Risk Associated With Valvular Regurgitation During Pregnancy.
Pregnancies in women with regurgitant valve lesions are generally considered low risk, but this has not been well studied. This study determined the frequency of adverse cardiac events (CEs) in pregnant women with moderate or severe regurgitant valve lesions. Maternal and fetal outcomes in women with moderate or severe chronic valve regurgitation enrolled in a prospective multicenter study on pregnancy outcomes were examined. Adverse CEs included heart failure, sustained arrhythmias, cardiac arrest, or death. A multivariate logistic regression model was used to identify determinants of CEs in women at the highest risk. Outcomes of 430 pregnancies in women with moderate or severe regurgitant lesions were examined: 145 with mitral regurgitation (MR), 101 with pulmonary regurgitation (PR), 71 with multivalve disease, 73 with tricuspid regurgitation (TR), and 40 with aortic regurgitation (AR). Most women had associated congenital or acquired heart disease. Adverse CEs occurred in 13% of pregnancies: 27% of pregnancies with multivalve disease; 15% with MR; 15% with TR; 5% with AR; and 3% with PR. Maternal mortality was rare. In women with MR, TR, or multivalve disease (n = 289), left ventricular systolic dysfunction (p = 0.001), pulmonary hypertension (p = 0.005), and cardiac events before pregnancy (p < 0.001) were important determinants of CEs during pregnancy. Women with AR and PR are at low risk for cardiac complications during pregnancy. While many women with MR, TR, and multivalve regurgitation do well during pregnancy, additional clinical variables help stratify those at highest risk. This new information will enhance the quality and precision of preconception counseling and pregnancy planning.


Solvolysis procedures for the determination of bound residues of the mycotoxin deoxynivalenol in fusarium species infected grain of two winter wheat cultivars preinfected with barley yellow dwarf virus.
A trichloroacetic acid treatment at 140 degrees C for 40 min was successfully established as a suitable solvolysis procedure for the recovery of bound deoxynivalenol or its derivatives in Fusarium-infected plants. Deoxynivalenol itself was not decomposed in the procedure. The derivative 15-acetyl-deoxynivalenol was chosen as a model compound for setting free deoxynivalenol in an acid-catalyzed deesterification reaction, developing the method. This is the first report using a trichloroacetic acid solvolysis procedure as a sample incubation step to free bound deoxynivalenol and determine free from bound deoxynivalenol in the sample. Between 13 and 63% of the total deoxynivalenol consisted of nonextractable deoxynivalenol. Deoxynivalenol contents in grain of the susceptible cultivar "Agent" infected with Fusarium spp. were 12-24 times higher when compared to those for the corresponding moderately resistant cultivar "Petrus". The highest deoxynivalenol amounts were determined in grain infected with Fusarium spp. as well as simultaneously infected with BYDV. This solvolysis procedure may be of importance for distinguishing between resistant and susceptible plants and their ability to immobilize (bound) mycotoxins as a plant defense mechanism.


Copy number variation associated with meiotic arrest in idiopathic male infertility.
To assess the association between copy number variations (CNVs) and meiotic arrest and azoospermic men. Genetic association study. University. Australian men: 19 with histologically confirmed meiotic arrest, 110 men with azoospermia in the absence of histologic data, and 97 fertile men (controls). None. The identification of CNV by microarray and/or multiplex ligation-dependent probe amplification (MLPA), and the localization of unique CNV encoded proteins to the human testis. Microarray identified two CNVs unique to meiosis arrest patients. One containing the MYRIP gene and a second containing LRRC4C and the long noncoding RNA LOC100507205. All three genes are transcribed in the human testis, and MYRIP and LRRC4C localize to meiotic cells. The reverse genetic screen for CNVs in meiosis genes identified in mouse models further identified CNVs including HSPA2 as being associated with azoospermia. These data raise the possibility that, while relatively rare, CNVs may contribute to human male infertility and that CNV screening should be incorporated into long-term plans for genome profiling as a diagnostic tool.


Machine-learning-based children's pathological gait classification with low-cost gait-recognition system.
Pathological gaits of children may lead to terrible diseases, such as osteoarthritis or scoliosis. By monitoring the gait pattern of a child, proper therapeutic measures can be recommended to avoid the terrible consequence. However, low-cost systems for pathological gait recognition of children automatically have not been on market yet. Our goal was to design a low-cost gait-recognition system for children with only pressure information. In this study, we design a pathological gait-recognition system (PGRS) with an 8 × 8 pressure-sensor array. An intelligent gait-recognition method (IGRM) based on machine learning and pure plantar pressure information is also proposed in static and dynamic sections to realize high accuracy and good real-time performance. To verifying the recognition effect, a total of 17 children were recruited in the experiments wearing PGRS to recognize three pathological gaits (toe-in, toe-out, and flat) and normal gait. Children are asked to walk naturally on level ground in the dynamic section or stand naturally and comfortably in the static section. The evaluation of the performance of recognition results included stratified tenfold cross-validation with recall, precision, and a time cost as metrics. The experimental results show that all of the IGRMs have been identified with a practically applicable degree of average accuracy either in the dynamic or static section. Experimental results indicate that the IGRM has 92.41% and 97.79% intra-subject recognition accuracy, and 85.78% and 78.81% inter-subject recognition accuracy, respectively, in the static and dynamic sections. And we find methods in the static section have less recognition accuracy due to the unnatural gesture of children when standing. In this study, a low-cost PGRS has been verified and realize feasibility, highly average precision, and good real-time performance of gait recognition. The experimental results reveal the potential for the computer supervision of non-pathological and pathological gaits in the plantar-pressure patterns of children and for providing feedback in the application of gait-abnormality rectification.


Asymmetric tumor-related alterations of network-specific intrinsic functional connectivity in glioma patients.
Resting-state functional MRI (rs-fMRI) allows mapping temporally coherent brain networks, and intra- and inter-network alterations have been described in different diseases. This prospective study investigated hemispheric resting-state functional connectivity (RSFC) differences in the default-mode network (DMN) and fronto-parietal network (FPN) between patients with left- and right-hemispheric gliomas (LH PAT, RH PAT), addressing asymmetry effects the tumor might have on network-specific intrinsic functional connectivity under consideration of the prognostically relevant isocitrate-dehydrogenase (IDH) mutation status. Twenty-seven patients (16 LH PAT, 12 IDH-wildtype) and 27 healthy controls underwent anatomical and rs-fMRI as well as neuropsychological assessment. Independent component analyses were performed to identify the DMN and FPN. Hemispheric DMN- and FPN-RSFC were computed, compared across groups, and correlated with cognitive performance. Patient groups did not differ in tumor volume, grade or location. RH PAT showed higher contra-tumoral DMN-RSFC than controls and LH PAT. With regard to the FPN, contra-tumoral RSFC was increased in both patient groups as compared to controls. Higher contra-tumoral RSFC was associated with worse cognitive performance in patients, which, however, seemed to apply mainly to IDH-wildtype patients. The benefit of RSFC alterations for cognitive performance varied depending on the affected hemisphere, cognitive demand, and seemed to be altered by IDH-mutation status. At the time of study initiation, a clinical trial registration was not mandatory at our faculty, but it can be applied for if requested.


Preventing Irritability and Temper Outbursts in Youth by Building Resilience.
Severe irritability and temper outbursts are risk factors for the onset of serious and lifelong mood disorders. In treating children and adolescents with severe irritability, clinicians should evaluate and address safety issues before acute stabilization of symptoms. Then, clinicians can initiate interventions to prevent the onset or relapses of the undesired behavior and its functional consequences. This review summarizes primary, secondary, and tertiary relapse prevention strategies, with an emphasis on strategies that build resilience in youth that mitigate the onset, recurrence, and progression of emotion dysregulation.


Isolation and characterization of three unusual membrane glycopeptides present in rat intestinal endoplasmic reticula.
Three glycopeptides have been isolated from the mucosal homogenates of the rat small intestine without using proteolysis. These glycopeptides appear to be localized exclusively in the membranes of the endoplasmic reticula. Although they have similar molecular weights of about 2550 and have similar amino acid compositions, they differ in the carbohydrate constituents. The major glycopeptide has 2 mol glucose per polypeptide chain while the two other glycopeptides contain 1 mol fucose, mannose and galactose with either 1 or 2 mol glucose. No hexosamine or sialic acid was detected in any of the glycopeptides. An unusual physical property was found associated with these glycopeptides. Below pH 6.5 they formed a precipitate which prevented them from diffusing through a dialysis membrane and allowed them to be rapidly purified following solubilization from the membrane. These glycopeptides appear to represent a new group of heretofore uncharacterized membrane constitutents which may play a role in some function specific for the endoplasmic reticula.


Sex-related ERP differences in deviance detection.
The effect of sex on neural mechanisms of auditory mismatch detection was examined using dense sensor array (128 channel) event-related potential recordings (ERPs). ERPs of 32 right-handed subjects (16 males) were recorded to frequent (85%, 880 Hz) and infrequent (15%, 1480 Hz) tones. There were no sex differences in mismatch negativity (80-180 ms), however, the fronto-central P2 (180-260 ms) was less positive in males (F=12.56, P<0.005) and the N2 (260-340 ms) was more negative in males (F=6.28, P<0.05). The increased negativity in males spanning the P2 and N2 may index a top-down process of attention bias towards novelty. This result supports the hypothesis of an adaptive, sexually dimorphic processing of novel events in humans.


Influence of interferon-based therapy on liver fibrosis progression in HIV/HCV coinfected patients: a retrospective repeated liver biopsy analysis.
Hepatitis C virus (HCV) coinfection is one of the leading causes of mortality in human immunodeficiency virus-infected patients. The current standard of care leads to cure only in a part of these patients. The course of the disease is determined by the rapidity of liver fibrosis progression (LFP). The influence of interferon on LFP in coinfected patients has yet not been evaluated by comparative liver biopsies. We extracted data of patients who had serial liver biopsies from a hospital database. Histopathological findings were compared to factors possibly linked to fibrosis progression. Furthermore, we studied the impact of response to interferon treatment on fibrosis progression. Hundred and twenty-six patients were included, 68 had received anti-HCV treatment, and 58 had not. The median time between the first and the last biopsy was 4 years. Worsened fibrosis was observed in 35 of 58 (60%) untreated patients, and 22 of 50 (44%) patients in the nonresponder/relapser group, and in 5 out of 18 (28%) in the SVR group. Liver fibrosis evolution was significantly better in patients achieving a SVR than in untreated and NR/R patients (p<0.02, odds-ratio [95% CI] for improvement vs. stability vs. worsening=3.16 [1.24-8.07]). This result persisted after adjustment for known predictors of liver fibrosis progression, HBsAg, CD4, and alcohol consumption: adjusted odds ratio=2.89 [1.09-7.68], p=0.03. HCV treatment can stop fibrosis progression and induce its regression. Nonresponders to treatment may even have a fast fibrosis progression. It remains to be clarified if the same factors that induce nonresponse to treatment may also induce faster fibrosis progression.


