"We Shall Tell them with Love, Inform them what we have Learnt and then Allow them to go" - Men's Perspectives of Self-Collected Cervical Cancer Screening in Rural Uganda: A Qualitative Inquiry.
Uganda has high incidence rates of cervical cancer (47.5/100,000/year) due to limited screening access. In settings where men hold most of the decision-making power, they play an important role in women's uptake of cervical cancer screening. We aimed to capture men's knowledge, beliefs and perspectives about cervical cancer, community-based screening and health system barriers. Focus group discussions were conducted with men in rural Uganda. Data were verbatim translated and transcribed into English. Transcripts were analysed in ATLAS.ti using a deductive approach of thematic content analysis and applied to an implementation research framework. Twenty-three men participated in focus groups. Men held poor knowledge of cervical cancer, its causes and treatment. Men felt screening would be acceptable by women if men and women were educated. Men highlighted health system barriers to accessing screening including: 1) poor-quality health services, 2) large distances to facilities/lack of affordable transportation and 3) lack of health workers/mistreatment by health workers. Men described supporting women through assisting with transportation, psychosocial support and sharing information. They requested services for men to be decentralized alongside community outreaches for cervical cancer screening. Engaging men in the implementation, education and planning of community-based cervical cancer screening programs is critical. Not engaging men is a missed opportunity to provide them with services and education. Concerted efforts must be made in educating men and reducing health system barriers to ensure rural women receive cervical cancer screening and follow-up care in low-income settings. Clinicaltrials.gov, NCT04000503; Registered 27 June 2019.


Simultaneous determination of hydroquinone, catechol and phenol in urine using high-performance liquid chromatography with fluorimetric detection.
A method was developed for simultaneous determination of urinary hydroquinone, catechol and phenol using high-performance liquid chromatography (HPLC) with variable-wavelength fluorimetric detection. Urine samples, after acid hydrolysis, were saturated with sodium sulphate and extracted by diethyl ether. The two buffers used for gradient elution were (A) 10 mM sodium acetate containing 0.5% (v/v) acetic acid and (B) the same as buffer A but containing an additional 20% (v/v) acetonitrile. Hydroquinone, catechol and phenol were separated in a C18 column and detected at 2.9, 6.8 and 13.6 min, respectively. The recovery and reproducibility were generally over 90%. Over 300 extracted samples were analysed and no change in column efficiency was noted. Comparisons were also made with HPLC using ultraviolet (UV) detection and with gas chromatography (GC). The proposed method appears to be more sensitive and reliable than other existing methods. This new method was also validated with urine samples collected from cigarette smokers and from refinery workers exposed to low concentrations of benzene.


ADAM17: A novel treatment target for aneurysms.
The mechanisms underlying abdominal aortic aneurysms (AAAs) are still not fully understood, previous researches showed ADAM17 is increased in aneurysm. We hypothesized that inhibiting ADAM17 can decrease AAA formation and progression. Aneurysm models were established in mouses and rats by aortic adventitial CaCl2 incubation and aortic pericardial patch angioplasty respectively. In mouse, control (no treatment) or SA/HA hydrogel loaded with TAPI-1 (ADAM17 inhibitor) were adventitial applied; in rat, control and TAPI-1 coated pericardial patch were used in rat aortic pericardial patch angioplasty. Samples were harvested on day 14 or 30 and analyzed by immunofluorescence. Bioinformatics analysis and immunostaining analysis were carried out to confirm the therapeutic potential of ADAM17 in the human AAA. ADAM17 was highly expressed in mouses, rats and human aneurysms. Adventitial application of SA/HA hydrogel loaded TAPI-1 or TAPI-1 conjugated pericardial patch can decrease AAA formation and progression in mouses and rats, respectively. Bioinformatic analysis showed ADAM17 promotes transformation of M1 macrophages and synthetic vascular smooth muscle cells, together with immunostaining analysis and results from animal models, the therapeutic potential of ADAM17 in the human AAA were confirmed. We showed that local delivery of ADAM17 inhibitor can inhibit aneurysm formation and progression in mouse and rat, these results showed ADAM17 plays an important role in the aneurysm formation and may be a potential treatment target.


How many additional parameters in a conversion model can be evaluated using "corresponding-site" events?
Contrary to a recent claim by B.C. Lamb and S.A. Zwolinski (1992), the frequencies of "corresponding-site" conversion events (all four chromatids involved in conversion at the same locus in the same meiotic cell) can be used to evaluate only two parameters not otherwise calculable: a coincidence parameter and the frequency of conversion-type events in which a normal 1:1 ratio is restored.


How to meet the lipid requirements of the premature infant.
Through effective use of tables and illustrations, the author discusses the lipid requirements of the premature infant and how these requirements may be met by examining the lipid composition of human milk and colostrum, cow's milk, infant formula, vegetable oils, and premature-infant formula. Also discussed are the variables that affect the composition of human milk and the question of term versus preterm milk.


The glutathionylation of p65 modulates NF-κB activity in 15-deoxy-Δ¹²,¹⁴-prostaglandin J₂-treated endothelial cells.
Protein glutathionylation is a posttranslational modification of cysteine residues with glutathione in response to mild oxidative stress. Because 15-deoxy-Δ12,14-prostaglandin J(2) (15d-PGJ(2)) is an electrophilic prostaglandin that can increase glutathione (GSH) levels and augment reactive oxygen species (ROS) production, we hypothesized that it induces NF-κB-p65 glutathionylation and would exert anti-inflammatory effects. Herein, we show that 15d-PGJ(2) suppresses the expression of ICAM-1 and NF-κB-p65 nuclear translocation. 15d-PGJ(2) upregulates the Nrf2-related glutathione synthase gene and thereby increases the GSH levels. Consistent with this, Nrf2 siRNA molecules abolish the inhibition of p65 nuclear translocation in 15d-PGJ(2)-induced endothelial cells (ECs). ECs treated with GSSG show increased thiol modifications of p65 and also a block in TNFα-induced p65 nuclear translocation and ICAM-1 expression, but not in IκBα degradation. However, the overexpression of glutaredoxin 1 was found to be accompanied by a modest increase in NF-κB activity. Furthermore, we found that multiple cysteine residues in p65 are responsible for glutathionylation. 15d-PGJ(2) was observed to induce p65 glutathionylation and is suppressed by a GSH synthesis inhibitor, buthionine sulfoximine, by catalase, and by Nrf2 siRNA molecules. Our results thus indicate that the GSH/ROS-dependent glutathionylation of p65 is likely to be responsible for 15d-PGJ(2)-mediated NF-κB inactivation and for the enhanced inhibitory effects of 15d-PGJ(2) on TNFα-treated ECs.


Academic performance in Jamaican children with sickle cell disease.
Children with sickle cell disease (SCD) are at risk for neurocognitive deficits that can affect school performance, and psychosocial functioning. The aim of this study was to assess the academic performance of school-aged children with SCD in Jamaica compared to their school peers. A cross-sectional survey of academic performance was done in a group of children 11 to 13 years of age, using a standardized state administered examination, the Grade Six Achievement Test (GSAT), covering 5 subjects. Scores were obtained from the Ministry of Education (MOE) for eligible children with SCD, as well as mean scores with standard deviation for unaffected classmates by gender. Socio-demographic and clinical data were obtained from our sickle cell clinic database and an interview administered questionnaire. Sixty-four children satisfied eligibility criteria. Children with SCD had lower percentage scores and significantly lower mean z-scores for 4 of 5 subjects (p < 0.05). Males had significantly lower mean z-scores compared with females. Thirty-seven children (57.8%) were classified as underperformers. Haemoglobin level was a significant predictor of subject score rank. Children with SCD in Jamaica perform worse in standardized school examinations than their class peers with boys being particularly vulnerable.


QUS characteristics in Normal Population: a Mini Review and our experience.
Quantitative ultrasound (QUS) is a bone densitometry method that is less expensive and more portable than DXA. It is also noninvasive. QUS parameters include speed of sound (SOS), broad band ultrasound attenuation (BUA), and stiffness index (SI). This study defined normal values of QUS parameters in Iranian men and women. QUS of heels measured in 258 Iranian men and women, aged 20-76 y/o. They were participants of Iranian Multicenter Osteoporosis study (IMOS), selected by randomized sampling. QUS device was an Achilles+ (GE-Lunar) device. Percentiles of SI (2.5%, 50%, and 97.5%) determined. We found a good agreement between the Iranian reference values and western reference (used by device) value in defining normal and osteoporotic people (κ = 0.875). Results from this study suggest that QUS of the heel may be a good method for diagnosis of low bone mass in different regions.


A Frailty Index based on clinical data to quantify mortality risk in dogs.
Frailty is defined as a decline in an organism's physiological reserves resulting in increased vulnerability to stressors. In humans, a single continuous variable, the so-called Frailty Index (FI), can be obtained by multidimensionally assessing the biological complexity of an ageing organism. Here, we evaluate this variability in dogs and compare it to the data available for humans. In dogs, there was a moderate correlation between age and the FI, and the distribution of the FI increased with age. Deficit accumulation was strongly related to mortality. The effect of age, when combined with the FI, was negligible. No sex-related differences were evident. The FI could be considered in epidemiological studies and/or experimental trials to account for the potential confounding effects of the health status of individual dogs. The age-related deficit accumulation reported in dogs is similar to that demonstrated in humans. Therefore, dogs might represent an excellent model for human aging studies.


Brain systems and long-term memory.
This paper focuses mainly on those findings derived from lesion studies on the rat which help to identify ensembles of neural structures concerned with the expression of previously learned responses. At the outset, the use of the lesion method in the search for those neurological circuits underlying memory is defended. This is followed by an evaluation of neocortical and subcortical systems in long-term memory. Subsequently, a modest list of tentative functional neural "complexes" involved in the maintenance of certain classes of learned responses is given, based largely upon the author's own research. It is concluded that the key to the understanding of the neurological substrates of long-term memory lies in the identification of those subcortical sites which interact with neocortical sites in the performance of complex learned tasks. The most likely subcortical sites involved in this interaction appear to inhabit the regions of the basal ganglia, limbic midbrain area, and ventral portions of the brainstem reticular formation.


