The analgesic efficacy of ultrasound-guided transversus abdominis plane block for retroperitoneoscopic renal surgery: a randomized controlled study.
Ultrasound-guided lateral transversus abdominis plane (TAP) block can provide definite analgesia to the anterior abdominal wall. However, whether this method is useful in renal surgery through the lateral abdominal wall pathway remains unknown. The study aimed to evaluate the analgesic efficacy of lateral TAP block for retroperitoneoscopic partial or radical nephrectomy. In this prospective, randomized, double-blind, placebo-controlled trial, eligible patients were randomized into two groups. After anaesthesia induction, ultrasound-guided lateral TAP block was performed with either 30 ml of 0.4% ropivacaine (Group T) or an equivalent volume of normal saline (Group C). The primary outcomes were opioid consumption during surgery and in the first 24 h after surgery. Secondary outcomes included postsurgical pain intensity immediately awakening from anaesthesia and at 0.5, 1, 2, 6, 12, and 24 h after surgery, as well as recovery variables including the incidence of postoperative nausea and vomiting (PONV), sleep quality, time to first ambulation, drainage and length of hospital stay. A total of 104 patients were enrolled and randomized (53 in Group T and 51 in Group C). Laparoscopic surgery was converted to open surgery in one patient of Group T; this patient was excluded from the outcome analysis. The opioid consumption during surgery (intravenous morphine equivalent dose: median 35.0 mg [interquartile range 18.0, 49.6] in Group C vs. 40.3 mg [20.9, 59.0] in Group T, P = 0.281) and in the first 24 h after surgery (10.8 mg [7.8, 21.7] in Group C vs. 13.2 mg [8.0, 26.6] in Group T, P = 0.311) did not differ significantly between groups. There were no significant differences between groups regarding the pain intensity at all time points after surgery and the recovery variables (all P > 0.05). Our results showed that, in patients undergoing retroperitoneoscopic renal surgery, preoperative lateral TAP did not decrease intra- and postoperative opioid consumption, nor did it relieve pain intensity or promote postoperative recovery in the first 24 h after surgery. However, the trial might be underpowered. This study was registered on November 4, 2017, in the Chinese Clinical Trail Registry with the identification number ChiCTR-INR-17013244 .


Efficacy of Topically Administered Rho-Kinase Inhibitor AR-12286 in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma.
To evaluate the efficacy of rho-associated protein kinase inhibitor, AR-12286 topical solution, for its effect in eyes with exfoliation syndrome (XFS) and ocular hypertension (OHT) or exfoliative glaucoma (XFG) and examine any lasting effect on intraocular pressure (IOP) after discontinuation. Prospective, double-masked, randomized, interventional study. Patients with XFS and OHT or XFG were enrolled. The study eyes were treated once daily with AR-12286, randomized to 0.5% or 0.7% for 24 weeks. Visits included baseline, 1, 4, and 12 weeks after drug initiation; at 12 weeks AR-12286 was discontinued for 1 week and was resumed at week 13. At the week 24 visit, AR-12286 was discontinued, and a final reexamination was performed at week 25. Ten patients were treated. Mean baseline IOP was 25±2.4 mm Hg, mean IOP was reduced to 19.1±2.3 mm Hg at 1 week (P<0.001), 17.5±3.6 mm Hg at 4 weeks (P<0.001), and 17.4±3.6 mm Hg at 12 weeks (P<0.001), yielding an average IOP reduction of 23.6%, 30%, and 30.4%, respectively. At the week 13 visit, 1 week after the drug was discontinued, mean IOP increased to 21.6±5.4 mm Hg (P=0.06 compared with baseline visit). At week 24, the mean IOP was 21.8±7.8 mm Hg (P=0.2, and AR-12286 was discontinued). At week 25, the mean IOP was 21.3±5.3 mm Hg (P=0.06). AR-12286 was well tolerated and provided statistically significant reduction in IOP in patients with XFS and OHT or XFG. This drug may represent an additional therapeutic paradigm for the treatment of XFG.


Protective Effects of Bombyx batryticatus Protein-Rich Extract Against Cisplatin-Induced Nephrotoxicity in HEK293 Cells and a Mouse Model.
Cisplatin, a potent and prominent chemotherapeutic drug, has considerable side effects, including nephrotoxicity, which limits its therapeutic application and efficacy. Therefore, the development of agents that protect normal cells while preserving cisplatin's chemotherapeutic properties is of utmost importance. This study aimed to explore the protective effects of Bombyx batryticatus protein-rich extract (BBPE) against cisplatin-induced nephrotoxicity in a cisplatin-treated mouse model and human embryonic kidney (HEK293) cells. Apoptosis was assessed in HEK293 cells to determine the cytoprotective effects of BBPE and its effects on the generation of cisplatin-induced reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) collapse. Although cisplatin induced nephrotoxicity in HEK293 cells, pretreatment with BBPE showed significant protective effects against cisplatin-induced nephrotoxicity by regulating the expression levels of pro- and antiapoptotic proteins. The cytoprotective effects of BBPE were mediated by decreased ROS production and MTP loss in cisplatin-treated HEK293 cells. The in vitro results were confirmed in the cisplatin-treated mouse model. Pretreatment with BBPE protected against cisplatin-induced nephrotoxicity by restoring malondialdehyde, superoxide dismutase, and catalase levels in kidney tissue and blood urea nitrogen and creatinine serum levels. Furthermore, histopathological assessment and terminal dUTP nick end-labeling staining showed that BBPE mitigated cisplatin-induced nephrotoxicity in kidney tissues. Overall, BBPE may act as a potent agent for alleviating cisplatin-induced nephrotoxicity, thereby increasing the safety of cisplatin-based chemotherapy.


Effects of COVID-19 on child health services utilization and delivery in rural Mozambique: a qualitative study.
Little is known about the COVID-19 pandemic-related disruptions in health services and the resilience of the health system response in rural low-resource settings. We conducted a phenomenological qualitative study (October-November 2020) to understand COVID-19-related influences on the utilization and delivery of child health services in Monapo district, rural Mozambique. We interviewed 36 caregivers with children <2.5 years, 21 health providers and 4 district health services staff using in-person in-depth interviews. Data were analysed using inductive thematic content analysis. Our findings showed that caregivers, providers and district health services staff unanimously reported a decrease in child consultations at the start of the pandemic. Administrative data from health facilities confirmed persisting declines in monthly consultations. Respondents explained reductions due to miscommunication about health facility operations, fear of COVID-19, reduced consultation schedules and reduced household incomes. Providers reported several challenges in delivering services including lack of caregiver compliance with risk mitigation measures, caregivers' fear of risk mitigation measures, perceived lack of caregiver knowledge about COVID-19 and lack of supplies and protective equipment. All respondents described how COVID-19 had increased food insecurity and food prices and reduced incomes and livelihoods. These negative economic consequences were perceived as the main reason for reported increases in cases of child malnutrition. Despite reductions, child health service utilization and delivery have largely continued throughout the COVID-19 pandemic, indicating an adaptive and resilient primary health system response in Monapo district. Our findings highlighted the persistent difficulties providers and caregivers face adhering to COVID-19 prevention and risk mitigation measures. A coordinated multi-sectoral response is needed to address the persistent negative economic impacts of the pandemic for young children and their families in rural areas.


Perceptions of early body image socialization in families: Exploring knowledge, beliefs, and strategies among mothers of preschoolers.
This study sought to explore parental perceptions of body image in preschoolers. We conducted semi-structured interviews with 30 primary caregivers of preschoolers to examine knowledge, beliefs, and strategies regarding early body image socialization in families. Thematic Analysis yielded three themes highlighting knowledge gaps, belief discrepancies, and limited awareness of strategies. Findings regarding knowledge: Most participants defined body image as objective attractiveness rather than subjective self-assessment (53%) and focused on negative body image. Beliefs: Although 97% of participants believed weight and shape impact children's self-esteem, 63% believed preschoolers too young to have a body image. Strategies: Most participants (53%) said family was a primary influence on body image, but identified few effective strategies and 63% said they did not do anything to influence children's body image. Findings suggested family body image socialization in preschoolers is occurring outside the awareness of parents and the concept of positive body image is underdeveloped.


Gluco-metabolic effects of oral and intravenous alcohol administration in men.
Ingestion of the calorically dense compound alcohol may cause metabolic disturbances including hypoglycaemia, hepatic steatosis and insulin resistance, but the underlying mechanisms are uncertain. The gastrointestinal tract is well recognised as a major influencer on glucose, protein and lipid metabolism, but its role in alcohol metabolism remains unclear. To examine the effects of oral and intravenous alcohol, respectively, on plasma concentrations of several gluco-regulatory hormones including serum/plasma insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 21 (FGF21). In a double-blinded, randomised, crossover design, we subjected 12 healthy men to intragastric ethanol infusion (IGEI) and an isoethanolaemic intravenous ethanol infusion (IVEI) (0.7 g alcohol per kg body weight), respectively, on two separate experimental days. Isoethanolaemia during the two alcohol administration forms was obtained (P = 0.38). During both interventions, plasma glucose peaked after ~30 min and thereafter fell below baseline concentrations. GIP and GLP-1 concentrations were unaffected by the two interventions. Insulin concentrations were unaffected by IGEI but decreased during IVEI. C-peptide, insulin secretion rate and glucagon concentrations were lowered similarly during IGEI and IVEI. FGF21 concentrations increased dramatically (nine-fold) and similarly during IGEI and IVEI. Alcohol does not seem to affect the secretion of incretin hormones but decreased insulin and glucagon secretion independently of gut-derived factors. IGEI as well as IVEI potently stimulate FGF21 secretion indicating a gut-independent effect of alcohol on FGF21 secretion in humans.


