INDUS - a composition-based approach for rapid and accurate taxonomic classification of metagenomic sequences.
Taxonomic classification of metagenomic sequences is the first step in metagenomic analysis. Existing taxonomic classification approaches are of two types, similarity-based and composition-based. Similarity-based approaches, though accurate and specific, are extremely slow. Since, metagenomic projects generate millions of sequences, adopting similarity-based approaches becomes virtually infeasible for research groups having modest computational resources. In this study, we present INDUS - a composition-based approach that incorporates the following novel features. First, INDUS discards the 'one genome-one composition' model adopted by existing compositional approaches. Second, INDUS uses 'compositional distance' information for identifying appropriate assignment levels. Third, INDUS incorporates steps that attempt to reduce biases due to database representation. INDUS is able to rapidly classify sequences in both simulated and real metagenomic sequence data sets with classification efficiency significantly higher than existing composition-based approaches. Although the classification efficiency of INDUS is observed to be comparable to those by similarity-based approaches, the binning time (as compared to alignment based approaches) is 23-33 times lower. Given it's rapid execution time, and high levels of classification efficiency, INDUS is expected to be of immense interest to researchers working in metagenomics and microbial ecology. A web-server for the INDUS algorithm is available at http://metagenomics.atc.tcs.com/INDUS/


1, 4-naphthoquinone efficiently facilitates the disintegration of pre-existing biofilm of Staphylococcus aureus through eDNA intercalation.
1, 4-naphthoquinone, a plant-based quinone derivative, has gained much attention for its effectiveness against several biofilm-linked diseases. The biofilm inhibitory effect of 1, 4-naphthoquinone against Staphylococcus aureus has already been reported in our previous study. We observed that the extracellular DNA (eDNA) could play an important role in holding the structural integrity of the biofilm. Hence, in this study, efforts have been directed to examine the possible interactions between 1, 4-naphthoquinone and DNA. An in silico analysis indicated that 1, 4-naphthoquinone could interact with DNA through intercalation. To validate the same, UV-Vis spectrophotometric analysis was performed in which a hypochromic shift was observed when the said molecule was titrated with calf-thymus DNA (CT-DNA). Thermal denaturation studies revealed a change of 8℃ in the melting temperature (Tm) of CT-DNA when complexed with 1, 4-naphthoquinone. The isothermal calorimetric titration (ITC) assay revealed a spontaneous intercalation between CT-DNA and 1, 4-naphthoquinone with a binding constant of 0.95 ± 0.12 × 108. Furthermore, DNA was run through an agarose gel electrophoresis with a fixed concentration of ethidium bromide and increasing concentrations of 1, 4-naphthoquinone. The result showed that the intensity of ethidium bromide-stained DNA got reduced concomitantly with the gradual increase of 1, 4-naphthoquinone suggesting its intercalating nature. To gain further confidence, the pre-existing biofilm was challenged with ethidium bromide wherein we observed that it could also show biofilm disintegration. Therefore, the results suggested that 1, 4-naphthoquinone could exhibit disintegration of the pre-existing biofilm of Staphylococcus aureus through eDNA intercalation.


Cataract incision-related corneal erosion: recurrent corneal erosion because of clear corneal cataract surgery.
Three patients developed recurrent corneal erosions (RCEs) over their cataract surgery corneal incisions. These cataract incision-related corneal erosions (CIRCEs) resulted in pain after cataract surgery. None had any physical findings for corneal erosion; thus, a new technique called the corneal sweep test was developed to identify the erosion. To the authors' knowledge, this is the first time this association between the clear corneal cataract incision and RCEs has been reported. Considering the high number of cataract surgeries performed around the world, it is important for ophthalmologists to recognize CIRCEs as a potential cause of ocular discomfort after clear corneal cataract surgery.


The value of ultrasound measurement of gallbladder wall thickness in predicting laparoscopic operability prior to cholecystectomy.
We prospectively analysed 51 consecutive cases who underwent laparoscopic cholecystectomy from June 1992 to February 1993. There were 35 cases of chronic cholecystitis and 16 cases of acute cholecystitis. All underwent pre-operative ultrasonography, complete blood cell count, liver function test and endoscopic retrograde cholangiopancreatography. Of those 44 had post-operative ultrasound within the first 2 d and again on the seventh day. In 35 cases of chronic cholecystitis, 31 of 32 cases with a pre-operative gallbladder (GB) wall thickness of less than 6 mm were successfully resected laparoscopically. All three cases with a GB wall thicker than 6 mm were converted to open cholecystectomy. In acute cholecystitis, the wall thickness of the laparoscopic cholecystectomy group ranged from 2 to 9 mm (average 4 mm) and the wall thickness of the conversion group was 4-7 mm (average 6 mm). Post-operative fluid accumulation was noted in 28 (63.6%) cases. There was no correlation between post-operative pyrexia, duration of post-operative pain, clinical complications and the presence of fluid accumulation in the GB fossa. However, of four cases with increasing fluid on the seventh day, three developed complications. We conclude that ultrasonography is valuable in chronic cholecystitis for selecting cases for laparoscopic cholecystectomy.


Multidisciplinary Care to Optimize Functional Mobility in Parkinson Disease.
This review elaborates on multidisciplinary care for persons living with Parkinson disease by using gait and balance impairments as an example of a treatable target that typically necessitates an integrated approach by a range of different and complementary professional disciplines. Using the International Classification of Functioning, Disability, and Health model as a framework, the authors discuss the assessment and multidisciplinary management of reduced functional mobility due to gait and balance impairments. By doing so, they highlight the complex interplay between motor and nonmotor symptoms, and their influence on rehabilitation. They outline how multidisciplinary care for Parkinson disease can be organized.


Effects of cascade dams on the occurrence and distribution of microplastics in surface sediments of Wujiang river basin, Southwestern China.
The influence of cascade dams on the migration of microplastics (MPs) was conducted by analyzing the spatial distribution of MPs in sediments of the Wujiang river basin (Wujiang river basin) in Southwest China. The results showed that the abundance of MPs in Wujiang river basin sediments ranged from 310 to 2620 items/kg dw (mean: 1354 items/kg dw, a high level compared with aquatic sediments worldwide). The main chemical components of these MPs were polypropylene and polyethylene. High abundance of MPs in tributary sediments suggested that tributary inputs contributed to the main stream and reservoirs. Statistical analysis showed that gross domestic product (GDP) and the basin area of cascade reservoirs, rather than hydraulic retention time and reservoir age, were the dominating factors in the distribution of MPs in the Wujiang river basin. The accumulation of MPs in cascade reservoirs implied the interception effect of cascade dams. The rapid development of cascade dam systems and the interception effect of dams should be taken into account when predicting the flux of MPs from rivers to the ocean. Heavy metals found on the surface of the MPs showed the compound pollution of MPs and heavy metals in dammed rivers and cascade reservoirs. Our results deepen the understanding of the migration of MPs in rivers alongside intensive cascade hydropower development.


Advances since the paper by Zander and Glass (1949) on the pursuit of healing methods for pulpal exposures: historical perspectives.
Clinical observations and experimental studies in humans and laboratory animals have demonstrated that healing and repair of pulpal exposures by caries, trauma, or iatrogenic causes are possible with a variety of wound treatment methods. Yet clinical trials have shown that predictable long-term pulp tissue preservation may be an elusive goal and has led to doubts about pulp capping and pulpotomy as valid clinical procedures. Nevertheless substantial knowledge has accumulated over the years on the mechanisms and the treatment factors that are important to promote/support continued vital pulp functions. This article highlights some key contributions to our current knowledge base, which have come to light during the more than 50 years since a pioneering experimental study by Zander and Glass was published in the Triple O journal.


Sleep quality, but not quantity, is associated with self-perceived minor error rates among emergency department nurses.
The emergency department (ED) is demanding and high risk. The impact of sleep quantity has been hypothesized to impact patient care. This study investigated the hypothesis that fatigue and impaired mentation, due to sleep disturbance and shortened overall sleeping hours, would lead to increased nursing errors. This is a prospective observational study of 30 ED nurses using self-administered survey and sleep architecture measured by wrist actigraphy as predictors of self-reported error rates. An actigraphy device was worn prior to working a 12-hour shift and nurses completed the Pittsburgh Sleep Quality Index (PSQI). Error rates were reported on a visual analog scale at the end of a 12-hour shift. The PSQI responses indicated that 73.3% of subjects had poor sleep quality. Lower sleep quality measured by actigraphy (hours asleep/hours in bed) was associated with higher self-perceived minor errors. Sleep quantity (total hours slept) was not associated with minor, moderate, nor severe errors. Our study found that ED nurses' sleep quality, immediately prior to a working 12-hour shift, is more predictive of error than sleep quantity. These results present evidence that a "good night's sleep" prior to working a nursing shift in the ED is beneficial for reducing minor errors.


Panax notoginseng saponin alleviates pulmonary fibrosis in rats by modulating the renin-angiotensin system.
Pulmonary fibrosis (PF) is a chronic, progressive, and often fatal interstitial lung disease. Traditional Chinese medicine formulations and their active ingredients have shown potential in the treatment of PF. Panax notoginseng saponin (PNS) is extracted from the widely used traditional Chinese medicinal herb Panax notoginseng (Burkill) F. H. Chen, exhibiting therapeutic effects in pulmonary diseases treatment. This study aimed to investigate the effects and elucidate possible potential mechanisms of PNS on bleomycin (BLM)-induced PF in rats. PF was induced in rats by intratracheal administration of bleomycin (BLM, 5 mg/kg). After disease model induction, the rats were treated with PNS (50, 100, or 200 mg/kg per day) or pirfenidone (PFD, 50 mg/kg per day) for 28 days. Lung function, histopathological changes, collagen deposition, and E- and N-cadherin levels in lung tissue were evaluated. The mechanism of action of PNS was investigated using tandem mass tag-based quantitative proteomics analysis. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were performed to verify the proteomic results. PNS treatment improved lung function, ameliorated the BLM-induced increase in the lung coefficient, attenuated the degree of alveolar inflammation and fibrosis, and reduced the elevated collagen level in PF rats. PNS treatment also down-regulated the expression of N-cadherin while up-regulating the expression of E-cadherin. Proteomic and bioinformatic analyses revealed that the renin-angiotensin system (RAS) was closely related to the therapeutic effect of PNS. Immunohistochemistry, Western blot, and ELISA results indicated that PNS exerted its anti-fibrotic effect via regulation of the balance between the angiotensin-converting enzyme (ACE)-angiotensin (Ang)II-AngII receptor type 1 (AT1R) and ACE2-Ang(1-7)-MasR axes. PNS ameliorates BLM-induced PF in rats by modulating the RAS homeostasis, and is a new potential therapeutic agent for PF.