Extracellular matrix during laminar pattern formation of neocortex in normal and reeler mutant mice.
The spatial and temporal distribution of extracellular matrix, which occupied the large extracellular spaces in the developing cerebral cortex, was studied during pre- and perinatal ontogenesis of normal and reeler mutant mice. Colloidal iron-staining material was localized principally in the marginal zone and subplate of normal mice, whereas in reeler mutants, most of the material was found in the outer layers of the cortex. Patterns of extracellular matrix localization in both genotypes followed the laminar pattern formation of cerebral cortex architecture. Histochemical ultrastructural visualization of this extracellular matrix and its susceptibility to enzymatic treatment suggested that the major components are glycosaminoglycans. Their possible role in relation to afferent axon targeting is discussed.


Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue.
γδ T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of γδ T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL) was used to induce angiogenesis in the lower leg of γδ T cell depleted mice and wildtype and isotype antibody-treated control groups. Gastrocnemius muscle tissue was harvested 3 and 7 days after FAL and assessed using (immuno-)histological analyses. Hematoxylin and Eosin staining showed an increased area of tissue damage in γδ T cell depleted mice 7 days after FAL. Impaired angiogenesis was demonstrated by lower capillary to muscle fiber ratio and decreased number of proliferating endothelial cells (CD31+/BrdU+). γδ T cell depleted mice showed an increased number of total leukocytes (CD45+), neutrophils (MPO+) and neutrophil extracellular traps (NETs) (MPO+/CitH3+), without changes in the neutrophils to NETs ratio. Moreover, the depletion resulted in a higher macrophage count (DAPI/CD68+) caused by an increase in inflammatory M1-like macrophages (CD68+/MRC1-). Altogether, we show that depletion of γδ T cells leads to increased accumulation of leukocytes and M1-like macrophages, along with impaired angiogenesis.


Trilobar holoprosencephaly ("triprosencephaly"): a unique type of cerebral malformation.
Little is known about the neuropathology of the median facial cleft syndrome, which presents as a combination of a wide range of teratological manifestations. We report a unique type of cerebral malformation combined with the median facial cleft syndrome in a 7-day-old female infant with malformations of toes and fingers, hypertelorism and a median cleft nose, as well as a frontally protruding, dorsomedian hornlike cele. At autopsy, the cranium presented facial clefts and bony defects, resulting in partitioning of the anterior cranial fossa into three compartments. The brain had malformative features of lobar holoprosencephaly combined with tripartition of frontal lobes, including an encephalomeningocystocele originating from a right accessory frontal lobe.


Rapid fabrication of porous silicon/carbon microtube composites as anode materials for lithium-ion batteries.
Herein, we present a simple and rapid method to synthesize porous silicon/carbon microtube composites (PoSi/CMTs) by adopting a unique configuration of acid etching solution. The CMTs can act as both conductive agent and buffer for Si volume change during the charge and discharge process. The highly reversible capacity and excellent rate capability can be ascribed to the structure, where porous silicon powders are wrapped by a network of interwoven carbon microtubes. The composites show specific capacities of more than 1712 mA h g-1 at a current density of 100 mA g-1, 1566 mA h g-1 at 200 mA g-1, 1407 mA h g-1 at 400 mA g-1, 1177 mA h g-1 at 800 mA g-1, 1107 mA h g-1 at 1000 mA g-1, 798 mA hg-1 at 2000 mA g-1, and 581 mA h g-1 at 3000 mA g-1 and maintain a value of 1127 mA h g-1 after 100 cycles at a current density of 200 mA g-1. Electrochemical impedance spectroscopy (EIS) measurements prove that charge transfer resistance of PoSi/CMT composites is smaller than that of pure PoSi. In this study, we propose a quick, economical and feasible method to prepare silicon-based anode materials for lithium-ion batteries.


Correlation of growth hormone secretion to sleep in the immature rat.
The correlation between growth hormone (GH) secretion and the sleep-wakefulness cycle in the 29-31 day-old male rat was studied by serial blood sampling through an intracardiac cannula at 10 min intervals from 12.00 to 18.00 h. E.e.g.s recorded continuously during the blood sampling period were scored into wakefulness and sleep, and the amount of sleep for every 10 min was plotted against the GH value as assessed by radioimmunoassay. The power spectrum analysis and the least-squares method applied to the time series of GH concentrations in the control rat, revealed that the mean periodicity was 3.12 +/- 0.09 h (mean +/- S.E. of the mean) in fourteen rats examined. For the animals in which the e.e.g. was recorded simultaneously with blood samplings, the cross-correlation analysis performed between the time series of the amount of sleep and the GH value revealed a significant positive correlation between the GH level and the amount of sleep during the preceding 10 min. The time series of the sleep amount and the GH value had mean periodicities of 3.09 +/- 0.17 and 3.05 +/- 0.13 h (mean +/- S.E. of the mean), respectively, in twenty-seven rats examined. 5. Sleep deprivation performed between 13.00 and 15.00 h was effective in preventing GH secretory bursts which otherwise should appear during this time period of the day. 6. Corticosterone measurement by protein-binding assay revealed that the procedure of sleep deprivation did not act as the 'stress' which has been known to inhibit GH secretion in the rat. These findings indicate that GH secretion in the rat is sleep-related, as has been proved in the human.


Exploring correlation between social determinants and overweight/obesity in children and youths with epilepsy.
This study aimed to explore the correlation between social determinants and overweight and obesity in children and youths with epilepsy. The study data were derived from the National Survey of Children's Health (NSCH) 2016-2017 and 2018-2019, a cross-sectional sample of young people aged 10-17. Three groups participated by weight: 423 in body mass index (BMI) 5th-84th group (normal weight), 108 in BMI 85th-94th group (overweight), and 124 in BMI ≥ 95th group (obesity). Multivariate ordinal logistic regression analyses were conducted. The three subgroups were divided to explore the correlation between social determinants and overweight and obesity. A total of 655 children were included. After adjusting for sex, age, race, use of cigarets, cigars, or pipe tobacco inside, afterschool activity, and physical activity, children in poor physical condition reported by their parents [OR = 1.573 (95% CI, 1.164-2.125)] were associated with overweight/obesity. There were negative correlations between parents with higher education and overweight/obesity, especially in children and youths with previous or current epilepsy groups. Also, overweight/obesity was correlated with the 200%-400% family poverty level (FPL) [the adjusted odds ratio (OR) = 0.156 (95% CI, 0.028-0.876)] and above 400% FPL [the adjusted OR = 0.121 (95% CI, 0.023-0.641)] in children and youths with mild symptoms of epilepsy, and above 400% FPL [the adjusted OR = 0.103 (95% CI, 0.023-0.460)] in children with moderate to severe epilepsy. Poor physical conditions were correlated with obesity in childhood epilepsy. Parents with higher education and FPLs were negatively correlated to childhood obesity. Therefore, this study was intended to advocate for a greater emphasis on BMI for children and youths with epilepsy in families with lower-educated and low-income groups.


The impact of transfer on pediatric trauma outcomes.
Recently, concerns have been raised over delays that result from transferring patients to designated trauma centers. This study aimed to assess whether transfer status had an impact on pediatric trauma outcomes. Using a local 1996-2014 pediatric trauma database containing 1541 patients, the following outcomes were tested: death, major complication, time to definitive treatment (TDT), hospital length of stay (LOS), and ICU length of stay (ICU LOS). Logistic, generalized linear, and Poisson regression models were used. Mortality and complication rates did not differ significantly between direct (mortality=52/1000, complications=54/1000) and transferred (mortality=59/1000; complications=67/1000) patients (mortality aRR: 1.17, 95% CI: 0.76-1.80, p=0.48; complication aRR: 1.13, 95% CI: 0.75-1.70, p=0.57). Transfer status was not a significant predictor of ICU LOS (p=0.72). Transfer status was a significant predictor of time to definitive treatment (transfer x-=17.4h vs. direct x-=2.6h, p=0.0035) and of LOS for severely injured patients (p=0.005). The significant predictors of pediatric trauma mortality were: ISS, transport mode, age, and TDT, and of major complication were ISS and TDT. Although transferred patients had longer time to specialized care, there were no significant differences in the mortality or complication rates between transferred and direct patients after adjusting for injury severity.


Carcinosarcoma of the ovary: MR and clinical findings compared with high-grade serous carcinoma.
To clarify imaging and clinical characteristics of ovarian carcinosarcoma (CS) compared with high-grade serous carcinoma (HGSC). We retrospectively reviewed MR imagings of 12 patients with CS and 30 patients with HGSC and evaluated tumor size, shape, appearance, nature of cystic and solid components, hemorrhage, and necrosis. Age, premenopausal or postmenopausal, histologic subtype, presence of endometriosis, tumor markers, and stage were also evaluated. These parameters were compared using the Mann-Whitney U test and the chi-square test/Fisher's exact test. The mean size of CSs was 13.6 cm, and significantly larger than that of HGSCs (mean 9.0 cm, p = 0.022). The stained-glass appearance (67% vs. 23%, p = 0.013), hemorrhage (100% vs. 50%, p = 0.003), necrosis (75.0% vs. 13%, p = 0.000), and endometriosis (33% vs. 7%, p = 0.012) were significantly more common in CSs. The postmenopausal ratio of CSs was 100% and significantly higher than that of HGSCs (70.0%, p = 0.041). Among the tumor makers, only CA-125 was significantly lower in CSs than in HGSCs (mean 715.1 U/ml vs. 1677.1 U/ml, p = 0.009). The stage distribution was similar and was not significantly different. CSs formed larger masses, and the stained-glass appearance, hemorrhage, and necrosis were more frequently observed in CSs.


