Tailored treatment of female indirect inguinal hernias by using single-port laparoscopic percutaneous internal ring suture: a comparison between children and adults.

PURPOSE: To compare the outcome of indirect inguinal hernias repaired by using single-port laparoscopic percutaneous internal ring suture (SPIRS) between the pediatric and adult females. METHODS: The medical records of females who were clinically assessed to have inguinal hernia from Oct. 2016 to May 2022 were reviewed. Patients who received laparoscopy for the diagnosis of the hernia type and customized treatment according to their hernia type were included, while those who chose other operation methods initially were excluded. The patients were divided into the adult and pediatric groups based on their age. The demographic characteristics, hernia types, operation durations, and outcomes were analyzed between these two groups. RESULTS: A total of 65 adults and 60 children were included in this study. The median age was 38 years. (range: 23-88) for group A and 3 years (range: 0.1-16) for group P. Indirect hernias were present in 85% of adults and 100% of children. All the indirect hernias were repaired by SPIRS uneventfully. Incidence of contralateral patent processus vaginalis was 24% in adults and 50% in children (p = 0.016). The average operation time was 22/46 min (one/two sides) for the adults and 9/15 min (one/two sides) for the pediatrics (p < 0.010 for both). The overall complication rates were 5.4% and 3.3% for the adult and pediatric group respectively (p = 0.106). No recurrence was observed in the pediatric group, but two adults experienced recurrence and another had chronic postoperative inguinal pain, necessitating reoperation. The mean follow-up period was 38.6 ± 15.4 months for adults and 42.8 ± 18.9 months for children (p = 0.198). CONCLUSION: Our results support that the pathogenesis of indirect inguinal hernia for the female adults is due to the non-obliteration of a congenital processus vaginalis. Tailored treatment of the female IIH by using single-port laparoscopic percutaneous internal ring suture may be an alternative for the management of female IHs.

Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.

BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. RESULTS: BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. CONCLUSIONS: These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.

Size at Birth, Postnatal Growth, and Reproductive Timing in an Australian Microbat.

Reproductive phenology, size at birth, and postnatal growth are important life history traits that reflect parental investment. The ability to document detailed changes in these traits can be a valuable tool in the identification and management of at-risk wildlife populations. We examined reproductive traits in a common, widespread Australian microbat, Chalinolobus gouldii, at two sites over two years and derived growth curves and age estimation equations which will be useful in the study of how intrinsic and extrinsic factors alter parental investment strategies. We found that male and female offspring did not differ significantly in their size at birth or their postnatal growth rates. Bats born in 2018 were smaller at birth but grew at a faster rate than those born in 2017. When date of birth was compared across sites and years, we found bats born in 2018 had a later median birthdate (by 18 days) and births were more widespread than those born in 2017. Cooler and wetter weather during late gestation (Nov) in 2018 may have prolonged gestation and delayed births. With many bats facing threatening processes it is important to study reproductive plasticity in common and widespread "model" species, which may assist in the conservation and management of threatened microbats with similar reproductive traits.

COVID-19 vaccination and dialysis patients: why the variable response.

Uremia affects all parts of the immune system. Since hemodialysis patients travel to the dialysis center three times per week and are surrounded by many other patients and staffs, these could predispose them to a greater risk of coronavirus disease of 2019 (COVID-19) infection. Mortality associated with COVID-19 infection is high in patients receiving dialysis. Currently, the World Health Organization has approved six types of vaccines (ChAdOx1-S, Ad26.COV2.S, BNT162b2, mRNA-1273, BBIBP-CorV and CoronaVac) for COVID-19. Literature data regarding the response rate toward COVID-19 vaccination in dialysis patients is inconclusive. The published response rates varied from 29.6% to 96.4%. The variable response rates across these clinical trials may be explained by different vaccine types, vaccine doses, criteria for positive immune response, timings of antibody detection, races and ethnicities. Side effects of COVID-19 vaccination comprise of pain at injection site, fatigue, myalgia, headache, low fever, syncope, pericarditis, etc. Clinical predictors of positive response toward COVID-19 vaccination include age, previous infection, immunosuppressive therapy, body mass index and serum albumin level. No one is safe until everyone is safe. Therefore, vaccination against COVID-19 infection in dialysis patients is an urgent issue of worldwide concern.

