compounds reveals that salicylate reacts ca. 10-fold faster than its structural analogs. This observation is consistent with a reaction mechanism involving a proton coupled electron transfer, because intra-molecular transfer of a proton from the phenolic hydroxyl group to the carboxylate group is possible only in salicylate, and is favored by the strong 6-membered ring intra-molecular hydrogen bond in this compound.


Comparison of the immunoreactivity of Trx2/Prx3 redox system in the hippocampal CA1 region between the young and adult gerbil induced by transient cerebral ischemia.
In the present study, we compared the immunoreactivities and levels of Trx/prx redox system, thioredoxin 2 (Trx2), thioredoxin reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), as well as neuronal death in the hippocampal CA1 region between the adult and young gerbil after 5 min of transient cerebral ischemia. At 4 days post-ischemia, pyramidal neurons (about 90%) in the adult stratum pyramidale of the CA1 region showed "delayed neuronal death (DND)"; however, at this time point, few pyramidal neurons showed DND in the young stratum pyramidale. At 7 days post-ischemia, about 56% of pyramidal neurons showed DND in the young stratum pyramidale. The immunoreactivities of all the antioxidants in the young sham-group were similar to those in the adult sham-group. At 4 days post-ischemia, the immunoreactivity of TrxR2, not Trx2 and Prx3 in the adult ischemia-group was dramatically decreased in CA1 pyramidal neurons. At this time point, the immunoreactivities of all the antioxidants in the young ischemia-group were apparently increased compared to the adult ischemia-group. From 7 days pots-ischemia, non-pyramidal cells showed the immunoreactivities of all the antioxidants in the ischemic CA1 region; however, in the young ischemia-groups, the immunoreactivities were much lower than those in the adult ischemia-groups. In brief, our results showed that the immunoreactivities of Trx2, TrxR2 and Prx3 were dramatically increased in CA1 pyramidal neurons of the young ischemia-groups at 4 days post-ischemia compared to those in the adult ischemia-groups induced by transient cerebral ischemia.


Spontaneous partial recovery of striatal dopaminergic uptake despite nigral cell loss in asymptomatic MPTP-lesioned female minipigs.
The Göttingen minipig is a large animal with a gyrencephalic brain that expresses -complex behavior, making it an attractive model for Parkinson's disease research. Here, we investigate the temporal evolution of presynaptic dopaminergic function for 14 months after injections of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the minipig using a multi-tracer longitudinal positron emission tomography (PET) design. We injected seven sedated minipigs with 1-2 mg/kg of MPTP, and two with saline, three times a week over four weeks. We monitored behavioral deficits using a validated motor scale and walking mat. Brains were imaged with (+)-⍺-[11C]-dihydrotetrabenazine ([11C]-DTBZ) and [18F]-dihydroxyphenylalanine ([18F]-FDOPA) PET at baseline and 1, 3, 10 and 14 months after MPTP injection, and immunohistochemistry was used to assess nigral cell loss. The minipigs showed mild bradykinesia and impaired coordination at early timepoints after MPTP. PET revealed decreases of striatal [11C]-DTBZ and [18F]-FDOPA uptake post-MPTP with partial spontaneous recovery of [18F]-FDOPA after 10 months. Postmortem analysis estimated an MPTP-induced nigral loss of 57% tyrosine hydroxylase+ and 43% Nissl-stained cells. Normal motor function despite substantial damage to the dopaminergic system is consistent with prodromal Parkinson's disease, and offers an opportunity for testing disease-modifying therapies. However, partial spontaneous recovery of dopamine terminal function must be taken into account in future studies.