The adapter protein FADD provides an alternate pathway for entry into the cell cycle by regulating APC/C-Cdh1 E3 ubiquitin ligase activity.
The E3 ubiquitin ligase APC/C-Cdh1 maintains the G0/G1 state, and its inactivation is required for cell cycle entry. We reveal a novel role for Fas-associated protein with death domain (FADD) in the cell cycle through its function as an inhibitor of APC/C-Cdh1. Using real-time, single-cell imaging of live cells combined with biochemical analysis, we demonstrate that APC/C-Cdh1 hyperactivity in FADD-deficient cells leads to a G1 arrest despite persistent mitogenic signaling through oncogenic EGFR/KRAS. We further show that FADDWT interacts with Cdh1, while a mutant lacking a consensus KEN-box motif (FADDKEN) fails to interact with Cdh1 and results in a G1 arrest due to its inability to inhibit APC/C-Cdh1. Additionally, enhanced expression of FADDWT but not FADDKEN, in cells arrested in G1 upon CDK4/6 inhibition, leads to APC/C-Cdh1 inactivation and entry into the cell cycle in the absence of retinoblastoma protein phosphorylation. FADD's function in the cell cycle requires its phosphorylation by CK1α at Ser-194 which promotes its nuclear translocation. Overall, FADD provides a CDK4/6-Rb-E2F-independent "bypass" mechanism for cell cycle entry and thus a therapeutic opportunity for CDK4/6 inhibitor resistance.


Synthesis of hybrid amorphous/crystalline SnO2 1D nanostructures: investigation of morphology, structure and optical properties.
The aim of the study was to prepare SnO2 nanowires via a combination of electrospinning and the sol-gel method from a polyvinylpyrrolidone (PVP)/dimetylformamide (DMF)/ethanol(EtOH)/tin(IV) chloride pentahydrate (SnCl4·5H2O) solution. The morphology, structure and chemical composition of the obtained PVP/SnO2 nanofibers and SnO2 nanowires were examined using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) as well as a scanning electron microscope (SEM) with an energy dispersive spectrometer (EDX). The optical property analysis was performed on the basis of UV-Vis spectra of absorbance as a function of the wavelength, based on which the rated values of band gaps of the fabricated 1D nanostructures were determined. The morphology analysis showed that the obtained amorphous SnO2 nanowires with crystalline protuberances were characterized by a diameter of 50 to 120 nm. Results demonstrated that nanowires with a ratio of 1:1 precursor to polymer in the spinning solution were characterized by the smallest diameter after calcination and the smallest energy gap of 3.3 eV among all investigated samples. The rest of the studied materials were characterized by a larger energy gap (3.8 and 3.9 eV).


"I am neither general nor diplomat": reflections on the Persian Gulf War by gifted Canadian adolescents.
Following the cease-fire in the 1991 Persian Gulf War, 97 students attending school programs for the gifted and talented in British Columbia, Canada, were invited to participate in an exploratory study consisting of a series of openended questions. In general, students believed that adults had learned little from the conflict and tended to hold to the same views after the war had ended. To avoid warfare, students suggested a number of options. They were critical of the role played by political and economic demands and the media, and described a range of personal emotions and behavioral changes which occurred during the period of hostilities. The role played by families in providing support and information during this time appeared to be substantial.


ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.
Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ(10) deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ(10) in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production.


A study of the relationship between child abuse and drug addiction in 178 patients: preliminary results.
Social histories and demographic data were collected on 178 patients--101 in the United States and 77 in Australia--in treatment for drug/alcohol addiction. The purpose of the study was to determine the degree to which a correlation exists between child abuse/neglect and the later onset of drug/alcohol addiction patterns in the abuse victims. The questionnaire explored such issues as family intactness, parental violence/abuse/neglect, parental drug abuse, sibling relationships and personal physical/sexual abuse histories, including incest and rape. The study determined that 84% of the sample reported a history of child abuse/neglect.


Rectal hemorrhage from ulcerated appendiceal stump nine years after appendectomy. Report of a case.
Significant lower gastrointestinal hemorrhage from an ulcerated appendiceal stump after remote uncomplicated appendectomy is reported. The diagnosis was established by pathologic examination of the surgical specimen, but the area of bleeding was localized by preoperative colonoscopy. Angiography or isotope scan might also have identified the site of more rapid bleeding.


Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects.
Non-synonymous single-nucleotide polymorphism (SNPs) in the gene for proprotein convertase subtilisin/kexin type 9 (PCSK9) can influence cholesterol and glucose metabolism, leading to increased risk of cardiovascular disease and diabetes. To determine the frequency of four common PCSK9 SNPs, L10Ins, A56V, I474V, and E670G, in a population sample (n = 98) of the Hail region of Kingdom of Saudi Arabia. Blood was collected from participants; serum cholesterol, blood glucose and glycated hemoglobin were determined; genomic DNA was extracted and PCR amplicons from SNP-containing PCSK9 exons were subjected to Sanger sequencing. Out of 98 participants. 10 (10.20%) carried none of the SNPs, 2 (2.04%) the L10ins/A56V linked SNPs, 35 (35.71%) the I474V SNP, 22 (22.45%) both the I474V and E670G SNPs, and 29 (29.59%) the E670G SNP. Of the 30 eucholesterolemic diabetics patients, 11 (36.66%) carried the I474V SNP, 10 (33.33%) the E679G SNP and 6 (20%) the I474V/E679G. SNPs. Of 63 diabetic patients, 26 (41.26%) carry I474V SNP and 22 (34.92%) carry E670G SNP. Our data demonstrated that the I474V and E670G PCSK9 variants are very frequent in the Hail region of Saudi Arabia and are found at even higher frequency among diabetics. Further investigations are needed to determine whether these variations or another variant segregating with them can explain its apparent association with diabetes in this population.


Attention-deficit hyperactivity disorder in school-age children in Gaborone, Botswana: Comorbidity and risk factors.
Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children. Its occurrence and pattern of presentation are unknown in Botswana. To determine the prevalence of attention-deficit hyperactivity disorder (ADHD), associated comorbid conditions and risk factors amongst school-age children in Botswana. Primary schools in Gaborone, Botswana. This study used a cross-sectional design. A two-stage random sampling technique was utilised to select learners from 25 out of the 29 public schools in the city. The Vanderbilt ADHD Diagnostic Rating Scale (VADRS), teacher and parent versions, was administered. Of the 1737 children, 50.9% (n = 884) were male, and their mean age was 9.53 years (s.d. = 1.97). The prevalence of ADHD was 12.3% (n = 213). The most prevalent presentation was the predominantly inattentive, 7.2% (n = 125). A family history of mental illness (odds ratio [OR] = 6.59, 95% CI: 1.36-32.0) and perinatal complications (OR = 2.16, 95% CI: 1.08-4.29) emerged as the independent predictors of ADHD. The prevalence of ADHD in Botswana is slightly higher than that reported in the literature, but the pattern of presentations and comorbidities is similar. A positive family history of mental illness and perinatal complications independently predicted ADHD. Mental health screening amongst families of the affected individuals and improved perinatal care should be considered as health care priorities in Botswana.


Collective relaxation dynamics and crystallization kinetics of the amorphous Biclotymol antiseptic.
We employ dielectric spectroscopy to monitor the relaxation dynamics and crystallization kinetics of the Biclotymol antiseptic in its amorphous phase. The glass transition temperature of the material as determined by dielectric spectroscopy is Tg = 290 ± 1K. The primary (α) relaxation dynamics is observed to follow a Vogel-Fulcher-Tammann temperature dependence, with a kinetic fragility index m = 86 ± 13, which classifies Biclotymol as a relatively fragile glass former. A secondary relaxation is also observed, corresponding to an intramolecular dynamic process of the non-rigid Biclotymol molecule. The crystallization kinetics, measured at four different temperatures above the glass transition temperature, follows an Avrami behavior with exponent virtually equal to n = 2, indicating one-dimensional crystallization into needle-like crystallites, as experimentally observed, with a time-constant nucleation rate. The activation barrier for crystallization is found to be Ea = 115 ± 22 kJ mol(-1).


Demography of the giant monocarpic herb Rheum nobile in the Himalayas and the effect of disturbances by grazing.
Perennity of giant rosette species in combination with a single 'big bang' reproduction followed by death of the genetic individual is relatively rare among plants. Such long-lived monocarpic plants are usually slow growing and can be found in deserts, bogs or in alpine regions of the tropics or sub-tropics. Due to their longevity, monocarpic perennials risk losing everything before reproduction, which make them particularly susceptible to disturbances. Because of the inherent difficulties in assessing whether long-lived populations are growing or declining, usually neither their demography nor the consequences of increasing grazing pressure are known. We used integral projection modelling (IPM) to measure the growth rate and passage time to flowering of Rheum nobile, a monocarpic perennial, and one of the most striking alpine plants from the high Himalayas. Rosettes which were no longer found due to disturbances or grazing by yaks were either treated as missing or as dead in two series of analysis, thereby simulating demography with and without the impact of grazing cattle. Data were collected from plants at 4500 m a.s.l. in Shangri-la County, Yunnan Province, south-west China. In four consecutive years (2011-2014) and in two populations, 372 and 369 individuals were measured, respectively, and size-dependent growth, survival and fecundity parameters were estimated. In addition, germination percentage, seedling survival and establishment probability were assessed. The probability of survival, flowering and fecundity were strongly size dependent. Time to reach flowering size was 33.5 years [95 % confidence interval (CI) 21.9-43.3, stochastic estimate from pooled transitions and populations]. The stochastic population growth rate (λs) of Rheum nobile was 1.013 (95 % CI 1.010-1.017). When disturbance by grazing cattle (yaks) was accounted for in the model, λs dropped to values <1 (0.940, 95 % CI 0.938-0.943). We conclude that natural populations of this unique species are viable, but that conservation efforts should be made to minimize disturbances by grazing and to protect this slow-growing flagship plant from the high Himalayas.


Nucleic acid binding proteins affect the subcellular distribution of phosphorothioate antisense oligonucleotides.
Antisense oligonucleotides (ASOs) are versatile tools that can regulate multiple steps of RNA biogenesis in cells and living organisms. Significant improvements in delivery, potency, and stability have been achieved through modifications within the oligonucleotide backbone, sugar and heterocycles. However, these modifications can profoundly affect interactions between ASOs and intracellular proteins in ways that are only beginning to be understood. Here, we report that ASOs with specific backbone and sugar modifications can become localized to cytoplasmic ribonucleoprotein granules such as stress granules and those seeded by the aggregation of specific ASO-binding proteins such as FUS/TLS (FUS) and PSF/SFPQ (PSF). Further investigation into the basis for ASO-FUS binding illustrated the importance of ASO backbone and hydrophobic 2' sugar modifications and revealed that the C-terminal region of FUS is sufficient to retain ASOs in cellular foci. Taken together, the results of this study demonstrate that affinities of various nucleic acid binding domains for ASO depend on chemical modifications and further demonstrate how ASO-protein interactions influence the localization of ASOs.


