Timing of light pulses and photoperiod on the diurnal rhythm of hippocampal neuronal morphology of Siberian hamsters.
Rapid remodeling of neurons provides the brain with flexibility to adjust to environmental fluctuations. In Siberian hamsters, hippocampal dendritic morphology fluctuates across the day. To reveal the regulatory mechanism of diurnal remodeling of hippocampal neurons, we investigated the effects of light signals applied under different photoperiodic conditions on dendritic morphology. A 4-h dark pulse during the morning of long days (LD) increased basilar dendritic length, as well as complexity of basilar dendrites of neurons in the CA1. A light pulse during the late night in short days (SD) reduced basilar dendrite branching and increased primary apical dendrites of CA1 neurons. Spine density of dentate gyrus (DG) dendrites was increased by a dark pulse in LD and spine density of CA1 basilar dendrites was decreased by a light pulse in SD. These results indicate that light signals induce rapid remodeling of dendritic morphology in a hippocampal subregion-specific manner. A light pulse in SD decreased hippocampal expression of fetal liver kinase 1 (Flk1), a receptor for vascular endothelial growth factor (VEGF), raising the possibility that VEGF-FLK1 signaling might be involved in the rapid decrease of branching or spine density of CA1 basilar dendrites by light.


A prospective study of nomogram-based adaptation of prostate radiotherapy target volumes.
A prospective clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer (HRPC) through the use of a nomogram to tailor radiotherapy target volumes. Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015. A set of validated prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center (MSKCC) prostate cancer nomogram to estimate risk of loco-regional spread (LRS). The nomogram risk estimates for extra-capsular extension (ECE), seminal vesicles involvement (SVI), and pelvic lymph nodes involvement (LNI) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases. A planning guide was used to delineate target volumes and organs at risk (OAR). Up to three dose levels were administered over 28 fractions; 70Gy for gross disease in the prostate +/- seminal vesicles (2.5Gy/fraction), 61.6Gy for subclinical peri-prostatic disease (2.2Gy/fraction) and 50.4Gy to pelvic nodes (1.8Gy/fraction). Data regarding protocol adherence, nomogram use, radiotherapy dose distribution, and acute toxicity were collected. Nomogram use 100 % of patients were treated for ECE, 88.9 % for SVI, and 70.4 % for LNI. The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases. The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis. Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % (159/171). Compliance with protocol for small bowel contouring was poor (59.3 %). Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % (191/196). Compliance with dose constraints for OAR was 88.2 % (285/323). Acute toxicity There were no grade 3 acute toxicities observed. 20/27 (74.1 %) and 6/27 (22.2 %) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively. We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC. This study has identified key learning points regarding this approach, including the importance of standardization and updating of risk quantification tools, and the utility of an observer to verify their correct use. ClincialTrials.gov identifier NCT01418040 . Hunter New England Human Research Ethics Committee (HNEHREC) reference number 12/08/15/4.02.


In vivo metabolism of platelet-activating-factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by the protozoan Tetrahymena pyriformis.
The metabolism of exogenous platelet-activating-factor was studied in the protozoan Tetrahymena pyriformis in vivo. When the cells are exposed to 1.10(-6) M PAF, the molecule is rapidly metabolized to 1-O-alkyl-2-acyl(long chain)-GPC, a major component of the protozoan membranes. The appearance of lyso-PAF from the first minutes even in low levels provides evidence that deacetylation is an intermediate step. After incubation for 30 min, transformation to aminoethyl phosphonolipids is also observed. The fate of PAF in concentrations 1.5.10(-11) M or 1.10(-8) M PAF, was the same. An amount of PAF depending on the external PAF concentration remained intact in the cell even after 1 h incubation. Our results suggest that the easily cultured protozoan can be a useful model for studying PAF's metabolism.


Immortalized differentiated hepatocyte lines derived from transgenic mice harboring SV40 T-antigen genes.
Hepatocytes of transgenic mouse fetuses harboring SV40 virus transforming gene sequences in the SV delta e-MGH fusion gene construct 202 driven by the mouse metallothionein (MT-I) enhancer [R. D. Palmiter, H. Y. Chen, A. Messing, and R. L. Brinster (1985) Nature (London) 316, 457-460] were cultured at Day 19 of gestation and established as a differentiated line expressing albumin and alpha-fetoprotein (AFP) mRNAs. Hepatocyte line FMH-202 contains integrated SV40 sequences, expresses SV40 T-antigen genes, and exhibits unlimited growth potential because it has been cultured 18 months without apparent decrease in cell viability or in growth rate that could suggest the occurrence of a crisis period. Immortalized cells multiply in chemically defined medium deficient in arginine with transferrin plus insulin, whereas EGF, insulin, and transferrin are obligatory requirements for fetal or newborn mouse hepatocyte multiplication in primary cultures. Cells did not grow in agar and were not tumorigenic in nude mice. Their immortalized, nonmalignant phenotype was further documented by low saturation densities of confluent monolayers showing no overgrowth, and by growth arrest in the absence of insulin with subsequent induction of DNA synthesis and resumption of cell growth in response to insulin. Thus, it appears that immortalized SV40 T-antigen-expressing hepatocytes are present in the liver of the transgenic mice. However, at later points in liver development the transforming activity of T-antigen becomes apparent and leads to hepatocellular carcinoma formation in vivo.


Environmental lead pollution threatens the children living in the Pearl River Delta region, China.
The objective of this study is to determine children's blood lead levels and identify sources of lead exposure. Childhood lead exposure constitutes a major pediatric health problem today in China. A blood lead screening survey program for children in the age group of 2-12 years residing in Pearl River Delta region, south of China, was carried out from Dec 2007 to Jan 2008. Blood lead levels and lead isotope ratios of a total of 761 participants were assessed by inductively coupled plasma mass spectroscopy. Measurements of urban environmental samples for source identification of children lead exposure were also performed. The geometric mean value of the children's blood lead levels was 57.05 μg/L, and 9.6% of them were higher than 100 μg/L. The blood lead levels were still much higher than those in developed countries. Based on the data of environmental lead source inventories, lead isotopic tracing revealed that there is about 6.7% past used gasoline Pb embedded in Shenzhen residential dust and about 15.6% in Guangzhou dust, respectively.


Polyglutamic Acid-Based Elastic and Tough Adhesive Patch Promotes Tissue Regeneration through In Situ Macrophage Modulation.
Adhesive patches are advanced but challenging alternatives to suture, especially in treating fragile internal organs. So far there is no suture-free adhesive patch based on metabolizable poly(amino acid) materials with excellent mechanical strength as well as immunomodulation functionality. Here, a polyglutamic acid-based elastic and tough adhesive patch modified by photosensitive groups on the surface to achieve robust light-activated adhesion and sealing of flexible internal organs is explored. With the porous internal morphology and excellent biodegradability, the patches promote regeneration through a macrophage-regulating microenvironment. Treated rabbits achieve rapid full-thickness gastric regeneration with complete functional structure within 14 d, suggesting its robust tissue adhesion and repair-promoting ability.


Feasibility Study of a Variant Procedure of Radical Breast Ductectomy (Dolichectomy) with a Perinipple Incision.
Papillomatosis and recurrent duct ectasia could be treated with terminal lactiferous ducts excision. In this study we describe a modified miniinvasive procedure of terminal lactiferous ducts excision with a perinipple approach to the lower or upper half of the nipple. This technique avoids the much more extensive periareolar incision and has excellent aesthetic results.


Multistage carcinogenesis in paediatric and adult cancers.
Retinoblastoma (RB) and the familial adenomatous polyposis/colorectal cancer (FAP/CRC) complex provide well-characterised examples of multistage carcinogenesis and inheritance of a predisposition to cancer. Retinoblastoma appears to conform to the simple two-step model first proposed by Knudson. The gene responsible for RB, now called Rb1, has been located in chromosome region 13q14. The Rb1 gene has been cloned and subjected to extensive analysis. It is probable that the Rb1 gene product has a role in the regulation of transcription. The familial form of RB occurs as the result of a germline mutation of one of the copies of the Rb1 gene. Colorectal cancer, in contrast, appears to be the result of four or five steps involving both activation of oncogenes and inactivation of antioncogenes. The FAP gene has been located in chromosome region 5q21 by genetic linkage, and a candidate gene, MCC (mutated in colon cancer), has been cloned. Other mutations in previously-identified genes that have been identified as important in the genesis of CRC include the activation of p53 and of Ki-ras. A gene lying in chromosome region 18q which is deleted in colorectal cancer, and hence named DCC has been cloned. Its protein product has sequence homology to neural cell adhesion molecules and other related cell-surface glycoproteins. Delineation of the genes involved in the development of tumours such as RB and CRC provides insight into the mechanisms by which sequential mutations result in carcinogenesis.


A simultaneous bilateral asymmetric hip fracture in an elderly patient: A case report and review of the literature.
Simultaneous bilateral hip fractures are usually associated with high energy trauma, seizures, metabolic diseases and bisphosphonates use. They are observed rarely in the elderly population after simple trauma and usually have the same fracture pattern (symmetric). We report a rare case of asymmetric fracture and discuss mechanism of injury and treatment, analyzing the literature. We report a case of an 86-year old woman with a simultaneous bilateral asymmetric hip fracture (trochanteric on the right side and subcapital on the left), occurred after a fall at home. The patient was surgically treated by open reduction and internal fixation with an intramedullary nail on the right and by hemiarthroplasty on the left performed during the same surgical session, with good results. Simultaneous bilateral hip fractures in the elderly are rare and usually are symmetric. In the majority of the cases these fractures are intracapsular and are treated by hemiarthroplasties. On the contrary, simultaneous bilateral hip fractures with a different pattern, as the described case, are extremely rare. The possible mechanism of injury is a spontaneous fracture on one side, which causes a fall the contralateral side. The surgical treatment may be performed bilaterally, treating first the trochanteric fracture. Simultaneous bilateral asymmetric hip fracture are extremely rare and may occur in elderly patient with a specific mechanism of injury. We believe that the trochanteric fracture should be operated first to avoid possible complications.