Teaching microfluidic diagnostics using Jell-O(®) chips.
Microfluidics has emerged as a versatile technology that has found many applications, including DNA chips, fuel cells, and diagnostics. As the field of microfluidic diagnostics grows, it is important to introduce the principles of this technology to young students and the general public. The objective of this project was to create a simple and effective method that could be used to teach key microfluidics concepts using easily accessible materials. Similar to the poly(dimethylsiloxane) soft lithography technique, a Jell-O(®) "chip" is produced by pouring a mixture of Jell-O(®) and gelatine solution into a mold, which is constructed using foam plate, coffee stirrers, and double-sided tape. The plate is transferred to a 4°C refrigerator for curing, and then the Jell-O(®) chip is peeled off for experimental demonstrations. Three types of chips have been fabricated with different molds: a JELLO mold, a Y-channel mold, and a pH-sensor mold. Using these devices, the basics of microfluidic diagnostics can be demonstrated in one or two class periods. The method described in this chapter provides teachers with a fast and inexpensive way to introduce this technology, and students with a fun and hands-on way to understand the basics of microfluidic diagnostics.


Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice.
Because biotin treatment may lower blood glucose in insulin-dependent diabetes, we chose to study such an effect in non-insulin dependent diabetes. Twenty-six diabetic KK mice, moderately hyperglycemic and insulin resistant, were treated for 10 weeks: 9 animals with 2 mg of biotin/Kg, 8 with 4 mg of biotin/Kg, and 9 with saline (controls). Blood glucose levels, oral glucose tolerance, insulin response to oral glucose, and blood glucose decrease in response to insulin were quantitated. Compared to controls, biotin treatment lowered post-prandial glucose levels, and improved tolerance to glucose and insulin resistance. Serum immunoreactive insulin levels in biotin-treated mice were like the controls.


Denali Inferior Vena Cava Filter Retrieval: Complications and Success Rates.
The present study was to evaluate the outcomes of Denali filter retrieval. We retrospectively reviewed 143 patients who received Denali filter insertion from September 2015 to April 2020. Ninety-seven patients who required removal of the filters were include in this study. Filters were retrieved with either standard or advanced techniques. Venography before and after retrieval was obtained to evaluate technical success, complications and duration of filter insertion. All 97 filters were retrieved successfully without complications. Ninety-two (94.8%) were retrieved with standard technique and 5 filters (5.2%) required the advanced technique. There were two cases with a filter angle greater than 15 degrees. Inferior vena cava penetration was shown in 17 patients (17.5%) on venography but was not associated with contrast media extravasation after filter removal. The Denali filter showed a high rate of successful retrieval without complications. This study adds value to previous studies and trials showing that the Denali filter is a reliable and safe filter that can potentially improve retrieval rates, with increasing use of this device.


Characterization of a new sustainable supramolecular solvent and application to the determination of oxy-PAHs in meat, seafood and fish tissues.
In this study we develop a green treatment method based on supramolecular solvents (SUPRASs) made up of reverse aggregates of short/medium chain length alcohols (C6-C10) in mixtures of water and a sustainable organic solvent (methyl-tetrahydrofuran). SUPRASs ingredients have low toxicity and can be obtained from renewable sources. The new SUPRASs were characterized and its suitability for determination of oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) in food was tested. Analysis was made by liquid chromatography coupled to high resolution mass spectrometry. The method provided quantification limits in the range 0.4-4 ng g-1 with low consumption of reagents (200uL of SUPRAS per sample) and it was based on simple agitation and centrifugation without concentration/evaporation steps. All target compounds (except 11-H-benzo[b]fluoren-11-one) were found in 7 out of 19 samples, mainly in fish and seafood samples, with levels in the range n.d. - 8 ng g-1.