Chronic Inflammatory Demyelinating Polyneuropathy.
Although there are close to 10 randomized trials showing efficacy for prednisone, intravenous immunoglobulin, or plasmapheresis in chronic inflammatory demyelinating polyneuropathy (CIDP), large differences in cost, side effect profiles, and ease of use create controversy over the therapy that is best. Most clinicians use intravenous immunoglobulin or prednisone as first-line therapy. Unfortunately, the clinical trials performed to date are not easily extrapolated to answer, "which agent is best for clinical practice" because they have used varying doses and duration of therapy, different diagnostic criteria for CIDP, and mixtures of patients who have failed previous therapy versus those with newly diagnosed disease. There are a number of small case series describing the efficacy of immune-modulating agents, such as azathioprine, cyclophosphamide, cyclosporine A, interferon-alpha, and mycophenolate mofetil. These studies generally use these medications as second-line agents for patients who failed corticosteroids or intravenous immunoglobulin. In the authors' practice, this lack of robust knowledge still relegates these to second-line or prednisone-sparing agents.


Social inequality in fetal growth: a comparative study of Denmark, Finland, Norway and Sweden in the period 1981-2000.
To examine the socioeconomic patterns and time trends in fetal growth in Denmark, Finland, Norway, and Sweden from 1981 to 2000. Data on all live-born singleton births was drawn from national population registries in each of the four countries (Denmark n = 1,077,584; Finland n = 400,442; Norway n = 929,458; Sweden n = 1,761,562). Slope index of inequality (SII) and mean differences in birthweight for gestational age, SII and risk differences in small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants. In all countries, gradients in fetal growth by parental education existed. Low parental education was associated with lower birthweight, increased risk of SGA and decreased risk of LGA. Mother's education exerted the strongest influence on outcomes, whereas father's education had a weaker effect. The educational gradients as measured by the SII were generally steepest in Denmark, followed by Norway, Sweden, and Finland. From 1981 to 2000, the educational gradients in birthweight decreased in all countries, except Denmark where it increased. All countries experienced small decreases in the educational gradient in SGA over time. The economic recession in Denmark in the 1980s was concurrent with an increase in disparities in fetal growth, whereas the economic recession in Finland and Sweden in the early 1990s did not substantially increase the socioeconomic inequality in fetal growth. The economic growth in the later part of the 1990s may have diminished the socioeconomic inequality in fetal growth in Finland, Norway, and Sweden.


Further investigation of the validity and reliability of the photographic figure rating scale for body image assessment.
Previous studies have not fully investigated the psychometric properties of the Photographic Figure Rating Scale (PFRS). In 2 studies, we report on the test-retest reliability and convergent validity of ratings derived from the PFRS. In Study 1, 322 female university students in Britain provided self-ratings on the PFRS and objectively measured body mass index (BMI); a subsample of 132 women also completed the task after 5 weeks. In Study 2, 243 women from the community in Austria completed the PFRS along with a battery of other body image scales. Results of Study 1 showed that ratings on the PFRS had good test-retest reliability (all rs > .87) and good convergent validity in relation to BMI. Results of Study 2 showed that PFRS-derived body dissatisfaction scores were significantly correlated with a range of body image variables. These results provide evidence for the convergent validity and good test-retest reliability of the PFRS.


The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study.
Crohn's disease (CD) commonly recurs after surgery, and a number of patients need repeated surgery, especially smokers and those with repeated surgeries or penetrating disease. Whether infliximab prevents postsurgical recurrence in high-risk CD remains unknown. In the present pilot open-labeled study, we investigated the safety and efficacy of scheduled infliximab, which was started early after surgery, in maintaining remission of CD patients who have undergone multiple surgeries due to penetrating disease. Eleven patients (nine male, two female; age range, 26-48 years) who had undergone repeated surgeries (median, 4; range, 2-5) for penetrating disease were enrolled. Two to 4 weeks after surgery, the patients were started on intravenous infliximab (5 mg/kg) at an 8-week interval. The primary end points were the proportion of patients in clinical remission at the end of the study, the rate of endoscopic/radiologic remission at 24 months, and the rate of adverse effects. One patient dropped out due to non-compliance, and ten patients were eligible for analysis. Clinical remission was maintained in six of ten patients (60.0%) at the end of the study. At 24 months, four out of ten patients were in endoscopic or radiological remission (40.0%). Two patients experienced adverse effects (18.2%), one of whom elected to withdraw from the study. The findings of no major safety concern and possible clinical benefit in our study suggest that further investigation of infliximab as a treatment for prevention of postsurgical recurrence in high-risk CD is warranted.


Beta-catenin triggers nuclear factor kappaB-dependent up-regulation of hepatocyte inducible nitric oxide synthase.
Disruption of cell-to-cell contacts, as observed in many pathophysiological conditions, prime hepatocytes for compensatory hyperplastic response that involves induction of several genes, including proto-oncogenes and other gene targets of beta-catenin signaling pathway. By using cultured hepatocytes and experimental models of adherens junction disruption we have investigated changes in beta-catenin subcellular localization and their relationships with inducible nitric oxide synthase (iNOS) expression. Two experimental models were employed: (a) rat hepatocytes obtained by collagenase liver perfusion within the first 48 h of culture; (b) 48-h old cultured hepatocytes, transiently transfected or not with a plasmid encoding for dominant/negative inhibitory kappa B-alpha, exposed to ethylene glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid/LiCl treatment. beta-Catenin signaling and cellular localization, iNOS expression and nuclear factor kappaB involvement, were investigated using morphological, cell and molecular biology techniques. E-cadherin-mediated disruption of cell-to-cell contacts induces early beta-catenin translocation from membrane to cytoplasm and nuclear compartments, events that are followed by up-regulation of c-myc, cyclin D1 and beta-transducin repeat-containing protein expression. This, in turn, resulted eventually in iNOS induction that was mechanistically related to nuclear factor kappaB activation, as unequivocally shown in cells expressing dominant negative inhibitory kappa B-alpha. Our data indicate that E-cadherin disassembly and concomitant inactivation of glycogen synthase kinase-3beta result in nuclear factor kappaB-dependent induction of iNOS in hepatocytes.


Reactions of the carcinogen N-acetoxy-4-acetamidostilbene with polynucleotides in vitro.
N-Acetoxy-4-acetamidostilbene (N-AcO-AAS) has been shown to react with mononucleosides to give numerous alkylation products [1]. In this work, homopolynucleotides, RNA and DNA were treated with N-[beta-14 C]-AcO-AAS, washed, degraded with S1 nuclease and acid phosphatase, and chromatographed on Sephadex LH-20. RNA prepared in vitro with 14C on cytosine, adenine or guanine was treated with non-radioactive N-AcO-AAS, then digested and chromatographed similarly. By this means, many of the adducts rising from nucleoside reactions were shown to result from treatment of nucleic acids with the same carcinogen, as well as a number of products which have not been matched to products of monomer alkylation. Labeled 1-(4-acetamidophenyl)-2-phenyl-1, 2-ethanediol was detected in the digest of RNA treated with radioactive N-AcO-AAS, suggesting that phosphate alkylation had taken place.


Neurologic disorders associated with visual loss in childhood.
Acquired visual loss in childhood is often a manifestation of more generalized neurologic dysfunction. This article includes a discussion of lesions of the cornea, lens, retina, anterior visual pathways, optic radiations, and visual cortex that are associated with other neurologic abnormalities in children.


Fourth-order coherent Raman spectroscopy in a time domain: applications to buried interfaces.
A Raman-based, nonlinear optical spectroscopy is a promising method for observing vibrational modes localized at buried interfaces. The principles of Raman excitation and interface-selective detection of coherent vibrations are described. Applications to air-liquid, liquid-liquid, air-solid, liquid-solid, and solid-solid interfaces are reviewed.


Differential effects of locus coeruleus lesions upon metabolic activity in CNS nuclei involved in cardiovascular regulation.
The alterations of local cerebral glucose utilization in 5 medullary and 6 supramedullary regions involved in cardiovascular regulation, which result from unilateral electrolytic lesions of the locus coeruleus, have been examined in conscious rats, using the quantitative autoradiographic [14C]2-deoxyglucose technique. Unilateral lesions of the locus coeruleus (72 h prior to study) did not result in any significant alteration in glucose utilization in any of medullary (e.g. nucleus of the tractus solitarius, dorsal motor nucleus of the vagus) or diencephalic (e.g. periventricular and paraventricular hypothalamic nuclei, lateral habenular nucleus) regions which were examined. However, the increased glucose utilization which occurred in some medullary nuclei (e.g. nucleus of the solitary tract, dorsal motor nucleus of the vagus) following administration of the alpha-receptor antagonist, phenoxybenzamine (30 mg/kg, i.v.), was significantly attenuated by lesions of the locus coeruleus, whereas the increased glucose utilization elicited in hypothalamic nuclei by the drug was unaffected by locus coeruleus lesions. In contrast, glucose utilization in the lateral habenular nucleus was elevated significantly following phenoxybenzamine only in animals bearing unilateral locus coeruleus lesion; the drug being without effect in this region in sham-lesioned rats. These differential consequences of locus coeruleus lesions upon glucose utilization in nuclei involved in cardiovascular regulation emphasize the complex nature of the influence of the locus coeruleus upon blood pressure control.


Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing.
Tissue repair is negatively affected by advanced age. Recent evidence indicates that hematopoietic cell-derived extracellular vesicles (EVs) are modulators of regenerative capacity. Here, we report that plasma EVs carrying specific surface markers indicate the degree of age-associated immunosenescence; moreover, this immunosenescence phenotype was accentuated by fracture injury. The number of CD11b+ Ly6Cintermediate Ly6Ghigh neutrophils significantly decreased with age in association with defective tissue regeneration. In response to fracture injury, the frequencies of neutrophils and associated plasma EVs were significantly higher in fracture calluses than in peripheral blood. Exposure of aged mice to youthful circulation through heterochronic parabiosis increased the number of neutrophils and their correlated Ly6G+ plasma EVs, which were associated with improved fracture healing in aged mice of heterochronic parabiosis pairs. Our findings create a foundation for utilizing specific immune cells and EV subsets as potential biomarkers and therapeutic strategies to promote resilience to stressors during aging.