Promoting wellness and recovery for persons with serious mental illness: a program evaluation.
This retrospective descriptive correlational study evaluated treatment satisfaction and the quality of life (QOL) of consumers with serious mental illness participating in a community mental health program that combined illness management and recovery strategies with a group appointment model. The Wellness Enhancement and Recovery Program (WERP) was evaluated to determine satisfaction with services and QOL of consumers over 3 years. Findings from the data analyses indicated that consumers in WERP were satisfied with treatment services and had a fair to good QOL. Satisfaction and QOL were moderately correlated.


The interaction between hippocampal cholinergic and nitrergic neurotransmission coordinates NMDA-dependent behavior and autonomic changes induced by contextual fear retrieval.
Re-exposing an animal to an environment previously paired with an aversive stimulus evokes large alterations in behavioral and cardiovascular parameters. Dorsal hippocampus (dHC) receives important cholinergic inputs from the basal forebrain, and respective acetylcholine (ACh) levels are described to influence defensive behavior. Activation of muscarinic M1 and M3 receptors facilitates autonomic and behavioral responses along threats. Evidence show activation of cholinergic receptors promoting formation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in dHC. Altogether, the action of ACh and NO on conditioned responses appears to converge within dHC. As answer about how ACh and NO interact to modulate defensive responses has so far been barely addressed, we aimed to shed additional light on this topic. Male Wistar rats had guide cannula implanted into the dHC before being submitted to the contextual fear conditioning (3footshocks/085 mA/2 s). A catheter was implanted in the femoral artery the next day for cardiovascular recordings. Drugs were delivered into dHC 10 min before contextual re-exposure, which occurred 48 h after the conditioning procedure. Neostigmine (Neo) amplified the retrieval of conditioned responses. Neo effects (1 nmol) were prevented by the prior infusion of a M1-M3 antagonist (fumarate), a neuronal nitric oxide synthase inhibitor (NPLA), a NO scavenger (cPTIO), a guanylyl cyclase inhibitor (ODQ), and a NMDA antagonist (AP-7). Pretreatment with a selective M1 antagonist (pirenzepine) only prevented the increase in autonomic responses induced by Neo. The results show that modulation in the retrieval of contextual fear responses involves coordination of the dHC M1-M3/NO/cGMP/NMDA pathway.


Surface Engineering of Porous Carbon for Self-Healing Nanocomposite Hydrogels by Mussel-Inspired Chemistry and PET-ATRP.
In this work, surface-functionalized microcapsules from porous carbon nanospheres (PCNs) were successfully prepared by mussel-inspired chemistry with polydopamine (PDA) and metal-free photoinduced electron transfer-atom transfer radical polymerization (PET-ATRP). These functional microcapsules are introduced into self-healing hydrogels to enhance their mechanical strength. The PCNs synthesized by a simple soft template method are mixed with linseed oil for loading of the biomass healing agent, and the microcapsules are first prepared by coating PDA. PDA coatings were used to immobilize the ATRP initiator for initiating 4-vinylpyridine on the surface of microcapsules by PET-ATRP. Using these functional microcapsules, the self-healing efficiency was about 92.5% after 4 h at ambient temperature and the healed tensile strength can be held at 2.5 MPa with a fracture strain of 625.2%. All results indicated that the surface-functionalized microcapsules for self-healing hydrogels have remarkable biocompatibility and mechanical properties.


A purified nucleoprotein fragment of the 30 S ribosomal subunit of Escherichia coli.
A '13 S' nucleoprotein fragment was isolated from a nuclease digest of Escherichia coli 30-S ribosomal subunits and purified to gel electrophoretic homogeneity. It contained two polynucleotides, of about 1.1 . 10(5) and 2.5 . 10(4) daltons, which separated when the fragment was deproteinized. The major protein components were S4, S7 and S9/11, with S15, S16, S18, S19 and S20 present in reduced amount.


Epidemiological profile of microbial keratitis in Alexandria-Egypt a 5 years retrospective study.
To evaluate the epidemiologic profile of microbial keratitis in Alexandria- Egypt, with special emphasis on risk factors, visual outcome and microbiological results. This retrospective study reviewed files of patients treated for microbial keratitis during a period of 5 years at Alexandria Ophthalmology Hospital Cornea Clinic, Alexandria- Egypt, between February 2017 and June 2022. The patients were evaluated for the risk factors e.g., trauma, eyelid disorders, co-morbidities, and contact lens use. They were also evaluated for their clinical picture, the identified microorganisms, visual outcomes, and complications. Non-microbial keratitis and incomplete files were excluded from the study. A total of 284 patients were diagnosed as microbial keratitis in our study. Viral keratitis was the most common cause of microbial keratitis (n = 118 (41.55%)), followed by bacterial keratitis (n = 77 (27.11%)), mixed keratitis (n = 51 (17.96%)), acanthamoeba keratitis (n = 22 (7.75%)) and the least cause was fungal keratitis (n = 16 (5.63%)). Trauma was the most common risk factor for microbial keratitis (29.2%). Fungal keratitis had a statistically significant association with trauma (p < 0.001), while the use of contact lenses had a statistically significant association with Acanthamoeba keratitis (p < 0.001). The percentage of culture-positive results in our study was 76.8%. Gram-positive bacteria were the most frequently isolated bacterial isolate (n = 25 (36.2%)), while filamentous fungi were the most frequently isolated fungi (n = 13(18.8%)). After treatment, there was a significant increase in the mean visual acuity among all groups; it was significantly higher in Acanthamoeba keratitis group with a mean difference of 0.262 ± 0.161 (p = 0.003). Viral keratitis followed by bacterial keratitis were the most frequent etiologic agents causing microbial keratitis found in our study. Although trauma was the most frequent risk factor for microbial keratitis, contact lens wear was found an important preventable risk factor for microbial keratitis in young patients. Performing culture properly whenever indicated before starting antimicrobial treatment increased the cultures' positive results.


Mitogenic andadjuvant activities of polysaccharides from the cellular slime mold, Dictyostelium discoideum NC-4.
Cell surface and extracellular polysaccharide fractions obtained from Dictyostelium discoideum NC-4 cultured in bacteria-free medium showed strong B-cell mitogenic activities. Upon periodate treatment of the extra-cellular polysaccharide fraction this activity completely disappeared. The extracellular polysaccharide fraction could also enhance the antibody response in vitro against sheep red blood cells.


Clovamide-rich extract from Trifolium pallidum reduces oxidative stress-induced damage to blood platelets and plasma.
Numerous plants (including clovers) have been widely used in folk medicine for the treatment of different disorders. This in vitro study was designed to examine the antioxidative effects of the clovamide-rich fraction, obtained from aerial parts of Trifolium pallidum, in the protection of blood platelets and plasma against the nitrative and oxidative damage, caused by peroxynitrite (ONOO(-)). Carbonyl groups and 3-nitrotyrosine in blood platelet and plasma proteins were determined by ELISA tests. Thiol groups level was estimated by using 5,5'-dithio-bis(2-nitro-benzoic acid, DTNB). Plasma lipid peroxidation was measured spectrophotometrically as the production of thiobarbituric acid reactive substances. The results from our work indicate that clovamide-rich T. pallidum extract may reveal the protective properties in the prevention against oxidative stress. The presence of clovamide-rich T. pallidum extract (12.5-100 μg/ml) partly inhibited ONOO(-)-mediated protein carbonylation and nitration. All the used concentrations of T. pallidum extract reduced lipid peroxidation in plasma. The antioxidative action of the tested extract in the protection of blood platelet lipids was less effective; the extract at the lowest final concentration (12.5 μg/ml) had no protective effect against lipid peroxidation. The present results indicate that the extract from T. pallidum is likely to be a source of compounds with the antioxidative properties, useful in the prevention against the oxidative stress-related diseases.


Pharmacotherapy of pediatric HIV infection.
The delivery of safe and effective antiretroviral therapy to children and adolescents is crucial to save the lives of millions of children worldwide. The immunologic response to human immunodeficiency infection is closely related to a child's development and creates age-specific parameters for the evaluation of therapeutic response to antiretroviral therapy. Similarly, the development and maturation of organ systems involved in drug absorption, distribution, metabolism, and elimination determines significant changes in the pharmacokinetics of antiretroviral drugs throughout childhood. The authors review the evolution in treatment of pediatric HIV from infancy through adolescence.


Congenital absence of the pectoralis muscles in two collegiate wrestling champions.
Deficiency of the pectoralis major is a relatively common muscle anomaly. There is little documentation, however, of what, if any, functional deficit the anomaly imparts. Therefore, two highly successful amateur wrestlers with unilateral congenital absence of the pectoralis minor and sternocostal head of the pectoralis major are reported. Cybex testing revealed no appreciable decrease in shoulder internal rotation strength but did show a 20%-30% decrease in shoulder horizontal adduction strength. Other patients similarly affected can be advised that their shoulder strength will be slightly decreased, but significant functional limitations are unlikely.


The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis.
The observation of bright liver echo pattern on ultrasound is commonly considered a sign of hepatic steatosis. However, the interference of liver fibrosis on sensitivity and specificity of bright liver echo pattern has caused many to question its effectiveness as a diagnostic tool. The objective of this study was to evaluate the sensitivity, specificity and predictive values of bright liver echo pattern for liver steatosis. We studied 235 consecutive patients suspected of having liver disease of various aetiologies. Median age was 52 years (range, 17-72 years), and there was a male/female ratio of 1:18. All patients underwent ultrasound examination before liver biopsy and was performed by two operators. The presence or absence of bright liver echo pattern and posterior attenuation or areas with different patterns of fat infiltration were noted. Histologic evaluation was performed and graded by Ishak score. Steatosis was categorised as absent, 0-2%, 3-29% to 30-49% or >50%. Interobserver concordance was high. Bright liver echo pattern was found in 67% of patients with steatosis of any degree and 89% of patients with steatosis of >or=30%. Only three patients without steatosis, who had a low Ishak score, demonstrated bright liver echo pattern on ultrasonography. The sensitivity, specificity, positive predictive value and negative predictive value of bright liver echo pattern for steatosis were 64%, 97%, 96.0% and 65%, respectively. Among the subgroup of patients who had steatosis of >or=30%, the sensitivity, specificity, positive predictive value and negative predictive value of bright liver echo pattern were 91%, 93%, 89% and 94%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of posterior attenuation and/or skip areas associated with bright liver echo pattern for steatosis were 89.7%, 100%, 100% and 92.3%, respectively. Univariate analysis showed bright liver echo pattern to be associated only with steatosis and not with fibrosis. We concluded that the presence of bright liver echo pattern is a sign of liver steatosis and that liver fibrosis does not interfere with ultrasound measurements. Posterior attenuation and/or skip areas are closely related to steatosis of >or=30%.


Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity.
Adoptive transfer of high-affinity chimeric antigen receptor (CAR) T cells targeting hematological cancers has yielded impressive clinical results. However, safety concerns regarding target expression on healthy tissue and poor efficacy have hampered application to solid tumors. Here, a panel of affinity-variant CARs were constructed targeting overexpressed ICAM-1, a broad tumor biomarker, using its physiological ligand, LFA-1. Anti-tumor T cell potency in vitro was directly proportional to CAR affinity and ICAM-1 density. In a solid tumor mouse model allowing simultaneous monitoring of anti-tumor potency and systemic off-tumor toxicity, micromolar affinity CAR T cells demonstrated superior anti-tumor efficacy and safety compared to their nanomolar counterparts. Longitudinal T cell tracking by PET/CT and concurrent cytokine measurement revealed superior expansion and contraction kinetics of micromolar affinity CAR T cells. Therefore, we developed an ICAM-1 specific CAR with broad anti-tumor applicability that utilized a reduced affinity targeting strategy to significantly boost efficacy and safety.


Hypothalamic mechanisms of obesity-associated disturbance of hypothalamic-pituitary-ovarian axis.
Ovulatory disorders are the most common clinical feature exhibited among obese women. Initiation of ovulation physiologically requires a surge of gonadotropin-releasing hormone (GnRH) released from GnRH neurons located in the hypothalamus. These GnRH neurons receive metabolic signals from circulation and vicinal neurons to regulate GnRH release. Leptin acts indirectly on GnRH via adjacent leptin receptor (LEPR)-expressing neurons such as proopiomelanocortin (POMC), neuropeptide Y (NPY)/agouti-related peptide (AgRP), and neuronal nitric oxide (NO) synthase (nNOS) neurons to affect GnRH neuronal activities. Additionally, hypothalamic inflammation also affects ovulation independent of obesity. Therefore, this review focuses on hypothalamic mechanisms that underlie the disturbance of hypothalamic-pituitary-ovarian (HPO) axis during obesity with an attempt to promote future studies and/or novel therapeutic strategies for ovulatory disorders in obesity.


Attention deficit hyperactivity disorder and substance use disorders.
During the past two decades, there has been an increased recognition that Attention Deficit Hyperactivity Disorder (ADHD) is overrepresented in treatment and community populations of both adolescents and adults with substance use disorders (SUDs). This chapter explores this relationship, including a review of the prevalence of this comorbidity, ADHD and the risk for the development of SUDs. Possible neurobiological underpinnings of the relationship are also discussed. Because of the salience of the association between smoking (tobacco) and ADHD, this topic is included in the discussion of substance use and SUDs.


Prospective evaluation of scrotal ultrasound and intratesticular perfusion by color-coded duplex sonography (CCDS) in TESE patients with azoospermia.
The objective of this study was to assess whether CCDS might improve the outcome of testicular sperm retrieval in patients with azoospermia. Furthermore, we evaluated potential sonographic alterations of the testis before and after trifocal and Micro-TESE. 78 patients were enrolled prospectively: 24 with obstructive azoospermia (OA) and 54 with non-obstructive azoospermia (NOA). 31 of 54 patients in the NOA group had negative surgical sperm retrieval. Testicular volume, hormonal parameters and sonographical findings were compared before and after TESE. The spermatogenetic score was determined for all retrieval sites. CCDS was performed at the upper, middle and lower segment of the testis. Ultrasound parameters and peak systolic velocity (PSV) were measured pre- and post-operatively. Testicular volume and epididymal head size were significantly increased in OA patients compared to NOA patients. Ultrasound parameters were comparable between NOA patients with and without successful sperm retrieval. A higher intratesticular PSV was significantly correlated with a better spermatogenic score in the corresponding sonographic position. However, after adjustment for other clinical confounders, PSV does not show a significant influence on the spermatogenic score. Testicular volume decreased significantly in all patients post-operatively after 6 weeks (p < 0.001). Finally, the PSV significantly increased in all patients 24 h after surgery and nearly returned to baseline levels after 6 weeks (p < 0.001). A higher intratesticular PSV may be helpful as a pre-operative diagnostic parameter in mapping for better sperm retrieval, but CCDS does not help to predict successful testicular sperm retrieval after adjustment for other clinical confounders.


Nutrient removal effect and characteristics of integrated floating beds at low temperature.
To investigate the effect of combined floating beds on nutrient removal under low temperature, an integrated floating bed with corn flakes (IFB-CF) and an integrated floating bed with light ceramsite (IFB-LC) were constructed in parallel. IFB-LC was used as control group under water temperatures of 9.3-14 °C and a water exchange time of 168 h. Nitrogen and phosphorus removal efficiency, the nutrient level of a hydrophyte (Oenanthe javanica), and the microbial population characteristics of the combined floating bed were investigated. For IFB-CF removal efficiencies, the degradation quantities of total nitrogen (TN), NO3--N, and NH4+-N for IFB-CF were 13.58 ± 0.67 mg/L, 4.40 ± 0.61 mg/L, and 9.21 ± 0.38 mg/L, respectively; in contrast, degradation quantities for IFB-LC were lower (6.41 ± 1.47 mg/L, 2.15 ± 0.40 mg/L, and 5.95 ± 0.46 mg/L, respectively). The reductions in COD (Chemical Oxygen Demand, using K2Cr2O7 as oxidizer) for IFB-LC and IFB-CF were 86.89% and 66.06%, respectively. Using the MiSeq high throughput sequencing method, we analysed microbial community structure and diversity on the base material surface of the IFB-CF and IFB-LC. The results showed 15 phyla, 165 genera, and 78 families on the surface of the IFB-CF. The phylum, genus, and family with the highest abundances were Proteobacteria (48.29%), Trichococcus (10.39%), and Comamonadaceae (12.45%), respectively. We identified 15 phyla, 144 genera, and 93 families on the surface of the IFB-LC. The phylum, genus, and family with the highest abundances were Proteobacteria (46.10%), Dyadobacter (22.67%), and Cytophagaceae (28.75%), respectively. The Chao, ACE, and Shannon & Simpson indices for the IFB-LC were 4081, 6295, and 5.10, and 0.05, respectively; for the IFB-CF they were 4938, 7461, 5.77, and 0.02, respectively. Catalase (CAT) and Peroxidase (POD) concentrations in Oenanthe javanica for IFB-LC were 35.48 u/gFW/min and 1.03 u/gFW/min, respectively; for IFB-CF they were 32.33 u/gFW/min and 1.25 u/gFW/min, respectively. The nutritional energies of IFB-CF and IFB-LC were 107 kJ/100g and 84 kJ/100g. Using the Mondal model of TN removal, k (half-saturation constant) values for IFB-LC and IFB-CF were 35.67 mg/L and 39.23 mg/L, respectively, with a correlation coefficient (R2) of 0.97.


Cell adhesion and junctional proteins in the developing skin of snakes indicate they coordinate the differentiation of the epidermis.
The development of scales and the sequence of epidermal layers during snake embryogenesis has been studied by immunofluorescence for the localization of cell adhesion, adherens, and communicating cell junctional proteins. At about 2nd/3rd of embryonic development in snakes the epidermis forms symmetric bumps at the beginning of scale formation, and they rapidly become asymmetric and elongate forming outer and inner surfaces of the very overlapped scales seen at hatching. The dermis separates a superficial loose from a deeper dense part; the latter is joined to segmental muscles and nerves, likely acting on scale orientation during snake movements. N-cam is present in the differentiating epidermis and mesenchyme of forming scales while L-cam is only/mainly detected in the periderm and epidermis. Mesenchymal N-cam is associated with the epidermis of the elongating dorsal scale surface and with the beta-differentiation that occurs in the overlapping outer surface of scales. Beta-catenin and Connexin-43 show a similar distribution, and they are mainly present in the periderm and differentiating suprabasal keratinocytes likely forming an intense connectivity during epidermal differentiation. Beta-catenin also shows nuclear localization in differentiating cells of the shedding and beta-layers at late stages of scale morphogenesis, before hatching. The study suggests that intensification of adhesion and gap junctions allows synchronization of the differentiation of suprabasal cells to produce the ordered sequence of epidermal layers of snake scales, starting from the shedding complex and the beta-layer.


Experimental assessment of a novel artificial anal sphincter with shape memory alloy.
Fecal incontinence caused by sphincter dysfunction is a difficult medical problem that has not been fully resolved. The artificial anal sphincter provides a new therapeutic strategy for fecal incontinence. In order to solve the biomechanical compatibility problem between the artificial anal sphincter and intestinal tissue in clinical application, a design of constant force artificial anal sphincter was assessed in this paper. The constant force properties and safety of this novel device were evaluated by an experiment conducted in pig intestines with various thicknesses. The constant force characteristic of the device was evaluated by the intestinal pressure of the pig intestine. The safety of the device was evaluated by the surface contact stress of the pig intestine clamped by an artificial anal sphincter. The average measured value of the intestinal pressure of the pig intestines with three thicknesses is about 55.3 mm Hg, the maximum pressure difference is 1 mm Hg, and the fluctuation error of constant clamping load is about 1.8%. The constant clamping load fluctuation error of the four measuring points of the pig intestines with three thicknesses is less than 2%. Even if the thickness of the pig intestines is changed, the measured contact stress value is lower than 10 kPa, which may avoid bit damage for the intestinal tissue. This study demonstrates that the novel artificial sphincter has constant force properties and safety, which prevent ischemic necrosis of soft tissues caused by excessive pressure. Therefore, this study raises the possibility of the long-term efficacy of artificial anal sphincter.


