Analysis of Patient-Dependent and Trauma-Dependent Risk Factors for Persistent Brachial Plexus Injury after Shoulder Dislocation.
Brachial plexus injuries (BPIs) caused by shoulder dislocation usually have a transient character and tend to resolve spontaneously. However, in some patients the symptoms can persist and require operative intervention. This work aims to determine the risk factors for persistent BPIs resulting from shoulder dislocation. The study comprised 73 patients (58 men, 15 women; mean age: 50 years) treated operatively between the years 2000 and 2016 for persistent BPIs resulting from shoulder dislocation. Patient age, gender, type of initial trauma, number of affected nerves, presence of accompanying injuries, and time interval from dislocation to its reduction were analysed. Elderly patients more often sustained multiple-nerve injuries, while single nerve injuries were more often observed in younger patients. Injury to a single nerve was diagnosed in 30% of the patients. Axillary nerve was most commonly affected. Fracture of the greater tuberosity of humerus coincided with total BPI in 50% of the cases. Longer unreduced period caused injury to multiple nerves. Analysis of our patient group against relevant literature revealed that persistent BPI after shoulder dislocation is more common in older patients. Injuries to ulnar and median nerves more often require operative intervention due to low potential for spontaneous recovery of these nerves.


Schistosoma mansoni: maturation rate and drug susceptibility of different geographic isolates.
The fecundities and drug susceptibilities of Schistosoma mansoni isolates from Senegal, Puerto Rico, and Kenya have been examined in mice. The Senegal parasite, obtained from the field in 1993, was shown to have a longer prepatent period (eggs first recovered in the faeces on Day 46 after infection) than those of two isolates, from Puerto Rico and Kenya, that had been maintained for a long period in the laboratory (faecal eggs recovered on Days 38 and 36 after infection, respectively). A Kenyan isolate, also collected from the field in 1994, was shown to mature more slowly than the laboratory-maintained Kenyan isolate. Tissue egg counts confirmed that early in infection the fecundity of the recently collected isolates from Senegal and Kenya was significantly lower than that of the long-term laboratory-maintained Kenyan isolate. Praziquantel and oxamniquine treatment of 8-week-old infections caused a significant (P < 0.001) reduction in worm burden in all isolates tested. However, the reduction in worm burden after praziquantel treatment of infections of the Senegal isolate (50% reduction) was significantly lower than the > 90% reductions in worm burdens after praziquantel treatment of mice infected with either of the Kenyan isolates (P < 0.001). The study confirms that despite being tolerant to praziquantel, the Senegal isolate is fully susceptible to oxamniquine. The praziquantel tolerance of the Senegal parasite is not solely attributed to the state of maturation of the parasite at the time of drug administration.


Inflammatory pseudotumour of liver--a case report.
A rare case of inflammatory pseudotumour of liver in a child is reported. The child presented with obstructive jaundice and was considered to have malignant tumour of liver clinically and by imaging modalities. Resection of left hepatic lobe with the mass was done. Histologically, the lesion consisted of an admixture of proliferation of lymphocytes, plasma cells and fibroblasts along with vasculitis and variable amount of hyaline fibrosis. Adjacent liver showed evidence of biliary cirrhosis and multiple microabscesses. Many of the previously reported cases were also diagnosed clinically and radiologically to be malignant tumours of liver. The case is reported to create awareness of this rare entity.


Relearning of locomotion in injured spinal cord: new directions for rehabilitation programs.
Locomotor activity-based rehabilitation programs seem to bring encouraging recovery to incomplete spinal cord injury paralytics. But in "complete" injuries recovery is long delayed and in small increments. Developmental and computer neural networks studies show that motor relearning requires the participation of redundant numbers of and activity-dependent competition of synapses among spinal interneurons. The present programs do not meet this prerequisite. They focus mainly on the mechanical (retraining) part while the neural (relearning) part plays a rather passive role. Here we suggest how retraining can be integrated with relearning by inductive lability procedures (Krishnan, 2003a, 2003b) with the objective of enhancing and hastening recovery.


Dermatological adverse reactions during anti-TNF treatments: focus on inflammatory bowel disease.
The clinical introduction of tumour necrosis factor (TNF) inhibitors has deeply changed the treatment of inflammatory bowel diseases (IBD). It has demonstrated impressive efficacy as compared to alternative treatments, allowing for the chance to achieve near-remission and long-term improvement in function and quality of life and to alter the natural history of Crohn's disease (CD) and ulcerative colitis (UC). As a consequence of longer follow-up periods the number of side effects which may be attributed to treatment with biologics is growing significantly. Cutaneous reactions are among the most common adverse reactions. These complications include injection site reactions, cutaneous infections, immune-mediated complications such as psoriasis and lupus-like syndrome and rarely skin cancers. We review the recent literature and draw attention to dermatological side effects of anti-TNF therapy of inflammatory bowel disease.


Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia.
Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants <32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants <28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD <28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.


Effects of prenatal maternal stress on the pituitary adrenocortical reactivity in guinea-pig pups.
Seven days before term, pregnant guinea-pigs were subjected to a psychosomatic stress. Adrenocorticotrophin (ACTH), cortisol and aldosterone concentrations increased in maternal and fetal plasma immediately after stress. In the offspring born from prenatally-stressed mothers that were resubjected to stress, the increases in plasma ACTH and cortisol level were lower than in the control offspring. Plasma aldosterone levels increased after stress in 12 days-old pups but did not change neither in 50 days-old animals nor in 12 days-old guinea-pigs born of prenatally stressed mothers. Thus prenatal stress of mother resulted in lowered response of pituitary-adrenocortical axis of offspring subjected to stress.


Preparation of monoclonal antibody against celangulin V and immunolocalization of receptor in the oriental armyworm, Mythimna separata walker (Lepidoptera: Noctuidae).
The botanical insecticide celangulin V (CA-V) is an insect digestive poison acting on midgut tissue of the target insect larvae. With the aim of localizing the receptor enacted by CA-V, monoclonal antibodies (MAbs) specific to the compound were developed. A hapten was synthesized by introducing a succinoyl into the CA-V structure and conjugated with three carrier proteins. From mice immunized with one conjugate, three MAbs were obtained with a potential capacity of detecting protein-bound residue forms of CA-V in the biological tissues. The oriental armyworm larvae ingested CA-V were examined by the technique of immuno-electron-microscopy (IEM) using the anti-CA-V MAb as the primary antibody and goat anti-mouse/IgG labeled with colloidal gold as the secondary antibody. Electron micrographs of the armyworm midgut tissues showed that the CA-V was associated with the midgut epithelia of the insects. These results demonstrated the existence of a receptor enacted by CA-V on the midgut cells of the oriental armyworm larvae.


In vitro assessment of long-term reliability of low-cost μECoG arrays.
Micro-electrocorticographic (μECοG) electrode arrays provide a minimally invasive, high-resolution neural interface with broad cortical coverage. Previously, we fabricated μECoG arrays at a lower cost than commercially available devices using low-cost industrial processes [1], [2]. Here, we report the in vitro electrical performance of five μECoG designs undergoing an accelerated aging protocol. The impedance and yield of the μECoG arrays were tracked over time. The equivalent lifetime at 37°C depended on the manufacturer and material stack-up, and ranged between 30 and greater than 760 days (ongoing). The main failure modes of these devices were delamination at the site of the electrode contact and broken traces due to metal dissolution. Based on these in vitro results, we offer several recommendations for μECoG designs suitable for chronic implantation.


HSV: The scout and assault for digestive system tumors.
More than 25% of all malignant tumors are digestive system tumors (DSTs), which mostly include esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, gallbladder cancer and cholangiocarcinoma, and colorectal cancer. DSTs have emerged as one of the prominent reasons of morbidity and death in many nations and areas around the world, posing a serious threat to human life and health. General treatments such as radiotherapy, chemotherapy, and surgical resection can poorly cure the patients and have a bad prognosis. A type of immunotherapy known as oncolytic virus therapy, have recently shown extraordinary anti-tumor effectiveness. One of the viruses that has been the subject of the greatest research in this field, the herpes simplex virus (HSV), has shown excellent potential in DSTs. With a discussion of HSV-1 based on recent studies, we outline the therapeutic effects of HSV on a number of DSTs in this review. Additionally, the critical function of HSV in the detection of cancers is discussed, and some HSV future possibilities are shown.


Octreotide-induced bradycardia.
Because of deleterious hemodynamic effects of octreotide in a nonacromegalic patient with a pancreatic fistula, we conducted a MEDLINE search of English-language journal articles to extract information on this complication of octreotide or somatostatin therapy. Few data are available regarding patients with disease states other than acromegaly. We believe octreotide should be considered when determining the cause of bradycardia.


Unveiling the Reduction Mechanism of Pu(IV) by Acetaldoxime.
The separation of plutonium (Pu) from spent nuclear fuel was achieved by effectively adjusting the oxidation state of Pu from +IV to +III in the plutonium uranium reduction extraction (PUREX) process. Acetaldoxime (CH3CHNOH) as a free salt reductant can rapidly reduce Pu(IV), but the reduction mechanism remains indistinct. Herein, we explore the reduction mechanism of two Pu(IV) ions by one CH3CHNOH molecule, where the second Pu(IV) reduction is the rate-determining step with the energy barrier of 19.24 kcal mol-1, which is in line with the experimental activation energy (20.95 ± 2.34 kcal mol-1). Additionally, the results of structure and spin density analyses demonstrate that the first and second Pu(IV) reduction is attributed to hydrogen atom transfer and hydroxyl ligand transfer, respectively. Analysis of localized molecular orbitals unveils that the reduction process is accompanied by the breaking of the Pu-OOH bond and the formation of the OOH-H and C-OOH bonds. The reaction energies confirm that the reduction of Pu(IV) by acetaldoxime is both thermodynamically and kinetically accessible. In this work, we elucidate the reduction mechanism of Pu(IV) with CH3CHNOH, which provides a theoretical understanding of the rapid reduction of Pu(IV).