[Role of impaired immune response regulatory processes in the pathogenesis of uveitis associated with rheumatic diseases].
The study was undertaken to define a role of immunological damage reactions in the pathogenesis of uveitis in the presence of rheumatic diseases on the basis of an in-depth analysis of the immunological characteristics of the disease. A complex immunological study was made in 76 rheumatic patients with uveitis in the acute phase of eye diseases. Among the patients, the males and females were 67.1 and 32.9%, respectively; their mean age was 41+/-6.4 years. The authors made CD typing of lymphocytes, by evaluating the processes of their activation and apoptosis, estimated the amount of the cytokines IL-4, IFN-gamma, TNF-alpha, and soluble TNF-alpha receptor in the serum and tear. The authors have established the following characteristics of an immune response in rheumatic patients with uveitis: a predominant impairment of cellular immunity with an increase in the processes of positive activation of lymphocytes and a reduction in the processes of their apoptosis; formation of Th1 deviation of systemic and local immune responses; elevated levels of the proinflammatory cytokine TNF-alpha in the blood and in the tear in particular. Humoral immunity was found to be activated with a rise in the levels of immunoglobulins of all classes and circulating immune complexes.


Physical analysis of Tn10- and IS10-promoted transpositions and rearrangements.
We have investigated by Southern blot hybridization the rate of IS10 transposition and other Tn10/IS10-promoted rearrangements in Escherichia coli and Salmonella strains bearing single chromosomal insertions of Tn10 or a related Tn10 derivative. We present evidence for three primary conclusions. First, the rate of IS10 transposition is approximately 10(-4) per cell per bacterial generation when overnight cultures are grown and plated on minimal media and is at least ten times more frequent than any other Tn10/IS10-promoted DNA alteration. Second, all of the chromosomal rearrangements observed can be accounted for by two previously characterized Tn10-promoted rearrangements: deletion/inversions and deletions. Together these rearrangements occur at about 10% the rate of IS10 transposition. Third, the data suggest that intramolecular Tn10-promoted rearrangements preferentially use nearby target sites, while the target sites for IS10 transposition events are scattered randomly around the chromosome.


Orthodontics for treating temporomandibular joint (TMJ) disorders.
Temporomandibular disorders (TMD) relate to discomfort of the temporomandibular joint (TMJ). The disorder is multifactorial with a degree of psychogenic influence varying throughout an individual's life with phases of symptoms affecting the quality of life. In an attempt to treat this complex group of disorders many treatment modalities have been identified some of which are also considered in other Cochrane reviews. The disorder also has a normal cycle of events appearing to spontaneously improve without treatment. To establish the effectiveness of orthodontic intervention in reducing symptoms in patients with TMD (compared with any control group receiving no treatment, placebo treatment or reassurance) and to establish if active orthodontic intervention leads to TMD. The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched. Handsearching of orthodontic journals and other related journals was undertaken in keeping with the Cochrane Collaboration handsearching programme. No language restrictions were applied. Authors of any studies were identified, as were experts offering legal advice, and contacted to identify unpublished trials. Most recent search: 13th April 2010. All randomised controlled trials (RCTs) including quasi-randomised trials assessing orthodontic treatment for TMD were included. Studies with adults aged equal to or above 18 years old with clinically diagnosed TMD were included. There were no age restrictions for prevention trials provided the follow-up period extended into adulthood. The inclusion criteria required reports to state their diagnostic criteria for TMD at the start of treatment and for participants to exhibit two or more of the signs and/or symptoms. The treatment group included treatment with appliances that could induce stable orthodontic tooth movement. Patients receiving splints for 8 to 12 weeks and studies involving surgical intervention (direct exploration/surgery of the joint and/or orthognathic surgery to correct an abnormality of the underlying skeletal pattern) were excluded. The outcomes were: how well were the symptoms reduced, adverse effects on oral health and quality of life. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in triplicate and independently by three review authors. As no two studies compared the same treatment strategies (interventions) it was not possible to combine the results of any studies. The searches identified 284 records from all databases. Initial screening of the abstracts and titles by all review authors identified 55 articles which related to orthodontic treatment and TMD. The full articles were then retrieved and of these articles only four demonstrated any data that might be of value with respect to TMD and orthodontics. After further analysis of the full texts of the four studies identified, none of the retrieved studies met the inclusion criteria and all were excluded from this review. There are insufficient research data on which to base our clinical practice on the relationship of active orthodontic intervention and TMD. There is an urgent need for high quality randomised controlled trials in this area of orthodontic practice.When considering consent for patients it is essential to reflect the seemingly random development/alleviation of TMD signs and symptoms.


Surface cAMP receptors mediate multiple responses during development in Dictyostelium: evidenced by antisense mutagenesis.
Cell surface cAMP receptors (cARs) have been implicated in multiple aspects of development in Dictyostelium. Antisense mutagenesis has recently provided strong evidence that cARs are necessary for aggregation (Klein et al., 1988. Science (Wash. DC). 241:1467-1472). We show here that the expression of cAR1 antisense mRNA which prevents the appearance of cAR1 antigen also prevents the expression of cAMP-binding activity and blocks multiple cAMP-mediated responses. Chemotactic sensitivity to cAMP was lost as were stimulus-induced cAMP and cGMP production. Furthermore, the expression of developmentally regulated marker genes, dependent on repeated cAMP stimulation, was altered. As a result, the developmental program was severely impaired; most of the cells failed to aggregate and undergo further differentiation.


Effects of carrier solution on insulin bioavailability.
The aim of our study is to assess the influence of the base solution on the availability of biologic insulin expressed in the value of total insulin using the radioimmunoassay method and to monitor the influence of the base solution on the total insulin concentration over time. Total insulin in a saline and in a total nutrient admixture was measured using the RIA method. In 15 experiments, the application of the saline by a perfusor (8 IU Actrapid HM, 100 IU/1 mL + 20 mL saline) was carried out at time intervals of baseline, 5, 10, 30, 60, 90, and 210 minutes. The application of the total nutrient admixture (8 IU Actrapid HM + 20 mL total nutrient admixture) was carried out in the same way. The MANOVA, ANOVA and paired t test with Bonferroni correction were then used for statistical evaluation. The average values of insulin concentration in saline at given time intervals were 21.5 +/- 11.3 mIU/L (5.4% of the theoretically calculated concentration). The level of insulin in the total nutrient admixture did not change over time, and it reached the values of 115.2 +/- 22.3 (28.8% of the theoretically calculated concentration). Changes in insulin concentration in time were found only in the saline (ANOVA time effect p < .001 for saline; p = .26 for total nutrient admixture). The availability of insulin was significantly higher in the total nutrient admixture solution than in the saline in the 3.5-hour experiment. The dependence of insulin concentration on time is present only in saline, and the main changes in insulin bioavailability are within first 60 minutes. The difference could be caused by smaller insulin absorption to the syringe walls and to the set, owing to the amino acids in the mixture. The question whether the amino acid concentration affects insulin bioavailability stays opened to other studies.


Impact of an educational pain management programme on nurses pain knowledge and attitudes in Kenya.
Pain is a common symptom for patients receiving palliative care, but can be relieved by effective pain management. Nurses play a critical part in implementing pain management effectively and must therefore have a solid foundation of knowledge and a positive attitude toward it. The purpose of this study was to implement and evaluate an educational pain management programme (PMP) for nurses in Kenya. The effects of the PMP were measured using a quasi-experimental pre-post test design. Twenty seven nurses from two units in a single health institution in Kenya participated in a baseline assessment using the Nurses Knowledge and Attitudes Survey Regarding Pain (NKASRP). Nine randomly selected nurses then received 7 hours of focused education. This group completed the assessment again both immediately after and 2 weeks after the PMP. A deficit in knowledge and attitudes related to pain management was prominent at baseline. The nurses who received the PMP scored significantly higher on the NKASRP following the PMP: mean scores were 18.44, 28.00, and 27.56 at baseline, first follow-up, and second follow-up assessment respectively. The PMP appears to be effective in improving nurses' pain knowledge and attitudes.


A novel nomogram and risk stratification for early metastasis in cervical cancer after radical radiotherapy.
This study aimed to establish an effective risk nomogram to predict the early distant metastasis (EDM) probability of cervical cancer (CC) patients treated with radical radiotherapy to aid individualized clinical decision-making. A total of 489 patients with biopsy-confirmed CC between December 2018 and January 2021 were enrolled. Logistic regression with the stepwise backward method was used to identify independent risk factors. The nomogram efficacy was evaluated by using the area under the receiver operating characteristic curve (AUC), C-index by 1000 bootstrap replications, etc. Finally, patients were divided into high- and low-risk groups of EDM based on the cut-off value of nomogram points. 36 (7.36%) CC patients had EDM, and 20 (55.6%) EDM had more than one metastatic site involved. Age below 51 (OR = 2.298, p < 0.001), tumor size larger than 4.5 cm (OR = 3.817, p < 0.001) and radiotherapy (OR = 3.319, p < 0.001) were independent risk factors of EDM. For the nomogram model, C-index was 0.701 (95% CI = 0.604-0.798), and 0.675 (95% CI = 0.578-0.760) after 1000 bootstrap resampling validations. The Hosmer-Lemeshow test demonstrated no overfitting (p = 0.924). According to the Kaplan-Meier curve of risk score, patients with high risk were more prone to get EDM (p < 0.001). This is the first research to focus on EDM in CC patients. We have developed a robust scoring system to predict the risk of EDM in CC patients to screen out appropriate cases for consolidation therapy and more intensive follow-up.