GC and GC-MS characterization of crude oil transformation in sediments and microbial mat samples after the 1991 oil spill in the Saudi Arabian Gulf coast.
The massive oil discharge in the Saudi Arabian coast at the end of the 1991 Gulf War is used here as a natural experiment to study the ability of microbial mats to transform oil residues after major spills. The degree of oil transformation has been evaluated from the analysis of the aliphatic and aromatic hydrocarbons by gas chromatography (GC) and GC coupled to mass spectrometry (GC-MS). The oil-polluted microbial mat samples from coastal environments exhibited an intermediate degree of transformation between that observed in superficial and deep sediments. Evaporation, photo-oxidation and water-washing seemed to lead to more effective and rapid elimination of hydrocarbons than cyanobacteria and its associated microorganisms. Furthermore, comparison of some compounds (e.g. regular isoprenoid hydrocarbons or alkylnaphthalenes) in the oil collected in the area after the spill or in the mixtures retained by cyanobacterial growth gave rise to an apparent effect of hydrocarbon preservation in the microbial mat ecosystems.


Regional and cell-type-specific afferent and efferent projections of the mouse claustrum.
The claustrum (CLA) is a conspicuous subcortical structure interconnected with cortical and subcortical regions. Its regional anatomy and cell-type-specific connections in the mouse remain not fully determined. Using multimodal reference datasets, we confirmed the delineation of the mouse CLA as a single group of neurons embedded in the agranular insular cortex. We quantitatively investigated brain-wide inputs and outputs of CLA using bulk anterograde and retrograde viral tracing data and single neuron tracing data. We found that the prefrontal module has more cell types projecting to the CLA than other cortical modules, with layer 5 IT neurons predominating. We found nine morphological types of CLA principal neurons that topographically innervate functionally linked cortical targets, preferentially the midline cortical areas, secondary motor area, and entorhinal area. Together, this study provides a detailed wiring diagram of the cell-type-specific connections of the mouse CLA, laying a foundation for studying its functions at the cellular level.


Quantitative depth-resolved microcirculation imaging with optical coherence tomography angiography (Part ΙΙ): Microvascular network imaging.
In this work, we review the main phenomena that have been explored in OCT angiography to image the vessels of the microcirculation within living tissues with the emphasis on how the different processing algorithms were derived to circumvent specific limitations. Parameters are then discussed that can quantitatively describe the depth-resolved microvascular network for possible clinical diagnosis applications. Finally, future directions in continuing OCT development are discussed.


Mercury transport and bioaccumulation in riverbank communities of the Alvarado Lagoon System, Veracruz State, Mexico.
The Alvarado Lagoon System (ALS) is located within the Papaloapan River Basin in southern Veracruz, Mexico. The ALS is a shallow system (2 m) connected to the Gulf of Mexico through a narrow sea channel. There are a large number of riverbank communities within the ALS that are dependent upon its biological productivity for comestible and economic subsistence. The purpose of this project was to determine the levels of mercury in water, sediment, fish, and hair samples from within the Papaloapan River Basin and to characterize the risk of Hg exposure to the individuals that reside in these communities. Water and fish samples were collected during the wet (September 2005) and dry (March 2003 and 2005) seasons. Hair samples, dietary surveys, and sediment samples were obtained during the wet and dry seasons of 2005. Total Hg in the water column ranged from 1.0 to 12.7 ng/L. A strong correlation (R(2)=0.82; p<0.001) between total Hg and total suspended solids in the water column suggests that particulate matter is a transport mechanism for Hg within the lagoon system. Total Hg in the sediments ranged from 27.5 to 90.5 ng Hg/g dry weight with no significant difference between the 2005 wet and dry seasons. There was a mild, but significant, correlation between total Hg and % carbon for the March 2005 sediment samples (R(2)=0.435; p=0.020), suggesting that Hg is associated with organic matter on the solid phase. Concentrations of total Hg in fish and shellfish harvested from the ALS ranged from 0.01 to 0.35 microg Hg/g wet. The levels of total Hg in hair ranged from 0.10 to 3.36 microg Hg/g (n=47) and 58% of the samples were above 1.00 microg Hg/g. The findings from this study suggest that individuals who frequently consume fish and shell fish containing low levels of Hg (<0.3 microg/g) can accumulate low to moderate body burdens of Hg, as indicated by hair Hg concentrations>1.0 microg/g, and may be at risk for experiencing low dose mercury toxicity.


Muscarinic and nicotinic activities of the novel acetylcholine analog acetylselenonium choline.
The present paper further characterizes the cholinergic properties of acetylselenonium choline (ASeCh, (CH3)2Se+CH2CH2OCOCH3). The data demonstrate that ASeCh possesses muscarinic receptor agonist properties as evidenced by vasodepressor and smooth muscle contractile activities which are enhanced by physostigmine and antagonized by atropine. ASeCh also possessed nicotinic agonist activity on frog rectus abdominis tissue which was potentiated by physostigmine, and blocked by d-tubocurarine. The relative potencies of ASeCh ranged from approximately 1% to approximately 6% of the potency of acetylcholine in the three types of preparations examined.


Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination.
Meiotic crossovers (COs) ensure proper chromosome segregation and redistribute the genetic variation that is transmitted to the next generation. Large populations and the demand for genome-wide, fine-scale resolution challenge existing methods for CO identification. Taking advantage of linked-read sequencing, we develop a highly efficient method for genome-wide identification of COs at kilobase resolution in pooled recombinants. We first test this method using a pool of Arabidopsis F2 recombinants, and recapitulate results obtained from the same plants using individual whole-genome sequencing. By applying this method to a pool of pollen DNA from an F1 plant, we establish a highly accurate CO landscape without generating or sequencing a single recombinant plant. The simplicity of this approach enables the simultaneous generation and analysis of multiple CO landscapes, accelerating the pace at which mechanisms for the regulation of recombination can be elucidated through efficient comparisons of genotypic and environmental effects on recombination.


Neprilysin inhibition does not alter dynamic of proenkephalin-A 119-159 and pro-substance P in heart failure.
As NEP degrades many substrates, the specific therapeutic mechanism of NEP inhibition with angiotensin receptor neprilysin inhibitor (ARNi) in heart failure with reduced ejection fraction (HFrEF) is not entirely evident. The aim of this study was to investigate the response of two substrates of NEP-the tachykinin and enkephalin systems-to the initiation of ARNi therapy in HFrEF. Between 2016 and 2018, 141 consecutive patients with stable HFrEF [74 with initiation of ARNi and 67 controls on continuous angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy] were prospectively enrolled. Plasma proenkephalin-A 119-159 (PENK) and pro-substance P (pro-SP) were serially determined. Proenkephalin-A 119-159 and pro-SP correlated strongly with each other (rs = 0.67, P < 0.001) and kidney function (rs = -0.66, P < 0.001 and rs = -0.54, P < 0.001) and modestly with NT-proBNP (rs = 0.32, P < 0.001 and rs = 0.24, P = 0.006, respectively). Concentrations of circulating PENK were slightly elevated after 1 and 2 year follow-up compared with baseline (BL) [BL median: 67.4 pmol/L (IQR: 57.3-89.8), 1 year: 83.5 pmol/L (IQR: 62.4-111.6), 2 years: 92.3 pmol/L (IQR: 63.1-101.9); BL vs. 1 year: P = 0.017 and BL vs. 2 years: P = 0.019] in the overall analysis, but lost significance at 2 year follow-up when assessed in paired subanalysis (P = 0.116). Plasma pro-SP levels remained comparable during the entire follow-up [BL median: 78.3 pmol/L (IQR: 67.9-90.6), 1 year: 75.9 pmol/L (IQR: 58.6-96.3), 2 years: 79.7 pmol/L (IQR: 59.9-105.3); P = ns for both timepoints]. Biomarker patterns of ARNi patients were independent from baseline therapy, that is, ACEi or ARB (P > 0.05 between groups). Although enkephalins and SP are known substrates of NEP, NEP inhibition by ARNi does not clearly affect the circulating precursors PENK and pro-SP in HFrEF.


The serum level of interleukin-6 in patients with intellectual disability and refractory epilepsy.
We aimed to study the influences of active epilepsy and intellectual disability (ID) on the serum interleukin-6 (IL-6) by determining levels in 74 patients with developmental disorder with epilepsy and 63 healthy controls. The patients showed significantly higher IL-6 levels than the controls (4.1±4.5pg/ml vs. 2.1±1.0pg/ml; p<0.001). High seizure frequency and severe intellectual disability emerged as predictors for elevated serum levels of IL-6.


Human B lymphocytes express the p75 component of the interleukin 2 receptor.
The nature of the interleukin 2 (IL-2) receptor on purified human B lymphocytes was examined. Both normal and malignant cells showed evidence of a 70-75,000 mol. wt (p75) IL-2 binding molecule as assessed by 125I-labeled IL-2 binding and receptor cross-linking. On normal, Tac-negative B lymphocytes the estimated number of p75 binding sites was 1100 per cell and the dissociation constant (Kd) was 1.7 nM. Consistent with this, cross-linking experiments demonstrated the presence of an IL-2 binding molecule of 70-75,000 mol. wt. Purified B cells from patients with hairy cell leukemia and chronic lymphocytic leukemia (CLL) also expressed the p75 IL-2 binding molecule. In the HCL samples, a small number of high-affinity IL-2 binding sites were detected (27-90) while the majority of binding sites (2100-10,800) were typical of low-affinity p55 Tac binding. IL-2 added to the purified normal and CLL B lymphocytes led to the induction of p55 Tac expression and the generation of high-affinity IL-2 receptors. This response to IL-2 was equivalent to the response observed when normal B lymphocytes were stimulated by Staphylococcus aureus Cowan I.


Offering small tangible rewards within social casino games increases in-play bets but does not impact real-money gambling.
Many video games incorporate gambling-like elements into their design (and vice versa). Social casino games - a type of video game that mimics gambling activities-are one such example. In the current experimental research, we examined whether offering tangible rewards (i.e., rewards with value outside the game) in a social casino game was associated with increased social casino game play and subsequent gambling. Participants (N = 213, Mage = 36.5, 55.3% female) were recruited from CloudResearch. They were randomly assigned to either a reward condition (n = 109) in which, following a week of social casino game play, participants could trade in their virtual credits for a bonus, or a control condition in which the possibility of reward was not presented (n = 104). Following the week of play, all participants were then provided with an opportunity to gamble in an online roulette game with their study compensation. Participants in the reward condition placed more bets and bet higher credit amounts in the social casino game than participants in the control condition. In contrast, no differences were found between the two groups regarding their decision to gamble with their remuneration. Participants who elected to gamble reported higher problem gambling severity and gambling-related cravings. There were no differences in impulsivity. These results suggest that offering tangible rewards in social casino games may increase social casino game play but not necessarily the decision to gamble with real-world money.


