Should primary anastomosis be considered more? A retrospective analysis of anastomotic complications in young children.
Little is known about intestinal anastomotic leakage and stenosis in young children (≤3 years of age). The purpose of this study is to answer the following questions: (1) what is the incidence of anastomotic stenosis and leakage in infants? (2) which surgical diseases entail the highest incidence of anastomotic stenosis and leakage? (3) what are perioperative factors associated with anastomotic stenosis and leakage? Patients who underwent an intestinal anastomosis during primary abdominal surgery in our tertiary referral centre between 1998 and 2018 were retrospectively included. Both general incidence and incidence per disease of anastomotic complications were determined. Technical risk factors (location and type of anastomosis, mode of suturing, and suture resorption time) were evaluated by multivariate Cox regression for anastomotic stenosis. Gender and American Society of Anaesthesiology (ASA) score of ≥III were evaluated by χ2 test for anastomotic leakage. In total, 477 patients underwent an anastomosis. The most prominent diseases are intestinal atresia (30%), Hirschsprung's disease (29%), and necrotizing enterocolitis (14%). Anastomotic stenosis developed in 7% (34/468) of the patients with highest occurrence in necrotizing enterocolitis (14%, 9/65). Colonic anastomosis was associated with an increased risk of anastomotic stenosis (hazard ratio (HR) =3.6, 95% CI 1.8 to 7.5). No technical features (type of anastomosis, suture resorption time and mode of suturing) were significantly associated with stenosis development. Anastomotic leakage developed in 5% (22/477) of the patients, with the highest occurrence in patients with intestinal atresia (6%, 9/143). An ASA score of ≥III (p=0.03) and male gender (p=0.03) were significantly associated with anastomotic leakage. Both anastomotic stenosis and leakage are major surgical complications. Identifying more patient specific factors can result in better treatment selection, which should not solely be based on the type of disease.


Experience of surgical management of rare cases of choledochal cyst in last five years-tertiary care reflection.
Choledochal Cyst (CC), also known as the biliary cyst, is one of the rare inherited anomalies of intrahepatic and/or extrahepatic biliary system characterised by varying degrees of cystic dilatation of the biliary tract without acute obstruction. The prevalence ranges from 1 in 13,000 people to 1 in 2 million people with preponderance in Asia1, particularly in Japan. Moreover, the presentation also varies in children and adults, and is usually vaguer and non-specific in adults. The prevalence is even lower in males, with female to male ratio being 3:1-4:12. We present here three cases of adult choledochal cysts excised in our surgical unit in the last five years. We discuss the aetiopathogenesis, presentation, diagnosis, surgical treatment, and complications of choledochal cysts based on the available literature. It is crucial to establish a multidisciplinary group of professionals, that comprises paediatric surgeons, pathologists, paediatric gastroenterologists, physiotherapists, nutritionists, oncologists, and radiologists, to get acceptable outcomes in diagnosing and treating children with choledochal cysts.


Maximal standard dose of parenteral iron for hemodialysis patients: an MRI-based decision tree learning analysis.
Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients. We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2* contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID) analysis. The CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%). The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex) and the hepcidin level also influenced liver iron content on MRI. The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products.


Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma.
Adenovirus-mediated gene therapies against brain tumors have been limited by the difficulty in tracking glioma cells infiltrating the brain parenchyma. Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSC) are particularly attractive cells for clinical use in cell-based therapies. In the present study, we evaluated the tumor targeting properties and antitumor effects of UCB-MSCs as gene delivery vehicles for glioma therapy. We efficiently engineered UCB-MSCs to deliver a secretable trimeric form of tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) via adenoviral transduction mediated by cell-permeable peptides. We then confirmed the migratory capacity of engineered UCB-MSCs toward tumor cells by an in vitro migration assay and by in vivo injection of UCB-MSCs into the tumor mass or the opposite hemisphere of established human glioma in nude mice. Moreover, in vitro coculture, experiments on Transwell plates, and in vivo survival experiments showed that MSC-based stTRAIL gene delivery has more therapeutic efficacy compared with direct injection of adenovirus encoding the stTRAIL gene into a tumor mass. In vivo efficacy experiments showed that intratumoral injection of engineered UCB-MSCs (MSCs-stTRAIL) significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with controls. These results suggest that human UCB-MSCs have potential use as effective delivery vehicles for therapeutic genes in the treatment of intracranial glioma.


Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins.
The aims of this study were to determine the antimicrobial susceptibility of Neisseria gonorrhoeae (NG) in our area, to analyze the molecular mechanisms involved in cephalosporins resistance, and to undertake molecular typing of our NG strains. Antimicrobial susceptibility was determined using the Etest. The genes penA, mtrR, penB, and ponA were studied. Molecular typing was performed by N. gonorrhoeae multiantigen sequence typing. Of 329 strains analyzed in 2013, none showed high-level cephalosporin resistance, but 8.2 % had resistance to cefixime [minimum inhibitory concentration (MIC) > 0.125 μg/mL] and 0.6 % to ceftriaxone (MIC > 0.125 μg/mL). Azithromycin resistance was documented in 4.3 % and ciprofloxacin resistance in 49.2 %. Among 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 58.3 % showed the penA mosaic pattern XXXIV, 98 % a Leu → Pro substitution at position 421 of the ponA gene, 100 % amino acid changes at positions 101 and 102 of the PorB1b porin, and 87.5 % of strains an adenine deletion in the promoter region of the MtrC-D-E efflux pump. A significant difference between strains with and without decreased cephalosporin susceptibility (MIC ≥ 0.125 μg/mL) was observed for these four genes. Of the 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 43.8 % belonged to the genogroup G1407 and 27.1 % belonged to the genogroup G2400. A significant association of G1407 with decreased susceptibility (MIC ≥ 0.125 μg/mL) and G2992 with susceptibility was found, and also between G1407 and mosaic pattern XXXIV and between G2400 and A501T substitution in penA. The NG resistance rate in our area is higher than the median of Europe. We have detected the emergence of G2400, which may be a source of antimicrobial resistance.


New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five.
H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKGKRTAR/G, PKGKRIAR/G, PKRKRAAR/G, and PKRKRTAR/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5.IMPORTANCE The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP- and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world.


Detection of soluble HFE associated with soluble transferrin receptor in human serum.
Hereditary hemochromatosis is an autosomal recessive disease, and 80-90% of patients exhibit Cys282Tyr or His63Asp mutations in the HFE gene. HFE, also known as major histocompatibility complex (MHC) class I-like molecule, binds to transferrin receptor 1 (TfR1) and β2-microglobulin at the cell surface, forming a complex. Some MHC class I molecules are known to be soluble, raising the possibility that HFE also has a soluble form. However, it is not known whether soluble HFE (sHFE) is present in human serum, and there has been no report on the possible binding between sHFE and soluble TfR (sTfR), which is the fragment of the extracellular domain of TfR1 released into the blood. In the present study, we purified an sTfR complex from pooled serum collected from healthy volunteers, showing that the main components of the complex are sTfR and transferrin. We also confirmed the existence of sHFE in this complex. This is the first report on the existence of sHFE in human serum.


Comparative study of the effect of atropine, P2AM, and Buscopan. Total belladonna and hyoscyamus alkaloids on parathion poisoning.
Among the available antidotes used against parathion poisoning, atropine and Buscopan are tolerated in relatively high doses by rats. Hyoscine (in very small doses), T. Bel. Alk. and T. Hyosc. Alk. (better results in small doses, also for dogs), P2AM (of superior antimuscarine action) are redommended with each of the preceding drugs than either alone or in combination with Buscopan.


Nonadrenergic mechanisms of cocaine-induced regional vascular responses in rats.
The pressor response to cocaine is a consequence of mesenteric vasoconstriction and hindquarters vasodilation as a result of activation of alpha 1- and beta-adrenergic receptors, respectively. In the present study, evidence for additional, nonadrenergic effects of cocaine-induced changes in regional blood flow was obtained using pulsed Doppler flowmetry in conscious rats. Cocaine produced dose-dependent initial peaks (within 1 min) in mean arterial pressure concomitant with an increase in hindquarters and mesenteric vascular resistance. The sustained, modest pressor response was associated with hindquarters vasodilation and bradycardia. The cocaine-induced vasodilation was enhanced by pretreatment with indomethacin (5 mg/kg), prevented by ibuprofen (12.5 mg/kg) or 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C, 10.5 mg/kg) pretreatment, and unaffected by meclofenamate administration (2.5 mg/kg). Equipotent local anesthetic doses of procaine produced equivalent hindquarters vasodilator responses and more modest pressor responses. Dial-urethane anesthesia did not affect hindquarters vasodilation in response to cocaine or procaine but did reduce the mesenteric vasoconstrictor and pressor responses. These data demonstrate that the cocaine-induced hindquarters vasodilation is not mediated solely by beta-adrenergic receptors but is also dependent upon eicosanoids. Furthermore, the cocaine-induced vasodilation may be due, in part, to a direct local anesthetic effect but is not dependent upon a locomotor or behavioral stress induced increase in blood flow.


Oxidative carbon-carbon bond formation via silyl bis-enol ethers: controlled cross-coupling for the synthesis of quaternary centers.
Unsymmetrical silyl bis-enol ethers have been developed as effective substrates for synthesizing quaternary centers from tetralone derivatives through oxidative carbon-carbon bond formation. The derived products are shown to be highly versatile intermediates that may be used to generate diverse structures such as cyclopentenones, 2H-pyrroles, and spirocyclic pyrrolidines.