An artificial intelligence algorithm for analyzing acetaminophen-associated toxic hepatitis.

INTRODUCTION: Very little artificial intelligence (AI) work has been performed to investigate acetaminophen-associated hepatotoxicity. The objective of this study was to develop an AI algorithm for analyzing weighted features for toxic hepatitis after acetaminophen poisoning. METHODS: The medical records of 187 patients with acetaminophen poisoning treated at Chang Gung Memorial Hospital were reviewed. Patients were sorted into two groups according to their status of toxic hepatitis. A total of 40 clinical and laboratory features recorded on the first day of admission were selected for algorithm development. The random forest classifier (RFC) and logistic regression (LR) were used for artificial intelligence algorithm development. RESULTS: The RFC-based AI model achieved the following results: accuracy = 92.5 ± 2.6%; sensitivity = 100%; specificity = 60%; precision = 92.3 ± 3.4%; and F1 = 96.0 ± 1.8%. The area under the receiver operating characteristic curve (AUROC) was approximately 0.98. The LR-based AI model achieved the following results: accuracy = 92.00 ± 2.9%; sensitivity = 100%; specificity = 20%; precision = 92.8 ± 3.4%; recall = 98.8 ± 3.4%; and F1 = 95.6 ± 1.5%. The AUROC was approximately 0.68. The weighted features were calculated, and the 10 most important weighted features for toxic hepatitis were aspartate aminotransferase (ALT), prothrombin time, alanine aminotransferase (AST), time to hospital, platelet count, lymphocyte count, albumin, total bilirubin, body temperature and acetaminophen level. CONCLUSION: The top five weighted features for acetaminophen-associated toxic hepatitis were ALT, prothrombin time, AST, time to hospital and platelet count.

Comparison of the novel ARCHITECT procalcitonin assay with established procalcitonin assay systems.

AIMS: This study assessed the performance of a new fully automated immunoassay, ARCHITECT B.R.A.H.M.S procalcitonin (PCT), comparing the results with other commercial assays on routine clinical specimens. METHODS: At nine sites from eight countries, precision analysis was carried out on controls by ANOVA. Threshold and linearity were verified according to standard procedures. Comparison of ARCHITECT B.R.A.H.M.S PCT with the Cobas®, LIAISON®, VIDAS® and Kryptor® PCT assays was evaluated using Passing-Bablok and Deming regression analyses. RESULTS: The within-laboratory standard deviation and %CV across all sites ranged from 0.005 to 0.008 and 2.7 to 4.1; 0.040 to 0.212 and 2.1 to 11.7; 1.628 to 4.191 and 2.5-6.3 for the three control levels, respectively. The mean slope (linearity analysis) across all sites ranged from 0.85 to 1.03, with a mean y-intercept ranging from -6.15 to + 1.71 and a correlation coefficient ranging from 0.94 to 1.00. The LoB, LoD, and LoQ claims were verified. Deming regression analysis of 1116 plasma or serum samples with PCT results detected across a dynamic assay range of 0.02-100 µg/l using the ARCHITECT B.R.A.H.M.S PCT assay yielded results of r = 0.989 vs. Roche Cobas®, r = 0.986 vs Kryptor® B.R.A.H.M.S, r = 0.987 vs BioMèrieux VIDAS® and r = 0.972 vs. Diasorin LIAISON®, respectively. Concordance at cut-offs of 0.25 µg/l and 0.50 µg/l were 96.9% and 98.1% with Roche Cobas®, 95.4% and 96.1% with B.R.A.H.M.S Kryptor®, 93.8% and 98.4% with BioMèrieux VIDAS®, and 92.7% and 93.9% with Diasorin LIAISON®. CONCLUSIONS: Compared with other assays, ARCHITECT B.R.A.H.M.S PCT offers excellent precision and low-end sensitivity.

Co-suppression of AtMIPS demonstrates cooperation of MIPS1, MIPS2 and MIPS3 in maintaining myo-inositol synthesis.