Volume and shape analysis of the Hippocampus and amygdala in veterans with traumatic brain injury and posttraumatic stress disorder.
There is a need to improve the understanding of the neurobiological underpinnings of traumatic brain injury (TBI). Individuals with TBI experience comorbidities such as posttraumatic stress disorder (PTSD) with considerable symptom overlap including depression and hyperarousal, confounding the ability to identify specific TBI-related brain changes. The aims of the current study were to investigate hippocampal and amygdalar volumes in Veterans with TBI with (TBI + PTSD, n = 32) and without (TBI - PTSD, n = 25) PTSD. Shape analysis was employed to reveal any relationship between the hippocampus and depressive symptoms in TBI subgroups. 32 TBI + PTSD, 25 TBI - PTSD, and 25 age-matched healthy male Veterans underwent an MRI scan on a 3 Tesla scanner and a clinical evaluation. The TBI + PTSD and the TBI + hyperarousal (met criteria for the hyperarousal symptom cluster, regardless of PTSD diagnosis) subgroup had trend-level larger left amygdalar volume than the TBI - PTSD subgroup and the TBI - hyperarousal subgroup, respectively. However, there was no significant difference between the TBI group as a whole and healthy controls (HC). There was a significant negative correlation between the Hamilton Rating Scale for Depression score (HAM-D) and left hippocampal volume and a positive correlation between the HAM-D score and left amygdalar volume in the TBI group. Left hippocampal volume was correlated with the HAM-D score only in the TBI + PTSD and not in TBI - PTSD subgroup. Shape analyses revealed a significant correlation between the HAM-D score and the CA1 and subiculum regions of the left hippocampus. Our results suggest that the amygdala may be a neuroanatomical correlate in mediating PTSD-like symptoms in Veterans with TBI. The results of shape analysis suggest that alterations in the CA1 and subiculum subregions of hippocampus may have a role in depression and PTSD.


Pharmacological characterization of 1-aminoindan-1,5-dicarboxylic acid, a potent mGluR1 antagonist.
We examined the pharmacological profile of 1-aminoindan-1,5-dicarboxylic acid (AIDA), a rigid (carboxyphenyl)glycine derivative acting on metabotropic glutamate receptors (mGluRs). In cells transfected with mGluR1a, AIDA competitively antagonized the stimulatory responses of glutamate and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] on phosphoinositide hydrolysis (pA2 = 4.21). In cells transfected with mGluR5a, AIDA displayed a much weaker antagonist effect. In transfected cells expressing mGluR2, AIDA (< or = 1 mM) did not affect the inhibition of forskolin-stimulated adenylate cyclase activity induced by (1S,3R)-ACPD, but at large concentrations, it displayed a modest agonist activity. In rat hippocampal or striatal slices, AIDA (0.1-1 mM) reduced the effects of (1S,3R)-ACPD on phospholipase C but not on adenylate cyclase responses, whereas (+)-alpha-methyl-4-carboxyphenylglycine (0.3-1 mM) was an antagonist on both transduction systems. In addition, AIDA (0.3-1 mM) had no effect on mGluRs coupled to phospholipase D, whereas (+)-alpha-methyl-4-carboxy-phenylglycine (0.5-1 mM) acted as an agonist with low intrinsic activity. In rat cortical slices, AIDA antagonized the stimulatory (mGluR1-mediated) effect of (1S,3R)-ACPD on the depolarization-induced outflow of D-[3H]aspartate, disclosing an inhibitory effect ascribable to (1S,3R)-ACPD activating mGluR2 and/or mGluR4. Finally, mice treated with AIDA (0.1-10 nmol i.c.v.) had an increased pain threshold and difficulties in initiating a normal ambulatory behavior. Taken together, these data suggest that AIDA is a potent, selective and competitive mGluR1 a antagonist.


Diagnostic value of certain mastitis markers in following up the clinical and bacteriological changes in pharmacotherapeutic studies.
Trends of certain mastitis markers were studied in udder quarters (n = 201) showing clinical symptoms of acute mastitis. Besides the clinical examination, before the first treatment (baseline sample), and about 3 weeks later, 17 to 24 days following the last treatment (control sample) milk samples were collected for bacteriological identification of the mastitis pathogens and for the determination of certain inflammatory markers: somatic cell count (SCC), N-acetyl-beta-D-glucosaminidase (NAGase) and alpha 1-antitrypsin (ATR) activities, as well as bovine serum albumin (BSA) and chloride (Cl-) concentrations. Based upon the clinical and bacteriological status as well as the SCC recorded at the control investigations, 6 groups were established (recovered, latently infected, subclinical mastitis: bacteriologically positive and negative, as well as clinical mastitis: bacteriologically positive and negative). As compared to the baseline samples, all parameters decreased in the case of recovered udder quarters, as well as in those with abated latent infection or subclinical mastitis at the time of control examination. Comparing the control samples of the different categories, characteristic differences were found in NAGase activity, indicating the grade of cytodamaging effect of mastitis. Of the other markers, ATR and Cl- proved to be more adequate for the differentiation than BSA. It can be concluded that, in addition to SCC, first of all NAGase can be recommended for use as an inflammatory parameter in pharmacodynamic studies. Besides these two parameters, ATR and Cl- can also be chosen as a possible third marker.


Breastfeeding promotion and protection in the Czech Republic.
The purpose of the article is to present the National Breastfeeding Promotion Programme in the Czech Republic in the course of the last decade. It summarizes the main strategies, education and training activities of the National Breastfeeding Committee, its collaboration with the Government, Parliament, IBFAN and UNICEF. The article reviews the relevant studies on infant feeding which illustrate the increase of the prevalence of breastfeeding in the course of the 1990's and reflect the effect of the programme. Recent negotiations with the Ministry of Health have outlined the implementation of the WHO global strategy for infant and young child feeding in the Czech Republic.


Lessons from experiences of accessing healthcare during the pandemic for remobilizing rheumatology services: a national mixed methods study.
To understand the impact of the coronavirus disease 2019 pandemic on access to healthcare services for patients with inflammatory and non-inflammatory musculoskeletal (MSK) conditions. Three established cohorts that included individuals with axial SpA, psoriatic arthritis and MSK pain completed a questionnaire between July and December 2020. In parallel, a subset of individuals participated in semistructured interviews. A total of 1054 people (45% female, median age 59 years) were included in the quantitative analyses. Qualitative data included 447 free-text questionnaire responses and 23 interviews. A total of 57% of respondents had tried to access care since the start of the UK national lockdown. More than a quarter reported being unable to book any type of healthcare appointment. General practice appointments were less likely to be delayed or cancelled compared with hospital appointments. Younger age, unemployment/health-related retirement, DMARD therapy, anxiety or depression and being extremely clinically vulnerable were associated with a greater likelihood of attempting to access healthcare. People not in work, those reporting anxiety or depression and poorer quality of life were less likely to be satisfied with remotely delivered healthcare. Participants valued clear, timely and transparent care pathways across primary care and specialist services. While remote consultations were convenient for some, in-person appointments enabled physical assessment and facilitated the development and maintenance of clinical relationships with care providers. We identified patient factors that predict access to and satisfaction with care and aspects of care that patients value. This is important to inform remobilisation of rheumatology services to better meet the needs of patients.


A morphometric study of the middle and lower cervical vertebral endplates and their components.
Cervical disc arthroplasty is a common method of treating cervical degenerative disease. However, the footprints of most prosthesis dimensions are obtained from data of Caucasian individuals. Besides, there is a large discrepancy between footprints of currently available cervical disc prostheses and anatomic dimensions of cervical endplates. We aimed to detail the three-dimensional (3D) anatomic morphology of the subaxial cervical vertebral endplate, utilizing high-precision, high-resolution scanning equipment, and provide a theoretical basis for designing appropriate disc prostheses for Chinese patients.A total of 138 cervical vertebral endplates were studied. Each endplate was digitized using a non-contact optical 3D range scanning system and then reconstructed to quantify diameters and surface area for the whole endplate and its components (central endplate and epiphyseal rim). The whole endplate and mid-plane concavity depth were measured.There is marked morphologic asymmetry, in that the cranial endplate is more concave than the corresponding caudal endplate, with endplate concavity depths of 2.04 and 0.69 mm, respectively. For the caudal endplates, the endplate concavity apex locations were always located in the posterior portion (81.42%), while in cranial endplates relatively even. The central endplate was approximately 60% of the area of the whole endplate and the anterior section of the ring was the widest. From C3/4 down to C6/7 discs, the vertebral endplate gradually became more elliptical. Chinese cervical endplate anatomic sizes are generally smaller than that of Caucasians. Although Korean and Chinese individuals both belong to the Asian population subgroup, the majority of anatomic dimensions differ. Singaporean cervical endplate morphology is very similar to that of Chinese patients.We performed a comprehensive and accurate quantitative description of the cervical endplate, which provide references to shape and profile an artificial cervical disc without sacrificing valuable bone stock. To design a device with footprint as large as possible to distribute the axial load, we suggest that additional attention should be paid to the marginal rim. It is essential to specifically design appropriate disc prosthesis for Chinese patients. To fit the morphologic and biomechanical variations, we also propose that the disc prostheses for different vertebral segments should be separately designed.


Retroviral-mediated expression of telomerase in normal human cells provides a selective growth advantage.
Retroviral infection of hTERT, the catalytic component of telomerase, into BJ fibroblasts (population doubling 28) resulted in reconstitution of telomerase activity, telomere maintenance, and extension of in vitro lifespan. The hTERT-infected cells also exhibited increased growth rate and colony forming efficiency relative to controls, while remaining contact-inhibited and maintaining a p53-mediated damage response following gamma-irradiation. All single cell-derived BJ-hTERT clones grew faster than the hTERT mass cultures and maintained telomeres; however, neither telomerase activity levels nor mean telomere length correlated with the growth rate. Introduction of hTERT rescued aged BJ fibroblasts from senescence via a telomere-dependent mechanism and provided renewed proliferative potential. Collectively, our data indicate that both early and late in the cellular lifespan of human cells, ectopic expression of telomerase using a retroviral system provides a growth advantage while maintaining normal cellular characteristics.