Minimally invasive subtotal colectomy and ileal pouch-anal anastomosis for fulminant ulcerative colitis: a reasonable approach?
This study was designed to evaluate the safety, feasibility, and short-term outcomes of three-stage minimally invasive surgery for fulminant ulcerative colitis. Using a prospective database, we identified all patients with ulcerative colitis who underwent minimally invasive surgery for both subtotal colectomy and subsequent ileal pouch-anal anastomosis at our institution from 2000 to 2007. Demographics and short-term outcomes were retrospectively evaluated. During seven years, 50 patients underwent minimally invasive subtotal colectomy for fulminant ulcerative colitis; 50 percent were male, with a median age of 34 years. All patients had refractory colitis: 96 percent were taking steroids, 76 percent were recently hospitalized, 59 percent had >/=5 kg weight loss, 57 percent had anemia that required transfusions, 30 percent were on biologic-based therapy, and 96 percent had >/=1 severe Truelove & Witts' criteria. Of these 50 procedures, 72 percent were performed by using laparoscopic-assisted and 28 percent with hand-assisted techniques. The conversion rate was 6 percent. Subsequently, minimally invasive completion proctectomy with ileal pouch-anal anastomosis was performed in 42 patients with a 2.3 percent conversion rate. Median length of stay after each procedure was four days. There was one anastomotic leak and no mortality. A staged, minimally invasive approach for patients with fulminant ulcerative colitis is technically feasible, safe, and reasonable operative strategy, which yields short postoperative length of stay.


In vitro measurement of temperature changes during implantation of cemented glenoid components.
It is unclear whether the increase in temperature during cement curing may cause osteonecrosis, leading to loosening of the glenoid component in shoulder arthroplasty. We therefore analyzed the temperature during implantation of cemented glenoid implants. 8 keeled and 8 pegged glenoids were implanted in standardized fashion in 8 pairs of scapulas. Temperature and pressure sensors were implanted at the bone-cement interface in the glenoid. Real-time measurements were made of temperature and pressure within the glenoid vault. In no case was the temperature reached high enough to endanger the surrounding bone. The mean increase in temperature was 5 degrees (0.5-6.9) in the keeled group and 2.7 degrees (1.7-3.6) in the pegged group. The mean maximum pressure in the keeled group was 50 kPa (20-100) and in the pegged group it was 113 kPa (60- 181). Both differences were statistically significant. The temperatures that occur during implantation of cemented components are low and probably not high enough to cause osteonecrosis in the surrounding bone.


Recurrent tetraamelia and pulmonary hypoplasia with multiple malformations in sibs.
A term amelic female infant was born to an apparently nonconsanguineous Arab Moslem couple. This was followed by the birth of 4 normal children. Afterwards, in 2 subsequent pregnancies, 2 amelic fetuses were diagnosed by transabdominal ultrasonography in the 18th and 12th week of gestation. Pregnancies were terminated and on autopsy both amelic fetuses had severe lung hypoplasia and aplasia of the peripheral pulmonary vessels. The first fetus also had apparently low-set ears and micrognathia, whereas the last had hydrocephaly and left cleft lip beside the lung hypoplasia and aberrant pulmonary artery. This appears to be a new autosomal recessive malformation syndrome.


Mechanical ventilation and middle ear effusions among tracheostomy-dependent children.
To determine the cumulative 24-month incidence of middle ear effusion (MEE) among tracheostomy-dependent children requiring ventilatory support. A prospective longitudinal cohort study included all children under 2 years of age with a tracheostomy placed at a tertiary care children's hospital between 2015 and 2020 that obtained at least one tympanometry exam. The development of MEE, defined as a flat tympanogram with normal external canal volume, and mechanical ventilation requirement at examination were recorded. Ninety-four children with a mean age at tracheostomy of 5.4 months (SD: 3.7) were included. During a mean follow-up of 18.3 months (SD: 14.6) (median: 14.1 months, interquartile range: 6.6-27.8), 192 tympanometry examinations were obtained with 59% (114/192) while requiring mechanical ventilation. Within 24 months after tracheostomy, 56.5% (95% CI: 48.9-64.4%) of children developed at least one MEE. Among those on mechanical ventilation, 74.0% (95% CI: 65.6-82.5%) developed MEE compared to 31.2% (95% CI: 21.4-44.0%) not on mechanical ventilation (HR: 2.97, 95% CI: 1.46-6.05, P = .003). A persistent MEE on two consecutive exams was not statistically more common for children on a ventilator (OR: 0.64, 95% CI: 0.01-6.95, P = .70). When controlling for age at exam, craniofacial syndrome, and newborn hearing test results on logistic regression, ventilator-dependence significantly predicted the presence of MEE (OR: 2.34, 95% CI: 1.18-4.68, P = .02). Children with a tracheostomy were more likely to develop MEE when requiring mechanical ventilation. Clinicians should recognize this risk factor and appropriately assess for development of MEE to mitigate adverse speech and language development outcomes in this vulnerable population.


Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment.
Reproductive function is controlled by a finely tuned balance of androgens and estrogens. Environmental toxicants, notably endocrine disrupting chemicals (EDCs), appear to be involved in the disruption of hormonal balance in several studies. To further describe the effects of selected EDCs on steroid secretion in female rats, we aim to simultaneously investigate the EDC concentration and the sex hormone balance in the ovaries. Therefore, an effective method has been developed for the quantification of the sex steroid hormones (testosterone, androstenedione, estradiol, and estrone) and four endocrine disrupting chemicals (bisphenol A, atrazine, and the active metabolites of methoxychlor and vinclozolin) in rat ovaries. The sample preparation procedure is based on the so-called "quick, easy, cheap, effective, rugged, and safe" approach, and an analytical method was developed to quantify these compounds with low detection limits by liquid chromatography coupled with a tandem mass spectrometer. This analytical method, applied to rat ovary samples following subacute EDC exposure, revealed some new findings for toxicological evaluation. In particular, we showed that EDCs with the same described in vitro mechanisms of action have different effects on the gonadal steroid balance. These results highlight the need to develop an integrative evaluation with the simultaneous measurement of EDCs and numerous steroids for good risk assessment.


Pharmacological inhibition of USP30 activates tissue-specific mitophagy.
Mitophagy is the regulated process that targets damaged or dysfunctional mitochondria for lysosomal-mediated removal. This process is an essential element of mitochondrial quality control, and dysregulation of mitophagy may contribute to a host of diseases, most notably neurodegenerative conditions such as Parkinson's disease. Mitochondria targeted for mitophagic destruction are molecularly marked by the ubiquitination of several outer mitochondrial membrane (OMM) proteins. This ubiquitination is positively regulated, in part, by the mitochondrial-targeted kinase PINK1 and the E3 ubiquitin ligase Parkin. In contrast, the reverse phenomenon, deubiquitination, removes ubiquitin from Parkin substrates embedded in the OMM proteins, antagonizing mitophagy. Recent evidence suggests that the mitochondrial deubiquitinase USP30 negatively regulates Parkin-mediated mitophagy, providing opportunities to identify USP30 inhibitors and test for their effects in augmenting mitophagy. Here we will characterize a USP30 inhibitor and demonstrate how the pharmacological inhibition of USP30 can augment stress-induced mitophagic flux. We have conducted mitophagy and mitochondrial analyses in cultured cells. We have determined the plasma pharmacokinetics of the USP30 inhibitor in mice and conducted analyses using the mt-Keima mice to measure in vivo mitophagy directly. The compound has minimal mitochondrial toxicity in cultured cells and is tolerated well in mice. Interestingly, we demonstrated tissue-specific induction of mitophagy following USP30 pharmacological inhibition. In particular, pharmacological inhibition of USP30 induces a significant increase in cardiac mitophagy without detriment to cardiac function. Our data support the evidence that USP30 inhibition may serve as a specific strategy to selectively increase mitophagic flux, allowing for the development of novel therapeutic approaches.


Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.
Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V). Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n = 306; MS, n = 8), or by voiding (SCI, n = 103; MS, n = 383). A total of n = 381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence. Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI". Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument. The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.


Immunoglobulin G4-Related Disease Responder Index Correlates With the Risk of 1-Year Relapse in Type 1 Autoimmune Pancreatitis.
Type 1 autoimmune pancreatitis (AIP) is a manifestation of immunoglobulin G4-related diseases (IgG4-RD). To evaluate the activity of the disease, the IgG4-RD responder index (RI) has been created. This study evaluated the IgG4-RD RI as prognostic factor of 1-year disease relapse. Patients diagnosed with type 1 AIP between January 2012 and December 2016, with available magnetic resonance imaging and IgG4 dosage, were enrolled. Immunoglobulin G4-RD RI was calculated at baseline (time 0), and at 3 to 6 and 12 to 18 months after the end of steroid therapy (time 1 and time 2, respectively). Thirty-three patients were included in the study. Immunoglobulin G4-RD RI was 8.9 (standard deviation [SD], 3.8) at time 0, 2.4 (SD, 3.1) at time 1 (P < 0.0001 vs time 0), and 4.2 (SD, 3.9) at time 2 (P = 0.02 vs time 1). Fourteen patients who relapsed within 1 year showed a higher mean value of IgG4-RD RI at time 0 (10.9; SD, 4.3) versus 19 who did not (7.4; SD, 2.6; P = 0.012). This difference was observed also at time 2 (6.8 vs 2.1; P = 0.002). Immunoglobulin G4-RD RI correlates with type 1 AIP disease activity, and it predicts disease relapse within 1 year.