[Determination of antibodies to the AIDS virus and the viral antigen by an immunoenzyme method using peroxidase and beta-lactamase].
The ELISA test using beta-lactamase for the detection of anti-AIDS virus antibodies and virus antigen in serum is described. The properties of this test system are compared with those of the system based on horseradish peroxidase conjugates.


Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making?
Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. Many clinicians might be sceptical that Bayesian analysis, a philosophical and statistical approach that combines prior beliefs with data to generate probabilities, provides more useful information about clinical trials than the frequentist approach. In this Personal View, we introduce clinicians to the rationale, process, and interpretation of Bayesian analysis through a systematic review and reanalysis of interventional trials in critical illness. In the majority of cases, Bayesian and frequentist analyses agreed. In the remainder, Bayesian analysis identified interventions where benefit was probable despite the absence of statistical significance, where interpretation depended substantially on choice of prior distribution, and where benefit was improbable despite statistical significance. Bayesian analysis in critical care medicine can help to distinguish harm from uncertainty and establish the probability of clinically important benefit for clinicians, policy makers, and patients.


Pain-related bias in the classification of emotionally ambiguous facial expressions in mothers of children with chronic abdominal pain.
This study sought to determine whether mothers of young people with chronic abdominal pain (CAP) compared to mothers of pain-free children show a pain recognition bias when they classify facial emotional expressions. One hundred demographically matched mothers of children with CAP (n=50) and control mothers (n=50) were asked to identify different emotions expressed by adults in 2 experiments. In experiment 1, participants were required to identify the emotion in a series of facial images that depicted 100% intensity of the following emotions: Pain, Sadness, Anger, Fear, Happiness, and Neutral. In experiment 2, mothers were required to identify the predominant emotion in a series of computer-interpolated ("morphed") facial images. In this experiment, pain was combined with Sad, Angry, Fearful, Happy, and Neutral facial expressions in different proportions-that is, 90%:10%, 70%:30%, 50%:50%, 30%:70%, 10%:90%. All participants completed measures of state and trait anxiety, depression, and anxiety sensitivity. In experiment 1, there was no difference in the performance of the 2 groups of mothers. In experiment 2, it was found that overall mothers of children with CAP were classifying ambiguous emotional expressions predominantly as pain. Mean response times for CAP and control groups did not differ significantly. Mothers of children with CAP did not report more anxiety, depression, and anxiety sensitivity compared to control mothers. It is concluded that mothers of children with CAP show a pain bias when interpreting ambiguous emotional expressions, which possibly contributes to the maintenance of this condition in children via specific parenting behaviours.


Development and usability evaluation of an electronic health report form to assess health in young people: a mixed-methods approach.
Electronic Patient-Reported Outcomes (ePROs) have potential to improve health outcomes and healthcare. The development of health-technology applications, such as ePROs, should include the potential users and be theoretically grounded. Swedish Youth Health Clinics (YHCs) offer primarily sexual and psychological healthcare for young people aged 12 to 25 years old. Young people in healthcare settings are considered a vulnerable group. The development of a collection of Patient-Reported Outcomes (PROs) in an Electronic Health Report Form (eHRF) for identifying health and health-related problems in young people, was preceded by a qualitative interview study, exploring young people's views on using an eHRF at YHCs and which questions about health an eHRF should contain. The aim of the current study was to develop and evaluate the usability of an eHRF prototype for identifying health and health-related problems in young people visiting YHCs. This study used a participatory design. During the development, an expert panel consisting of eight researchers and one Information Technology worker, participated. A wide literature search was performed to find PROs to construct an eHRF prototype to cover health areas. A mixed methods usability evaluation included 14 participants (young people, healthcare professionals, and an expert panel). The development resulted in an eHRF prototype, containing ten reliable and valid health questionnaires addressing mental-, physical-, and sexual health and social support, a self-efficacy question, and background questions, in total 74 items. The interviews in the usability evaluation resulted in three categories describing the usability of the eHRF: 'Captures the overall health of young people but needs clarification', 'Fun, easy, and optional and will keep young people's interest', and 'Potential contribution to improve the health consultation'. The quantitative results support the usability of the eHRF for YHCs. The participatory approach contributed to development of the eHRF prototype to cover health areas adapted for the target population. The usability evaluation showed that the eHRF was usable and had the potential for self-reflection and contributions to cooperation between young people and healthcare professionals during the health consultation.


Differential role of calmodulin and calcium ions in the stabilization of the catalytic domain of adenyl cyclase CyaA from Bordetella pertussis.
The catalytic adenyl cyclase (AC) domain of the protein CyaA from Bordetella pertussis is activated by interaction with the C terminal lobe of calmodulin (C-CaM). The AC/C-CaM complex displays an elongated shape, but hydrodynamics measurements on the isolated AC domain allowed to characterize the shape of the protein as spherical. Here, we study by molecular dynamics simulations the complexes between AC and the apo and Ca(2+)-loaded C-CaM, as well as the isolated AC, to characterize the features of AC conformational variability and of AC/C-CaM interaction. The removal of calcium ions from C-CaM increases the AC flexibility, but the removal of C-CaM induces a dramatic drift of the AC conformation. Isolated AC conformations show a general tendency to become less elongated, as the two protein extremities (regions SA and CB) tend to get closer. An analysis of the energetic influences between the C-CaM and the AC regions shows a simple influence scheme, in agreement with the high affinity of AC to CaM. In this scheme, a single influence is observed from C-CaM to the region CA of the AC domain. This influence is correlated to the presence of hydrogen bonds involving residues from C-CaM, and from regions CA, C-terminal tail, and catalytic loop of AC. This study reveals a C-CaM/AC interaction picture where C-CaM stabilizes AC by a steric hindrance on the conformational drift of SA, whereas the Ca(2+) ions allow further stabilization by the establishment of a hydrogen bond network extending from C-CaM to the AC catalytic loop.


Surgery for extra-articular trismus: a systematic review.
The aim of this systematic review was to identify operations that are used to improve mouth opening in patients with extra-articular trismus (caused by cancer and its treatment, oral submucous fibrosis, or noma) and to find out if they work. We searched the electronic databases PubMed, Embase, Cinahl, and the Cochrane collaboration, and then systematically selected papers before we assessed their quality, extracted the data, and did a meta-analysis. We analysed 32 studies that included 651 patients, the median (IQR) size of which was 11 (7-26). The quality of the methods used and of reporting were relatively low. Median (IQR) duration of follow-up was 12 (8-22) months. Operations resulted in a weighted mean (SD) increase in mouth opening of 19.3 (6.3) mm. None of the operations was better than the others for the improvement of mouth opening. We conclude that operations can improve mouth opening in extra-articular trismus, but the evidence is of moderate quality and there is a need for further research.


Early self-awareness following traumatic brain injury: comparison of brain injury and orthopedic inpatients using the Functional Self-Assessment Scale (FSAS).
To examine the Functional Self-Assessment Scale (FSAS) in hospitalized orthopedic patients with no brain dysfunction, and compare results to prior self-awareness data collected with brain injury patients. Comparison of patient and staff ratings on FSAS using paired sample t tests. Thirty-one adult volunteers hospitalized on National Rehabilitation Hospital (NRH) orthopedic treatment unit. FSAS was used to compare patient and staff ratings of patient performance on tasks relevant for inpatient rehabilitation. Subjects were screened to rule out brain impairment. Statistically significant but very small differences were found between orthopedic patients and therapist ratings using the FSAS. However, brain injury patients' ratings show a significantly larger discrepancy between self-therapist ratings than do orthopedic patients. Impaired self-awareness is related to brain injury rather than nonspecific factors in rehabilitation inpatients.


Cryptosporidia in immunocompetent patients with gastroenteritis.
In a prospective study Cryptosporidium spp. were detected in nine immunocompetent patients (0.6%). The frequency was remarkably higher in children in the 0 to 14 year age group (1.6%), surpassed only by Salmonella spp. and Campylobacter spp. The predominant clinical features were watery diarrhea, abdominal pain, and vomiting. Comparison of the epidemiological data of the patients with those of a control group showed that contact persons with enteritis and drinking of unpasteurized milk were significantly associated with cryptosporidiosis.


Kaposi sarcoma of penis and genitalia: a disease of our times.
Penile and/or genital involvement may be an early manifestation of AIDS-related Kaposi sarcoma. Diagnosis may be suggested by history, and epidemiologic and sociologic data. Precise diagnosis can be documented by the urologist by early recognition and biopsy of genital lesions. Early awareness and treatment may control this potentially virulent disease.


Relevance of endoglin, IL-1α, IL-1β and anti-ovarian antibodies in females with multiple sclerosis.
Few studies support the concept of reduced fertility in females with multiple sclerosis (MS). Recently we reported on reduced serum levels of Anti-Müllerian Hormone (AMH) in reproductive-age females with MS, suggestive of reduced ovarian reserve. The cause for this observation is not evident and remains speculative. The aim of the study is to examine possible immunological mechanisms interfering with fertility, as well as ovarian reserve that might affect the reproductive potential in women with MS. ELISA experiments were done to detect anti-ovarian antibodies (AOA), endoglin and interleukin (IL)-1α/-1β in sera of 85 MS females, including 15 women with known low AMH level as a marker of ovarian reserve, compared to 63 healthy controls. Groups did not differ with respect to age, smoking habits, BMI, and use of oral contraceptives. MS females showed significantly increased endoglin values compared to healthy controls. Remarkable, the highest endoglin values were found in subjects with low AMH. AOA were neither detectable in MS patients nor control subjects. IL-1α and IL-1β levels did not differ between groups. Our data established no relevance of IL-1α/-1β or AOA in ovarian insufficiency/dysfunction but suggests the involvement of endoglin in RRMS.


