Meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure.
To investigate the experiences of young women with spontaneous premature ovarian failure with regard to the initial presenting symptom, promptness of diagnosis, and patient education. We asked 50 patients previously diagnosed with spontaneous premature ovarian failure to participate in a structured interview survey consisting of 38 true-or-false, multiple-choice, and open-ended questions. Disturbance in menstrual pattern was the most common initial symptom in the 48 women who completed the interview (44 of 48, 92%). Over half of the 44 women who presented with this complaint reported visiting a clinician's office three or more times before laboratory testing was performed to determine the diagnosis. Over half of them reported seeing three or more different clinicians before diagnosis. In 25% of women it took longer than 5 years for the diagnosis of premature ovarian failure to be established. Patients who spent more than 5 minutes with the clinician discussing the diagnosis were significantly more likely to be satisfied with the manner in which they were informed (P <.001). Ninety percent of participants were college graduates, and 40% had graduate degrees. Women with spontaneous premature ovarian failure perceived a need for more aggressive evaluation of secondary amenorrhea and oligomenorrhea. Loss of menstrual regularity can be a sign of ovarian insufficiency, and the associated estrogen deficiency is a well-established risk factor for osteoporosis.


Brain surgery in the bush: adapting techniques and technology to fit the developing world.
The critical shortage of surgical services in many areas of the world has profound effects on local communities. Approximately 11% of global disease burden can be attributed to causes that are surgically treatable. Efforts have been made to recruit professionals from developed nations to compensate for the lack of such expertise. However, this practice has created a cycle of dependency on foreign-trained physicians and the medical tools they bring. Recognition of this problem calls for adaptation of a novel problem-solving approach. This article describes techniques and technology available in east Africa that have been adapted to allow basic and emergency neurosurgery to be performed in the absence of complex medical infrastructure and equipment. Commonplace items found in the local environment can be used to emulate more sophisticated instruments, and community-specific engineering programs can be developed to provide locally produced appropriate technology that promotes independence from Western sources. The local economy benefits from much-needed stimulation when these tools are created locally, and this allows for readily available replacement and repair. More studies are under way to identify problems and implement interventions that are realistic and appropriate for these populations.


Stability of E-type prostaglandins in triacetin.
A drug delivery system for E-type prostaglandins is described. In this system, consisting of drug dissolved in triacetin and filled into soft gelatin capsules, normally unstable prostaglandins show excellent stability at room temperature.


Risk of Adverse Clinical Outcomes in Hyponatremic Adult Patients Hospitalized for Acute Medical Conditions: A Population-Based Cohort Study.
Hyponatremia has been associated with excess long-term morbidity and mortality. However, effects during hospitalization are poorly studied. The objective of this work is to examine the association of hyponatremia with the risk of in-hospital mortality, 30-day readmission, and other short-term adverse events among medical inpatients. A population-based cohort study was conducted using a Swiss claims database of medical inpatients from January 2012 to December 2017. Hyponatremic patients were 1:1 propensity-score matched with normonatremic medical inpatients. The primary outcome was a composite of all-cause in-hospital mortality and 30-day hospital readmission. Secondary outcomes were intensive care unit (ICU) admission, intubation rate, length-of-hospital stay (LOS), and patient disposition after discharge. After matching, 94 352 patients were included in the cohort. Among 47 176 patients with hyponatremia, 8383 (17.8%) reached the primary outcome compared with 7994 (17.0%) in the matched control group (odds ratio [OR] 1.06 [95% CI, 1.02-1.10], P = .001). Hyponatremic patients were more likely to be admitted to the ICU (OR 1.43 [95% CI, 1.37-1.50], P < .001), faced a 56% increase in prolonged LOS (95% CI, 1.52-1.60, P < .001), and were admitted more often to a postacute care facility (OR 1.38 [95% CI 1.34-1.42, P < .001). Of note, patients with the syndrome of inappropriate antidiuresis (SIAD) had lower in-hospital mortality (OR 0.67 [95% CI, 0.56-0.80], P < .001) as compared with matched normonatremic controls. In this study, hyponatremia was associated with increased risk of short-term adverse events, primarily driven by higher readmission rates, which was consistent among all outcomes except for decreased in-hospital mortality in SIAD patients.


Engineered domain swapping indicates context dependent functional role of RNA G-quadruplexes.
RNA domain swapping typically demonstrates conservation of the native function of the domain in a non-native context. In contrast, we employed RNA engineering to demonstrate deviation of G-quadruplex (GQ) function that is contingent upon its context dependent location, which is opposite to their native functional role. Known translation repressing RNA GQs were engineered into human VEGF IRES A replacing the endogenous GQ domain essential for translation. Alternatively, the translation inhibitory GQ motif within the 5'-UTR of MT3-MMP mRNA was replaced with two known GQ motifs that are essential for translation. The results indicate that the engineered GQ domains can adopt GQ structures in a foreign environment with a functional role reversal to accommodate the need of the endogenous swapped motifs. The observations establish the functionality and context dependent modularity of RNA GQ structures.


Development and evaluation of a novel xeno-free culture medium for human-induced pluripotent stem cells.
Human-induced pluripotent stem cells (hiPSCs) are considered an ideal resource for regenerative medicine because of their ease of access and infinite expansion ability. To satisfy the sizable requirement for clinical applications of hiPSCs, large-scale, expansion-oriented, xeno-free, and cost-effective media are critical. Although several xeno-free media for hiPSCs have been generated over the past decades, few of them are suitable for scalable expansion of cultured hiPSCs because of their modest potential for proliferation and high cost. In this study, we developed a xeno-free ON2/AscleStem PSC medium (ON2) and cultured 253G1 hiPSCs on different matrices, including iMatrix-511 and gelatin nanofiber (GNF) in ON2. Over 20 passages, we evaluated cell proliferation by doubling times; pluripotency by flow cytometry, immunofluorescence staining and qRT-PCR; and differentiation ability by three germ layer differentiation in vitro and teratoma formation in severe combined immunodeficiency mice, followed by histological analysis. In addition, we compared the maintenance effect of ON2 on hiPSCs with StemFit® AK02 (AK02N) and Essential 8™ (E8). Besides 253G1 hiPSCs, we cultivated different hiPSC lines, including Ff-l01 hiPSCs, ATCC® ACS-1020™ hiPSCs, and Down's syndrome patient-specific ATCC® ACS-1003™ hiPSCs in ON2. We found that 253G1 hiPSCs in ON2 demonstrated normal morphology and karyotype and high self-renewal and differentiation abilities on the tested matrices for over 20 passages. Moreover, 253G1 hiPSCs kept on GNF showed higher growth and stemness, as verified by the shorter doubling time and higher expression levels of pluripotent markers. Compared to AK02N and E8 media, 253G1 hiPSCs grown in ON2 showed higher pluripotency, as demonstrated by the increased expression level of pluripotent factors. In addition, all hiPSC lines cultivated in ON2 were able to grow for at least 10 passages with compact clonal morphology and were positive for all detected pluripotent markers. Our xeno-free ON2 was compatible with various matrices and ideal for long-term expansion and maintenance of not only healthy-derived hiPSCs but also patient-specific hiPSCs. This highly efficient medium enabled the rapid expansion of hiPSCs in a reliable and cost-effective manner and could act as a promising tool for disease modeling and large-scale production for regenerative medicine in the future.


A case of neuropathic brachioradial pruritus caused by cervical disc herniation.
A 64-year-old woman presented to an outpatient clinic with a 2-year history of itch, burning sensation and intermittent paresthesias within the innervation territory of the sixth cervical nerve root on the right dorsal forearm. No dermatological diseases, trauma to the affected extremity or the spine, or familial pruritus were reported. Dermatological examination, skin biopsy, laser Doppler imaging, neurological physical examination and cervical MRI scan. Brachioradial pruritus caused by cervical disc herniation. Ventral spinal fusion with cage implantation.


Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study.
To characterize and identify prognostic factors for 28-day mortality among patients with hospital-acquired fungemia (HAF) in the Intensive Care Unit (ICU). A sub-analysis of a prospective, multicenter non-representative cohort study conducted in 162 ICUs in 24 countries. Of the 1156 patients with hospital-acquired bloodstream infections (HA-BSI) included in the EUROBACT study, 96 patients had a HAF. Median time to its diagnosis was 20 days (IQR 10.5-30.5) and 9 days (IQR 3-15.5) after hospital and ICU admission, respectively. Median time to positivity of blood culture was longer in fungemia than in bacteremia (48.7 h vs. 38.1 h; p = 0.0004). Candida albicans was the most frequent fungus isolated (57.1%), followed by Candida glabrata (15.3%) and Candida parapsilosis (10.2%). No clear source of HAF was detected in 33.3% of the episodes and it was catheter-related in 21.9% of them. Compared to patients with bacteremia, HAF patients had a higher rate of septic shock (39.6% vs. 21.6%; p = 0.0003) and renal dysfunction (25% vs. 12.4%; p = 0.0023) on admission and a higher rate of renal failure (26% vs. 16.2%; p = 0.0273) at diagnosis. Adequate treatment started within 24 h after blood culture collection was less frequent in HAF patients (22.9% vs. 55.3%; p < 0.001). The 28-day all cause fatality was 40.6%. According to multivariate analysis, only liver failure (OR 14.35; 95% CI 1.17-175.6; p = 0.037), need for mechanical ventilation (OR 8.86; 95% CI 1.2-65.24; p = 0.032) and ICU admission for medical reason (OR 3.87; 95% CI 1.25-11.99; p = 0.020) were independent predictors of 28-day mortality in HAF patients. Fungi are an important cause of hospital-acquired BSI in the ICU. Patients with HAF present more frequently with septic shock and renal dysfunction on ICU admission and have a higher rate of renal failure at diagnosis. HAF are associated with a significant 28-day mortality rate (40%), but delayed adequate antifungal therapy was not an independent risk factor for death. Liver failure, need for mechanical ventilation and ICU admission for medical reason were the only independent predictors of 28-day mortality.