Use of mouthguards and headgear in organized sports by school-aged children.
Sports-related orofacial trauma is a serious problem that can be prevented by wearing protective mouthguards and headgear. While this equipment is available, few studies have been done of wearing practices. This study assesses the wearing practices using data from the Child Health Supplement of the 1991 National Health Interview Survey. Results indicate that football was the only sport in which the majority of children used mouthguards and headgear. While statistically significant differences (p<.05) were found in use of the equipment in all sports by grade level, gender, parent's education, ethnicity, and by region of the the country, these differences were not consistent across sports. Healthy People 2000 calls for extending requirements for use of orofacial protective devices to all organizations sponsoring sports that pose risk to injury. Given the complex nature of the findings, multifaceted initiatives that include the promulgation of rules must be developed and tested to determine what approaches are effective in ensuring consistent use.


Paranasal sinuses and middle ear infections: what do they have in common?
Otitis media and sinusitis are among the most common pediatric diseases and they share common features. Although the anatomy, physiology and disease processes are not identical, knowledge of the pathophysiology of middle ear disorders often provides to the pediatrician a useful understanding of sinus diseases. The same risk factors identified for otitis media may play a pivotal role in the development of sinusitis. Moreover, as both paranasal sinuses and middle ear acquire respiratory pathogens from nasopharynx, acute sinusitis is usually caused by the same bacterial pathogens that cause acute otitis media, with a major role for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, while anaerobes may predominate in chronic disease. A responsibility of bacterial biofilms in chronic sinusitis, similarly to otitis media, has been recently suggested. Biofilms, three-dimensional aggregates of bacteria, are refractory to antibiotics and thus might explain why some patients improve while on antibiotics but relapse after completion of therapy.


ABCB1, CYP2B6, and CYP3A4 genetic polymorphisms do not affect methadone maintenance treatment in HCV-positive patients.
The aim of this study was to determine the influence of ABCB1, CYP2B6, and CYP3A4 genetic polymorphisms on methadone metabolism in patients with hepatitis C virus (HCV) undergoing methadone maintenance treatment (MMT). The study included 35 participants undergoing MMT, who were divided in three groups: HCV-positive (N=12), HCV-negative (N=16), and HCV clinical remission (CR) (N=7). The concentrations of methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were determined with gas chromatography-mass spectrometry. The patients were genotyped for ABCB1 rs1045642, CYP2B6 rs3745274, CYP3A4 rs2242480, and CYP3A4 rs2740574 polymorphisms. Differences between single nucleotide polymorphism (SNP) genotypes and methadone-to-EDDP ratio were analysed with one-way ANOVA, which showed no significant difference between the genes (p=0.3772 for ABCB1 rs1045642, p=0.6909 for CYP2B6 rs3745274, and p=0.6533 for CYP3A4 rs2242480). None of the four analysed SNP genotypes correlated with methadone-to-EDDP concentration ratio. A major influence on it in hepatitis C-positive patients turned out to be the stage of liver damage.


Successful novel use of tofacitinib for type II refractory coeliac disease.
Refractory coeliac disease (RCD) occurs when patients with confirmed CD have continuous or recurrent malabsorption and enteropathy after at least 12 months on a gluten-free diet. Differentiating between type I and type II RCD is key as the latter is associated with T-cell aberrancy and considered prelymphoma, with high mortality rates. Current treatment regimens for type II RCD include corticosteroids, biologics and chemotherapy, but there are no proven therapies for this serious condition. Our patient is a middle-aged woman who developed postpartum type II RCD. When she failed multiple drug classes, we did a trial of tofacitinib. Our clinical experience with use of a janus kinase inhibitor was successful, with no associated adverse events. This is the first report in the literature of RCD remission in response to tofacitinib. The use of this novel agent shows promise in reversing this potentially fatal condition.


RNA polymerases from Bacillus subtilis and Escherichia coli differ in recognition of regulatory signals in vitro.
Adaptation of bacterial cells to diverse habitats relies on the ability of RNA polymerase to respond to various regulatory signals. Some of these signals are conserved throughout evolution, whereas others are species specific. In this study we present a comprehensive comparative analysis of RNA polymerases from two distantly related bacterial species, Escherichia coli and Bacillus subtilis, using a panel of in vitro transcription assays. We found substantial species-specific differences in the ability of these enzymes to escape from the promoter and to recognize certain types of elongation signals. Both enzymes responded similarly to other pause and termination signals and to the general E. coli elongation factors NusA and GreA. We also demonstrate that, although promoter recognition depends largely on the sigma subunit, promoter discrimination exhibited in species-specific fashion by both RNA polymerases resides in the core enzyme. We hypothesize that differences in signal recognition are due to the changes in contacts made between the beta and beta' subunits and the downstream DNA duplex.


Paraganglioma and pheochromocytoma upon maternal transmission of SDHD mutations.
The SDHD gene encodes a subunit of the mitochondrial tricarboxylic acid cycle enzyme and tumor suppressor, succinate dehydrogenase. Mutations in this gene show a remarkable pattern of parent-of-origin related tumorigenesis, with almost all SDHD-related cases of head and neck paragangliomas and pheochromocytomas attributable to paternally-transmitted mutations. Here we explore the underlying molecular basis of three cases of paraganglioma or pheochromocytoma that came to our attention due to apparent maternal transmission of an SDHD mutation. We used DNA analysis of family members to establish the mode of inheritance of each mutation. Genetic and immunohistochemical studies of available tumors were then carried out to confirm SDHD-related tumorigenesis. We found convincing genetic and immunohistochemical evidence for the maternally-related occurrence of a case of pheochromocytoma, and suggestive evidence in a case of jugular paraganglioma. The third case appears to be a phenocopy, a sporadic paraganglioma in an SDHD mutation carrier with no immunohistochemical or DNA evidence to support a causal link between the mutation and the tumor. Microsatellite analysis in the tumor of patient 1 provided evidence for somatic recombination and loss of the paternal region of chromosome 11 including SDHD and the maternal chromosome including the centromere and the p arm. Transmission of SDHD mutations via the maternal line can, in rare cases, result in tumorigenesis. Despite this finding, the overwhelming majority of carriers of maternally-transmitted mutations will remain tumor-free throughout life.


Subacute sclerosing panencephalitis: clinical and demographic characteristics.
To determine the clinical and demographic characteristics of children diagnosed with Subacute sclerosing panencephalitis (SSPE). Case series. The Aga Khan University Hospital, Karachi, from January 2000 to June 2012. A retrospective analysis was done, regarding medical charts of 43 children under the age of 16 years with a discharge diagnosis of SSPE. Demographic and clinical characteristics were recorded. RESULTS were expressed as percentages. Most of the 43 patients were male (72%). The average age at presentation was 8.7 years with average duration of symptoms being 100.6 days. History of measles was present in 17 patients (39.5%). All children had seizures at presentation and 65% had cognitive impairment. Most patients required poly therapy for control of seizures. Sodium valproate was the most commonly used anti-epileptic agent; Isoprinosine was tried in 22 (51%) patients. CSF for antimeasles antibodies was positive in approximately 86% of the 40 (93%) children. EEG showed burst suppression pattern in 36 (83.7%) cases. Forty-two patients (97.6%) were discharged home in a vegetative state. SSPE is progressive neurodegenerative disorder. It can be prevented by timely immunization against measles. Measles antibody in the CSF is diagnostic for SSPE and is helpful in early diagnosis. Most patients experience a gradual but progressive decline in motor and cognitive functions.


Inventory of metal complexes circulating in plant fluids: a reliable method based on HPLC coupled with dual elemental and high-resolution molecular mass spectrometric detection.
Description of metal species in plant fluids such as xylem, phloem or related saps remains a complex challenge usually addressed either by liquid chromatography-mass spectrometry, X-ray analysis or computational prediction. To date, none of these techniques has achieved a complete and true picture of metal-containing species in plant fluids, especially for the least concentrated complexes. Here, we present a generic analytical methodology for a large-scale (> 10 metals, > 50 metal complexes) detection, identification and semiquantitative determination of metal complexes in the xylem and embryo sac liquid of the green pea, Pisum sativum. The procedure is based on direct injection using hydrophilic interaction chromatography with dual detection by elemental (inductively coupled plasma mass spectrometry) and molecular (high-resolution electrospray mass spectrometry) mass spectrometric detection. Numerous and novel complexes of iron(II), iron(III), copper(II), zinc, manganese, cobalt(II), cobalt(III), magnesium, calcium, nickel and molybdenum(IV) with several ligands including nicotianamine, citrate, malate, histidine, glutamine, aspartic acid, asparagine, phenylalanine and others are observed in pea fluids and discussed. This methodology provides a large inventory of various types of metal complexes, which is a significant asset for future biochemical and genetic studies into metal transport/homeostasis.


The epidemiology of surgically repaired aneurysms in the United States.
The purpose of this study was to determine the results of surgery for hospitalized cases of aneurysms in the United States, thereby providing a standard of comparison for new techniques proposed to treat aneurysms. Data on hospitalized aneurysm cases were collected from the National Hospital Discharge Survey, a comprehensive database of patients hospitalized in the United States for treatment from the years 1984 to 1994. The National Hospital Discharge Survey samples non-federal, acute-care hospitals with an average length of stay of less than 30 days. All the cases had a diagnosis of or a surgical procedure for a non-cerebral aneurysm. In the year 1994, 51,949 non-cerebral aneurysms were repaired in the United States, and 75% of these procedures were abdominal aortic aneurysm (AAA) surgeries. The operative mortality rates for AAA were higher than previously reported from multi-institutional studies and were found to be 8.4% for elective repair and 68% for emergency AAA repair. The number of aneurysm surgeries per thousand population varied by region: surgery rates were more frequent in the Northeast and less frequent in the West. Surgical volume appeared to decrease for smaller hospitals and increase for larger hospitals for the period between 1990 and 1994. The overall mortality rates for all aneurysm surgeries diminished with hospital size. However, no significant difference was found for the rates of elective AAA repair between hospital sizes. The percentage of men with aneurysms who underwent surgery for repair was significantly higher than for women with aneurysms. In addition, the AAA repair rates increased for men from 1985 to 1994, and the number of women reported with repaired AAAs remained constant. The location of aneurysm, urgency of repair, region, sex, and hospital size are important factors related to patient treatment and outcome. These data provide a standard of comparison against which surgeons can compare their own results, and they provide a benchmark for the evaluation of interventional techniques proposed to treat aneurysms.