A multicenter, phase III trial of hemocoagulase Agkistrodon: hemostasis, coagulation, and safety in patients undergoing abdominal surgery.
Hemocoagulase Agkistrodon for injection is a single component thrombin which has passed phases I and II clinical trials. The purpose of this phase III clinical trial was to evaluate the effect of Hemocoagulase Agkistrodon on hemostasis and coagulation in abdominal skin and subcutaneous incisions and to assess the safety of this agent in surgical patients. This is a phase III, prospective, randomized, double-blind, and controlled multicenter clinical trial including 432 consecutive patients randomized into either a study group (injected with hemocoagulase Agkistrodon at 2 U, n = 324) or a control group (injected with hemocoagulase Atrox, n = 108). The hemostatic time, hemorrhagic volume, hemorrhagic volume per unit area, blood coagulation, and adverse events were measured and compared between the two groups. The mean hemostatic time in the study group was (36.8 +/- 18.7) seconds; the hemorrhagic volume was (3.77 +/- 3.93) g; and the hemorrhagic volume per unit area was (0.091 +/- 0.125) g/cm(2). In the control group, the corresponding values were (38.1 +/- 19.7) seconds, (4.00 +/- 4.75) g, and (0.095 +/- 0.101) g/cm(2), respectively. No significant difference in values existed between the two groups (P > 0.05). Blood coagulation results and hepatic and renal function were also similar between the two groups. Adverse events were reported in two cases, but were deemed non-drug-related. Hemocoagulase Agkistrodon has good hemostatic and coagulative function and is safe for the use of arresting capillary hemorrhage that occurs while incising the abdomen during surgery.


Kinetic model for the regulation of redox reaction in steroid transformation by Arthrobacter globiformis cells.
A kinetic model of hydrocortisone transformation was developed in studies of the kinetics of biochemical systems. The regulatory bases of the model are the biosynthesis of steroid-transforming enzymes and their activity, the level of endogenous substrates, the respiratory chain activity, and the initial concentrations of reagents. When compared, the experimental data completely coincide with the results of the computer modeling, the coincidence being not only qualitative but also quantitative. It indicates that the model suggested can be used for further studies of other transformations of steroid compounds, as well as for transformation of steroid compounds under close-to-biotechnological conditions. The results obtained by means of this model permit one to trace in dynamics the behavior of a number of parameters characterizing the process which is very difficult or not feasible to do in a biochemical experiment. The following was shown: (1) the behavior of the respiratory chain (the reversible transition of its oxidized and reduced forms); (2) the change of the transmembrane potential of hydrogen ions within a far larger stretch of time than is feasible to register in a biochemical experiment; (3) the regulation of the activity of 20beta-hydroxysteroid dehydrogenase and 1, 2-reductase not only by the change in the level of endogenous substrates, but also by means of their biosynthesis; and (4) the regulatory role of 3-ketosteroid-1-en-dehydrogenase.


[Person and motivation: awarding system as a tool for managing health personnel].
Seeing that nurses are heading towards a new era of responsibility, it follows that it is essential to motivate professional nurses. To this end, one needs must consider the degree to which the assumption of responsibility is closely linked to motivation in one's work. The article suggests close thought on the importance of incentives, which may decisively contribute to both personnel management and organisational procedures. Incentives are a tool for personnel management because they represent a combination of inputs through which the administration seeks to increase the probability that, in this case, nurses behave, and thus act, appropriately to reach company aims, hereby avoiding actions deemed ineffective. Rewarding those who produce valid results favours a good working climate, both reinforcing and boosting the motivation and commitment to being good professionals. With this aim in mind, a questionnaire is suggested, to be given to 75 nurses in a University General Hospital in the Regione Lazio; the research objective is to examine themes, such as the participation, satisfaction and motivation of the nursing staff at work as well as the role that tools of incentive cover in the real professional context. Only by having recourse to a true scenario of the working milieu, can one understand the points of strength and weakness so as to make useful changes involving first the person and then the administration.


Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial.
To determine whether primary peritoneal drainage improves survival and outcome of extremely low birth weight (ELBW) infants with intestinal perforation. Optimal surgical management of ELBW infants with intestinal perforation is unknown. An international multicenter randomized controlled trial was performed between 2002 and 2006. Inclusion criteria were birthweight >or=1000 g and pneumoperitoneum on x-ray (necrotizing enterocolitis or isolated perforation). Patients were randomized to peritoneal drain or laparotomy, minimizing differences in weight, gestation, ventilation, inotropes, platelets, country, and on-site surgical facilities. Patients randomized to drain were allowed to have a delayed laparotomy after at least 12 hours of no clinical improvement. Sixty-nine patients were randomized (35 drain, 34 laparotomy); 1 subsequently withdrew consent. Six-month survival was 18/35 (51.4%) with a drain and 21/33 (63.6%) with laparotomy (P = 0.3; difference 12% 95% CI, -11, 34%). Cox regression analysis showed no significant difference between groups (hazard ratio for primary drain 1.6; P = 0.3; 95% CI, 0.7-3.4). Delayed laparotomy was performed in 26/35 (74%) patients after a median of 2.5 days (range, 0.4-21) and did not improve 6-month survival compared with primary laparotomy (relative risk of mortality 1.4; P = 0.4; 95% CI, 0.6-3.4). Drain was effective as a definitive treatment in only 4/35 (11%) surviving neonates, the rest either had a delayed laparotomy or died. Seventy-four percent of neonates treated with primary peritoneal drainage required delayed laparotomy. There were no significant differences in outcomes between the 2 randomization groups. Primary peritoneal drainage is ineffective as either a temporising measure or definitive treatment. If a drain is inserted, a timely "rescue" laparotomy should be considered. Trial registration number ISRCTN18282954; http://isrctn.org/


Use of the preparticipation physical examination form to screen for the female athlete triad in Canadian interuniversity sport universities.
The purpose of this study was to survey universities affiliated with Canadian Interuniversity Sport on existing screening protocols for the female athlete triad, and to identify any potential areas for improvement of this system. Surveys were faxed or e-mailed to Canadian Interuniversity Sport-affiliated universities in Canada, and preparticipation physical examination (PPE)/medical history forms from each institution were analyzed. The Fowler Kennedy Sports Medicine Clinic at the University of Western Ontario. In 2000, of the 48 universities, 35 responded (73.0% response rate). In 2002, 39 of 49 universities responded (79.6%). Although the majority of institutions surveyed implement a PPE form (80.0% in 2000, 87.2% in 2002), only 70.6% to 75.0% of these institutions actually conduct a follow-up when deemed necessary. However, the number of forms including a specific female section increased from 46.4% in 2000 to 61.8% in 2002. Also encouraging is the percentage of universities attempting to increase awareness of the triad disorders (33.3% in 2002 vs. 14.3% in 2000). It is interesting to note that in over half of the institutions surveyed both years, the athletic therapist or trainer is responsible for analyzing the completed PPE forms. This study has shown substantial improvement from 2000 to 2002 in the development of the PPE across Canada, even in a relatively short period of 2 years. However, this study also demonstrates the lack of uniformity within Canada of the PPE forms. There remains a need to improve the PPE form to target a section of the form specifically to female athletes, or else cases may be missed. The triad is also not found solely in sports where leanness is associated with better performance. Better efforts need to made to increase awareness of the triad and its risks among female athletes, as well as provide educational opportunities for athletic therapists, who are the first line of intervention in many cases. The key to successful prevention and intervention is education. This study demonstrates the need for education for all people directly involved with the athlete, and the need to work together to promote a healthy and realistic body image and increase awareness of the female athlete triad among athletes.


Ki-1 large cell anaplastic lymphoma--a clinicopathological study.
Ki-1 large cell anaplastic lymphoma is a recently described variant of malignant lymphoma. A retrospective study of 10 cases of Ki-1 lymphoma was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi to document its clinical and morphological features. The morphological features were evaluated by a study of paraffin embedded sections stained with haematoxylin and eosin stains. Immunohistochemical stains for BER-H2 and leucocyte common antigen (LCA) were performed in all cases. The age of the patients ranged from 2 to 60 years and male to female ratio was 2.3:1. Cervical lymphadenopathy was the most common presentation. Histologically, there was a complete effacement of the lymph node architecture in 8 cases. The Reed-Sternberg like cells were seen in 2 and histiocyte like cells in 7 cases. Immunohistochemically all cases were positive for BER-H2. It is suggested that the possibility of Ki-1 lymphoma should be considered in all cases of lymphoma with pleomorphic morphology.


Juvenile Hippocampal CA2 Region Expresses Aggrecan.
Perineuronal nets (PNNs) are distributed primarily around inhibitory interneurons in the hippocampus, such as parvalbumin-positive interneurons. PNNs are also present around excitatory neurons in some brain regions and prevent plasticity in these neurons. A recent study demonstrated that PNNs also exist around mouse hippocampal pyramidal cells, which are the principle type of excitatory neurons, in the CA2 subregion and modulate the excitability and plasticity of these neurons. However, the development of PNNs in the CA2 region during postnatal maturation was not fully investigated. This study found that a main component of PNNs, aggrecan, existed in the pyramidal cell layer of the putative CA2 subarea prior to the appearance of the CA2 region, which was defined by the CA2 marker protein regulator of G protein signaling 14 (RGS14). We also found that aggrecan immunoreactivity was more evident in the anterior sections of the CA2 area than the posterior sections, which suggests that the function of CA2 PNNs varies along the anterior-posterior axis.


Corymbulosins D-H, 2-Hydroxy- and 2-Oxo-clerodane Diterpenes from the Bark of Laetia corymbulosa.
A bioactive CH3OH-CH2Cl2 (1:1) extract of the bark of Laetia corymbulosa provided five new clerodane diterpenes with an isozuelanin skeleton, designated as corymbulosins D-H (1-5), as well as the known corymbulosins B (6) and C (7), for which the relative configurations were not previously determined. The structures of 1-5 were characterized on the basis of 1D and 2D NMR spectroscopic and HRMS analysis. The absolute configurations of all isolated compounds 1-7 were verified through chemical methods, including modified Mosher esterifications or oxidation of the hydroxy group at C-2, ECD experiments, and spectroscopic data comparison. The isolated compounds were evaluated for antiproliferative activity against a small panel of human cancer cell lines.