Pediatric Dance-Related Injuries Treated in Emergency Departments in the United States, 2000-2020.
This study investigated the characteristics and trends of children aged 3 to 19 years treated in US emergency departments for dance-related injuries. Retrospective analysis of data from the National Electronic Injury Surveillance System from 2000 through 2020 was conducted. An estimated 489,119 children received emergency treatment for a dance-related injury, averaging 23,291 children annually, and the rate of injury increased 68.1% during the 21-year study period. Girls accounted for 80.3% and children aged 15 to 19 years accounted for 46.5% of cases. Sprains/strains were the most frequent diagnosis (44.4%), and lower extremities were the most commonly injured body region (56.4%). Compared with other body regions, patients aged 3 to 10 years were more likely to sustain head/neck injuries (odds ratio, 3.94, 95% confidence interval, 3.42-4.52) than 11- to 19-year-olds. Falls and noncontact mechanisms of injury accounted for 35.6% and 32.1% of injuries, respectively. Unstructured dance activity was associated with 30.8% of dance-related injuries overall and 67.0% among children aged 3 to 5 years. Ballet/pointe dancers frequently sustained lower extremity sprains/strains (39.2%). Compared with other dance types, break dancing was more commonly associated with injuries to an upper extremity than other body regions (odds ratio, 4.76, 95% confidence interval, 3.66-6.19). The rate of pediatric dance-related injuries treated in US emergency departments is increasing. Unstructured dance activity was an important source of dance-related injury, especially among children aged 3 to 5 years. The injury diagnosis and body region injured varied by child age and type of dance. Additional targeted prevention efforts should be implemented that address the injury characteristics of dancer subgroups.


The effects of melatonin on oxidative stress and prevention of primordial follicle loss via activation of mTOR pathway in the rat ovary.
Mammalian Target of Rapamycin (mTOR) signaling pathway has important roles in the regulation of puberty onset, gonadotropin secretion, follicular development and ovulation. Melatonin (N-acetyl-5-methoxytryptamine) is a lipophilic hormone has multiple functions in regulating the fertility. Recent studies have shown that melatonin affected the number or maturation of follicles in the ovary. The aim of this study was to investigate the effects of melatonin on mTOR expression and quantity of follicle in rat ovary. In the present study, a total of 45 female rats were randomly divided into three groups. Group 1; Control (C), Group 2: Vehicle (V) and Group 3; Melatonin (M). Melatonin was administered intraperitoneally at a dose of 50 mg/kg/day for 30 days in Melatonin group. The effects of Melatonin on the expression of mTOR and downstream components were determined by Western Blot and Reverse Transcriptase PCR analysis. Upon Western Blot and RT-PCR evaluations, we detected higher expression and activation of mTOR, P70S6K, PKCalpha, PCNA and higher numbers of primordial follicles in melatonin group compared with V and C group. In addition to this results, melatonin decreased oxidative stress markers, such as MDA, on the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin in rat ovary. This study indicated that melatonin may have a significant protective effect on primordial follicles and increase the expression of mTOR and downstream components in rat ovary. Melatonin treatment may have a beneficial effect on fertility.


Comparisons of planar and tomographic gamma scintigraphy to measure the penetration index of inhaled aerosols.
The quantitative measurement of regional aerosol deposition in human lungs using two-dimensional (2D) gamma scintigraphy has proven to be useful in therapeutic and diagnostic aerosol studies. The penetration index (PI) has been defined as the ratio of activity in a peripheral lung zone to a central lung zone, but the ability to discriminate between aerosol deposition in the large airways and lung parenchyma is reduced by the fact that the latter overlies the former in the central zone. To overcome this, we used a three-dimensional (3D) technique. Seven healthy subjects inhaled isotonic saline aerosols containing 99mTc-DTPA on two occasions. The droplets had a mass median aerodynamic diameter (MMAD) of either 2.6 or 5.5 microns (with geometric standard deviations [sigma g] of 1.4 and 1.7, respectively). Transmission tomography was performed on each subject to delineate lung boundaries in 2D and 3D. After inhalation, anterior (A) and posterior (P) images were collected and a tomographic study performed. Mid-lung slices were taken from coronal (CC) and transverse (TC) sections. PI was calculated on the 2D images (AP and P) and the 3D slices (CC and TC) using exactly defined regions. The PI values were smaller for the large droplet aerosol (5.5 microns) in all subjects and methods. The relative differences in PI between large and small (2.6 microns) droplet studies (d values) were greater and less variable for the 3D methods (TC, 56.5 +/- 11.4% and CC, 52.4 +/- 12.3%) compared to the 2D methods (P, 25.4 +/- 17.1% and AP, 38.3 +/- 15%; p less than 0.005). We found the 3D methods to be more sensitive for discriminating between aerosol deposition in large and small airways than were the conventional 2D methods.


Activation of antioxidant defenses in whole saliva by psychosocial stress is more manifested in young women than in young men.
Psychosocial stress has been long known to have deleterious effects on health. Nevertheless, an exposure to moderate stressors enhances resilience and promotes health benefits. Male and female organisms differ in many aspects of health and disease. The aim of this study was to investigate antioxidant activity and oxidative damage in saliva in a psychosocial stress paradigm in men and women. Here, we show that an acute stressor of moderate strength augments antioxidant activity and decreases oxidative damage in whole saliva of young people. An examination stress caused a significant increase of catalase activity, accompanied by a decrease of levels of oxidized proteins. Levels of thiobarbituric acid-reacting substances did not increase at stress, indicating that lipid peroxidation was not activated. The stress-induced alterations were more manifested in young women compared to young men. Thus, antioxidant protective mechanisms are more activated by a moderate stressor in young women than in young men.


Distinct palisade tissue development processes promoted by leaf autonomous signalling and long-distance signalling in Arabidopsis thaliana.
Plants develop palisade tissue consisting of cylindrical mesophyll cells located at the adaxial side of leaves in response to high light. To understand high light signalling in palisade tissue development, we investigated leaf autonomous and long-distance signal responses of palisade tissue development using Arabidopsis thaliana. Illumination of a developing leaf with high light induced cell height elongation, whereas illumination of mature leaves with high light increased cell density and suppressed cell width expansion in palisade tissue of new leaves. Examination using phototropin1 phototropin2 showed that blue light signalling mediated by phototropins was involved in cell height elongation of the leaf autonomous response rather than the cell density increase induced by long-distance signalling. Hydrogen peroxide treatment induced cylindrical palisade tissue cell formation in both a leaf autonomous and long-distance manner, suggesting involvement of oxidative signals. Although constitutive expression of transcription factors involved in systemic-acquired acclimation to excess light, ZAT10 and ZAT12, induced cylindrical palisade tissue cell formation, knockout of these genes did not affect cylindrical palisade tissue cell formation. We conclude that two distinct signalling pathways - leaf autonomous signalling mostly dependent on blue light signalling and long-distance signalling from mature leaves that sense high light and oxidative stress - control palisade tissue development in A. thaliana.


Highlights on the development of A(2A) adenosine receptor agonists and antagonists.
Although significant progress has been made in the past few decades demonstrating that adenosine modulates a variety of physiological and pathophysiological processes through the interaction with four subtypes of a family of cell-surface G-protein-coupled receptors, clinical evaluation of some adenosine receptor ligands has been discontinued. Major problems include side effects due to the wide distribution of adenosine receptors, low brain penetration (which is important for the targeting of CNS diseases), short half-life of compounds, or a lack of effects, in some cases perhaps due to receptor desensitization or to low receptor density in the targeted tissue. Currently, three A(2A) adenosine receptor agonists have begun phase III studies. Two of them are therapeutically evaluated as pharmacologic stress agents and the third proved to be effective in the treatment of acute spinal cord injury (SCI), while avoiding the adverse effects of steroid agents. On the other hand, the great interest in the field of A(2A) adenosine receptor antagonists is related to their application in neurodegenerative disorders, in particular, Parkinson's disease, and some of them are currently in various stages of evaluation. This review presents an update of medicinal chemistry and molecular recognition of A(2A) adenosine receptor agonists and antagonists, and stresses the strong need for more selective ligands at the A(2A) human subtype.


Directed Assembly of Soft Anisotropic Nanoparticles by Colloid Electrospinning.
Directed assembly of triblock copolymer worms to produce nanostructured fibers is achieved via colloid electrospinning. These copolymer worms are conveniently prepared by polymerization-induced self-assembly in concentrated aqueous dispersion. Addition of a second water-soluble component, poly(vinyl alcohol), is found to be critical for the production of well-defined fibers: trial experiments performed using the worms alone produce only spherical microparticles. Transmission electron microscopy studies confirm that the worm morphology survives electrospinning and the worms become orientated parallel to the main axis of the fibers during their generation. The average deviant angle (θdev ) between the worm orientation and fiber axis decreases from 17° to 9° as the worm/PVA mass ratio increases from 1.15:1 to 5:1, indicating a greater degree of worm alignment within fibers with higher worm contents and smaller fiber diameters. Thus triblock copolymer fibers of ≈300 ± 120 nm diameter can be readily produced that comprise aligned worms on the nanoscale.


B5, a thioredoxin reductase inhibitor, induces apoptosis in human cervical cancer cells by suppressing the thioredoxin system, disrupting mitochondrion-dependent pathways and triggering autophagy.
The synthetic curcumin analog B5 is a potent inhibitor of thioredoxin reductase (TrxR) that has potential anticancer effects. The molecular mechanism underlying B5 as an anticancer agent is not yet fully understood. In this study, we report that B5 induces apoptosis in two human cervical cancer cell lines, CaSki and SiHa, as evidenced by the downregulation of XIAP, activation of caspases and cleavage of PARP. The involvement of the mitochondrial pathway in B5-induced apoptosis was suggested by the dissipation of mitochondrial membrane potential and increased expression of pro-apoptotic Bcl-2 family proteins. In B5-treated cells, TrxR activity was markedly inhibited with concomitant accumulation of oxidized thioredoxin, increased formation of reactive oxygen species (ROS), and activation of ASK1 and its downstream regulatory target p38/JNK. B5-induced apoptosis was significantly inhibited in the presence of N-acetyl-l-cysteine. Microscopic examination of B5-treated cells revealed increased presence of cytoplasmic vacuoles. The ability of B5 to activate autophagy in cells was subsequently confirmed by cell staining with acridine orange, accumulation of LC3-II, and measurement of autophagic flux. Unlike B5-induced apoptosis, autophagy induced by B5 is not ROS-mediated but a role for the AKT and AMPK signaling pathways is implied. In SiHa cells but not CaSki cells, B5-induced apoptosis was promoted by autophagy. These data suggest that the anticarcinogenic effects of B5 is mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis and autophagy.