KEY MESSAGE: Co-suppressed MIPS2 transgenic lines allow bypass of the embryo lethal phenotype of the previously published triple knock-out and demonstrate the effects of MIPS on later stages of development. Regulation of inositol production is of interest broadly for its effects on plant growth and development. The enzyme L-myo-inositol 1-phosphate synthase (MIPS, also known as IPS) isomerizes D-glucose-6-P to D-inositol 3-P, and this is the rate-limiting step in inositol production. In Arabidopsis thaliana, the MIPS enzyme is encoded by three different genes, (AtMIPS1, AtMIPS2 and AtMIPS3), each of which has been shown to produce proteins with biochemically similar properties but differential expression patterns. Here, we report phenotypic and biochemical effects of MIPS co-suppression. We show that some plants engineered to overexpress MIPS2 in fact show reduced expression of AtMIPS1, AtMIPS2 and AtMIPS3, and show altered vegetative phenotype, reduced size and root length, and delayed flowering. Additionally, these plants show reduced inositol, increased glucose levels, and alteration of other metabolites. Our results suggest that the three AtMIPS genes work together to impact the overall synthesis of myo-inositol and overall inositol homeostasis.

Hydrazo-CEST: Hydrazone-Dependent Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agents.

The rapid formation of hydrazones under physiological conditions was exploited for the detection of aldehydes through chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI). A metal-free, diamagnetic contrast agent derived from N-amino anthranilic acid was introduced, which selectively "turned-on" upon hydrazone formation through an effect termed Hydrazo-CEST. While the hydrazine form of the probe produced no CEST-MRI signal enhancement, the formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk water signal through the CEST effect, as measured by 300 MHz 1 H NMR, 3 T and 7 T MRI. Both the electronic contributions of the N-amino anthranilate and the aldehyde binding partner were shown to directly impact the exchange rate of the proton on the ring-proximal nitrogen, and thus the imaging signal. Additionally, the presence of the carboxylic acid moiety ortho to the hydrazine was necessary not only for contrast production, but also for rapid hydrazone formation and prolonged hydrazone product stability under physiological conditions. This work provided the first example of an MRI-based contrast agent capable of a "turn on" response upon reaction with bioactive aldehydes, and outlined both the structural and electronic requirements to expand on Hydrazo-CEST, a novel, hydrazone-dependent subtype of diamagnetic CEST-MRI.

Anatomically realistic ultrasound phantoms using gel wax with 3D printed moulds.

Here we describe methods for creating tissue-mimicking ultrasound phantoms based on patient anatomy using a soft material called gel wax. To recreate acoustically realistic tissue properties, two additives to gel wax were considered: paraffin wax to increase acoustic attenuation, and solid glass spheres to increase backscattering. The frequency dependence of ultrasound attenuation was well described with a power law over the measured range of 3-10 MHz. With the addition of paraffin wax in concentrations of 0 to 8 w/w%, attenuation varied from 0.72 to 2.91 dB cm-1 at 3 MHz and from 6.84 to 26.63 dB cm-1 at 10 MHz. With solid glass sphere concentrations in the range of 0.025-0.9 w/w%, acoustic backscattering consistent with a wide range of ultrasonic appearances was achieved. Native gel wax maintained its integrity during compressive deformations up to 60%; its Young's modulus was 17.4 ± 1.4 kPa. The gel wax with additives was shaped by melting and pouring it into 3D printed moulds. Three different phantoms were constructed: a nerve and vessel phantom for peripheral nerve blocks, a heart atrium phantom, and a placental phantom for minimally-invasive fetal interventions. In the first, nerves and vessels were represented as hyperechoic and hypoechoic tubular structures, respectively, in a homogeneous background. The second phantom comprised atria derived from an MRI scan of a patient with an intervening septum and adjoining vena cavae. The third comprised the chorionic surface of a placenta with superficial fetal vessels derived from an image of a post-partum human placenta. Gel wax is a material with widely tuneable ultrasound properties and mechanical characteristics that are well suited for creating patient-specific ultrasound phantoms in several clinical disciplines.

Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose?

The acquisition and early maturation of infant microbiota is not well understood despite its likely influence on later health. We investigated the contribution of the maternal microbiota to the microbiota of infant gut and nose in the context of mode of delivery and feeding. Using 16S rRNA sequencing and specific qPCR, we profiled microbiota of 42 mother-infant pairs from the GUSTO birth cohort, at body sites including maternal vagina, rectum and skin; and infant stool and nose. In our study, overlap between maternal vaginal microbiota and infant faecal microbiota was minimal, while the similarity between maternal rectal microbiota and infant microbiota was more pronounced. However, an infant's nasal and gut microbiota were no more similar to that of its own mother, than to that of unrelated mothers. These findings were independent of delivery mode. We conclude that the transfer of maternal vaginal microbes play a minor role in seeding infant stool microbiota. Transfer of maternal rectal microbiota could play a larger role in seeding infant stool microbiota, but approaches other than the generally used analyses of community similarity measures are likely to be needed to quantify bacterial transmission. We confirmed the clear difference between microbiota of infants born by Caesarean section compared to vaginally delivered infants and the impact of feeding mode on infant gut microbiota. Only vaginally delivered, fully breastfed infants had gut microbiota dominated by Bifidobacteria. Our data suggest that reduced transfer of maternal vaginal microbial is not the main mechanism underlying the differential infant microbiota composition associated with Caesarean delivery. The sources of a large proportion of infant microbiota could not be identified in maternal microbiota, and the sources of seeding of infant gut and nasal microbiota remain to be elucidated.

The adaptive decision-making, risky decision, and decision-making style of Internet gaming disorder.

BACKGROUND: Persistent gaming, despite acknowledgment of its negative consequences, is a major criterion for individuals with Internet gaming disorder (IGD). This study evaluated the adaptive decision-making, risky decision, and decision-making style of individuals with IGD. METHODS: We recruited 87 individuals with IGD and 87 without IGD (matched controls). All participants underwent an interview based on the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) diagnostic criteria for IGD and completed an adaptive decision-making task; the Preference for Intuition and Deliberation Scale, Chen Internet Addiction Scale, and Barratt Impulsivity Scale were also assessed on the basis of the information from the diagnostic interviews. RESULTS: The results demonstrated that the participants in both groups tend to make more risky choices in advantage trials where their expected value (EV) was more favorable than those of the riskless choice. The tendency to make a risky choice in advantage trials was stronger among IGD group than that among controls. Participants of both groups made more risky choices in the loss domain, a risky option to loss more versus sure loss option, than they did in the gain domain, a risky option to gain more versus sure gain. Furthermore, the participants with IGD made more risky choices in the gain domain than did the controls. Participants with IGD showed higher and lower preferences for intuitive and deliberative decision-making styles, respectively, than controls and their preferences for intuition and deliberation were positively and negatively associated with IGD severity, respectively. CONCLUSIONS: These results suggested that individuals with IGD have elevated EV sensitivity for decision-making. However, they demonstrated risky preferences in the gain domain and preferred an intuitive rather than deliberative decision-making style. This might explain why they continue Internet gaming despite negative consequences. Thus, therapists should focus more on decision-making styles and promote deliberative thinking processes to mitigate the long-term negative consequences of IGD.

Identifying environmental correlates of intraspecific genetic variation.

Genetic variation is critical to the persistence of populations and their capacity to adapt to environmental change. The distribution of genetic variation across a species' range can reveal critical information that is not necessarily represented in species occurrence or abundance patterns. We identified environmental factors associated with the amount of intraspecific, individual-based genetic variation across the range of a widespread freshwater fish species, the Murray cod Maccullochella peelii. We used two different approaches to statistically quantify the relative importance of predictor variables, allowing for nonlinear relationships: a random forest model and a Bayesian approach. The latter also accounted for population history. Both approaches identified associations between homozygosity by locus and both disturbance to the natural flow regime and mean annual flow. Homozygosity by locus was negatively associated with disturbance to the natural flow regime, suggesting that river reaches with more disturbed flow regimes may support larger, more genetically diverse populations. Our findings are consistent with the hypothesis that artificially induced perennial flows in regulated channels may provide greater and more consistent habitat and reduce the frequency of population bottlenecks that can occur frequently under the highly variable and unpredictable natural flow regime of the system. Although extensive river regulation across eastern Australia has not had an overall positive effect on Murray cod numbers over the past century, regulation may not represent the primary threat to Murray cod survival. Instead, pressures other than flow regulation may be more critical to the persistence of Murray cod (for example, reduced frequency of large floods, overfishing and chemical pollution).

Copepods' Response to Burgers' Vortex: Deconstructing Interactions of Copepods with Turbulence.

This study examined the behavioral response of two marine copepods, Acartia tonsa and Temora longicornis, to a Burgers' vortex intended to mimic the characteristics of a turbulent vortex that a copepod is likely to encounter in the coastal or near-surface zone. Behavioral assays of copepods were conducted for two vortices that correspond to turbulent conditions with mean dissipation rates of turbulence of 0.009 and 0.096 cm(2) s(-3) (denoted turbulence level 2 and level 3, respectively). In particular, the Burgers' vortex parameters (i.e., circulation and rate of axial strain rate) were specified to match a vortex corresponding to the median rate of dissipation due to viscosity for each target level of turbulence. Three-dimensional trajectories were quantified for analysis of swimming kinematics and response to hydrodynamic cues. Acartia tonsa did not significantly respond to the vortex corresponding to turbulence level 2. In contrast, A. tonsa significantly altered their swimming behavior in the turbulence-level-3 vortex, including increased relative speed of swimming, angle of alignment of the trajectory with the axis of the vortex, ratio of net-to-gross displacement, and acceleration during escape, along with decreased turn frequency (relative to stagnant control conditions). Further, the location of A. tonsa escapes was preferentially in the core of the stronger vortex, indicating that the hydrodynamic cue triggering the distinctive escape behavior was vorticity. In contrast, T. longicornis did not reveal a behavioral response to either the turbulence level 2 or the level 3 vortex.

CBAP promotes thymocyte negative selection by facilitating T-cell receptor proximal signaling.

T-cell receptor (TCR)-transduced signaling is critical to thymocyte development at the CD4/CD8 double-positive stage, but the molecules involved in this process are not yet fully characterized. We previously demonstrated that GM-CSF/IL-3/IL-5 receptor common ß-chain-associated protein (CBAP) modulates ZAP70-mediated T-cell migration and adhesion. On the basis of the high expression of CBAP during thymocyte development, we investigated the function of CBAP in thymocyte development using a CBAP knockout mouse. CBAP-deficient mice showed normal early thymocyte development and positive selection. In contrast, several negative selection models (including TCR transgene, superantigen staphylococcal enterotoxin B, and anti-CD3 antibody treatment) revealed an attenuation of TCR-induced thymocyte deletion in CBAP knockout mice. This phenotype correlated with a reduced accumulation of BIM upon TCR crosslinking in CBAP-deficient thymocytes. Loss of CBAP led to reduced TCR-induced phosphorylation of proteins involved in both proximal and distal signaling events, including ZAP70, LAT, PLCγ1, and JNK1/2. Moreover, TCR-induced association of LAT signalosome components was reduced in CBAP-deficient thymocytes. Our data demonstrate that CBAP is a novel component in the TCR signaling pathway and modulates thymocyte apoptosis during negative selection.

Gout patients have an increased risk of developing most cancers, especially urological cancers.

OBJECTIVES: Inflammation and hyperuricaemia, which are the major characteristics of gout disease, are thought to be associated with carcinogenesis and anti-carcinogenesis, respectively. Therefore, we aimed to explore the causal effect on cancers from those with gout disease. METHOD: New gout patients without a history of cancer were included from 1998 to 2000, and they had been followed up from 2001 to 2008 to observe the incidence of cancers from national outpatient records in Taiwan. RESULTS: A total of 8408 male gout patients and 25,010 male controls were included by matching gout patients' age and year and month of first diagnosis during the including period. The mean ages at diagnosis were 51.03 ± 14.52 and 50.90 ± 14.45 years for gout patients and controls, respectively. The overall incidence of all cancers was 9.82 cases per 1000 person-years among gout patients compared to 4.35 cases per 1000 person-years among controls after 8 years of follow-up. The age-adjusted standardized incidence ratios (SIRs) were 2.26 [95% confidence interval (CI) 2.06-2.49], 3.31 (95% CI 2.55-4.31), 3.14 (95% CI 2.12-4.64), and 2.18 (95% CI 1.34-3.56) for all cancers, prostate cancer, bladder cancer, and renal cancer, respectively. The cumulative hazard ratios (HRs) were significantly higher in gout patients than in controls with regard to developing prostate, bladder, and renal cancers (all p < 0.001). CONCLUSIONS: This study shows that gout patients are more likely to develop most cancers, especially the urological cancers: prostate, bladder, and renal cancers. The data also support the hypothesis of a link between metabolic syndrome (MetS) and cancer disorders.