Costs and outcomes of VCT delivery models in the context of scaling up services in Indonesia.
To evaluate costs and outcomes of voluntary counselling and testing (VCT) service delivery models in urban Indonesia. We collected primary data on utilization, costs and outcomes of VCT services in a hospital clinic (568 clients), HIV community clinic (28 clients), sexually transmitted infection (STI) community clinic (784 clients) and prison clinic (574 clients) in Bandung, Indonesia, in the period January 2008-April 2009. The hospital clinic diagnosed the highest proportion and absolute number of HIV infections, but with the lowest average CD4 cell count and with the highest associated travelling and waiting time. The prison clinic detected fewer cases, but at an earlier stage, and all enrolled in HIV care. The community clinics detected the smallest number of cases, and only 0-8% enrolled in HIV care. The unit cost per VCT was highest in the hospital clinic (US$74), followed by the STI community clinic (US$65), the HIV community clinic (US$39) and the prison (US$23). We propose a reorientation of the delivery models for VCT and related HIV/AIDS treatment in this setting. We call for the scaling up of community clinics for VCT to improve access, promote earlier detection and to perform (early) treatment activities. This would reduce the burden of the hospital clinic to orient itself towards the treatment of AIDS patients. This is one of very few studies addressing this issue in Asia and the first of its kind in Indonesia, which has a rapidly growing HIV epidemic. The conceptual framework and overall conclusions may be relevant to other low-income settings.


Leisure-time management and subjective well-being among older adults: A three-wave longitudinal survey.
As older adults have longer leisure time and the types and influences of leisure activities they participate in are diverse, appropriate management of their leisure time would be important to optimize their subjective well-being. Although greater use of time management in educational and occupational settings is associated with better job performance, academic achievement, and the well-being of workers and students, few studies have investigated time management in leisure settings. This study aimed to examine the longitudinal association between leisure-time management and subjective well-being among older adults. Data on 879 individuals in Nada Ward, Kobe, Japan were obtained from a three-wave questionnaire-based longitudinal survey (Wave 1: December 2017 to January 2018; Wave 2: after one year; Wave 3: after three years). In each survey, leisure-time management (newly developed in this study) and subjective well-being (simplified Japanese version of the World Health Organization Five Well-Being Index) were measured. This study used a cross-lagged model to analyze the longitudinal association between leisure-time management and subjective well-being after considering their inverse association. The cross-lagged model indicated that that the standardized path coefficients from leisure-time management in Wave 1 to subjective well-being in Wave 2 (0.13, p<0.001) and from leisure-time management in Wave 2 to subjective well-being in Wave 3 (0.06, p=0.042) were positive and significant. This study found that leisure-time management is a determinant of subjective well-being among older adults. This finding indicates that the management of leisure time elevates one's subjective well-being among them.


Plasma concentrations of angiotensin II and aldosterone during acute left ventricular failure in the dog. Effect of converting enzyme inhibition.
Acute left ventricular failure was induced in anesthetized dogs by left coronary embolization. Treatment with the converting enzyme inhibitor enalaprilat (MK-422) was then given. Hemodynamic registrations confirmed the development of left ventricular failure. Plasma concentrations of angiotensin II and aldosterone rose significantly. Treatment with enalaprilat was accompanied by significant reductions in heart preload and afterload and in plasma hormone concentrations.


Oxidative stress and ATPase6 mutation is associated with primary ovarian insufficiency.
Primary ovarian insufficiency (POI) is a heterogeneous, multifactorial disorder. Though genetic anomalies, infections, autoimmune disorder and hormonal imbalance are few of the causes of POI, in the majority of patients (50-60%) no etiology has been identified. Mitochondrial bioenergetics and biogenesis play an important role in oocyte and embryo development, whereas mtDNA integrity and content are essential for the normal development of oocytes. ATPase6 helps to maintain the mt genome integrity, and mutations in ATPase6 are associated with overproduction of reactive oxygen species (ROS) in a variety of diseases; however, its role in POI has not been evaluated. Therefore, we planned to evaluate the potential role of ATPase6 gene mutations and associated oxidative stress in idiopathic cases of POI. This pilot study included: 20 cases of POI with FSH level of >40 mIU/ml; 4 cases of occult ovarian insufficiency (occult OI) with irregular menses and mean FSH levels of 16.4 mIU/ml; and 20 age-matched healthy female controls (FSH 2-5 mIU/ml). ROS levels in blood plasma were measured by luminol-dependent chemiluminescence assay and the ROS values were expressed as relative light unit per minute (RLU/min). mtDNA ATPase6 gene was amplified and sequenced from the blood lymphocyte DNA. Of all, 50% patients showed nucleotide changes in the ATPase6 gene, as compared to 10% in controls, and the majority of these mutations were non-synonymous. ATPase6 mt.8684 C>T and mt.9094 C>T were found to be significantly (P < 0.005) higher in cases as compared to controls. ROS levels were found to be significantly (P < 0.005) higher in POI and occult OI patients compared to controls and nucleotide changes were found to positively correlate with ROS levels. Moreover, ROS production was found to positively correlate (r = 0.7038, P < 0.001) with FSH levels of the patients (POI and OI) compared to controls. This pilot study clearly demonstrates for the first time ATPase6 gene nucleotide alterations and elevated ROS levels in idiopathic cases of POI. Therefore, it may be possible that OS associated with ATPase6 gene mutation may be causal in idiopathic cases of premature OI. However, larger studies with inclusion of more cases of both POI and occult OI are required to strongly establish the correlation between oxidative stress and mitochondrial nucleotide alterations in the pathogenesis of POI. Such cases with OS-induced POI may benefit immensely by early diagnosis and prompt antioxidant administration.


A prospective study on the pathogenesis of catheter-associated bacteriuria in critically ill patients.
Updating the pathogenesis of catheter-associated bacteriuria (CA-bacteriuria) in the intensive care unit (ICU) is needed to adapt prevention strategies. Our aim was to determine whether the main pathway of CA-bacteriuria in ICU patients was endoluminal or exoluminal. In a prospective study, quantitative urine cultures were sampled from catheter sampling sites, collector bags and the catheter outer surface near the meatus from days 1 to 15 after catheterization. The endoluminal pathway was CA-bacteriuria (defined as 102 CFU/mL) first in collector bags and then in catheters. The exoluminal pathway was CA-bacteriuria first in catheters, on day 1 in early cases and after day 1 in late cases. Of 64 included patients, 20 had CA-bacteriuria. Means of catheterization days and incidence density were 6.81 days and 55.2/1000 catheter-days. Of 26 microorganisms identified, 12 (46.2%) were Gram positive cocci, 8 (30.8%) Gram negative bacilli and 6 yeasts. Three (11.5%) CA-bacteriuria were endoluminal and 23 (88.5%) exoluminal, of which 10 (38.5%) were early and 13 (50%) late. Molecular comparison confirmed culture findings. A quality audit showed good compliance with guidelines. The exoluminal pathway of CA-bacteriuria in ICU patients predominated and surprisingly occurred early despite good implementation of guidelines. This finding should be considered in guidelines for prevention of CA-bacteriuria.


Quantitative 1H NMR method for analyzing primaquine diphosphate in active pharmaceutical ingredients.
Thermal analysis, Fourier Transform IR, the isotropic chemical shift of 1H NMR in different solvents, their temperature dependence and spin-lattice relaxation time constant (T1), solution 1D and 2D NMR, and solid-state 13C and 31P NMR (magic angle spinning NMR) were employed to obtain full information and elucidate the structures of primaquine diphosphate (PQD) samples used for quality controlling malaria medicines. Additionally, a simple, rapid, specific, and reliable quantitative method (qNMR) was developed to determine the PQD level in the raw material of active pharmaceutical ingredients (APIs). The method was developed using ethylene carbonate (EC) as the internal standard and dimethylsulfoxide-d6 (DMSO-d6) as the NMR solvent. For the API qNMR, 1H NMR signals at 3.82 and 1.22 ppm were used. The qNMR methodology, through the linearity, range, LOD and LOQ, stability, precision, robustness, and accuracy, was validated within the requirements of guidelines. The accuracy of the qNMR was evaluated by comparing it to a pharmacopeial HPLC technique and there were no statistical differences (p > 0.05). The proposed qNMR method authentically supports and endorses the current pharmacopoeial methods used for determining the PQD content.


Envelope protein E1 as vaccine target for western equine encephalitis virus.
Western equine encephalitis virus (WEEV) is a mosquito-borne RNA virus which causes lethal infection in humans and equines. There are no commercial vaccines or anti-WEEV drugs available for humans. We used replication-defective, human adenovirus serotype-5 (HAd5) as a delivery vector for developing WEEV vaccine. Our previous study found delivery of both E1 and E2 envelope proteins of WEEV by HAd5 vector offers complete protection against lethal challenge of WEEV. In this paper, we constructed a HAd5-vectored E1 vaccine, Ad5-E1. Mice given single-dose vaccination of Ad5-E1 were completely protected against both homologous and heterologous WEEV strains. The protection was rapid, which was achieved as early as day 7 after vaccination. In addition, Ad5-E1 induced a strong WEEV-specific T cell response. Our data suggest E1 is a potential target for developing single-dose, fast-acting, HAd5-vectored vaccine for WEEV.


Two-staged nuclear transfer can enhance the developmental ability of goat-sheep interspecies nuclear transfer embryos in vitro.
The technique of interspecies somatic cell nuclear transfer, in which interspecies cloned embryos can be reconstructed by using domestic animal oocytes as nuclear recipients and endangered animal or human somatic cells as nuclear donors, can afford more opportunities in endangered animal rescue and human tissue transplantation, but the application of this technique is limited by extremely low efficiency which may be attributed to donor nucleus not fully reprogrammed by xenogenic cytoplasm. In this study, goat fetal fibroblasts (GFFs) were used as nuclear donors, in vitro-matured sheep oocytes were used as nuclear recipients, and a two-stage nuclear transfer procedure was performed to improve the developmental ability of goat-sheep interspecies clone embryos. In the first stage nuclear transfer (FSNT), GFFs were injected into the ooplasm of enucleated sheep metaphase-II oocytes, then non-activated reconstructed embryos were cultured in vitro, so that the donor nucleus could be exposed to the ooplasm for a period of time. Subsequently, in the second stage nuclear transfer, FSNT-derived non-activated reconstructed embryo was centrifuged, and the donor nucleus was then transferred into another freshly enucleated sheep oocyte. Compared with the one-stage nuclear transfer, two-stage nuclear transfer could significantly enhance the blastocyst rate of goat-sheep interspecies clone embryos, and this result indicated that longtime exposure to xenogenic ooplasm benefits the donor nucleus to be reprogrammed. The two-stage nuclear transfer procedure has two advantages, one is that the donor nucleus can be exposed to the ooplasm for a long time, the other is that the problem of oocyte aging can be solved.


Real-time kinetics and affinity analysis of the interaction between protein A and immunoglobulins G derived from different species on silica colloidal crystal films.
Kinetic and affinity analysis of protein interactions reveals information on their related activities in biological processes. Herein, we established a system for evaluating the kinetics and affinity of the interaction between protein A and various IgG species on the surface of silica spheres of silica colloidal crystal (SCC) films by the extraordinary optical interference capabilities of 190 nm silica spheres after self-assembly. The equilibrium association constant (KA) was calculated by the equilibrium Langmuir model and nonlinear least-squares analysis of time-dependent data. The relative protein A/IgG binding affinity is human > rabbit >cow >goat. In addition, the competitive interaction of distinct species of IgG with protein A at the interface of SCC films was studied and performed. These findings may help with the use of protein A and other recognition components in a number of sensor types. Furthermore, this research might offer a novel approach to determining the kinetics and affinity of proteins on the surface of spheres particles, which may contribute to the development of the application of spheres particles in pharmaceutical science, biomedical engineering, and other techniques.


Al-, Ga-, Mg-, or Li-doped zinc oxide nanoparticles as electron transport layers for quantum dot light-emitting diodes.
Colloidal quantum dots and other semiconductor nanocrystals are essential components of next-generation lighting and display devices. Due to their easily tunable and narrow emission band and near-unity fluorescence quantum yield, they allow cost-efficient fabrication of bright, pure-color and wide-gamut light emitting diodes (LEDs) and displays. A critical improvement in the quantum dot LED (QLED) technology was achieved when zinc oxide nanoparticles (NPs) were first introduced as an electron transport layer (ETL) material, which tremendously enhanced the device brightness and current efficiency due to the high mobility of electrons in ZnO and favorable alignment of its energy bands. During the next decade, the strategy of ZnO NP doping allowed the fabrication of QLEDs with a brightness of about 200 000 cd/m2 and current efficiency over 60 cd/A. On the other hand, the known ZnO doping approaches rely on a very fine tuning of the energy levels of the ZnO NP conduction band minimum; hence, selection of the appropriate dopant that would ensure the best device characteristics is often ambiguous. Here we address this problem via detailed comparison of QLEDs whose ETLs are formed by a set of ZnO NPs doped with Al, Ga, Mg, or Li. Although magnesium-doped ZnO NPs are the most common ETL material used in recently designed QLEDs, our experiments have shown that their aluminum-doped counterparts ensure better device performance in terms of brightness, current efficiency and turn-on voltage. These findings allow us to suggest ZnO NPs doped with Al as the best ETL material to be used in future QLEDs.


Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.
Myelin figures, or zebra bodies, seen on electron microscopy were historically considered pathognomonic of Fabry disease, a rare lysosomal storage disorder caused by alpha-galactosidase A deficiency and associated with X-linked recessive mode of inheritance. More recently, iatrogenic phospholipidosis has emerged as an important alternate cause of myelin figures in the kidney. We report two families with autosomal dominant nephropathy presenting with proteinuria and microscopic hematuria, and the kidney biopsies were notable for the presence of myelin figures and zebra bodies. Laboratory and genetic work-up for Fabry disease was negative. Genetic testing in both families revealed the same heterozygous missense mutation in LMX1B (C.737G>A, p.Arg246Gln). LMX1B mutations are known to cause nail-patella syndrome, featuring dysplastic nails and patella with or without nephropathy, as well as isolated LMX1B-associated nephropathy in the absence of extrarenal manifestations. LMX1B mutation-associated nephropathy should be considered in hereditary cases of proteinuria and/or hematuria, even in the absence of unique glomerular basement membrane changes indicative of nail-patella syndrome. In addition, LMX1B mutation should be included in the differential diagnosis of myelin figures and zebra bodies on kidney biopsy, so as to avoid a misdiagnosis.


Associations of glycated albumin and fructosamine with glycaemic status in urban black South Africans.
The associations of glycated albumin (GA) and fructosamine (FA) as alternate tests for diabetes screening in South Africans were examined to overcome shortcomings with oral glucose tolerance tests (OGTTs). Based on OGTTs, glycaemic status included 1) normal glucose, 2) dysglycaemia (impaired fasting glucose, impaired glucose tolerance, newly diagnosed diabetes), and 3) known diabetes. Among 1092 participants, >21 years, mean GA (16.9%) and FA (230.2 μmol/l) increased significantly by age and worsening glycaemic status and were significantly higher in women vs. men and BMI (kg/m2) ≥ 30 vs. <30. For dysglycaemia, correlations of GA and FA with fasting and 2-hour glucose levels were higher in obese (0.576 to 0.688) vs. non-obese (-0.010 to 0.522). Optimal GA threshold to identify dysglycaemia was 15.35% and comparable, but with lower sensitivity (0.54) and specificity (0.55), to Asian studies. For FA, the optimal cut-point of 227.0 μmol/l approximated that described in the literature. Dysglycaemia and known diabetes were associated with GA, while only known diabetes was related to FA, in models adjusted for age, gender and obesity. Potential exists for GA and/or FA as alternative measures of dysglycaemia in clinical practice in Africans, but longitudinal studies are required to clearly elucidate their utility.


Significance of the T2*-weighted gradient echo brain imaging in patients with infective endocarditis.
Although aneurysm formation accompanying parenchymal hemorrhage is one of devastating complications in the central nerves system (CNS), imaging studies of the brain are not routinely warranted in patients with infective endocarditis (IE). To assess the clinical importance for detecting silent lesions in the central nervous system, we investigated hypointense signal spots detected on the brain T2*-weighted MR imaging in patients with IE. Eleven patients with IE were retrospectively reviewed. Seven patients (63.6%) showed hypointense signal spots on T2*-weighted MR images. The number of hypointense signal spots increased within only a few weeks in five patients. The brain T2*-weighted MR imaging in patients with IE may have a potential role to detect CNS lesions with clinical significance of potentially high risk of intracranial hemorrhage. T2*-weighted hypointense signal spots may be specific to brain involvement, and be quite useful in monitoring CNS lesions associated with IE, even if they are asymptomatic.


Anaesthetic management of thoracotomy in the presence of chronic carbon dioxide retention.
A patient suffering from chronic carbon dioxide retention with persistent pneumothorax, following spontaneous rupture of an emphysematous bulla, underwent thoracotomy. The surgical and anaesthetic management are reported.


Diagnostic Accuracy of Sagittal TSE-T2W, Variable Flip Angle 3D TSET2W and High-resolution 3D Heavily T2W Sequences for the Stenosis of Two Localizations: The Cerebral Aqueduct and the Superior Medullary Velum.
This study aimed to investigate the accuracy of conventional Sagittal Turbo spin Echo T2-weighted (Sag TSE-T2W), variable flip angle 3D TSE (VFA-3D-TSE) and high-resolution 3D heavily T2W (HR-3D-HT2W) sequences in the diagnosis of primary aqueductal stenosis (PAS) and Superior Medullary Velum Stenosis (SMV-S), and the effect of stenosis localization on diagnosis. Seventy-seven patients were included in the study. The diagnosis accuracy of the HR-3D-HT2W, Sag TSE-T2W and VFA-3D-TSE sequences, was classified into three grades by two experienced neuroradiologists: grade 0 (the sequence has no diagnostic ability), grade 1 (the sequence diagnoses stenosis but does not show focal stenosis itself or membrane formation), and grade 2 (the sequence makes a definitive diagnosis of stenosis and shows focal stenosis itself or membrane formation). Stenosis localizations were divided into three as Cerebral Aquaduct (CA), Superior Medullary Velum (SMV) and SMV+CA. In the statistical analysis, the grades of the sequences were compared without making a differentiation based on localization. Then, the effect of localization on diagnosis was determined by comparing the grades for individual localizations. In the sequence comparison, grade 0 was not detected in the VFA-3D-TSE and HR-3DHT2W sequences, and these sequences diagnosed all cases. On the other hand, 25.4% of grade 0 was detected with the Sag TSE-T2W sequence (P<0.05). Grade 1 was detected by VFA-3D-TSE in 23% of the cases, while grade 1 (12.5%) was detected by HRH-3D-T2W in only one case, and the difference was statistically significant (P<0.05). When the sequences were examined according to localizations, the rate of grade 0 in the Sag TSE-T2W sequence was statistically significantly higher for the SMV localization (33.3%) compared to CA (66.7%) and SMV+CA (0%) (P<0.05). Localization had no effect on diagnosis using the other sequences. In our study, we found that the VFA-3D-TSE and HR-3D-HT2W sequences were successful in the diagnosis of PAS and SMV-S contrary to the Sag TSE-T2W sequence and especially SMV localization decreases the diagnostic accuracy of Sag TSE-T2W sequence.


A change worth the making. Implementing primary nursing.
Adopting primary nursing can be a difficult task, involving a great deal of planning, and change for all nursing staff. One haematology ward, however, found it resulted in improved satisfaction for both patients and nurses.


[Planimetric measurement of the regurgitant orifice area using tridimensional transoesophageal echocardiography for aortic regurgitation, reproducibility and feasibility].
Aortic regurgitation is mainly evaluated by trans-thoracic echocardiography using multi-parametric qualitative and semi quantitative tools. All those parameters can fail to meet expectations, resulting in an imperfect diagnostic reliability and assessment of aortic regurgitation severity can be challenging. We sought to evaluate feasibility and intra- and inter-observer reproducibility of aortic regurgitant orifice area measured by planimetry with tridimensional trans-esophageal echocardiography on patients with at least grade 2/4 aortic regurgitation. Consecutive patients with at least grade 2/4 aortic regurgitation measured by trans-thoracic echocardiography and referred for trans-esophageal echocardiography for any reason were included. Planimetric reconstructions of regurgitant orifice area were studied and reproducibility indexes between senior and junior observers were calculated. Twenty-three patients were included in this study. Intra- and inter-observer reproducibility were excellent with an ICC of 0.95 [0.88-0.98], P<0.0001 and 0.91 [0.79-0.96], P<0.0001, respectively. Mean length of the measurement was 6.6±0.9min [CI95% 6.23-7.01]. Planimetric measurement of the aortic regurgitant orifice using tridimensional trans-esophageal echocardiography seems to be feasible and has great intra- and inter-observer reproducibility. Reconstruction durations were compatible with a daily use. There is a need now to investigate the reliability of this measurement as compared with the reference technique.