Cryptococcal meningitis: clinical, diagnostic and therapeutic overviews.
Cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality in patients with AIDS. Among the human immunodeficiency virus (HIV)-seropositive subjects, cryptococcal meningitis is the second most common cause of opportunistic neuro-infection. Current trends are changing due to the marked improvement of quality and length of life produced by highly active antiretroviral therapy (HAART). The introduction of generic HAART in India has resulted in an increase in the number of individuals getting treatment for HIV infection, as the cost of highly active antiretroviral therapy (HAART) has decreased 20- fold. Cryptococcal meningitis occurs in non-HIV patients who are immunodeficient due to diabetes, cancer, solid organ transplants, chemotherapeutic drugs, hematological malignancies etc and rarely in healthy individuals with no obvious predisposing factors. Diagnosis of cryptococcal meningitis is fairly straightforward once the diagnosis is considered in the differential diagnosis of chronic meningitis. Treatment of a patient with cryptococcal infection is a challenge for both the physician and the patient, but rewarding, as many would recover with timely and adequate antifungal therapy.


A ku70 null mutant improves gene targeting frequency in the fungal pathogen Verticillium dahliae.
To overcome the challenges met with gene deletion in the plant pathogen Verticillium dahliae, a mutant strain with impaired non-homologous end joining DNA repair was generated to improve targeted gene replacement frequencies. A V. dahliae 991 ΔVdku70 null mutant strain was generated using Agrobacterium tumefaciens-mediated transformation. Despite having impaired non-homologous end joining DNA repair function, the ΔVdku70 strain exhibited normal growth, reproduction capability, and pathogenicity when compared with the wild-type strain. When the ΔVdku70 strain was used to delete 2-oxoglutarate dehydrogenase E2, ferric reductase transmembrane component 3 precursor, and ferric reductase transmembrane component 6 genes, gene replacement frequencies ranged between 22.8 and 34.7% compared with 0.3 and 0.5 % in the wild-type strain. The ΔVdku70 strain will be a valuable tool to generate deletion strains when studying factors that underlie virulence and pathogenesis in this filamentous fungus.


Location and Types of Treatment for Prostate Cancer After the Veterans Choice Program Implementation.
The Veterans Choice Program (VCP) was implemented in 2014 to help veterans gain broader access to specialized care outside of the Veterans Health Administration (VHA) facilities by providing them with purchased community care (CC). To describe the prevalence and patterns in VCP-funded purchased CC after the implementation of the VCP among veterans with prostate cancer. This cohort study used VHA administrative data on veterans with prostate cancer diagnosed between January 1, 2015, and December 31, 2018. These veterans were regular VHA primary care users. Analyses were performed from March to July 2023. Driving distance (in miles) from residence to nearest VHA tertiary care facility. The location (VHA or purchased CC) in which treatment decisions were made was ascertained by considering 3 factors: (1) location of the diagnostic biopsy, (2) location of most of the postdiagnostic prostate-specific antigen laboratory testing, and (3) location of most of the postdiagnostic urological care encounters. The main outcome was receipt of definitive treatment and proportion of purchased CC by treatment type (radical prostatectomy [RP], radiotherapy [RT], or active surveillance) and by distance to nearest VHA tertiary care facility. Quality was evaluated based on receipt of definitive treatment for Gleason grade group 1 prostate cancer (low risk/limited treatment benefit by guidelines). The cohort included 45 029 veterans (mean [SD] age, 67.1 [6.9] years) with newly diagnosed prostate cancer; of these patients, 28 866 (64.1%) underwent definitive treatment. Overall, 56.8% of patients received definitive treatment from the purchased CC setting, representing 37.5% of all RP care and 66.7% of all RT care received during the study period. Most patients who received active surveillance management (92.5%) remained within the VHA. Receipt of definitive treatment increased over the study period (from 5830 patients in 2015 to 9304 in 2018), with increased purchased CC for patients living farthest from VHA tertiary care facilities. The likelihood of receiving definitive treatment of Gleason grade group 1 prostate cancer was higher in the purchased CC setting (adjusted relative risk ratio, 1.79; 95% CI, 1.65-1.93). This cohort study found that the percentage of veterans receiving definitive treatment in VCP-funded purchased CC settings increased significantly over the study period. Increased access, however, may come at the cost of low care quality (overtreatment) for low-risk prostate cancer.


Trueperella bernardiae bloodstream infection following onco-gynaecologic surgery and literature review.
Trueperella bernardiae is a Gram-positive commensal bacillus of the human skin and oropharynx. It is known as an opportunistic human pathogen causing surgical wound, skin, and soft tissue, osteoarticular, and bloodstream infections (BSIs) with severe complications. We report a case of surgical wound related T. bernardiae BSI following onco-gynaecologic surgery together with a comprehensive literature review of T. bernardiae infections to alert clinicians about this emerging pathogen.


The increasing problem in Tayside of cervical cancer in younger women.
The incidence of cervical carcinoma in younger women is increasing in Tayside despite a decrease in the overall incidence. However, stage for stage, we did not encounter a poorer survival in younger patients. A number of patients had been sterilised or had a pregnancy when cytological screening was available and not made use of. There were also some false negative smears which were reclassified for retrospective analysis. We would recommend cervical screening every three years and careful inspection of the cervix and a smear taken in cases of abnormal gynaecological symptoms such as post coital bleeding.


Tuberculosis Osteomyelitis as an Indolent Bone Mass.
Tuberculosis (TB) is a pulmonary disease with potential extrapulmonary manifestations that is caused by the bacteria Mycobacterium tuberculosis. Despite advancements in treatment, TB remains a worldwide public health concern. TB osteomyelitis accounts for approximately 3-5% of all extrapulmonary TB cases. We present a case of humeral TB osteomyelitis in a 22-month-old female with no pulmonary or systemic symptoms. This case offers insight into the diagnosis and management of TB osteomyelitis. A 22-month-old previously healthy Haitian-American female presented with a one-month history of a palpable mass over the anterolateral aspect of the proximal humerus without overlying erythema or soft tissue swelling. No additional symptoms were reported. She had no recent sick contacts but had visited Haiti during her infancy. Right proximal humerus X-ray and subsequent MRI revealed proximal humeral osteomyelitis with an intraosseous Brodie's abscess. Incision and drainage extracted caseous material, which tested positive for Mycobacterium tuberculosis via a polymerase chain reaction. The diagnosis was confirmed via positive QuantiFERON-TB Gold and purified protein derivative testing. The patient was treated with levofloxacin, isoniazid, pyrazinamide, pyridoxine, and rifampin during the hospitalization. Following discharge, she was continued on her antibiotic regimen and managed by the Florida Department of Health. Post-discharge, X-rays at three and twelve months showed evidence of lesion healing. TB osteomyelitis is a rare manifestation of TB infection, which may present insidiously without systemic or pulmonary symptoms. As timely treatment is vital to preventing complications, bone masses of unknown etiology should be investigated for TB infection, even without additional symptoms.


Essential oil of Zygophyllum album inhibits key-digestive enzymes related to diabetes and hypertension and attenuates symptoms of diarrhea in alloxan-induced diabetic rats.
Zygophyllum album L. (Zygophyllaceae), commonly known as Bougriba, is widely used to treat diabetes, digestive tract spasm, and hypertension in folk medicine, in Tunisia. This study investigates the antidiabetic, antidiarrheal, and antihypertensive activities of the leaves of the essential oil from Zygophyllum album (OZA) in alloxan-induced diabetic rats. The oil was obtained by hydrodistillation and analyzed by GC-MS. Males rats were divided into four groups: control, diabetic-untreated group, diabetic-treated group with acarbose (10 mg/kg), and diabetic-treated rats with OZA (200 mg/kg) for 30 d. At the end of the experimental period, the OZA significantly decreased the activity of α-amylase in pancreas and serum of the diabetic rats by 43% and 38%, respectively, which led to reduce the serum glucose level by 60% and lower of glycated hemoglobin (HbA1c) rate by 17% as compared with untreated diabetic animals. Moreover, the OZA treatment attenuated symptoms of diarrhea, improved lipid disorders, and hypertension through inhibiting the pancreatic lipase and angiotensin-converting enzyme (ACE) activities by 47% and 25%, respectively, in serum of diabetic rats. OZA showed a good effect in the management of diabetes mellitus and exerted preventive action from related hypertension.


Invasive Streptococcus pneumoniae in children, Malawi, 2004-2006.
Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible.


Comparison of genetic changes between interphase and metaphase nuclei in monitoring CML and APL treatment using DC-FISH technique.
In leukemias, the monitoring techniques on the response after the treatment have clinical importance for evaluating new therapeutic approaches and identifying the risk of relapse. In this study, genetic changes before and after chemotherapy in interphase and metaphase nuclei of bone morrow of adults with provisional diagnosis of leukemia were compared to understand the molecular characterization and pathogenesis of the leukemia for the classification of diagnosis and prognosis. We examined bone morrow cells of 47 chronic myeloid leukemia (CML) cases (29 of 47 at the time of diagnosis, 31 of 47 after chemotherapy) with the bcr/abl translocation probes and of 10 acute promyelocytic leukemia (APL) cases (7 of 10 at the time of diagnosis, 4 of 10 after chemotherapy) with the PML/RARalpha translocation probes by using dual color-flourescence in situ hybridization (DC-FISH). For each case, 400 interphase nuclei and 11 to 25 metaphases nuclei were analysed. The ratios of translocations before and after chemotherapy were compared between interphase and metaphase nuclei. After chemotherapy, though, translocations were detected in interphase nuclei of 29 of the 31 CML and 4 of the 4 APL cases, these translocations were determined in metaphase nuclei of only 14 of the 31 CML and 1 of the 4 APL cases with very low ratios (p < 0.01). The results showed that the rates of translocation positive interphase nuclei were higher than the rates of translocation positive metaphase nuclei (p < 0.01) after chemotherapy, so there may be some factors effecting proliferative activity of metaphase formation in leukemias.


[The effects of hearing level on auditory performance in infants with hearing aids].
The purpose of this study is to investigate the effects of hearing level on auditory performance in infants with hearing aids and provide a clinical database for their hearing and speech habilitation. A total of 32 infants with prelingual hearing loss participated in this study, ranging in age at hearing aid fitting from 3 to 34 months with a mean of 16 months. According to their hearing level, they were divided into three groups. Infants in group A were with moderate hearing loss (41-60 dB HL). Infants in group B were with severe hearing loss (61-80 dB HL). Infants in group C were with profound hearing loss (>81 dB HL). The infant-toddler meaningful auditory integration scale (IT-MAIS) was used to evaluate their auditory performance. The evaluation was performed before hearing aid fitting and 1, 3, 6, 9, 12 months after fitting. The mean scores of auditory performance showed significant improvements with time of hearing aid use for the three groups of infants (P < 0.05). The mean score of auditory performance for group A at 3 months after fitting was significantly superior in comparison with the scores before hearing aid fitting and at 1 month after fitting (P < 0.05). The mean score of auditory performance for group B at 6 months after fitting was significantly superior in comparison with the scores before hearing aid fitting and at 1, 3 months after fitting (P < 0.05). The mean score of auditory performance for group C at 9 months after fitting was significantly superior in comparison with the scores before hearing aid fitting and at 1, 3, 6 months after fitting (P < 0.05). There were no significant differences in mean scores between group A and B at each evaluating interval (P > 0.05). However, significant differences were observed between group A and C at 3, 6, 9, 12 months after fitting (P < 0.05). Significant differences were also shown between group B and C at 1, 3, 6, 9, 12 months after fitting (P < 0.05). Auditory performance of infants with prelingual hearing loss developed significantly with the use of hearing aids within the first year after fitting. The degree of hearing loss in infants had significant influence on the development of auditory performance.


A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma.
Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma. Patients received a fixed-dose of 250 mg/day given subcutaneously for four consecutive days followed by three drug-free days per week in a 28-day cycle. A total of 44 patients were enrolled in the intent to treat population, with 59.1% having received previous therapy. The median time to progression and overall survival was 1.7 months and 9 months, respectively. Forty-one patients are included in the efficacy analysis. One (2.4%) patient achieved a partial response, six (14.6%) patients had stable disease as best response, and 30 (73.2%) had progressive disease. At the end of six cycles of treatment, three of the 41 evaluable patients had non-progressive disease. Treatment was generally well tolerated. Injection site bruising occurred in 45% of patients. Serious bleeding did occur in two patients and three patients developed a positive anti-platelet antibody test during the study. One of these four patients experienced an associated thrombosis. In patients with advanced melanoma, PI-88 demonstrates an overall survival and time to progression similar to standard chemotherapy. Although the current study did not meet the primary end-point of progression free survival of >or=20%, there is some evidence of activity and further investigation is warranted.


Combined target site (kdr) mutations play a primary role in highly pyrethroid resistant phenotypes of Aedes aegypti from Saudi Arabia.
Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area are reported here. Aedes aegypti collected from each city were raised to adults and assayed for resistance to permethrin, deltamethrin (with and without the synergist piperonyl butoxide, PBO), fenitrothion, and bendiocarb. Two fragments of the voltage-gated sodium channel (Vgsc), encompassing four previously identified mutation sites, were sequenced and subsequently genotyped to determine associations with resistance. Expression of five candidate genes (CYP9J10, CYP9J28, CYP9J32, CYP9M6, ABCB4) previously associated with pyrethroid resistance was compared between assay survivors and controls. Jeddah and Makkah populations exhibited resistance to multiple insecticides and a similarly high prevalence of resistance to deltamethrin compared to a resistant Cayman strain, with a significant influence of age and exposure duration on survival. PBO pre-exposure increased pyrethroid mortality significantly in the Jeddah, but not the Makkah strain. Three potentially interacting Vgsc mutations were detected: V1016G and S989P were in perfect linkage disequilibrium in each strain and strongly predicted survival, especially in the Makkah strain, but were in negative linkage disequilibrium with 1534C, though some females with the Vgsc triple mutation were detected. The candidate gene CYP9J28 was significantly over-expressed in Jeddah compared to two susceptible reference strains, but none of the candidate genes was consistently up-regulated to a significant level in the Makkah strain. Despite their proximity, Makkah and Jeddah exhibit significant differences in pyrethroid resistance phenotypes, with some evidence to suggest a different balance of mechanisms, for example with more impact associated with CYP450s in the Jeddah strain, and the dual kdr mutations 989P and 1016G in the more resistant Makkah strain. The results overall demonstrate a major role for paired target site mutations in pyrethroid resistance and highlight their utility for diagnostic monitoring.


High Plasma Lipid Levels Reduce Efficacy of Adenovirus-Mediated Gene Therapy.
Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. Here we demonstrate that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE-/- mice have much higher plasma transgene levels compared to LDLR-deficient mice. We also found that specific lipoprotein receptors play an important role in adenoviral transduction. These findings suggest that high plasma lipid levels, especially apoE-containing lipoproteins, reduce efficacy of adenoviral transduction in mice, which implies that high cholesterol levels in humans could be protective against viral infections and also lead to insufficient transgene expression in clinical trials using adenoviral vectors.


Anatomic Landmarks for Localization of the Vertical Segment of Facial Nerve on Multislice CT Multiplanar Reconstruction Images.
The facial nerve decompression via mastoid is simple and easy to expose the vertical segment of the facial nerve (VFN). The objective of this study was to find out the relationship between the VFN and anatomic landmarks to facilitate prediction of the location of VFN during facial nerve decompression. The different landmarks were cochlear window (CW), oval window (OW), promontorium tympani (PT), and mastoid antrum (MA). Parameters of 140 patients (280 observations) with healthy middle ears were measured on high-resolution spiral multislice computed tomographic multiplanar reconstruction (MPR) images that were parallel to the base plane. The data gained were analyzed by statistical method and were also analyzed with respect to side and gender. The angle between orientation of VFN to the CW of the longest distance and horizontal axis was larger on the left side than that of the right (P < 0.05). Our results may provide more detailed information to predict the location of VFN during facial nerve decompression through mastoid.


[Detection of the expression level of S100C gene in lung cancer tissue by RT-PCR and construction and identification of prokaryotic expression vector].
To analyze the expression level of S100C gene in lung cancer tissue and to construct prokaryotic expression vector pET30a-S100C in order to select fusion antibody in further study. mRNA expression level of S100C gene in lung cancer tissue and ambient tissue in 26 cases was detected by RT-PCR with beta-actin as references. The full-length cDNA of S100C was cloned by RT-PCR. The amplified DNA fragments were ligated into pET30a vector and then transformed into E. coli stain JM109. The positive clones were screened out and indentified. The expression level of S100C in lung cancer tissue was lower than that in ambient tissue. The difference between the two groups was statistically significant (P < 0.05). The prokaryotic expression vector of S100C was successfully constructed. The sequence homogenuity was up to 100%. The down-regulation expression of S100C gene probably takes important part in the carcinogenisis of lung cancer.


Dermoid cyst with a congenital sinus tract over the left sternoclavicular joint: a case report and literature review.
Dermoid cysts are rare benign tumors that arise from ectopic epiblastic inclusions and account for 0.4% to 1.5% of all tumors. They are usually 1 to 5 cm in size and composed of a pasty semisolid material. The orbital dermoid cyst is the most common type. Dermoid cysts can also occur in the spinal cord, ovaries, and pancreas. We encountered a 24-year-old man with a dermoid cyst over the left sternoclavicular joint. He reported intermittent secretion of a white tofu-like exudate from an underlying congenital sinus tract since birth. The secretion had turned hemorrhagic for the last month and had been accompanied by progressive swelling and pruritus for 1 week. Ultrasonography and magnetic resonance imaging revealed characteristics of a dermoid cyst, and histopathological examination confirmed the diagnosis. The patient underwent surgical excision of the cyst under local anesthesia. The incision healed well with no postoperative complications. Considering that a dermoid cyst has the potential to become infected or progress into squamous cell carcinoma, its removal at an early stage is suggested. Few reports in the literature have described a dermoid cyst that secretes hemorrhagic contents from a congenital sinus tract. We present this case to provide a reference for clinicians.


Creation of nano eye-drops and effective drug delivery to the interior of the eye.
Nano eye-drops are a new type of ophthalmic treatment with increased potency and reduced side effects. Compounds in conventional eye-drops barely penetrate into the eye because the cornea, located at the surface of eye, has a strong barrier function for preventing invasion of hydrophilic or large-sized materials from the outside. In this work, we describe the utility of nano eye-drops utilising brinzolamide, a commercially available glaucoma treatment drug, as a target compound. Fabrication of the nanoparticles of brinzolamide prodrug increases the eye penetration rate and results in high drug efficacy, compared with that of commercially available brinzolamide eye-drops formulated as micro-sized structures. In addition, the resulting nano eye-drops were not toxic to the corneal epithelium after repeated administration for 1 week. The nano eye-drops may have applications as a next-generation ophthalmic treatment.