Correlation between the topologically close-packed structure and the deformation behavior of metallic Cu64.5Zr35.5.
The topologically close-packed (TCP) structural characteristics in a model metallic glass (MG) of Cu64.5Zr35.5 have been investigated by molecular dynamics simulations. A group of structural indicators based on the largest standard cluster (LaSC) have been correlated with the non-affine displacement (D2) of atoms, so as to reveal the hidden correlation between local structures and deformation behavior of Cu64.5Zr35.5 during compression. It was found that the 15 types of Top-10 LaSCs are all TCP-like ones, among which the most numerous icosahedron (Z12 and 1-Z12) decreases in population sharply and moderately during respectively the elastic and yield region of compression; while in the fluid-flow region, the number of all Top-10 LaSCs tends to be almost constant. Low-D2 atoms prefer to link with each other; while medium-D2 atoms act as transition structures between backbone areas and deformation areas. Most interestingly, the deformation response of TCP-like atoms is not only determined by its nearest neighbor characteristics, but also depends on the linkage with other atoms. In addition, icosahedral atoms with a higher degree of medium range five-fold symmetry (MRFFS) are more resistant to the stress-induced deformation. Therefore, the TCP characteristics, including its nearest neighbor feature and the inter-connection between TCP LaSCs, are closely related with the deformation behavior of atoms, especially the MRFFS (up to 5 layers) of icosahedral atoms. These findings shed new light on the understanding of the relationship between microstructure and deformation response of MGs, which will promote the development of deformation theory of MGs.


BsmI vitamin D receptor polymorphism and pathogenesis of parathyroid adenoma.
The role of vitamin D receptor (VDR) gene polymorphism in the pathogenesis of hyperparathyrodism is not clear yet. The aim of this study was to examine the role of BsmI VDR gene polymorphism in patients with primary hyperparathyrodism (PHP) secondary to adenomas. Fifty-two postmenopausal women with PHP, mean age 64.5 years, were compared with a normal age-matched female population (n = 81). Distribution of BsmI polymorphism in PHP group was: Bb 54% (28/52); BB 21% (11/52); bb 25% (13/52). In the control group, the distribution in PHP group as follows: Bb 49% (40/81); BB 16% (13/81); bb 35% (28/81). No statistical differences were found between the two groups. In the PHP group, no statistical associations were found between different allelic distribution and age, creatinine, hematocrit, phosphorus, alkaline phosphatase (ALP), total calcium, serum parathyroid hormone (PTH), or gland weight. This data suggest that at least in this group, BsmI VDR gene polymorphism appears to be without relevance in clinical presentation and possibly tumorigenesis in PHP secondary to adenomas.


[Chromosome markers of drug resistance as the selectors of potential vaccinal strains].
Mutations resulting in acquisition of the resistance to rifampicin, streptomycin, neamine, polymyxin M, mecillinam and high concentrations of nalidixic acid were studied with respect to their effect on virulence of Shigella flexneri by transduction of the markers from the spontaneous avirulent mutants to the initial strain. It was shown that the acquisition of the determinants of the resistance to rifampicin, streptomycin, neamine (nea A) and high concentration of nalidixic acid resulted in 100 per cent of the cases in losing the transductant capacity for causing keratoconjunctivitis in guinea-pigs. With the mutations resulting in the acquisition of resistance to neamine (nea B) and mecillinam virulence was lost only in a part of the clones (33 and 53 per cent respectively). The changes in the pathogenic properties of the transductants with the acquired markers of the resistance to the above antibiotics were associated with impairment of the bacterial cell vital structures. It is suggested that the genetically characterized avirulen immunogenetic mutants be used as potential vaccinal strains.


Side-by-Side Comparison of Compensation Beads Used in Polychromatic Flow Cytometry.
Compensation or unmixing is essential in analyzing multiparameter flow cytometry data. Errors in data correction, either by compensation or unmixing, can completely change the outcome or mislead the researchers. Owing to limited cell numbers, researchers often use synthetic beads to generate the required single stains for the necessary calculation. In this study, the capacity of synthetic beads to influence data correction is evaluated. Corrected data for human peripheral blood cells were generated using cell-based compensation from the same cells or bead-based compensation to identify differences between the methods. These data suggest that correction with beads on full-spectrum and conventional cytometers does not always follow the basic flow compensation/unmixing expectations and alters the data. Overall, the best approach for bead-based correction for an experiment is to evaluate which beads and fluorochromes are most accurately compensated/unmixed.


Multicopy plasmids affect replisome positioning in Bacillus subtilis.
The DNA replication machinery, various regions of the chromosome, and some plasmids occupy characteristic subcellular positions in bacterial cells. We visualized the location of a multicopy plasmid, pHP13, in living cells of Bacillus subtilis using an array of lac operators and LacI-green fluorescent protein (GFP). In the majority of cells, plasmids appeared to be highly mobile and randomly distributed. In a small fraction of cells, there appeared to be clusters of plasmids located predominantly at or near a cell pole. We also monitored the effects of the presence of multicopy plasmids on the position of DNA polymerase using a fusion of a subunit of DNA polymerase to GFP. Many of the plasmid-containing cells had extra foci of the replisome, and these were often found at uncharacteristic locations in the cell. Some of the replisome foci were dynamic and highly mobile, similar to what was observed for the plasmid. In contrast, replisome foci in plasmid-free cells were relatively stationary. Our results indicate that in B. subtilis, plasmid-associated replisomes are recruited to the subcellular position of the plasmid. Extending this notion to the chromosome, we postulated that the subcellular position of the chromosomally associated replisome is established by the subcellular location of oriC at the time of initiation of replication.


Substitution of thoracic oesophagus by interposition of a pedicled gastric tube, preserving LES function: clinical and histological follow-up.
Assessment of clinical evolution and histological findings in a group of animals experimentally operated on to substitute the thoracic oesophagus with a gastric tube. Six piglets underwent oesophageal replacement with a gastric tube, constructed from the greater curvature of stomach and pedicled on the gastroepiploic vessels, which was interposed between the oesophageal stumps. At follow-up, all animals were found to be growing and eating normally, apart from case no 1 (stenosis of the lower oesophageal anastomosis). Ph-metry showed a neutral pH on the gastric tube. Postmortem histological analysis of the gastric tube and native oesophagus samples did not show any significant lesions, except in case no 1 (inflammation of the gastric tube and upper oesophagus due to food stasis). The technique of substitution of the oesophagus with an interposed pedicled gastric tube can be a breakthrough in existing surgical methods of oesophageal replacement.


Pharmacist Involvement in Addressing Public Health Priorities and Community Needs: The Allegheny County Racial and Ethnic Approaches to Community Health (REACH) Project.
Community-clinical linkages are connections between community and clinical sectors to improve population health, and community-based pharmacists are well positioned to implement this strategy. We implemented a novel approach to community-clinical linkages in African American communities in which community-based pharmacists implement screenings for chronic disease and social determinants of health, make referrals to clinical and social services, and follow up with patients to support linkage to care in nontraditional health care settings. The community-based pharmacist navigation program works with multisector partners to increase referrals and access to existing health and social service programs. We used a mixed-methods evaluation approach to collect and analyze data on program characteristics and the linkage intervention. From February 2019 to March 2020, 702 African American community members received preventive health screenings, and 508 (72%) were referred to clinical and social services. Pharmacists demonstrated the ability to implement clinical preventive services in nontraditional health care settings and improve access to care through the provision of community-clinical linkages.


Study on the region-specific expression of epididymis mRNA in the rams.
The epididymis is divided into three regions including the caput, corpus and cauda. Gene expression profiles in different regions indicate the different functions of epididymis which are crucial for sperm maturation. In this study, three one-year-old rams was used as the experimental animal. Transcriptome sequencing technology was used to sequence mRNA in the caput, corpus and cauda of the epididymis. Based on the spatiotemporal-specific expression pattern in the epididymis, the mRNA expression profiles of the three parts of the epididymis were analysed. Region-specifically expressed genes were analysed by GO and KEGG analyses to screen the key genes involved in sheep sperm maturation. We obtained 129, 54 and 99 specifically expressed genes in the caput, corpus and cauda, respectively. And twenty specific expressed genes related to sperm maturation were used to construct functional networks. The heatmap showed that 6 genes of LCN protein family were highly expressed in the head of epididymis of sheep. We infer that sperm maturation is gradual in the epididymis and that there are significant differences in epididymal gene expression patterns between different species. This provides a data resource for analysing the regulatory mechanism of epididymis genes related to sperm maturation in rams.


Synthesis of Aryl C-Glycosides via Iron-Catalyzed Cross Coupling of Halosugars: Stereoselective Anomeric Arylation of Glycosyl Radicals.
We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl C-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP. The chemoselective nature of the reaction allows the use of synthetically versatile acetyl-protected glycosyl donors and the incorporation of various functional groups on the aryl moieties, producing a diverse array of aryl C-glycosides, including Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), and a prevailing diabetes drug. The cross-coupling reaction proceeds via generation and stereoselective trapping of glycosyl radical intermediates, representing a rare example of highly stereoselective carbon-carbon bond formation based on iron catalysis. Radical probe experiments using 3,4,6-tri-O-acetyl-2-O-allyl-α-d-glucopyranosyl bromide (8) and 6-bromo-1-hexene (10) confirm the generation and intermediacy of the corresponding glycosyl radicals. Density functional theory (DFT) calculations reveal that the observed anomeric diastereoselectivity is attributable to the relative stability of the conformers of glycosyl radical intermediates. The present cross-coupling reaction demonstrates the potential of iron-catalyzed stereo- and chemoselective carbon-carbon bond formation in the synthesis of bioactive compounds of certain structural complexity.