Dissemination of multidrug resistant bacteria to the polar environment - Role of the longest migratory bird Arctic tern (Sterna paradisaea).
The ever-increasing prevalence of antibiotic-resistant bacteria(ARB), primarily due to the frequent use and misuse of antibiotics, is an issue of serious global concern. Migratory birds have a significant role in dissemination of ARB, as they acquire resistant bacteria from reservoirs and transport them to other environments which are relatively less influenced by anthropogenically. We have investigated the prevalence of ARB in a long-distance migratory bird, the Arctic tern (Sterna paradisaea) captured from the Svalbard Archipelago. The birds were tagged with geolocators to track their extraordinary long migration, and the cloacal samples were collected before the migration and after the migration by recapturing the same birds. The tracking of 12 birds revealed that during the annual cycle they underwent a total of 166 stopovers (11-18, mean = 3.8) and recovery points along the Atlantic Ocean. Twelve major bacterial genera were identified from Arctic tern cloacal samples, which are dominated by Staphylococcus spp. and Aerococcus spp. The bacterial isolates showed resistance against 16 antibiotics (before migration) and 17 antibiotics (after migration) out of 17 antibiotics tested. Resistance to β-lactam and quinolone class of antibiotics were frequent among the bacteria. The study highlights the potential role of Arctic tern in the dissemination of multidrug resistant bacteria across far and wide destinations, especially to the polar environments.


Insulin attenuates leptin-induced STAT3 tyrosine-phosphorylation in a hepatoma cell line.
Leptin, the 16 kDa protein product of the ob gene, is secreted by adipocytes. The long form leptin receptor (ObRb) is expressed at high levels in the hypothalamus, and regulates appetite and energy expenditure. The fact that serum concentration of leptin is correlated with body mass index (BMI) suggests reduced sensitivity to leptin. Even though hyperinsulinemia and hyperleptinemia could coexist in obese humans, little is known about the interaction of insulin and leptin. In this study, we examined the effect of insulin on leptin signaling using Huh 7 cells transiently transfected with ObRb cDNA. Insulin inhibits leptin-induced STAT3 phosphorylation in a time- and dose-dependent manner without affecting Janus tyrosine kinases (JAKs) JAK2 phosphorylation. Okadaic acid prevents the inhibitory effect of insulin on leptin-induced STAT3 activation.


Correlation analysis between IL-35, IL-36γ, CCL27 and psoriasis vulgaris.
Evaluating the serum level of IL-35, IL-36γ and CCL27 cytokines expression in patients with psoriasis and to explore their correlation with disease severity. To explore the role of these cytokines in the pathogenesis of psoriasis vulgaris and to guide clinical practice. Thirty patients with psoriasis vulgaris (PV) were treated with routine drug treatment for7 weeks, and 30 healthy controls were used as control group. Peripheral blood of the PV group before and after treatment and control group were detected by double-antibody sandwich ELISA. The expression levels of IL-35, IL-36γ and CCL27 in peripheral blood were analyzed statistically. The expression of IL-35 in the peripheral blood of the pre-PV group (187.54 ± 172.41) was significantly lower than that of the control group (310.52 ± 174.22) and the PV treatment group (417.75 ± 47.07). The level of IL-36γ in peripheral blood of pre-PV group (295.11 ± 27.91) was higher than that of control group (155.40 ± 45.66) and PV treatment group (209.86 ± 27.91). The level of CCL27 in peripheral blood of patients pre-PV treatment (479.06 ± 285.80) was significantly higher than that of the control group (341.53 ± 98.72) and the group after PV treatment (316.56 ± 245.53). There was a negative correlation between IL-35 and IL-36γ levels in serum (r= -0.826, p < .001); IL-36γ was positively correlated with CCL27 level (r = 0.906, p < .001); IL-35 and CCL27 levels were negative correlation (r= -0.810, p < .001). IL-36γ and CCL27 may be involved in the pathogenesis of psoriasis as a pro-inflammatory factor. IL-35 may be involved in the pathogenesis of psoriasis as an anti-inflammatory factor.


Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex.
Changes in the expression of somatostatin (SRIF) have been observed in the brains of HIV encephalitis. Since gp120 is thought to play a major role in AIDS-associated abnormalities in the brain, we addressed the question: Does gp120 alter the functional expression of human fetal SRIF neurons in culture and if so, is this effect fetal-age dependent? Aggregate cultures, obtained from cortices of nine fetuses (14.9-20.7 weeks), were exposed for 7 days to BDNF or BDNF+gp120; BDNF induced production of SRIF during the subsequent 24-48 h was assessed. Similar effects of BDNF and gp120 were observed in the 9 brain-cultures. A 7-day exposure to BDNF alone led to a significant increase in SRIF production (p=0.014), whereas exposure to gp120 alone did not. Co-exposure to BDNF and gp120 led to an increase in BDNF-induced SRIF production which was significantly greater than that after BDNF alone (p=0.006). These effects were BDNF- and gp120-dose dependent and they were not accompanied by changes in DNA content of the aggregates nor in lactate dehydrogenase activity in the medium; indicating that gp120 did not lead to a major loss of cell integrity. These results are consistent with a synergistic effect of BDNF and gp120 leading to enhanced functional expression of the signalling pathway(s) mediating BDNF induction of SRIF production; an effect expressed by fetal brains throughout the 2nd trimester of gestation. Thus, this culture system can serve as a model to study the mechanism(s) underlying the early interactions between gp120 BDNF in the developing human brain.


β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4.
Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/SMAD3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/SMAD3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions.


Anemia and associated factors among 6 to 59 months age children attending health facilities in Kombolcha town, Northeast Ethiopia: a facility-based cross-sectional study.
Childhood anemia is an important public health problem in Ethiopia. The northeast part of the country is among the areas affected by recurrent drought. Despite its significance, studies are scarce on childhood anemia particularly, in the study area. This study aimed to assess the proportion and factors associated with anemia among under-five children in Kombolcha town. A facility-based cross-sectional study was conducted among 409 systematically selected 6 to 59 months aged children visited health institutions in Kombolcha town. Data were collected using structured questionnaires from mothers/caretakers. The data entry and analysis were done using EpiData version 3.1 and SPSS version 26 respectively. Binary logistic regression was fitted to identify factors associated with anemia. Statistical significance was declared at p-value ≤ 0.05. The effect size was reported using the adjusted odds ratio with its 95% confidence interval. Of the participants, 213(53.9%) were males with a mean age of 26 months (SD ± 15.2). The proportion of anemia was 52.2% (95% CI, 46.8-57%). Being in the age of 6-11 months (AOR = 6.23, 95% CI: 2.44, 15.95), 12-23 months (AOR = 3.74, 95%CI: 1.63, 8.60), having low dietary diversity score (AOR = 2.61, 95% CI: 1.55, 4.38), having a history of diarrhea (AOR = 1.87, 95% CI: 1.12, 3.12) and having the lowest family monthly income (AOR = 16.97, 95% CI: 4.95, 58.20) were positively associated with anemia. Whereas, maternal age ≥ 30 years (AOR = 0.37 (0.18, 0.77) and exclusive breastfeeding until six months (AOR = 0.27, 95% CI: 0.16, 0.45) were negatively associated with anemia. Childhood anemia was a public health problem in the study area. Child age, maternal age, exclusive breastfeeding, dietary diversity score, diarrhea, and family income were significantly associated with anemia.


A phase I trial of high-dose continuous-infusion hydroxyurea.
Hydroxyurea inhibits ribonucleotide reductase, resulting in depletion of intracellular deoxynucleotide pools and inhibition of DNA repair. It has been used in a variety of malignancies and is usually given orally. Deoxynucleotide depletion is directly related to the concentration of and duration of exposure to hydroxyurea; thus, prolonged continuous infusion may result in increased therapeutic efficacy. A total of 30 patients were treated on this trial, designed to determine the maximum tolerated doses (MTD) of intravenous hydroxyurea given as a 24- or 48-h continuous infusion. The MTD for the 24-h infusion was 13,520 mg/m2 following a bolus of 1,690 mg/m2, and the mean (+/- SD) plasma steady-state concentration was 1.93 +/- 0.52 mM. For the 48-h infusion, the MTD was 17,576 mg/m2 following a bolus of 2,197 mg/m2 and the mean steady-state level was 1.43 +/- 0.31 mM. The dose-limiting toxicity on both schedules was marrow suppression manifesting as neutropenia and thrombocytopenia. Pharmacokinetic analysis revealed decreasing clearance with increasing dose, implying that drug elimination is saturable. Pharmacodynamic analysis showed a slight correlation between steady-state plasma levels and the degree of marrow suppression.


Adsorption of Cu2+, Pb2+, and Cd2+ onto oiltea shell from water.
Agro-processing waste oiltea shell (OTS) has been previously proven effective in removing dye from water by adsorption. This study further evaluated its capability to adsorb heavy metals in aqueous solution. Adsorbent dosage, pH, ion concentration, temperature, and contact time were investigated in batch experiments. Pseudo-second order kinetic better described the adsorption process for the three ions. Langmuir equation was more suitable for Cu2+ and Cd2+, while Freundlich for Pb2+. The maximum adsorption capacity was 22.4 (Pb2+), 12.1 (Cu2+), and 14.2 mg/g (Cd2+), respectively. The adsorption was spontaneous and endothermic. Adsorption was then performed in column and Thomas model was fitted, based on which the maximum adsorption capacity was 7.42 (Cu2+), 4.17 (Pb2+), and 18.02 mg/g (Cd2+), respectively. High removal rate of metal ions and dye methylene blue was also achieved from their mixture solution. OTS is therefore a promising biosorbent in treating wastewater with organic and inorganic pollutants.