Investigating the efficacy and safety of calcipotriol/betamethasone dipropionate foam and laser microporation for psoriatic nail disease-A hybrid trial using a smartphone application, optical coherence tomography, and patient-reported outcome measures.
There is a lack of efficacious topical treatments for patients suffering from psoriatic nail disease (PND). We investigated the efficacy of Calcipotriol-Betamethasone Dipropionate (Cal/BD) foam with and without ablative fractional laser (AFL) in patients with PND. A total of 144 nails from 11 patients were treated in a 24-week long, open-label, randomized, intra-patient controlled proof-of-concept hybrid trial. In addition to daily Cal/BD foam application, half of each patient's psoriatic nails were randomized to receive optical coherence tomography (OCT)-guided AFL treatment at baseline, 6-, and 12-week follow-ups. In-clinic assessment (N-NAIL), patient-reported outcomes (PROMs), and drug consumption were supplemented by remote evaluation of 15 subclinical OCT features, smartphone app-based safety monitoring, and photo-based assessment (NAPSI). After 24 weeks of Cal/BD foam treatment, patients achieved a significant improvement (p < 0.001) in both clinical (N-NAIL -76%, NAPSI -68%) and subclinical (OCT -43%) PND severity as well as a 71% reduction in PROMs. AFL-assisted Cal/BD treatment led to higher clinical (N-NAIL -85%, NAPSI -78%) and OCT-assessed (-46%) reduction of PND signs than Cal/BD alone (N-NAIL -66%, NAPSI -58%, OCT -37%), but did not reach statistical significance. Smartphone app images documented adverse events and mild local skin reactions, particularly erythema (75%), laser-induced swelling (28%), and crusting (27%). This hybrid trial demonstrated a reduction in clinical NAPSI and N-NAIL scores, subclinical OCT features, and PROMs, suggesting that Cal/BD foam is a safe and efficacious treatment for PND. Larger trials are warranted to prove the clinical benefit of AFL pretreatment as a Cal/BD delivery enhancer.


Hepatitis B surface antigen in blood donors. An epidemiologic study.
Of 8085 volunteer donors attending the blood bank at SCTIMST screened for hepatitis B surface antigen (HBsAg) carrier state by counterimmunoelectrophoresis, 103 (1.27%) were HBsAg positive. The personal data of donors showed a higher rate of HBsAg among men than women and in the age group of 21 to 30 years than in the other age groups. A significantly higher rate was noted among donors belonging to the lower socioeconomic group (p less than 0.05).


Infection and persistence of varicella-zoster virus in lymphoblastoid Raji cell line.
Infection of Raji cells by varicella-zoster virus (VZV) resulted in permissive infection with establishment of a persistently infected lymphoblastoid cell line. VZV antigens of the membrane and nuclear type, as detected by the indirect immunofluorescence membrane antigen (IFAMA) and anticomplement immunofluorescence (ACIF) tests, were observed. Minute amounts of infectious virus were detected by co-cultivation of VZV-infected Raji cells (Raji-VZV), with permissive human embryo fibroblasts (HEF). The virus isolated was found to be similar to the parent strain. Transient induction of Epstein-Barr viral capsid antigen (EB-VCA) was also observed. The persistently infected Raji-VZV cell line, when free of EB-VCA, was found suitable for measuring antibodies to varicella-zoster virus. The possible interaction in the infected Raji cells between EBV, which is implicated in human malignancy, and VZV which belongs also to the herpes group of viruses, is discussed.


A motif in the V3 domain of the kinase PKC-θ determines its localization in the immunological synapse and functions in T cells via association with CD28.
Protein kinase C-θ (PKC-θ) translocates to the center of the immunological synapse, but the underlying mechanism and its importance in T cell activation are unknown. Here we found that the V3 domain of PKC-θ was necessary and sufficient for localization to the immunological synapse mediated by association with the coreceptor CD28 and dependent on the kinase Lck. We identified a conserved proline-rich motif in V3 required for association with CD28 and immunological synapse localization. We found association with CD28 to be essential for PKC-θ-mediated downstream signaling and the differentiation of T helper type 2 cells (T(H)2 cells) and interleukin 17-producing helper T cells (T(H)17 cells) but not of T helper type 1 cells (T(H)1 cells). Ectopic expression of V3 sequestered PKC-θ from the immunological synapse and interfered with its functions. Our results identify a unique mode of CD28 signaling, establish a molecular basis for the immunological synapse localization of PKC-θ and indicate V3-based 'decoys' may be therapeutic modalities for T cell-mediated inflammatory diseases.