The smallest worthwhile effect of primary care physiotherapy did not differ across musculoskeletal pain sites.
To determine and compare estimates of the smallest worthwhile effect (SWE) for physiotherapy in neck, shoulder, and low-back pain patients and to investigate the influence of sociodemographic, clinical, and psychological factors on these estimates. A structured telephone interview was conducted before treatment was commenced in 160 patients referred for primary care physiotherapy. The benefit-harm trade-off method was used to estimate the SWE of physiotherapy for the following outcomes; pain, disability, and time to recovery, compared with the improvement achieved without any treatment (natural course). Regression analyses were used to assess the influence of sociodemographics, clinical variables, and intake scores on pain, disability, and psychological scales. The median SWE for improvements on pain and disability was 20% (interquartile range 10%-30%), and the SWE for time to recovery was 10 days (interquartile range 7-14 days) over a period of 6 weeks. These estimates did not differ with respect to pain location (neck, shoulder, or back) and were generally unaffected by sociodemographic, clinical, and psychological factors. People with neck, shoulder, and low-back pain need to see at least 20% of additional improvement on pain and disability compared with natural recovery to consider that the effect of physiotherapy is worthwhile, given its costs, potential side effects, and inconveniences.


[Computer volume reconstruction of the anatomical structure of the brain].
The possibility of constructing three-dimensional computer models of the brain and intrabrain structures on the basis of stereotaxic atlases for calculating the geometry of structures and modeling stereotaxic operations was considered. A special program (Contour-1) was developed on the basis of the Kristiansen-Zedenberg's and Ganapatchi-Denechi algorithms with the use of the OpenGL library. Some problems were revealed, which do not allow one to construct three-dimensional models of the geometry of intrabrain structures (breaks between the sections of the brain, insufficient accuracy of the alignment of the images of sections relative one another, etc.).


The negative effect of heavy work life during adolescence on height development of young males.
The aim of this study was to determine the physical development level of post-adolescent automotive repair workers who had been employed in heavy work during adolescence, a critical developmental period. Young workers (Group 1, N = 106, Mean age = 18.33, SD = 0.65) employed an average of 6 years in workshops in the capital of Turkey, Ankara. For the control group, two groups of the same age but having a difference in terms of socioeconomic status were chosen. The first one of these was comprised of individuals who had the same socioeconomic status as the laborers (Group 2, N = 106, Mean age = 18.33, SD = 0.65) but were not laborers. The second control group was composed of individuals from the higher socioeconomic levels of society (Group 3, N = 100, Mean Age = 18.45 SD = 0.63). Weight, height and measures were taken from the individuals and the body mass index (kg/m2) was calculated. The results of the analysis show that, although all the variables of the labor group were lower than Group 2, the difference is only significant for the height variable (p < 0.05). These findings reveal that, having completed a critical developmental period such as adolescence after being employed in heavy work, the automotive repair youngsters are prone to chronic developmental retardation.


[Diastolic function of the left ventricle in elderly patients with ischemic heart disease before and after the coronary shunting operation].
In order to assess the effect of coronary shunting (CS) on the diastolic function of the left ventricle (DFLV) in sick people of elderly and old age with ischemic heart disease stress-Doppler-echocardiogram was performed on 45 men at the age of 65 to 75 years before and after CS. The patients were formed into two groups on the basis of preoperative study of DFLV. Group I consisted of patients who had no myocardial infarction (MI) or who have had small-focal MI, parameters of transmitral blood flow in rest corresponded to impaired diastolic function on the "disturbed relaxation" type. Group II consisted of patients who have had transmural (large-focal) MI and whose DFLVcorresponded to the "pseudonormal blood flow" type (by S. Appleton). Analysis of indices of transmitral blood flowin rest before and after the operation showed its normalizing effect on DFLV in Group I. DFLV parameters in Group II demonstrated positive effect of the operation and were most pronounced when parameters of transmitral blood flow in stress were compared before and after CS. Thus, surgical revascularization of myocardium facilitates improvement of DFLV which can in its turn serve as an additional criterion of assessment of adequacy of CHD surgical treatment of sick people of elderly and old age with post infarction cardio sclerosis of various degree of manifestation.


Induction of suspension feeding in spionid polychaetes by high particulate fluxes.
The feeding behavior of three species of spionid polychaetes varied with water velocity. At moderate flows the worms ceased deposit feeding, formed their feeding tentacles into helices, and lifted them into the water column to capture material in suspension. This behavior was apparently a response to increased flux of suspended matter at high flows rather than to flow velocity alone. Organisms capable of switching their feeding behavior may be common in dynamically variable benthic environments.


Ciliatasecones A-C, three rearranged limonoids from Toona ciliata var. yunnanensis.
Ciliatasecones A-C (1-3), three rearranged limonoids with a novel ring-seco model and an unprecedented cycle system, were isolated from the root bark of Toona ciliata var. yunnanensis. Ciliatasecones A-B (1-2) share a novel cyclopenta[b]furan ring C/D system through C-9/11-seco and C-11/14 ether linkage. Ciliatasecone C (3) was found to possess a rare rearranged six-membered lactone ring B between C-7 and C-9. Plausible biogenetic pathway speculation indicated that C-9/11 cleavage and oxygen bridge formation played the key roles in the framework rearrangement of 1-3.


An unusual clinical vignette of oro-pharyngeal discomfort: Pterygoid Hamulus syndrome.
A straightforward clinical reasoning is always difficult in patients with persistent orofacial pain with vague symptoms. Craniofacial pain or Orofacial pain can have a mixture of causes ranging from neurogenic, myogenic, and psychogenic factors intertwined amidst the intricate anatomy with a high vascular network. This plethora of uncertainty blurs the judgment for such patients to whom we provide care. We hereby present a case of a 17 year old female with vague pain on talking, chewing and even swallowing when initially examined; this chronic orofacial pain often worsened her quality of life. The aim of this manuscript is to present a case of Pterygoid Hamulus syndrome that was misdiagnosed as glossopharyngeal and myofascial neuralgia. The condition was managed by surgical excision of the elongated pterygoid hamulus, following a recurrence of her symptoms. The patient was relieved of pain only after the surgical excision of the elongated hamulus. The surgery was decided upon only after conservative management had not provided much relief and the manuscript also discusses the ambiguous composite pain referral pattern in Pterygoid Hamulus syndrome.


Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease.
Aberrant phosphorylation of the neuronal cytoskeleton is an early pathological event in Alzheimer's disease (AD), but the underlying mechanisms are unclear. Here, we demonstrate in the brains of AD patients that neurofilament hyperphosphorylation in neocortical pyramidal neurons is accompanied by activation of both Erk1,2 and calpain. Using immunochemistry, Western blot analysis, and kinase activity measurements, we show in primary hippocampal and cerebellar granule (CG) neurons that calcium influx activates calpain and Erk1,2 and increases neurofilament phosphorylation on carboxy terminal polypeptide sites known to be modulated by Erk1,2 and to be altered in AD. Blocking Erk1,2 activity either with antisense oligonucleotides to Erk1,2 mRNA sequences or by specifically inhibiting its upstream activating kinase MEK1,2 markedly reduced neurofilament phosphorylation. Calpeptin, a cell-permeable calpain inhibitor, blocked both Erk1,2 activation and neurofilament hyperphosphorylation at concentrations that inhibit calpain-mediated cleavage of brain spectrin. By contrast, inhibiting Erk1,2 with U-0126, a specific inhibitor of Mek1,2, had no appreciable effect on ionomycin-induced calpain activation. These findings demonstrate that, under conditions of calcium injury in neurons, calpains are upstream activators of Erk1,2 signaling and are likely to mediate in part the hyperphosphorylation of neurofilaments and tau seen at early stages of AD as well as the neuron survival-related functions of the MAP kinase pathway.


Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins.
The carcinogen-induced rat mammary carcinoma model, developed a quarter of a century ago by Dr. Charles Brenton Huggins, is today the standard laboratory animal model in the study of human breast cancer. This model has a number of features that make it particularly attractive to the experimental oncologist, e.g., tumor induction ease and reliability, organ site specificity, tumors of ductal origin, tumors of predominantly carcinomatous histopathological characteristics, tumors of varying growth factor and/or hormone responsiveness, and the potential to examine tumor initiation and promotion processes. Since the development of this model, an extensive literature describing the biological behavior and responsiveness of these tumors has been provided. The purpose of this communication is to condense, summarize, and integrate this vast literature into a single review with the intent on facilitating information acquisition and conceptualism by both the new and the established experimental oncologist. In addition, and equally important, this communication is a tribute to Dr. Huggins, whose pioneering efforts in the development of this model and whose scientific contributions and dedication to the oncological sciences in general have made an important and lasting impact on us all.


Promotion of colorectal neoplasia in experimental murine ulcerative colitis.
The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown. To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment. Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases. In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone. Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.