Relationship of increased levels of circulating intercellular adhesion molecule 1 after heart transplantation to rejection: human leukocyte antigen mismatch and survival.
Noninvasive methods to assess immune activation would be helpful in optimizing therapy after heart transplantation to reduce rejection (acute and chronic) and complications caused by excessive immunosuppressive therapy. Intercellular adhesion molecule 1 has been shown to play an important role in T-cell activation and allograft rejection. A soluble form of intercellular adhesion molecule 1 has been discovered to be circulating in plasma. To test the hypothesis that increased levels of circulating intercellular adhesion molecule 1 may have prognostic value as a marker of immune activation, we examined whether levels of circulating intercellular adhesion molecule 1 during the early postoperative period correlated with endomyocardial biopsy scores, soluble interleukin-2 receptor levels, human leukocyte antigen mismatch, and survival. For the first 3 weeks after surgery, serum was obtained once weekly on the same day as endomyocardial biopsy samples from 52 patients who survived more than 30 days after heart transplantation. A sandwich enzyme-linked immunosorbent assay was used to measure circulating intercellular adhesion molecule 1 and soluble interleukin-2 receptor. Increased circulating intercellular adhesion molecule 1 levels did not correlate with endomyocardial biopsy scores but were associated with greater mismatch at the human leukocyte antigen-B and -DR loci (p = 0.02). A significant correlation was found (p = 0.002) between circulating intercellular adhesion molecule 1 levels and soluble interleukin-2 receptor, albeit with a low r value of 0.27. Survival was reduced in patients with high levels of circulating intercellular adhesion molecule 1 (p = 0.006) or soluble interleukin-2 receptor (p = 0.001) with the greatest reduction in survival when both were elevated.(ABSTRACT TRUNCATED AT 250 WORDS)


Discrimination and the Health of African Americans: The Potential Importance of Intersectionalities.
Research examining associations between self-reported experiences of discrimination overall (e.g. potentially due to race, gender, socioeconomic status, age, etc…) and health -particularly among African-Americans - has grown rapidly over the past two decades. Yet recent findings suggest that self-reported experiences of racism alone may be less impactful for the health of African-Americans than previously hypothesized. Thus, an approach that captures a broader range of complexities in the study of discrimination and health among African-Americans may be warranted. This article presents an argument for the importance of examining intersectionalities in studies of discrimination and physical health in African-Americans, and provides an overview of research in this area.


[Neandertal DNA in Africans].
Sophisticated analyses of current human populations compared to a high-coverage Neandertal genome sequence indicate that, contrary to the previous consensus, African genomes carry a small but significant amount of Neandertal-specific DNA. This indicates back-migration into Africa of modern humans (carrying some Neandertal sequences) and underlines the complexity of ancient human migrations.


NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo.
Nitric oxide (NO) and reactive oxygen species (ROS) have fundamentally important roles in the regulation of vascular tone and remodeling. Although arterial disease and endothelial dysfunction alter NO and ROS levels to impact vasodilation and vascular structure, direct measurements of these reactive species under in vivo conditions with flow alterations are unavailable. In this study, in vivo measurements of NO and H2O2 were made on mesenteric arteries to determine whether antioxidant therapies could restore normal NO production in spontaneously hypertensive rats (SHR). Flow was altered from approximately 50-200% of control in anesthetized Wistar-Kyoto rats (WKY) and SHR by selective placement of microvascular clamps on adjacent arteries while NO and H2O2 were directly measured with microelectrodes. Relative to WKY, SHR had significantly increased baseline NO and H2O2 concentrations (2,572 +/- 241 vs. 1,059 +/- 160 nM, P < 0.01; and 26 +/- 7 vs. 7 +/- 1 microM, P < 0.05, respectively). With flow elevation, H2O2 but not NO increased in SHR; NO but not H2O2 was elevated in WKY. Apocynin and polyethylene-glycolated catalase decreased baseline SHR NO and H2O2 to WKY levels and restored flow-mediated NO production. Suppression of NAD(P)H oxidase with gp91ds-tat decreased SHR H2O2 to WKY levels. Addition of topical H2O2 to increase peroxide to the basal concentration measured in SHR elevated WKY NO to levels observed in SHR. The results support the hypothesis that increased vascular peroxide in SHR is primarily derived from NAD(P)H oxidase and increases NO concentration to levels that cannot be further elevated with increased flow. Short-term and even acute administration of antioxidants are able to restore normal flow-mediated NO signaling in young SHR.


Second-generation Asian American women's gendered racial socialization.
Utilizing an intersectional framework (Crenshaw, 1989) and socioecological theory (Bronfenbrenner, 1979), we investigated the gendered racialized messages Asian American women receive growing up, otherwise known as gendered racial socialization, from their family, peers, and mass media. Consensual Qualitative Research was used to analyze interview data from 12 second-generation Asian American women. The results demonstrated that (a) family socialization messages included gendered racial discrimination, body image and physical appearance, marital/dating attitudes, role responsibilities and expectations, and academic/work expectations, (b) peer socialization included oppressive messages (e.g., physical objectification, denial of identity, lack of presence) and affirming messages (e.g., positive self-concept messages), and (c) mass media socialization included oppressive messages (e.g., lack of representation, stereotypical depictions), and affirming messages (e.g., messages about empowerment). These messages impacted Asian American women's views on their body image and physical appearance, self-esteem, career/work, mental health, and critical consciousness. Implications and findings of the need to dismantle interlocking oppressive forces are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Modular and Versatile Trans-Encoded Genetic Switches.
Current bacterial RNA switches suffer from lack of versatile inputs and are difficult to engineer. We present versatile and modular RNA switches that are trans-encoded and based on tRNA-mimicking structures (TMSs). These switches provide a high degree of freedom for reengineering and can thus be designed to accept a wide range of inputs, including RNA, small molecules, and proteins. This powerful approach enables control of the translation of protein expression from plasmid and genome DNA.


Refractory Sweet Syndrome Treated with Anakinra.
Sweet syndrome, otherwise known as acute febrile neutrophilic dermatosis, is an uncommon disorder characterized by the abrupt onset of painful cutaneous lesions, often with fever and leukocytosis, in patients with underlying infection, malignancy, pregnancy, or drug exposure. We present a case of a young female with long-standing Sweet syndrome refractory to standard treatments and several immunomodulators whose symptoms were ultimately controlled with anakinra.


Catalysis-linked inactivation of fluoroacetate dehalogenase by ammonia: a novel approach to probe the active-site environment.
Fluoroacetate dehalogenase from Moraxella sp. B (FAc-DEX) catalyzes the hydrolytic dehalogenation of fluoroacetate and other haloacetates. Asp(105) of the enzyme acts as a nucleophile to attack the alpha-carbon of haloacetate to form an ester intermediate, which is subsequently hydrolyzed by a water molecule activated by His(272) [Liu, J.Q., Kurihara, T., Ichiyama, S., Miyagi, M., Tsunasawa, S., Kawasaki, H., Soda, K., and Esaki, N. (1998) J. Biol. Chem. 273, 30897-30902]. In this study, we found that FAc-DEX is inactivated concomitantly with defluorination of fluoroacetate by incubation with ammonia. Mass spectrometric analyses revealed that the inactivation of FAc-DEX is caused by nucleophilic attack of ammonia on the ester intermediate to convert the catalytic residue, Asp(105), into an asparagine residue. The results indicate that ammonia reaches the active site of FAc-DEX without losing its nucleophilicity. Analysis of the three-dimensional structure of the enzyme by homology modeling showed that the active site of the enzyme is mainly composed of hydrophobic and basic residues, which are considered to be essential for an ammonia molecule to retain its nucleophilicity. In a normal enzyme reaction, the hydrophobic environment is supposed to prevent hydration of the highly electronegative fluorine atom of the substrate and contribute to fluorine recognition by the enzyme. Basic residues probably play a role in counterbalancing the electronegativity of the substrate. These results demonstrate that catalysis-linked inactivation is useful for characterizing the active-site environment as well as for identifying the catalytic residue.


HIV viral load measurement: knowledge, attitudes and practices of health workers, Burkina Faso
Approximately a quarter of people living with HIV (PLHIV) had their plasma viral load (PVL) measured in 2020 in Burkina Faso. The purpose of this study was to assess the knowledge, attitudes, and practices (KAP) of health workers regarding HIV PVL measurement. A cross-sectional study was conducted among health workers involved in the care of PLHIV in the 13 regions of Burkina Faso in 2021. Scores were constructed to assess their KAP on PVL measurement. Factors associated with knowledge and practices were identified by logistic regression. A total of 255 health workers were surveyed. The majority had good knowledge (73%) and favorable attitudes (93%). However, 40% had inadequate practices. Taking into account the availability of a laboratory to carry out PVL tests within the health center, having a coordinating role increased the likelihood of having good knowledge, while not having a medical qualification reduced this likelihood. Good practices were more common among health workers working at the second level of the health pyramid. Interventions to increase the demand for a measurement of PVL are essential to improve the care of PLHIV. For example, future investigations could explore the role of mediators in increasing the demand for PVL among PLHIV and their caregivers.


[Migration of the microfilariae in the hemocoel of the vector (author's transl)].
Two stochastic models try to assess the limitation phenomenon. The first one lets suppose that a limited number of crossing sites for microfilariae are present on stomach wall. The second one lets suppose that microfilariae are inactivated either by reinforcement of the vector physiological mechanism (blood coagulation, peritrophic membrane, etc...) or by microfilarian mutual inhibition. Datae on five filaria-vector sets have been analysed. The first model given by a single type of curve fits with the datae concerning three sets. The second model shows that different types of curves are optional. In this case five sets of datae can be ajusted, moreover this model allows for a given set.