Characteristics of motor unit discharge in subjects with hemiparesis.
We studied the discharge rates and recruitment characteristics of single motor units in paretic and contralateral arm muscles of 6 hemiparetic subjects. Motor unit activity in biceps brachii was recorded at different elbow torques, and the activity related both to the mean level of surface electromyographic activity, and to the degree of weakness. In 3 of the 6 subjects, there were significant reductions in mean discharge rate of motor units in the paretic muscle. All 6 subjects showed compression of the range of motoneuron recruitment forces, and a failure to increase motor unit discharge rate during voluntary force increases in paretic muscles. These rate reductions could potentially alter the precise match of motoneuron properties to the mechanical properties of the innervated muscle fibers, and reduce the efficiency of muscle contraction. This reduction could lead, in turn to increased effort, to fatigue, and ultimately to a sense of weakness for voluntary force generation.


Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly.
Synaptic vesicle fusion is mediated by SNARE proteins-VAMP2 on the vesicle and Syntaxin-1/SNAP25 on the presynaptic membrane. Chaperones Munc18-1 and Munc13-1 cooperatively catalyze SNARE assembly via an intermediate 'template' complex containing Syntaxin-1 and VAMP2. How SNAP25 enters this reaction remains a mystery. Here, we report that Munc13-1 recruits SNAP25 to initiate the ternary SNARE complex assembly by direct binding, as judged by bulk FRET spectroscopy and single-molecule optical tweezer studies. Detailed structure-function analyses show that the binding is mediated by the Munc13-1 MUN domain and is specific for the SNAP25 'linker' region that connects the two SNARE motifs. Consequently, freely diffusing SNAP25 molecules on phospholipid bilayers are concentrated and bound in ~ 1 : 1 stoichiometry by the self-assembled Munc13-1 nanoclusters.


Oseltamivir inhibits both viral entry and release but enhances apoptosis of cells infected with influenza A H1N1.
Oseltamivir (Tamiflu) has been shown to be effective as a treatment and chemoprophylaxis for influenza virus infections. However, the safety consideration of oseltamivir should not be overlooked because adverse events associated with the drug have frequently been reported after the use of Tamiflu for the treatment of influenza patients. Here, we investigated oseltamivir's influence on viral load, apoptosis, and cytokine response of influenza A H1N1-infected A549 or THP-1 cells. In addition, we analyzed the effect of the drug on the function of influenza-infected NK cells after oseltamivir treatment. The results of our study suggest that oseltamivir may inhibit both viral entry and release but may also enhance apoptosis of infected cells and interfere with NK cell function during influenza infection.


Magnetic palm kernel biochar potential route for phenol removal from wastewater.
The pollution of water resources due to the disposal of industrial wastes that have organic material like phenol is causing worldwide concern because of their toxicity towards aquatic life, human beings and the environment. Phenol causes nervous system damage, renal kidney disease, mental retardation, cancer and anaemia. In this study, magnetic palm kernel biochar is used for removal of phenol from wastewater. The effect of parameters such as pH, agitation speed, contact time and magnetic biochar dosage are validated using design of experiments. The statistical analysis reveals that the optimum conditions for the highest removal (93.39%) of phenol are obtained at pH of 8, magnetic biochar dosage of 0.6 g, agitation speed at 180 rpm and time of 60 min with the initial concentration of 10 mg/L. The maximum adsorption capacities of phenol were found to be 10.84 mg/g and Langmuir and Freundlich isotherm models match the experimental data very well and adsorption kinetic obeys a pseudo-second order. Hence, magnetic palm kernel can be a potential candidate for phenol removal from wastewater.