Comparison of DNA double-strand break rejoining as measured by pulsed field gel electrophoresis, neutral sucrose gradient centrifugation and non-unwinding filter elution in irradiated plateau-phase CHO cells.
The initial (up to 30 min) rate of DNA double-strand break (dsb) rejoining was measured in irradiated plateau-phase CHO cells, in a set of parallel experiments using the same cell suspension, by means of non-unwinding filter elution, neutral sucrose gradient centrifugation, and two pulsed-field gel electrophoresis assays: asymmetric field inversion gel electrophoresis (AFIGE) and clamped homogeneous electric field (CHEF) gel electrophoresis. The rate of DNA dsb rejoining was compared to the rate of rejoining of chromatin breaks measured, also in the same cell population, using the technique of premature chromosome condensation (PCC). Two radiation exposures, 25 Gy and/or 50 Gy, were used and applied to the individual parts of the experiments according to the sensitivity of the assay under investigation. Similar values for the initial rate of DNA dsb rejoining were obtained with all assays used, with t 1/2 ranging between 10 and 12 min after exposure to 25 Gy and between 15 and 20 min after exposure to 50 Gy. The initial rate of rejoining of chromatin breaks was slower than that of DNA dsb and occurred with t 1/2 of 87 min. The results suggest that all major techniques currently used for assaying rejoining of DNA dsb give similar results despite their widely different biophysical basis, and indicate that more information is required before a direct correlation between rejoining of DNA dsb and rejoining of chromatin breaks can be established.


Validation of rotational thromboelastometry during cardiopulmonary bypass: A prospective, observational in-vivo study.
Rotational thromboelastometry (ROTEM) is a whole blood point-of-test used to assess the patient's coagulation status. Three of the available ROTEM tests are EXTEM, INTEM and HEPTEM. In the latter, heparinase added to the INTEM reagent inactivates heparin to reveal residual heparin effect. Performing ROTEM analysis during cardiopulmonary bypass (CPB) might allow the anaesthesiologist to anticipate the need for blood products. The goal of this study was to validate ROTEM analysis in the presence of very high heparin concentrations during CPB. Prospective, observational trial. Single University Hospital. Twenty patients undergoing coronary artery bypass grafting. ROTEM analysis was performed before heparin administration (T0), 10 min after heparin (T1), at the end of CPB (T2) and 10 min after protamine (T3). The following tests were performed: EXTEM, INTEM, and HEPTEM. Heparin concentrations were measured at T1 and at the end of bypass (T2). At T1, EXTEM differed from baseline for coagulation time: +26.7 s (18.4 to 34.9, P < 0.0001), α: -3° (1.0 to 5.4, P = 0.006) and A10: -4.4 mm (2.3 to 6.5, P = 0.0004). INTEM at T0 was different from HEPTEM at T1 for coagulation time: + 47 s (34.3 to 59.6, P > 0.0001), A10: -2.3 mm (0.5 to 4.0, P = 0.01) and α -2° (1.0 to 3.0; P = 0.0007). At T2, all parameters in EXTEM and HEPTEM related to fibrin-platelet interaction deteriorated significantly compared to T1. At T3, EXTEM and INTEM were comparable to EXTEM and HEPTEM at T2. HEPTEM and EXTEM measurements are valid in the presence of very high heparin concentrations and can be performed before protamine administration in patients undergoing cardiac surgery with CPB. clinicaltrials.gov Identifier: NCT01455454.


Effectiveness of a Theory-Based Digital Animated Video Intervention to Reduce Intention and Willingness to Sext Among Diploma Students: Cluster Randomized Controlled Trial.
Sexting refers to the exchange of sexually explicit digital content in the form of texts, photos, or videos. In recent years, sexting has become a public health concern. Surveys in Malaysia show a high prevalence of young adults engaged in sexting. Given that sexting is associated with sexual risk behavior, cyberbullying, and mental health issues, this behavior needs intervention to alleviate the resulting public health burden. However, there is a scarcity of theory-based intervention programs on the prevention of intention and willingness to sext among young adults. This study aimed to develop and implement a sexting intervention module guided by the prototype willingness model (PWM), delivered using web-based animated video, and evaluate its effectiveness among diploma students from a public higher educational institution. The primary outcomes were intention and willingness to sext, while the secondary outcomes were knowledge, attitude, perceived norms, and prototype perceptions of sexting. This 2-armed, parallel, single-blinded cluster randomized controlled trial was conducted in a public higher educational institution in the state of Melaka, Malaysia. Diploma students from 12 programs were randomly allocated into intervention and control groups. Both groups answered a self-administered web-based questionnaire assessing the outcomes at the baseline. The intervention group received a newly developed intervention module based on the PWM in the form of 5 animated videos posted on a private YouTube platform, while the control group was put on the waitlist. The intervention group was encouraged to discuss any issues raised with the researchers via WhatsApp private chat after viewing the videos. All participants were observed immediately and 3 months postintervention. Data analysis was performed with SPSS (version 26; IBM Corp). A generalized linear mixed model was used to determine the effectiveness of the intervention. There were a total of 300 participants with an attrition rate of 8.3% (n=25). After adjusting for age, sex, relationship status, and the amount of time spent on the web, there were significant differences in the intention to sext (β=-.12; P=.002; Cohen d=0.23), willingness to sext (β=-.16; P<.001; Cohen d=0.40), knowledge (β=.12; P<.001; Cohen d=0.39), attitude (β=-.11; P=.001; Cohen d=0.31), perceived norms (β=-.06; P=.04; Cohen d=0.18), and prototype perceptions (β=-.11; P<.001; Cohen d=0.35) between the intervention and control groups over 3 months. In this study, the sexting intervention module using the PWM that was delivered via web-based animated videos was effective in reducing intention and willingness to sext as well as in improving knowledge of sexting, attitudes, perceived norms, and prototype perceptions. Therefore, relevant agencies involved in the promotion of sexual and reproductive health among young adults in Malaysia can consider the implementation of this module. Thai Clinical Trial Registry TCTR20201010002; https://www.thaiclinicaltrials.org/show/TCTR20201002001.


Reinstated ethanol-seeking in rats is modulated by environmental context and requires the nucleus accumbens core.
The reinstatement of ethanol (EtOH)-seeking induced by an EtOH-predictive light-tone stimulus is enhanced in an environment associated with prior EtOH self-administration (SA) compared with a context associated with EtOH unavailability (Tsiang & Janak, 2006). Here we hypothesized that EtOH-seeking would be elicited by the conditioned sensory stimulus properties of EtOH and that this reinstatement would be similarly modulated by context. We also determined whether pharmacologically inactivating the nucleus accumbens (NAc), a key structure in relapse circuitry, would attenuate reinstated EtOH-seeking. Rats lever-pressed for oral EtOH (10% v/v) in operant conditioning chambers distinguished by specific visual, olfactory and tactile stimuli. Responding was then extinguished by withholding EtOH in a different context. EtOH-seeking, expressed as elevated responding without EtOH delivery, was subsequently tested by presenting an oral EtOH prime (two aliquots of 0.1 mL EtOH) in either the extinction or the prior EtOH-SA context. Rats received a microinfusion (0.3 microL/hemisphere) of saline or GABA agonists (muscimol/baclofen) into the NAc core or shell immediately before the reinstatement test. Robust EtOH-seeking was observed in the prior EtOH-SA but not the extinction context in saline-pretreated rats. This effect was significantly attenuated by inactivating the NAc core but not shell. Conversely, NAc shell inactivation significantly elevated lever-pressing in the extinction context. These data suggest that the sensory stimulus properties of oral EtOH can reinstate EtOH-seeking when experienced in the appropriate context and that functional activity in the NAc core is required for this effect. In contrast, the shell may normally inhibit incorrect behavioral responses.


Prevalence of metabolic syndrome and its risk factors in patients with continuous ambulatory peritoneal dialysis in South China.
Metabolic syndrome (MS) is prevalent and widely proved as a predictor of cardiovascular disease (CVD) and Type 2 diabetes mellitus (T2DM) in general population. However, there was no large sample study concerning MS in patients on continuous ambulatory peritoneal dialysis (CAPD). We aimed to study the prevalence, risk factors of MS, and the relationship between CVD and MS in CAPD patients in South China. This singlecenter cross-sectional study was conducted in patients on CAPD. Demographic, clinical, and anthropometric data were collected and compared between the patients with and without MS. Logistic Regression analysis was used to identify the independent risk factors of MS. A total of 511 CAPD patients were enrolled. Compared to patients without MS, patients with MS tended to be diabetic, female, and older. Fasting waist circumference, waist-to-hip ratio, visceral fat area, as well as white blood cell, platelet, globulin, and high sensitivity C reactive protein in peripheral blood were significantly higher in MS than in non-MS group. But diastolic blood pressure was significantly lower in patients with MS than in patients without MS. Logistic regression showed old age (OR: 1.50, p < 0.001), higher level of WBC (OR: 1.41, p < 0.001), and glucose load of dialysate (GLD) (OR: 1.50, p = 0.002) were independent associated factors of MS and MS was an independent associated factor of CVD (OR: 2.37, p < 0.001). MS was prevalent in CAPD patients in our center and an independent associated factor of CVD. Old age, higher levels of WBC, and GLD were associated with MS independently.


Microbial inactivation by microwave radiation in the home environment.
The study reported here looked at the survival of microorganisms (heterotrophic plate counts, total coliforms, E. coli, and bacterial spores) in a consumer-type microwave oven. Kitchen sponges, scrubbing pads, and syringes were experimentally contaminated with wastewater and subsequently exposed to microwave radiation. At 100 percent power level, it was found that the heterotrophic plate count (i.e., total bacterial count) of the wastewater was reduced by more that 99 percent within 1 to 2 minutes, and the total coliform and E. coli were totally inactivated after 30 seconds of microwave radiation. Bacterial phage MS2 was totally inactivated within 1 to 2 minutes. Spores of Bacillus cereus were more resistant than the other microorganisms tested, and were completely eradicated only after 4-minute irradiation. Similar inactivation rates were obtained in wastewater-contaminated scrubbing pads. Microorganisms attached to plastic syringes were more resistant to microwave irradiation than those associated with kitchen sponges or scrubbing pads. It took 10 minutes for total inactivation of the heterotrophic plate count and 4 minutes for total inactivation of total coliform and E. coli. A 4-log reduction of phage MS2 was obtained after 2 minutes; 97.4 percent reduction was observed after 12 minutes. The authors also observed a higher inactivation of B. cereus spores in syringes placed in a ceramic container than of spores in syringes placed in a glass container. This finding could have some implications for the design of containers to be used in exposure of medical devices to microwave radiation. The article discusses the implications of these findings for consumer safety in the home environment.