The biology of pulmonary exacerbations in bronchiectasis.
Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite evidence on clinical and biological aspects of bronchiectasis, exacerbations still remain poorly understood.Although the scientific community recognises that bacterial infection is a cornerstone in the development of bronchiectasis, there is a lack of data regarding other trigger factors for exacerbations. In addition, a huge amount of data suggest a primary role of neutrophils in the stable state and exacerbation of bronchiectasis, but the inflammatory reaction involves many other additional pathways. Cole's vicious cycle hypothesis illustrates how airway dysfunction, airway inflammation, infection and structural damage are linked. The introduction of the concept of a "vicious vortex" stresses the complexity of the relationships between the components of the cycle. In this model of disease, exacerbations work as a catalyst, accelerating the progression of disease. The roles of microbiology and inflammation need to be considered as closely linked and will need to be investigated in different ways to collect samples. Clinical and translational research is of paramount importance to achieve a better comprehension of the pathophysiology of bronchiectasis, microbiology and inflammation both in the stable state and during exacerbations.


Short-wave diathermy in the clinical management of musculoskeletal disorders: a pilot observational study.
Musculoskeletal disorders are the most common cause of pain and functional limitation in the general population. The study aim was to evaluate short-wave diathermy (SWD) effects on pain and quality of life in people with musculoskeletal disorders. Eighty participants (31 men, mean age 56 ± 12.49 years) were enrolled, recruiting from outpatient clinics at the Rehabilitation Unit, University Hospital, Padova. Inclusion criteria were pain lasting more than 15 days, pain visual analog scale (VAS) score higher than 50/100 mm, and a diagnosis of osteoarthritis, neck/back pain, or tendinopathies. All participants underwent ten sessions of percutaneous SWD, 3 times/week. Each session lasted 15-20 min, with frequencies of 4 or 8 MHz and heat intensity between 40 and 60 W. Outcomes were assessed before and after treatment. Primary outcome was pain reduction, evaluated by short form McGill pain questionnaire, which includes VAS and present pain intensity (PPI). Secondary outcome was improvement in social and work-related activity limitations. Participants were grouped based on classification of pain [nociceptive and neuropathic pain (group A) vs nociceptive only (group B)]. VAS and PPI improved significantly (p < 0.01). No difference in pain reduction (VAS and PPI) emerged between the groups. Limitations due to pain in work-related and non-work-related activities decreased (p < 0.01); use of pain medications was reduced at T1 vs T0 (p < 0.01). Our results suggest that SWD is effective in reducing musculoskeletal pain in the short term, providing relief and improving quality of life.


Semiconductor nanocrystals for biological imaging.
Conventional organic fluorophores suffer from poor photo stability, narrow absorption spectra and broad emission spectra. Semiconductor nanocrystals, however, are highly photo-stable with broad absorption spectra and narrow size-tunable emission spectra. Recent advances in the synthesis of these materials have resulted in the generation of bright, sensitive, extremely photo-stable and biocompatible semiconductor fluorophores. Commercial availability facilitates their application in a variety of unprecedented biological experiments, including multiplexed cellular imaging, long-term in vitro and in vivo labeling, deep tissue structure mapping and single particle investigation of dynamic cellular processes. Semiconductor nanocrystals are one of the first examples of nanotechnology enabling a new class of biomedical applications.


Bacteriological study of urine samples from leprosy patients: a preliminary communication.
A.F.B. and biological structures related to its multiplication reported previously from skin and blood of patients were seen also in their urine. Implications of these findings in transmission and possible application in detecting sub-clinical infections should be studied.


Genitourinary involvement and management in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are devastating hypersensitivity disorders that cause epidermal cell death and can affect all epidermal surfaces, including the urethra, vagina, labial and scrotal skin. Despite the well-described ocular and orofacial manifestations of SJS/TEN, there is a paucity of reports on the genitourinary (GU) symptoms and their management. Specifically, consulting services often ask the pediatric urology team if it is safe to place a urethral catheter, but there is no data in the literature to help guide management. The present study sought to review all pediatric cases of SJS/TEN in a tertiary care hospital to determine the incidence and optimal management of GU manifestations, including the use of urethral catheters. With IRB approval, cases of SJS and TEN that were managed as an inpatient between January 2008 and June 2015 were retrospectively reviewed in order to identify the extent of GU involvement/manifestations, the treatment provided, use of urethral catheterization and long-term follow-up or complications. Thirty-one patients (15 female, 16 male; age range 2-18 years) presented with SJS or TEN over the study period. Etiologies for SJS/TEN included mycoplasma infection (48%) and medications (45%). Incidences of GU manifestations at presentation and their management are shown in Summary Table. Overall, 74% of patients had genital involvement of skin lesions. In 12 cases (39%), urology consultation was obtained. Twenty patients (61%) complained of dysuria and one child had gross hematuria in the setting of meatal lesion. Petroleum jelly was used in the majority of patients. A urethral catheter was placed in eight patients (25.8%, four female, four male) with a range of duration of 7-23 days. No patient developed hematuria or any other complications (i.e. strictures or urinary symptoms) after catheter removal. One boy required lysis of penile adhesions in the short-term. One of each gender developed penile and labial adhesions on long-term follow-up that self-resolved. GU involvement in SJS/TEN occurred in almost three-quarters of patients and was managed conservatively like other skin/mucosal manifestations. Long-term sequelae were rare and urethral catheterization appeared to be safe, without any short-term or long-term complications.


Low-dose doxorubicin in the management of advanced carcinoma of the prostate.
Twenty-one patients with advanced metastatic carcinoma of the prostate, no longer responsive to conventional therapy, were treated with weekly low-dose doxorubicin (Adriamycin). Twelve had an impressive subjective response in terms of pain relief and improved performance status and in nine this was maintained for 3 or more months.


Benefits of prolonged infusion of beta-lactam antibiotics in patients with sepsis: personal perspectives.
In the current era of relatively scarce antibiotic production and significant levels of antimicrobial resistance, optimization of pharmacokinetics and pharmacodynamics of antibiotic therapy is mandatory. Prolonged infusion of beta-lactam antibiotics in comparison to the intermittent infusion has the theoretical advantage of better patient outcomes. Apparently, conflicting data in the literature possibly underestimate the benefits of prolonged infusion of antibiotic treatment. We provide our perspective on the subject based on our experience and by critically evaluating literature data. In our opinion, the available data are suggestive of the beneficial role of prolonged infusion of beta-lactams in regard to piperacillin/tazobactam and carbapenems after administering a loading dose. While more data from randomized controlled trials are necessary to solidify or negate the evident benefits of prolonged infusion of the aforementioned antibiotics, clinicians should strongly consider this mode of administration of relevant antibiotics, especially in patients with severe infections.


Patient-Reported Outcomes at Return to Sport After Lateral Ankle Sprain Injuries: A Report From the Athletic Training Practice-Based Research Network.
Limited evidence exists regarding the assessment of single-item patient-reported outcomes when patients are medically cleared to return to sport after a lateral ankle sprain (LAS) injury. To evaluate self-reports of improvement in health status, pain, function, and disability at return to sport after an LAS. Descriptive study. Sixty-nine athletic training facilities across 24 states. A total of 637 patients (males = 53.2%) who were diagnosed with an LAS, restricted from sport after injury, and subsequently medically cleared to return to sport within 60 days were included. Descriptive statistics were used to summarize scores for health status (Global Rating of Change), pain (Numeric Pain Rating Scale), function (Global Rating of Function), and disability (Global Rating of Disability). Mann-Whitney U tests were used to compare score differences between sexes. A Kaplan-Meier analysis was performed to provide a visual depiction of sex differences in the time to return to sport. Most patients sustained an LAS injury while participating in basketball, football, or soccer and were cleared to return to sport 8 days after injury. More than two-thirds of patients reported a meaningful improvement in health status between the time of injury and return to sport. However, many noted deficits related to pain (65.1%), function (86.2%), or disability (35.8%) at return to sport. No differences were seen between males and females for pain (P = .90), function (P = .68), change in health status (P = .45), or disability (P = .21) at return to sport, although males returned to sport slightly sooner than females (P = .025). Despite self-perceived improvements in health status since the time of injury, patients typically returned to sport with deficits in pain, function, and disability after an LAS. Patients may be returning to unrestricted sport participation before they feel their bodies have fully recovered from the injury.


Abortion among adolescents in Cuba.
To understand which adolescents in Havana, Cuba, seek abortions and reasons for pregnancy termination. The sample included all adolescents (n = 248) under the age of 20 years who sought pregnancy termination over a 1-month period in 1995. The participants completed a questionnaire exploring a range of issues including age of onset of sexual intercourse, pregnancy history, and reasons for pregnancy termination. There was no difference in age of onset of sexual intercourse between pregnant adolescents who did and did not seek an abortion. Three fourths of all adolescents who aborted a pregnancy were students, and interruption of studies was a major reason for pregnancy termination. Other reasons included being a single mother and poor socioeconomic conditions. More than half of those who sought to terminate their pregnancy did so at a clinic outside of the community in which they lived. As in other countries, in Cuba, concerns over education interruption remain the predominant reason for abortion. Likewise, while abortion has been legal and widely available in Cuba since 1969, there remains sufficient stigma so that over half of young women seek pregnancy termination outside their community of residence.


An association between fetal abdominal wall defects and elevated levels of human chorionic gonadotropin in mid-trimester.
We analysed maternal serum human chorionic gonadotropin (hCG) in 16 pregnancies with fetal abdominal wall defects previously identified prenatally by elevated maternal serum alpha-fetoprotein (AFP) or at birth. The AFP levels had a mean of 6.38 MOM (range 0.34-15.65), as expected with these defects. The hCG levels had a mean of 1.82 MOM (range 0.23-4.11). The hCG levels in five pregnancies (31.25 per cent) were above 2.30 MOM. Elevated levels of hCG may be associated with fetal abdominal wall defects.


Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department.
To determine the value of fosphenytoin compared with phenytoin for treating patients admitted to an emergency department following a seizure. Cost-minimization analysis performed from a hospital perspective. Hospital emergency department. Two hundred fifty-six patients participating in a comparative clinical trial. Estimation of adverse event rates and resource use. In our base case, phenytoin was the preferred option, with an expected total treatment cost of $5.39 compared with $110.14 for fosphenytoin. One-way sensitivity analyses showed that the frequency and cost of treating purple glove syndrome (PGS) possibly could affect the decision. Monte Carlo simulation showed phenytoin to be the preferred option 97.3% of the time. When variable costs of care are used to calculate the value of phenytoin compared with fosphenytoin in the emergency department, phenytoin is preferred. The decision to administer phenytoin was very robust and changed only when both the frequency and cost of PGS was high.