Impact of urbanization on Bellandur Lake, Bangalore--a case study.
Lake and river water is the prime source for drinking, irrigation and other domestic purposes. Bellandur Lake is one of the major Lakes of Bangalore city. The addition of effluents from urbanized Bangalore city has changed the characteristics of the Lake from being a natural ecologically healthy Lake to an artificial reservoir of domestic sewage and industrial effluents. The DO of the Bellandur Lake water ranged from 3.8-6.3 mg/l. The Bellandur lake water BOD ranged from 89-99 mg/l due to absorption of pollutants by aquatic flora in lake system. If the present state of affairs continues for long, the Bellandur Lake may soon become an ecologically inactive Lake.


Predictive profiling of gram-negative antibiotics in CagA oncoprotein inactivation: a molecular dynamics simulation approach.
Gastric cancer (GC) is the fifth most prevalent form of cancer worldwide. CagA - positive Helicobacter pylori infects more than 60% of the human population. Moreover, chronic infection of CagA-positive H. pylori can directly affect GC incidence. In the current study, we have repurposed FDA-approved antibiotics that are viable alternatives to current regimens and can potentially be used as combination therapy against the CagA of H. pylori. The 100 FDA-approved gram negative antibiotics were screened against CagA protein using the AutoDock 4.2 tool. Further, top nine compounds were selected based on higher binding affinity with CagA. The trajectory analysis of MD simulations reflected that binding of these drugs with CagA stabilizes the system. Nonetheless, atomic density map and principal component analysis also support the notion of stable binding of antibiotics to the protein. The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases.


CT coronary angiography is feasible for the assessment of coronary artery disease in chronic dialysis patients, despite high average calcium scores.
Significant obstructive coronary artery disease (CAD) is common in asymptomatic dialysis patients. Identifying these high risk patients is warranted and may improve the prognosis of this vulnerable patient group. Routine catheterization of incident dialysis patients has been proposed, but is considered too invasive. CT-angiography may therefore be more appropriate. However, extensive coronary calcification, often present in this patient group, might hamper adequate lumen evaluation. The objective of this study was to assess the feasibility of CT-angiography in this patient group. For this analysis all patients currently participating in the ICD2 trial (ISRCTN20479861), with no history of PCI or CABG were included. The major epicardial vessels were evaluated on a segment basis (segment 1-3, 5-8, 11 and 13) by a team consisting of an interventional and an imaging specialist. Segments were scored as not significant, significant and not interpretable. A total of 70 dialysis patients, with a mean age of 66±8 yrs and predominantly male (70%) were included. The median calcium score was 623 [79, 1619]. Over 90% of the analyzed segments were considered interpretable. The incidence of significant CAD on CT was 43% and was associated with cardiovascular events during follow-up. The incidence of cardiovascular events after 2-years follow-up: 36% vs. 0% in patients with no significant CAD (p<0.01). Despite the high calcium scores CT-angiography is feasible for the evaluation of the extent of CAD in dialysis patients. Moreover the presence of significant CAD on CT was associated with events during follow-up.


Congenital dyserythropoietic anaemia type II: a rare entity.
Congenital dyserythropoietic anaemias (CDAs) are a group of rare hereditary disorder characterised by ineffective erythropoiesis and dyserythropoiesis. Among the three variants, type II is the most common. The authors are presenting two cases of CDA type II in two sisters.


Outbreak of Campylobacteriosis Following a Dairy Farm Visit: Confirmation by Genotyping.
In April-May 2014, an outbreak of campylobacteriosis occurred after a preschool visit to a dairy farm in the South Western part of Sweden. During the visit, a meal, including unpasteurized milk, was served. A retrospective cohort study using a web-based questionnaire was performed among the participants (n = 30) of the farm visit. A total of 24 of the 30 (80%) cohort members completed the questionnaire. Eleven cases were identified, and Campylobacter jejuni was isolated from eight of them. Seven of the cases were 2- to 7-year-old children. We found the highest attack rates among those who usually drink milk (45%) and those who consumed unpasteurized milk during the farm visit (42%). No cases were unexposed (risk ratio incalculable). As result of the farm investigation, Campylobacter was isolated from cattle on the farm. Genotyping with pulsed-field gel electrophoresis and whole genome sequencing confirmed that human and cattle isolates of C. jejuni belonged to one cluster. Thus, cattle on the farm are considered the source of infection, and the most likely vehicle of transmission was contaminated unpasteurized milk. We recommend consumption of heat-treated milk only and increased awareness of the risk of consuming unpasteurized milk.


Potential usefulness of basic fibroblast growth factor as a treatment for stroke.
Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.


Effect of heat-treated canola meal and glycerol inclusion on performance and gastrointestinal development of Holstein calves.
The objectives of this study were to assess the effect of using heat-treated canola meal (CM) and glycerol inclusion in starter mixtures on starter intake, growth, and gastrointestinal tract development in Holstein bull calves. In the first study, a protocol for the heat treatment of CM was evaluated by comparing commercial CM that was exposed to 0, 100, 110, or 120°C of heat treatment for 10 min. Following heat treatment, in situ crude protein (CP) ruminal degradability and estimated intestinal CP digestibility were assessed. It was observed that the degradable fractions of dry matter and CP in CM decreased linearly with increasing temperature of heat treatment. The estimated intestinal CP digestibility was greatest when CM was heated to 110°C. In the second study, 28 bull calves were used in a randomized complete block design. Calves were fed pelleted starters containing CM or CM that was heat-treated to 110°C for 10 min. Diets also contained 0 or 5% glycerol on a dry matter basis. The study lasted 51 d, ending on the first day of weaning. Starter intake, average daily gain (ADG), ruminal short-chain fatty acid concentrations, morphology of the rumen and small intestine, gene expression (MCT1, GPR41, GPR43, UTB, AQP3, PEPT1, PEPT2, ATB0+, and EAAC1) in the ruminal, jejunal, and ileal epithelium, and brush border enzyme activities in the duodenum, jejunum, and ileum were investigated. Few interactions between heat-treated CM and glycerol inclusion were observed. Feeding heat-treated CM did not affect starter intake. However, feeding heat-treated CM to calves tended to reduce ADG and decreased the weight of ruminal and jejunal tissue. Heat treatment did not affect gene expression or brush border enzyme activities in the small intestine. Glycerol inclusion tended to increase cumulative starter intake and increased cumulative body weight gain. Use of glycerol reduced ruminal pH and increased the concentration of ruminal short-chain fatty acids. Additionally, glycerol inclusion increased abomasal, duodenal, jejunal, and cecal digesta weights and tended to increase the weight of the jejunal tissue. Glycerol supplementation tended to downregulate the expression of MCT1 in the ruminal epithelium, and upregulated the expression of MCT1 in the epithelium of proximal jejunum. In conclusion, heat treatment of CM may negatively affect calf growth and gastrointestinal tract development. Glycerol inclusion may increase starter intake, ADG, ruminal fermentation, and intestinal development in calves when CM is used as a main source of protein in pelleted starter mixture.


Effects of 17β-estradiol and 2-methoxyestradiol on the oxidative stress-hypoxia inducible factor-1 pathway in hypoxic pulmonary hypertensive rats.
The present study aimed to investigate the effects of 17β-estradiol (E2) and 2-methoxyestradiol (2ME) on the oxidative stress-hypoxia inducible factor-1 (OS-HIF-1) pathway in hypoxic pulmonary hypertensive rats. Female Sprague-Dawley rats were divided randomly into 4 groups, as follows: i) Control (Group A); ii) ovariectomy (OVX) + hypoxia (Group B); iii) OVX + hypoxia + E2 injection (Group C); and iv) 2ME injection (Group D). The rats were maintained under hypoxic conditions for 8 weeks, and mean pulmonary artery pressure (mPAP) and pulmonary arteriole morphology were measured. The reactive oxygen species, superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (Cu/ZnSOD) levels in serum were also measured. MnSOD and HIF-1α expression levels in lung tissue were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. The mPAP and arterial remodeling index were significantly elevated following chronic hypoxia exposure; however, experimental data revealed a reduced response in E2 and 2ME intervention rats. Compared with Group A, Group B had significantly elevated oxidative stress levels, as illustrated by increased serum ROS levels, decreased serum SOD and MnSOD levels and decreased MnSOD mRNA and protein expression levels in lung tissue. Furthermore, HIF-1α mRNA and protein expression in Group B was significantly elevated compared with Group A. E2 and 2ME intervention significantly attenuated the aforementioned parameter changes, suggesting that E2 and 2ME partially ameliorate hypoxic pulmonary hypertension. The underlying mechanism of this may be associated with the increase in MnSOD activity and expression and reduction in ROS level, which reduces the levels of transcription and translation of HIF-1α.


Pediatric anaplastic large cell lymphoma presenting as generalized lymphadenopathy.
Because a finding of generalized lymphadenopathy can be associated with such a wide range of diseases and conditions, determining its cause can sometimes be challenging. Infectious causes are the most common; however, it is important also to consider other entities in the workup. Here we present the case of a 3-year-old girl with generalized lymphadenopathy and fever, in whom the cause of the symptoms was initially thought to be infectious. Ultimately, however, anaplastic large cell lymphoma (ALCL) was diagnosed. Using this case as a backdrop, we discuss the wide range of systemic illnesses that the differential diagnosis of generalized lymphadenopathy encompasses--including infectious, autoimmune, and oncological disorders. We discuss the different findings typically seen in the various entities that figure prominently in the differential, and we outline investigations that can help narrow it. Finally, we present an overview of ALCL, one of the more rare pediatric malignancies.