Enhancement of sensitivity to cisplatin by orobol is associated with increased mitochondrial cytochrome c release in human ovarian carcinoma cells.
Based on our previous report showing that orobol, a potent phosphatidylinositol 4-kinase (PI4K) inhibitor, produced cisplatin (DDP) sensitivity, we have determined the mechanism of orobol-sensitization effect. Orobol produced >2-fold DDP sensitivity in human ovarian carcinoma 2008 cells and its DDP-resistant variant 2008/C13*5.25 cells (C13). Because orobol had no effect on conventional mechanisms such as DDP accumulation or cellular metallothionein and glutathione content, we have focused on the apoptotic signaling pathway. Orobol induced a significant increase in apoptosis in DDP-treated cells, as estimated by frequency of condensed nuclear chromatin with Hoechst 33342 stain, although orobol alone did not have any effect on apoptotic potential. The caspase-3-inhibiting peptide Ac-DEVD-CHO completely inhibited the orobol sensitization effect but did not block DDP cell cytotoxicity per se. Orobol rendered both of these cells resistant to rhodamine 123 (Rh) by more than 2.5-fold, indicating significant decrease of mitochondrial membrane potential (DeltaPsim). Confocal laser microscopy of cells stained with the mitochondria (MT)-specific dye Rh revealed that orobol decreased Rh-fluorescent intensity. Electron microscopy of these cells showed that orobol induced swelling and condensation of MT. Orobol suppressed both naturally expressed and the DDP-induced Bcl-2 expression significantly. Orobol and DDP treatment reduced cytochrome c level in MT determined by Western blot analysis, indicating increased amount of cytochrome c release from MT, whereas orobol alone did not alter the amount of cytochrome c in MT. These results indicate that orobol produced DDP sensitivity in human ovarian carcinoma cells by inducing apoptosis through the MT-dependent signaling pathway.


Distribution of calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity in the trigeminal ganglion and mesencephalic trigeminal nucleus of the cat.
The distribution of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) in the cat trigeminal ganglion (TrG) and mesencephalic trigeminal nucleus (MTN) was studied by the indirect immunofluorescent technique and unlabelled peroxidase-antiperoxidase method. A positive reaction for both CGRP and NPY was found only in the TrG primary afferent neurons. Between 40% and 50% of the perikarya displayed CGRP-LI whereas few of the trigeminal principal neurons (approximately 1%) showed NPY-LI. Most of the CGRP-immunoreactive cells were small to medium-sized (20-40 microns in diameter) and were distributed throughout the ganglion. NPY appeared specifically in medium-sized to large-sized trigeminal neurons (up to 60 microns). CGRP and NPY also occurred in varicose nerve fibres running among the cell bodies and in pericellular baskets around a small number of large unstained ganglion cells. In contrast, CGRP- and NPY-LI were present only in the nerve fibres and terminals of the cat MTN. The immunoreactive varicosities travelled towards the negative MTN neurons and formed basket-like arborizations around their cell bodies. Synaptic contact between the immunolabelled axonal profiles and perikarya of trigeminal primary afferent neurons could not be seen in the TrG and MTN of the cat. The results provide further evidence for the interrelation between sensory and autonomic systems.


Switching prostaglandin analogues and 24-hour IOP fluctuations.
To evaluate the fluctuations in 24h mean intraocular pressure (IOP) when switching prostaglandin analogues in patients with glaucoma. Fourteen patients with primary open angle glaucoma were evaluated with monthly 24-hour IOP curves, using a monthly switching pattern of prostaglandin analogues and brinzolamide during 3 years of follow-up. Average IOP and average fluctuation (peak to through difference) were significantly higher with brinzolamide than with any of the analogues. There was no significant difference in either parameter with the different prostaglandin analogues, regardless of the order in which they were evaluated, or even if a month on brinzolamide was intercalated between the analogues. Brinzolamide was less effective than prostaglandin analogues in reducing 24-hour mean IOP and its fluctuations. Switching analogues had no significant effect on mean IOP or mean IOP fluctuations.


Changes of cholinesterases in the blood and some tissues following administration of tacrin and its two derivatives to rats.
Tacrin, its 7-methoxy-(MEOTA) and 7-hydroxy-(HYOTA) derivatives were i.m. administered to rats in a dose of 1.2 x LD50 and acetylcholinesterase (blood, hippocampus, frontal cortex, basal ganglia, septum and diaphragm) or butyrylcholinesterase (liver) activities were detected. The inhibitory effect of the examined substances in vivo decreased in the following order: tacrin HYOTA > MEOTA. The marked inhibition of the enzymes studied following administration of all three compounds in the frontal cortex could suggest importance of this structure for action of these drugs.


Psychosocial issues among paediatric health-care workers posted in intensive care unit during COVID-19 pandemic: A questionnaire-based survey (Psy-Co-19 survey).
To understand the moral distress experienced by health-care workers (HCWs) in the COVID paediatric intensive care unit (PICU). We also aimed to assess the psychological well-being and the coping mechanisms used by HCWs. A prospective observational cross-sectional study was conducted from July to September 2021, involving all HCWs who worked in the COVID PICU. Moral distress using Moral Distress for Health-care Professionals (MMD-HPs) scale, psychological well-being using Trauma Screening Questionnaire (TSQ) and coping strategies adopted by HCWs using Brief-COPE (Coping Orientation to Problems Experienced) were measured. One hundred and eighty-four HCW data were examined. The most common causes of moral distress among HCWs were compromised patient care caused by a lack of resources and caring for more patients than they could safely handle. Moral distress was the same regardless of the HCWs' job profile, marital status, number of children or age. The TSQ revealed psychological stress in 23.3% of HCWs with Post-traumatic Stress Disorder, significantly higher in HCWs under the age of 30 and without children. Few HCWs turned to substance use, self-blame or denial as coping mechanisms; instead, acceptance, self-distraction and emotional support were the most frequently used. The most common reasons for moral and psychological distress perceived by participants were insufficient staff and organisational support. Younger HCWs and those without children experienced higher levels of psychological distress. HCWs' typical coping mechanisms are constructive, such as seeking help and support from others, reframing situations and meditation. Health-care administrators must develop a framework to assist HCWs in dealing with such serious issues.


Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms.
Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.


A review of mechanical ventilation strategies in children following the Fontan procedure.
This article briefly outlines the development of the Fontan operation, and details ventilation strategies after such surgery.


Molecular species of phosphatidylinositol, phosphatidic acid and diacylglycerol in a phytohemagglutinin-stimulated T-cell leukemia line.
Addition of phytohemagglutinin to JURKAT cells, a human T-cell leukemia line, induced a rapid breakdown of phosphatidylinositol 4,5-bisphosphate (and may also be phosphatidylinositol 4-phosphate) and an accumulation of phosphatidic acid. The accumulation and disappearance of the various molecular species of phosphatidic acid, diacylglycerol and phosphatidylinositol (PtdIns) in response to phytohemagglutinin was studied in JURKAT cells. The cells were prelabeled with [2-3H]glycerol for 2 days and 3H-labeled lipids were isolated from the cells after incubation for 2 min at 37 degrees C in the absence or in the presence of phytohemagglutinin. The isolated 3H-labeled lipids were separated into individual molecular species by reverse-phase HPLC after conversion to their 1,2-[3H]diacylglycerol acetate derivatives either by acetolysis or by acetylation. Stimulation with phytohemagglutinin induced a 2-fold increase in [3H]phosphatidic acid. The molecular species of the accumulated [3H]phosphatidic acid consisted of polyenoic species, which were almost absent in the [3H]phosphatidic acid of the unstimulated cells. Stearoylarachidonoyl species of [3H]phosphatidic acid accumulated most prominently. Although an accumulation of [3H]diacylglycerol was hardly measurable in the phytohemagglutinin-stimulated cells, the HPLC analysis of the molecular species of [3H]diacylglycerol showed a 2-fold increase in the stearoylarachidonoyl species in the stimulated cells. Stimulation with phytohemagglutinin had almost no effect on the composition of molecular species of [3H]PtdIns. The stearoylarachidonyl species is the most abundant molecular species of PtdIns in JURKAT cells. These results suggest that the [3H]diacylglycerol moiety of [3']phosphatidic acid originates from inositol lipid(s). The results also suggest a rapid and preferential phosphorylation of the diacylglycerol formed by receptor-stimulated hydrolysis of inositol lipid(s).


Percutaneous treatment of congenital splenic cysts: drainage and sclerotherapy with polidocanol.
Congenital "true" splenic cysts are rare lesions. Therapeutic methods for the management of these lesions have been based on preserving splenic function due to the immunologic role of spleen. We report three different cases of congenital splenic cysts treated by percutaneous drainage and polidocanol sclerotherapy. This less invasive treatment appears to be safe and effective after 6 to 36 months of follow-up.