The Second National Ballistics Imaging Comparison (NBIC-2).

In response to the guidelines issued by the American Society of Crime Laboratory Directors/Laboratory Accreditation Board (ASCLD/LAB-International) to establish traceability and quality assurance in U.S. crime laboratories, NIST and the ATF initiated a joint project, entitled the National Ballistics Imaging Comparison (NBIC). The NBIC project aims to establish a national traceability and quality system for ballistics identifications in crime laboratories utilizing ATF's National Integrated Ballistics Information Network (NIBIN). The original NBIC was completed in 2010. In the second NBIC, NIST Standard Reference Material (SRM) 2461 Cartridge Cases were used as reference standards, and 14 experts from 11 U.S. crime laboratories each performed 17 image acquisitions and correlations of the SRM cartridge cases over the course of about half a year. Resulting correlation scores were collected by NIST for statistical analyses, from which control charts and control limits were developed for the proposed quality system and for promoting future assessments and accreditations for firearm evidence in U.S. forensic laboratories in accordance with the ISO 17025 Standard.

The role of monocytes and SLC11A1 polymorphisms in the pathogenesis of Chlamydia-induced reactive arthritis.

OBJECTIVES: To investigate the role that monocytes and solute carrier family 11 member A1 (SLC11A1) gene polymorphisms play in the pathogenesis of reactive arthritis (ReA). METHODS: SLC11A1 274C/T and 823C/T polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The phagocytic activity of monocytes was analysed by flow cytometry after they were co-cultured with Chlamydia trachomatis. The inclusions in the monocytes were demonstrated by immunohistochemistry staining. Bactericidal activity was determined by immunofluorescence staining with the recovered inclusions. RESULTS: There was no significant difference in the phagocytic activity of monocytes between the ReA patients and healthy controls. The bactericidal activity of monocytes from the healthy controls was more efficient than that from the ReA patients. The patients with SLC11A1 823T tended to have a higher bactericidal activity of monocytes than those with SLC11A1 823 C/C. Moreover, the bactericidal activity of monocytes in the patients with SLC11A1 274T seemed to decrease in comparison with that in the patients with SLC11A1 274C/C. CONCLUSIONS: The bactericidal activity of monocytes in patients with ReA is lower than that in healthy controls. The SLC11A1 274C/T and 823C/T polymorphisms may be associated with the decreased bactericidal activity of the monocytes.

The age-risk relationship of haematologic malignancies in female patients with systemic lupus erythematosus: a nationwide retrospective cohort study.

BACKGROUND: The risks of haematologic malignancies in female patients with systemic lupus erythematosus (SLE) have been observed to be higher in young age groups than in old age groups. However, the age-risk relationship between haematologic malignancies and SLE is poorly defined. DESIGN AND METHODS: A retrospective cohort study was conducted nationwide with newly diagnosed SLE female patients during the period of 1997 to 2001 using the database acquired from the Taiwan National Health Research Institute. Each patient in the study was randomly frequency matched with five SLE-free people based on age. The subsequent developments of haematologic malignancies were observed until the date haematologic cancer was diagnosed or December 2008. The age-adjusted standardized incidence ratios (SIRs), the incidence per 1000 person-years, the follow-up duration to the diagnosis of haematologic malignancies and the cumulative hazard rates of haematologic malignancies between SLE and controls were analysed. RESULTS: A total of 35 lymphoid and 14 myeloid malignancies were observed among 9349 female SLE patients. Further, significantly higher incidences of both lymphoid and myeloid malignancies were found in SLE patients (SIR: 3.30, 95% confidence interval (CI) = 2.20-4.93 and SIR: 2.86, 95% CI = 1.49-5.09). Also, two peaks of risk ratios for lymphoid malignancies were found in patients aged 21-30 years and 41-50 years. It was observed that the follow-up duration for haematologic malignancies was significantly shorter in SLE patients than in controls (73.21 vs. 105.25 months, respectively). In addition, higher cumulative hazard rates in both lymphoid and myeloid malignancies were found in SLE patients (p < 0.0001). CONCLUSION: Female SLE patients have a higher incidence of haematologic malignancy in different age groups, and with shorter incubating time than SLE-free people.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication.

BACKGROUND: Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. METHODS: The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. RESULTS: Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. CONCLUSIONS: We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.