Effect of cigarette smoke on salivary proteins and enzyme activities.
Exposure of human plasma in vitro to gas-phase cigarette smoke (CS) causes a marked modification of plasma proteins as measured by protein carbonyl assay. Aldehydes present in CS may cause this elevation of protein carbonyls by reacting with sulfhydryl groups of proteins. Saliva is the first body fluid to confront the inhaled CS. Thus, in vitro exposure of saliva to nine "puffs" of CS also showed a distinct increase in protein carbonyls. Ascorbate and desferrioxamine mesylate had little effect on protein carbonyl formation, while GSH and N-acetylcysteine considerably inhibited the accumulation of protein carbonyls due to CS exposure. Following the exposure to CS, the activities of several salivary enzymes-amylase, lactic dehydrogenase (LDH), and acid phosphatase-were found to be significantly reduced (34, 57, and 77%, respectively). However, CS had no effect on the activities of aspartate aminotransferase and alkaline phosphatase. Addition of 1 mM of GSH and N-acetylcysteine considerably protected LDH and amylase activities, suggesting that sulfhydryl groups are affected in LDH and amylase. On the other hand, addition of 1 mM ascorbate caused a further loss of LDH and amylase activities, which could be partially prevented by the addition of desferrioxamine mesylate, implicating metal-catalyzed oxidation processes. Finally, loss of acid phosphatase activity was completely unaffected by any of the above antioxidants. It is concluded that the loss of salivary enzyme activities may be due to various agents in the CS that affect the enzyme activities via different mechanisms.


PPAR-γ with its anti-inflammatory and anti-fibrotic action could be an effective therapeutic target in IBD.
Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence of a chronic inflammation that usually occurs during Inflammatory Bowel Disease (IBD). The relationship between inflammation and fibrosis in IBD remains still unclear and nevertheless the recent pharmacological progresses, currently the only resolutive therapeutic strategy is surgery, especially when complications (stricture, stenosis and obstruction of intestinal tracts) appear. As many different cellular types and molecular mechanisms are implicated in the pathogenesis of IBD, the identification of molecules able to counteract this process could be crucial. This is a literature review of several articles published on PubMed databases. A number of researches suggest that Proliferator-Activated Receptor-gamma (PPAR-γ) has both anti-inflammatory and anti-fibrotic effects in many organs. PPAR-γ has been demonstrated to be able to downregulate pro-inflammatory cytokines production such as Interleukin (IL)-4,-5,-6 but also to interfere with profibrotic molecules as Platelet-Derived Growth Factor (PDGF), IL-1 and Transforming Growth Factor Beta (TGF-β), the main promoter of fibrosis. In preliminary clinical trials and in experimental models of intestinal fibrosis, natural and chemical PPAR-γ ligands have ameliorated the fibrotic process. Since PPAR-γ could play a crucial role in the development of the disease, the research of new molecules, capable of ameliorating both inflammation and fibrosis lesions, as PPAR-γ agonists, could represent a valid and effective therapeutic approach for the prevention and treatment of IBD and intestinal fibrosis.


Metallic nonsuperconducting phase and D-wave superconductivity in Zn-substituted La1.85Sr0.15CuO4
Measurements of the resistivity, magnetoresistance, and penetration depth were made on films of La1.85Sr0.15CuO4, with up to 12 at. % of Zn substituted for the Cu. The results show that the quadratic temperature dependence of the inverse square of the penetration depth, indicative of d-wave superconductivity, is not affected by doping. The suppression of superconductivity leads to a metallic nonsuperconducting phase, as expected for a pairing mechanism related to spin fluctuations. The metal-insulator transition occurs in the vicinity of k(F)l approximately 1, and appears to be disorder driven, with the carrier concentration unaffected by doping.


Single-photon microscopy to study biomolecular condensates.
Biomolecular condensates serve as membrane-less compartments within cells, concentrating proteins and nucleic acids to facilitate precise spatial and temporal orchestration of various biological processes. The diversity of these processes and the substantial variability in condensate characteristics present a formidable challenge for quantifying their molecular dynamics, surpassing the capabilities of conventional microscopy. Here, we show that our single-photon microscope provides a comprehensive live-cell spectroscopy and imaging framework for investigating biomolecular condensation. Leveraging a single-photon detector array, single-photon microscopy enhances the potential of quantitative confocal microscopy by providing access to fluorescence signals at the single-photon level. Our platform incorporates photon spatiotemporal tagging, which allowed us to perform time-lapse super-resolved imaging for molecular sub-diffraction environment organization with simultaneous monitoring of molecular mobility, interactions, and nano-environment properties through fluorescence lifetime fluctuation spectroscopy. This integrated correlative study reveals the dynamics and interactions of RNA-binding proteins involved in forming stress granules, a specific type of biomolecular condensates, across a wide range of spatial and temporal scales. Our versatile framework opens up avenues for exploring a broad spectrum of biomolecular processes beyond the formation of membrane-less organelles.


'You sort of switch off': exploring mindlessness in injecting drug users' accounts of blood.
Risk of blood borne virus among injecting drug users is high and is a significant challenge for public health efforts. Mindlessness/mindfulness theory provides an alternative lens through which to understand social phenomena. Interview transcripts of 32 current and former injectors were explored for evidence of mindless injecting (or automatic behaviour). Mindlessness in injecting practices can be important as opportunities to reduce injecting risk can emerge from understanding 'expert' approaches to injecting. Further work is required to generate fuller understandings of this construct on injecting drug use and to incorporate carefully and sensitively this tool into health promotion efforts.


Factors influencing caries status and treatment needs among pregnant women attending a maternity hospital in Udaipur city, India.
To estimate the prevalence and severity of dental caries along with the treatment needs; to determine the factors that influence dental caries status among pregnant women attending a district maternity hospital in Udaipur, India. Study sample comprised of 206 pregnant women attending a district maternity hospital in Udaipur, India. Clinical data were collected on dental caries by DMFT and treatment needs as described in World Health Organization Dentition status and Treatment needs. The overall caries prevalence was 87%. Mean caries experience differed significantly among women in various trimesters, it was found to be 3.59 and 3.00 in 1st and 2nd trimester subjects respectively while it was greatest (4.13) among those in 3rd trimester. One surface filling was the most predominant treatment need. Age and occupation of husband explained a variance of 6.8% and 4.2% for decayed and filled components respectively while the only predictor for missing teeth and DMFT that explained a variance of 9.6% and 5.7% respectively was trimester of pregnancy. Dental caries experience and the need for one surface restoration increased with age. Trimester of pregnancy was a significant predictor for missing teeth and DMFT, while decayed teeth and filled teeth were influenced by age and socio-economic level respectively. Key words:Dental caries, treatment needs, pregnant, age, trimester.


Predicting treatment outcomes of major depressive disorder by early improvement in painful physical symptoms: a pooled analysis of double-blind, placebo-controlled trials of duloxetine.
We determined if early improvement in painful physical symptoms (PPS) can be a predictor of remission in the treatment of major depressive disorder (MDD). We included randomized, double-blind, parallel-group clinical trials of duloxetine (40-60 mg/day) versus placebo for the acute treatment of MDD with associated PPS. Only those studies using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Brief Pain Inventory - Short Form (BPI-SF) were included. Three studies met all criteria and included male or female outpatients aged ≥18 years who met the diagnostic criteria for MDD, had a MADRS total score ≥20, and had at least moderate pain (BPI-SF average pain score ≥3). Positive predictive values (PPVs) and negative predictive values (NPVs) of early improvement in PPS for remission were analyzed. PPVs were the proportion of patients with remission (MADRS total score ≤10) at week 8 out of patients who experienced early improvement in BPI-SF average pain score (≥30% decrease from baseline at week 1, 2, or 4). NPVs were the proportion of patients without remission (MADRS total score >10) at week 8 out of patients who did not experience early improvement in PPS. Data from 1,320 patients were analyzed (duloxetine N=641 and placebo N=679). The overall remission (MADRS total score ≤10 at week 8) rate for the duloxetine group was significantly higher than the placebo group (38.5% vs 21.8%; P<0.0001). For both treatment groups, PPVs of early improvement in BPI-SF (30% improvement from baseline) were higher than the overall remission rate for all weeks examined (weeks 1, 2, and 4); in general, NPVs of early improvement in BPI-SF for nonremission were higher than the overall nonremission rate. Early improvement in PPS can be a useful clinical indicator of subsequent treatment outcome for MDD patients with associated PPS.


[From the health plan to teaching and learning plan: pathways for the planning of CME in the Provincia Autonoma of Bolzano (Italy)].
Evidence based medicine (EBM) proposes a step by step pathway, that represents today an useful methodological reference to make clinical decisions. The authors propose that this methodological approach (define the problem; searche the best evidence; evaluation of the results in conjunction with the skills and experience that the health worker has already acquired; evaluation of the whole process), can be used to guide the questions in the use of CME. CME experience in the Provincia Autonoma of Bolzano (Italy) is shortly reported, emphasizing the involvement of the different stakeholders in planning and verification of teaching and learning.


Giant radiation-induced color halos in quartz: solution to a riddle.
The radii of radiation-induced color halos(RICHs) surrounding radioactive mineral inclusions in mica generally correspond closely to the calculated range of common uranogenic and thorogenic alpha particles in mica. Many exceptions are known, however, and these variants have led investigators to some rather exotic interpretations. Three RICHs found in quartz are identified as aluminum hole-trapping centers. Whereas the inner radii of these RICHs closely match the predicted range of the most energetic common alphas(39 micrometers), the color centers observed extend to 100 micrometers. Migration of valence-band holes down a radiation-induced charge potential might account for enigmatic RICHs. Such RICHs provide natural experiments in ultraslow charge diffusion.


DNA adduct formation from tobacco-specific N-nitrosamines.
Tobacco-specific N-nitrosamines are a group of carcinogens derived from the tobacco alkaloids. They are likely causative factors for cancers of the lung, esophagus, pancreas, and oral cavity in people who use tobacco products. The most carcinogenic tobacco-specific nitrosamines in laboratory animals are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and N'-nitrosonornicotine (NNN). DNA adduct formation from NNK and NNN has been studied extensively and is reviewed here. NNK is metabolically activated by cytochromes P450 to intermediates which methylate and pyridyloxobutylate DNA. The resulting adducts have been detected in cells and tissues susceptible to NNK carcinogenesis in rodents. The methylation and pyridyloxobutylation pathways are both important in carcinogenesis by NNK. NNK also induces single strand breaks and increases levels of 8-oxodeoxyguanosine in DNA of treated animals. NNAL, which like NNK is a potent pulmonary carcinogen, is also metabolically activated to methylating and pyridyloxobutylating intermediates. NNN pyridyloxobutylates DNA in its rat target tissues, esophagus and nasal mucosa. Methyl and pyridyloxobutyl DNA adducts are detected in human tissues. The methyl adducts most likely result in part from exposure of smokers to NNK, but these adducts are also detected in non-smokers. Some of the methyl adducts detected in non-smokers may be due to environmental tobacco smoke exposure. There are also potential dietary and endogenous sources of these adducts. Pyridyloxobutyl DNA adducts in human tissues result mainly from exposure to tobacco-specific N-nitrosamines. In laboratory animals, DNA adduct formation and carcinogenicity of tobacco-specific N-nitrosamines are closely correlated in many instances, and it is likely that similar relationships will hold in humans.


Measuring Outcomes in Psoriatic Arthritis: Comparing Routine Assessment of Patient Index Data and Psoriatic Arthritis Impact of Disease.
To examine the construct validity of Routine Assessment of Patient Index Data 3 (RAPID3) and Psoriatic Arthritis Impact of Disease (PsAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, poly articular disease, enthesitis, and dactylitis, and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PRO). Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014 and 2016. PARC is a longitudinal observational cohort study conducted at 4 US institutions. In this cross-sectional study, construct validity was assessed by examining Spearman correlation coefficients for RAPID3 and PsAID with physician-reported disease activity measures and other PRO [e.g., Medical Outcomes Study Short Form-12 physical component summary/mental component summary (SF-12 PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F)]. Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PsAID12 as outcomes of interest and the hypothesized contextual factors as covariates. Among 401 patients enrolled in PARC, 347 completed RAPID3 or PsAID12. Of these, most were white females with a mean age of 51.7 years (SD 14.02). RAPID3 and PsAID were highly correlated (r = 0.90). These measures were also correlated with the SF-12 PCS (r = -0.67) and FACIT-F (r = -0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression. RAPID3 and PsAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PsAID12.


Restoration and preservation of first metatarsal length using the distraction scarf osteotomy.
The authors reviewed the records of 8 patients who underwent a distraction scarf osteotomy of the first metatarsal, and report the radiographic outcomes achieved with this procedure. The osteotomy was used to reestablish or maintain the length of the first metatarsal, without the use of a structural bone graft. The osteotomy was used as part of a revisional procedure for a failed bunionectomy in 4 patients. In the remaining patients, the procedure was used to preserve the length of the first metatarsal in conjunction with a Lapidus arthrodesis. The first and second metatarsals were measured radiographically, and the length of the first metatarsal was expressed as a percentage of the length of the second metatarsal. The average proportional increase in first metatarsal length obtained in the patients undergoing correction of the shortened first metatarsal was 7.08%, and the difference between the pre- and postoperative length of the first metatarsal was statistically significant (P = .0013) in these patients. Relative shortening of the first metatarsal was avoided in those patients undergoing distraction scarf osteotomy in conjunction with Lapidus arthrodesis. ACFAS Level of Clinical Evidence: 4.


Left atrial appendage occlusion for stroke prevention in atrial fibrillation in Europe: results of the European Heart Rhythm Association survey.
The purpose of this EP wire survey was to assess clinical practice in relation to the use of left atrial appendage occlusion (LAAO) devices for stroke prevention in atrial fibrillation (AF) among members of the European Heart Rhythm Association research network. The average number of performed LAAO was 10.6 per year and most (73%) centres performed ≤10 procedures per year. We found that LAAO was being performed for stroke prevention in AF, for the most common indication being 'the patient has absolute contraindication to long term oral anticoagulants'. Among survey respondents, LAAO procedures are most often performed by interventional cardiologists. Experience varied widely, and this was reflected in the wide range of thromboembolic and procedural (tamponade, bleeding) complications reported by the respondents to this EP wire survey.


Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats.
To study the combinative effects of nanocerium and selenium in a murine model of diabetes. Cerium oxide (CeO(2)) nanoparticles (60 mg/kg per day) and sodium selenite (5 μmol/kg per day) alone or in combination, or the metal form of CeO(2) (60 mg/kg) were administered for 2 wk by intraperitoneal injection to streptozotocin-induced diabetic rats. At the end of treatment blood was collected, liver tissue dissected and then oxidative stress markers, extent of energy depletion and lipid profile were evaluated. Antioxidant enzymes and high density lipoprotein decreased whereas oxidative stress, adenosine diphosphate/adenosine triphospahte levels, cholesterol, triglyceride and low density lipoprotein increased on induction of diabetes. All were improved by a combination of nanocerium and sodium selenite. There was a relative amelioration by CeO(2) nanoparticles or sodium selenite alone, but the metal form of CeO(2) showed no significant improvement. The combination of nanocerium and sodium selenite is more effective than either alone in improving diabetes-induced oxidative stress.


Ephrin-mediated restriction of ERK1/2 activity delimits the number of pigment cells in the Ciona CNS.
Recent evidence suggests that ascidian pigment cells are related to neural crest-derived melanocytes of vertebrates. Using live-imaging, we determine a revised cell lineage of the pigment cells in Ciona intestinalis embryos. The neural precursors undergo successive rounds of anterior-posterior (A-P) oriented cell divisions, starting at the blastula 64-cell stage. A previously unrecognized fourth A-P oriented cell division in the pigment cell lineage leads to the generation of the post-mitotic pigment cell precursors. We provide evidence that MEK/ERK signals are required for pigment cell specification until approximately 30min after the final cell division has taken place. Following each of the four A-P oriented cell divisions, ERK1/2 is differentially activated in the posterior sister cells, into which the pigment cell lineage segregates. Eph/ephrin signals are critical during the third A-P oriented cell division to spatially restrict ERK1/2 activation to the posterior daughter cell. Targeted inhibition of Eph/ephrin signals results in, at neurula stages, anterior expansion of both ERK1/2 activation and a pigment cell lineage marker and subsequently, at larval stages, supernumerary pigment cells. We discuss the implications of these findings with respect to the evolution of the vertebrate neural crest.


[Dental abnormalities after treatment for childhood cancer].
Childhood cancer therapy often increases the risk of dental complications, such as tooth and roots agenesis, microdontia, abnormal development of tooth enamel, increased risk of cavity and other abnormalities. In a comparison with other late adverse effects of chemotherapy, radiotherapy and hematopoietic stem cell transplantion, a relative small number of clinical stud-ies observing patients for more than two years after completion of anticancer treatment was published. In this article, we review the incidence of dental abnormalities caused by commonly used anticancer treatment modalities as well as discuss their risk factors. Early identification of high-risk patients, early detection and management of dental abnormalities and better education of patients or their guardians, may have an impact on quality of life of cancer survivors.


Persistent functional atrioventricular block in two patients with prolonged QT intervals: elucidation of the mechanism of block.
This article describes two infants with prolonged QT interval and intermittent second-degree atrioventricular block. An asymptomatic 14-month-old child with persistent 2:1 atrioventricular conduction since birth underwent electrophysiology study including measurements with a contact monophasic action potential catheter. During 2:1 conduction, atrioventricular block occurred distal to the site of the His-bundle recording. Monophasic action potential duration was closely related to prior RR intervals. Single premature atrial or ventricular depolarizations during 1:1 conduction followed by a pause, lead to monophasic action potential prolongation and subsequent 2:1 atrioventricular conduction, which was perpetuated by the resulting long RR intervals. Paired premature ventricular contractions or short bursts of ventricular pacing elicited monophasic action potential shortening and subsequent 1:1 atrioventricular conduction that was perpetuated by the resulting short RR intervals. A second infant presented at birth with a prolonged QT interval, ventricular tachycardia, and episodes of second-degree atrioventricular block with persistent 2:1 atrioventricular conduction. The atrioventricular block was repeatedly elicited by single premature ventricular contractions and terminated by ventricular couplets. We conclude that the atrioventricular block in both patients is functional in nature and results from the interrelationships between ventricular rate, action potential duration, and His-Purkinje system refractoriness.


Prevalence and Missed Cases of Respiratory Distress Syndrome Disease Amongst Neonatal Deaths Enrolled in the Kenya Child Health and Mortality Prevention Surveillance Network (CHAMPS) Program Between 2017 and 2021.
Objectives. To describe RDS in neonatal deaths at the CHAMPS-Kenya site between 2017 and 2021. Methods. We included 165 neonatal deaths whose their Causes of death (COD) were determined by a panel of experts using data from post-mortem conducted through minimally invasive tissue specimen testing, clinical records, and verbal autopsy. Results. Twenty-six percent (43/165) of neonatal deaths were attributable to RDS. Most cases occurred in low birthweight and preterm neonates. From these cases, less than half of the hospitalizations were diagnosed with RDS before death, and essential diagnostic tests were not performed in most cases. Most cases received suboptimal levels of supplemental oxygen, and critical interventions like surfactant replacement therapy and mechanical ventilation were not adequately utilized when available. Conclusion. The study highlights the urgent need for improved diagnosis and management of RDS, emphasizing the importance of increasing clinical suspicion and enhancing training in its clinical management to reduce mortality rates.


The experience of physiological and psychosocial alcohol-related harms across adolescence and its association with alcohol use disorder in early adulthood: A prospective cohort study.
Different forms of alcohol-related harm (e.g., hangovers, fighting) may confer differential risk of clinically relevant alcohol problems. We examine: (i) patterns of transition in experiencing alcohol-related harms across adolescence; (ii) whether factors in early adolescence predict transition patterns; and (iii) whether transition patterns predict later alcohol use disorder (AUD) symptoms. We used a longitudinal Australian cohort (n = 1828) to model latent class transition patterns of alcohol-related harms across three timepoints (Mage = 13.9, 16.8, 18.8 years). Regression models assessed whether child, peer, and parent factors in early adolescence (Mage = 12.9) predicted harms transition patterns and whether these patterns predicted AUD symptoms in early adulthood (Mage = 19.8). Five transition patterns characterized most of the cohort (n ≈ 1609, 88.0%): (i) minimal harms (n ≈ 381, 20.8%); (ii) late physiological harms (n ≈ 702, 38.4%); (iii) early physiological harms (n ≈ 226, 12.4%); (iv) late all harms (n ≈ 131, 7.2%); and (v) gradual all harms (n ≈ 169, 9.2%). With late physiological harms as the reference, females had increased risk of experiencing early physiological harms (relative risk [RR]: 2.15; 99.5% CI: 1.19, 3.90). Late all harms (RR: 1.71; CI: 1.19, 2.47) and gradual all harms (RR: 1.84; CI: 1.37, 2.47) were each associated with increased odds of meeting criteria for AUD, even when patterns of alcohol consumption are considered. Adolescents display heterogeneous transition patterns across physiological and psychosocial alcohol-related harms. Females are at greater risk of experiencing early physiological harms. Experience of both physiological and psychosocial harms in late adolescence is an important and potentially modifiable precursor to clinically relevant alcohol problems in early adulthood.


Neonatal resuscitation 2: an evaluation of manual ventilation devices and face masks.
The key to successful neonatal resuscitation is effective ventilation. Little evidence exists to guide clinicians in their choice of manual ventilation device or face mask. The expiratory tidal volume measured at the mask (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation. To compare the efficacy of (a) the Laerdal infant resuscitator and the Neopuff infant resuscitator, used with (b) round and anatomically shaped masks in a model of neonatal resuscitation. Thirty four participants gave positive pressure ventilation to a mannequin at specified pressures with each of the four device-mask combinations. Flow, inspiratory tidal volume at the face mask (V(TI(mask))), V(TE(mask)), and airway pressure were recorded. Leakage from the mask was calculated from V(TI(mask)) and V(TE(mask)). A total of 10,780 inflations were recorded and analysed. Peak inspiratory pressure targets were achieved equally with the Laerdal and Neopuff resuscitators. Positive end expiratory pressure was delivered with the Neopuff but not the Laerdal device. Despite similar peak pressures, V(TE(mask)) varied widely. Mask leakage was large for each combination of device and mask. There were no differences between the masks. During face mask ventilation of a neonatal resuscitation mannequin, there are large leaks around the face mask. Airway pressure is a poor proxy for volume delivered during positive pressure ventilation through a mask.


Apparent gene conversion between beta-tubulin genes yields multiple regulatory pathways for a single beta-tubulin polypeptide isotype.
We have determined the complete nucleotide sequences of two chicken beta-tubulin genes, beta 1 and beta 2. These genes display an unusual pattern of segmental homology which indicates that they originally arose by gene duplication and have subsequently coevolved by a process that included localized gene conversion or intergenic recombination. Since the beta-tubulin polypeptides encoded by the two genes are virtually identical (99.5%), particularly in the major beta-tubulin isotype defining regions, they almost certainly constitute a single isotypic class of beta tubulin. However, the regulatory properties of the two genes are highly divergent as indicated by analysis of their patterns of expression in different chicken cell types. beta 1 is the major transcript detected in skeletal muscle myoblasts, whereas beta 2 is the major beta-tubulin transcript in cultured sympathetic neurons. The existence of these two genes appears to derive from a regulatory requirement whereby the expression of a single tubulin isotype is mediated through different regulatory programs in development and differentiation. These results thus provide direct experimental support for the hypothesis that gene conversion and intergenic recombination play an important role in evolution by uncoupling the evolution of structural genes from the regulatory sequences which control them.


A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer.
Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case-control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.


Distraction osteogenesis for obstructive apneas in patients with congenital craniofacial malformations.
Infants with congenital craniofacial malformations often have associated severe mandibular hypoplasia causing obstruction of the hypopharynx by retroposition of the base of the tongue into the posterior pharyngeal airway. Management depends on the severity of the airway obstruction. Most cases can be managed by prone positioning until the infant outgrows the problem at 3 to 6 months of age. In more critical cases, monitoring of oxygen saturation, temporary placement of a nasopharyngeal tube, and placement of an endotracheal tube will be useful procedures. Tracheotomy is an effective method for more severe cases, but longstanding tracheotomies result in high morbidity and occasional mortality. Mandibular distraction was performed in seven patients, ranging in age from 1 to 18 months, with critical obstructive apnea secondary to mandibular hypoplasia characterized by an apnea/hypopnea index greater than 20 apneas per hour and oxygen saturation below 80 percent. Two patients were tracheotomized previously. Mandibular lengthening, from 16 to 25 mm on the left side and from 10 to 22 mm on the right, was achieved in 21 to 25 days. Improvement of airway obstruction parameters was measured on polysomnograms and lateral cephalograms. Mandibular lengthening by gradual distraction is a successful method for young patients with severe mandibular hypoplasia causing critical obstructive apneas. Avoidance of tracheotomy or early decannulation in previously tracheotomized patients is a great advantage for patients with congenital craniofacial malformation.


[Xiaochaihu Tang for treatment of chronic hepatitis B: a systematic review of randomized trials].
Xiaochaihu Tang was a compound traditional Chinese herbal medicine recorded in ancient Chinese medical book Shanghanlun, and has been widely used for chronic liver diseases especially in Japan. To assess the beneficial effects and safety of Xiaochaihu Tang, for chronic hepatitis B (CHB). Electronic and manual searches were conducted and the search ended in November 2009. We included randomized clinical trials testing Xiaochaihu Tang against placebo, non-specific treatment, antivirals, or combined with antivirals against antivirals alone. Selection of trials for inclusion, assessment of methodological quality by Jadad score, data extraction and data syntheses were conducted according to the Cochrane Hepato-Biliary Group methods. Sixteen randomized trials (involving 1 601 CHB patients) with various methodological quality were included. One trial published in English had good quality, while other trials published in Chinese were of poor quality. The pooled results showed that Xiaochaihu Tang combined with antiviral drugs was more effective in serum loss of hepatitis B viral markers and in improving liver function compared with antiviral drugs alone. Xiaochaihu Tang was not different from placebo in terms of viral clearance or improving liver function. However, Xiaochaihu Tang was superior to non-specific treatment in liver function improvement. There were no adverse effects reported in the trials regarding Xiaochaihu Tang, but adverse effects were reported in patients treated by interferon, and severe adverse effects occurred in few cases. Xiaochaihu Tang in this review appears to be effective in improving liver function and clearance of serum hepatitis B viral markers in patients with chronic hepatitis B. However, due to poor methodological quality in the majority of included trials the potential benefits need to be confirmed in rigorous clinical trials following international standards.


[The biochemical correlates of the individual typological characteristics of rat behavior].
The review of data (results of the authors' investigations and data from the literature) concerning neurochemical correlates of individual behavior in rats is presented. The "emotional resonance" test was used for behavioral selection of rats. Individual behavior in this test is related to the differences in free radical mediated processes, membrane lipid content, nitric oxide synthase activity and cAMP pattern in cerebral macrostructures. Behavior-related differences were revealed in intact animals, and in response to environmental factors. These differences depend on age; they may be global or specific for selected brain regions and/or related to interhemispheric lateralization of biochemical parameters.


Computed tomography as a tool for percutaneous coronary intervention of chronic total occlusions.
Chronic total occlusions (CTO) constitute a major challenge in percutaneous coronary revascularisation (PCI). The development of new interventional strategies, the availability of purpose made tools including dedicated catheters and wires, as well as increasing expertise by the operators, have contributed to the modest success rates which today hover around 75%. Case selection is of utmost importance since failure of this high risk procedure with its typically high radiation doses, high contrast doses and increased complication rates is associated with long term adverse events. Imaging of the coronary arteries using the gold standard of invasive coronary angiography allows characterisation of the chronic total occlusion and is often able to predict the probability of successful recanalisation. Multislice computed tomography (MSCT) is increasingly being utilised as a non-invasive diagnostic imaging modality to detect coronary artery disease. Its ability to provide information on the soft tissue (including plaque) surrounding the lumen has been applied to better define the morphological features of CTOs. In fact, the amount of calcification, tortuosity and actual length of the occluded segment which are established predictors of success, are all better characterised by MSCT. Three dimensional reconstruction of the coronary anatomy and its integration with two dimensional fluoroscopy images during the actual CTO-PCI procedure may help to identify the best angiographic projection, offering a directional guide at the angiographically "missing segment". More technological advances are needed to optimise this multi-modality imaging integration. Whether this will result in better success rates for CTO-PCI is still the subject of ongoing research. It is then that we can evaluate the true benefit of the use of MSCT for CTO against the risk from excessive radiation associated with this strategy.


[Relation of the survival of kidney transplants to their initial functional integrity].
The influence of the initial functional capacity of renal transplants on the term of their survival was studied in 107 patients who were subjected to 118 transplantations of cadaveric kidneys. If the transplant function was restored within the first days after the operation 61% of the transplants were functioning during a year. In cases with a delayed function resulting from acute insufficiency of the transplanted kidney the good functioning was observed in 28% of all the transplants. The data obtained show the importance of further studies of the ways of the amendment of the quality of kidney transplants.