Carbon dioxide fumigation for controlling bed bugs.
We investigated the potential of carbon dioxide (CO2) fumigation as a method for controlling bed bugs, Cimex lectularius L. The effect of bed bug developmental stage, temperature, and CO2 concentration on the minimum time to kill 100% of bed bugs was determined. The minimum CO2 concentration lethal to all bed bug stages was approximately 30% with 24 h exposure time at 25 degrees C. The minimum fumigation time required to kill 100% of eggs using 100% CO2 at 20, 25, and 30 degrees C were 3, 7, and 8 h, respectively; the minimum fumigation time to kill 100% of adult males/nymphs were 8, 13, and 14 h, respectively. The minimum time to kill 100% of adult males/nymphs using 50 and 70% CO2 at 25 degrees C were 18 and 16 h, respectively. We found that eggs were not completely killed after 24 h fumigation when the CO2 concentration was lower than 80%. Thus, bed bug eggs were more susceptible to 100% CO2 fumigation than nymphs and adult males but more tolerant than nymphs and adult males with lower CO2 concentration (50-80%). There were no significant differences among nymphs, adult males, and adult females in their susceptibility to 100% CO2 fumigation. A 24 h fumigation in sealed 158 liter (42 gallon) heavy duty garbage bags filled 90% full with fabric materials and/or boxes and 1,350 g dry ice per bag was sufficient to kill all stages of bed bugs hidden in the materials at room temperature (23-24 degrees C). Sealed heavy duty garbage bags maintained > or = 94% CO2 for at least 24 h. Custom-made double zipper plastic bags (122 x 183 cm) were also used to evaluate the effectiveness of CO2 fumigation for controlling bed bugs. Each bag was filled with fabric and boxes to 50-90% full. Bed bugs were hidden in various locations of each bag. CO2 was introduced into the bags through a CO2 cylinder. CO2 fumigation lasting 24-48 h was sufficient to kill all stages of bed bugs at room temperature, depending on the quantity of materials placed in each bag and whether CO2 was introduced one or two times at the onset. CO2 is an effective alternative to conventional fumigants for eliminating bed bugs hiding in infested household items such as clothing, shoes, books, electronics, sofas, and so forth.


Use of recombinant activated factor VII for massive postpartum hemorrhage.
We hypothesised that patients with massive postpartum hemorrhage (PPH), defined as blood loss >1,500 ml,may benefit from the use of activated recombinant factor VII (rFVIIa). Design. Retrospective cohort study. Setting.Department of Obstetrics & Gynaecology, Dow University of Health Sciences. Thirty-four women with a diagnosis of massive PPH. All patients with PPH who were admitted to the Department of Obstetrics &Gynecology and Surgical Intensive Care Unit of Civil Hospital Karachi, Pakistan, were included in the study. From March 2005 to October 2006, 34 patients fulfilled the criteria of massive PPH, of which 18 received rFVIIa to control bleeding, and 16 patients did not. Availability and cost of rFVIIa were the factors in drug allocation. Main outcome measures. Maternal mortality, correction of coagulopathy, the amount of blood products transfused and preservation of fertility. Patients receiving rFVIIa had lower maternal mortality (5/18, 28% versus 8/16, 50%, OR: 0.04 (0.002, 0.83)), and received a lower number of packed red cell transfusions (4.0 ± 4.46 versus 9.61 ± 6.7, p value 0.007), against the comparison group. Patients receiving rFVIIa had lower activated partial thromboplastin (median: 13.0; 25-75th percentile: -25.0, -8.0, signed rank p<0.0001), and lower prothrombin times (median: -8.8; 25-75th percentile: -24.2, -4.8), after administration of drug.There was no significant difference in the rate of hysterectomy between the 2 groups (11/18 (61%) versus 6/16 (38%)). No adverse event attributable to rFVIIa was observed in the study. Activated recombinant factor VII can be a lifesaving drug in patients with massive PPH.


Design and implementation of elliptical mantle cloaks for polarization decoupling of two tightly spaced interleaved co-frequency patch array antennas.
In this paper, we utilized the method of mantle cloaking to decouple/isolate two densely packed interleaved patch array antennas operating at the same frequency but with orthogonal polarizations. To reduce mutual coupling between the adjacent elements, vertical strips, as a type of elliptical mantle cloaks, are located in close proximity to the patches. At the operating frequency of f0 = 3.7 GHz, the edge-to-edge spacing of the elements of the two interleaved arrays is less than λ0/80 (1 mm) and the center-to-center spacing of each array element is 0.7 λ0 (57 mm). The proposed design is implemented using 3D printing technology, and its performance in terms of return loss, efficiency, gain, radiation patterns, and isolation is measured for evaluation. The results show the radiation characteristics of the arrays are perfectly retrieved after cloaking similar to the isolated arrays. Decoupling tightly spaced patch antenna arrays on a single substrate paves the way to achieve miniaturized communication systems with full duplex operation or dual polarization communication.


Electron microscopy study of early lytic replication forms of bacteriophage P1 DNA.
P1 replication intermediates were isolated from the intracellular DNA of lytically infected cells and analyzed by electron microscopy. At early times in infection replication intermediates were mainly of two types, circular theta- and sigma-shaped molecules plus a small proportion of linear bubble-shaped molecules. At later times in infection sigma molecules were the predominant replicating form. In contrast, sigma molecules were rarely found in recombination deficient, recA, infected cells. These observations show that early P1 DNA synthesis occurs, in part, by a circular mode of replication and imply that transition to a later, probably rolling circle, phase of replication is controlled by the bacterial general recombination system.


Clinical and histological features in pediatric and adolescent/young adult patients with renal disease: a cross-sectional analysis of the Japan Renal Biopsy Registry (J-RBR).
Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR). This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age < 15 years) and 6,532 AYA (age 15-30 years) patients. Although chronic nephritic syndrome was the most common clinical diagnosis at age > 5 years, nephrotic syndrome was the most frequent diagnosis at age < 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age. To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients.


Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients.
The effect of doxazosin, an alpha 1-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved. After 12 weeks of treatment (mean doxazosin dose 5.6 +/- 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mm Hg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml.min-1.kg-1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol.l-1 before and 10.9 mmol.l-1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mumol.l-1. Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients.


Quantitative evaluation of somatotrophic cells (SC) in the adenohypophysis of normal and diabetic male Chinese hamsters.
The pituitary of genetically diabetic Chinese hamsters contains significantly (p less than 0.001) greater numbers of somatotrophes than pituitary of non-diabetics. This may play a role in the aetiopathology of diabetes in this species or at least contribute to the maintenance of hyperglycaemia.


Magnetic resonance imaging of the knee with ultrashort TE pulse sequences.
We wished to assess the feasibility of imaging the knee with ultrashort TE (UTE) pulse sequences. Five volunteers and 16 patients were studied with UTE (TE=0.08 ms) sequences including later echoes. Conventional fat-suppressed images and difference images were also produced by subtracting a later echo from the first. Gadodiamide enhancement was used. High signal was obtained in tendons, ligaments, menisci and periosteum. Normal contrast enhancement was seen in these structures. Deep and superficial layers were seen in the articular cartilage. Cartilage defects were identified. The red zone could be differentiated from the white zone of the meniscus. Meniscal tears and degeneration were observed with low signal on subtraction images. Enhancement was seen within the anterior and posterior cruciate ligaments and associated scar tissue. Ultrashort TE imaging provides new options to visualize anatomy, manipulate conspicuity, observe contrast enhancement and demonstrate disease of the knee.


Association of homocysteine with IVF/ICSI outcomes stratified by MTHFR C677T polymorphisms: a prospective cohort study.
What is the association between homocysteine (Hcy) and IVF/intracytoplasmic sperm injection (ICSI) outcomes, stratified by methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms? This prospective cohort study recruited 1011 infertile women undergoing IVF/ICSI treatment for the first time at the International Peace Maternity and Child Health Hospital between June 2015 and March 2018. The concentration of total serum Hcy was significantly negatively associated with clinical pregnancy and implantation rate. When adjusted for maternal and paternal age and educational level, maternal body mass index, and FSH and oestradiol concentrations, logistic regression analysis showed that women with higher Hcy had a higher risk of unsuccessful pregnancy. After stratification by MTHFR C677T polymorphisms and adjustment for confounding factors, a higher risk of unsuccessful pregnancy and a significantly lower implantation rate only existed in women with higher Hcy concentration in the MTHFR C677T TT genotype. There was no significant association between Hcy concentrations and other ovarian stimulation outcomes (oocytes retrieved, metaphase II stage oocytes, fertilization rate, cleavage rate, high-quality embryo rate) or neonatal outcomes (preterm birth, gestational age at delivery, Caesarean section, birthweight, small for gestational age, large for gestational age or birth defects). Hcy is highly negatively associated with clinical pregnancy and implantation rate during the first IVF/ICSI cycle, especially in women carrying the MTHFR C677T TT genotype. Other factors with impacts on reproductive outcomes, such as stage of embryo transferred, other factors involved in folate metabolism, preimplantation genetic testing, etc., should be taken into account in further research.


Blood immune indexes can predict lateral lymph node metastasis of thyroid papillary carcinoma.
To explore the clinical significance of blood immune indexes in predicting lateral lymph node metastasis (LLNM) of thyroid papillary carcinoma (PTC). The pathological data and preoperative blood samples of 713 patients that underwent thyroid surgery at affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine from January 2013 to June 2021 were collected as the model group. The pathological data and preoperative blood samples of 177 patients that underwent thyroid surgery in the same hospital from July 2021 to October 2021 were collected as the external validation group. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors of LLNM in PTC patients. A predictive model for assessing LLNM in PTC patients was established and externally validated using the external data. According to univariate and multivariate logistic regression analyses, tumor diameter (P < 0.001, odds ratios (OR): 1.205, 95% confidence interval (CI): 1.162-1.249) and the preoperative systemic immune-inflammation index (SII) (P = 0.032, OR: 1.001, 95% CI: 1.000-1.002) were independent risk factors for distinguishing LLNM in PTC patients. When the Youden index was the highest, the area under the curve (AUC) was 0.860 (P < 0.001, 95% CI: 0.821-0.898). The externally validated AUC was 0.827 (P < 0.001, 95% CI: 0.724-0.929), the specificity was 86.4%, and the sensitivity was 69.6%. The calibration curve and the decision curve indicated that the model had good diagnostic value. Blood immune indexes can reflect the occurrence of LLNM and the biological behavior of PTC. The predictive model established in combination with SII and tumor diameter can effectively predict the occurrence of LLNM in PTC patients.