Azodicarbonamide (ADCA): A reconsideration of classification as a respiratory sensitiser.
Azodicarbonamide (ADCA) is widely used by industry in the manufacture of a variety of products. ADCA has been classified as a respiratory allergen, and the purpose of this article was to consider whether this classification is appropriate based upon the available data. Here both clinical experience and relevant experimental data have been reviewed. Although there have been reports of an association between workplace exposure to ADCA and symptoms of respiratory allergy and occupational asthma, the evidence is less than persuasive, with in many instances a lack of properly controlled and executed diagnostic procedures. In addition, ADCA fails to elicit positive responses in mouse and guinea pig predictive tests for skin sensitisation; a lack of activity that is regarded as being inconsistent with respect to respiratory sensitising potential. Collectively, the data reviewed here do not provide an adequate basis for the classification of ADCA as a respiratory allergen.


Efficient Sum of Outer Products Dictionary Learning (SOUP-DIL) and Its Application to Inverse Problems.
The sparsity of signals in a transform domain or dictionary has been exploited in applications such as compression, denoising and inverse problems. More recently, data-driven adaptation of synthesis dictionaries has shown promise compared to analytical dictionary models. However, dictionary learning problems are typically non-convex and NP-hard, and the usual alternating minimization approaches for these problems are often computationally expensive, with the computations dominated by the NP-hard synthesis sparse coding step. This paper exploits the ideas that drive algorithms such as K-SVD, and investigates in detail efficient methods for aggregate sparsity penalized dictionary learning by first approximating the data with a sum of sparse rank-one matrices (outer products) and then using a block coordinate descent approach to estimate the unknowns. The resulting block coordinate descent algorithms involve efficient closed-form solutions. Furthermore, we consider the problem of dictionary-blind image reconstruction, and propose novel and efficient algorithms for adaptive image reconstruction using block coordinate descent and sum of outer products methodologies. We provide a convergence study of the algorithms for dictionary learning and dictionary-blind image reconstruction. Our numerical experiments show the promising performance and speedups provided by the proposed methods over previous schemes in sparse data representation and compressed sensing-based image reconstruction.


Integrated molecular profiling of SOD2 expression in multiple myeloma.
Reactive oxygen species are known to be involved in several cellular processes, including cell signaling. SOD2 is a key enzyme in the conversion of reactive oxygen species and has been implicated in a host of disease states, including cancer. Using an integrated, whole-cell approach encompassing epigenetics, genomics, and proteomics, we have defined the role of SOD2 in multiple myeloma. We show that the SOD2 promoter is methylated in several cell lines and there is a correlative decrease in expression. Furthermore, myeloma patient samples have decreased SOD2 expression compared with healthy donors. Overexpression of SOD2 results in decreased proliferation and altered sensitivity to 2-methoxyestradiol-induced DNA damage and apoptosis. Genomic profiling revealed regulation of 65 genes, including genes involved in tumorigenesis, and proteomic analysis identified activation of the JAK/STAT pathway. Analysis of nearly 400 activated transcription factors identified 31 transcription factors with altered DNA binding activity, including XBP1, NFAT, forkhead, and GAS binding sites. Integration of data from our gestalt molecular analysis has defined a role for SOD2 in cellular proliferation, JAK/STAT signaling, and regulation of several transcription factors.


The effect of additional shading utilizing agriphotovoltaic structures on the visual qualities and metabolites of broccoli.
Agriphotovoltaic (APV) systems allow the simultaneous production of crops and electricity in the same land area. Since the reduction of yield caused by APV systems is important for food security, studies to improve the yield have been conducted steadily. However, there have been limited data on the appearance, quality, and metabolomic changes of crops. Therefore, in this study, we evaluated the visual qualities and metabolites as well as the yield of broccoli grown using an APV system during the fall season. In addition, additional shading treatment was performed, and the same qualities were evaluated. In the spring season, an additional cultivar that does not express anthocyanins was cultivated. Glucosinolate content was more sensitive to the seasonal environment and the type of cultivar than it was to treatment type. The additional shading treatment had a positive effect on the visual qualities of anthocyanin-expressing broccoli cultivar regardless of the season, and we observed that even a cultivar that does not express anthocyanins can be greener. Regardless of cultivar, higher chlorophyll content was detected in broccoli florets with additional shading treatment under the APV system. In addition, reduced anthocyanin content was observed (6.1 mg g-1 DW; about 20% of that obtained on open-field). Aspartic acid content was enhanced upon additional shading treatment. Pathway analysis revealed changes in anthocyanin, alanine, aspartic acid, and glutamic acid metabolism. Overall, our findings suggests that it is possible to produce crops with better visual qualities by utilizing APV systems.


The face of AIDS: Effects of physical attractiveness and target gender on inferred mode of HIV infection.
We examined the effects of physical attractiveness on the assumed mode of HIV acquisition. 176 students read a description of an HIV-positive target whose photograph was placed above the description. A 2 (target gender) by 2 (attractive or unattractive target) factorial design was used. Unattractive targets were perceived as more likely to have acquired HIV through homosexual relationships. Further, men were perceived as more likely than women to have acquired HIV homosexually. Attractiveness did not bias health-care allocations regarding the infected target.


Improving access to effective care for people with chronic respiratory symptoms in low and middle income countries.
Chronic respiratory symptoms are amongst the most common complaints among low and middle-income country (LMICs) populations and they are expected to remain common over the 10 to 20 year horizon. The underlying diseases (predominantly chronic obstructive pulmonary disease, asthma and tuberculosis) cause, and threaten to increasingly cause, substantial morbidity and mortality. Effective treatment is available for these conditions but LMICs health systems are not well set up to provide accessible clinical diagnostic pathways that lead to sustainable and affordable management plans especially for the chronic non communicable respiratory diseases. There is a need for clinical and academic capacity building together with well-conducted health systems research to underpin health service strengthening, policy and decision-making. There is an opportunity to integrate solutions for improving access to effective care for people with chronic respiratory symptoms with approaches to tackle other major population health issues that depend on well-functioning health services such as chronic communicable (e.g. HIV) and non-communicable (e.g. cardiovascular and metabolic) diseases.


Chronic comorbidity in multiple sclerosis is associated with lower incomes and dissolved intimate relationships.
The social and economic consequences of comorbidity in multiple sclerosis (MS) are largely unexplored. Differences were investigated in income and in the rate of broken relationships between cases of MS with and without chronic comorbidity. We conducted a nationwide cohort study including all incident cases of MS in Denmark with clinical MS onset between 1980 and 2005. The difference in income was investigated at MS onset and 5 and 10 years after MS onset. The difference in the rate of broken relationships was investigated in subjects who were in a relationship at MS onset or who entered a relationship after MS onset. We used logistic, multiple linear and Poisson regression analyses. Cases of MS with somatic comorbidity had increased odds of low incomes both 5 years {odds ratio (OR), 1.41 [95% confidence interval (CI), 1.19-1.67; P < 0.0005]} and 10 years [OR, 1.37 (95% CI, 1.17-1.60); P < 0.0005] after MS onset. The odds of a low income with psychiatric comorbidity was increased 10 years after MS onset [OR, 3.06 (95% CI, 1.47-6.37); P = 0.003]. The rate of broken relationships was increased in cases of MS with any somatic comorbidity [incidence rate ratio, 1.46 (95% CI, 1.32-1.61); P < 0.0005]. Our results underscore the burden of comorbidity in MS on patients, their partners and society.


Endoscopic intraventricular surgery for treatment of hydrocephalus and loculated CSF space in children less than one year of age.
Controversy exists regarding whether children under 1 year of age have a higher risk of treatment failure after neuroendoscopic procedures for the treatment of hydrocephalus than older children. We retrospectively reviewed the surgical management and clinical outcome of 15 infants who underwent neuroendoscopic surgery for the treatment of CSF space loculation and hydrocephalus. We performed 8 third ventriculostomies, 3 endoscopic arachnoid cyst fenestrations, 2 aqueductoplasties, 1 septostomy and in 1 patient, three endoscopic fenestrations for isolated ventricular compartments. Two of the third ventriculostomies, 1 of the aqueductoplasties and the 1 septostomy failed, and these patients underwent placement of a ventriculoperitoneal shunt. In all other patients, symptoms and signs related to hydrocephalus or CSF space loculation were relieved effectively after the endoscopic procedure. We conclude that neuroendoscopy presents an effective alternative for the treatment of hydrocephalus and CSF loculation in infants less than 1 year of age.


[A case of hepatocellular carcinoma presented as a huge intrahepatic hematoma].
Spontaneous intrahepatic bleeding is a rare condition. In the absence of trauma, intrahepatic hematoma may be due to underlying liver disease. We report a case of hepatocellular carcinoma in the patient who had huge intrahepatic hematoma without definite intrahepatic tumor at the time of initial presentation. A 54-year-old man was admitted to our hospital with a sudden onset of upper abdominal pain. Initial abdominal CT scan showed huge hematoma measuring more than 13 cm in diameter in the right lobe of the liver. However, there was no enhancing lesion in the liver. Laboratory data showed high alanine aminotransferase, alpha-fetoprotein and positive HBsAg. The MRI and angiography could not also depict any mass in the liver. The patient was treated with percutaneous drainage on the intrahepatic hematoma. The cytology from drainaged blood revealed no malignant cell. After hematoma decreased, follow-up CT scan depicted an enhancing tumor in the liver. He underwent right hepatic lobectomy and histopathological examination showed hepatocellular carcinoma.


Autonomy development in adolescents with insulin dependent diabetes mellitus.
This descriptive study investigated autonomy development among young adolescents with insulin-dependent diabetes mellitus (IDDM); assessed relationships among behavioral, cognitive, and emotional autonomy; and determined the relationships between these types of autonomy and metabolic control. Developmental and family theory provided the framework for this study. This investigation suggested that the pattern of autonomy for adolescents with IDDM is congruent with that of adolescents without chronic illness. The three autonomy types are conceptually distinct and one aspect of emotional autonomy was related to poorer metabolic control. Daughters and adolescents in one-parent families scored higher on this component.


Ambition and vision at student awards.
Eighty entries from students from schools of architecture and interior design all over the world were whittled down to just eight in the 2009 Architects for Health (AfH) Student Health Awards. Jaime Bishop, a director of Fleet Architects, AfH executive board member, and the competition's organiser, describes the shortlisted and winning entries, discusses how candidates addressed the brief, and explains how the winner and two "runners-up" were chosen.


MHC class II-dependent T-T interactions create a diverse, functional and immunoregulatory reaction circle.
Unlike conventional T cells, innate-like T cells such as natural killer (NK) T cells are selected by homotypic T-cell interactions. Recently, a few reports have shown that T-T CD4(+) T cells can be generated in a similar manner to that for NKT cells. These two types of cells share common functional properties such as rapid response to antigenic encounters and the potential for a panoply of cytokine secretion. However, T-T CD4(+) T cells differ from NKT cells in that they are restricted by highly polymorphic major histocompatibility complex (MHC) II molecules and have a diverse T-cell receptor repertoire. Additional example of T-T interactions was recently reported in which peripheral T cells re-circulate to the thymus and participate in the thymocyte selection process. In this review, we dissect the cellular mechanisms underlying the production of T-T CD4(+) and NKT cells, with particular emphasis on the differences between these two T-cell prototypes. Finally, we propose that T-T CD4(+) T cells serve two major functions: one as an acute-phase reactant against viral infection and the other is the generation of anti-ergotypic CD4(+) T cells for regulatory purposes. All of these features make it possible to create a diverse set of functional cells through MHC class II-restricted T-T interactions.


Pre-protective effect of lipoic acid on injury induced by H2O2 in IPEC-J2 cells.
Alpha-lipoic acid (LA) is considered to be a universal antioxidant. The intestine is very sensitive to a wide range of stressors for it exposed in a complex microenvironment that usually contained excess free radicals. The objective of this study was to evaluate the pre-protective effect of LA on intestinal epithelial cell injury induced by H2O2. In this research, IPEC-J2 cells were divided into three groups: the control group, the H2O2-treated group, and the LA pre-protective group. Cell viability, intracellular ROS, DNA damage integrity, and antioxidant enzyme activity of all groups were measured. Quantitative reverse transcription-PCR was used to determine the influence of oxidative stress and LA on the GH/IGF-1 axis in IPEC-J2 cells. The research selected 1 mM H2O2 and 10 μg/ml as modeling concentration. The data indicated that H2O2 can significantly increase the intracellular free radicals, leading to serious DNA damage and significantly reduce superoxide dismutase, glutathione peroxidase, catalase, and lipase activity. LA-protected IPEC-J2 cells against H2O2-induced injury by scavenging hydroxyl radical. In the current study, LA pre-protective group share a lower intracellular ROS and lower DNA damage compare to H2O2-treated group (P < 0.01); and also, a higher lipase activity were detected in LA pre-protective group compare to H2O2-treated group (P < 0.05). But the mechanism between oxidative stress, LA effect, and GH/IGF-1 axis is still unknown. The model used in the current study is also suitable for other feed additive screening.


Effect of butylated hydroxytoluene (BHT) on the aerobic biodegradation of a model vegetable oil in aquatic media.
Antioxidants added to vegetable oils to prevent lipid oxidation significantly affect their biodegradation in impacted aquatic environments. In this study, the effect of butylated-hydroxytoluene (BHT) on the biodegradation of glyceryl trilinoleate, a model vegetable oil highly susceptible to autoxidation, was determined. Biodegradation experiments were conducted in respirometric microcosms at an oil loading of 333 gal acre(-1) (0.31 L m(-2)) and BHT concentrations ranging from 0 to 800 mg kg(-1) (0, 50, 100, 200, 400, and 800 mg kg(-1)). Competition between polymerization and biodegradation of the oil was observed at all BHT concentrations and was significant in the microcosms not supplemented with the antioxidant. In all microcosms, intractable rigid polymers unavailable for bacterial degradation were formed. Infrared analysis evidenced the advanced stages of the oil autoxidation. After 19 weeks of incubation, only about 41% of the oil was mineralized in the microcosms with no BHT. However, mineralization exceeded 67% in the microcosms with added antioxidant and did not significantly increase with increasing BHT concentrations. Biodegradation rate constants were calculated by nonlinear regression and were not significantly different in the microcosms with added BHT (k = 0.001 h(-1)). Higher k values were measured in the microcosms lacking the antioxidant (k = 0.0023 h(-1)), most likely due to the increased oxygen consumption associated with the autoxidation process in this case. No toxicity was detected in all biotic microcosms at the end of the incubation period, while high toxicity (EC(50) = 4.78%) was measured in the abiotic blanks with no antioxidant and was attributed to the accumulation of autoxidation products.


Macrophage phenotype in response to ECM bioscaffolds.
Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (MECM) is distinct from both the classically activated IFNγ+LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an MECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers.


Wall shear stress in the human eye microcirculation in vivo, segmental heterogeneity and performance of in vitro cerebrovascular models.
Wall shear stress (WSS) is a very important hemodynamic parameter implicated in many physiological and pathological phenomena. In order to study these phenomena, it is more convenient to use in vitro models before testing on animals and humans. Dynamic in vitro cerebrovascular models are considered capable of simulating the in vivo hemodynamic conditions, but only few of them seem to meet the criteria for this task. It is now clear that in the human eye microcirculation a significant pulsation exists at the pre-capillary arterioles with average WSS values more than twice those in the venular side, for the same diameters. WSS heterogeneity is in support of segmental heterogeneity i.e. the endothelial phenotypic and functional difference among arterioles, capillaries and venules. In this review paper, the importance of WSS is described in detail and two more microvascular segments are proposed: a pre-capillary arteriolar and a post-capillary venular segment. The accurate hemodynamic simulation in all microvascular segments seems to be a prerequisite step in the development of dynamic in vitro blood brain barrier (BBB) models and microfluidic platforms on chip. Endothelial cells in the cardiovascular system seem to have sophisticated role acting like cardiovascular processing sensors (CPSs).


Affective factors and learning behaviour in secondary school mathematics and English lessons for average and low attainers.
This study had two broad aims; firstly, to investigate the predictive relationships between i) overall subject affective factors (attitude and subjective norm), ii) specific lesson factors (behaviour intention, perceived preventive factors and self efficacy) and iii) learning behaviour during lessons; and secondly, to investigate the consistency of these affective factors across English and maths, and whether there were differences between average and low attaining pupils in these affective factors. Twenty-eight boys and girls, aged 11-14 years, in an inner city comprehensive school were assessed for these factors in two subjects over two occasions. It was found that neither attitude nor subjective norm were consistently predictive of intentions. The lesson specific factors (behaviour intention, preventive factors and self efficacy), which were inter-related, were moderately predicted by past learning behaviour, and were each predictive of subsequent learning behaviour. Pupils were also consistent in their affective perspectives to learning maths and English, though few differences were found between average and low attaining pupils. The significance of the findings is discussed in terms of the theoretical links between self efficacy and reasoned action approaches, the context of assessment and the nature of behaviour intention.


[Effect of primary lesion resection on the prognosis of patients with advanced breast cancer].
Objective: To explore the effect of the resection of the primary lesion on the prognosis for patients with stage Ⅳ breast cancer. Methods: A total of 132 breast cancer patients who were first diagnosed as stage Ⅳ in the Hebei Cancer Hospital from June 2008 to June 2015 were divided into two groups: the primary resection group (n=85) and the unresection group (n=47). The influences of primary resection, timing of operation, lymph node removal or dissection and radiotherapy on the prognosis of stage Ⅳ breast cancer patients were analyzed. Results: Multivariate Logistic regression analysis showed that visceral metastasis was an independent influencing factor for primary lesion resection in stage Ⅳ breast cancer patients (OR=2.590, 95% CI: 1.090-6.159). Multivariate Cox regression analysis showed that primary resection was an independent factor for the improvement of prognosis in stage Ⅳ breast cancer patients (OR=0.582, 95% CI: 0.400-0.847). The median overall survival (OS) was 37.20 months in the resection group, which was higher than 24.10 months in the unresection group (χ(2)=8.108, P=0.004). Among patients aged ≥50 years old, the median OS was 39.30 months in the resection group and 23.03 months in the unresection group, and the difference was statistically significant (χ(2)=14.191, P<0.001). The median OS was 38.00 months in the 66 patients with the operation time from diagnosis to resection of primary lesion<6 months (n=66), and 35.20 months for ≥6 months (n=19) (χ(2)=4.430, P=0.035), the difference was statistically significant (χ(2)=4.430, P=0.035). The median OR of axillary lymph node dissection and axillary lymph node excision group were 45.37 months and 33.44 months, respectively, the difference was statistically significant (χ(2)=7.832, P=0.005). The median OS of postoperative radiotherapy group and non-radiotherapy group were 44.80 months and 33.20 months, respectively, the difference was not statistically significant (χ(2)=2.950, P=0.086). Conclusion: Resection of the primary lesion may prolong the survival time of some advanced breast cancer patients.


Neurodevelopmental and neurophysiological actions of thyroid hormone.
For over 100 years, thyroid hormones have been known to be essential for neonatal neurodevelopment but whether they are required by the foetal brain remains a matter of controversy. For decades, the prevailing view was that thyroid hormones are not necessary until after birth because circulating levels in the foetus are very low and the placenta forms an efficient barrier to their transfer from the mother. Clinical observations of good neurological outcome following early treatment of congenital hypothyroidism were used to support the view that thyroid hormones are not required early in neurodevelopment. Nevertheless, the issue remained contentious because of findings that the severity of foetal neurological deficit due to maternal iodine deficiency correlated with the degree of maternal thyroxine (T4) deficiency. Furthermore, neurological damage in these cases could be prevented by correction of maternal T4 deficiency before mid-gestation. This observation led to the opposing view, supported by epidemiological studies of neurological cretinism, that maternal thyroid hormones are important and necessary for early foetal neurodevelopment. It is now clear that thyroid hormones are essential for both foetal and post-natal neurodevelopment and for the regulation of neuropsychological function in children and adults. In recent years, this controversial subject has progressed very rapidly following remarkable progress in understanding of the molecular mechanisms of thyroid hormone action. This article reviews the contributions of molecular biology and genetics to our new understanding of the physiological effects of thyroid hormones on neurodevelopment and in the adult brain.


Do good actions inspire good actions in others?
Actions such as sharing food and cooperating to reach a common goal have played a fundamental role in the evolution of human societies. Despite the importance of such good actions, little is known about if and how they can spread from person to person to person. For instance, does being recipient of an altruistic act increase your probability of being cooperative with a third party? We have conducted an experiment on Amazon Mechanical Turk to test this mechanism using economic games. We have measured willingness to be cooperative through a standard Prisoner's dilemma and willingness to act altruistically using a binary Dictator game. In the baseline treatments, the endowments needed to play were given by the experimenters, as usual; in the control treatments, they came from a good action made by someone else. Across four different comparisons and a total of 572 subjects, we have never found a significant increase of cooperation or altruism when the endowment came from a good action. We conclude that good actions do not necessarily inspire good actions in others. While this is consistent with the theoretical prediction, it challenges the majority of other experimental studies.


[How to make a budget for fund applications].
There has been an enhanced focus on the use of foundation grants in the past year. This article gives an example on how to make a budget for fund applications.


The significance of reflective supervision for infant mental health work.
Parent-infant work is inherently relational and occurs in the intersubjective space between parent, infant, and worker. This space can be charged with primitive, unmet needs of both parent and infant, and this in turn can trigger these same states in the worker. The challenge for workers is to remain open to being affected by and responsive to these feeling states when their own early and possibly preconscious responses and coping strategies are being stirred. If these remain out of awareness, they can manifest as avoidance and denial, and this can be reflected in the system and result in limited service delivery. This article emphasizes the significance of reflective supervision for parent-infant work and suggests that it needs to be an integral part of the system of service delivery. I am grateful to the infant mental health workers who allowed me to use examples of their work in this article, and thank Dr Jon Jureidini for his encouragement and support.


Sutureless versus Conventional Aortic Valve Replacement: Outcomes in 70 High-Risk Patients Undergoing Concomitant Cardiac Procedures.
In elderly, high-risk surgical patients, sutureless aortic valve replacement (AVR) can often be an alternative to conventional AVR; shorter aortic cross-clamp and cardiopulmonary bypass times are the chief advantages. We compared the outcomes of sutureless AVR with those of conventional AVR in 70 elderly patients who underwent concomitant cardiac surgical procedures. We retrospectively analyzed the cases of 42 men and 28 women (mean age, 70.4 ± 10.3 yr; range, 34-93 yr) who underwent cardiac operations plus AVR with either a sutureless valve (group 1, n=38) or a conventional bioprosthetic or mechanical valve (group 2, n=32). Baseline patient characteristics were similar except for worse New York Heart Association functional status and the prevalence of diabetes mellitus in group 1. In group 1, the operative, cross-clamp, and cardiopulmonary bypass times were shorter (all P=0.001), postoperative drainage amounts were lower (P=0.009), hospital stays were shorter (P=0.004), and less red blood cell transfusion was needed (P=0.037). Echocardiograms before patients' discharge from the hospital showed lower peak and mean aortic gradients in group 1 (mean transvalvular gradient, 8.4 ± 2.8 vs 12.2 ± 5.2 mmHg; P=0.012). We found that elderly, high-risk patients who underwent multiple cardiac surgical procedures and sutureless AVR had better hemodynamic outcomes and shorter ischemic times than did patients who underwent conventional AVR.


Studies on the interaction of bleomycin A2 with rat lung microsomes. I. Characterization of factors which influence bleomycin-mediated DNA chain breakage.
The interaction of bleomycin A2 with rat lung microsomes has been investigated to determine whether DNA chain breakage or microsomal lipid peroxidation occurred, as these reactions could contribute significantly to bleomycin-induced lung injury. In the presence of calf thymus DNA and NADPH or NADH, significant oxygen-dependent, bleomycin-mediated DNA chain breakage was observed. In the absence of DNA, however, bleomycin did not stimulate microsomal lipid peroxidation. Moreover, incubation of bleomycin with rat lung microsomes in the absence of DNA resulted in a time-dependent decline in the ability to bleomycin to subsequently mediate DNA damage. This microsome-catalyzed inactivation of bleomycin was found to be dependent on both oxygen and NADPH, suggesting that a similar mechanism may be involved in bleomycin-mediated DNA damage and bleomycin inactivation. In addition to microsomes from rat lung, microsomes from mouse and rabbit lung and from rat liver and kidney catalyzed bleomycin-mediated DNA damage. These observations suggest that although a bleomycin-microsome interaction and subsequent DNA damage could be involved in bleomycin-induced lung injury, this interaction alone cannot account for the organ-specific toxicity of bleomycin toward the lung.


[Which contribution of wastewater treatment plants in the fight against antimicrobial resistance?]
Due to the massive use of antibiotics, antimicrobial resistance (AMR) continues to spread, endangering global disease control and environmental quality. The sources of bacteria or antimicrobial resistance genes are linked to human activities: urban, hospital and industrial discharges, livestock farms). The role of sanitation systems-sewerage, wastewater treatment and sludge treatment (WWTP)-in the problem of AMR has not yet been clearly established by the scientific community. The data available to date show that they eliminate part of the bacteria, genes and antibiotics, although this is not their primary vocation. WWTPs thus play an important filtering role to limit dissemination in the environment. On the other hand, some authors warn against their potential involvement in the selection of new resistant germs, given the conditions conducive to the exchange of genetic material between microbial strains of various types and exposed to selective agents. Today, knowledge of the mechanisms involved in the selection of antibiotic resistance and the fate of bacteria and resistance genes within sanitation systems remains limited. Research is needed to better characterize the contribution of wastewater systems and the performance of wastewater, recycled water, stormwater and sludge treatment processes.


A Selective Inhibitor of Ubiquitin-Specific Protease 4 Suppresses Colorectal Cancer Progression by Regulating β-Catenin Signaling.
Dysregulation of deubiquitinating enzymes (DUBs), which regulate the stability of key proteins, has been implicated in many human diseases, including cancers. Thus, DUBs can be considered as potential therapeutic targets for many diseases. Among them, USP4 has been proposed as a promising target for colon cancer drugs since USP4 controls the stability of β-catenin, a key factor in the Wnt signaling involved in the tumorigenesis of colorectal cancer. However, developing potential DUB inhibitors has been hindered because many DUBs harbor similar active site structures and show broad substrate specificities. By performing in vitro deubiquitinating activity assays using a chemical library, we identified several potential DUB inhibitors. Among them, only neutral red (NR) showed selective inhibitory activity on USP4 in a cell-based assay system. In colon cancer cells, NR affected the protein stability of β-catenin, as shown by immunoblotting, and it affected the target gene expression of β-catenin, as shown by quantitative real-time PCR. NR's potential as an anticancer drug was further estimated by colony formation and cell migration assays and by using a mouse xenograft model. We identified NR as an uncompetitive inhibitor of USP4 and validated its effects in colorectal cancer. NR-treated cells showed decreased β-catenin stability and reduced expression of β-catenin target genes. Additionally, treating colon cancer cells with NR significantly reduced colony formation and cell migration, and injecting NR into a mouse xenograft model reduced the tumor volume. The current results suggest that NR could be developed as an anticancer drug targeting USP4, and they support the possibility of developing specific DUB inhibitors as therapeutic agents.


Defective mRNA in myotonic dystrophy accumulates at the periphery of nuclear splicing speckles.
Nuclear speckles are storage sites for small nuclear RNPs (snRNPs) and other splicing factors. Current ideas about the role of speckles suggest that some pre-mRNAs are processed at the speckle periphery before being exported as mRNA. In myotonic dystrophy type 1 (DM1), the export of mutant DMPK mRNA is prevented by the presence of expanded CUG repeats that accumulate in nuclear foci. We now show that these foci accumulate at the periphery of nuclear speckles. In myotonic dystrophy type 2 (DM2), mRNA from the mutant ZNF9 gene is exported normally because the expanded CCUG repeats are removed during splicing. We now show that the nuclear foci formed by DM2 intronic repeats are widely dispersed in the nucleoplasm and not associated with either nuclear speckles or exosomes. We hypothesize that the expanded CUG repeats in DMPK mRNA are blocking a stage in its export pathway that would normally occur at the speckle periphery. Localization of the expanded repeats at the speckle periphery is not essential for their pathogenic effects because DM1 and DM2 are quite similar clinically.


Is memantine a breakthrough in the treatment of moderate-to-severe Alzheimer's disease?
Over stimulation of the NMDA receptor by glutamate has long been considered to have a role in Alzheimer's disease (AD). Memantine, a non-competitive antagonist of NMDA receptors, has recently been tested in moderate-to-severe AD. At 28 weeks, there was a small significant mean difference of 0.3 in favour of memantine, showing benefit in the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) global score. The other primary efficacy variable was the Alzheimer's disease Cooperative Study Activities of Daily Living Inventory, modified for more severe dementia (ADCS-ADL-sev) and there was significantly less deterioration in the ADCSADL-sev score in the memantine group than in the placebo group (2.1 versus 3.4, respectively). As there are no drugs commonly used for their effectiveness in moderate-to-severe AD, any drug that causes a benefit, however small, as memantine has been shown to do in this trial, represents a breakthrough.


A heuristic vulnerability/stress model of schizophrenic episodes.
A tentative model of schizophrenic psychotic episodes is presented, based on the evidence that certain characteristics of individuals may serve as vulnerability factors and that environmental stressors may precipitate psychotic periods in vulnerable individuals. Certain information-processing deficits, autonomic reactivity anomalies, and social competence and coping limitations are viewed as potential vulnerability factors. Stressors in the form of discrete life events as well as the prevailing level of social environmental stress are seen as factors that interact with preexisting vulnerability characteristics to produce vicious circles, which lead, in turn, to psychotic episodes. A distinction among stable vulnerability indicators, mediating vulnerability factors, and episode indicators is suggested to differentiate types of abnormalities that characterize individuals prone to or manifesting schizophrenic disorder. Some major areas of unresolved questions in relation to this view of schizophrenic psychotic episodes are discussed.