New dual-channel microtip transducer catheter for urethral pressure profile and cystometry.
Urethral pressure profilometry performed with a dual-channel microtipped transducer catheter and its use in the clinical investigation of female urinary stress incontinence and bladder hyperreflexia are described. A technique for performing filling and voiding cystometry in conjunction with dual-channel profilometry also is discussed.


Effect of nonpeptide NK1 receptor antagonist L-703,606 on the edema formation in rats at early stage after deep partial-thickness skin scalding.
To investigate the effect and the relevant potential mechanism of nonpeptide neurokinin 1 (NK1) receptor antagonist L-703,606 in the edema formation after burn injury. L-703,606 treatment was performed in Sprague-Dawley (SD) rats at early stage after deep partial-thickness skin scalding. One hundred and fifty two adult male SD rats were used in the study and randomly divided into sham scald (SS, n=8), scald control (SC, n=48), and L-703,606 treatment (LT, n=48) groups. The rats in SC and LT groups were subjected to 20% total body surface area (TBSA) deep partial-thickness skin scalding. Modified Evans blue extravasation, tracing electron microscopy by lanthanum nitrate and mean water content assay were employed to observe and detect the changes of vascular permeability, ultrastructure and edema formation in adjacent tissue to the wounds and in the jejuna of rats at early stage (72 h) after scald. The pathological increase of vascular permeability in the periwound tissue and jejunum of rats in LT group were significantly lower than that in SC group (P<0.01), and recuperated earlier. Meanwhile, the changes of water contents of corresponding tissues in LT group were lighter than those in SC group (P<0.01). The ultrastructural changes of the microvessels in the peri-wound tissue of LT group showed that the junctions between microvascular endothelium cells were more narrow than those of SC group, moreover, and the number of opening and the engorgement and cavitation of the vascular endothelium cells decreased, the areosis and edema in perivascular tissue lightened, and the precipitation of the high eletron density lanthanum tracing agent in the interspace of the tissue decreased significantly in LT group. It is concluded that nonpeptide NK1-receptor antagonist L-703,606 could lighten the vascular permeability and edema formation in the periwound tissue and jejunum, and accelerate the normalization process of pathological changes in the tissues of rats after scald.


The anatomical arrangement of the myocardial cells making up the ventricular mass.
The architectural arrangement of the myocytes within the ventricular mass remains a highly contentious topic. It has recently been suggested by several distinguished surgeons that the overall myocardial structure is disposed in the form of a 'ventricular myocardial band'. There are, however, major anatomic deficiencies in this hypothesis, because the heart is formed on the basis of a modified blood vessel, rather than a collection of discrete muscular entities resembling the skeletal musculature. There is ample alternative evidence, nonetheless, already existing to provide a suitable explanation for the 'forceful reciprocal twisting' of the ventricular mass that is seen by cardiac surgeons during operative procedures. We provide here, therefore, a review of the anatomical studies we have performed separately and conjointly over a period of nearly 30 years. As before, we show that there is no anatomic evidence to support the concept of the 'ventricular myocardial band'. The overall arrangement is for the myocytes to be supported as the muscular components of a continuous and complex mass, the supporting collagenous fibrous matrix possessing epimysial, perimysial, and endomysial components. It had already been discussed at length during the previous century why there was no anatomic evidence to support the existence of separate 'muscles' within the ventricular continuum. There are no fibrous sheaths within the ventricular walls that permit the myofibres to be dissected on the basis of muscle bundles having a discrete origin and insertion, as is the case with the arrangement of the skeletal muscles. We have never sought ourselves, however, to deny the central helical nature of the overall architecture of the ventricular walls. The anatomic evidence supporting an overall helical nature for the ventricular myocardium has existed for over 150 years. All the available evidence, nonetheless, shows that these helical patterns are to be found throughout the walls, and in no way constitute a unique myocardial band.


Comparison of two ActiGraph accelerometer generations in the assessment of physical activity in free living conditions.
The aim of this study was to compare physical activity measured using GT1M ActiGraph and GT3X ActiGraph accelerometers in free living conditions. Twenty-five adults wore GT1M and GT3X Actigraph accelerometers simultaneously during a typical weekday of activity. Data were uploaded from the monitor to a computer at the end of test (one day). Previously established thresholds were used for defining time spent at each level of physical activity, physical activity was assessed at varying intensities comparing data from the two accelerometers by ANOVA and Bland and Altman statistical analysis. The concordance correlation coefficient between accelerometers at each intensity level was 0.99. There were no significant differences between accelerometers at any of the activity levels. Differences between data obtained in minutes with the GT1M accelerometer and the GT3X monitor were to 0.56, 0.36, 0.52 and 0.44% for sedentary, light, moderate and vigorous, respectively. The Bland and Altman method showed good agreement between data obtained for the two accelerometers. Findings suggest that the two accelerometers provided similar results and therefore the GT3X may be used in clinical and epidemiological studies without additional calibration or validation studies.


Assessment of the Toxic Metals Pollution of Soil and Sediment in Zarafshon Valley, Northwest Tajikistan (Part II).
This study discusses contamination of soils and sediments with trace elements such as Mn, Ba, W, V, Co, Cr, Zn, Ni, As, Sb Hg as well as Th and U, the influence of natural and anthropogenic factors on the distribution of elements and the ecological state of the Zarafshon Valley. The elemental composition of 116 soil and sediment samples were analyzed by the neutron activation analysis. The calculation of the geoaccumulation index (Igeo), contamination factor (CF) and pollution load index (PLI) showed that some places in the investigated region with developed the industrial zones (around mining and processing plants of "Anzob", "Konchoch", "Kumargi bolo" and "Mogiyon") are mostly polluted by As, Sb, Hg, and in rare cases, the high concentration of W and V were determined. In addition, they were considered the distribution of radioactive elements-thorium and uranium and their ratio in the soil and sediments. Moreover, in the investigated area, strong anomalies of Th and U were not found. It turned out that the content of Th and U are local in nature and do not have a noticeable effect on the environment.


[Development of speech and facial skull growth after primary velopharyngoplasty in lip-jaw-palate clefts].
A two-armed, prospective, randomized study was performed to evaluate the influence of primary velopharyngoplasty on speech and facial growth in patients with cleft lip and palate. Forty-two patients born between 1978 and 1982 were included. All patients were treated with an intravelar veloplasty, and 21 patients simultaneously with a velopharyngoplasty according to Sanvenero-Rosselli. The patients were examined at the age of 5, 10, 15, and 18 years according to the recommendations of the research group of the German Association of Craniomaxillofacial Surgery for minimal documentation. Patients treated with primary velopharyngoplasty showed a higher deficit in transversal growth of the maxilla of 0.6 mm in the molar region in adolescence in comparison to the control group. The sagittal growth of the maxilla was reduced at 2.6 degrees in the SNA angle. A statistically significant decrease in growth of the maxilla caused by primary velopharyngoplasty was not detectable (p > 0.05). The incidence of rhinophonia and dyslalia did not differ significantly. Primary velopharyngoplasty did not lead to speech improvement either in childhood or in adolescence. With regard to a potential decrease in growth of the maxilla and the disadvantages of a hindered nasal respiration, a primary velopharyngoplasty therefore does not seem to be indicated.


Drosophila hold'em is required for a subset of meiotic crossovers and interacts with the dna repair endonuclease complex subunits MEI-9 and ERCC1.
Three Drosophila proteins, ERCC1, MUS312, and MEI-9, function in a complex proposed to resolve double-Holliday-junction intermediates into crossovers during meiosis. We report here the characterization of hold'em (hdm), whose protein product belongs to a single-strand-DNA-binding superfamily of proteins. Mutations in hdm result in reduced meiotic crossover formation and sensitivity to the DNA-damaging agent methyl methanesulfonate. Furthermore, HDM physically interacts with both MEI-9 and ERCC1 in a yeast two-hybrid assay. We conclude that HDM, MEI-9, MUS312, and ERCC1 form a complex that resolves meiotic recombination intermediates into crossovers.


[Effect of preoperative gamma therapy on the state of the cardiovascular system in oncological patients].
Forty patients with tumors of the esophagus, cardia and rectum, subjected preoperatively to gamma-therapy (500 rad for 6 days) and 24 patients subjected only to the operation (the control group) were examined for the heart rate, arterial pressure, minute and stroke heart volumes and circulatory volume (AFS--J131) before and after irradiation and 1, 3, 5 days following the operation. Gamma-therapy was found to result in more poor hemodynamic indices whether the heart is irradiated or not. In irradiation of the heart region (cancer of the esophagus and cardia) much poorer hemodynamic indices were noted.


Cambiarenes: Single-Step Synthesis and Selective Zwitterion Binding of a Clip-Shaped Macrocycle with a Redox-Active Core.
A novel macrocyclic host molecule was synthesized that forms in a single step from commercially available starting materials. The core of the macrocycle backbone possesses two quinone rings and, thus, it is redox-active. Host-guest binding involving the clip-shaped cavity indicates selective binding of pyridine N-oxides based on the electron density of and steric bulk around the anionic oxygen.


Identification of antibacterial substances of Lactobacillus plantarum DY-6 for bacteriostatic action.
The antimicrobial activity of lactic acid bacteria is closely related to its metabolites. Our results showed that Lactobacillus plantarum DY-6 had the highest antibacterial activities among the seven bacteria tested in this study. To fully understand the active antimicrobial substances in L. plantarum DY-6, the cell-free supernatant (CFS) were analyzed. Our data indicated that the antibacterial effect of the CFS was positively correlated with the growth of the bacteria, and the main antibacterial substances were lactic acid, acetic acid, propionic acid, caprylic acid, and decyl acid. Finally, this study demonstrated that the antibacterial active substance produced by the lactic acid bacteria could destroy the cell membrane structure of the bacteria, causing bacteria to fail to grow and reproduce normally, thereby exerting a bacteriostatic action. Taken together, our current findings would provide an effective method for rapid screening of antimicrobial substances.


Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including ∼15,000 women.
To evaluate the association between the number of oocytes retrieved and cumulative live birth rates. Retrospective multicenter analysis using individual patient data. Tertiary referral hospitals. In total, 14,469 patients were analyzed. The study included the first cycle of patients stimulated for IVF/intracytoplasmic sperm injection (ICSI) from 2009 to 2014. All patients included in the analysis had either delivered a baby or had used all their embryos after their first stimulated cycle. All patients had vitrification as cryopreservation method. All women were followed up for at least 2 years. Ovarian stimulation with GnRH antagonist protocol for IVF/ICSI. The primary outcome was the cumulative live birth rate defined as the delivery of at least one live-born infant (>24 weeks of gestation) in the fresh or in the subsequent frozen-thawed cycles in relation to the number of oocytes retrieved. Only the first delivery was considered in the analysis. The secondary outcome was live birth after the fresh IVF/ICSI cycle only. Cumulative live birth rates steadily increased with the number of oocytes, reaching 70% when ≥25 oocytes were retrieved. Interestingly, no plateau in cumulative live birth rates was observed, but a moderate increase of 5.1% on average was detected beyond 27 oocytes. Regarding the fresh cycle outcome, live birth probability increased up to seven oocytes retrieved and remained relatively unchanged (increase or decrease of ≤5%) between seven and 20 oocytes retrieved. However, a drop in fresh live birth rates was identified thereafter, which could be attributed to the progressive increase in "freeze-all" cycle rate with the number of oocytes retrieved, exceeding 20% in patients with >20 oocytes retrieved. This is the largest multicenter study evaluating for the first time the impact of ovarian response on cumulative live birth rate. The significant progressive increase of cumulative live birth rate with the number of oocytes in our study suggests that ovarian stimulation may not have a detrimental effect on oocyte/embryo quality in good-prognosis women less than 40 year old. Nevertheless, although very high ovarian response may further increase cumulative live birth rates, ovarian stimulation should be rational and avoid extreme response in terms of oocytes retrieved to preserve patients' convenience and safety and avoid ovarian hyperstimulation syndrome or other iatrogenic complications.


A case series to investigate food-related fear learning and extinction using in vivo food exposure in anorexia nervosa: A clinical application of the inhibitory learning framework.
Anorexia nervosa is characterized by severe malnutrition. This study tested the hypothesis that fear of food is a learned behaviour and evaluated the feasibility and effectiveness of gradual exposure to food to improve eating behaviour in people with anorexia nervosa. Eighteen women were recruited and completed baseline self-reports. They were interviewed regarding early experiences of eating and the development of food-related anxiety. Participants received eight sessions of in vivo food exposure. Findings indicated that fear of food is a learned behaviour, associated with catastrophic thoughts around the consequences of eating and safety behaviours. Patients consumed at least half of the food item selected in all but one session. Body mass index increased, and food restriction, eating concern, eating disorder-related preoccupations, and overall anxiety reduced (medium/large ES). Findings corroborate an anxiety-based model of anorexia nervosa and support the relevance of targeting food-related fears using exposure-based protocols.


[Reuse process of positive pressure powered air-filter protective hoods].
To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic. The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method. Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing. The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.


Laparoscopic revision to total gastrectomy or fistulo-jejunostomy as a definitive surgical procedure for chronic gastric fistula after laparoscopic sleeve gastrectomy.
Staple-line leaks (SLL) after sleeve gastrectomy (SG) are a rare but serious complication requiring radiologic and endoscopic interventions with varying degrees of success. When failed, a chronic gastrocutaneous fistula forms with decreasing chances of closure with time. Definitive surgical management of chronic SLL after SG include laparoscopic revision to total/subtotal gastrectomy (LTG/LSTG) or a fistulo-jejunostomy (LRYFJ), both with Roux-en-Y reconstruction. Comparison of SG revisions to LTG/LSTG versus LRYFJ as a definitive treatment for chronic SLL. High-volume bariatric unit. Retrospective review of a prospectively maintained database identified 17 patients with chronic gastric fistula after SG that were revised to either LTG/LSTG or LRYFJ between September 2011 and May 2020. Demographic characteristics, clinical data, quality of life, and laboratory values for both options were compared. Of the 17 conversions, 8 were revised to LTG/LSTG and 9 to LRYFJ. Mean age and body mass index at revision were 36.85 years (range, 21-66 yr) and 29 kg/m2 (range, 21-36 kg/m2), respectively. Average preoperative endoscopic attempts was 5 (range, 1-16). The overall average operation time of revision was 183 minutes (range, 130-275 min) with no significant difference between either conversion options. Mean follow-up time was 46.5 months (range, 1-81 mo) and was available for 10 patients (58.8%). Food intolerance was significantly better after revision to LRYFJ (n = 6/6, 100% versus n = 1/5, 20%, P < .05). There were no significant differences between revisional procedures and laboratory abnormalities. Laparoscopic revision to LRYFJ is a safe and feasible treatment for chronic SLL.


Di-aqua-bis-(4-ferrocenyl-1,1,1-tri-fluoro-4-oxobutan-2-olato)cobalt(II).
In the title compound, [CoFe2(C5H5)2(C9H5F3O2)2(H2O)2], the central Co atom has an octa-hedral coordination geometry defined by two chelating tri-fluoro-methyl-β-diketone ferrocene ligands and two aqua ligands, with the latter in a cis disposition. The Cp rings in both ferrocene groupings are close to eclipsed. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into [100] chains.


The turnover of F-actin-bound ADP in vivo.
A procedure for estimating the rate of turnover of F-actin-bound ADP in vivo is described. A turnover rate of 0.88 h-1 was determined for mouse muscle F-actin. The validity of the method when used to estimate the turnover rate of F-actin per se is discussed in relation to the possible exchange of F-actin-bound ADP.


Combination of metabolome and proteome analyses provides insights into the mechanism underlying growth differences in Acipenser dabryanus.
To analyze the differences between different-sized Acipenser dabryanus, we randomly selected 600 3-month-old A. dabryanus juveniles. Four months later, the blood and white muscle of these fish were analyzed. The results showed no significant difference in the length-weight relationship (LWR) b value between the large and small A. dabryanus. The levels of serum growth hormone (gh) and insulin-like growth factor 1 (igf1) in the large A. dabryanus were significantly lower than those in the small, whereas the activity levels of Total superoxide dismutase (T-sod) and catalase (cat) were opposite to the results of gh and igf1. A total of 212 and 245 metabolites showed significant changes in the positive and negative polarity mode, respectively. Among 3,308 proteins identified, 69 proteins showed upregulated expression, and 185 proteins showed downregulated expression. These results indicated that the growth advantage of A. dabryanus was closely related to glycolysis, protein synthesis, and antioxidant function.


In vitro cariostatic effects of various iron supplements on the initiation of dental caries.
Previous animal and laboratory studies have shown the possible cariostatic effect of iron. The purpose of this study was to in vitro study the effect of different concentrations of four iron supplements on the initiation of dental caries. Four products of iron supplements were used namely fre-in-sol, ferotonic, feromin and ferose. Two hundred extracted teeth were distributed randomly into 10 groups. Eight groups were from the four iron products in two concentrations (100% and 50%) in addition to the positive and negative control groups. Mutans streptococci bacteria (6715) grown in Todd Hewitt Broth were used. Assessment of decalcification and cavitation was done daily for 60 days. It showed that different iron - supplement products play cariostatic effect in the initiation of the dental caries. With the exception of 100% and 50% ferose, both 100% and 50% concentrations of all supplements have cariostatic effect. The mean dates for decalcification varied with lowest for the positive control (12.2 days) and the highest was for 50% feromin. Cavitation was seen in the positive control and 100% ferose groups with mean on the first day of cavitation of 57 days. It was concluded that iron may have cariostatic effect on the in vitro development of dental caries in human teeth.


Isolation, stability and bioactivity of Jatropha curcas phorbol esters.
Jatropha curcas seed oil, which can be utilized for biodiesel production upon transesterification, is also rich in phorbol esters (PEs). In this study, PEs from J. curcas oil (Jatropha factors C₁ and C₂ (purified to homogeneity), Jatropha factors C₃ and (C₄+C₅) (obtained as mixtures) and PE-rich extract (containing all the above stated Jatropha factors) were investigated. The concentrations of Jatropha PEs were expressed equivalent to Jatropha factor C₁. In the snail (Physa fontinalis) bioassay, the order of potency (EC₅₀, μg/L) was: PE-rich extract<factor C₃ mixture<factor C₂<factor C₁<factor (C₄+C₅). In the Artemia salina bioassay, the order of potency (EC₅₀, mg/L) was: factor C₂<factor C₃ mixture<factor C₁<factor (C₄+C₅) mixture. In addition, Jatropha PEs exhibited platelet aggregation (ED₅₀, μM, factor C₂<factor C₃ mixture<factor C₁<factor (C₄+C₅) mixture. The stability of a PE-rich extract was evaluated and found to be low at room temperature but favourable in ethanol over a range of temperatures. By integrating the isolation methodology developed in this study in the Jatropha biodiesel industry, PEs could be obtained as value-added co-products.


Doppler ultrasound-guided percutaneous nephrolithotomy with two-step tract dilation for management of complex renal stones.
To report our experience and assess the safety and efficacy of Doppler ultrasound-guided percutaneous nephrolithotomy (PCNL) with 2-step tract dilation for complex renal stones. From March 2009 to February 2011, 262 patients underwent PCNL. Eighty-three patients had a complete and 105 had partial staghorn calculus, and 74 had a renal pelvic stone of >2 cm in diameter. Thirty-five patients had renal surgical history. Doppler ultrasound-guided PCNL with 2-step tract dilation were performed. Stones were fragmented and cleared using a combination of ultrasonic and pneumatic lithotripters. All PCNL procedures were successful. Successful access to the collecting system was 100%. Although most of the cases (231/262) were managed satisfactorily by a single tract, a second tract was used in 31 cases. Mean operation time was 56 minutes (range 25-145). The primary stone-free rate of PCNL was 80.9%. There were 39 auxiliary procedures (13 second PCNL and 26 extracorporeal shock wave lithotripsy). One month after treatment, the overall stone-free rate was 92.7%. Five patients (1.9%) received blood transfusion. Eight patients (3.1%) with a postoperative fever of ≥38.5°C were cured by intravenous antibiotics. No other severe complications occurred. The mean postoperative stay was 3.8 days (range 2-12). Doppler ultrasound-guided PCNL with 2-step tract dilation for complex renal stones is safe, effective, and worthy of wider use in clinical practice.


Investigating young women's motivations to engage in early mammography screening in Switzerland: results of a cross-sectional study.
The scientific and public debate concerning organized mammography screening is unprecedentedly strong. With research evidence concerning its efficacy being ambiguous, the recommendations pertaining to the age-thresholds for program inclusion vary between - and even within - countries. Data shows that young women who are not yet eligible for systematic screening, have opportunistic mammograms relatively often and, moreover, want to be included in organized programs. Yet, to date, little is known about the precise motivations underlying young women's desire and intentions to go for, not medically indicated, mammographic screening. A cross-sectional online survey was carried out among women aged 30-49 years (n = 918) from Switzerland. The findings show that high fear (β = .08, p ≤ .05), perceived susceptibility (β = .10, p ≤ .05), and ego-involvement (β = .34, p ≤ .001) are the main predictors of screening intentions among women who are not yet eligible for the systematic program. Also, geographical location (Swiss-French group: β = .15, p ≤ .001; Swiss-Italian group: β = .26, p ≤ .001) and age (β = .11, p ≤ .001) play a role. In turn, breast cancer knowledge, risk perceptions, and educational status do not have a significant impact. Young women seem to differ inherently from those who are already eligible for systematic screening in terms of the factors underlying their intentions to engage in mammographic screening. Thus, when striving to promote adherence to systematic screening guidelines - whether based on unequivocal scientific evidence or policy decisions - and to allow women to make evidence-based, informed decisions about mammography, differential strategies are needed to reach different age-groups.


A patient-centred approach to biological treatment decision making for psoriasis: an expert consensus.
Each individual psoriasis patient has different expectations and goals for biological treatment, which may differ from those of the clinician. As such, a patient-centred approach to treatment goals remains an unmet need in psoriasis. The aim of this study was to review available data on patients' and physicians' decision criteria and expectations of biological treatment for moderate-to-severe psoriasis with the aim of developing a core set of questions for clinicians to ask patients routinely to understand what is important to them and thus better align physicians' and patients' expectations of treatment with biologics and its outcomes. A literature search was conducted to identify key themes and data gaps. Aspects of treatment relevant when choosing a biological agent for an individual patient were identified and compared to an existing validated instrument. A series of questions aimed at helping the physician to identify the particular aspects of treatment that are recognised as important to individual psoriasis patients was developed. Key findings of the literature search were grouped under themes of adherence, decision-making, quality of life, patient/physician goals, communication, patient-reported outcomes, satisfaction and patient benefit index. Several aspects of treatment were identified as being relevant when choosing a biological agent for an individual patient. The questionnaire is devised in two parts. The first part asks questions about patients' experience of psoriasis and satisfaction with previous treatments. The second part aims to identify the treatment attributes patients consider to be important and may as such affect their preference for a particular biological treatment. The questionnaire results will allow the physician to understand the key factors that can be influenced by biological drug choice that are of importance to the patient. This information can be used be the physician in clinical decision making. The questionnaire has been developed to provide a new tool to better understand and align patients' and physicians' preferences and goals for biological treatment of psoriasis.


Analysis of region-specific changes in gene expression upon treatment with citalopram and desipramine reveals temporal dynamics in response to antidepressant drugs at the transcriptome level.
The notion that the onset of action of antidepressant drugs (ADs) takes weeks is widely accepted; however, the sequence of events necessary for therapeutic effects still remains obscure. We aimed to evaluate a time-course of ADs-induced alterations in the expression of 95 selected genes in 4 regions of the rat brain: the prefrontal and cingulate cortices, the dentate gyrus of the hippocampus, and the amygdala. We employed RT-PCR array to evaluate changes during a time-course (1, 3, 7, 14, and 21 days) of treatments with desipramine (DMI) and citalopram (CIT). In addition to repeated treatment, we also conducted acute treatment (a single dose of drug followed by the same time intervals as the repeated doses). Time-dependent and structure-specific changes in gene expression patterns allowed us to identify spatiotemporal differences in the molecular action of two ADs. Singular value decomposition analysis revealed differences in the global gene expression profiles between treatment types. The numbers of characteristic modes were generally smaller after CIT treatment than after DMI treatment. Analysis of the dynamics of gene expression revealed that the most significant changes concerned immediate early genes, whose expression was also visualized by in situ hybridization. Transcription factor binding site analysis revealed an over-representation of serum response factor binding sites in the promoters of genes that changed upon treatment with both ADs. The observed gene expression patterns were highly dynamic, with oscillations and peaks at various time points of treatment. Our study also revealed novel potential targets of antidepressant action, i.e., Dbp and Id1 genes.


Simultaneous detection of cancerous exosomal miRNA-21 and PD-L1 with a sensitive dual-cycling nanoprobe.
Simultaneous detection of specific exosomal surface proteins and inner microRNAs are hampered by their heterogeneity, low abundance and spatial segregation in nanovesicles. Here, we design a dual-cycling nanoprobe (DCNP) to enable single-step simultaneous quantitation of cancerous exosomal surface programmed death-ligand 1 (PD-L1) (ExoPD-L1) and miRNA-21 (ExomiR-21) directly in exosome lysates, without resorting to either RNA extraction or time-consuming transmembrane penetration. In this design, DNA molecular machine-based dual-recognition probes co-assemble onto gold nanoparticle surface for engineering 'silent' DCNPs, which enable signal-amplified synchronous response to dual-targets as activated by ExomiR-21 and ExoPD-L1 within 20 min. Benefiting from cycling amplification of the molecular machine, DCNPs sensor achieves detection limits of tumor exosomes, ExoPD-L1 and ExomiR-21 down to 10 particles/μL, 0.17 pg/mL and 66 fM, respectively. Such a sensitive dual-response strategy allows simultaneous tracking the dynamic changes of ExoPD-L1 and ExomiR-21 expression regulated by signaling molecules or therapeutics. This approach further detects circulating ExoPD-L1 and ExomiR-21 in human plasma to differentiate breast cancer patients from healthy individuals with high accuracy, showing great potential of DCNPs for simultaneous profiling exosomal surface and inside biomarkers, and for clinical precision diagnosis.


Vasomotor responses recorded using the in situ perfusion of a portion of the rat cerebral circulation.
A simple method whereby an area of the rat cerebral circulation can be perfused in situ in the dead animal has been developed. A modified Krebs/Henseleit perfusate was passed at a constant flow rate through one internal carotid artery and recovered from the transverse sinus following ligature of the arterial system of the opposite side and all venous returns to the heart. Rubber latex injections indicated that the main perfusion pathway was unilateral via the middle, anterior, and posterior cerebral arteries. The basilar and cerebellar arteries were not involved. Vasoconstrictor substances, such as 5-hydroxytryptamine (5HT), noradrenaline, and related catecholamines, gave reproducible, dose-related responses, when tested over experimental periods of 4-5 hrs. Although the preparation had no intrinsic vascular tone, vasodilator substances, such as acetylcholine, isoprenaline, histamine, or the purines, adenosine, ATP, ADP, and AMP, could be tested against various levels of tone induced by the addition of 5HT to the perfusate. On the basis of these preliminary results, the preparation appears suitable for qualitative and quantitative investigations of the responses of the rat cerebral circulation to a wide range of vasoactive substances.


Raman and Luminescent Spectra of Sulfonated Zn Phthalocyanine Enhanced by Gold Nanoparticles.
Sulfonated Zn phthalocyanine, as a prospective photosensitizer in the photodynamic therapy of tumors, is investigated by means of Raman, infrared, and fluorescence spectroscopies. Conventional and surface-enhanced spectra from this photosensitizer are obtained and compared. Gold nano-islands attached to silica cores (Au-SiO2) are proposed as nanostructures providing plasmonically enhanced signals. Pronounced enhancement of Raman and infrared spectral bands from sulfonated Zn phthalocyanine allows their more convenient assignment with vibrational modes of sulfonated Zn phthalocyanine. In comparison to Raman and IR, the fluorescence is less enhanced by Au-SiO2 particles.


Arthroscopic treatment of synovial chondromatosis of the shoulder and biceps tendon sheath.
We present a case of synovial chondromatosis of the shoulder in a 22-year-old man. The patient was initially treated with arthroscopic debridement and partial synovectomy of the shoulder joint. Eighteen months later, the patient returned with similar symptoms. However, repeat radiographic studies showed involvement of both the shoulder and biceps tendon sheath. The patient was taken back to the operating room for an arthroscopic debridement of the shoulder joint and debridement of the biceps tendon sheath through an open approach. Use of the arthroscope to evaluate and treat this patient allowed him to return to normal activities much sooner than a formal open synovectomy would have allowed. Additionally, the morbidity associated with arthroscopic techniques is much lower than that of open procedures. In cases of synovial chondromatosis, the results in terms of efficacy and recurrence rates of each method appear comparable.


Aggregation Induced Emission Switching Based Ultrasensitive Ratiometric Detection of Biogenic Diamines Using a Perylenediimide-Based Smart Fluoroprobe.
In recent years, the widely explored phenomenon "aggregation-induced emission (AIE)" has played a crucial role in the development of luminescent materials for light-emitting applications. In the same direction, the contribution of its sister concept "AIE switching" has been impressive. In comparison, the application of this concept in the field of biosensing or bioimaging is still in its infancy. Therefore, to shed light into the sensing of bioanalytes, we have developed a new perylenediimide (PDI)-based small fluorescent probe, benzoannulated PDI (Bp(Im)2MA), that selectively detects diamines and biogenic amines (BAs) in solution via an "AIE-switching" phenomenon. The synthesized probe containing the bay-annulated anhydride moiety exhibits strong cyan emission in solution. In the mechanism, we have shown that the terminal free amine group of BAs readily reacts with a highly reactive anhydride moiety, which opens the cyclic anhydride moiety. In the open conformation, the free amine group along with a carboxylate group modulates the polarity of the system strikingly. Because of this induced polarity, the monomer of Bp(Im)2MA-BAs conjugate aggregated in solution, thereby exhibiting a significant change in emission property in solution. This method may also be called a very simple and straightforward "naked eye" detection of BAs in solution, with a nanomolar detection limit. A detailed spectroscopic and microscopic investigation demonstrated the existence of the aggregated state. As the reporter dye also emits strongly in the solid state (yellowish orange), it therefore instantly made vapor-phase detection of BAs feasible. Finally, this vapor-phase detection of BAs by the probe was applied very effectively in the determination of spoilage of raw fish.


Bipolar haemostatic forceps versus standard therapy by haemoclip + / - epinephrine injection as initial endoscopic treatment in active non-variceal upper GI bleeding: study protocol for a prospective, randomized multicentre trial (BeBop-Trial).
Patients with active nonvariceal upper gastrointestinal bleeding (NVUGIB) usually require urgent endoscopic treatment. Standard therapy (ST) using haemoclip + / - epinephrine injection is not always successful. Bipolar haemostatic forceps (HemoStat/Pentax®) are an approved medical device for the treatment of gastrointestinal bleeding. However, their use as a primary endoscopic treatment for active NVUGIB has not yet been proven in a randomized prospective study. This is a prospective, randomized, multicentre superiority trial (n ≥ 5). Patients with active NVUGIB will be randomized (1:1) to ST and to experimental therapy (ET) by application of bipolar haemostatic forceps. In the case of failed initial treatment within 15 min, crossover treatment will be attempted first. Rescue treatment (e.g. via over-the-scope-clip) will then be allowed after 30 min. All patients will also receive standard therapy with proton pump inhibitors. Forty-five patients per treatment arm are required to demonstrate an absolute difference of 25.4% with a power of 80% and a significance level of 0.05. The hypothesis of the study is that bipolar haemostatic forceps are superior to ST in terms of successful primary haemostasis and the absence of recurrent bleeding within 30 days (combined endpoint). The 1:1 randomization is also ethically justifiable for this study, as both procedures are approved for the intervention in question. To further increase the safety of the patients in the study, crossover treatment and rescue treatment are planned. The prospective design seems feasible in a reasonable time frame (recruitment period of 12 months), as nonvariceal upper gastrointestinal bleeding is common. Anticoagulants and/or antiplatelet drugs could be an important confounding factor in the statistical analysis that needs to be taken into account and calculated if necessary. In conclusion, this randomized, prospective, multicentre study could make an important contribution to answering the question of whether bipolar haemostatic forceps could be the first-line therapy in the endoscopic treatment of stage Forrest I a + b NVUGIB. ClinicalTrials.gov NCT05353062. Registered on April 30 2022.


Ubiquitin conjugating enzyme E2 M promotes apoptosis in osteoarthritis chondrocytes via Wnt/β-catenin signaling.
In this study, the role of ubiquitin conjugating enzyme E2 M (UBE2M) and molecular mechanisms associated with osteoarthritis (OA) were explored. Cartilage tissues and corresponding healthy tissues from OA patients were isolated. Our data suggested that the expression level of UBE2M in OA patients was significantly higher compared to that in healthy individuals (P < 0.01). The apoptosis of human OA chondrocytes was inhibited when silencing UBE2M and increased when overexpressing UBE2M. XAV939, as a tankyrase 1 inhibitor, could block the signaling pathway of Wnt/β-catenin, which significantly reversed the change introduced by UBE2M. The expression level of cytoplasmic β-catenin in siUBE2M cells dramatically increased, and the expression levels of nuclear β-catenin, cleaved caspase-3 (C-caspase-3), and MMP13 remarkably downregulated. Moreover, the ubiquitination of Axin was enhanced by the overexpression of UBE2M. The expression level of Axin significantly decreased in OA chondrocytes with UBE2M overexpression and increased after MG132 treatment. Moreover, UBE2M enhanced the apoptosis of OA chondrocytes by activating the Axin-dependent Wnt/β-catenin pathway. In this process, UBE2M downregulated Axin in an ubiquitination-dependent degradation pathway and subsequently activated Wnt/β-catenin signaling.


Detection of lipopolysaccharides in polyacrylamide gels by transfer to nitrocellulose followed by immunoautoradiography with antibody and 125I-protein A: "LPS blotting".
Lipopolysaccharides (LPS), which constitute the somatic (O) antigen of gram-negative bacteria, were used to demonstrate the procedure of LPS blotting involving the electrophoretic transfer of electrophoretically resolved LPS from sodium dodecyl sulfate-polyacrylamide gels to nitrocellulose filters. Immobilized LPS could then be immunoautoradiographically visualized in situ by reaction with specific anti-LPS antibody and subsequent binding of radioiodinated Staphylococcus protein A. LPS blotting is expected to provide an efficient and specific means of investigating the LPS (O) antigens of gram-negative bacteria.


Crystal structure of two quaternary complexes of dethiobiotin synthetase, enzyme-MgADP-AlF3-diaminopelargonic acid and enzyme-MgADP-dethiobiotin-phosphate; implications for catalysis.
The crystal structures of two complexes of dethiobiotin synthetase, enzyme-diaminopelargonic acid-MgADP-AlF3 and enzyme-dethiobiotin-MgADP-Pi, respectively, have been determined to 1.8 A resolution. In dethiobiotin synthetase, AlF3 together with carbamylated diaminopelargonic acid mimics the phosphorylated reaction intermediate rather than the transition state complex for phosphoryl transfer. Observed differences in the binding of substrate, diaminopelargonic acid, and the product, dethiobiotin, suggest considerable displacements of substrate atoms during the ring closure step of the catalytic reaction. In both complexes, two metal ions are observed at the active site, providing evidence for a two-metal mechanism for this enzyme.


Transcriptional phase variation at the flhB gene of Pseudomonas putida DOT-T1E is involved in response to environmental changes and suggests the participation of the flagellar export system in solvent tolerance.
Frameshift mutations in a poly(G) track at the flhB gene of Pseudomonas putida DOT-T1E are responsible for the diminished swimming of this strain on semisolid medium, which contrasts with the high swimming ability of P. putida KT2440, which does not exhibit a poly(G) track at the flhB gene. We previously showed that a mutant lacking FlhB was more sensitive to solvents than the wild-type strain (Segura et al., J. Bacteriol., 183:4127-4133, 2001). In this study, we show that swimming ability correlates with solvent tolerance in P. putida DOT-T1E, so that growth conditions favoring a functional flhB gene (growth on semisolid medium) resulted in increased innate tolerance to a sudden toluene shock.


New approaches on the use of tunicates (Ciona robusta) for toxicity assessments.
After the accidental release of crude oil in marine environment, dispersants are applied on sea surface transferring oil into the water column where it can be broken down by biodegradation, thereby reducing potential pollution to coastal areas. Before they can be used in the wild, the ecotoxicity of such dispersants is usually evaluated with toxicity assays using algae, crustacean and fishes. Nowadays, there is a need to find alternative species to reduce the use of vertebrates both for ethical considerations and for reducing the cost of bioassays. Ciona robusta is a solitary ascidian that inhabits shallow waters and marine coastal areas. This species has been recently adopted as valuable biological model for ecotoxicity studies, thanks to its rapid embryonic and larval development, resemblance to vertebrates, and low risk of ethical issues. On this ground, the lethal and sublethal toxicity of two dispersants has been evaluated on Ciona juveniles. At this stage, the organisms become filter-feeders and the morphological alterations of the organs can be easily observed. The median lethal concentrations at 96 h (96hLC50) for Dispersant 1 (non-ionic surfactant) and for Dispersant 2 (mixture of non-ionic surfactants and anionic surfactants) are 41.6 mg/L (38.6-44.9) and 92.5 mg/L (87.7-97.5), respectively. The Ciona juvenile model was compared to Dicentrarchus labrax fish juveniles test, and it showed increased sensitivity for Ciona to these compounds. These results suggest that 96 h mortality test bioassay could be a good alternative method to 96 h mortality assay with D. labrax, limiting the use of vertebrates for dispersant toxicity.


Carotid arterial intima–media thickness and arterial stiffness in pre-eclampsia: analysis with a radiofrequency ultrasound technique.
Whether arterial elasticity is reduced in preeclampsia has been investigated only rarely. This study aimed to characterize in vivo the carotid arterial intima–media thickness (IMT) and mechanical properties in women with pre-eclampsia by employing a radiofrequency ultrasound technique. We included 22 late-onset pre-eclamptic pregnant women and 28 normotensive pregnant women who were matched for age (29 ± 6 vs. 27 ± 3, P=0.09) and gestational age (36.0 ± 3.2 vs. 35.8 ± 2.4 weeks, P=0.802). All women were nulliparous with singleton pregnancy. The pre-eclamptic women had a significantly higher arterial pressure than did the normotensive women (P<0.0001). All women underwent right common carotid arterial measurements with an ultrasound machine equipped with automatic Quality IMT (QIMT) and Quality Arterial Stiffness (QAS) capability. At follow-up examination 18 months after parturition, measurements were repeated in 10 of the pre-eclamptic women and 11 of the normotensive women. In pre-eclamptic compared with normotensive pregnancy, carotid arterial IMT (459 ± 95 vs. 351 ± 85 μm, P=0.0001), internal diameter (7.8 ± 0.5 vs. 7.2 ± 0.4 mm, P<0.0001), pulse wave velocity (7.1 ± 1.7 vs. 6.0 ± 1.5 m/s, P=0.007), augmentation index (7.9 ± 9.2 vs. −5.0 ± 5.6%, P<0.0001) and arterial wall tension (55.0 ± 6.5 vs. 38.6 ± 4.9 mmHg/cm, P<0.0001) were significantly greater, and the distensibility coefficient (0.020 ± 0.009 vs. 0.029 ± 0.011 1/kPa, P=0.006) was significantly smaller, remaining so after adjusting for body mass index and carotid arterial pressure. Eighteen months after parturition, carotid arterial internal diameter, pressure and wall tension remained greater in the pre-eclamptic group. Carotid arterial remodeling, including changes in arterial internal diameter and wall thickness, and arterial stiffening occur in pre-eclampsia but this may reverse, to some extent, postpartum. QIMT and QAS techniques together could provide a comprehensive assessment of carotid arterial remodeling.