Alterations in hippocampal extracellular amino acids and purine catabolites during limbic seizures induced by folate injections into the rabbit amygdala.
The effects on hippocampal extra- and intracellular amino acids of focal injection of folic acid into the amygdala in the rabbit were studied with brain dialysis. Folate seizures were accompanied by pronounced elevations of extracellular alanine and phosphoethanolamine. The increase of extracellular alanine was related to an enhanced level of this amino acid in total hippocampal tissue, whereas phosphoethanolamine was unaltered in tissue biopsies. Folate seizures did not significantly affect extracellular aspartate and extracellular glutamate was only slightly elevated (50-75% over baseline values). The tissue concentration of glutamate remained at control levels during the seizures and tissue aspartate was decreased by 28%. Extracellular glutamine decreased rapidly after folate injection with a concomitant increase of total hippocampal glutamine. Neither extra- nor intracellular taurine was affected by folate epilepsy. The experiments also encompassed measurements of the extracellular purine catabolites inosine, hypoxanthine and xanthine. Folic acid-induced epilepsy produced changes in these compounds indicative of moderately accelerated degradation of adenosine 5'-triphosphate. The findings support the view of glutamate as a mediator of epilepsy-related brain damage. It is, however, questionable if the small enhancement of extracellular glutamate is enough to provoke neuronal necrosis associated with folate epilepsy.


Peptides related to FKBP 39-45 loop possess immunostimulative potency.
Taking into account the sequential homology existing between thymopoietin II, the DNA-binding domain of p53 protein and FKBP (FK-506 binding protein), a series of fragments of human and bovine FKBP containing a fragment Ser39-Pro45 were synthesized. In the humoral in vitro test all the peptides act as stimulators. Whereas in the in vivo test peptides derived from bovine FKBP show an immunostimulative and those from human FKBP an immunosuppressive activity. However, after blocking the Asp residue by a Bzl group the peptide V appears to be an immunostimulator. The data obtained suggest that these peptides can influence the immune system by blocking the FKBP receptor.


Ultra-weak photon emission as a non-invasive tool for the measurement of oxidative stress induced by UVA radiation in Arabidopsis thaliana.
All living organisms emit ultra-weak photon emission as a result of oxidative processes caused by the physical or chemical stress factors. In the present study, the effect of oxidative stress induced by the exposure of the plant model Arabidopsis thaliana to ultraviolet A (UVA) radiation was studied using ultra-weak photon emission. When Arabidopsis plants and leaves were exposed to UVA radiation, two kinetically distinguished phases in the ultra-weak photon emission decay were observed: the fast decay phase (τ1=0.805±0.024 min) and slow decay phase (τ2=4.321±0.166 min). The spectral analysis of the UVA radiation-induced ultra-weak photon emission showed that the photon emission during the fast decay phase is from both blue-green and red regions of the spectrum, whereas the photon emission during the slow decay phase is solely from the blue-green region of the spectrum. These observations reveal that triplet excited carbonyls contribute to ultra-weak photon emission during both fast and slow decay phases, whereas chlorophylls participate in the ultra-weak photon emission solely during the fast decay phase. It is illustrated here that the ultra-weak photon emission serves as a non-invasive method for the monitoring of oxidative stress in plants caused by UVA radiation.