Restoration of hepatic glucokinase expression corrects hepatic glucose flux and normalizes plasma glucose in zucker diabetic fatty rats.
We examined in 20-week-old Zucker diabetic fatty (ZDF) rats whether restoration of hepatic glucokinase (GK) expression would alter hepatic glucose flux and improve hyperglycemia. ZDF rats were treated at various doses with an adenovirus that directs the expression of rat liver GK (AdvCMV-GKL) dose dependently, and various metabolic parameters were compared with those of nondiabetic lean littermates (ZCL rats) before and during a hyperglycemic clamp. Viral infection per se did not affect hepatic GK activity, since expression of a catalytically inactive form of GK did not alter endogenous hepatic GK activity. ZDF rats compared with ZCL rats have lower hepatic GK activity (11.6 +/- 1.9 vs. 32.5 +/- 3.2 mU/mg protein), marked hyperglycemia (23.9 +/- 1.2 vs. 7.4 +/- 0.3 mmol/l), higher endogenous glucose production (80 +/- 3 vs. 38 +/- 3 micromol x kg(-1) x min(-1)), increased glucose-6-phosphatase flux (150 +/- 11 vs. 58 +/- 8 micromol x kg(-1) x min(-1)), and during a hyperglycemic clamp, a failure to suppress endogenous glucose production (80 +/- 7 vs. -7 +/- 4 micromol x kg(-1) x min(-1)) and promote glucose incorporation into glycogen (15 +/- 5 vs. 43 +/- 3 micromol/g liver). Treatment of ZDF rats with different doses of AdvCMV-GKL, which restored hepatic GK activity to one to two times that of ZCL rats, normalized plasma glucose levels and endogenous glucose production. During a hyperglycemic clamp, glucose production was suppressed and glucose incorporation into glycogen was normal. Alteration of hepatic GK activity in ZDF rats has profound effects on plasma glucose and hepatic glucose flux.


Activation of AMPKα1 is essential for regulatory T cell function and autoimmune liver disease prevention.
Regulatory T cells (Treg cells) are crucial for maintaining immune tolerance. Compromising the regulatory function of Treg cells can lead to autoimmune liver disease. However, how Treg cell function is regulated has not been fully clarified. Here, we report that mice with AMP-activated protein kinase alpha 1 (AMPKα1) globally knocked out spontaneously develop immune-mediated liver injury, with massive lymphocyte infiltration in the liver, elevated serum alanine aminotransferase levels, and greater production of autoantibodies. Both transplantation of wild-type bone marrow and adoptive transfer of wild-type Treg cells can prevent liver injury in AMPKα1-KO mice. In addition, Treg cell-specific AMPKα1-KO mice display histological features similar to those associated with autoimmune liver disease, greater production of autoantibodies, and hyperactivation of CD4+ T cells. AMPKα1 deficiency significantly impairs Treg cell suppressive function but does not affect Treg cell differentiation or proliferation. Furthermore, AMPK is activated upon T cell receptor (TCR) stimulation, which triggers Foxp3 phosphorylation, suppressing Foxp3 ubiquitination and proteasomal degradation. Importantly, the frequency of Treg cells and the phosphorylation levels of AMPK at T172 in circulating blood are significantly lower in patients with autoimmune liver diseases. Conclusion: Our data suggest that AMPK maintains the immunosuppressive function of Treg cells and confers protection against autoimmune liver disease.


Numerous granulocyte transfusions to a patient with severe aplastic anemia without severe complication.
One of the most important morbidity causes of aplastic anemia is invasive fungal infections. It could not be possible to take control of infection without neutrophils despite the recent developments in the antifungals. In this presented case, a patient with severe aplastic anemia, granulocyte transfusion were administered as 46 times because of the presence of widely invasive aspergillosis and resistance. Only fever reaction was observed as a complication of transfusion amongst the other complications such as acute lung damage, alloimmunisation, and graft-versus-host disease. Granulosit transfusions should not be avoided in patients who had an indication for.


Cotranslational protein folding on the ribosome monitored in real time.
Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding of a small five-helix protein domain-the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK-in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains.


Mosquitoes and other arthropod macro fauna associated with tank bromeliads in a Peruvian cloud forest.
Mosquitoes and other macro arthropods were collected in September 2008 from bucket bromeliads in the vicinity of the Wayqecha Cloud Forest Research Center in southeastern Peru, an area for which there are no published data. Range extensions of culicid species are reported.


Surgical stimulation of the uveoscleral outflow. Experimental studies on enucleated human eyes.
Six series of experiments were performed on 45 isolated cadaver eyes. In the first series, the outflow facility of the human sclera was measured, in the others, five surgical techniques for stimulating the uveo-scleral outflow were evaluted with the help of a constant pressure perfusion technique. It was found that the scleral C-value was pressure independent and its average value was equal to 0.0036 mm3/min/mmHg per 1 cm2 (100 mm2) of scleral surface. After the implantation of a scleral strip into the supra-uveal space, the mean increase in the total C-value was 23% of its initial value, ranging from 7 to 35%. After cyclodialysis the C-value increment varied from 17% to 66%, averaging 30%. The average increase in the outflow facility amounted to 60% (range 24--96%) in those cases where implantation of the scleral strip in the suprauveal space was combined with cyclodialysis. After implantation of a scleral strip, combined with subscleral sinusotomy, the C-value increment varied from 18 to 71%, averaging 41%. After cyclodialysis combined with goniospasis, the mean increase in the outflow facility coefficient was 62% (range 43%--108%).


The Transitional Age Brain: "The Best of Times and the Worst of Times".
Over the past two decades, there have been substantial developments in the understanding of brain development and the importance of environmental inputs and context. This paper focuses on the neurodevelopmental mismatch that occurs during the epoch we term the 'transitional age brain' (ages 13-25) and the collateral behavioral correlates. We summarize research findings supporting the argument that, because of this neurodevelopmental mismatch, transitional age youth are at high risk for engaging in behaviors that lead to negative outcomes, morbidity, and mortality. We highlight the need to develop new, neuroscience-inspired health promotion and illness prevention approaches for transitional age youth.


Purification and properties of a kinase from Escherichia coli K-12 that phosphorylates two periplasmic transport proteins.
The phosphorylation in vivo and in vitro of the arginine-ornithine and the lysine-arginine-ornithine (LAO) periplasmic transport proteins of Escherichia coli K-12 was previously reported (Celis, R. T. F. (1984) Eur. J. Biochem. 145, 403-411). The phosphorylative reaction required ATP (as a direct energy donor), Mg2+, and a kinase that can be released by osmotic shock treatment of the cells. The enzyme was purified to electrophoretic homogeneity. The enzyme exhibited an ATPase activity and a kinase activity. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate gave an apparent molecular weight of 43,000 for the enzyme. The native protein showed the same molecular weight, suggesting that the protein is a monomer. The protein showed an apparent isoelectric point of 4.8 on isoelectric focusing. The two enzymatic reactions required a divalent cation and the apparent Km value for Mg2+ for the kinase activity was 0.5 mM. Mn2+ and Co2+ served as well as Mg2+, whereas Zn2+ and Ca2+ did not support activity. The ATPase activity of the enzyme yielded an apparent Km value for ATP of 50 microM. A similar value, Km of 100 microM, was calculated for the kinase activity with different concentrations of ATP. The enzyme showed a pH optimum of 7.3.


Evaluation of IL-23p19/Ebi3 (IL-39) gingival crevicular fluid levels in periodontal health, gingivitis, and periodontitis.
IL-23p19/Ebi3 (IL-39) was described as a new IL-12 family member. The aim of this study is to evaluate the gingival crevicular fluid (GCF) IL-39 levels in periodontal diseases and health and to correlate them to GCF levels of IL-1β and periostin. Sixty-six adult patients were included in the study. The study design was comprised of three groups, each containing 22 individuals: the periodontally healthy (PH), gingivitis (G), and periodontitis (P) groups. The clinical periodontal parameters were recorded and GCF samples were collected from the participants. GCF interleukin (IL)-39, IL-1β, and periostin levels were examined using the enzyme-linked immunosorbent assay. GCF IL‑1β, periostin, and IL-39 levels were higher in the P and G groups than in the PH group (p < 0.001). Positive correlations were detected between all GCF biochemical parameters and clinical periodontal parameters (p < 0.05). In the multivariate generalized linear regression analysis, the P (β = 37.6, 95% CI = 22.9-52.4) and G (β = 28.4, 95% CI = 15.8-41) groups were associated with GCF IL-39 levels (p < 0.001). IL-39 levels were elevated in the presence of periodontal disease paralleling the increase in IL‑1β and periostin levels. IL-39 may have a role in the periodontal inflammation process. IL-39, a new cytokine from the IL-12 family, can be a possible predictor marker of periodontal diseases.


The effect of various dietary factors on the size distribution of lymph fat particles in rat.
By means of cellulose acetate electrophoresis and measurement of radio-activity, lipoproteins (d less than or equal to 1,006) of lymph collected from rats fed a diet containing fats added to labeled fatty acids for 20-24 hr, have been separated into two kinds differing in their size. Fats with different saturated and unsaturated fatty acid content were tested: corn oil, lard, mutton tallow, tripalmitin, corn oil-lard mixture, and randomized palmitic-linoleic triglycerides. Factors studied were: (a) increased amounts of these fats given alone or included in a test meal; (b) added amounts of nutrients (other than fats) in the test meal; (c) adaptation to a diet containing 20% fat for 10 days. The major part of the labeled lymph lipid was always transported by the smaller particles. Size distribution of lymph fat particles was influenced by some of the factors studied. Generally, unsaturated fats produced higher amounts of larger particles.


Accuracy of end-on fluoroscopy in predicting implant position in relation to the vertebral canal in dogs.
To evaluate the accuracy of end-on fluoroscopy in predicting implant position in relation to the vertebral canal in the canine thoracolumbar vertebral column. In vitro imaging and anatomic study. Canine cadaveric thoracolumbar vertebral columns (n = 5). Smooth Steinmann pins were inserted bicortically into the thoracolumbar vertebral columns between T10 and L7 using recommended insertion angles. Penetration of the spinal canal was not strictly avoided. After pin placement, end-on fluoroscopy images were obtained of each pin. Pin position was subsequently assessed by four evaluators and determined to either being out of the vertebral canal or in, with the latter being additionally divided into partially or completely penetrating the canal. To assess potential differences in modalities, fluoroscopy images were gray-scale inverted and evaluated again later by the same four individuals. Correct identification of pin position in relationship to the vertebral canal was assessed for both fluoroscopy images. Anatomic preparation of the spines was used for verification of pin position in relation to the spinal canal. Some data from this study were compared with historical data on accuracy using orthogonal radiography and computed tomography (CT). Overall sensitivity and specificity of F to detect vertebral canal penetration was 98.8 % (95% confidence interval (CI), 96.0-99.6) and 98.0% (95% CI, 77.0-99.9), respectively. For Fi, sensitivity and specificity were 97.0% (95% CI, 91.5-99.0) and 98.5% (95% CI, 81.5-99.9) respectively. F exceeded Fi for the sensitivity of detecting pin penetration into the vertebral canal (p = 0.039) but specificities were not different (p = 0.585). When comparing to historical data, the overall accuracy of end-on fluoroscopy (F) and inverted fluoroscopy (Fi) was statistical better than conventional radiographic assessment (p < 0.001). End-on fluoroscopy is a highly accurate method for the assessment of pin position in relationship to the thoracolumbar spinal canal in cadaveric dogs. End-on fluoroscopy, with or without inversion, is accurate in identifying vertebral canal violation by bicortically placed Steinmann pins. When CT is not available, end-on fluoroscopy might be a valuable imaging modality to determine pin position in the canine vertebral column.