Burning mouth syndrome and peripheral neuropathy in patients with type 1 diabetes mellitus.
Burning mouth syndrome (BMS) has been attributed secondarily to diabetes, poor glycemic control, and diabetic neuropathy. The prevalence and predictor factors of BMS were compared in type 1 diabetes mellitus (T1DM) and nondiabetic subjects. An assessment of 371 adult T1DM subjects and 261 control subjects participating in a cross-sectional epidemiological study of oral health complications of diabetes was performed. Subjects were participants of the Pittsburgh Epidemiology of Diabetes Complications study. Prevalence of BMS was determined by response to the following questions: "Do you now or in the last month had any persistent uncomfortable sensations in your mouth or tongue? If yes, would you describe the feeling as tingling, burning, sore, numb, or other?" Burning mouth syndrome symptoms were reported by 28 T1DM and control subjects (4.6%). Eleven had oral pathologies that might explain the BMS, including atrophy of the tongue papillae, fissured tongue, denture stomatitis, and candidiasis. The prevalence of BMS within the two groups with no pathologies was similar; 12/371 (3.2%) vs. 5/233 (2.1%). Multivariate analyses of the 12 T1DM subjects with BMS found significant associations for female gender (P=.042) and a diagnosis of diabetic peripheral neuropathy (P=.024). In this T1DM population, BMS or related discomforts occurred slightly more frequently than in the control group. Symptomatic T1DM subjects were more likely to be female who had also developed peripheral neuropathy. These findings and other similarities between BMS and diabetic peripheral neuropathy suggest that a neuropathic process may be an underlying source of BMS in some patients who have no apparent oral abnormality.


Development of novel therapeutics for all individuals with CF (the future goes on).
Despite the major advances and successes in finding and establishing new treatments that tackle the basic defect in Cystic Fibrosis (CF), there is still an unmet need to bring these potentially curative therapies to all individuals with CF. Here, we review aspects of what is still missing to treat all individuals with CF by such approaches. On the one hand, we discuss novel holistic (high-throughput) approaches to elucidate mechanistic defects caused by distinct classes of mutations to identify novel drug targets. On the other hand, we examine therapeutic approaches to correct the gene in its own environment, i.e., in the genome.


Chromosome-level genome of the globe skimmer dragonfly (Pantala flavescens).
The globe skimmer dragonfly (Pantala flavescens) is a notable Odonata insect distributed in nature fields and farmlands worldwide, and it is commonly recognized as a natural enemy because it preys on agricultural pests and health pests. As one of the sister groups of winged insects, odonatan species are key to understanding the evolution of insect wings. We present a high-quality reference genome of P. flavescens, which is the first chromosome-level genome in the Palaeoptera (Odonata and Ephemeroptera). The assembled genome size was 662 Mb, with a contig N50 of 16.2 Mb. Via Hi-C scaffolding, 648 Mb (97.9%) of contig sequences were clustered, ordered, and assembled into 12 large scaffolds, each corresponding to a natural chromosome. The X chromosome was identified by sequence coverage depth. The repetitive sequences and gene density of the X chromosome are similar to those of autosomal sequences, but the X chromosome shows a much lower degree of heterozygosity. Our analysis shows that the effective population size experienced 3 declining events, which may have been caused by climate change and environmental pollution. The genome of P. flavescens provides more information on the biology and evolution of insects and will help for the use of this species in pest control.


Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience.
Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44]. The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.


An MRI-based Study to Investigate If the Patella is Truly Centred between the Femoral Condyles in the Coronal Plane.
An AP knee radiograph is considered adequate if the patella is centred between the femoral condyles. Our previous studies demonstrated a tendency for lateral patellar deviation on an AP view orthogonal to the posterior femoral condyles. However, findings were based on cadaveric samples limited by the lack of soft tissue effects on patellar positioning. After excluding those with deformity or damage to osseous or ligamentous structures, 106 knee MRI scans were randomly selected. Patellar centring was calculated as a percentage of total distal femoral intercondylar width and represented how lateral the centre of the patella is located with respect to the midpoint of the femoral condyles. Multiple regression analysis was performed to determine the relationship between patellar centring and age, gender, anatomic lateral distal femoral angle (aLDFA), medial proximal tibial angle (MPTA) and tibial tuberosity to trochlear groove (TT-TG) distance. There were 35 males and 71 females included in the study with a mean age of 29 ± 14 years. Mean patellar centring was 8 ± 4%. There was a statistically significant correlation between TT-TG distance and positive (lateral) patellar centring (standardised β = 0.36, p <0.01). There were no associations between aLDFA and MPTA with patellar centring. This study demonstrates that the patella is rarely perfectly centred and is usually positioned slightly laterally within the femoral condyles in an AP view orthogonal to the posterior aspect of the femoral condyles. The use of supine MRI scans makes this data relevant to a patient on the operating room table. Shah NS, Kyriakedes JC, Liu RW. An MRI-based Study to Investigate If the Patella is Truly Centred between the Femoral Condyles in the Coronal Plane. Strategies Trauma Limb Reconstr 2022;17(2):63-67.


Mesh reconstruction preventing sacral herniation.
Sacral hernias are uncommon defects developing through the pelvic floor after partial or total sacrectomy. We report on a 29-year-old woman, who has been under our care with a cystic formation after perineosacral resection of a rhabdomyosarcoma and partial sacrectomy. The cystic tumor was resected and a mesh repair performed to prevent sacral herniation. The current literature is summarized; etiology and management recommendations of this rare complication are discussed.


Acute complications of catheter therapy for congenital heart disease.
Although therapeutic catheter procedures for congenital heart disease are still developing, the number of procedures being performed allows statistically relevant review of the acute complications. Between January 1, 1984, and February 1, 1987, 417 such procedures were performed at The Children's Hospital, Boston; the age range of the patients was 1 day to 51 years (median 4 years, 6 months). Catheter procedures consisted predominantly of vascular dilations (peripheral pulmonic stenosis, 97; valvular pulmonic stenosis, 67; valvular aortic stenosis, 62; recurrent coarctation, 49) and embolizations (double umbrella device, 36; steel coils, 45). Overall, there were 50 acute complications (12%); 24 (6%) were major and 26 (6%) were minor. The mortality rate was 3 of 417 (0.7%). Complication rates varied between 4% for dilation of recurrent coarctation and 40% for dilation of aortic stenosis. The age of the patients was a factor in complications of vascular access (11 patients), 8 of which occurred in patients younger than 6 months (median 5), and in cardiac arrest and ventricular fibrillation (4 patients, 3 of whom were younger than 6 months [median 3]). No statistically significant trend toward diminishing overall complication rates was discerned over the 37 months of this study.


Interleukin-1β induced Stress Granules Sequester COX-2 mRNA and Regulates its Stability and Translation in Human OA Chondrocytes.
Enhanced and immediate expression of cyclooxygenase-2 (COX-2) mRNA is observed in IL-1β-stimulated OA chondrocytes but the synthesis of protein found significantly delayed. Here we investigated the role of stress granules (SGs), ribonucleoprotein complexes that regulate mRNA translation, in the delayed translation of COX-2 mRNAs in IL-1β-stimulated OA chondrocytes. Stimulation of human chondrocytes with IL-1β activated the stress response genes and the phosphorylation of eIF2α that triggered the assembly of SGs. Using combined immunofluorescence staining of SGs markers and COX-2 protein, RNA fluorescence in situ hybridization and RNA immunoprecipitation, the COX-2 mRNAs were found sequestered in SGs in IL-1β-stimulated OA chondrocytes. No increase in COX-2 protein expression was observed during the persistence of SGs but enhanced expression of COX-2 protein was noted upon clearance of the SGs. Inhibition of SGs clearance blocked COX-2 mRNA translation whereas blocking the assembly of SGs by TIA-1 depletion resulted in rapid and increased production of COX-2 and PGE2. Our findings show for the first time assembly of SGs and sequestration of COX-2 mRNAs in human OA chondrocytes under pathological conditions. Post-transcriptional regulation of COX-2 mRNAs translation by SGs indicates a role in IL-1β-mediated catabolic response that could be therapeutically targeted in OA.


Significance thresholds for quantitative trait locus mapping under selective genotyping.
In the case of selective genotyping, the usual permutation test to establish statistical significance for quantitative trait locus (QTL) mapping can give inappropriate significance thresholds, especially when the phenotype distribution is skewed. A stratified permutation test should be used, with phenotypes shuffled separately within the genotyped and ungenotyped individuals.


6-Mercaptopurine (6-MP) induces cell cycle arrest and apoptosis of neural progenitor cells in the developing fetal rat brain.
6-Mercaptopurine (6-MP), an analogue of hypoxanthine, is used in the therapy of acute lymphoblastic leukemia and causes fetal neurotoxicity. To clarify the mechanisms of 6-MP-induced fetal neurotoxicity leading to the cell cycle arrest and apoptosis of neural progenitor cells, pregnant rats were treated with 50 mg/kg 6-MP on embryonic day (E) 13, and the fetal telencephalons were examined at 12 to 72 h (h) after treatment. Flow-cytometric analysis confirmed an accumulation of cells at G2/M, S, and sub-G1 (apoptotic cells) phases from 24 to 72 h. The number of phosphorylated histone H3-positive cells (mitotic cells) decreased from 36 to 72 h, and the phosphorylated (active) form of p53 protein, which is a mediator of apoptosis and cell cycle arrest, increased from 24 to 48 h. An executor of p53-mediated cell cycle arrest, p21, showed intense overexpression at both the mRNA and protein levels from 24 to 72 h. Cdc25A protein, which is needed for the progression of S phase, decreased at 36 and 48 h. In addition, phosphorylated cdc2 protein, which is an inactive form of cdc2 necessary for G2/M progression, increased from 24 to 48 h. These results suggest that 6-MP induced G2/M arrest, delayed S-phase progression, and finally induced apoptosis of neural progenitor cells mediated by p53 in the fetal rat telencephalon.


Crystal structure of Sulfolobus acidocaldarius aspartate carbamoyltransferase in complex with its allosteric activator CTP.
Aspartate carbamoyltransferase (ATCase) is a paradigm for allosteric regulation of enzyme activity. B-class ATCases display very similar homotropic allosteric behaviour, but differ extensively in their heterotropic patterns. The ATCase from the thermoacidophilic archaeon Sulfolobus acidocaldarius, for example, is strongly activated by its metabolic pathway's end product CTP, in contrast with Escherichia coli ATCase which is inhibited by CTP. To investigate the structural basis of this property, we have solved the crystal structure of the S. acidocaldarius enzyme in complex with CTP. Structure comparison reveals that effector binding does not induce similar large-scale conformational changes as observed for the E. coli ATCase. However, shifts in sedimentation coefficients upon binding of the bi-substrate analogue PALA show the existence of structurally distinct allosteric states. This suggests that the so-called "Nucleotide-Perturbation model" for explaining heterotropic allosteric behaviour, which is based on global conformational strain, is not a general mechanism of B-class ATCases.


Simultaneous determination of tetracylines and quinolones antibiotics in egg by ultra-performance liquid chromatography-electrospray tandem mass spectrometry.
We report here an ultra-performance liquid chromatography coupled with tandem mass spectrometric (MS/MS) method for the simultaneous quantitation of multiclass veterinary drugs in egg. The analysis of the target compounds, including 7 tetracyclines and 4 types of quinolones, may be accomplished in 15 min of total run time. The egg was extracted with ethylenediaminetetraacetic acid-Mcllvaine buffer solution and further purified using a polymer-based Oasis HLB solid-phase extraction cartridge. A C18 column was used to separate the analytes followed by MS/MS using an electrospray ion source. The overall average recoveries of the analytes based on matrix-fortified calibration ranged from 71 to 112% with acceptable relative standard deviations of <20% for 6 trials. For all of the target compounds, the limits of quantitation ranged between 0.02 and 4.29 microg/kg. The proposed method is sufficiently sensitive and highly selective.


Cerebrospinal fluid (CSF) and serum S100B: release and wash-out pattern.
S100B is an important brain specific protein for monitoring damage and activation of astrocytes. Using a straight forward, non-resource demanding in-house ELISA technique we measured S100B in cerebrospinal fluid (CSF) and serum in patients with traumatic brain injury (TBI) (serum), subarachnoid hemorrhage (SAH) (CSF, serum), intracranial hemorrhage (ICH) (CSF, serum), normal controls (NC) (serum) and a reference population (CSF, N=409). The release and wash-out pattern found in CSF and serum are discussed in relation to the three main determinants for increased brain specific protein levels in body fluids: (i) total mass effect; (ii) pathology; and (iii) time effect.


High-resolution virtual brain modeling personalizes deep brain stimulation for treatment-resistant depression: Spatiotemporal response characteristics following stimulation of neural fiber pathways.
Over the past 15 years, deep brain stimulation (DBS) has been actively investigated as a groundbreaking therapy for patients with treatment-resistant depression (TRD); nevertheless, outcomes have varied from patient to patient, with an average response rate of ∼50%. The engagement of specific fiber tracts at the stimulation site has been hypothesized to be an important factor in determining outcomes, however, the resulting individual network effects at the whole-brain scale remain largely unknown. Here we provide a computational framework that can explore each individual's brain response characteristics elicited by selective stimulation of fiber tracts. We use a novel personalized in-silico approach, the Virtual Big Brain, which makes use of high-resolution virtual brain models at a mm-scale and explicitly reconstructs more than 100,000 fiber tracts for each individual. Each fiber tract is active and can be selectively stimulated. Simulation results demonstrate distinct stimulus-induced event-related potentials as a function of stimulation location, parametrized by the contact positions of the electrodes implanted in each patient, even though validation against empirical patient data reveals some limitations (i.e., the need for individual parameter adjustment, and differential accuracy across stimulation locations). This study provides evidence for the capacity of personalized high-resolution virtual brain models to investigate individual network effects in DBS for patients with TRD and opens up novel avenues in the personalized optimization of brain stimulation.


Myocardial perfusion defects after radiation therapy and anthracycline chemotherapy for left breast cancer: a possible marker of microvascular damage. Three cases and review of the literature.
Radiation therapy to the thorax may induce early and late cardiac adverse effects if large parts of the heart have been included in the irradiation field and particularly if anthracycline-containing chemotherapy is concomitantly administered. We describe 3 cases of cardiotoxicity in patients with left breast cancer treated with anthracycline-containing chemotherapy and left thoracic radiotherapy. In 2 cases we observed asymptomatic electrocardiographic abnormalities of ventricular repolarization mimicking anterior myocardial ischemia and SPECT reversible myocardial perfusion defects. In 1 case we observed echocardiographic abnormalities of left ventricular wall motion and reversible myocardial perfusion abnormalities. We recommend close cardiac monitoring of patients treated with anthracycline chemotherapy and left thoracic radiotherapy to better understand the clinical impact of these abnormalities.


Epidemiology of chronic dacryocystitis and success rate of external dacryocystorhinostomy in Nepal.
To study the epidemiology of chronic dacryocystitis and the success rate of external dacryocystorhinostomy (DCR) in Nepal. This is a retrospective descriptive and interventional case series. A total of 662 records of patients with chronic dacryocystitis due to nasolacrimal duct obstruction, who were treated by means of external DCR without bicanalicular silastic tube intubation, were studied. Mean for age with standard deviation and confidence intervals were calculated. The significance of the difference in means was calculated using the unpaired t-test. Of 662 patients, 67.6% were female. The mean age of the patients was 27.4 +/- 13.7 years (SE = 0.53, 95% CI = 26.34-28.46). Chronic dacryocystitis due to nasolacrimal duct obstruction was found in 86 patients (13.0%) from the high hills (mean age = 35.3 +/- 11.4 years, 95% CI = 32.85-37.75), but most patients (576, 87.0%) were from the subtropical lowlands with a monsoon climate (mean age = 26.9 +/- 13.3 years, 95% CI = 25.8-28.0; p = < 0.01). An overall success rate of 88.6% (89.8% for high-hill patients and 87.4% for those from the lowlands) was obtained after DCR. Chronic dacryocystitis is more common in the subtropical plains of Nepal with a monsoon climate than in the high hills. It is predominantly found in pre-menopausal females. External DCR without bicanalicular silastic tube intubation is an effective method for treating chronic dacryocystitis due to NLDO in these patients.


Spinel ZnCr2O4 nanorods synthesized by facile sol-gel auto combustion method with biomedical properties.
In this study, spinel zinc chromite nanorods (ZnCr2O4 NRs) were successfully manipulated by a simple sol-gel auto combustion process employing urea as fuel. The sample was only required to sinter at 500 °C for 2 h to obtain the single crystalline phase. The phase formation, crystallinity, and surface topography of synthesized ZnCr2O4 NRs were explored by X-ray diffraction (XRD), UV-Vis reflectance spectroscopy (UVDRS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray (EDX) spectroscopy, and vibrating sample magnetometry (VSM). XRD analysis confirms the formation of spinel ZnCr2O4 NRs. The FTIR spectrum displays the two vibrational peaks of Cr-O, and Zn-O at 489 and 615 cm-1, correspondingly. These vibrational bonds were correlated with ZnCr2O4 and revealed the production of cubic spinel ZnCr2O4 NRs. FESEM indicates the presence of hexagonal-rod-shaped particles. EDX spectrum demonstrates the elemental composition of the ZnCr2O4 NRs and confirms the primary peak of Zn, Cr, and O. The obtained ZnCr2O4 NRs exhibit an antiferromagnetic behavior. The bandgap energy of ZnCr2O4 NRs was ascertained and was shown to be 3.45 eV. Furthermore, the antifungal and antibacterial effect of ZnCr2O4 NRs was examined against pathogenic strains by disc diffusion technique. Besides these, the antimalarial activity of ZnCr2O4 NRs was studied against Plasmodium falciparum. Thus, the as-synthesized ZnCr2O4 NRs showed significant antibacterial, antifungal and antimalarial activity and may be helpful for research opening a novel horizon in nanomedicine. Graphical abstract.


Genome replication affects transcription factor binding mediating the cascade of herpes simplex virus transcription.
In herpes simplex virus type 1 (HSV-1) infection, the coupling of genome replication and transcription regulation has been known for many years; however, the underlying mechanism has not been elucidated. We performed a comprehensive transcriptomic assessment and factor-binding analysis for Pol II, TBP, TAF1, and Sp1 to assess the effect genome replication has on viral transcription initiation and elongation. The onset of genome replication resulted in the binding of TBP, TAF1, and Pol II to previously silent late promoters. The viral transcription factor, ICP4, was continuously needed in addition to DNA replication for activation of late gene transcription initiation. Furthermore, late promoters contain a motif that closely matches the consensus initiator element (Inr), which robustly bound TAF1 postreplication. Continued DNA replication resulted in reduced binding of Sp1, TBP, and Pol II to early promoters. Therefore, the initiation of early gene transcription is attenuated following DNA replication. Herein, we propose a model for how viral DNA replication results in the differential utilization of cellular factors that function in transcription initiation, leading to the delineation of kinetic class in HSV-productive infection.


Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls.
The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. Both PON1 activity and concentration were significantly lower by 16.7% and 19.2% (both P < 0.05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established.


Internuclear ophthalmoplegia, prenuclear paresis of contralateral superior rectus, and bilateral ptosis.
A patient with infarction of the paramedian part of the lower midbrain on the right side is described, in whom internuclear ophthalmoplegia and bilateral ptosis were associated with limitation of elevation of the contralateral eye from paresis of the superior rectus. Supranuclear paresis was suggested by partial dissociation between phasic and tonic components of upward gaze. It is suggested that the right-sided lesion involved the rostral median longitudinal fasciculus before it reached the oculomotor nucleus, the central caudal nucleus medially situated in the lower end of the oculomotor nucleus, and the prenuclear fibres from the posterior commissure to the ipsilateral nucleus of the contralateral superior rectus. A supranuclear lesion may be suspected when there is a complex association of dysconjugate palsy of oculomotor muscles.