Release of acetylcholinesterase from the guinea-pig substantia nigra during peripheral nerve stimulation.
A soluble form of acetylcholinesterase is released from the substantia nigra in both a spontaneous and drug-induced fashion. The aim of this study was to see whether this phenomenon was also sensitive to a non-pharmacological event. During electrical stimulation of the intact sciatic nerve, there was an increase in the activity of acetylcholinesterase, measured in perfusates of the guinea-pig substantia nigra in vivo. This increase was not due to spontaneous fluctuations in acetylcholinesterase release, plasma contamination, tissue damage or release of acetylcholinesterase from a non-specific site. The possible pathways mediating this phenomenon are discussed.


Cerebral perfusion change of venous hypertension on near-infrared spectroscopy signals after operation for dural arteriovenous fistula.
A dural arteriovenous fistula (AVF) is an arteriovenous shunt in the dura and is associated with a risk of intracranial hemorrhage and neurologic deficit. The morbidity of this disease depends on venous hypertension, and the classification of this disease is based on the pattern of venous drainage. The pattern of venous drainage relates to the clinical features of the disease, especially to the probability of intracranial hemorrhage. We report 1 case of dural AVF with retrograde leptomeningeal venous drainage. Cerebral hemodynamics were monitored using near-infrared spectroscopy imaging before, during, and after the 2-stage operative treatment. Preoperative functional near-infrared spectroscopy (fNIRS) showed an increase in deoxyhemoglobin (HbR) during a motor task. After partial coil embolization of the shunt points (stage 1), HbR increased during the first half of the task and decreased later, whereas oxyhemoglobin (HbO2) decreased in the first half of the task and increased later. After complete embolization (stage 2), fNIRS showed a pattern similar to that of a normal adult. The patient's symptoms improved gradually, and angiography showed a reduction of the retrograde venous drainage and venous congestion after this 2-stage operation. The reduction in venous hypertension may be the underlying mechanism behind the changes observed with fNIRS.


Regulating Fbw7 on the road to cancer.
The F-box protein Fbw7 targets for degradation critical cellular regulators, thereby controlling essential processes in cellular homeostasis, including cell cycle, differentiation and apoptosis. Most Fbw7 substrates are strongly associated with tumorigenesis and Fbw7 can either suppress or promote tumor development in mouse models. Fbw7 activity is controlled at different levels, resulting in specific and tunable regulation of the abundance and activity of its substrates. Here we highlight recent studies on the role of Fbw7 in controlling tumorigenesis and on the mechanisms that modulate Fbw7 function.


Expression of the putative Duchenne muscular dystrophy gene in differentiated myogenic cell cultures and in the brain.
Duchenne muscular dystrophy (DMD), a sex-linked degenerative disorder of the muscle, is one of the most common lethal genetic diseases in man. It affects about one male in 3,500, with an estimated one-third of cases being caused by new mutations. A less severe disease, Becker's muscular dystrophy (BMD), maps to the same chromosomal locus and is most probably an allelic form of DMD. Both diseases are sometimes associated with various degrees of mental retardation; the molecular basis of these phenotypes is unknown (for review, see ref. 1). The giant DMD gene spans approximately 2,000 kilobases (kb) (0.05% of the human genome) and encodes a 14-kb mRNA. The tissue-specificity of its expression has not been precisely determined. Monaco et al., using Northern blots, reported expression of the gene in human fetal skeletal muscle and small intestine but not in human fetal brain, or in human cultured myoblasts and transformed B and T cells. More recently, expression was detected in mouse skeletal and cardiac muscle, but not in mouse brain. Here we show, using a ribonuclease protection assay, that the DMD gene is developmentally regulated in rat and mouse myogenic cell cultures, and that it is expressed in rat and mouse striated muscle, in mouse smooth muscle and in rat, mouse and rabbit brain. We could not detect transcripts in other non-muscle tissues.


The current status of quantitative SPECT/CT in the assessment of transthyretin cardiac amyloidosis.
Nuclear medicine bone scans differentiate ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders, helping to make the diagnosis without biopsy. Standard bone scans are not absolutely quantitative, so are assessed by comparing the heart to other tissues. The standard visual scoring system compares heart to bone. This accurately diagnoses ATTR-CM and has been validated in a multicenter study, but has limitations. Semiquantitative techniques including heart/contralateral thorax (H/CL) and heart/whole body ratio (H/WB) improve on visual scoring but still rely on extracardiac sites as comparators. Absolute quantitation of myocardial uptake using quantitative SPECT should help overcome these shortcomings. In ATTR-CM, this technique is practical, accurately makes the diagnosis and provides information that is not identical to visual scores. However, more work needs to be done. The reproducibility in ATTR-CM must be tested. Larger studies need to be undertaken to determine whether quantitative SPECT measurements can assess prognosis, disease progression or treatment response. As ATTR-CM is relatively uncommon multicenter trials will help recruit enough subjects to answer these questions. Accurate measurement techniques are needed in ATTR-CM to enable appropriate use of proven therapy and to conduct trials of new therapeutic agents. Quantitative bone scans offer a promising avenue.


Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation.
Microglia, the resident immune cells of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the retinas of mice ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age, and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, C3 and CFB, previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS.


Poor response to hepatitis C treatment in elderly patients.
Treatment of genotype 1 chronic hepatitis C in elderly patients has been associated with low rates of a sustained virological response (SVR), but the reasons are unclear. To determine the SVR rate in patients ≥ 60 years with genotype 1 chronic hepatitis C treated with Peg-IFN and ribavirin, and to identify risk factors related to treatment response in this specific group of patients. Material and methods. Patients were divided into < 60 years (non-elderly) and ≥60 years (elderly) and were compared regarding clinical, laboratory and histological characteristics and response to treatment. A total of 231 patients were included in the study. The elderly group (n=89) presented a predominance of women, more advanced hepatic disease, higher glucose, cholesterol and LDL levels, lower hemoglobin levels, and a larger proportion of overweight subjects. The SVR rate was lower (25% vs 46%) and anemia, ribavirin dose reduction and use of filgrastim and erythropoietin were more frequent in elderly patients. Negative predictive factors of SVR in the whole group (n = 231) were glucose ≥ 100 mg/dL and age ≥ 60 years. In the elderly group, only pretreatment variables (lower serum glucose and higher hemoglobin levels) were associated with SVR. The SVR rate was low in elderly patients. However, this poor response was not due to poor tolerance, but mainly to pretreatment conditions. Among elderly patients, the best candidates for hepatitis C treatment are those with elevated pretreatment hemoglobin levels and adequate glycemic control.


Hematological Profiles and Clinical Outcome of COVID-19 Among Patients Admitted at Debre Markos Isolation and Treatment Center, 2020: A Prospective Cohort Study.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is coronavirus isolated from SARS patients. As far as the researchers' knowledge, there was paucity of studies conducted in Ethiopia, particularly in the study area. As immune protection is arisen from our blood cells, assessing their level will provide a clue for controlling the disease and monitoring the prognosis. This study will also provide additional information for clinical intervention and patient management. This study aimed to investigate the hematological profile and clinical outcome of coronavirus disease-19 (COVID-19) among patients admitted to the Debre Markos Isolation and Treatment Center (DMITC). A prospective cohort study was conducted among 136 COVID-19 adult patients at DMITC from January 1, 2020 to March 30, 2021. Data related to clinical, hematological profiles and socio-demographic factors were collected, entered into Epi data, and analyzed using STATA 14.2 software. Multivariable logistic regression was applied to determine the predictor variable and a p-value <0.05 was considered significant. Of 136 COVID-19 patients, 28.68% had died. The mean age of patients was 47.21±1.29 years. The hematological profile of the patients revealed that 28% had abnormal leukocyte, 23% abnormal lymphocyte, 44.85% abnormal granulocyte, 22.06% abnormal monocyte, 30.15% abnormal RBC and 87% abnormal platelet counts. The prevalence of anemia was 13.24%. Leukocytosis (mainly granulocytosis and monocytosis) and lymphopenia, were the predominant abnormal findings of complete blood cell count (CBC) analysis of the patient's blood. Most of the patients had abnormally low platelet counts. RBC count and hematocrit determination were the only significant predictors of death. The clinician could manage cases according to the hematological findings of the patients. Further experimental studies should be conducted to determine hematological parameter changes and the clinical outcome of the disease.


A useful procedure in the treatment of chronic olecranon bursitis.
An operation for chronic olecranon bursitis is described and the results of 11 cases reviewed. It is suggested that a number of patients with this condition have a prominent olecranon process or spur. The technique involves excision of the olecranon process only, the bursa itself is preserved. The overlying skin remains undamaged and this manoeuvre avoids the unpleasant sequelae that may follow its removal. The operation appears to give satisfactory results.


Drinking water quality monitoring and surveillance for safe water supply in Gangtok, India.
To ascertain the quality of drinking water being supplied, water quality monitoring and surveillance was conducted in Gangtok city at various treatment stages, service reservoirs, distribution network, public standposts, and households. No significant change in raw water quality was observed on day-to-day basis. Residual chlorine was found in the range of nil to 0.2 mg/l in the sump water/finished water. Throughout the year (i.e., during summer, winter, and monsoon seasons), the total coliform and fecal coliform counts were ranged from nil to 7 CFU/100 ml and nil to 3 CFU/100 ml, respectively, in sump water of Selep and VIP complex water treatment plant; however, at consumer end, those were observed as nil to 210 CFU/100 ml and nil to 90 CFU/100 ml, respectively. These variations in bacterial counts among the different service reservoirs and consumer ends may be attributed to the general management practices for maintenance of service reservoirs and the possibility of enroute contamination. Evaluation of the raw water quality indicates that the water is suitable for drinking after conventional treatment followed by disinfection. The finished water quality meets the level of standards described as per Bureau of Indian Standard specifications (BIS:10500 1991) for potability in terms of its physicochemical characteristics.