The serological detection of Bovine papillomavirus's E5 oncoprotein antibodies in horses.
Equine sarcoids (ES) are known globally as the most frequent skin tumour affecting horses. These tumours affect the horse's monetary value, they can affect the horse's welfare and can be difficult and expensive to treat. Bovine papillomavirus (BPV) is considered to be the aetiological agent of this tumour, as BPV 1, 2 and 13 have been detected in ES. This is the only known natural cross species infection by a papillomavirus. The BPV genome can be divided into two coding regions: The early region E which encodes the transforming proteins E5, E6 and E7 as well as the replication and transcription regulatory proteins E1 and E2 and the late region encoding the structural proteins of the virus L1 and L2. The E5 oncoprotein is believed to downregulate MHC 1 and as a result, escapes an immune reaction with affecting the cells cycle and eventually allows the viral affected cells to proliferate into ES. We have constructed an ELISA test by utilising the C terminal peptide of the E5 oncoprotein and explored the possibility of IgG antibodies existence in horses to the E5 oncoprotein. For this study we have examined 136 horses, some showing ES lesions (80 horses) and some without ES lesions (56 horses). By using our ELISA test, we have shown that antibodies to the E5 oncoprotein are in fact present and that from a certain level seem to be found only in ES positive horses. Therefore, proving that an immune response to this protein can be expected.


Cytopreparation of duodenal biopsy fixative improves detection rate of giardia in clinically suspected cases.
Giardia intestinalis is a flagellated protozoan, frequently documented as an agent for enteric illness worldwide. Laboratory procedures for diagnosis include stool examination, antigenic detection assays and, at times, mucosal biopsy. We hypothesised that the formalin fixative used as a preservative for mucosal biopsy can be a good diagnostic sample for detecting surface mucosal and luminal infective agents such as giardia. The aim of the study was to find out the utility of processing the remaining formalin fixative as a complementary diagnostic method for detecting giardia. This study included 200 cases of duodenal biopsies sampled over 6 months. The biopsies were picked up using clean forceps and the remaining fixative was processed using standard cytospin protocol. The cytospin preparation and formalin-fixed paraffin-embedded tissue sections were examined by two pathologists independently blinded to each others findings. On cytology, trophozoites of giardia were detected in 23 out of 200 cases (11.50%). The cytomorphology of pear-shaped organism with paired flagella and nuclei is very diagnostic. One case also showed presence of cryptosporidium spores. No other intestinal parasite was seen. Out of the 23 positive cytology samples, only 12 (6%) corresponding formalin-fixed paraffin-embedded tissue sections showed presence of giardia. Concurrent examination of duodenal biopsy and the formalin fixative cytopreparation in cases with high index of clinical suspicion of giardiasis proved to be a useful adjunct to biopsy diagnosis of giardiasis, which was statistically significant (P < .0001). This approach adds negligible cost and effort but with good diagnostic yield. We recommend that the formalin cytopreparation be used as a complementary technique to biopsy for cases suspected of intestinal parasitic infection.


Phosphatase-resistant analogues of lysophosphatidic acid: agonists promote healing, antagonists and autotaxin inhibitors treat cancer.
Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein-coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically-stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX.


Spinocerebellar ataxia type 7 mimicking Kearns-Sayre syndrome: a clinical diagnosis is desirable.
Spinocerebellar ataxias are a group of autosomal dominant cerebellar degenerative disorders, which are characterized by clinical and genetic variability. Spinocerebellar ataxia type 7 (SCA7) is less variable in clinical presentation than other SCAs. We present a pediatric patient with 13 and 70 trinucleotide CAG repeats within SCA7 gene and no family history, whose presentation mimicked Kearns-Sayre syndrome (KSS). We review the differential diagnosis of cerebellar ataxia with vision loss secondary to retinal pigmentary dystrophy. This paper supports concept of a desirable clinical diagnosis to avoid multiple genetic or invasive testing in children with neurodegenerative disorders.


Growth hormone stimulates the proliferation of cultured chondrocytes from rabbit ear and rat rib growth cartilage.
The effect of growth hormone (GH) on various growth processes is generally considered to be indirect, mediated by GH-dependent plasma factors--somatomedins--which are produced mainly in the liver. In vitro, somatomedins stimulate a number of processes that apparently are associated with cell growth. It has been difficult, however, to induce skeletal growth by the administration of somatomedins in vivo. Daily injections of a partially purified somatomedin preparation failed to induce accumulated longitudinal bone growth using the intravital marker tetracycline or by measuring the nose-to-tail length. Administration of insulin-like growth factor I (IGF I) which is probably identical to somatomedin C, to hypophysectomized rats has been reported to increase the width of the epiphyseal plate. But although this suggests an in vivo effect of IGF I on longitudinal bone growth, such an effect has not been directly demonstrated. Recently, we reported that local administration of human GH (hGH) into the proximal cartilage growth plate of the tibia of hypophysectomized rats stimulated longitudinal bone growth on the side injected with the hormone. Furthermore, we have identified specific binding sites for hGH in cultured chondrocytes from rabbit ear and epiphyses. Here, we show that hGH, but not the structurally related polypeptides ovine prolactin or human prolactin, stimulates DNA synthesis in chondrocytes from rabbit ear and from rat rib growth plate, cultured in a chemically defined medium without the addition of serum. Our results suggest that GH directly initiates proliferation in mammalian chondrocytes.


Diffusional kurtosis imaging of parotid glands in Sjögren's syndrome: Initial findings.
To explore the role of diffusion kurtosis imaging (DKI) of parotid glands in diagnosing Sjögren's syndrome (SS). A total of 40 patients with SS and 40 healthy volunteers underwent 3.0T magnetic resonance imaging (MRI) including DKI, which generated the apparent diffusion coefficient (ADC), corrected diffusion (D), and diffusional kurtosis (K) values. The MR nodular grade was determined on the basis of MR morphological findings. The parotid ADC, D, and K values in patients with SS were significantly higher than those of healthy volunteers (P = 0.011, < 0.001, 0.022, respectively). The parotid ADC and D values in patients with SS of MR nodular grade 0 were significantly higher than those of healthy volunteers (all P < 0.001). The parotid D value showed an accuracy of 75.0% and 87.9% in diagnosing patients with SS and MR nodular grade 0, respectively. The parotid ADC and D values correlated negatively, while the K values correlated positively with the MR nodular grade significantly in patients with SS (r = -0.741, -0.605, 0.424, all P < 0.001). All parotid DKI parameters differed significantly among patients with SS at different MR nodular grades (all P < 0.001). Parotid DKI parameters hold great potential in diagnosing SS, especially in early-stage SS without MR morphological changes. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1409-1417.


Global health education for medical students: New learning opportunities and strategies.
A new course was offered to introduce basic global health concepts to all first year Johns Hopkins medical students, that took advantage of new distance learning capacity to connect medical students in Baltimore with students and faculty in Uganda, Ethiopia, Pakistan and India. Lessons learned from the launch of this new course will optimize the conduct of future global health courses at JHUSOM and may be of value to other institutions. Feedback from the Hopkins students was obtained through an on-line structured course evaluation questionnaire. Unstructured student and faculty feedback from partners institutions was solicited via email. Students reported high levels of satisfaction with the course content and format, as well as achievement of course competencies and objectives. Distance learning can support unique, high-quality medical educational experiences that leverage technology and global connectivity, but also the power of group learning and "South-to-North" capacity building.


Immunolocalization of androgen receptor and estrogen receptors alpha and beta in human fetal testis and epididymis.
Expression and cellular localization of the androgen receptor (AR) and estrogen receptor (ER) isoforms were determined using antibodies specific to these receptors and to specific cell types. Gonads and genitourinary structures were removed from 5 human male fetuses 7 to 22 weeks of gestational age. Sections were stained with antibodies to AR, ERalpha and ERbeta, P450 scc and smooth muscle actin. AR was present in undifferentiated gonadal cells, peritubular myoid cells and in some Leydig and stromal cells at 7 weeks of gestation. The number of AR positive peritubular myoid cells remained constant through 22 weeks of gestation but the number of AR positive stromal cells continued to increase through 22 weeks. ERalpha was apparent by 12 weeks of gestation with perinuclear staining of Leydig cells, peaked at 16 weeks and then diminished. ERbeta was first observed at 7 weeks in undifferentiated gonadal cells. By 12 weeks of gestation ERbeta was apparent in germ cells, PTMC and Leydig cells. In the epididymis AR was expressed in the epithelium and stroma of the efferent ductules and the ductus epididymis by 7 weeks of gestation with increased expression by 12 weeks. A similar pattern of staining was observed for ERbeta. By contrast, staining of ERalpha was observed only in the epithelium of the epididymis from 7 weeks of gestation onward with no apparent ERalpha staining in the tail of the epididymis. These findings are compatible with the well-known roles of androgen signaling in sexual differentiation and spermatogenesis in humans. The role of estrogens in the developing human testis and epididymis remains unknown.


Detection of estrogen receptor by immunohistochemistry in pulmonary adenocarcinoma.
The distinction between primary adenocarcinoma and metastatic breast carcinoma in the lung is important for therapeutic purposes. There is a good deal of morphologic overlap between primary pulmonary adenocarcinoma and breast carcinoma metastatic in the lung. Many diagnosticians rely upon the presence of estrogen receptor (ER) in tumors of the lung in women in order to make a pathologic diagnosis of metastatic breast carcinoma. There are conflicting data in the literature regarding the presence of ER in lung carcinomas. In this study, we examined primary lung adenocarcinomas with monoclonal antibodies to two different clones to ER (clone 6F11 and clone 1D5), and progesterone receptor by the immunoperoxidase method in order to ascertain if ER is detectable in primary lung adenocarcinomas. Twenty-five resected solitary pulmonary nonmucinous bronchioalveolar carcinomas (15 female, 10 male) and 20 resected solitary pulmonary adenocarcinomas of no special type (12F, 8 mol/L) were studied by the immunohistochemical method using heat-induced epitope retrieval. Immunostaining was semiquantitated, and positive results included nuclear staining for ER and progesterone receptor. All of these tumors were documented as primary pulmonary adenocarcinomas clinically and pathologically. Nuclear ER was seen only with the 6F11 clone, in 56% of the bronchioalveolar type and 80% of the no special type. No nuclear ER was seen in carcinomas utilizing the 1D5 clone. There was no progesterone receptor detectable in carcinomas. Estrogen receptor is present in the majority of lung adenocarcinomas, and detection of ER in lung adenocarcinomas is dependent upon the antibody clone that is used. Epitope recognition may account for the differences in immunoreactivity between these two antibodies, although a cross-reactive antibody reaction cannot be completely excluded. Further study is warranted to discern the nature of the 6F11 clone immunoreactivity with nuclei of lung adenocarcinomas. The clinical significance and ramifications of ER in pulmonary adenocarcinomas remain unknown. Caution should be exercised by clinicians and pathologists in accepting a diagnosis of metastatic breast carcinoma in lung based on the presence of ER detected by clone 6F11.


Overview of missing data techniques.
Missing data frequently arise in the course of research studies. Understanding the mechanism that led to the missing data is important in order for investigators to be able to perform analyses that will lead to proper inference. This chapter will review different missing data mechanisms, including random and non-random mechanisms. Basic methods will be presented using examples to illustrate approaches to analyzing data in the presence of missing data.


Transvaginal iliococcygeus fixation for posthysterectomy vaginal vault prolapse repair.
Posthysterectomy vaginal vault prolapse repair is a surgical challenge. Successful surgical management using native tissue can be achieved via the vaginal approach by iliococcygeus fascia fixation. However, although iliococcygeus fascia fixation is technically simple and has a low morbidity, it is not commonly performed. The aim of the video is to provide anatomic views and the surgical steps necessary to achieve successful transvaginal iliococcygeus fascia fixation for vaginal vault prolapse repair. A 60-year-old woman with symptomatic stage III vaginal vault prolapse was admitted for transvaginal iliococcygeus fascia fixation according to the described technique. Surgery was successful without complications. The final examination showed good apical support and preservation of vaginal length. This step-by-step video tutorial may be an important tool to improve practical surgical knowledge. In particular, proper suture positioning requires adequate pararectal space preparation and levator ani exposure, as shown in the video. Transvaginal iliococcygeus fascia fixation is an alternative technique for apical support without the use of synthetic prosthetic materials. This technique may be indicated when an abdominal approach or a synthetic device is not recommended.


Rehabilitation of adult patients on extracorporeal membrane oxygenation: A scoping review.
The objective of this study was to conduct a scoping review to comprehensively map the breadth of literature related to the rehabilitation of adult patients whilst on extracorporeal membrane oxygenation (ECMO) and identify gaps and areas for future research. This review was conducted using recommended frameworks for methods and reporting including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We searched seven databases from inception to June 2021 and included all study designs and grey literature. Eligibility screening was completed by two independent reviewers according to inclusion and exclusion criteria, with any disagreement resolved by consensus or with consultation with a third reviewer. Two independent reviewers extracted data related to intervention characteristics, patient outcomes, feasibility, safety, hospital outcomes, and mortality using a custom-designed piloted form. Of 8507 records, 185 original studies met inclusion criteria, with the majority being small retrospective studies. Rehabilitation was more commonly reported in patients on veno-venous rather than veno-arterial ECMO. Ambulation was the most commonly reported intervention (51% of studies). Critical gaps were identified including incomplete reporting of the intervention along with heterogeneity in the type and timing of outcome measures. Less than 50% of patients met eligibility criteria to participate, but screening for eligibility was infrequently reported (9% of studies). Delivery of rehabilitation during ECMO may be facilitated by an expert multidisciplinary team, along with a strategy that targets low sedation levels and an upper body cannulation approach. Rehabilitation during ECMO is an emerging area of research and mostly consisted of small retrospective single-centre studies. Future research requires more robust methodological designs that include comprehensive screening of potential candidates with reporting of eligibility, more detailed descriptions of the rehabilitation interventions, inclusion of a core outcome set with defined measurement instruments, and consistent timing of outcome measurement.


Prediction of ground reaction forces during gait based on kinematics and a neural network model.
Kinetic information during human gait can be estimated with inverse dynamics, which is based on anthropometric, kinematic, and ground reaction data. While collecting ground reaction data with a force plate is useful, it is costly and requires regulated space. The goal of this study was to propose a new, accurate methodology for predicting ground reaction forces (GRFs) during level walking without the help of a force plate. To predict GRFs without a force plate, the traditional method of Newtonian mechanics was used for the single support phase. In addition, an artificial neural network (ANN) model was applied for the double support phase to solve statically indeterminate structure problems. The input variables of the ANN model, which were selected to have both dependency and independency, were limited to the trajectory, velocity, and acceleration of the whole segment's mass centre to minimise errors. The predicted GRFs were validated with actual GRFs through a ten-fold cross-validation method, and the correlation coefficients (R) for the ground forces were 0.918 in the medial-lateral axis, 0.985 in the anterior-posterior axis, and 0.991 in the vertical axis during gait. The ground moments were 0.987 in the sagittal plane, 0.841 in the frontal plane, and 0.868 in the transverse plane during gait. The high correlation coefficients(R) are due to the improvement of the prediction rate in the double support phase. This study also proved the possibility of calculating joint forces and moments based on the GRFs predicted with the proposed new hybrid method. Data generated with the proposed method may thus be used instead of raw GRF data in gait analysis and in calculating joint dynamic data using inverse dynamics.


Voiding cystourethrography with synchronous measurements of pressures and flow in the diagnosis of subvesical obstruction in men: a radiological view.
Cystourethrography with synchronous urodynamic monitoring was done in 90 men who were diagnosed radiologically as having normal function or bladder outlet obstruction. The separation was based on the caliber of the bladder outlet measured on spot roentgenograms at peak voiding: less than 4 mm. for obstructed and more than 6 mm for normal voiding. The radiological observations are discussed together with the measurements of bladder capacity, residual urine, intravesical pressures and voiding flow rate. The separation between normal men and those with obstruction according to radiologically determined calibers had a strong impact on the distribution of the maximum flow rates. Observations on the onset of micturition suggest that in normal voiding the contracting detrusor meets a simultaneously relaxing bladder neck without interposition of an isometric phase. The patients with subvesical obstruction presented with 2 forms of isometric overload, either as uninhibited contractions or as a variable isometric time lag between the onset of detrusor contraction and opening of the bladder neck. The pre-voiding isometric pressure increase is believed to be an abnormal finding that distinguishes the normal state from obstruction and other disorders. A characteristic decrease in subtracted intravesical pressure at the opening of the bladder neck in patients with uninhibited contractions conceivably indicates that bladder instability is caused by an abnormal reflex originating in the tightened bladder neck. Voiding cystourethrography was an accurate means of diagnosis of subvesical obstruction, especially owing to its ability to quantitate the caliber of a narrowed zone.


Oral acetaminophen-induced spinal 5-hydroxytriyptamine release produces analgesic effects in the rat formalin test.
The mechanism by which acetaminophen produces its analgesic effects is not fully understood. One possible mechanism is the activation of the spinal 5-hydroxytryptamine (5-HT) receptor, although direct evidence of spinal 5-HT release has not yet been reported. N-arachidonoylphenolamine (AM404), a metabolite of acetaminophen, is believed to be the key substance that contributes to the analgesic effects of acetaminophen. In this study, we examined whether acetaminophen and AM404 induce spinal 5-HT release and the mechanism through which spinal 5-HT receptor activation exerts analgesic effects in a rat formalin test in an inflammatory pain model. Spinal 5-HT release was examined by intrathecal microdialysis in conscious and freely moving rats. Acetaminophen was administered orally, and AM404 was administered intracerebroventricularly. In rat formalin tests, oral acetaminophen and intracerebroventricular AM404 induced significant spinal 5-HT release and produced analgesic effects. The analgesic effect of oral acetaminophen was partially antagonized by intrathecal administration of WAY100135 (a 5-HT1A receptor antagonist) and SB269970 (a 5-HT7 receptor antagonist). In contrast, the analgesic effect of intracerebroventricular AM404 was completely antagonized by WAY100135, while SB269970 had no effect. Our data suggest that while oral acetaminophen and intracerebroventricular AM404 activate the spinal 5-HT system, the role of the spinal 5-HT system activated by oral acetaminophen differs from that activated by intracerebroventricular AM404.


Improved monitoring framework for local planning in the water, sanitation and hygiene sector: From data to decision-making.
Today, a vast proportion of people still lack a simple pit latrine and a source of safe drinking water. To help end this appalling state of affairs, there is a pressing need to provide policymakers with evidences which may be the basis of effective planning, targeting and prioritization. Two major challenges often hinder this process: i) lack of reliable data to identify which areas are most in need; and ii) inadequate instruments for decision-making support. In tackling previous shortcomings, this paper proposes a monitoring framework to compile, analyze, interpret and disseminate water, sanitation and hygiene information. In an era of decentralization, where decision-making moves to local governments, we apply such framework at the local level. The ultimate goal is to develop appropriate tools for decentralized planning support. To this end, the study first implements a methodology for primary data collection, which combines the household and the waterpoint as information sources. In doing so, we provide a complete picture of the context in which domestic WASH services are delivered. Second, the collected data are analyzed to underline the emerging development challenges. The use of simple planning indicators serves as the basis to i) reveal which areas require policy attention, and to ii) identify the neediest. Third, a classification process is proposed to prioritize among various populations. Three different case studies from East and Southern African countries are presented. Results indicate that accurate and comprehensive data, if adequately exploited through simple instruments, may be the basis of effective targeting and prioritization, which are central to sector planning. The application of the proposed framework in the real world, however, is to a certain extent elusive; and we point out to conclude two specific challenges that remain unaddressed, namely the upgrade of existing decision-making processes to enhance transparency and inclusiveness, and the development of data updating mechanisms.


The Painful Long Head of the Biceps Brachii: Nonoperative Treatment Approaches.
The long head of the biceps has garnered increased attention and interest due to the high prevalence of pain that can be a primary condition or occur secondary to shoulder dysfunction. The successful treatment of biceps tendinopathy is dependent on an accurate diagnosis and recognizing all causative factors. The treatment program will be individualized with a rehabilitation program designed to restore strength and flexibility and restore normal tendon mechanics.


Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice.
Precursors for Thy-1(+) dendritic epidermal T cells (DETC) develop as Vgamma3(+) T cells in the fetal thymus and become distributed in the adult skin. DETC are variably distributed from site to site and from strain to strain. To elucidate the basis of strain variation, we first compared the density of DETC in the ear epidermis among different mouse strains. In the ear epidermis, we detected the highest level of DETC in C57BL/6 mice, intermediate levels in C3H and CBA/J mice, and the lowest levels in other strains including BALB/c and 129 mice. Although BALB/c and 129+Ter/Sv mice showed higher levels of DETC in the abdomen than in the ear, the levels were significantly lower than C57BL/6 mice. Furthermore, in neonatal abdominal epidermis we detected considerably lower numbers of DETC in BALB/c and 129+Ter/Sv mice than in C57BL/6 mice. In contrast, Vgamma3(+) DETC precursors in the fetal thymus are rather increased in 129+Ter/Sv mice. These results suggest that fewer DETC precursors are seeded in the neonatal skin of BALB/c and 129+Ter/Sv mice and that their expansion in the skin during neonatal to adult stages does not reach the levels in C57BL/6 mice.


Finding activity through rigidity: syntheses of natural products containing tricyclic bridgehead carbon centers.
Covering: up to 2022Tricyclic bridgehead carbon centers (TBCCs) are a synthetically challenging substructure found in many complex natural products. Here we review the syntheses of ten representative families of TBCC-containing isolates, with the goal of outlining the strategies and tactics used to install these centers, including a discussion of the evolution of the successful synthetic design. We provide a summary of common strategies to inform future synthetic endeavors.


Radiofrequency tissue ablation: effect of hepatic blood flow occlusion on thermal injuries produced in cirrhotic livers.
Radiofrequency thermal ablation has been used as a treatment for several types of hepatic malignancies. Many of these lesions exist in the presence of cirrhosis. Limitations exist to the size of the ablations and, subsequently, the efficacy of treatment. Hepatic vascular inflow occlusion has been advocated as an adjunctive measure to increase the efficacy of the ablation. We present a model in the human cirrhotic liver that demonstrates the advantage of blood flow occlusion during radiofrequency ablation. Five patients with advanced endstage liver disease scheduled to have orthotopic liver transplantation were enrolled in this study. After laparotomy and before hepatectomy, radiofrequency ablation was performed without and with hepatic blood flow occlusion. After hepatectomy, the liver was sectioned, the area of ablation was measured in three dimensions, and the volume of ablation calculated. Three of the patients had had previously placed transjugular intrahepatic portosystemic shunt. The mean volume of the ablation without blood flow occlusion was 22.5 +/- 7.4 cm(3) and that with blood flow occlusion was 48.4 +/- 24.0 cm(3) (P =.05). Ablation area is increased significantly with hepatic blood flow occlusion in the human cirrhotic liver. This result may have application in the treatment of larger (>3 cm) hepatic malignancies.


The voltage-sensitive dye di-4-ANEPPS slows conduction velocity in isolated guinea pig hearts.
Voltage-sensitive dyes are important tools for mapping electrical activity in the heart. However, little is known about the effects of voltage-sensitive dyes on cardiac electrophysiology. To test the hypothesis that the voltage-sensitive dye di-4-ANEPPS modulates cardiac impulse propagation. Electrical and optical mapping experiments were performed in isolated Langendorff perfused guinea pig hearts. The effect of di-4-ANEPPS on conduction velocity and anisotropy of propagation was quantified. HeLa cells expressing connexin 43 were used to evaluate the effect of di-4-ANEPPS on gap junctional conductance. In electrical mapping experiments, di-4-ANEPPS (7.5 μM) was found to decrease both longitudinal and transverse conduction velocities significantly compared with control. No change in the anisotropy of propagation was observed. Similar results were obtained in optical mapping experiments. In these experiments, the effect of di-4-ANEPPS was dose dependent. di-4-ANEPPS had no detectable effect on connexin 43-mediated gap junctional conductance in transfected HeLa cells. Our results demonstrate that the voltage-sensitive dye di-4-ANEPPS directly and dose-dependently modulates cardiac impulse propagation. The effect is not likely mediated by connexin 43 inhibition. Our results highlight an important caveat that should be taken into account when interpreting data obtained using di-4-ANEPPS in cardiac preparations.


Incidence and management of gastrointestinal bleeding with continuous flow assist devices.
Continuous flow left ventricular assist devices (CF-LVADs) have emerged as the standard of care for patients in advanced heart failure (HF) requiring long-term mechanical circulatory support. Gastrointestinal (GI) bleeding has been frequently reported within this population. A retrospective analysis of 101 patients implanted with the Heart Mate II from January 2005 to August 2011 was performed to identify incidence, etiology, and management of GI bleeding. Univariate and multivariate regression analysis was conducted to identify related risk factors. A significant incidence of GI bleeding (22.8%) occurred in our predominantly destination therapy (DT) (93%) population. Fifty-seven percent of the patients with bleeding episodes bled from the upper GI (UGI) tract (with 54% bleeding from gastric erosions and 37% from ulcers/angiodysplasias), whereas 35% of patients bled from the lower GI (LGI) tract. Previous history of GI bleeding (odds ratio [OR], 22.7; 95% CI, 2.2-228.6; p=0.008), elevated international normalized ratio (INR) (OR, 3.9; CI, 1.2-12.9; p=0.02), and low platelet count (OR, -0.98; CI, 0.98 -0.99; p=0.001) were independent predictors of GI hemorrhage. Recurrent bleeding was more common in older patients (mean, 70 years; p=0.01). The majority of bleeders (60%) rebled from the same site. Management strategies included temporarily withholding anticoagulation, decreasing the speed of LVADs, and using octreotide. Octreotide did not impact the amount of packed red blood cells used, rebleeding rates, length of hospital stay, or all-cause mortality. Only 1 patient died as a direct consequence of GI bleeding. Multiple factors account for GI bleeding in patients on CF-VADs. A previous history of bleeding increases risk significantly and warrants careful monitoring.


Chemical modification and composition of tetrameric isozyme K of alkaline phosphatase from harp seal intestinal mucosa.
1. The carbohydrate content of isozyme K of alkaline phosphatase (EC 18.104.22.168) from harp seal intestinal mucosa was examined. The presence of N-acetylglucosamine, N-acetylgalactosamine and considerable amounts of mannose residues was shown. 2. The amino acid content of seal alkaline phosphatase was determined. A high extent of homology (85%) between bovine and seal alkaline phosphatases was demonstrated. 3. By chemical modification lysine, dicarboxylic acids, arginine and tyrosine residues of tetrameric seal alkaline phosphatase are located near or at the active site. By contrast, the modification of either thiol or imidazole groups resulted in no alterations of the enzyme activity. 4. It has been demonstrated that inorganic phosphate is an inhibitor of alkaline phosphatase and entirely prevents the enzyme inactivation with succinic anhydride.


Quantification of [11C]GB67 binding to cardiac alpha1-adrenoceptors with positron emission tomography: validation in pigs.
An increase in human cardiac alpha(1)-adrenoceptor (alpha(1)-AR) density is associated with various diseases such as myocardial ischemia, congestive heart failure, hypertrophic cardiomyopathy and hypertension. Positron emission tomography (PET) with an appropriate radioligand offers the possibility of imaging receptor function in the normal and diseased heart. [(11)C]GB67, an analogue of prazosin, has been shown in rats to have potential as a PET ligand with high selectivity to alpha(1)-AR. However, alpha(1)-AR density is up to ten times higher in rat heart compared to that in man. The aim of the present preclinical study was to extend the previous evaluation to a large mammal heart, where the alpha(1)-AR density is comparable to man, and to validate a method for quantification before PET studies in man. Seven [(11)C]GB67 PET studies, with weight-adjusted target dose of either 5.29 MBq kg(-1) (pilot, test-retest and baseline-predose studies) or 8.22 MBq kg(-1) (baseline-displacement studies), were performed in four anaesthetised pigs (39.5 +/- 3.9 kg). Total myocardial volume of distribution (V (T)) was estimated under different pharmacological conditions using compartmental analysis with a radiolabelled metabolite-corrected arterial plasma input function. A maximum possible blocking dose of 0.12 mumol kg(-1) of unlabeled GB67 was given 20 min before [(11)C]GB67 administration in the predose study and 45 min after administration of [(11)C]GB67 in the displacement study. In addition, [(15)O]CO (3,000 MBq) and [(15)O]H(2)O, with weight adjusted target dose of 10.57 MBq kg(-1), were also administered for estimation of blood volume recovery (RC) of the left ventricular cavity and myocardial perfusion (MBF), respectively. [(11)C]GB67 V (T) values (in ml cm(-3)) were estimated to be 24.2 +/- 5.5 (range, 17.3-31.3), 10.1 (predose) and 11.6 (displacement). MBF did not differ within each pig, including between baseline and predose conditions. Predose and displacement studies showed that specific binding of [(11)C]GB67 to myocardial alpha(1)-ARs accounts for approximately 50% of V (T). The present study offers a methodology for using [(11)C]GB67 as a radioligand to quantify human myocardial alpha(1)-ARs in clinical PET studies.


Spectrum of primary immune deficiency at a tertiary care hospital.
To report various primary immune deficiencies diagnosed in children at a tertiary care hospital, their clinical manifestations and laboratory profile. Case records of children diagnosed to have primary immunodeficiency disorders over a period of 24 months at a tertiary care hospital in northern India were evaluated. Twenty-seven children (M: F=3.5: 1) with mean age of 5.4 +/- 4.6 yrs (2 mo-16 yr) were diagnosed to have primary immunodeficiency. Thirteen children had chronic granulomatous disease (CGD), 4 had severe combined immunodeficiency (SCID), 4 had hypogammaglobulinemia, 2 had Ataxia telangiectasia, and one each had DiGeorge syndrome, Wiskott Aldrich syndrome, hyper IgM syndrome and leukocyte adhesion defect. Common mode of presentation were recurrent/ persistent pneumonia in 19, recurrent/ persistent diarrhea in 10, deep seated abscesses in 8, allergy in 3, disseminated tuberculosis infection in 2, extensive fungal infections in 2 and 1 each of disseminated cytomegalovirus (CMV) infection, disseminated BCG disease, otitis media and meningitis. Family history of sibling deaths was elicited in 2 families. Infectious agents were isolated in 16 cases. From a single center 27 patients with primary immune deficiency could be identified by chart review, suggesting need for high index of suspicion for diagnosis of primary immune deficiency in India. Though the exact prevalence is not known there is need to make a registry to document the magnitude of problem of these disorders.


A pH- and thermo-responsive poly(amino acid)-based drug delivery system.
A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N,N-diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed.


Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study.
To examine the relationship between hyperuricaemia, haemoconcentration and maternal and fetal outcomes in hypertensive pregnancies. Retrospective analysis of a database of hypertensive pregnancies. St George Hospital, a major obstetric unit in Australia. A cohort of 1880 pregnant women without underlying hypertension or renal disease, referred for management of pre-eclampsia or gestational hypertension. Demographic, clinical and biochemical data at time of referral and delivery were collected for each pregnancy. Women were grouped according to diagnosis (pre-eclampsia or gestational hypertension) and logistic regression analysis was used to determine the relationship between uric acid, haemoglobin, haematocrit and adverse outcomes; an α level of P < 0.01 was used for statistical significance. Composites of adverse maternal and fetal outcomes. In women with 'benign' GH (without proteinuria or any other maternal clinical feature of pre-eclampsia) gestation-corrected hyperuricaemia was associated with increased risk of a small-for-gestational-age infant (OR 2.5; 95% CI 1.3-4.8) and prematurity (OR 3.2; 95% CI 1.4-7.2), but not with adverse maternal outcome. In the whole cohort of hypertensive pregnant women (those with pre-eclampsia or gestational hypertension) the risk of adverse maternal outcome (OR 2.0; 95% CI 1.6-2.4) and adverse fetal outcome (OR 1.8; 95% CI 1.5-2.1) increased with increasing concentration of uric acid. Hyperuricaemia corrected for gestation provided additional strength to these associations. Haemoglobin and haematocrit were not associated with adverse pregnancy outcome. Hyperuricaemia in hypertensive pregnancy remains an important finding because it identifies women at increased risk of adverse maternal and particularly fetal outcome; the latter, even in women with gestational hypertension without any other feature of pre-eclampsia.


Magnitude and determinants of body dysmorphic disorder among female students in Saudi public secondary schools.
Recent estimates have indicated that the weighted community prevalence of body dysmorphic disorder (BDD) is rising. This study aimed to identify the prevalence and determinants of BDD among female adolescents in Jeddah, KSA. A cross-sectional study was conducted among female students in governmental secondary schools. Students presenting with abnormal health conditions were excluded. A multi-stage stratified sampling technique was used to select the target number of students (N = 495). BDD screening was performed using a BDD questionnaire. The students' mean (standard deviation) age was 16.78 (1.11) years, and the prevalence of BDD was 12.3% (95% confidence interval: 9.6-15.5%). The body parts associated with the most concern were the skin (18.4%), hair (10.7%), teeth (9.9%), and nose (9.5%). Psychosocial assessment showed that the body part of concern was associated with sadness in 20.6%, avoidance reactions in 17.6%, and problems in school, work, or other activities in 3.8% while playing a role in social relationships in 21.5%. The aspects associated with the highest risk included the skin (odds ratio (OR) = 8.33, p < 0.001), followed by body fat (OR = 8.17, p < 0.001) and the nose (OR = 7.35, p < 0.001). With the number of affected body parts, the prevalence of BDD increased from 21.7% (one body part) to 60%. In this study, BDD was a common, difficult-to-recognise disorder with a prevalence of one in eight female Saudi adolescents. It was associated with marked changes in social interactions, self-esteem, and quality of life.


Development and validation of five behavioral indices of flood adaptation.
In the current context of climate change, climate forecasts for the province of Quebec (Canada) are a lengthening of the thunderstorm season and an increase in episodes of intense precipitations. These changes in the distribution of precipitations could heighten the intensity or frequency of floods, a natural hazard that concerns 80% of Quebec's riverside municipalities. For the health and safety of the at-risk population, it is very important to make sure they have acquired necessary adaptive behaviors against flooding hazard. However, there has been no assessment of these flood adaptation behaviors to date. Thus, the aim of this study was to develop and validate five indices of adaptation to flooding. A sample of 1951 adults completed a questionnaire by phone. The questionnaire, specifically developed for this study, measured whether they did or did not adopt the behaviors that are proposed by public health officials to protect themselves against flooding. The results of the item, confirmatory factor, and multiple correspondence analyses contributed to the development of five indices corresponding to the adaptation behaviors to adopt according to the chronology of events: (a) pre-alert preventive behaviors, (b) behaviors to carry out after the alert is issued, (c) behaviors to adopt during a flood not requiring evacuation, (d) behaviors to adopt during a flood requiring evacuation, and (e) post-flood behaviors. The results of this study also showed that people who perceive a risk of flooding in their home in the next 5 years tend to adopt more preventive behaviors and adaptation behaviors than those who perceive little or no risk at all. They also reveal that people who feel more adverse effects on their physical or mental health tend to adopt more adaptive behaviors than those who feel little or no adverse effects on their health. Across a series of psychometric analyses, the results showed that these flood adaptation indices could properly measure a vast range of adaptive behaviors according to the chronology of events. Therefore, researchers, public health agencies, and professionals can use them to monitor the evolution of individuals' adaptive behaviors during floods.


Comparison of cone-beam computed tomography cephalometric measurements using a midsagittal projection and conventional two-dimensional cephalometric measurements.
This study investigated whether it is possible to use a two-dimensional (2D) standard in three-dimensional (3D) analysis, by comparing the angles and lengths measured from a midsagittal projection in 3D cone-beam computed tomography (CBCT) with those measured by 2D lateral cephalometric radiography (LCR). Fifty patients who underwent both LCR and CBCT were selected as subjects. CBCT was reoriented in 3 different methods and the measuring-points were projected onto the midsagittal plane. Twelve angle values and 8 length values were measured on both LCR and CBCT and compared. Repeated measures analysis of the variance revealed statistically significant differences in 7 angular and 5 linear measurements among LCR and 3 types of CBCT (p < 0.05). Of these 12 measurements, multiple comparisons showed that 6 measurements (ANB, AB to FH, IMPA, FMA, Co-Gn, Go-Me) were not significantly different in pairwise comparisons. LCR was significantly different from 3 types of CBCT in 3 angular (SN to FH, interincisal angle, FMIA) and 2 linear (S-Go, Co-ANS) measurements. The CBCT method was similar for all measurements, except for 1 linear measurement, i.e., S-N. However, the disparity between the mean values for all parameters was within the range of clinical measurement error. 3D-CBCT analysis, using midsagittal projection, is a useful method in which the 2D-LCR normative values can be used. Although the measurements changed with reorientation, these changes were not clinically significant.


Fatigue accumulation and twitch potentiation during complex MVC-relative profiles.
Fatigue accumulation can be significantly influenced by post-activation potentiation (PAP). This phenomenon leads to increased force generating capacity after a series of conditioning efforts. The purpose of our study was to examine how the order of force demands impacted muscle fatigue accumulation, and how fatigue was affected by potentiation. We had 33 participants complete one of four different force orders, consisting of 5 cycles of 12-s submaximal isometric "task plateaus". Every order consisted of 8 force plateaus of the different intensity, arranged in a different ways. A subset of 18 participants then received a stimulated muscle twitch, and all participants performed a brief MVC. Each task plateau was followed by a 12s long 10% MVC "reference plateau" also followed by twitch and MVC. Overall, the order of the force presentation only had an impact on fatigue levels and twitch potentiation during the first cycle. Maximum voluntary forces decreased, and twitch forces increased, at different rates between orders during the first cycle. At the end of each cycle, there was no difference between any of the orders in terms of twitch potentiation or decrease in MVC force. In a task that features identical force patterns, arranged in different orders, the order did not affect the final fatigue accumulation or potentiation level.


Who's got the global advantage? Visual field differences in processing of global and local shape.
Much evidence suggests that we first perceive the overall layout of a scene or object followed later by the details. This coarse-to-fine temporal dynamic in visual processing is also found in Navon's classical paradigm where information at the global level of compound stimuli is processed faster than information at the local level (global precedence effect), and where information at the global level has larger effects on local level responses than local level information has on global level responses (asymmetric interference effects). Traditionally, global shape primacy in Navon's paradigm has been linked with a right hemisphere preference (left visual field advantage) for global shape processing, and a left hemisphere preference (right visual field advantage) for local shape processing. This link, however, has been based on measures which confound global precedence and interference effects. Indeed, when these measures are de-confounded, we find no evidence for larger global precedence effects in the left compared with the right visual field in a large sample of participants (N = 337). In comparison, global-to-local interference effects are found to be stronger in the left than in the right visual field. We argue that these findings can be accounted for by assuming that the right hemisphere plays a special role in integrating shape information across spatial scales, that is, without assuming the existence of a right hemisphere preference for global shape processing per se.


Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.
The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and safety results observed in children warrants further studies on FDC of arterolane maleate and PQP dispersible tablets. Clinical Trial Registry India: CTRI/2009/091/000531.


Role of Probiotics for Recurrent UTIs in the Twenty-First Century: a Systematic Review of Literature.
Urinary tract infections (UTIs) are a common problem, especially in women. Recurrent UTIs (rUTIs) are difficult to treat and while prophylactic antibiotics can be an effective strategy, they worsen antimicrobial resistance and incur side effects. We conducted a systematic review of literature to assess the role of probiotics in management of UTIs. All English language articles reporting on randomised trials and cohort studies were selected, while paediatric patients (< 18 years) and patients with neurogenic bladders were excluded. A total of 9 articles (772 patients) met the inclusion criteria with a mean age of 34.2 years (range 18-65 years). A variety of different probiotics were used. Two studies concluded that probiotics could reduce risk of rUTIs; however, the remainder provided inconclusive results. A key advantage demonstrated, however, was the limited side effect profile and tolerance, which allows for good patient compliance with this treatment strategy. There exists only limited clinical evidence to support the role of probiotics in the management of rUTIs, and based on the current evidence, probiotics can be a potential measure to reduce rUTIs, although further randomised studies will help delineate its formal position in the treatment algorithm.


Health status and health care costs for publicly funded patients with schizophrenia started on clozapine.
The study examined the effect of clozapine treatment on the health care costs and health status of people with schizophrenia who are supported by public funds. Thirty-three patients with schizophrenia hospitalized in a state facility were interviewed within one week of starting clozapine and six months later. Health status was assessed with four clinical rating scales measuring severity of psychopathology, negative symptoms, depression, and quality of life. Cost and health care utilization data were collected for the six months before and after initiation of clozapine. Only 52 percent of the subjects stayed on clozapine for six months. Subjects who continued on clozapine were more likely to be discharged within six months than those who did not continue. Six months after clozapine was started, health care costs showed a sayings of $11,464 per person, even after adjustment for pretreatment costs, and health status was improved. For subjects who continued on clozapine for six months, clozapine treatment was associated with reduced days of psychiatric hospital care, reduced overall costs despite increased outpatient treatment and residential costs, and improved health status.


Detection of mold on the food surface using YOLOv5.
The study aimed to identify different molds that grow on various food surfaces. As a result, we conducted a case study for the detection of mold on food surfaces based on the "you only look once (YOLO) v5" principle. In this context, a dataset of 2050 food images with mold growing on their surfaces was created. Images were obtained from our own laboratory (850 images) as well as from the internet (1200 images). The dataset was trained using the pre-trained YOLOv5 algorithm. A laboratory test was also performed to confirm that the grown organisms were mold. In comparison to YOLOv3 and YOLOv4, this current YOLOv5 model had better precision, recall, and average precision (AP), which were 98.10%, 100%, and 99.60%, respectively. The YOLOv5 algorithm was used for the first time in this study to detect mold on food surfaces. In conclusion, the proposed model successfully recognizes any kind of mold present on the food surface. Using YOLOv5, we are currently conducting research to identify the specific species of the detected mold.


Lifetime use of non-nicotine drugs in electronic cigarette devices among a sample of individuals in substance use disorder treatment.
Limited data are available on other substance use in e-cigarettes (OSUE). The aim of this research was to determine the prevalence and predictors of OSUE among a sample of individuals in substance use disorder (SUD) treatment. In 2019, we surveyed 553 individuals from 18 residential SUD treatment programs in California, USA. Individuals reporting any lifetime use of an e-cigarette containing nicotine (n = 279) were asked about ever use of drugs other than nicotine in their e-cigarette. Those who reported use of non-nicotine drugs in their e-cigarette also reported what psychoactive drugs were used. Among all the participants, 25 % (n = 139) . reported ever engaging in OSUE. The most common drugs used in vaping devices were marijuana/THC/hash, (70.5 %, n = 98) and amphetamines/methamphetamine (51.1 %, n = 71). Among those who had engaged in OSUE, 44.6 % (n = 62) had vaped drugs for which they sought treatment. Older persons (OR = 0.93, CI 0.91, 0.95) and African Americans (OR = 0.48, CI 0.24, 0.94) were less likely to have ever engaged in OSUE, while persons in treatment for opioid use were more likely (OR = 1.71, CI 1.08, 2.71). Among a sample of clients in SUD treatment, about 25% had ever engaged in OSUE, with THC/marijuana and amphetamines most commonly reported. Further research is needed to evaluate the OSUE to understand the reasons for use and implications among persons enrolled in SUD treatment.


Laryngopharyngeal reflux disease with nocturnal gastric acid breakthrough while on proton pump inhibitor therapy.
Laryngopharyngeal reflux disease (LPRD) with nocturnal recovery of gastric acid secretion (nocturnal acid breakthrough: NAB) with proton pump inhibitors (PPI) was first reported. A 79-year-old Japanese woman complained of globus pharyngeus and mild heartburn was examined with the use of tetra-probe 24-h pH monitoring. She had been treated for reflux esophagitis (GERD) for 12 months prior to her visit to our office. She took Lansoprazole (30 mg/day) before dinner every day. The tetra-probe 24-h pH monitoring revealed that the recovery of gastric acid secretion occurred 6.5 h after taking the dose of PPI. The intragastric pH dropped < 4 at about 23:00 and remained below that level for 4 h and 50 min. The 24-h pH-metry at each probe showed that the nocturnal recovery of gastric acid secretion with PPI (NAB on PPI) influenced gastroesophageal and laryngopharyngeal refluxes. The symptoms of the pharynx and esophagus disappeared after taking H2 receptor antagonist (H2RA) additionally before bedtime.


Effect of Extended-Release Niacin on Carotid Intima Media Thickness, Reactive Hyperemia, and Endothelial Progenitor Cell Mobilization: Insights From the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial.
Thirty-eight patients with intermediate (30%-60% diameter stenosis) saphenous vein graft lesions were randomized to extended-release niacin (ER-niacin) or placebo for 12 months. We sought to evaluate the impact of ER-niacin on carotid intima media thickness (CIMT), endothelial function, and endothelial progenitor cell (EPC) mobilization. Carotid B-mode ultrasound was used to image the common and internal carotid arteries, at baseline and at 12 months after enrollment. Reactive hyperemia peripheral arterial tonometry, as assessed with EndoPAT 2000 (Itamar Medical, Inc) and EPC mobilization assessed with flow cytometry, were measured at enrollment, and at 1 and 12 months. The baseline clinical characteristics were similar in the two study groups. High-density lipoprotein cholesterol levels tended to increase more in the ER-niacin group (5.9 ± 8.7 mg/dL vs 1.4 ± 7.1 mg/dL; P=.14). Between baseline and 12 months, right common carotid artery (0.96 ± 0.44 mm vs 0.70 ± 0.24 mm; P=.04), and left common carotid artery (0.80 ± 0.30 mm vs 0.70 ± 0.20 mm; P=.08) CIMT tended to decrease in the ER-niacin group, compared with no change in the placebo group. The change in logarithmic reactive hyperemia index between 1 month and 12 months was similar in patients receiving ER-niacin vs placebo (0.003 ± 0.12 vs -0.058 ± 0.12; P=.39), whereas EPC mobilization increased in the ER-niacin group and decreased in the placebo group (8.65 ± 28.41 vs -5.87 ± 30.23 EPC colony forming units/mL of peripheral blood; P=.02). ER-niacin did not have a significant impact on CIMT or endothelial function, but increased EPC mobilization.


Rotors Drift Toward and Stabilize in Low Power Regions in Heterogeneous Models of Atrial Fibrillation.
Atrial fibrillation (AF) afflicts more than 33 million people worldwide. Success of therapy strategies remains poor and better understanding of the arrhythmia and how to device more effective therapies are needed. The aim of this work is to study the role of electric power distributions in rotors and AF dynamics. For this purpose, single cell and tissue simulations were performed to study the effect of ionic currents gradients and fibrosis in rotor's drifting. The root mean square of the ionic (Pion), capacitance (Pc) and electrotonic (Pele) power was computed over action potentials. Single cell simulations were performed for different values of IK1 and ICaL and number of coupled myofibroblasts. Tissue simulations were performed in presence of IK1 and ICaL gradients and diffused fibrosis. Single cell simulations showed that Pion and Pc increased with IK1, while decreased by increasing ICaL. Increasing the number of coupled myofibroblasts reduced Pion and Pc, whereas Pele increased. Finally, in tissue simulations rotors drifted to regions with low power and anchored in regions with higher density of blunted ionic induced power gradients.


Filtered dark-field and pure Z-contrast: two novel imaging modes in a Scanning Transmission Electron Microscope.
For the investigation of biological objects with a Scanning Transmission Electron Microscope (STEM) the dark-field imaging mode is the one used most often. We will show, regarding calculations that we have done which took into account the finite angle of the illumination and multiple scattering processes, that the collected amount of inelastically scattered electrons with an annular dark-field detector is higher then normally expected. According to the above calculations, we designed a new detection system to enable us to acquire three different images (inelastic, filtered dark-field and filtered bright-field) simultaneously.


[Restrictions in participation in women with fibromyalgia syndrome. An explorative pilot study].
Patients with fibromyalgia syndrome are often severely restricted in their ability to participate in everyday activities and in social interaction. The aim of this study was to document female patients' subjectively-perceived limitations in participation and to develop material to generate items for a specific participation questionnaire. We collected data from 8 groups of women with fibromyalgia syndrome (n=38), and developed a hierarchical system of categories using the patients' statements (ATLAS.ti; Qualitative Data Analysis). Our final group of categories contains 10 superordinate categories. Women with fibromyalgia syndrome often describe restrictions in their relationships with other people, and the impaired ability to engage in social and leisure activities. They speak of difficulties at the workplace, while doing housework, and complain about a lack of understanding and awareness on the part of the general public. Fibromyalgia syndrome patients admit to be extremely impaired in a variety of social roles. Their statements have enabled us to develop a questionnaire that reflects the range of factors restricting participation from the patient's perspective.


Atorvastatin attenuates cardiomyocyte loss in adult rats from protein-restricted dams.
Statins are cholesterol-lowering drugs that have been proved to prevent cardiac events. Their direct effects on cardiac remodeling, when administered in programmed protein restricted animals, still are unknown. Wistar male 6-month-old offspring from dams fed normal protein (NP, 19% of protein) or low-protein (LP, 5% of protein) during pregnancy and first 10 days after birth were studied. After weaning, male pups were allocated to untreated or treated groups with atorvastatin (low and high doses, 5 or 30 mg.kg.day) in two different periods (from 21 days old to 3 months old and from 3 to 6 months old). The blood pressure (BP) was 30% greater in untreated LP offspring than in treated offspring (from 165 +/- 6 mm Hg to 127 +/- 3 mm Hg, P < .01). After 1 month of treatment, only untreated LP offspring continued with high BP. Compared with untreated LP offspring, atorvastatin reduced blood glucose (less 30%, P < .05) and cardiomyocyte size (less 24%, P < .05), whereas untreated LP offspring had greater interstitial fibrosis (plus 74%, P < .01), reduction of myocardial vascularization (less 25%, P < .01) and major reduction of cardiomyocyte number (less 38%, P < .01) than treated LP offspring. Atorvastatin from 3 to 6 months olds in both low and high doses (but not from 0 to 3 months) has beneficial effects improving myocardial vascularization by diminishing fibrosis and cardiomyocyte loss.


The healing characteristics of autogenous saphenous vein used in the reconstruction of previously implanted arterial saphenous vein grafts.
Aortocoronary saphenous vein grafts with early isolated stenoses pose the technical problem of how to deal with these grafts at reoperation. The advisability of using a portion of old graft when reconstructing these grafts was examined. An experimental model was devised in which the anatomical and pathological interfaces between fresh vein and previously inserted vein were studied. Superficial femoral artery from the thigh of 15 dogs was replaced by reversed autogenous saphenous vein. Four months later, the animals were divided into two groups. Group 1 consisted of 8 animals that underwent transection and reimplantation of the middle 4 cm of the vein graft in exactly the same position in which it had been. In Group 2, the 7 animals had the middle 4 cm of the graft replaced with newly harvested reversed saphenous vein. Six months after initial vein graft implantation, the animals were studied. No critical stenoses were seen in the grafts. Pathological study of Group 1 grafts revealed fibrous graft disease of uniform severity throughout the graft, thereby demonstrating that new anastomoses in an old graft do not affect graft disease. Group 2 grafts revealed that the severity of disease in the new interposed segment of the vein graft was less than in the old retained portions of the graft. No untoward reaction causing acceleration of graft disease occurred between old and new vein. Operations using undiseased portions of old vein grafts should be considered a viable option in repeat coronary revascularization for early stenoses.


A qualitative study exploring the influence of a talent management initiative on registered nurses' retention intentions.
The aim of this study is to explore the influence of a talent management scheme in an English National Health Service (NHS) Trust on registered nurses' retention intentions. The retention of nurses is a global challenge, and talent management initiatives can play a role in improving retention. Talent management in its broadest sense is a way in which an organization recruits and retains the workforce that it needs to optimize the services it delivers. In this qualitative study, eight in-depth semi-structured interviews were conducted with registered nurses who had participated in a talent management initiative, at an English acute NHS Trust. Data were collected in July 2019. The talent management initiative influenced positive retention intentions. Retention of nurses was facilitated by the creation of networks and networking. Networks and networking can be viewed as a form of social capital, which was a facilitating factor for positive retention intentions for nurses. Talent management initiatives for nurses should be developed and directed to include the building of networks and networking to enable development of social capital. Although this talent management scheme is within the NHS, the issue of nursing retention is global. Application of learning from this paper to other health care systems is possible.


Tumor necrosis factor-alpha and interleukin-1beta mediate the production of nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic cystitis in mice.
We investigated the participation of nitric oxide in ifosfamide induced hemorrhagic cystitis in mice, and the involvement of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in the induction of nitric oxide production in this model. Hemorrhagic cystitis was induced in mice by 100 to 400 mg./kg. ifosfamide and evaluated 6, 12, 24 or 48 hours thereafter by certain parameters, including vesical edema measurements, microscopic analysis and immunohistochemical testing for inducible nitric oxide synthase. Ifosfamide injected mice were pretreated with 10 to 40 mg./kg. of the nitric oxide synthesis inhibitor L-NG-nitroarginine methyl ester, 80 mg./kg. of mesna, a chemical antagonist of acrolein and the urotoxic metabolite of ifosfamide, 50 microl. antiserum against TNF-alpha and IL-1beta per mouse, 45 mg./kg. of the selective TNF-alpha synthesis inhibitor thalidomide or 200 mg./kg. of the TNF-alpha and IL-1beta synthesis inhibitor pentoxifylline. Ifosfamide induced vesical edema, which peaked 12 hours after ifosfamide injection. Microscopic analysis revealed vascular congestion, edema, hemorrhage, fibrin deposition, neutrophil infiltration and epithelial denudation. Inducible nitric oxide synthase immunolocalization demonstrated intense reactivity to inducible nitric oxide synthase in the cytoplasm of bladder epithelial cells, which showed diffuse necrosis. Pretreatment with mesna reduced the increases in vesical edema, while treatment with L-NG-nitroarginine methyl ester, antiserum to TNF-alpha or IL-1beta, thalidomide or pentoxifylline inhibited vesical edema and microscopic alterations. Antiserum treatments also inhibited the expression of inducible nitric oxide synthase in the urothelium. Nitric oxide produced by inducible nitric oxide synthase is involved in urothelial damage and in the inflammatory events leading to hemorrhagic cystitis after ifosfamide administration in mice. The induction of inducible nitric oxide synthase in the urothelium appears to depend on the synergistic effect of IL-1beta and TNF-alpha.


Application of NIRS to the quantity control of pharmaceuticals ketoprofen assay in different pharmaceutical formulae.
The possibility of using reflectance NIRS to assay 2-(benzoylphenyl)-propionic acid (Ketoprofen) in solid-state and gel preparations is investigated. The number of samples and amplitude of the percentage content distribution of the samples is examined in order to define the best possible calibration system.


Cardiac non-Hodgkin's lymphoma: clinical characteristics and trends in survival.
The purpose of this study was to describe the clinical characteristics and outcomes in cardiac non-Hodgkin's lymphoma (NHL). A retrospective analysis of 94 cases of NHL with biopsy-proven cardiac involvement in PubMed between 1990 and 2015. Among cases with cardiac involvement, diffuse large B-cell lymphoma was the most common histologic subtype (58%), followed by T-cell lymphoma (16%), Burkitt's lymphoma (9%), and small lymphocytic lymphoma (6%). Symptomatic heart failure was the most common clinical presentation (34%), and 20% of patients had no cardiac symptoms. Median survival was 3 months (range, 0-72) among all patients. Patients who presented with heart failure had inferior outcomes. Patients with primary, vs. secondary, cardiac involvement had a trend toward superior outcomes. Importantly, chemotherapy treatment was associated with a prolongation in median survival (18 vs. 1 month, HR 0.16, 95% CI, 0.47-0.54, P = 0.0003), and patients diagnosed in the chemo-immunotherapy era demonstrated a trend toward better outcomes. Median survival was not reached among patients with B-cell malignancies who were alive for 1 month after the diagnosis. Pathologic lymphomatous involvement of cardiac tissue should be considered in the evaluation of patients with NHL. Durable remissions can be achieved in B-cell NHL with cardiac involvement, and thus, therapy should be considered in such cases.


GB virus-C--a virus without a disease: we cannot give it chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is an illness in search of an infectious etiology. GB virus-C (GBV-C) virus is a flavivirus with cell tropism and host defense induction qualities compatible with a role in producing the syndrome. The GBV-C genome is detectable in 4% of the population and 12% of the population is seropositive. The present study evaluated the association between infection with GBV and CFS. We used a commercial EIA to detect antibodies against the GBV-C E2 protein and a quantitative real-time RT-PCR assay to detect active GBV-C infection. Sera were from a case control study of CFS in Atlanta, Georgia. The Fisher's exact two-tailed test was used for statistical analysis. Two of 12 CFS patients and one of 21 controls were seropositive for prior GBV-C infection and one control had viral RNA detected, indicating active infection. The results are not statistically different. We found no evidence that active or past infection with GBV is associated with CFS.


Anthelmintic activity of continuous low doses of fenbendazole into the rumen of sheep.
Fenbendazole (FBZ) was continuously infused for 30 days into the rumen of 103 lambs which had mature or developing benzimidazole-susceptible or thiabendazole-resistant Haemonchus contortus and susceptible Trichostrongylus colubriformis infections. Ovicidal, larvicidal and adulticidal activities were exhibited against benzimidazole-susceptible and benzimidazole-resistant H. contortus worms by FBZ at a dose level of greater than or equal to 0.2 mg kg-1 body weight day-1. Reasonably consistent high level efficacy against H. contortus was obtained with dose levels greater than 0.4 mg kg-1. Excellent control of susceptible T. colubriformis worms was achieved with the lowest dose tested of 0.4 mg kg-1 day-1. The intraruminal infusion critical study method is a tool to determine the feasibility of incorporating a candidate anthelmintic compound in a continuous sustained-release rumen device formulation. The anthelmintic profile of FBZ obtained by low-level intraruminal administration suggests that it would be a potential candidate.


Expert consensus on the attributes and competencies required for rural and remote junior physicians to work effectively in isolated indonesian communities.
Indonesian physicians working in rural and remote areas must be equipped not only with generic competencies but also with the attributes and skills necessary to provide health care services without compromising quality. This study sought to reach a consensus on the attributes and competencies that are viewed as essential and important for working effectively as an early career doctor in rural and remote practice in Indonesia. A two-round Delphi study was conducted by reference to 27 consenting physicians working in rural and remote Indonesia. Forty-three items covering 9 attributes and 34 competencies were sent to these physicians to be rated on a Likert scale ranging from 1 to 5 in terms of their importance for effective rural and remote practice. Nine attributes and 29 competencies progressed to Round 2. All nine attributes and 29 competencies were identified as essential or important for junior physicians' ability to be effective in their practice. The essential attributes included professional quality related to prioritising the rural community. The essential competencies included medical skills, professional behaviour, interprofessional skills, health promotion and connection to the rural community. The consensus thus reached on these essential and important attributes and competencies can inform curriculum development for the undergraduate and postgraduate training of junior rural and remote physicians.