Effects of varicocele repair in adults on ultrasonographically determined testicular volume and on semen profile.
We determined the effect of varicocele repair on testicular volume according to scrotal ultrasonography, reported to provide the best approximation of actual testicular volume. Forty-four men with left varicocele (mean age +/- standard deviation, 33.4 +/- 5.4 years) underwent varicocele repair. We performed both scrotal ultrasonography with color Doppler imaging and semen analysis before and after varicocele repair. Among these patients, 19 had a clinical left varicocele, 22 had clinical left and subclinical right varicoceles, and 3 had clinical left and right varicoceles. We calculated testicular volumes using the formula: Length x Width x Height x 0.71. For all 44 patients, mean left and total testicular volume improved significantly after varicocele repair (increases of 1.5 and 2.4 mL, respectively) as did semen profile data such as sperm per unit volume and percentage of motile sperm. In the 19 men with a clinical left varicocele, mean left testicular volume increased significantly (by 1.5 mL) after left varicocele repair, in association with increases in sperm per unit volume and motility percentage. In the 25 men with clinical left varicocele plus a subclinical or clinical right varicocele, mean left and total testicular volume improved significantly after repair of right and left varicoceles (increases of 1.5 and 2.7 mL, respectively). However, right testicular volume showed no significant increase in any patient group. Varicocele repair in adults with a clinical left varicocele increased left testicular volume and improved semen profiles.


[The use of laparoscopy in urology: report of 141 cases].
To modify laparoscopy in urology. From May 1992 to Nov. 1996, 141 patients (110 males and 31 females) were subjected to laparoscopy in the treatment of urological diseases. The age of the patients ranged from 9 to 76 years (mean 39 years). Five patients had nephrectomy, 12 adrenalectomy, 48 renal cyst resection, 61 high ligation of internal spermatic vein, 5 pelvic staging lymphadenectomy, 9 orchiectomy, and 1 removal of bladder diverticulum. The rate of successful operation was 95.7% and that of complications was 2.22%. The mean hospitalization was 4.9 +/- 4.1 days. Laparoscopy can be used widely in clinical practice.


[Pyloric stenosis management in France in 1999: a postal survey].
The aim of this postal survey was to know how were treated infants with hypertrophic pyloric stenosis in France in 1999. A questionnaire was sent to all French members of the Association Des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (Adarpef). Half the cases of pyloric stenosis treated in France in 1999 were related by the survey. Preoperative management was short lasting (24 h) while the advised guidelines regarding biologic criteria for operation were poorly followed. Nevertheless, crush induction was only performed in 80%. The management of infants with pyloric stenosis must be improved, at least to obtain the generalization of crush induction.


Morphological Variants of Renal Carcinoma in Radical Nephrectomy Specimens.
To determine the morphological variants of Renal Cell Carcinoma (RCC) to detect the commonest histopathological type with special focus to the newly introduced entity Clear Cell Papillary Renal Cell Carcinoma (CCPRCC). Case series. Department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. Paraffin embedded blocks of 32 cases of radical nephrectomy specimens for renal mass were selected from records of Pathology Department, BMSI. Cases were excluded due to inadequate biopsies. Remaining 30 cases of renal cell carcinoma were included in study. H & E staining was done for all cases and PAS stain was employed for a few cases. All cases were reviewed under light microscope. The 30 cases of renal cell carcinoma included 21 (70%) clear cell renal cell carcinoma, 03 (10%) clear cell papillary renal cell carcinoma, 02 (6.6%) papillary renal cell carcinoma and 04 (13.33%) hybrid tumors. Majority of cases (53.3%) found in age range between 40 - 60 years while 23.33% cases were found in 7th and 6.6% in 8th decade of life. While 16.66% cases were in younger age group that is between 31 - 40 years of age. Sixty percent cases of right radical nephrectomies and 40% cases of left radical nephrectomies. CCRCC was most common histopathologic type followed by CCPRCC, hybrid tumors and PRCC.


Bacterial luciferase activity and the intracellular redox pool in Escherichia coli.
In this study, we analyzed the activity of a bacterial luciferase (LuxAB of Vibrio fischeri) expressed under the control of a consensus-type promoter, lacUV5, in Escherichia coli, and found that activity declines abruptly upon entry into the stationary growth phase. Since this decline was reproducibly observed in strains cultured in various growth media, we refer to this phenomenon as ADLA (Abrupt Decline of Luciferase Activity) and define the time point when activity begins to decline as T (0). Because the levels of luciferase proteins (LuxA and LuxB) remained constant before and after T (0), ADLA cannot be due to the repression of luciferase gene expression. Further analyses suggested that a decline in the supply of intracellular reducing power for luciferase was responsible for ADLA. We also found that ADLA was alleviated or did not occur in several mutants deficient in nucleoid proteins, suggesting that ADLA is a genetically controlled process involved in intracellular redox flow.


GPR54 and rGnRH I gene expression during the onset of puberty in Nile tilapia.
The Kiss1/GPR54 system has recently been shown to play a key role in the onset of puberty in mammals. Growing evidence suggests that this system is also conserved across vertebrates although very few studies so far have been performed in lower vertebrates. The aims of this study were firstly in the teleost Nile tilapia to screen tissues for GPR54 expression levels, secondly to measure the expression patterns of GPR54 and GnRH I receptor (rGnRH I) in whole brains during the onset of puberty and finally to determine the effects of continuous illumination (LL) on receptor expression levels. Results confirmed that GPR54 was predominantly expressed in the brain and pituitary of adult tilapia. Furthermore, a significant increase of GPR54 gene expression was found in tilapia brains at 11 weeks post hatch (wph) followed by rGnRH I at 13 wph just prior to the histological observation of vitellogenic oocytes and active spermatogenesis in ova and testes at 17 wph. These results suggest a correlation between the increase of GPR54 expression in the brain and the onset of puberty. Finally, a significant effect of LL was observed on GPR54 expression levels which were characterized by a delayed surge with significantly lower levels than those of control fish. The current study not only suggests a link between the Kiss1/GPR54 system and the onset of puberty in a tropical batch spawning teleost that would be a highly conserved feature across vertebrates but also that the transcriptional mechanisms regulating GPR54 expression could be directly or indirectly influenced by light.


Fabrication of covalent organic frameworks and its selective extraction of fluoronitrobenzenes from environmental samples.
In this study, porous covalent organic frameworks (COFs, named as COFs-SWMU) were synthesized for the first time via a facile approach by using 4,4',4''-methylidynetri-anilin and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde as precursors under ambient temperature. The COFs-SWMU were characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy, thermogravimetric analysis, etc. The COFs-SWMU exhibited a relatively high specific surface area and desirable thermal stability. The adsorption performance of COFs-SWMU towards fluoronitrobenzenes (FNBs, including 1-fluoro-2-nitrobenzene, 1-fluoro-3-nitrobenzene, 1-fluoro-4-nitrobenzene, 2,4-difluoronitrobenzene, 3,4-difluoronitrobenzene, and 3,4-dinitrofluorobenzene) was investigated on the basis of adsorption capacity and partition coefficient (PC). The adsorption kinetics and isotherm of COFs-SWMU for FNBs were studied in detail. Further, a simple, fast and sensitive method which combined COFs-SWMU based extraction with high-performance liquid chromatography-diode array detection, was proposed for the analysis of FNBs in environmental samples. Desirable linearity (R2>0.9998) in the range of 0.1-100 μg•mL-1, low limits of detection (LODs; 0.1‒0.15 μg•mL‒1), low limits of quantitation (LOQs; 0.28‒0.40 μg•mL‒1), and desirable precision (RSDs, 0.24-2.83% for intraday and 1.13-6.92% for interday) are obtained. Finally, the COFs-SWMU were applied to the effective extraction of FNBs from environmental samples, and desirable recovery results were obtained.


A site of intrinsic bending in a highly repeated element of Plasmodium berghei genome.
The basic element of the 2.3 kb repetitive family, present in approximately 300 copies in the Plasmodium berghei genome, contains a bent DNA region. Indications of this given by anomalies in electrophoretic behaviour were confirmed by computational analysis of sequence data.


Direct projections from thalamic intralaminar nuclei to extra-striate visual cortex in the cat traced with horseradish peroxidase.
Thalamic projections to the visual cortex were investigated using the Horseradish peroxidase tracing technique. Besides confirmation of a distinct origin of thalamic projections to striate and extra-striate visual cortex, afferents of the intralaminar nuclei (ILN) to visual cortex were demonstrated. These projections of ILN were shown to be specific in that they terminate in areas 18, 19 and Clare Bishop but not area 17. The coupling of these intralaminar projections on to the extra-striate visual system is considered with respect ot orientation of gaze.


Meningeosis Neoplastica in Patients with Glioblastoma: Analysis of 36 Cases.
Meningeosis neoplastica is a rare manifestation of high-grade gliomas and is usually associated with a devastating outcome. The aim of this bicenter series was to investigate the clinical course and outcome of patients with meningiosis neoplastica. This case series included patients in whom surgery was performed for World Health Organization grade IV primary and secondary glioblastoma (GBM) at the University Medical Center Göttingen, Göttingen, Germany between 2009 and 2021 and Burdenko Institute of Neurosurgery, Moscow, Russia between 2012 and 2018. Inclusion criteria were manifestation of clinical and neuroradiologic signs of leptomeningeal, ependymal, or spinal dissemination of GBM at various time points during the course of the disease. Meningeosis neoplastica was found in 36 patients. Nine patients developed spinal metastases and 12 ependymal dissemination and 15 patients had a leptomeningeal manifestation of high-grade glioma. The median age of patients at first diagnosis of primary tumor was 56 years. Typical symptoms were headache, nausea, vomiting, and acute paraplegia. The median overall survival was 11 months and progression-free survival was 8 months. Meningeosis neoplastica developed a median 2 months after the initial tumor diagnosis. Salvage therapies included ventriculoperitoneal shunting, decompression of spinal metastases, and spinal radiation therapy. The median time between meningeosis manifestation and death was 3 months. Meningeosis neoplastica is a rare manifestation of GBM. It has a poor prognosis. The overall survival after the manifestation of meningeosis was barely longer than 3 months. Salvage therapies did not improve the outcome in our patient cohort.