Is maternal anemia among tribal women being neglected? A study from Southern Rajasthan.
Poor birth outcomes have been linked to maternal anemia. Tribal women are at higher risk of malnutrition and disease due to sociocultural barriers and poor educational status. The data on the prevalence of maternal anemia and its associated factors among pregnant tribal women are limited. A community-based cross-sectional study was conducted among 429 pregnant tribal women for maternal anemia from August 2021 to June 2022. A structured questionnaire was employed to collect sociodemographic data. The prevalence of anemia was 85.7%, with a mean hemoglobin level of 9.21 ± 1.3 g/dL. On applying WHO 2011 anemia criteria for pregnant women, 25.0% had mild anemia, 73.4% had moderate anemia, and 1.6% had severe anemia. The significant factors associated with anemic condition were household condition, monthly income, and husband's occupation. The higher prevalence of anemia among pregnant tribal women is alarming that necessitates a rethinking of health infrastructure and outreach in tribal dominant areas.


Psychotherapeutic approach in acne treatment.
From a medical psychological point of view, acne vulgaris can be schematically divided into two clinical pictures: (1) the common adolescent eruption, more mind-influencing and thus somatopsychic; (2) the less frequent acne of adults (young adults for the most part), both as a continuation of adolescent acne and, more rarely, as a never before experienced cutaneous affection, and thus psychosomatic in a strict sense. We believe that the dermatologist can treat both of these clinical manifestations, even from a psychological aspect, from the very first visit with the patient using the first step in psychotherapy: counseling. The principal points of this approach are presented, with special attention to the differences to be considered in the two clinical pictures specified as well as to the opportuneness and timing of an eventual liaison consultation with psychologists/psychiatrists in realizing other therapeutic strategies.


Top-down and middle-down approach by fraction collection enrichment using off-line capillary electrophoresis - mass spectrometry coupling: Application to monoclonal antibody Fc/2 charge variants.
The characterization of complex protein mixtures represents one of the biggest challenge in many research fields such as biological or biopharmaceutical sciences. Out of all categories, monoclonal antibodies (mAbs) and related products drawn the most interest due to their strong therapeutic potency and specificity. Because of their intrinsic complexity due to a large number of micro-heterogeneities, there is a crucial need for analytical methods to provide comprehensive in-depth characterization of these proteins. In this work, we developed a methodology using CE-UV/MALDI-MS to perform top-down or middle-down characterization after fraction collection enrichment applied to intact protein and mAbs samples. The performance of the method was evaluated with the rapid separation of three intact protein mixture. Good robustness of CZE separation and quality of MALDI-MS spectra and MALDI-ISD spectra of each protein confirms the usefulness of sample enrichment to obtain adequate quantity of deposed protein for top-down analysis and the proof of principle of the method. In a second step, the method was applied to the middle-down characterization of Fc/2 cetuximab variants. Identification of around 9% sequence coverage of Fc/2 cetuximab fragments allows to conclude on the feasibility of the strategy for middle-down characterization of Fc/2 cetuximab variants using CE-UV/MALDI-MS. Moreover, MALDI-ISD fragmentation of Fc/2 cetuximab variants confirm separation phenomenon based on the formation of Fc/2 dimers with and without C-terminal truncation.


Better prediction for FGR (fetal growth restriction) with the sFlt-1/PIGF ratio: A case-control study.
The aim of this study was to check whether the sFlt-1/PIGF ratio, established as the biomarker for preeclampsia, reduces the false positive rate of late fetal growth restriction (FGR) detection by ultrasound biometry.This was a prospective case-control study, conducted at one regional maternity hospital in Romania. Study participants included singleton pregnancy women for whom the estimated fetal weight (EFW) at 28 to 35 weeks was < 10 percentiles and as controls, pregnant women with EFW >10 percentiles. All pregnancies were dated in the first trimester by crown-rump-length. We also recorded maternal characteristics, pregnancy and neonatal outcomes.The primary outcome measures were the relation between the sFlt-1/PIGF ratio and incidence of FGR. Secondary outcome was establishing a threshold for statistical significance of the marker and influence of other conditions (e.g., pre-eclampsia) on the accuracy of the marker in FGR prediction.Included in the study were 37 pregnant women and 37 controls.When we used ultrasound (US) biometry and maternal risk factors to estimate EFW <10 percentiles, the sensitivity was 44.4% with a specificity of 89% for an FPR (false positive result) of 10%. When we combined the US biometry and maternal risk factors with sFlt1/PIGF ratio, for a cut off of 38, the sensitivity was 84.21%, and the specificity was 84.31% for an FPR of 10%. The cut off value (36) did not change if we considered all cases of SGA, including those with associated preeclampsia or if we considered only FGR cases without associated preeclampsia.When associated with maternal factors and US biometry, the sFlt1/PIGF ratio enhanced the sensitivity for detecting late FGR.


The effects of cigarette smoke on the progression of septic pseudarthrosis of the tibia treated by Ilizarov external fixator.
The authors conducted a study to evaluate the effects of cigarette smoke on the healing of septic pseudarthrosis of the tibia treated by ilizarov external fixator. A total of 31 patients of both sexes were chosen, and the healing time in relation to the habit of smoking was examined. The results have shown that the healing time in non-smokers as compared to smokers was shorter by 33%. The difference is highly significant. This shows that abstention from smoking during treatment should be given maximum importance in prevention.


NMDA receptors in the visual cortex of young kittens are more effective than those of adult cats.
Acidic amino acids, such as glutamate and aspartate, are thought to be excitatory transmitters in the cerebral neocortex and hippocampus. Receptors for these amino acids can be classified into at least three types on the basis of their agonists. Quisqualate-preferring receptors and kainate-preferring receptors are implicated in the mediation of synaptic transmission in many regions including the hippocampus and visual cortex, whereas N-methyl-D-aspartate (NMDA)-preferring receptors are thought to be involved in modulating synaptic efficacy, for example in longterm potentiation, a form of synaptic plasticity in the hippocampus. In the visual cortex of the cat and monkey, it is well established that synaptic plasticity, estimated by susceptibility of binocular responsiveness of cortical neurons to monocular visual deprivation, disappears after the 'critical' period of postnatal development. Here we report that during the critical period in young kittens, a selective NMDA-receptor antagonist blocks visual responses of cortical neurons much more effectively than it does in the adult cat. This suggests that NMDA receptors may be involved in establishing synaptic plasticity in the kitten visual cortex.


Iron starvation leads to oxidative stress in Anabaena sp. strain PCC 7120.
We establish here that iron deficiency causes oxidative stress in the cyanobacterium Anabaena sp. strain PCC 7120. Iron starvation leads to a significant increase in reactive oxygen species, whose effect can be abolished by treatment with the antioxidant tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl). Oxidative stress induced by iron starvation could be a common feature of photosynthetic bacteria.


Adequacy evaluation of the annual colonoscopic surveillance and individual difference of disease phenotypes in Lynch syndrome.
Regular endoscopic surveillance for Lynch syndrome is reported to reduce colorectal cancer (CRC)-related mortality. However, the appropriate surveillance intervals are still unclear. We evaluated the adequacy of annual colonoscopy and investigated the differences in tumor occurrence rates between individual patients. In total, 25 patients with Lynch syndrome who underwent colonoscopic surveillance between 2007 and 2016 at the Iwakuni Clinical Center were included. We retrospectively investigated the surveillance frequency and the clinical features associated with tumor development. Colonoscopic surveillance was performed every 397 days on average. A total of 101 tumors, including 8 intramucosal carcinomas and 15 carcinomas, were observed within the study period. Annual colonoscopy detected six malignancies, including a carcinoma requiring surgery. Tumor incidence was associated with tumor existence in the initial colonoscopies (P = 0.018). Patients with a tumor occurrence rate of 0.4 tumors per year during our observation period were significantly more likely to have malignancies detected during regular surveillance than patients who had a lower occurrence rate (P < 0.001). Malignancy occurrence rate was strongly associated with tumor occurrence rate (P < 0.001, R2 = 0.44). Annual colonoscopic surveillance for Lynch syndrome patients was effective in reducing the risk of CRC progression, but was insufficient to completely avoid surgery. Because the tumor occurrence rate differed substantially between individuals, more intensive surveillance was required for high-risk patients.


[Color Doppler ultrasound of uterine, fetoplacental and fetal blood vessels in the 2nd trimester in normal pregnancies].
We investigated 69 healthy women with normal pregnancy and delivery in order to establish normal values for the second trimester of gestation. In a cross-sectional study we measured the pulsatility index (PI), the maximal systolic velocity (V-MAX) and the mean velocity (V-MEAN) in the uterine arteries (UAA), the umbilical artery (UA), the fetal thoracic aorta (FTA) and the middle cerebral artery (MCA) from the 14th to the 24th week of gestation. A regression analysis shows a significant slope of the PI of UAA and UA (p < 0.01), whereas in contrast to the UA there is no significant difference of the median values of the UAA-PI from the 18th week of gestation. With progressive gestation V-MEAN of UAA increases more (p < 0.001) than V-MAX (p < 0.05) as a result of the increasing diastolic blood flow. In the UA there is also a significant rising trend of V-MAX and V-MEAN (p < 0.0001). No significant changes of the PI of FTA and MCA are seen, although there is a slight increasing trend. After the 20th week in the MCA a marked tendency to high PI-values is observed, whereas there is a change between different flowpatterns prior to the 20th week. V-MAX and V-MEAN of FTA increases significantly, but there is no change in the MCA. Our results for UAA and UA correspond to the known morphologic changes in the utero- and fetoplacental vessels in the second trimester and are comparable to other results. Particularly the physiology of the cerebral perfusion needs to be investigated more intensively. These normal values provide a good basis for early and complex assessment of a disturbed perfusion in the second trimester.


Neuromonitoring for Proximal Fibular Osteochondroma Excision.
The peroneal nerve is at risk when excising tumors in the proximal fibula. The rate of nerve injuries during proximal fibular tumor resection varies from 3% to 20%. Our goal was to report our experience with resection of osteochondromas in the proximal fibula and describe the technique and utility of neuromonitoring during excision of proximal fibular osteochondromas (PFO). Patients with a diagnosis of symptomatic PFO who had undergone excision at one institution from 1994 to 2018 were included. An institutional review board-approved retrospective review was performed. Intraoperative neuromonitoring was provided from 2006 on by a single group utilizing a multimodality protocol. This study contains 29 patients who had excision of osteochondromas in the proximal fibula. Of these 29 consecutively monitored patients, there were 34 involved extremities. Intraoperative neuromonitoring alerts occurred in 10/29 (34.5%) procedures, which included 3 electromyography (EMG) (30%), 2 motor-evoked potential (20%), 1 somatosensory-evoked potential (10%), and 4 alerts with a combination of EMG/motor-evoked potential/somatosensory-evoked potential changes (40%). The interventions that were taken resulted in resolution of the neuromonitoring changes in all procedures. Postoperatively, we noted 2 (6.9%) new mild sensory deficits, which resolved during follow up. There were 3 patients in whom pre-existing sensory-motor deficits improved but not completely after surgery, 1 motor weakness, and 2 with residual paresthesia. In those initially presenting with paresis, there was improvement in 8 of the 8 extremities by the last follow-up visit. Pain as a symptom was resolved in all cases. There were no iatrogenic foot drop injuries. The average follow up was 32.2 months. Neuromonitoring during PFO excision demonstrated a high number of alerts, all of which resolved following timely corrective action. The use of neuromonitoring may help decrease the risk of iatrogenic postoperative neurological deficits following fibular osteochondroma surgery. Level IV.


Comparison of the risk factors for pre-term delivery and intrauterine growth retardation.
In a follow-up study of the pregnant women interviewed in the Nutrition Canada survey, we investigated predictors of intrauterine growth retardation (less than or equal to 10th percentile of the birthweight-gestational age distribution for the 1972 Canadian population), and pre-term delivery (less than 37 completed weeks of gestation), by classifying these two endpoints as either small-for-gestational age and not pre-term (SGA-NPT), or not small-for-gestational age but pre-term (NSGA-PT). Education, age, household income level, number of previous livebirths, number of cigarettes smoked per day while pregnant, alcohol consumption (spirits only), serum Vitamin C and haemoglobin levels, pre-pregnancy weight, height, and sex of the infant were related to NSGA-PT deliveries in univariate analyses; serum Vitamin A, smoking history, calorie intake, height and pre-pregnancy weight were similarly associated with the risk of SGA-NPT outcomes. When considered jointly in multivariate logistic regression analysis, however, the significant predictors were reduced to: height and pre-pregnancy weight for SGA-NPT and mother's education, sex of the infant, and household income level for NSGA-PT.


Intravascular large B-cell lymphoma presenting with reticular telangiectasia on the trunk and panhypopituitarism: an autopsy case.
A 75-year-old woman developed redness and swelling on her truncal skin, spreading from the lower abdomen to left thigh, 2 months before being admitted to our hospital. She was urgently hospitalised because of her worsening respiratory condition. On admission, she had reticular telangiectasia, diffuse skin induration on the lower abdomen and panhypopituitarism. She was diagnosed with intravascular large B-cell lymphoma (IVLBCL) by the third random abdominal skin biopsy. After histopathological examination at autopsy, we made a final diagnosis of IVLBCL causing respiratory failure and panhypopituitarism. This is the rare case of IVLBCL-induced panhypopituitarism showing visible skin lesions.


Extracorporeal membrane oxygenation with double venous drainage.
We report on a successful configuration strategy of extracorporeal membrane oxygenation(ECMO) in two consecutive cases of acute lung injury. A 60-year-old woman with Streptococcus pneumoniae infection and a 22-year-old man with hemothorax were admitted to our hospital with failing lungs. Although treatment with a ventilator was started, oxygenation could not be maintained. ECMO with a femoro-femoral circuit was performed, which showed a slight improvement in oxygenation. However, not enough oxygen support was provided. To minimize the venous mixture at the right atrium, we added venous drainage from the right jugular vein which resulted in better oxygenation and patient survival.


Diffuse alveolar hemorrhage due to ketorolac tromethamine.
Drug-induced lung disease (DILD) is a common but frequently missed diagnosis. Therefore, a high index of clinical suspicion and familiarity with the clinical syndromes associated with DILD are important in making the diagnosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the mostly commonly used classes of medications. NSAIDs are safe when used at prescribed doses. Side effects from use of NSAIDs are not uncommon and can affect almost every organ system in the body. NSAIDs are notorious for causing pulmonary toxicity, the common ones being bronchospasm and hypersensitivity reactions. Diffuse alveolar hemorrhage (DAH) secondary to NSAIDs is uncommon. Here, we report a case of DAH secondary to the use of ketorolac tromethamine.


Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors.
We examined the progesterone receptor (PgR) gene in tissue from both primary human breast tumors and normal placentas, detecting restriction fragment length polymorphisms (RFLPs) with the restriction endonucleases Pst I/Sst I and HindIII. There was a general agreement of the Pst I and Sst I polymorphisms in any individual tumor, suggesting that they define two alleles in the human PgR locus, one being characterized by a deletion of about 300 base pairs with respect to the other. Both primary human breast tumor specimens (n = 36) and human term placentas (n = 48) displayed similar allele frequencies and typical mendelian distribution of these Pst I/Sst I alleles. The previously reported HindIII PgR RFLP was also investigated in 132 breast tumors. The HindIII PgR gene RFLP did not display typical mendelian distribution in the breast tumors; the factors affecting the HindIII allele frequencies are presently unknown. Neither the HindIII RFLP nor the deletion defined by Pst I and Sst I correlated with PgR expression as determined by a ligand-binding assay, suggesting that neither is related to the heterogeneity of PgR expression seen in breast tumors.


Creatine monohydrate supplemented in swine finishing diets and fresh pork quality: III. Evaluating the cumulative effect of creatine monohydrate and alpha-lipoic acid.
The objective of this study was to evaluate short-duration supplementation of alpha-lipoic acid (ALA) and creatine monohydrate (CMH) to improve fresh pork quality. Forty-eight commercial hybrid barrows were blocked by BW and randomly allotted to one of four treatments: 1) no CMH or ALA; 2) supplementation of 24 g of CMH(-1) x pig(-1) x d(-1); 3) supplementation of 600 mg ALA(-1) x pig(-1) x d(-1); or 4) combined CMH and ALA supplements. Twelve pigs per treatment were individually penned with ad libitum access to water and a finishing diet. Treatments were hand-fed to individual pigs daily (divided into three equal doses) for 5 d before slaughter at 113 kg BW in two separate groups of 24 pigs each. Intramuscular pH was recorded at 45 min postmortem and again at 24 h in the ham semimembranosus (SM) and the longissimus muscle (LM) between the 10th and 11th rib. A Meatcheck (SFK Technology, Peosta, IA) conductivity probe was inserted in the same anatomical locations as pH measurement, providing an index value (PY) from 0 to 100 (a higher index value indicates more intact muscle cells and higher water-holding capacity). Color (L, a, b values) measurements were obtained at 24 h postmortem on the ham gluteus medius (GM), SM, and LM. Two 2.54-cm-thick loin chops were removed from the loin for determination of Warner-Bratzler shear force and glycolytic potential. The intact SM and the posterior portion of the boneless loin were vacuum-packaged and stored for 7 d to determine purge loss. Creatine-supplemented pigs had a higher (P = 0.03) PY value in the SM (66.67) at 45 min postmortem than either ALA, singularly (63.50), or in the combined CMH/ALA (62.27) treatments. (A higher PY index indicates superior water-holding capacity.) Lipoic acid supplementation resulted in the highest pH at 45 min (P = 0.029). These results justify further evaluation of the potential positive influence of supplementing alpha-lipoic acid to improve pork quality.


N1-dansyl-spermine and N1-(n-octanesulfonyl)-spermine, novel glutamate receptor antagonists: block and permeation of N-methyl-D-aspartate receptors.
The effects of several N-sulfonyl-polyamines, including N1-dansyl-spermine (N1-DnsSpm) and N1-(n-octanesulfonyl)-spermine (N1-OsSpm), were studied at recombinant N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus laevis oocytes. N1-DnsSpm and N1-OsSpm inhibited NMDA receptors and were approximately 1000-fold more potent than spermine in oocytes voltage-clamped at -70 mV. Block by N1-DnsSpm and N1-OsSpm was strongly voltage dependent, being more pronounced at hyperpolarized membrane potentials. With the Woodhull model of voltage-dependent channel block, the values of Kd(0) were 779 microM, 882 microM, and 7.4 mM and those of z delta were 2.58, 2.57, and 1.07 for N1-DnsSpm, N1-OsSpm, and spermine, respectively. This suggests that an increase in the voltage dependence of block together with an increase in affinity contributes to the increased potencies of N1-DnsSpm and N1-OsSpm compared with spermine. Sensitivity to N1-DnsSpm was reduced by mutation NR1(N616Q) and was increased by mutations NR1(N616G) and NR2A(N615G). The NR1(N616G) and NR2A(N615G) mutations decreased the Kd(0) value of N1-DnsSpm without affecting z delta, whereas the NR1(N616Q) mutation reduced z delta. These mutations may alter the accessibility of part of the polyamine binding site within the channel pore or directly alter the properties of that site. Block by N1-DnsSpm (0.3 microM) was almost complete at -100 mV, and there was no relief of block at extreme negative membrane potentials (-100 to -200 mV) at wild-type NR1/NR2A channels. In contrast, block by N1-DnsSpm was partially relieved at extreme negative potentials at receptors containing NR1(N616G) or NR2A(N615G), suggesting that N1-DnsSpm can permeate these mutant channels but not wild-type NR1/NR2A channels. This is hypothesized to be due to an increase in the pore size of channels containing NR1(N616G) or NR2A(N615G), which allows passage of the bulky head group of N1-DnsSpm. In contrast to N1-DnsSpm, N1-OsSpm could easily permeate wild-type NR1/NR2A channels, presumably because the head group of N1-OsSpm can pass through the narrowest part of the channel pore. N-Sulfonyl-polyamines such as N1-DnsSpm and N1-OsSpm represent a new class of polyamine antagonists with which to study glutamate receptor ion channels.