Studies on the prevalence of Hepatitis C virus infection in diabetic patients attending a tertiary health-care facility South-west Nigeria.
Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide. The objective of this study is to evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. A total number of one hundred and eighty diabetic patients were recruited for this study. Consented subjects made up of 71(39.4%) males and 109(60.56%) females were recruited for the study. While one-Hundred (100) Non-Diabetics (Controls) were also recruited for the study. Structured questionnaires were administered to the consented participants to obtain relevant data. Sera samples were assayed for antibodies to HCV using an enzyme linked immunosorbent assay [Inteco Diagnostic Limited]. ELISA technique. Overall prevalence of HCV infection among diabetes patients assayed was 13.3% out of which 8(11.3%) was obtained from the male subjects compared to 16 (14.7%) seropositivity recorded among the females (P = 0.511; P > 0.05). Considering age distribution, Subjects aged 41-50 years recorded, 9 (22.5%) positivity (P = 0.238; P > 0.05).Considering educational status of subjects screened, 22 (14.9%) positivity was rescored among subjects who have attained tertiary status of education.(P = 0.574;P > 0.05).Risk factors considered showed that, 7 (18.9%) seropositive subject were alcoholic consumers(P value = 0.2621;P > 0.05) while 5 (8.9%) recorded history of sharing sharp objects P = 0.2427;P > 0.05). Our study shows a slightly higher prevalence of hepatitis C infection in type 2 diabetics. This call for urgent routine screening exercise among diabetic patients for HCV infection. This study also emphasizes the need for public enlightenment on the association between HCV infection and T2DM, to avert possible complications among diabetic patients.


Relation between lipid peroxidation and iron concentration in mouse liver after acute and subacute cadmium intoxication.
In this study the effect of acute and subacute cadmium (Cd) intoxication on iron (Fe) concentration and lipid peroxidation (LPO) was investigated in the livers of Swiss mice. Animals were divided into two groups: the Cd group--mice intoxicated with Cd and controls. In acute time-response studies, Fe and malondialdehyde (MDA) levels were determined at 4, 6, 12, 24 and 48 h after a single oral dose of Cd (20 mg Cd/kg b.w.). In the subacute experiment, mice were given 10 mg Cd/kg b.w. orally every day for 14 days; Fe and MDA contents were determined in liver after 1 and 2 weeks. Acute Cd intoxication induced a significantly increased hepatic Fe content after 4 and 6h, and a statistically significant increase in MDA 6, 12 and 24h after Cd administration, although a significantly decreased MDA level was observed after 48 h. The results suggest development of early oxidative stress in livers of mice after acute intoxication with Cd. The decreased MDA observed after 48 h occurred presumably due to the adaptive response of the organism. Subacute Cd intoxication induced a significant decrease of hepatic Fe and MDA levels at both investigated time intervals compared with control. These results indicate a positive correlation between hepatic Fe and MDA content and suggest that prolonged Cd intoxication decreases hepatic LPO indirectly, by reducing the Fe content of mouse liver.


Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge.
Myocardial infarction, stroke, and sepsis trigger systemic inflammation and organism-wide complications that are difficult to manage. Here, we examined the contribution of macrophages residing in vital organs to the systemic response after these injuries. We generated a comprehensive catalog of changes in macrophage number, origin, and gene expression in the heart, brain, liver, kidney, and lung of mice with myocardial infarction, stroke, or sepsis. Predominantly fueled by heightened local proliferation, tissue macrophage numbers increased systemically. Macrophages in the same organ responded similarly to different injuries by altering expression of tissue-specific gene sets. Preceding myocardial infarction improved survival of subsequent pneumonia due to enhanced bacterial clearance, which was caused by IFNɣ priming of alveolar macrophages. Conversely, EGF receptor signaling in macrophages exacerbated inflammatory lung injury. Our data suggest that local injury activates macrophages in remote organs and that targeting macrophages could improve resilience against systemic complications following myocardial infarction, stroke, and sepsis.


N-acyl homoserine lactone-mediated modulation of plant growth and defense against Pseudoperonospora cubensis in cucumber.
N-acyl-homoserine lactones (AHLs), a well-described group of quorum sensing molecules, may modulate plant defense responses and plant growth. However, there is limited knowledge regarding the defense responses of non-model crops to AHLs and the mechanism of action responsible for the modulation of defense responses against microbial pathogens. In the present study, long-chain N-3-oxo-tetradecanoyl-l-homoserine lactone (oxo-C14-HSL) was shown to have a distinct potential to prime cucumber for enhanced defense responses against the biotrophic oomycete pathogen Pseudoperonospora cubensis and the hemibiotrophic bacterium Pseudomonas syringae pv. lachrymans. We provide evidence that AHL-mediated enhanced defense against downy mildew disease is based on cell wall reinforcement by lignin and callose deposition, the activation of defense-related enzymes (peroxidase, β-1,3-glucanase, phenylalanine ammonia-lyase), and the accumulation of reactive oxygen species (hydrogen peroxide, superoxide) and phenolic compounds. Quantitative analysis of salicylic acid and jasmonic acid, and transcriptional analysis of several of genes associated with these phytohormones, revealed that defense priming with oxo-C14-HSL is commonly regulated by the salicylic acid signaling pathway. We also show that treatment with short- (N-hexanoyl-l-homoserine lactone) and medium-chain (N-3-oxo-decanoyl-l-homoserine lactone) AHLs promoted primary root elongation and modified root architecture, respectively, resulting in enhanced plant growth.


Automated measurements of follicle diameter: a chance to standardize?
This study describes the use of an automated measurement of follicular diameter using the new Sono-Automatic Volume Calculation (Sono-AVC) software and compares the accuracy of automated measures and the time taken for such measures to those made manually from two-dimensional and three-dimensional ultrasound. Sono-AVC provides measurements of follicular diameter that are more accurate than the manual measures and has the potential to improve the clinical work flow because the time taken for the measurements is significantly shorter.


Nijmegen breakage syndrome (NBS).
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies.


[Adenoma and adenocarcinoma of the iris and ciliary body epithelium in the dog].
An adenoma and an adenocarcinoma of the anterior uvea in two dogs are described clinically--follow-up included--and ophthalmopathologically. Incidence, therapy, differential diagnosis and prognosis of these epithelial neoplasms in the anterior uvea are discussed.


Change of female partner and postejaculatory performance of young and old rhesus males.
This study was undertaken to determine whether a change of female partner following ejaculation would reduce the postejaculatory interval (PEI). The male subjects were seven old (mean age 22.4 years) and five young (mean age 12.2 years) rhesus males (Macaca mulatta). The female subjects were four ovariectomized females rendered sexually receptive by treatment with estradiol benzoate. Introduction of a different female following ejaculation significantly reduced the PEI and latency to a second ejaculation in both young and old males. However, a different female did not reduce latencies to preejaculatory levels. The potential for enhanced sexual performance was retained in old rhesus males.


Heat resistance of allograft tissue.
Lyophilized allograft musculoskeletal tissue is generally intended to be stored at "ambient" or "room" temperature, and usually is kept in climate controlled indoor storage areas. However, there is a question of what temperature extremes tissue may see, especially during transportation, in that these extremes may exceed even the limits of "ambient" conditions. Temperatures may become quite hot, but only for a few hours and only during daytime. Damage from high temperatures, if it occurs, is expected to be evident by damage to the collagen component of bone, soft tissue, and demineralized bone, as well as to the growth factors contained in demineralized bone. If damage is significant, then temperature monitoring requirements for lyophilized allograft tissue might be necessary. To answer this question, a literature review was carried out to look at the short-term temperature resistance of collagen and demineralized bone. Both collagen and the growth factors in demineralized bone show remarkable short term tolerance to elevated temperatures in the dry state, and it was concluded that temperature excursions of 50 degrees C or less, lasting for a few days or less, would not cause any significant deterioration. This means that temperature monitoring also should not be required.


A review of vaccine research and development: human acute respiratory infections.
Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.


Metabolism of apolipoproteins A-I and A-II and its influence on the high density lipoprotein subfraction distribution in males and females.
Rate zonal ultracentrifugation of plasma samples from ten healthy age-matched volunteers (five males, five females) indicated that the high density lipoprotein subfraction ratio (HDL2:HDL3) in females was significantly higher than in males. The cause of this phenomenon was investigated by simultaneous examination of the metabolism of the major HDL apoproteins (apoA-I and apoA-II) in both groups. The results show that there is no significant sex-related difference in the plasma pool size, fractional catabolic rate, or synthetic rate of either apoprotein. We conclude that the increased HDL2:HDL3 ratio in femalse versus males does not derive from measurable differences in the metabolic handling of either apoprotein.