Role of vascular endothelial growth factor (VEGF) and placenta-derived growth factor (PlGF) in regulating human haemopoietic cell growth.
Vascular endothelial growth factor (VEGF) and placental derived growth factor (PlGF) stimulate cell proliferation and differentiation by binding to their specific receptors, Flk-1/KDR and Flt-1 respectively. Flk-1/KDR-deficient murine embryos manifest failure of blood-island formation and vasculogenesis. The aim of this study was to directly evaluate the importance of VEGF, PlGF/Flt-1 and Flk-1/KDR receptor ligand interactions in regulating normal and malignant human haemopoiesis. Addition of VEGF and PlGF failed to enhance survival or cloning efficiency of human haemopoietic progenitors isolated from adult bone marrows, fetal livers or cord blood samples. This finding may be explained by the apparent absence of mRNA encoding Flt-1 and Flk-1/KDR receptors on stem cell rich CD34+ c-kit-R+ Rh123(low) cells. Further studies revealed that Fit-1 R mRNA, but not Flk-1/KDR mRNA was first detectable in the more mature cells isolated from haemopoietic colonies. Accordingly, VEGF receptors are either absent, or expressed at very low level, on human haemopoietic stem/progenitor cells. Of interest, normal and malignant human haemopoietic cells appeared to secrete VEGF protein. However, in contrast to normal haemopoietic progenitors, VEGF co-stimulated HEL cell proliferation as well as CFU-GM colony formation from approximately 15% of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) patients studied. Therefore, although VEGF appeared to have minimal effects on normal haemopoietic cell growth it would appear to drive malignant haemopoietic cell proliferation to some degree. Of more importance, however, we speculate that VEGF may play an very important role in leukaemogenesis by stimulating growth of vascular endothelium, thereby providing a sufficient blood supply to feed the growing haematological tumour.


Phenobarbital drinking curves after varied water deprivation.
The phenobarbital dose-drinking response curves were obtained for 11 1/2 and 23 1/2 hr of water deprivation in rats. The results indicated that the same quadratic curve was found in both cases displaced as a function of degree of deprivation. These results are explicable by regarding phenobarbital as an adequate stimulus for drinking or by disinhibiting drinking if level of inhibition is not directly concerned with regulation of water ingestion per se. The response to phenobarbital upon the days following injection is similar for both degrees of deprivation investigated.


Efficacy and safety of Wuling capsule for insomnia disorder: a systematic review and meta-analysis of randomized controlled trials.
Wuling capsule has been used in treatment of insomnia disorder in China for decades, but the reported treatment efficacy of different studies was not consistent. This study intended to evaluate the efficacy and safety of Wuling capsule for insomnia disorder, so as to provide evidence for clinical application. Eight databases (MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database and Wanfang) were searched from inception to September 14, 2021. Randomized controlled trials (RCTs) comparing Wuling capsule with controls in adults with insomnia disorder were eligible. The primary outcome was sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), and the secondary outcomes were severity of insomnia disorder measured by Sleep Dysfunction Rating Scale (SDRS) and adverse events. This study was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. Nineteen RCTs with a total of 1850 participants were included. In terms of sleep quality assessed by PSQI, Wuling capsule significantly lowered PSQI score (MD: -1.92, 95% CI: [-2.34, -1.50], P < 0.00001, I2 = 95%) compared to controls, and the effect of Wuling capsule was significantly better than control no matter when Wuling capsule as monotherapy (MD: -1.71, 95% CI: [-2.33, -1.09], P < 0.00001, I2 = 97%) or as adjunctive therapy (MD: -2.10, 95% CI: [-2.66, -1.55], P < 0.00001, I2 = 90%). Wuling capsule was more effective for the treatment duration lasted 8 weeks (MD: -2.57, 95% CI: [-3.52, -1.62], P < 0.00001, I2 = 93%) than 4 weeks (MD: -1.68, 95% CI: [-2.13, -1.22], P < 0.00001, I2 = 95%). In terms of severity of insomnia disorder measured by SDRS, Wuling capsule significantly reduced SDRS score (MD: -4.21, 95% CI: [-4.95, -3.46], P < 0.00001, I2 = 0%) compared to benzodiazepines. Wuling capsule significantly reduced adverse events compared to controls (RR: 0.47, 95% CI: [0.34, 0.65], P < 0.00001, I2 = 43%). Wuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. Clinical trials with higher quality designs are needed.


Structure of wyosine, the condensed tricyclic nucleoside of torula yeast phenylalanine transfer ribonucleic acid.
Large-scale isolation of the minor nucleoside wyosine of torula yeast tRNA(Phe) was accomplished by a combination of enzymatic digestion and reversed-phase chromatography: the wyosine-containing nucleotide fraction, which was obtained by partial digestion of unfractionated tRNA (1 g) with nuclease P1, was concentrated by reversed-phase column chromatography followed by complete digestion with nuclease P1/alkaline phosphatase. The nucleoside mixture thus obtained was purified by reversed-phase HPLC, providing wyosine (70 microg). Comparison of this nucleoside with a chemically synthesized authentic sample has unambiguously established that the structure of wyosine is 4,6-dimethyl-3-beta-D-ribofuranosyl-3,4-dihydro-9H-imidazo[1,2-a]purin-9-one (2).


Depression and Diabetes Mellitus Multimorbidity Is Associated With Loss of Independence and Dementia Poststroke.
Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003-2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X2=5.4; P=0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHRDepression=1.57 [1.24-1.98]) and incident dementia (aHRDepression=1.85 [1.40-2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHRDiabetes=1.20 [1.12-1.29]; aHRDepression=1.19 [1.04-1.37]), incident dementia (aHRDiabetes=1.14 [1.06-1.23]; aHRDepression=1.27 [1.08-1.49]), stroke/transient ischemic attack readmission (aHRDiabetes=1.18 [1.10-1.26]; aHRDepression=1.24 [1.07-1.42]), and all-cause mortality (aHRDiabetes=1.29 [1.23-1.36]; aHRDepression=1.16 [1.05-1.29]). The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.


Management of prelabor rupture of membranes at term. A randomized study.
To compare the rate of obstetric interventions, length of labor, and maternal morbidity in pregnancies with prelabor rupture of membranes at term after either early or late induction of labor in both primiparous and pluriparous women. Prospective, randomized study. 362 women with singleton pregnancies, cephalic presentations, gestational age of 36 completed weeks or more were allocated at random to induction with oxytocin either 6 hours after PROM (n = 62) (early) or 24 hours (n = 62) (late). Those eligible, but not participating in the study, totalled 238 women. MAIN OBSTETRIC MEASURES: Time of spontaneous labor in the late induction group, length of labor, obstetric intervention rate, maternal morbidity, and the degree of histologic chorioamnionitis. The length of labor was longer in the late induction group than in the early induction group in both primiparous and pluriparous (p < 0.05). There were no overall differences in the rate of obstetric interventions or maternal morbidity, but there were marked differences between primiparous and pluriparous women. Increasing time span between the period from rupture of membranes to delivery increased the degree of histologic chorioamnionitis. If a woman wants a short labor, she will benefit from early induction. We did not find statistical differences in the rate of obstetric intervention or in the maternal morbidity, but there was a tendency towards adverse effects of late induction.


Toxicity and inhibition of bacterial growth by series of alkylphenol polyethoxylate nonionic surfactants.
Laboratory experiments measured the effects of five alkylphenol polyethoxylate nonionic surfactants on the microbial degradation of glucose and pentachlorophenol (PCP) by a pure culture of Sphingomonas chlorophenolicum RA2 (RA2) that was unable to biodegrade the surfactants. The surfactants with mid-range hydrophile-lipophile balance (HLB) values of 13.5-15 were the most biocompatible with substrate degradation. Monomers of the surfactant with the lowest HLB value of 12.3 inhibited RA2 growth on both glucose and PCP. The surfactant with the highest HLB of 17.9 was only inhibitory to glucose biodegradation at 3000mg/L, a concentration well above its CMC. The surfactants were more inhibitory of RA2 biodegradation of PCP compared to glucose, which is likely due to interactions with membrane-associated PCP-degrading enzymes rather than bioavailability limitations. These results may prove helpful in selecting surfactants for use enhancing surfactant-amended remedial applications involving biodegradation or oil dispersion.


Single-fiber EMG with concentric electrodes in lambert-eaton myasthenia.
We analyzed jitter recordings made with concentric needle electrode (CNE) single-fiber electromyography (SFEMG) in Lambert-Eaton myasthenia (LEM). Fifteen subjects diagnosed with LEM were studied using CNE-SFEMG in the extensor digitorum (ED) and tibialis anterior (TA) muscles. CNE-SFEMG in the ED and TA was also used to evaluate 12 and 10 healthy controls (HCs), respectively. Ten men and 5 women were diagnosed with LEM based on an increase of 100% in compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation. All patients exhibited markedly greater jitter in the ED (88.8 ± 23.2 µs) and TA (92.2 ± 30.2 µs) than HCs (28.3 ± 3.4 µs and 30.9 ± 5.1 µs, respectively). CNE-SFEMG is sensitive for discovering abnormalities in neuromuscular transmission in LEM. Muscle Nerve 56: 253-257, 2017.