Biopharmaceuticals: recent approvals and likely directions.
Some 160 biopharmaceuticals have now gained medical approval and several hundred are in the pipeline. Most are protein-based, although two nucleic acid-based products are now on the US/European market. An increasing proportion of approvals are engineered in some way and advances in alternative production systems and delivery methods will also likely impact upon the approvals profile over the remainder of this decade.


Analysis of COVID-19 Spread in Tokyo through an Agent-Based Model with Data Assimilation.
In this paper, we introduce an agent-based model together with a particle filter approach to study the spread of COVID-19. Investigations are mainly performed on the metropolis of Tokyo, but other prefectures of Japan are also briefly surveyed. A novel method for evaluating the effective reproduction number is one of the main outcomes of our approach. Other unknown parameters are also evaluated. Uncertain quantities, such as, for example, the probability that an infected agent develops symptoms, are tested and discussed, and the stability of our computations is examined. Detailed explanations are provided for the model and for the assimilation process.


Upper limb kinematic differences between breathing and non-breathing conditions in front crawl sprint swimming.
The purpose of this study was to determine whether the breathing action in front crawl (FC) sprint swimming affects the ipsilateral upper limb kinematics relative to a non-breathing stroke cycle (SC). Ten male competitive swimmers performed two 25m FC sprints: one breathing to their preferred side (Br) and one not breathing (NBr). Both swim trials were performed through a 6.75m(3) calibrated space and recorded by six gen-locked JVC KY32 CCD cameras. A paired t-test was used to assess statistical differences between the trials, with a confidence level of p<0.05 accepted as significant. Swimmers were slower (3%) when breathing. Within the entry phase, swimmers had a slower COM horizontal velocity (3.3%), less shoulder flexion (8%), abduction (33%) and roll (4%) when breathing. The pull phase was longer in duration (14%) swimmers had a shallower hand path (11%), less shoulder abduction (11%), a slower hand vertical acceleration (30%) and slower centre of mass (COM) horizontal velocity (3%) when breathing. In the push phase, swimmers had a smaller elbow range of motion (ROM) (38%), faster backwards hand speed (25%) and faster hand vertical acceleration (33%) when breathing. Swimmers rolled their shoulders more (12%) in the recovery phase when breathing. This study confirms that swim performance is compromised by the inclusion of taking a breath in sprint FC swimming. It was proposed that swimmers aim to orient their ipsilateral shoulder into a stronger position by stretching and rolling the shoulders more in the entry phase whilst preparing to take a breath. Swimmers should focus on lengthening the push phase by extending the elbow more and not accelerating the hand too quickly upwards when preparing to inhale.


Coexpression network analysis identified Krüppel-like factor 6 (KLF6) association with chemosensitivity in ovarian cancer.
Although most patients with ovarian cancer (OC) are initially sensitive to paclitaxel/carboplatin combination chemotherapy, eventually they develop resistance to chemotherapy drugs and experience disease relapse. OC is the most lethal gynecological malignancy, and the five-year survival rate is extremely low. Thus, research on specific biomarkers and potential targets for chemotherapy-resistant patients with OC is needed. In our study, genes in the top 10% of variance in data set GSE30161 from chemoresistant and chemosensitive OC tissues were determined to conduct a weighted gene coexpression network analysis (WGCNA). The magenta module was most strongly related to OC chemoresponse. Gene ontology enrichment analysis indicated that the function of the magenta module primarily focused on transcription regulation, cell cycle control, and apoptosis modulation. Integration of the WGCN with the protein-protein interaction network identified five candidate genes. These five genes were verified using the GSE51373 test set, and Krüppel-like factor 6 ( KLF6) was identified as tightly linked to OC chemosensitivity. The receiver operating characteristic (ROC) curve showed that KLF6 differentiated chemoresistant from chemosensitive OC tissues. The Kaplan-Meier online database indicated that high KLF6 expression was associated with poor OC prognosis. Gene set enrichment analysis determined that the KLF6 mechanism was potentially associated with cell cycle, mTOR, and DNA-damage repair signaling pathways. In conclusion, KLF6 was identified in association with OC chemoresistance, and the mechanism of KLF6-mediated chemoresistance may involve the cell cycle, mTOR, and DNA-damage repair signaling pathways.


Potent Protection Against MPP+-Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine.
Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson's disease (PD). As evidenced by the increase in cell survival, as well as the decrease in the number of Hoechst-stained apoptotic nuclei and the level of intracellular accumulation of reactive oxygen species, DT-010 at 3-30 µM substantially protected against MPP+-induced neurotoxicity in both PC12 cells and primary cerebellar granule neurons, a protection that was more potent and efficacious than its parent molecules DSS and TMP. Very encouragingly, we found that DT-010, but not DSS or TMP, could enhance myocyte enhancer factor 2D (MEF2D) transcriptional activity using luciferase reporter gene assay. The neuroprotective effects of DT-010 could be blocked by pharmacologic inhibition of PI3K pathways with LY294002, or MEF2D pathway with short hairpin RNA-mediated knockdown of MEF2D. Furthermore, western blot analysis revealed that DT-010 potentiates Akt protein expression against MPP+ to down-regulate MEF2D inhibitor GSK3β. Taken together, the results suggest that DT-010 prevents MPP+-induced neurotoxicity via enhancing MEF2D through the activation of PI3K/Akt/GSK3β pathway. DT-010 may be a potential candidate for further preclinical study for preventing and treating PD.


Lithium dilution cardiac output measurements in isoflurane-anaesthetised goats: Jugular versus cephalic lithium chloride administration.
The administration of lithium chloride (LiCl) for cardiac output (CO) measurement via a peripheral instead of a central vein has been described previously as a valid alternative route in pigs and dogs. The aim of the study was to compare CO measurements after administration of LiCl using two peripheral veins, cephalic or jugular, in goats. Ten adult, female, experimental goats undergoing bilateral stifle arthrotomy were recruited for the study. Paired CO measurements were taken two minutes apart during stable conditions in isoflurane-anaesthetised goats. Forty-two paired CO measurements were taken in total, and the median (range) of paired CO measurement per goat were 4.5 (3-6). The mean (SD) CO using the cephalic and jugular vein for injection of LiCl was 5.28 (1.29) L min-1 and 5.20 (1.24) L min-1 respectively. The Bland-Altman analysis showed an acceptable agreement with a mean bias of 1.33% with limits of agreement (LoA) of -18.43 to 21.09%. The percentage of error was 25%. The four-quadrant plot analysis showed a poor agreement (71%) between the two routes. The polar plot showed a poor trending ability. An 86% inclusion rate (18/21 points) was reached with a ± 35° radial sector size. The findings revealed that the agreement between the two routes is not as precise as the authors expected, however the results are comparable with studies published previously.


[Treatment of nasopharyngeal carcinoma in children].
To evaluate the clinical efficacy of the ARAR0331 protocol for treatment of childhood nasopharyngeal carcinoma. The clinical data of eight children with nasopharyngeal carcinoma between May 2004 and May 2012 were retrospectively studied. The eight patients included six boys and two girls, and the onset age was between 3 and 13 years. Six patients were in AJCC Stage Ⅲ, one was in StageⅡA and one was in Stage ⅣA. One patient had been treated with combined radiotherapy and chemotherapy which mainly included EAP, BEP and EA. The other seven patients had been treated with the ARAR0331 protocol provided by the America Children's Oncology Group (COG). The patient who had been treated with combined radiotherapy and chemotherapy developed multiple bony metastasis during the chemotherapeutic period. Four out of seven patients who had been treated with ARAR0331 protocol achieved complete remission, and two achieved partial remission. The seven patients were followed-up from 8 to 75 months and the survival rate was 100%. The ARAR0331 protocol treatment-related complications included radiodermatitis, mucocitis and nausea. Late toxicity was not found. Based on the limited cases, ARAR0331 protocol appears to be effective and safe for childhood nasopharyngeal carcinoma.


Ambulatory blood pressure monitoring of patients with heart failure. A new prognosis marker.
To evaluate the relationship between 24-hour ambulatory arterial blood pressure monitoring and the prognosis of patients with advanced congestive heart failure. We studied 38 patients with NYHA functional class IV congestive heart failure, and analyzed left ventricular ejection fraction, diastolic diameter, and ambulatory blood pressure monitoring data. Twelve deaths occurred. Left ventricular ejection fraction (35.2 +/-7.3%) and diastolic diameter (72.2 +/- 7.8mm) were not correlated with the survival. The mean 24-hour (SBP24), waking (SBPw), and sleeping (SBPs) systolic pressures of the living patients were higher than those of the deceased patients and were significant for predicting survival. Patients with mean SBP24, SBPv, and SBPs >/=105mmHg had longer survival (p=0.002, p=0.01 and p=0.0007, respectively). Patients with diastolic blood pressure sleep decrements (dip) and patients with mean blood pressure dip </= 6mmHg had longer survival (p=0.04 and p=0.01, respectively). In the multivariate analysis, SBPs was the only variable with an odds ratio of 7.61 (CI: 1.56; 3704) (p=0.01). Patients with mean SBP<105mmHg were 7.6 times more likely to die than those with SBP >/= 105 mmHg Ambulatory blood pressure monitoring appears to be a useful method for evaluating patients with congestive heart failure.


Arthroscopic tenotomy for treatment of biceps tendon luxation in two apprehension police dogs.
A 7.5-year-old 37.8-kg (83.2-lb) sexually intact male German Shepherd Dog (dog 1) and a 2.6-year-old 28.2-kg (62.0-lb) sexually intact male Dutch Shepherd (dog 2), both apprehension police dogs, were admitted for evaluation of left and right thoracic limb lameness, respectively. In both dogs, signs of pain were elicited on palpation of the shoulder joint in the affected limb, and a distinct popping of the biceps brachii tendon (BT) was palpable on the craniomedial aspect of the affected joint on flexion and extension and was associated with moderate signs of pain. Biceps brachii tendon luxation (BTL) was diagnosed with dynamic musculoskeletal ultrasonography (both dogs) and MRI (dog 1). Arthroscopic BT release by tenotomy was performed in both dogs. Lameness appeared to have resolved by 8 weeks after surgery and had not recurred by the last follow-up communications at 36 and 9 months after surgery for dogs 1 and 2, respectively. Both dogs successfully returned to their level of work performed before their injury. Our findings for the dogs of the present report suggested that arthroscopic BT release could be considered a viable treatment option for BTL in dogs, including police dogs or other high-performance athletic dogs. Although our findings provided encouraging results, further research, best conducted with a multicenter prospective randomized study, would be needed to establish the most reliable treatment of BTL in high-performance athletic or working dogs.