A liquid chromatography/electrospray ionization mass spectrometry (LC-MS/MS) assay for the determination of irinotecan (CPT-11) and its two major metabolites in human liver microsomal incubations and human plasma samples.
A sensitive, rapid LC-MS/MS assay has been developed and validated for the simultaneous quantification of CPT-11 and its two principal metabolites, 7-ethyl-10-hydroxycamptothecin (SN-38), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxy-camptothecin (APC) in human liver microsomal fractions and plasma. The method was linear over the ranges of 1.56-100 ng/mL, 3.13-150 ng/mL, and 0.78-100 ng/mL for CPT-11, SN-38, and APC, respectively. The total run time was 7.0 min. This assay offers advantages in terms of expediency, recovery of analytes, and suitability for the analysis of CPT-11 and its metabolites in various biological fluids.


Consequences of Aneuploidy in Cancer: Transcriptome and Beyond.
Cancer cells differ from normal healthy cells in multiple aspects ranging from altered cellular signaling through metabolic changes to aberrant chromosome content, so called aneuploidy. The large-scale changes in copy numbers of chromosomes or large chromosomal regions due to aneuploidy alter significantly the gene expression, as several hundreds of genes are gained or lost. Comparison of quantitative genome, transcriptome and proteome data enables dissection of the molecular causes that underlie the gene expression changes observed in cancer cells and provides a new perspective on the molecular consequences of aneuploidy. Here, we will map to what degree aneuploidy affects the expression of genes located on the affected chromosomes. We will also address the effects of aneuploidy on global gene expression in cancer cells as well as whether and how it may contribute to the physiology of cancer cells.


Effect of oral administration of different combinations of killed bacteria on some depressed macrophage functions in tumor-bearing rats.
In the present study, we compared the ability of different bacterial species administered orally in various combinations to restore some depressed peritoneal macrophage functions in tumor-bearing rats. Phagocytosis, killing of Candida albicans and chemotactic response of resident peritoneal cells from treated tumor-bearing rats were influenced by different associations of bacteria. In particular, when Staphylococcus aureus was administered together with other bacterial species, the phagocytic activity of peritoneal cells was restored to normal values, and intracellular killing of C. albicans was enhanced. The results are discussed in relation to the possible influence of mucosal bacterial flora on the level of activation of peritoneal macrophages. The possibility that bacterial species can influence in various ways immunocompetent cells in relation to the different chemical composition of some common structures is also discussed.


Temporal variations in PAH concentrations in Quercus ilex L. (holm oak) leaves in an urban area.
Temporal variations of polycyclic aromatic hydrocarbon (PAH) concentrations in leaves of a Mediterranean evergreen oak, Quercus ilex L., were investigated in order to assess the suitability of this species to biomonitor PAH air contamination. Leaf samples were collected at six sites of the urban area of Naples (Italy) and at a control site in the Vesuvius National Park, in May and September 2001, and in January and May 2002. PAH extraction was conducted by sonication in dichloromethane-acetone and quantification by GC-MS. In winter, leaf total PAH concentrations showed, at all the urban sites, values 2-fold higher than in all the other samplings, reflecting the temporal trend reported for PAH air contamination in the Naples urban area. Moreover, leaf PAH concentrations showed, at all the urban sites, a decrease in May 2002 after the winter accumulation. At the control site leaf PAH concentrations showed lower values and smaller temporal variations than at the urban sites. The findings support the suitability of Q. ilex leaves to monitor temporal variations in PAH contamination. The highest winter concentrations of total PAHs were due to the medium molecular weight PAHs that increased with respect to both low and high molecular weight PAHs. The medium molecular weight PAHs showed the same temporal trend both at the urban and remote sites.