Scope of linear estimators of tidal and occluded volumes using thoracoabdominal indications of breathing movement coordination.
The basic theory for respiratory inductive plethysmography (RIP) applications was re-examined, refined and tested. A realistic model of the RIP interpretation of respiratory mechanics related tidal volumes (VT) to a linear combination of ribcage and abdomen movements. Lissajous plots of asynchronous thoracoabdominal movements revealed their net effect equivalent to the superposition of synchronous and antipathetic respiration modes at right angles, along the principal axes specific to the combined motion. Predictors of relative changes in VT, degree of asynchrony and volume thus being occluded were developed via least squares estimation theory, with an optional validation facility. The approach enabled clinically adequate analysis of 452 h of RIP data from 29 postoperative patients. Correct identification of only seven complete apnoeas in 111 incidences of obstruction during periodic, variable, asynchronous or paradoxical natural breathing was substantiated via non-invasive airflow monitoring. The modelling helped clarify RIP limitations--the possibility of misleading indications from obese or abnormal physiques or movement artefacts degrading its otherwise nearly optimal performance. Nevertheless, our uncalibrated predictors had better theoretical basis, improved reliability and more convenient practical utility than the traditional approach of calibrating RIP by spirometry prior to non-invasive monitoring and identifying and classifying apnoeas.


HLA and complement typing in olivo-ponto-cerebellar atrophy.
HLA antigen typing was carried out in a family with an autosomal dominant form of spinocerebellar degeneration [possibly olivoponto cerebellar atrophy (O.P.C.A.)--Type 1]. Eleven ataxic patients, three possibly ataxic subjects, two unrelated spouses and 13 clinically normal at risk siblings were typed for ABO and Rh blood groups, HLA-A and HLA-B antigens, C4 component of the complement and a number of other serum proteins (Clq, beta-1A, beta-1C, C5, beta-lipoproteins). No solid evidence for linkage between the ataxia gene and the HLA or C4 loci could be demonstrated in this family. Certain serum proteins, and particularly beta-lipoproteins were found to be significantly reduced in some sub-groups of subjects.


Characterization of a Newcastle disease virus isolated from apparently normal guinea fowl (Numida melagridis).
This report describes the isolation and molecular characterization of Newcastle disease virus isolated from an apparently normal guinea fowl (Numida melagridis). With a mean death time of 54 h and intracerebral pathogenicity index of 1.80, the isolate has been identified as velogenic by biological methods. Fusion protein cleavage site amino acid sequence analysis of the isolate indicated the presence of two pairs of basic amino acids at the C-terminus of the F2 region and phenylalanine at the N-terminus of the F1 region, confirming the velogenic nature of the isolate. Phylogenetic analysis of the isolate revealed that this isolate is genotypically related to other neurotropic velogenic isolates like Iowa/Salsbury, Texas GB, Kansas/Manhattan and mesogenic Michigan.


[Ochratoxin a (OTA) in coffee - Comparison of german data from 1995-1999 and 2000-2002].
Ochratoxin A concentrations from a total of 1223 samples from green, roasted and ground, decaffeinated and low acid and instant coffee analysed during 1995-1999 and 2000-2002 by German Official Food Control Laboratories were compared. Median concentrations, determined by statistical process analysis decreased within each group from the early group up to 2002. The rates of rejection were calculated on the basis of the recent data for green and roasted and ground coffee which may occur when particular maximum residue limits were set. Contamination rates from green coffee showed significant differences in their OTA concentrations depending on their geographical origin.


A Practical Approach to Echocardiographic Imaging in Patients With Hypertrophic Cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is frequently unrecognized or misdiagnosed. The recently published consensus recommendations from the American Society of Echocardiography provided recommendations for the utilization of multimodality imaging in the care of patients with HCM. This document provides an additional practical framework for optimal image and measurement acquisition and guidance on how to tailor the echocardiography examination for individuals with HCM. It also provides resources for physicians and sonographers to use to develop HCM imaging protocols.


Identification of hemoglobins in single erythrocytes by electrophoresis.
We present here a method for electrophoretic identification of hemoglobin variants in many individual erythrocytes simultaneously, which is made possible by instruments developed in our laboratory. The system spaces and aligns the erythrocytes along a common origin and prevents 'doubling' of cells. Unambiguous separation of different hemoglobins (Hbs) occurred from single erythrocytes, such as Hbs A, C, F. Staged micrographs showed that hemoglobins of differing mobility from a single cell arise from a single point source of hemoglobin. In principle this capability is applicable to other proteins and could facilitate investigation at a cellular level into a variety of questions pertaining to gene action.


Transient evolution of permeability and friction in a slowly slipping fault activated by fluid pressurization.
The mechanisms of permeability and friction evolution in a natural fault are investigated in situ. During three fluid injection experiments at different places in a fault zone, we measured simultaneously the fluid pressure, fault displacements and seismic activity. Changes in fault permeability and friction are then estimated concurrently. Results show that fault permeability increases up to 1.58 order of magnitude as a result of reducing effective normal stress and cumulative dilatant slip, and 19-to-60.8% of the enhancement occurs without seismic emissions. When modeling the fault displacement, we found that a rate-and-state friction and a permeability dependent on both slip and slip velocity together reasonably fit the fault-parallel and fault-normal displacements. This leads to the conclusion that the transient evolution of fault permeability and friction caused by a pressure perturbation exerts a potentially dominant control on fault stability during fluid flow.


Cytotoxic endothelial cell antibodies in mixed connective tissue disease.
We examined the presence of anti-endothelial cell antibodies in the sera of 44 patients with mixed connective tissue disease (MCTD). Warm antibodies against endothelial cells were found in 45.4% of patients; the presence of these antibodies was positively correlated with anti-monocyte antibodies (P less than 0.01) but not with anti-lymphocytic antibodies. Strong correlations were found between the presence of these antibodies and abnormalities of pulmonary ventilatory capacity, neurophysiologic and myocardial function. Anti-endothelial antibodies were related to the high rate of spontaneous abortion noted in female MCTD patients. The identification of the antigen identified by MCTD sera in endothelial cells would help in understanding disease manifestations.


Anthraquinone extract from Rheum officinale Bail improves growth performance and Toll-Relish signaling-regulated immunity and hyperthermia tolerance in freshwater prawn Macrobrachium nipponense.
This study was aimed to investigate the facilitation of anthraquinone extract on growth performance, immunity, and antioxidant capacity of the oriental river prawn (Macrobrachium nipponense), and whether it could ameliorate the hyperthermia stress. A 12-week rearing experiment was conducted with 0, 125, 250, 500, and 1000 mg kg-1 anthraquinone extract from Rheum officinale Bail-supplemented diets (AE0, AE125, AE250, AE500, and AE1000), and followed a 48-h thermal stress with 32℃ incubation. Results indicate AE250 and AE500 significantly improved the growth performance and feed utilization, the optimum level was estimated to be 251.22 mg kg-1 based on the regression analysis of special growth ratio (SGR). Meanwhile, AE250 and AE500 improved antioxidant enzyme activity and immune-related protein concentration of iNOS-NO signaling. Under thermal stress, AE250 and AE500 improved the heat tolerance, and Toll-Relish signaling was active to the resistance. These results indicate anthraquinone extract could be used as an effective immunostimulant to improve growth performance, physiological balance and protect organism form environmental hyperthermia stress. This may provide insights for immunostimulant development in aquaculture production.


The distribution and density of ET-1 and its receptors are different in human right and left ventricular endocardial endothelial cells.
Evidence suggests that endocardial endothelial cells (EECs) may play a role in the regulation of cardiac function by releasing ET-1. Furthermore, reports in the literature suggested that differences may exist in peptide receptor distribution between the left and right EECs. In this study, we verified if the distribution and density of ET-1 and its receptors could be different in right as compared to left ventricular EECs, and whether this difference may affect ET-1-induced increase of intracellular calcium. Using immunofluorescence and 3D confocal microscopy, our results showed that in both cell types, the ET(A) receptor is present and is homogeneously distributed throughout the two cell types. The relative density of the ET(A) receptor is similar in both right and left ventricular EECs. The ET(B) receptor is also present in right and left ventricular EECs, however, the relative density of the ET(B) receptor is higher in the nucleus as compared to the cytosol. In addition, the ET(B) receptor density was found to be higher in left EECs as compared to right EECs. In addition, our results showed that ET-1 is present in the cytosol and the nucleus of both types of cells and that the relative density of ET-1 is higher in right as compared to left ventricular EECs. Moreover, using the Fura-2 calcium measurement technique, our results showed that in left ventricular EECs, both ET(A) and ET(B) receptor activation mediated the effect of ET-1 on intracellular calcium, whereas in right ventricular EECs, this effect was solely mediated by the ET(A) receptor. In conclusion, our results showed that ET-1 and its receptors are present in both right and left ventricular EECs. However, the distribution and relative density of ET-1 and its receptors seem to be different in right EECs as compared to left EECs.


Evaluating the ability of a locally focused culling program in removing chronic wasting disease infected free-ranging white-tailed deer in Illinois, USA, 2003-2020.
In northern Illinois, chronic wasting disease (CWD) was first identified in free-ranging white-tailed deer (Odocoileus virginianus; hereafter referred to as "deer") in 2002. To reduce CWD transmission rates in Illinois, wildlife biologists have conducted locally focussed culling of deer since 2003 in areas where CWD has been detected. We used retrospective spatial, temporal and space-time scan statistical models to identify areas and periods where culling removed higher than expected numbers of CWD-positive deer. We included 490 Public Land Survey "sections" (∼2.59 km2 ) from 15 northern Illinois counties in which at least one deer tested positive for CWD between 2003 and 2020. A negative binomial regression model compared the proportion of CWD positive cases removed from sections with at least one CWD case detected in the previous years, "local area 1 (L1)," to the proportion of CWD cases in adjacent sections-L2, L3, and L4-designated by their increasing distance from L1. Of the 14,661 deer removed and tested via culling, 325 (2.22 %) were CWD-positive. A single temporal CWD cluster occurred in 2020. Three spatial clusters were identified, with a primary cluster located at the border of Boone and Winnebago counties. Four space-time clusters were identified with a primary cluster in the northern portion of the study area from 2003 to 2005 that overlapped with the spatial cluster. The proportion of CWD cases removed from L1 (3.92, 95% CI, 2.56-6.01) and L2 (2.32, 95% CI, 1.50-3.59) were significantly higher compared to L3. Focussing culling efforts on accessible properties closest to L1 areas results in more CWD-infected deer being removed, which highlights the value of collaborations among landowners, hunters, and wildlife management agencies to control CWD. Continuous evaluation and updating of the culling and surveillance programs are essential to mitigate the health burden of CWD on deer populations in Illinois.