Betacellulin overexpression in the mouse ovary leads to MAPK3/MAPK1 hyperactivation and reduces litter size by impairing fertilization.
The epidermal growth factor receptor (EGFR) and its ligands are emerging as key molecules in regulating female reproduction. Here, we used a transgenic mouse model to evaluate whether and at which level of the reproduction cascade higher-than-normal levels of the EGFR ligand betacellulin (BTC) in the reproductive organs affect fertility. Western blots and immunohistochemistry revealed increased BTC levels in uterus and ovaries from transgenic females, particularly evident in granulosa cells of antral follicles. Onset of puberty, estrous cyclicity, and the anatomy and histology of reproductive organs at puberty were not altered as compared to control females. Fertility tests revealed a reduction (~50%) in litter size as the major reproductive deficit of transgenic females. Embryo implantation was delayed in transgenic females, but this was not the reason for the reduced litter size. Transgenic females produced a normal number of oocytes after natural ovulation. The in vivo fertilization rate was significantly reduced in untreated transgenic females but returned to normal levels after superovulation. Impaired oocyte fertilization in the absence of superovulation treatment was associated with MAPK3/MAPK1 hyperactivation in BTC transgenic ovaries, whereas similar levels of MAPK3/MAPK1 activation were detected in transgenic and control ovaries after superovulation treatment. Thus, tight regulation of MAPK3/MAPK1 activity appears to be essential for appropriate granulosa cell function during oocyte maturation. Our study identified hitherto unknown effects of BTC overabundance in reproduction and suggests BTC as a novel candidate protein for the modulation of fertility.


[Family members in the intensive care unit: effects and mastering the situation. A review of qualitative studies].
Having a family member in the intensive care unit is a very stressful and demanding situation for the whole family. The aim of this study is to explore how family members are affected by critical illness and how they deal with this situation. A literature review with focus on qualitative studies was carried out to get a deeper insight and understanding of families who have a relative in intensive care unit. 15 qualitative studies have been analysed. For family members the situation is characterised by uncertainty, overwhelming feelings, as well additional responsibilities, and diverging family roles. Family members always put their ill relative in first place, and they do not articulate needs for themselves. They cope with this burdening situation by trying to be near to their relative, with or without being integrated into care. They search for honest information, get social support from significant others, and try to keep realistic hope all the time. The article also shows boundaries in this field of research, and discusses transferability and limitations of the findings.


Formation of polar cytoplasmic domains (teloplasms) in the leech egg is a three-step segregation process.
Segregation and proliferation of mitochondria, leading to formation of the teloplasms (pole plasms), were studied in eggs of the leech T. rude by immunocytochemistry, fluorescent time lapse video imaging, confocal and electron microscopy. The translocation of mitochondria was analyzed after loading the egg with either Rhodamine 123 or a Mitotracker. Mitochondrial proliferation was assessed after pulse labeling with BrdU. The involvement of the cytoskeleton in the segregation process was determined by drug action. The teloplasms form during the first interphase as consequence of a 3-step sequential process of mitochondrial redistribution throughout the egg cytoplasm. The first step is a microtubule dependent process of ectoplasm thickening due to centrifugal mitochondrial transportation from the neighboring endoplasm. During the second step mitochondria move in the plane of the ectoplasm to become concentrated at the wall of rings (polar rings) and bands of contraction. This process appears to mostly depend on actin. The furrowing pattern of the egg during this step can be modified by cold treatment and seems to be determined during oogenesis. During the third step the ectoplasm flows to either of the poles in conjunction with bipolar displacement of the polar rings and shortening of the contraction bands. This step depends on both microtubules and microfilaments. Mitochondria of first interphase eggs have three special features: (1) they move in clusters, (2) their movement depends on both microtubules and microfilaments and (3) they proliferate continuously. During the first interphase the polarized meiotic egg becomes a bipolar cell.


Joint Attention and Vocabulary Development: A Critical Look.
Joint attention - parents' and children's coordinated attention to each other and to a third object or event - is believed to play a causal and critical role in early word learning. However, joint attention, as conventionally defined and measured, relies only on overt indicators of attention, is studied predominantly in the visual modality, and varies by culture. Moreover, word learning can occur without joint attention in typical development, in autistic development, and in Williams syndrome, and joint attention can occur without commensurate word learning in Down syndrome. Thus, the assumption that joint attention is a necessary and sufficient precursor to vocabulary learning is not universally supported.


Noninvasive assessment of fetal pulmonary blood flow in experimental pulmonary hypertension in the fetal lamb.
The aim of this study was to assess pulmonary arterial blood flow changes induced by the creation of a systemic arteriovenous fistula (120 d gestation) in the fetal lamb using Doppler technique. Doppler echocardiographic assessment of the pulmonary artery blood flow performed 1, 6, and 14 d after surgery showed that mean pulmonary arterial blood flow in the left or right pulmonary artery was 224 +/- 58 mL/min at day 1 in the fistula group, significantly higher than in the control group (113 +/- 22 mL/min; p < 0.01, ANOVA test) whether no difference was found at days 6 and 14. The mean inner diameter of the left pulmonary artery measured on postmortem lung arteriograms compared favorably to the one measured on day 14 at the same level on ultrasound. The mean left pulmonary arterial blood flow, measured at birth on day 14 after surgery, using ultrasonic flow transducer, was not statistically different from the one measured by Doppler on day 14. Our data demonstrate that echocardiography allows accurate assessment of pulmonary arterial blood flow in utero, providing evidence suggesting transient high pulmonary blood flow that did not last >6 d after the creation of a systemic fistula.


ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens.
Atypical antipsychotic drugs (APDs) such as clozapine, olanzapine, quetiapine, risperidone, and ziprasidone are serotonin (5-HT)(2A) antagonists and relatively weaker dopamine (DA) D(2) antagonists, with variable 5-HT(2C) antagonist properties. The ability of atypical APDs to preferentially increase DA release in the cortex compared to the limbic system is believed to be due in part to their antagonism of 5-HT(2A) and D(2) receptors and believed to contribute to their beneficial effects on cognition, negative, and psychotic symptoms. Previous studies from this laboratory using microdialysis have shown that pretreatment of the 5-HT(2A) antagonist M100907 with the typical APD and D(2) antagonist haloperidol produced an increase in the medial prefrontal cortex (mPFC), but not in the nucleus accumbens (NAC), DA release. However, pretreatment with the 5-HT(2A/2C) receptor antagonist SR46349-B with haloperidol increased both mPFC and NAC DA release, suggesting that both 5-HT(2A) and 5-HT(2C) properties may be important for atypical APD effects. The purpose of this study was to examine the effects of a novel putative atypical APD ACP-103 on mPFC and NAC DA release using in vivo microdialysis in freely moving rats that are awake. ACP-103 is an inverse agonist at both 5-HT(2A) and 5-HT(2C) receptors and has intermediate affinities for 5-HT(2C) receptors relative to their affinities for 5-HT(2A) receptors compared to M100907 and SR46349-B. In addition, the effects of ACP-103 were compared to M100907 and SR46349-B, and ACP-103 was also coadministered with haloperidol. ACP-103 10.0 mg/kg, but not 3.0 mg/kg, increased DA release in the mPFC, while neither dose increased DA release in the NAC. Like M100907, ACP-103 (3.0 mg/kg) potentiated 0.1 mg/kg haloperidol-induced DA release in the mPFC while inhibiting that in the NAC. However, ACP-103 (3.0 mg/kg), similar to SR46349-B, potentiated a high dose of haloperidol (1.0 mg/kg)-induced DA release in both regions. The potent 5-HT(2C) antagonist SB242084 1.0 mg/kg significantly potentiated 0.1 mg/kg haloperidol-induced DA release in both the mPFC and NAC. However, SB242084, at 0.2 mg/kg, significantly potentiated DA release only in the NAC. Moreover, SB242084 0.2 mg/kg potentiated DA release in the NAC produced by the combination treatment of 3 mg/kg ACP-103 and 0.1 mg/kg haloperidol. These data suggest that the relative extent of 5-HT(2A) and 5-HT(2C) antagonism, as well as the extent of D(2) receptor blockade, has a critical influence on DA release in the mPFC and NAC and may be a determining factor in the action of this class of atypical APDs on these two potentially clinically relevant parameters.


The Role of Ribonucleases and sRNAs in the Virulence of Foodborne Pathogens.
Contaminated food is the source of many severe infections in humans. Recent advances in food science have discovered new foodborne pathogens and progressed in characterizing their biology, life cycle, and infection processes. All this knowledge has been contributing to prevent food contamination, and to develop new therapeutics to treat the infections caused by these pathogens. RNA metabolism is a crucial biological process and has an enormous potential to offer new strategies to fight foodborne pathogens. In this review, we will summarize what is known about the role of bacterial ribonucleases and sRNAs in the virulence of several foodborne pathogens and how can we use that knowledge to prevent infection.