Relevance of class, molecular weight and isoelectric point in predicting human light chain amyloidogenicity.
The ability to predict the amyloidogenicity of certain light chains may facilitate an earlier diagnosis of AL amyloidosis and, possibly, lead to more effective treatment. Using current methods, available in clinical chemistry laboratories, we assessed the class, the relative molecular mass (Mr) and the isoelectric point of urinary monoclonal light chains from 35 patients with AL amyloidosis (A+) and 51 without amyloidosis (A-). The light chain class (LCC) was lambda in 77% and 45% of A+ and A- patients, respectively. Light chain fragments (LCF) with low Mr (12-18 x 10(3) were detected in the urine of 30/35 A+ patients and in 15/51 A- ones. The mean (SD) isoelectric point (pI) of A+ light chains was 4.8 (1.1) while in A- patients it was 6.2 (1.6). Univariate analysis showed significant differences between the two groups for the three parameters. Discriminant analysis gave a function which allowed a correct allocation of 81% of the cases between the two groups.


Tri-substituted imidazole analogues of SB203580 as inducers for cardiomyogenesis of human embryonic stem cells.
The p38α mitogen-activated protein kinase (MAPK) inhibitor SB203580 had been reported to enhance the cardiomyogenesis of human embryonic stem cells (hESCs). To investigate if tri-substituted imidazole analogues of SB203580 are equally effective inducers for cardiomyogenesis of hESCs, and if there is a correlation between p38α MAPK inhibition and cardiomyogenesis, we designed and synthesized a series of novel tri-substituted imidazoles with a range of p38α MAPK inhibitory activities. Our studies demonstrated that suitably designed analogues of SB203580 can also be inducers of cardiomyogenesis in hESCs and that cell growth is affected by changes in the imidazole structures.


Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts.
Hyaluronan (HA)-receptors (mainly CD44 and RHAMM) are overexpressed in a wide variety of cancers including ovarian tumors, and HA-bioconjugates have been developed to enhance selective entry of cytotoxic drugs into HA receptor-expressing cancerous cells. Here, we evaluated the potential application of a new HA-paclitaxel bioconjugate, ONCOFID-P, for intraperitoneal (IP) treatment of ovarian cancer. In vitro cytotoxic effect of ONCOFID-P was first assessed on CD44(+) OVCAR-3 and SKOV-3 human ovarian cancer cell lines. Studies were performed in female Balb/c athymic mice IP implanted with OVCAR-3 or SKOV-3 and treated with IP ONCOFID-P, and IP and intravenous (IV) free paclitaxel, at their maximum tolerated dose (MTD 168, 80 and 80 mg/kg, total dose, respectively). The potential detrimental effect of the IP ONCOFID-P and IP free paclitaxel on hematopoiesis was also assessed on peripheral blood, bone marrow and spleen. Results show that ONCOFID-P cytotoxicity against both OVCAR-3 and SKOV-3 cell lines was somewhat less effective than free paclitaxel. Conversely, in in vivo experiments, IP treatment with ONCOFID-P was overall more effective than IV and IP free paclitaxel in inhibiting intra-abdominal tumor dissemination, abrogating ascites, prolonging survival and curing mice. ONCOFID-P and IP free paclitaxel were equivalent in terms of myelotoxicity, although the former was administered at a two-fold higher dose. Present data strongly support the development of ONCOFID-P for locoregional treatment of ovarian cancer.


[Vesicles, pustules and vesiculopustules in early childhood].
Vesicles, pustules and vesiculopustules are frequent in newborns and infants and mostly self-limiting. In order to differentiate the rare life-threatening diseases and to therefore initiate the treatment in a timely manner, knowledge of vesicular, pustular and vesiculopustular dermatoses in early childhood is necessary.


Exploring the experience of supporting a loved one through a medically assisted death in Canada.
To explore the experience of family and close friends of patients seeking medical assistance in dying (MAID) in Canada. Qualitative study using semistructured interviews. A clinic in Vancouver, BC, that provides MAID services. Eighteen support people for patients seeking MAID. Clinic patients seeking MAID identified their primary support people during consultations for an assisted death evaluation. Identified support people were invited to participate in the study, and those who were interested were asked to contact the interviewers. Semistructured interviews were conducted, transcribed, coded, and subjected to content analysis to elucidate common themes. All participants were supportive of their loved one's wish for assisted death and they provided emotional and practical support in preparation for MAID. Support persons talked about the journey they went through from their loved one's diagnosis to the MAID request to the actual death. Some were initially opposed but changed their minds after seeing the suffering their loved ones endured. The time before the assisted death involved saying goodbye and, for some, ceremonial rituals (celebration of life, poems, singing, etc). Those interviewed after their loved one's assisted death found the death peaceful and reported that it offered advantages compared with natural death in their loved one's individual circumstances. This study provides insight into experiences of support people coping with a loved one who is seeking or has sought MAID in the context of a country unfamiliar with the legal process of a planned and hastened death. Participants were supportive of their loved one's wishes for assistance in death to end suffering and found the process to be peaceful overall.


Influence of serotonin on myocardial blood flow in the presence and absence of a coronary arterial stenosis: observations in domestic swine.
This study tested the hypothesis that 5-HT may impair coronary flow regulation by inappropriately increasing arteriolar tone in the coronary circulation. Ten closed chest, domestic swine were studied both in the presence and in the absence of a severe artificial intraluminal coronary stenosis. A 5-French micromanometer catheter with fluid lumen was placed in the left anterior descending coronary artery and used to record pressure and infuse 5-HT (40 and 100 micrograms/min) into the coronary circulation. For the stenosis phase of the protocol the catheter was embedded in the artificial stenosis. Hemodynamics, regional myocardial blood flow (microsphere technique), coronary vascular resistance, lactate consumption, and oxygen metabolism were measured at control and at 5 min of each 5-HT dose. In the absence of coronary artery stenosis (i.e., full vasodilatory reserve), there was no change in regional myocardial blood flow or coronary vascular resistance during 5-HT infusion. In the presence of a severe coronary stenosis (i.e., limited vasodilator reserve) 5-HT produced a significant (P less than 0.05) decrease versus control in the distal left anterior descending: circumflex zone endocardial blood flow ratio (0.63 +/- 0.19, mean +/- 1 SD, to 0.55 +/- 0.15) and a significant (P less than 0.05) increase versus control in endocardial (50.6 +/- 16.6 to 61.2 +/- 19.8 mm Hg/ml/min/g) and transmural (49.9 +/- 9.5 to 57.2 +/- 12.8) coronary vascular resistance. Thus, 5-HT does not impair coronary flow regulation when full vasodilatory reserve is present. When coronary vasodilatory reserve is impaired by the presence of a severe proximal stenosis, 5-HT causes modest impairment of endocardial flow regulation.


The Predictive Value of Neutrophil-to-Lymphocyte Ratio for Hodgkin's Lymphoma Diagnosis in Patients with Asymptomatic Cervical Lymphadenopathy.
In patients with asymptomatic cervical lymphadenopathy, the physician often has to choose between evaluation via follow-up or open biopsy. Follow-up evaluation may lead to a delayed diagnosis of lymphoma, while an open biopsy is associated with surgical risks and costs. This dilemma can be avoided using predictive parameters. In the present study, we aimed to investigate whether neutrophil-to-lymphocyte ratio (NLR), a parameter which can be assessed quickly with ease and at low cost, has predictive value for Hodgkin's lymphoma diagnosis in patients with asymptomatic cervical lymphadenopathy. A total of 46 patients with asymptomatic cervical lymphadenopathy who underwent open biopsy were included in the study. Based on the biopsy results, the patients were divided into two groups, Hodgkin lymphoma (26 patients) and reactive lymphadenopathy (20 patients). The mean NLR in the groups was calculated and compared based on the results of complete blood count performed before biopsy. We found that mean NLR (P = 0.022) and mean neutrophil count (P = 0.046) were higher and mean lymphocyte count was lower (P = 0.054) in patients with Hodgkin's lymphoma compared to those in patients with reactive lymphadenopathy. Our results indicate that a high NLR may have predictive value for Hodgkin's lymphoma diagnosis in patients with asymptomatic cervical lymphadenopathy.


Hepatocyte growth factor and omega-3-enriched feeds have a synergistic effect on mucosal mass in an animal model of inflammatory bowel disease.
Hepatocyte growth factor (HGF) decreases intestinal inflammation and cytokine levels in an animal model of inflammatory bowel disease (IBD). Luminal omega-3 (OM-3) is anti-angiogenic, reduces inflammation, and may decrease symptoms in patients with Crohn's disease. This study evaluates the synergism of HGF and OM-3. Twenty adult female transgenic HLA-B27 rats were divided into 4 groups: group 1: regular feeds, IV saline; group 2: OM-3-enriched feeds, IV saline; group 3: regular feeds, IV HGF (150 µg/kg per day); and group 4: OM-3-enriched feeds, IV HGF(150 µg/kg per day). Rats were killed at 14 days after pump placement. Small and large bowel mucosa was harvested, and DNA and protein were extracted and quantified. Statistical analysis was done by analysis of variance with post-hoc Tukey's HSD test. Content of protein and DNA in the ileum were significantly increased by supplementation of HGF (P < .001, P < .01, respectively) alone. OM-3 significantly increased protein content but not DNA (P = .02, P = 0.3, respectively). Combined, they had a synergistic effect greater than either supplement alone (P = .0001, P = .002, respectively). In the colon, HGF and OM-3 did not significantly increase protein or DNA content individually or together. This is the first demonstration of the synergistic effect of a growth factor (HGF) and a dietary supplement (OM-3) in an immunologic model of IBD.