Cytogenetic findings in two cases of carcinoma in situ of the cervix uterus.
Karyotypic analysis of two cases of carcinoma in situ of the cervix uterus, studied on direct preparations by G-banding, revealed numerical and structural abnormalities characteristic of invasive cancers. Abnormalities of chromosome No. 1 were present in both cases. The chromosome No. 1 changes involved isochromosome formation of the long arm (i(1q)) in one case and monosomy in the other. The other chromosomes showing structural aberrations were Nos. 8, 11, and 21. One case revealed the presence of double minute chromatin bodies. The prognosis in both cases was good following excision of the tumor.


Effect of mefloquine on hepatic drug metabolism in the rat: comparative study with primaquine.
The effect of the new antimalarial drug mefloquine (MQ) on hepatic drug metabolism in the rat has been studied in vitro and in vivo using three different substrates, aminopyrine, ethinyloestradiol and tolbutamide. Comparative studies have been performed with primaquine (PQ). In vitro, both MQ and PQ inhibited aminopyrine N-demethylase activity and the concentration required to produce 50% inhibition was 0.2 mM for MQ and approximately 0.1 mM for PQ. Lineweaver-Burk plots indicated inhibition by both antimalarials to be non-competitive. Both MQ and PQ produced comparable inhibition of ethinyloestradiol metabolism in vitro with the percentage recovery of the major metabolite, 2-hydroxyethinyloestradiol being reduced from 49.3 +/- 10.8 to 5.1 +/- 3.1 (0.5 mM MQ) and 1.5 +/- 0.4% (0.5 mM PQ, mean +/- S.D.). Following acute administration of MQ and PQ to rats (25 mg kg-1) recovery of hydroxytolbutamide the major metabolite of tolbutamide, was reduced. In the period 0-8 hr, MQ caused a reduction in recovery from 54.4 +/- 3.1 to 9.3 +/- 3.4% and PQ from the control level to 32.2 +/- 14.1%. There is therefore clear evidence that MQ inhibits hepatic microsomal enzymes both in vitro and in vivo. The more pronounced effect of MQ in vivo, in comparison with PQ, is probably a reflection of differences in the kinetics of the two antimalarials. The range of substrates studied indicate a non-selective and widespread inhibitory effect of these drugs on oxidative enzymes.


Accounting for the Growth of Observation Stays in the Assessment of Medicare's Hospital Readmissions Reduction Program.
Decreases in 30-day readmissions following the implementation of the Medicare Hospital Readmissions Reduction Program (HRRP) have occurred against the backdrop of increasing hospital observation stay use, yet observation stays are not captured in readmission measures. To examine whether the HRRP was associated with decreases in 30-day readmissions after accounting for observation stays. This retrospective cohort study included a 20% sample of inpatient admissions and observation stays among Medicare fee-for-service beneficiaries from January 1, 2009, to December 31, 2015. Data analysis was performed from November 2021 to June 2022. A differences-in-differences analysis assessed changes in 30-day readmissions after the announcement of the HRRP and implementation of penalties for target conditions (heart failure, acute myocardial infarction, and pneumonia) vs nontarget conditions under scenarios that excluded and included observation stays. Thirty-day inpatient admissions and observation stays. The study included 8 944 295 hospitalizations (mean [SD] age, 78.7 [8.2] years; 58.6% were female; 1.3% Asian; 10.0% Black; 2.0% Hispanic; 0.5% North American Native; 85.0% White; and 1.2% other or unknown). Observation stays increased from 2.3% to 4.4% (91.3% relative increase) of index hospitalizations among target conditions and 14.1% to 21.3% (51.1% relative increase) of index hospitalizations for nontarget conditions. Readmission rates decreased significantly after the announcement of the HRRP and returned to baseline by the time penalties were implemented for both target and nontarget conditions regardless of whether observation stays were included. When only inpatient hospitalizations were counted, decreasing readmissions accrued into a -1.48 percentage point (95% CI, -1.65 to -1.31 percentage points) absolute reduction in readmission rates by the postpenalty period for target conditions and -1.13 percentage point (95% CI, -1.30 to -0.96 percentage points) absolute reduction in readmission rates by the postpenalty period for nontarget conditions. This reduction corresponded to a statistically significant differential change of -0.35 percentage points (95% CI, -0.59 to -0.11 percentage points). Accounting for observation stays more than halved the absolute decrease in readmission rates for target conditions (-0.66 percentage points; 95% CI, -0.83 to -0.49 percentage points). Nontarget conditions showed an overall greater decrease during the same period (-0.76 percentage points; 95% CI, -0.92 to -0.59 percentage points), corresponding to a differential change in readmission rates of 0.10 percentage points (95% CI, -0.14 to 0.33 percentage points) that was not statistically significant. The findings of this study suggest that the reduction of readmissions associated with the implementation of the HRRP was smaller than originally reported. More than half of the decrease in readmissions for target conditions appears to be attributable to the reclassification of inpatient admission to observation stays.


Experiences of Norwegian community midwives with caring for vulnerable pregnant women - A national cross-sectional study.
The study aimed to describe Norwegian community midwives' care for vulnerable pregnant women. It assessed vulnerability factors midwives identified and the type of care they provided. Factors associated with use of identification tools and care of vulnerable pregnant women were investigated. A quantitative, cross-sectional study. Data collected via an anonymous online survey conducted spring 2020. Of approximately 700 eligible community midwives in Norway, 257 (36.7%) participated. Community midwives who worked primarily in the community, in close to full-time positions (>80%) and who were responsible for >100 women a year in large community clinics were more likely to identify vulnerable pregnant women than midwives who worked in combined hospital and community posts, less than 80% in the community and at smaller community centres. Attended a training progam called 'Early Start' (Tidlig Inn) was associated with an increased use of standardized identification tools. Almost all community midwives reported providing vulnerable women with more frequent consultations, individual and culturally personalized care, and relevant information about support options. Community midwives appeared to be aware of their role as a midwife in the care of vulnerable pregnant women. They reported encountering vulnerable pregnant, identifying them by actively using methods to do so and addressing their needs in various ways. This study suggests that specific training increases midwives' ability to identify vulnerable pregnant women. Further research is needed to assess how midwives experience interdisciplinary collaboration in caring for these women.


Trends in the two-component system's role in the synthesis of antibiotics by Streptomyces.
Despite the advances in understanding the regulatory networks for secondary metabolite production in Streptomyces, the participation of the two-component systems (TCS) in this process still requires better characterization. These sensing systems and their responses to environmental stimuli have been described by evaluating mutant strains with techniques that allow in-depth regulatory responses. However, defining the stimulus that triggers their activation is still a task. The transmembrane nature of the sensor kinases and the high content of GC in the streptomycetes represent significant challenges in their study. In some examples, adding elements to the assay medium has determined the respective ligand. However, a complete TCS description and characterization requires specific amounts of the involved proteins that are most difficult to obtain. The availability of enough sensor histidine kinase concentrations could facilitate the identification of the ligand-protein interaction, and besides would allow the establishment of its phosphorylation mechanisms and determine their tridimensional structure. Similarly, the advances in the development of bioinformatics tools and novel experimental techniques also promise to accelerate the TCSs description and provide knowledge on their participation in the regulation processes of secondary metabolite formation. This review aims to summarize the recent advances in the study of TCSs involved in antibiotic biosynthesis and to discuss alternatives to continue their characterization. KEY POINTS: • TCSs are the environmental signal transducers more abundant in nature. • The Streptomyces have some of the highest number of TCSs found in bacteria. • The study of signal transduction between SHKs and RRs domains is a big challenge.


Metal-organic framework derived yolk-shell NiS2/carbon spheres for lithium-sulfur batteries with enhanced polysulfide redox kinetics.
Yolk-shell NiS2/carbon spheres (yolk-shell NiS2/C) have been synthesized by one-step annealing of yolk-shell Ni-metal-organic framework spheres. In particular, both the inner yolk sphere and the outer shell of yolk-shell NiS2/C can provide catalytically active sites for the redox of polysulfide confined in the yolk-shell structure, providing enhanced redox kinetics. A yolk-shell NiS2/C-sulfur cathode exhibits a high rate capacity of 569 mA h g-1 at 2C and shows excellent cycling stability, demonstrating the superiority of the yolk-shell structure.


Cerebral palsy: definition, assessment and rehabilitation.
Over the last 25 years the definition and classification of cerebral palsy (CP) have evolved, as well as the approach to rehabilitation. CP is a disorder of the development of movement and posture, causing activity limitations attributed to nonprogressive disturbances of the fetal or infant brain that may also affect sensation, perception, cognition, communication, and behavior. Motor control during reaching, grasping, and walking are disturbed by spasticity, dyskinesia, hyperreflexia, excessive coactivation of antagonist muscles, retained developmental reactions, and secondary musculoskeletal malformations, together with paresis and defective programing. Weakness and hypoextensibility of the muscles are due not only to inadequate recruitment of motor units, but also to changes in mechanical stresses and hormonal factors. Two methods, the General Movements Assessment and the Test of Infant Motor Performance, now permit the early detection of CP, while the development of valid and reliable outcome measures, particularly the Gross Motor Function Measure (GMFM), have made it possible to evaluate change over time and the effects of clinical interventions. The GMFM has further led to the development of predictive curves of motor function while the Gross Motor Classification System and the Manual Ability Classification System provide standardized means to classify the severity of the movement disability. With the emergence of the task-oriented approach, the focus of therapy in rehabilitation has shifted from eliminating deficits to enhancing function across all performance domains by emphasizing fitness, function, participation, and quality of life. There is growing evidence supporting selected interventions and interest for the therapy and social integration of adults with CP.


A method for studying controlled substance use: a preliminary investigation.
This study examined relapse following treatment in a smoking reduction program. Twenty-two smokers with an average daily smoking rate of 25.7 cigarettes were provided a reduction-oriented smoking self-management program. Subjects were then classified on the basis of their reduction at posttreatment. A 50% or greater reduction from pretreatment qualified subjects as successful reducers. To provide further understanding of controlled smoking, subjects who successfully maintained at least a 50% reduction (at three month follow-up) were compared to those subjects who were unable to maintain that level of reduced smoking. A set of cognitive, smoking history, and reduction motivation variables were used to compare the two groups in a stepwise discriminant function analysis. Two variables, internal locus of control and self-label as a nonsmoker, produced an overall correct classification rate of 88.9%. Multiple regression analyses further demonstrated the importance of these two cognitive variables; self-label and internal locus of control accounted for 50.4% of the variance in smoking at three months follow-up. The implications of these findings for future study of controlled smoking are discussed.


ERK and p38 MAPK inhibition controls NF-E2 degradation and profibrotic signaling in renal proximal tubule cells.
Transforming growth factor-β (TGF-β) mediates fibrotic manifestations of diabetic nephropathy. We demonstrated proteasomal degradation of anti-fibrotic protein, nuclear factor-erythroid derived 2 (NF-E2), in TGF-β treated human renal proximal tubule (HK-11) cells and in diabetic mouse kidneys. The current study examined the role of mitogen-activated protein kinase (MAPK) pathways in mediating NF-E2 proteasomal degradation and stimulating profibrotic signaling in HK-11 cells. HK-11 cells were pretreated with vehicle or appropriate proteasome and MAPK inhibitors, MG132 (0.5 μM), SB203580 (1 μM), PD98059 (25 μM) and SP600125 (10 μM), respectively, followed by treatment with/without TGF-β (10 ng/ml, 24 h). Cell lysates and kidney homogenates from FVB and OVE26 mice treated with/without MG132 were immunoblotted with appropriate antibodies. pUse vector and pUse-NF-E2 cDNA were transfected in HK-11 cells and effects of TGF-β on JNK MAPK phosphorylation (pJNK) was examined. We demonstrated activation of p38, ERK, and JNK MAPK pathways in TGF-β treated HK-11 cells. Dual p38 and ERK MAPK blockade prevented TGF-β-induced pSer82Hsp27, fibronectin and connective tissue growth factor (CTGF) expression while preserving NF-E2 expression. Blockade of JNK MAPK inhibited TGF-β-induced CTGF expression without preserving NF-E2 expression. MG132 treatment prevented TGF-β-induced pJNK in HK-11 cells and in type 1 diabetic OVE26 mouse kidneys, demonstrating that TGF-β- and diabetes-induced pJNK occurs downstream of proteasome activation. A direct role for NF-E2 in modulating pJNK activation was demonstrated by NF-E2 over-expression. ERK and p38 MAPK promotes NF-E2 proteasomal degradation while proteasome activation promotes pJNK and profibrotic signaling in renal proximal tubule cells.


Observation of stimulated emission by direct three-photon excitation.
Multiphoton processes, predicted theoretically in 1931, were for a long time considered to be mainly of academic interest. This view changed when it was shown that a two-photon absorption process could, because of a quadratic dependence of excitation on intensity, produce a spatially confined excitation useful for three-dimensional data storage and imaging. Two-photon absorption has received considerable attention recently because of the development of highly efficient two-photon-sensitive materials, leading to numerous technological applications. These successes have created interest in exploring applications based on three-photon excitations. For a three-photon process, a longer excitation wavelength such as those common in optical communications can be used. Also, the cubic dependence of the three-photon process on the input light intensity provides a stronger spatial confinement, so that a higher contrast in imaging can be obtained. Here we report the observation of a highly directional and up-converted stimulated emission as an amplified spontaneous emission, produced in an organic chromophore solution by a strong simultaneous three-photon absorption at 1.3 microm. This achievement suggests opportunities for a three-photon process in frequency-upconversion lasing, short-pulse optical communications, and the emerging field of biophotonics.


Rejoinder to Commentaries on Lyu, Bolt and Westby's "Exploring the Effects of Item Specific Factors in Sequential and IRTree Models".
We respond to the commentaries on Lyu, Bolt and Westby's "Exploring the effects of item specific factors in sequential and IRTree models." The commentaries raise important points that allow us to clarify our theoretical expectation for item specific factors in many educational and psychological test items. At the same time, we agree with the commentaries in acknowledging challenges associated with providing empirical evidence for their presence and reflect on strategies that might support their estimation. We maintain that the principal concern is the ambiguity item specific factors create in attempting to interpret or use the parameters beyond the first node.


Alternative approaches to the medical management of angina pectoris: acupuncture, electrical nerve stimulation, and spinal cord stimulation.
Complementary or alternative modalities of medical treatment have been gaining attention as primary or supplementary therapies in cardiovascular disease pain management. However, definitive research in these areas has been limited by the inability to perform placebo-controlled trials when evaluating these treatments. Preliminary studies have suggested a possible benefit from acupuncture, electrical nerve stimulation, and spinal cord stimulation in the treatment of patients with angina pectoris and coronary artery disease.


Adding l-lysine derivatives to the genetic code of mammalian cells with engineered pyrrolysyl-tRNA synthetases.
We report a method for site-specifically incorporating l-lysine derivatives into proteins in mammalian cells, based on the expression of the pyrrolysyl-tRNA synthetase (PylRS)-tRNA(Pyl) pair from Methanosarcina mazei. Different types of external promoters were tested for the expression of tRNA(Pyl) in Chinese hamster ovary cells. When tRNA(Pyl) was expressed from a gene cluster under the control of the U6 promoter, the wild-type PylRS-tRNA(Pyl) pair facilitated the most efficient incorporation of a pyrrolysine analog, N(epsilon)-tert-butyloxycarbonyl-l-lysine (Boc-lysine), into proteins at the amber position. This PylRS-tRNA(Pyl) system yielded the Boc-lysine-containing protein in an amount accounting for 1% of the total protein in human embryonic kidney (HEK) 293 cells. We also created a PylRS variant specific to N(epsilon)-benzyloxycarbonyl-l-lysine, to incorporate this long, bulky, non-natural lysine derivative into proteins in HEK293. The recently reported variant specific to N(epsilon)-acetyllysine was also expressed, resulting in the genetic encoding of this naturally-occurring lysine modification in mammalian cells.


Higher family and individual resilience and lower perceived stress alleviate psychological distress in female breast cancer survivors with fertility intention: a cross-sectional study.
The aim of this study was to explore how family resilience and individual resilience reduce perceived stress and psychological distress in young female breast cancer survivors with fertility intention. From June 2020 to June 2021, female breast cancer survivors were selected from the cancer centers of 10 tertiary Level A general hospitals in five cities of Sichuan Province. The survivors completed the Chinese versions of the Family Resilience Assessment Scale, Connor-Davidson Resilience Scale, Perceived Stress Scale, and a self-report distress thermometer. A multiple mediation effects test and structural equation modeling were used to explore the relationships among family resilience, individual resilience, perceived stress, and psychological distress. The direct effect of family resilience on perceived stress was β = -0.320 (95% confidence interval -0.365, -0.271, P < 0.01). The direct effect of family resilience on psychological distress was β = -0.263 (95% confidence interval -0.363, -0.153, P < 0.001). The direct effect of family resilience on individual resilience was β = 0.593 (95% confidence interval 0.542-0.640, P < 0.001). The indirect effect of family resilience on psychological distress was β = -0.322 (95% confidence interval -0.373, -0.274, P < 0.001). Both perceived stress and individual resilience mediated the relationship between family resilience and psychological distress. Furthermore, a partial mediating effect of perceived stress and individual resilience on family resilience and psychological distress was observed. Young female breast cancer survivors in China experience moderate levels of psychological distress.


Formation of Polychlorinated Biphenyls on Secondary Copper Production Fly Ash: Mechanistic Aspects and Correlation to Other Persistent Organic Pollutants.
Emission of unintentionally formed polychlorinated biphenyls (PCBs) from industrial thermal processes is a global issue. Because the production and use of technical PCB mixtures has been banned, industrial thermal processes have become increasingly important sources of PCBs. Among these processes, secondary copper smelting is an important PCB source in China. In the present study, the potential for fly ash-mediated formation of PCBs in the secondary copper industry, and the mechanisms involved, were studied in laboratory thermochemical experiments. The total PCB concentrations were 37-70 times higher than the initial concentrations. Thermochemical reactions on the fly ash amplified the potential toxic equivalents of PCBs. The formation of PCBs over time and the effect of temperature were investigated. Based on analyses of PCB homologue profiles with different reaction conditions, a chlorination mechanism was proposed for forming PCBs in addition to a de novo synthesis mechanism. The chlorination pathway was supported by close correlations between each pair of adjacent homologue groups. Formation of PCBs and multiple persistent organic pollutants, including polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated naphthalenes, occurred during the tests, indicating that these compounds may share similar formation mechanisms.


Novel Interventional Therapies to Modulate the Autonomic Tone in Heart Failure.
Heart failure (HF) represents a significant and expanding public health burden associated with increasing prevalence and exponential growth in related health care costs. Contemporary advances in both pharmacological and nonpharmacological therapies have often been restricted in application and benefit. Given the critical role of the autonomic nervous system (ANS) in maintaining cardiovascular homeostasis in the failing heart, there has been increasing interest in the role of ANS modulation as a therapeutic modality in HF. In this review, we highlight the anatomy of the ANS and its role in the pathophysiology of HF, as well as metrics of its assessment. Given the limitations associated with pharmacological ANS modulation, including lack of specificity and medication intolerance, we focus in this review on contemporary nonpharmacological ANS modulation therapies. For each therapy-vagal nerve stimulation, carotid baroreceptor stimulation, spinal cord stimulation, and renal denervation-we review the rationale for modulation, pre-clinical and clinical assessments, as well as procedural considerations and limitations. We conclude by commenting on novel technologies and strategies for ANS modulation on the horizon.


Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation.
Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum that lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens, and livers of the treated recipients. No accumulation of immature NK cell progenitors was observed. The NK cells from IL-15-treated recipients displayed an activated phenotype and were lytically active toward tumor targets in vitro to a similar degree as did those cells from recipients treated with control plasmid. This suggests that the predominant effect of IL-15 was a quantitative increase in total NK cell numbers and not qualitative changes in NK cell functions. No toxicities or adverse effects were observed. Studies performed in transplanted mice bearing renal carcinoma tumors demonstrated that this mode of hIL-15 gene delivery resulted in increased antitumor responses. These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT.