Demarcated opacity in primary teeth increases the prevalence of molar incisor hypomineralization.
This cross-sectional study aimed to assess the prevalence of molar incisor hypomineralization (MIH) and its relationship with the number of primary teeth with developmental defects of enamel (DDE). A representative population-based sample of 731 schoolchildren was randomly selected from the public school system in Curitiba, Brazil. Schoolchildren aged 8 years with fully erupted permanent first molars and incisors were eligible for the study. MIH and DDE were classified by four calibrated examiners (kappa > 0.75) according to EAPD criteria and to the FDI-modified DDE index. Clinical data were collected in a school environment. Socioeconomic information was collected through a self-administered semistructured questionnaire applied to the children's caregivers. Statistical analyses were carried out using Poisson multiple regression with robust variance (α = 0.05). MIH prevalence was 12.1% (95%CI: 10-15), and opacities were the most prevalent defect. Socioeconomic factors were not associated with MIH. Children with demarcated opacity in primary teeth presented a higher prevalence of MIH than those without DDE in primary teeth. In the multiple analysis, the increase of one primary tooth affected by demarcated opacity increased the prevalence of MIH by 33% (PR = 1.33, 95%CI: 1.15-1.53, p < 0.001). Asian children had a higher prevalence of MIH (PR = 2.91, 95%CI: 1.08-8.09 p = 0.035) than did Caucasian children.Conclusion: Based on these findings, the prevalence of MIH in Curitiba was 12.1%. Demarcated opacity in primary teeth could be considered a predictor of MIH.


Impact of moderate blast exposures on thrombin biomarkers assessed by calibrated automated thrombography in rats.
Severe blast exposures are frequently complicated with fatal intracranial hemorrhages. However, many more sustain low level blasts without tissue damage detectable by brain imaging. To investigate effects of nonlethal blast on thrombin-related biomarkers, rats were subjected to two different types of head-directed blast: 1) moderate "composite" blast with strong head acceleration or 2) moderate primary blast, without head acceleration. Thrombin generation (TG) ex vivo after blast was studied by calibrated automated thrombography (CAT). In the same blood samples, we assessed maximal concentration of TG (TGmax), start time, peak time, mean time, and concentrations of protein markers for vascular/hemostatic dysfunctions: integrin α/β, soluble endothelial selectin (sE-selectin), soluble intercellular cell adhesion molecule-1 (sICAM-1), and matrix metalloproteinases (MMP)-2, MMP-8, and MMP-13. Blast remarkably affected all TG indices. In animals exposed to "composite" blast, TGmax peaked at 6 h (∼4.5-fold vs. control), sustained at day 1 (∼3.8-fold increase), and declined to a 2-fold increase over control at day 7 post-blast. After primary blast, TGmax also rose to ∼4.2-fold of control at 6 h, dropped to ∼1.7-fold of control at day 1, and then exhibited a slight secondary increase at 2-fold of control at day 7. Other TG indices did not differ significantly between two types of blast exposure. The changes were also observed in other microvascular/inflammatory/hemostatic biomarkers. Integrin α/β and sICAM-1 levels were elevated after both "composite" and primary blast at 6 h, 1 day, and 7 days. sE-selectin exhibited near normal levels after "composite" blast, but increased significantly at 7 days after primary blast; MMP-2, MMP-8, and MMP-13 slightly rose after "composite" blast and significantly increased (∼2-4-fold) after primary blast. In summary, CAT may have a clinical diagnostic utility in combination with selected set of microvascular/inflammatory biomarkers in patients subjected to low/moderate level blast exposures.


Hematuria in patients with Beta-thalassemia major.
Our information about renal involvement in beta-thalassemia major is limited. Recently, few studies have reported proteinuria, hypercalcuria, phosphaturia, and oversecretion of tubular damage markers; however, hematuria has not yet been meticulously studied in these patients. We investigated hematuria in patients with beta-thalassemia major. Urinalysis was performed in 500 patients with beta-thalassemia major under a regular blood transfusion program. In those with hematuria (at least 3 to 5 erythrocytes per high-power field) a second urinalysis was done at the next transfusion time. The patients ranged in age from 6 months to 32 years. The male-female ratio was 1.05:1. Hematuria was detected in 55 (10.6%), including 9.8% of those younger than 20 years and 20.0% of those older than 20 years. Hematuria was persistent in 79.2% of the second urinalyses. Sixty-four percent of the patients with hematuria were females. A blood transfusion program had been started during the first year of life in 81% percent of the patients with hematuria. Sterile pyuria was detected in 4% and proteinuria in 16% of the patients with hematuria, while these figures in patients without hematuria were 2.1% (P = .56) and 1.4% (P = .002), respectively. We found that in patients with beta-thalassemia major, the risk of hematuria rises with age. Moreover, proteinuria seems to be more common in those with hematuria. Further studies are needed to ascertain the importance of these findings.


Evolution of the HLA-DR1 gene family. Structural and functional analysis of the new allele "DR-BON".
The molecules of the MHC are highly polymorphic and involve in Ag presentation; their striking genetic polymorphism allows probable interactions with a large variety of antigenic fragments when these are presented to the TCR. It is therefore of interest to explore the extent of this polymorphism and the mechanisms of its generation. We have studied the class II HLA-DR blank allele DR-BON that has been previously defined by MLR, restriction fragment length polymorphism, and two-dimensional gel electrophoresis. A cDNA library was constructed from a DR-BON homozygous typing cell and cDNA corresponding to DR alpha- and DR beta-chains were sequenced. By comparison with other known alpha- and beta-chain sequences it is shown that the alpha-chain is invariant and the beta-chain differs from DR1 by only six nucleotides, clustered in the third variable region with three amino acid changes at position 67, 70, and 71. The short DNA stretch of sequence encoding the 67-71 region is also present in other DR alleles: DR4/Dw10, DRw13, and some DRw11 specificities. Therefore we propose that a gene conversion-like event has occurred between the DRB1 *0101 (DR1/Dw1) gene and one of these three DRB1 genes. Extensive typing has been performed with a DR-BON-specific 17-mer oligonucleotide. Cross-hybridization with other genes than the ones expected from DNA sequence comparison was not observed. A selected panel of DR-BON reactive T cell clones shows three patterns of reactivity. Some clones are strictly DR-BON specific; some cross-reacted with DRw13 and a few cross-reacted with other haplotypes. The role of different epitopes of the third variable region of HLA-DR beta chain in allo-reaction is discussed.


Solute-dependent activation of cell motility in strongly hypertonic solutions in Dictyostelium discoideum, human melanoma HTB-140 cells and walker 256 carcinosarcoma cells.
Published data concerning the effects of hypertonicity on cell motility have often been controversial. The interpretation of results often rests on the premise that cell responses result from cell dehydration, i.e. osmotic effects. The results of induced hypertonicity on cell movement of Dictyostelium discoideum amoebae and human melanoma HTB-140 cells reported here show that: i) hypertonic solutions of identical osmolarity will either inhibit or stimulate cell movement depending on specific solutes (Na(+) or K(+), sorbitol or saccharose); ii) inhibition of cell motility by hypertonic solutions containing Na(+) ions or carbohydrates can be reversed by the addition of calcium ions; iii) various cell types react differently to the same solutions, and iv) cells can adapt to hypertonic solutions. Various hypertonic solutions are now broadly used in medicine and to study modulation of gene expression. The observations reported suggest the need to examine whether the other responses of cells to hypertonicity can also be based on the solute-dependent cell responses besides cell dehydration due to the osmotic effects.


The natural history of recurrent hepatitis C and what influences this.
1. Liver failure and liver cancer from chronic hepatitis C are the most common indications for liver transplantation and numbers of both are projected to double over the next 20 years. 2. Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation and associated with accelerated progression to cirrhosis, graft loss and death. 3. Graft and patient survival is reduced in liver transplant recipients with recurrent HCV infection compared to HCV-negative recipients. 4. The natural history of chronic hepatitis C is accelerated following liver transplantation compared C, with 20% progressing to cirrhosis by 5 years. However, the rate of fibrosis progression is not uniform and may increase over time. 5. The rates of progression from cirrhosis to decompensation and from decompensation to death are also accelerated following liver transplantation. 6. Multiple host, donor and viral factors are associated with rapid fibrosis progression and HCV-related graft failure. 7. Over the last decade, graft and patient survival rates have improved following liver transplantation for non-HCV disease but not for HCV-cirrhosis. This may reflect worsening donor quality and changes in immunosuppression strategies over recent years. 8. Viral eradication by antiviral therapy prevents disease progression and improves survival. 9. The severity of recurrent hepatitis C at one year post-transplant predicts subsequent progression to cirrhosis. Annual protocol biopsies are recommended to help determine need for antiviral therapy. 10. The projected impact of recurrent hepatitis C on graft and patient survival can only be avoided by the development of safe and effective antiviral strategies which can both prevent initial graft infection and eradicate established hepatitis C recurrence.


Neurodevelopmental outcomes after initial childhood anesthetic exposure between ages 3 and 10 years.
Epidemiologic studies examining the association between anesthetic exposure and neurodevelopmental outcomes have primarily focused on exposures occurring under 3 years of age. In this study, we assess outcomes associated with initial anesthetic exposure occurring between 3 and 10 years of age. We used data from the Western Australian Pregnancy Cohort (Raine) Study to examine the risk of cognitive deficit at age 10 in children with initial anesthetic exposure between 3 and 5 years and between 5 and 10 years of age compared with children unexposed at those ages. The cohort included 2868 children born from 1989 to 1992 evaluated using a range of neuropsychological tests. A modified multivariable Poisson regression model was used to determine the adjusted association of initial anesthetic exposure in each age group with outcomes. Exposed and unexposed children were found to have similar neuropsychological test results except for the McCarron Assessment of Neuromuscular Development (MAND) motor function scores. Even after adjusting for demographic and comorbidity differences, children exposed to anesthesia had a higher risk of motor deficit after initial exposure between ages 3 and 5 years (adjusted risk ratio, 2.32; 95% confidence interval, 1.42-3.79) and between 5 and 10 years (adjusted risk ratio, 2.33; 95% confidence interval, 1.21-4.48) compared with unexposed children. Initial exposure to anesthesia after age 3 had no measurable effects on language or cognitive function. Decreased motor function was found in children initially exposed after age 3 even after accounting for comorbid illness and injury history. These results suggest that there may be distinct windows of vulnerability for different neurodevelopmental domains in children.


Lipoprotein particle size and concentration by nuclear magnetic resonance and incident type 2 diabetes in women.
Diabetic dyslipoproteinemia is characterized by low HDL cholesterol and high triglycerides. We examined the association of lipoprotein particle size and concentration measured by nuclear magnetic resonance (NMR) spectroscopy with clinical type 2 diabetes. This was a prospective study of 26,836 initially healthy women followed for 13 years for incident type 2 diabetes (n = 1,687). Baseline lipids were measured directly and lipoprotein size and concentration by NMR. Cox regression models included nonlipid risk factors (age, race, smoking, exercise, education, menopause, blood pressure, BMI, family history, A1C, and C-reactive protein). NMR lipoproteins were also examined after further adjusting for standard lipids. Incident diabetes was significantly associated with baseline HDL cholesterol, triglycerides, and NMR-measured size and concentration of LDL, IDL, HDL, and VLDL particles. The associations of these particles differed substantially by size. Small LDL(NMR) and small HDL(NMR) were positively associated with diabetes (quintile 5 vs. 1 [adjusted hazard ratios and 95% CIs], 4.04 [3.21-5.09] and 1.84 [1.54-2.19], respectively). By contrast, large LDL(NMR) and large HDL(NMR) were inversely associated (quintile 1 vs. 5, 2.50 [2.12-2.95] and 4.51 [3.68-5.52], respectively). For VLDL(NMR), large particles imparted higher risk than small particles (quintile 5 vs. 1, 3.11 [2.35-4.11] and 1.31 [1.10-1.55], respectively). Lipoprotein particle size remained significant after adjusting for standard lipids and nonlipid factors. In this prospective study of women, NMR lipoprotein size and concentrations were associated with incident type 2 diabetes and remained significant after adjustment for established risk factors, including HDL cholesterol and triglycerides.


Impulse Control Disorders in Dopamine Agonist-Treated Hyperprolactinemia: Prevalence and Risk Factors.
There are growing reports of dopamine agonist (DA)-induced impulse control disorders (ICDs) in hyperprolactinemic patients. However, the magnitude of this risk and predictive factors remain uncertain. To determine ICD prevalence and risk factors in DA-treated hyperprolactinemic patients compared to community controls. Multicenter cross-sectional analysis of 113 patients and 99 healthy controls. Participants completed a neuropsychological questionnaire consisting of the Depression Anxiety Stress Scale (DASS21), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP-S), Hypersexual Behavior Inventory (HBI), Hypersexual Behavior Consequences Scale and Social Desirability Response Set Scale. Demographic and clinical data were collated to determine ICD risk factors. Patients testing positive for an ICD were offered a semistructured psychological interview. Patients were more likely than controls to test positive by QUIP-S for any ICD (61.1 vs 42.4%, P = .01), hypersexuality (22.1 vs 8.1%, P = .009), compulsive buying (15.9 vs 6.1%, P = .041) and punding (18.6 vs 6.1%, P = 0.012), and by HBI for hypersexuality (8.0 vs 0.0%, P = 0.004). Independent risk factors were male sex (odds ratio [OR] 13.85), eugonadism (OR 7.85), Hardy's tumor score and psychiatric comorbidity (OR 6.86) for hypersexuality, and age (OR 0.95) for compulsive buying. DASS21 subset scores were higher in patients vs controls and in patients with vs without different ICDs. Only 19/51 (37.3%) interviewed patients were aware of the relationship between DAs and ICDs before the study. DA therapy poses a high, previously underestimated risk of ICDs, especially in the form of hypersexuality in eugonadal men.


Large Loop Excision of the Transformation Zone Versus True Cone Biopsy Electrode Excision: A Randomized Trial.
The aim of the study was to compare two conization techniques, large loop excision of the transformation zone (LLETZ), and true cone biopsy electrode excision (TCBEE) in women with cervical dysplasia. In a randomized clinical trial, we compared LLETZ and TCBEE in women undergoing surgical treatment of cervical dysplasia in a 1:1 ratio. The primary endpoint was resection margin status (RMS), secondary endpoints were fragmentation of the surgical specimen, resection volume, operation time, time to complete hemostasis, blood loss, intraoperative and postoperative complications, surgeon's preference, and patient's postoperative pain, estimated by an 11-level visual analog scale (nVAS11), and a 5-level pictogram. One hundred seventy-two women were randomized. No difference in the primary outcome, resection margin status, was observed between LLETZ and TCBEE (involved margins: 12/91 [13%] vs 7/81 [9%], respectively; p = .4). However, fragmentation rate (1 vs >1 fragment: 85 [93%] and 6 [7%] for LLETZ vs 63 [78%] and 18 [22%] for TCBEE; p = .004) and surgeon preference (nVAS11: 1 [0-2] vs 3 [1-7]; p < .001) favored LLETZ. Postoperative pain, however, was lower after TCBEE (nVAS11: 1 [0-3] vs 0 [0-2]; p = .02). The secondary outcome parameters resection volume, operation time, time to complete hemostasis, blood loss, intraoperative complications, and postoperative complications were not different between the study groups. In a multivariate analysis, age, body mass index, and parity did not affect the primary and secondary outcome parameters. LLETZ and TCBEE are equally safe and efficacious procedures, but specimen fragmentation and surgeon preference favor loop excision.


Cone-beam tomography with discrete data sets.
Sufficiency conditions for cone-beam data are well known for the case of continuous data collection along a cone-vertex curve with continuous detectors. These continuous conditions are inadequate for real-world data where discrete vertex geometries and discrete detector arrays are used. In this paper we present a theoretical formulation of cone-beam tomography with arbitrary discrete arrays of detectors and vertices. The theory models the imaging system as a linear continuous-to-discrete mapping and represents the continuous object exactly as a Fourier series. The reconstruction problem is posed as the estimation of some subset of the Fourier coefficients. The main goal of the theory is to determine which Fourier coefficients can be reliably determined from the data delivered by a specific discrete design. A Fourier component will be well determined by the data if it satisfies two conditions: it makes a strong contribution to the data, and this contribution is relatively independent of the contribution of other Fourier components. To make these considerations precise, we introduce a concept called the cross-talk matrix. A diagonal element of this matrix measures the strength of a Fourier component in the data, while an off-diagonal element quantifies the dependence or aliasing of two different components. One reasonable approach to system design is to attempt to make the diagonal elements of this matrix large and the off-diagonal elements small for some set of Fourier components. If this goal can be achieved, simple linear reconstruction algorithms are available for estimating the Fourier coefficients. To illustrate the usefulness of this approach, numerical results on the cross-talk matrix are presented for different discrete geometries derived from a continuous helical vertex orbit, and simulated images reconstructed with two linear algorithms are presented.


Adipokine gene expression in peripheral blood of adult and juvenile dermatomyositis patients and their relation to clinical parameters and disease activity measures.
Recently adipokines have been implicated in the regulation of immune and inflammatory responses in autoimmune disease. To investigate the role of adipokines in adult and pediatric patients with newly diagnosed dermatomyositis (DM), we analyzed peripheral blood and skeletal muscle gene expression of four adipokines: visfatin, leptin, adiponectin and resistin. Peripheral blood mononuclear cells (PBMCs) were collected for 21 adult DM, 26 juvenile DM, 5 non-disease adult controls, and 6 non-disease pediatric controls at two time points: baseline and 6 months. Muscle biopsies from 5 adult DM patients and 5 non-disease adult controls were collected at baseline. Similarly, muscle biopsies from 7 juvenile DM patients and 5 non-disease pediatric controls were collected at baseline. The gene expression levels of leptin, adiponectin, resistin, visfatin and related inflammatory cytokines, IL-6, TNF- α, and housekeeping genes GAPDH, B2M, and ACTB were generated using a custom RT(2) Profiler PCR Array. Visfatin gene expression levels in peripheral blood were significantly higher in newly diagnosed adult DM cases compared to non-disease controls (P = 0.004) and these levels correlated with baseline clinical parameters such as age (r = 0.34, P = 0.020), male sex (r = -0.35, P = 0.017), prednisone use (r = -0.42, P = 0.006), and DMARD use (r = 0.35, P = 0.025). No significant association was found between change in visfatin gene expression levels and change in disease activity measures. While visfatin gene expression was significantly up-regulated in muscle tissue of juvenile DM patients (P = 0.028), in adult DM patients only a trend towards significance was observed (P = 0.08). Also, muscle gene expression levels of resistin were significantly elevated in both adult and juvenile DM patients compared respectively to non-disease adult and pediatric controls. Furthermore, an association between peripheral blood resistin gene expression and DM disease activity, including global, muscle, and extra-skeletal disease activity was also observed. Peripheral blood visfatin gene expression and muscle resistin gene expression are significantly increased in newly diagnosed adult DM patients. Further longitudinal studies should explore the possibility of using gene expression levels of adipokines such as visfatin and resistin as novel clinical diagnostic biomarkers in DM.


Phytoestrogen content of purified, open- and closed-formula laboratory animal diets.
Phytoestrogens exert estrogenic effects on the central nervous system, induce estrus, and stimulate growth of the genital tract of female animals. Over 300 plants and plant products, including some used in laboratory animal diets, contain phytoestrogens. Therefore, the source and concentration of phytoestrogens in rodent diets were determined. Twelve rodent diets and six major dietary ingredients were assayed for phytoestrogens (daidzein, genistein, formononetin, biochanin A, and coumestrol), using high-performance liquid chromatography. Three rodent diets recently formulated to reduce phytoestrogen content also were assayed. Formononetin, biochanin A, and coumestrol were not detected. Soybean meal was the major source of daidzein and genistein; their concentrations were directly correlated to the percentage of soybean meal in each diet. High, variable concentrations of daidzein and genistein are present in some rodent diets, and dietary phytoestrogens have the potential to alter results of studies of estrogenicity. Careful attention should be given to diet phytoestrogen content, and their concentration should be reported. A standardized, open-formula diet in which estrogenic substances have been reduced to levels that do not alter results of studies that are influenced by exogenous estrogens is recommended.


The prevalence and persistence of depression and anxiety following myocardial infarction.
OBJECTIVES: This study was designed to assess the prevalence and persistence of symptoms of depression and anxiety during the first 12 months following acute myocardial infarction (MI). DESIGN AND METHODS: In a prospective study, 288 MI patients were assessed for symptoms of depression and anxiety using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) in hospital, 2-15 days following MI, and 4 and 12 months subsequently. RESULTS: During hospitalization, 89 (30.9%) and 75 (26.1%) patients registered elevated BDI scores (>/=10) and state anxiety scores (>/=40), respectively. The 4 and 12 month prevalence rates were 37.7% and 37.2% for depressive symptoms, and 41.8% and 40.0% for anxious symptoms, respectively. Depression and anxiety were highly co-morbid, with 51% of patients experiencing significant levels of depressive and anxious symptoms at baseline. More than half the patients with complete BDI and state anxiety data experienced either elevated symptoms of anxiety or depression throughout the first year following MI. CONCLUSIONS: Symptoms of depression and anxiety are prevalent, persistent problems during the first year following MI. This study highlights the importance of routine psychological assessment for MI patients both in hospital and after discharge.


Bird assemblage response to restoration of fire-suppressed longleaf pine sandhills.
The ecological restoration of fire-suppressed habitats may require a multifaceted approach. Removal of hardwood trees together with reintroduction of fire has been suggested as a method of restoring fire-suppressed longleaf pine (Pinus palustris) forests; however, this strategy, although widespread, has not been evaluated on large spatial and temporal scales. We used a landscape-scale experimental design to examine how bird assemblages in fire-suppressed longleaf pine sandhills responded to fire alone or fire following mechanical removal or herbicide application to reduce hardwood levels. Individual treatments were compared to fire-suppressed controls and reference sites. After initial treatment, all sites were managed with prescribed fire, on an approximately two- to three-year interval, for over a decade. Nonmetric multidimensional scaling ordinations suggested that avian assemblages on sites that experienced any form of hardwood removal differed from assemblages on both fire-suppressed sites and reference sites 3-4 years after treatment (i.e., early posttreatment). After >10 years of prescribed burning on all sites (i.e., late posttreatment), only assemblages at sites treated with herbicide were indistinguishable from assemblages at reference sites. By the end of the study, individual species that were once indicators of reference sites no longer contributed to making reference sites unique. Occupancy modeling of these indicator species also demonstrated increasing similarity across treatments over time. Overall, although we documented long-term and variable assemblage-level change, our results indicate occupancy for birds considered longleaf pine specialists was similar at treatment and reference sites after over a decade of prescribed burning, regardless of initial method of hardwood removal. In other words, based on the response of species highly associated with the habitat, we found no justification for the added cost and effort of fire surrogates; fire alone was sufficient to restore these species.


Regulation of the breakdown rates of biotin-containing proteins in Swiss 3T3-L1 cells.
1. Degradation rate constants for individual biotin-labelled proteins were measured in Swiss 3T3-L1 adipocytes that had been incubated with inhibitors of autophagy or of lysosomal proteolysis. 2. Inhibitory effects produced by 10 mM-3-methyladenine and a combination of 5 mM-NH4Cl and leupeptin (50 micrograms/ml) were approximately equal. The inclusion of NH4Cl did not significantly enhance the responses to 3-methyladenine, suggesting that autophagy was already maximally inhibited. 3. The extent of inhibition by 3-methyladenine or by the NH4Cl/leupeptin mixture was similar for the cytosolic enzyme acetyl-CoA carboxylase and for the three mitochondrial carboxylases. This inhibition averaged 50%. The breakdown rate of a more-stable 38 kDa biotin-containing mitochondrial protein was more responsive to the inhibitory agents. These results are best explained by mitochondrial proteolysis occurring via a combination of the degradation of whole mitochondria within autophagic vacuoles, supplemented by the selective intramitochondrial breakdown of more labile proteins. 4. A number of intermediate products in the degradation of biotin-containing proteins were detected. Differences in the patterns of radioactivity between these peptides after incubation of cells in the presence of inhibitors of the breakdown process provided evidence that some peptides were produced before autophagy, others as a result of intralysosomal inhibition, while at least one was associated with intramitochondrial proteolysis.


Developmental dissociations between lexical reading and comprehension: evidence from two cases of hyperlexia.
We report two cases of developmental hyperlexia - JY and AD - who performed at normal levels or above in converting print into speech, but who were very impaired in spoken and written word comprehension. Our investigations focussed on whether these cases displayed evidence for normal acquisition of lexical reading skills, as indexed by unimpaired performance for age in reading aloud a set of irregular words, despite poor acquisition of semantic knowledge of the same words. In both cases, this dissociation was evident. The pattern of results was also demonstrated at an item level: the two cases showed no significant differences in reading accuracy for irregular words which they could define than for those which they could not. The results provide further evidence for the existence of a direct-lexical route from orthography to phonology, which is not necessarily mediated by semantic knowledge.


Production and characterization of a conserved M2e peptide-based specific IgY antibody: evaluation of the diagnostic potential via conjugation with latex nanoparticles.
Antibodies play an important role in combating and controlling viral diseases such as influenza. Immunoglobulin Y (IgY) antibodies have several advantages such as a less invasive manufacturing process, ease of isolation, higher affinity compared with IgG antibodies, and cost-effectiveness. To date, although specific IgY production has been performed for different strains of influenza A, to the best of our knowledge, an IgY against the M2e peptide has not been produced. In the current study, IgY antibodies are produced, purified, and characterized using the M2e peptide sequence for the first time with the intent to apply them for the diagnosis of influenza A virus. Anti-M2e IgY antibodies are obtained from eggs using a two-step purification method. The activity and characterization of the antibodies are determined using an enzyme-linked immunosorbent assay, a nano-spectrophotometer, an SDS-Page assay, and a Western Blot analysis. Finally, anti-M2e IgY antibodies are conjugated to the latex nanoparticles, and the reaction between the influenza A virus and the nanoparticles is demonstrated using light microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy. In conclusion, this study shows that anti-M2e IgY antibodies can contribute to the diagnosis, treatment, and prevention of the influenza A virus.


Effective indicators for diagnosis of oral cancer using optical coherence tomography.
A swept-source optical coherence tomography system is used to clinically scan oral precancer and cancer patients for statistically analyzing the effective indicators of diagnosis. Three indicators are considered, including the standard deviation (SD) of an A-mode scan signal profile, the exponential decay constant (alpha) of an A-mode-scan spatial-frequency spectrum, and the epithelium thickness (T) when the boundary between epithelium and lamina propria can still be identified. Generally, in abnormal mucosa, the standard deviation becomes larger, the decay constant of the spatial-frequency spectrum becomes smaller, and epithelium becomes thicker. The sensitivity and specificity of the three indicators are discussed based on universal and individual relative criteria. It is found that SD and alpha are good diagnosis indicators for moderate dysplasia and squamous cell carcinoma. On the other hand, T is a good diagnosis indicator for epithelia hyperplasia and moderate dysplasia.


Adipose tissue concentrations of arsenic, nickel, lead, tin, and titanium in adults from GraMo cohort in Southern Spain: An exploratory study.
Adipose tissue has been acknowledged as a potential target for obesogenic pollutants, including toxic metal(loid)s. However, the presence of these chemicals in the adipose tissue has been poorly characterized. To examine the distributions of adipose tissue concentrations of five toxic metal(loid)s (i.e., arsenic [As], nickel [Ni], lead [Pb], tin [Sn], and titanium [Ti]) in adults, and potential socio-demographic and lifestyle factors associated with metal(loid) concentrations. The study population consisted of a subsample of 228 subjects from GraMo cohort in Southern Spain (N = 387). Adipose tissue samples were intra-operatively collected from adults recruited in 2003-2004 in two public hospitals, and concentrations of metal(loid)s in adipose tissue were analyzed in 2015 by High-Resolution Inductively Coupled Plasma Mass Spectrometry. Data on socio-demographic and lifestyle factors were obtained by baseline questionnaire completion. Linear and multinomial regression was used to identify factors associated with metal(loid) levels. Ni, Pb, Sn, and Ti were detected in all adipose tissue samples, and As in 51% of them. Ni was the metal showing the highest median concentration (0.56 μg/g), followed by Ti (0.31 μg/g), Pb (0.08 μg/g), Sn (0.06 μg/g), and As (0.003 μg/g). Predictors of As levels included area of residence, social class, and oily fish intake; for Ni: area of residence and consumption of cheese, meat, eggs, and canned food; for Pb: vegetables intake and industrial occupation; for Sn: age, body mass index, and consumption of lean fish, eggs, and milk; and cheese intake for Ti. Some of these predictors were sex-specific, particularly those regarding dietary intake. This exploratory study provides the first evidence of the occurrence of Ni, Pb, Sn, Ti, and As in adipose tissue from adult population, and highlights the potential of this tissue as a biological matrix for studying exposure levels and chronic health effects of toxic metal(loid)s.


A Struggle for Survival: Meaning of Late Life in a Rural District in Uganda: A Qualitative Study.
Background: Between 2015 and 2050, the aging population of Uganda (aged 50 years and older) will be nearly doubled. Therefore, later-life problems have become an area of increasing research and policy interest. This study aimed at exploring how aging people living in extreme poverty in a low-income country experience their everyday life and what kind of meaning systems employed by them to understand and cope with their living conditions. Methods: We conducted a qualitative interview with 14 participants in the Buikwe district. In this interview, 11 women and 3 men were included, and a thematic analysis was employed for data processing and analysis. Results: Unanimously, all participants reported their condition as extreme poverty. The key informants (KIs) emphasized respect from descendants and the community as a foundation for a meaningful later life. In contrast, this aspect has been ever mentioned by no caregivers but by only one care-receiver. The willingness/ability of children to support the elderly who are in need of support formed a major part of the reflections of care-receivers, which would be decisive for their position in the society and the respect they would receive. In addition, both Christianity and traditional beliefs as well as beliefs in witchcraft and ancestral spirits were employed as a basis for actions and reflections. Discussion: The question arises whether life in extreme poverty conditions can be perceived as meaningful. Respect was mentioned as fundamental by the KIs, thereby giving priority to social relations as the most meaningful factor for living a meaningful life. The ability and willingness of the possible descendants for support as the focus of care-receivers might be a more down-to-earth description of this aspect but without using the same level of abstraction. For the majority, due to their belief system did not serve as a source of consolation their main focus was on social relationships for support. To improve the wellbeing of the old people, their sense of meaning must be restored through a system, guaranteeing the coverage of basic needs and measures to restore dignity through a reintegration in both community and congregations. Social service agencies who are targeting the elderly people need to work toward this objective.


Integrated phytobial heavy metal remediation strategies for a sustainable clean environment - A review.
Heavy metal contamination in the environment is a global threat which accelerated after the industrial revolution. Remediation of these noxious elements has been widely investigated and multifarious technologies have been practiced for many decades. Phytoremediation has attracted much attention from researchers. Under this technology, heavy metal hyperaccumulator plants have been extensively employed to extract extraordinary concentrations of heavy metals but slow growth, limited biomass and stresses caused by heavy metals imperil the efficiency of hyperaccumulators. Plant growth promoting rhizobacteria (PGPR) can help overcome/lessen heavy metal-induced adversities. PGPR produce several metabolites, including growth hormones, siderophores and organic acids, which aid in solubilization and provision of essential nutrients (e.g. Fe and Mg) to the plant. Hyperaccumulator plants may be employed to remediate metal contaminated sites. Use of PGPR to enhance growth of hyperaccumulator plant species may enhance their metal accumulating capacity by increasing metal availability and also by alleviating plant stress induced by the heavy metals. Combined use of hyperaccumulator plants and PGPR may prove to be a cost effective and environmentally friendly technology to clean heavy metal contaminated sites on a sustainable basis. This review discusses the current status of PGPR in improving the growth and development of hyperaccumulator plants growing in metal contaminated environments. The mechanisms used by these rhizosphere bacteria in increasing the availability of heavy metals to plants and coping with heavy metal stresses are also described.


Novel electrospun nanotholits/PHB scaffolds for bone tissue regeneration.
Nanotholits is an osteoinductor or be, stimulates the bone regeneration, enabling bigger migration of the cells for formation of the bone tissue regeneration mainly because nanotholits are rich in minerals considered essential to the bone mineralization process on a protein matrix (otolin) as hydroxiapatite. In order to improve its biodegrability and bioresorption in new platforms for tissue engineering, it was electrospun PHB/nanotholits from aqueous solutions of this polymer at concentrations of nanotholits 1% (w/v) and compared morphological and thermal properties with PHB/nanotholits casting films. Electrospun PHB/nanotholits mats presents more symmetric nanopore structure than casting films mats observed by SEM images mainly because the orientation of pores along the longitudinal direction of the electrospun fibers. Nanotholits influences in PHB electrospun/casting was analyzed using transmission infrared spectroscopy (FTIR). TGA showed similar thermal properties but DSC showed distinct thermal properties and crystallinity process of the developed bionanocomposite mainly because of different processing.


Secondary zoospores in the algal endoparasite Maullinia ectocarpii (Plasmodiophoromycota).
The present paper deals with the ultrastructure of zoospores produced by the plasmodiophorid Maullinia ectocarpii, living in the marine algal host Ectocarpus siliculosus. The zoospores described here are very similar to secondary zoospores of Polymyxa graminis and Phagomyxa sp. (the latter an algal endoparasite, also). Our results indicate that M. ectocarpii produces two types of plasmodia, and suggest that is a species with a complete life cycle, as it is known for all the Plasmodiophormycota that have been studied. Sporogenic and sporangial plasmodia produce, respectively, primary zoospores with parallel flagella within thick walled resting sporangia, and secondary zoospores with opposite flagella within thin walled sporangia.


Nutritive Value of Grasses in Semi-arid Rangelands of Ethiopia: Local Experience Based Herbage Preference Evaluation versus Laboratory Analysis.
We examined the nutritive value of common grass species in the semi-arid rangelands of Borana in southern Ethiopia using local experience based herbage preference (LEBHP) perception and laboratory techniques. Local pastoralists in the study area were asked to identify common grass species and rank them according to the species' preferences and palatability to cattle. The pastoralists listed a total of 15 common grass species which were then sampled during the main rain and cold dry seasons and analyzed for crude protein (CP), Neutral Detergent Fiber (NDF), Acid Detergent Fiber (ADF) and ash content to verify pastoralists' claim regarding the quality of individual species. The relative feed value (RFV) and dry matter digestibility (DMD) were also calculated using NDF and ADF contents. Spearman's rank correlation was used to examine possible relationships between laboratory results and pastoralists' experience on grass quality. Cenchrus ciliaris, Chrysopogon aucheri, Digitaria milanjiana, Eragrostis papposa and Panicum maximum were the top five species based on LEBHP perception. There were indications of inconsistency in terms of LEBHP perception among the different pastoral communities. The chemical composition of all grass species showed significant (p<0.05) variation between sites, seasons and species. The results showed that the CP values for the Borana rangelands were in the range of 8.7% in the main rain season to 5.1% for the cold dry season. The fiber constituents were relatively low in the main rain season compared to the cold dry season. Overall, Digitaria milanjiana had the highest CP (16.5%) content, while the least was recorded with Heteropogon contortus (10.8) and Aristida adoensis (9.8%) during the main rain season. It seems that the spatial variability of landscapes within the wider geographical regions, soil properties and texture, and land-use patterns probably contributed to site differences in species quality. Generally, the RFV of individual grass species was significantly (p<0.05) varied between and within sites. The ranking of species by pastoralists according to their preferences by cattle was highly correlated with the chemical composition of laboratory results of individual grass species with 'r' values for CP (0.94), ash (0.95), NDF (-0.98), ADF (-0.93) and ADL (-0.93). We suggest the complimentary use of LEBHP and laboratory techniques in evaluating the nutritive quality of rangeland forage species for sustainable animal production.


Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells.
Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.


Unexpected self-lofting and dynamical confinement of volcanic plumes: the Raikoke 2019 case.
Recent research has provided evidence of the self-lofting capacity of smoke aerosols in the stratosphere and their self-confinement by persistent anticyclones, which prolongs their atmospheric residence time and radiative effects. By contrast, the volcanic aerosols-composed mostly of non-absorptive sulphuric acid droplets-were never reported to be subject of dynamical confinement. Here we use high-resolution satellite observations to show that the eruption of Raikoke volcano in June 2019 produced a long-lived stratospheric anticyclone containing 24% of the total erupted mass of sulphur dioxide. The anticyclone persisted for more than 3 months, circumnavigated the globe three times, and ascended diabatically to 27 km altitude through radiative heating of volcanic ash contained by the plume. The mechanism of dynamical confinement has important implications for the planetary-scale transport of volcanic emissions, their stratospheric residence time, and atmospheric radiation balance. It also provides a challenge or "out of sample test" for weather and climate models that should be capable of reproducing similar structures.


APIC Megasurvey 2020: Methodology and overview of results.
In 2015, The Association for Professionals in Infection Control and Epidemiology (APIC) conducted the first MegaSurvey of its members to understand key aspects of their practice. Given the evolving role of Infection preventionists (IPs), it is important to understand changes in and the current practice environments of IPs, their demographics, the organizations in which they practice and the relative importance of different domains of IP practice. The MegaSurvey 2020 was a cross-sectional, electronic survey of IPs conducted by APIC between January 21 and February 28, 2020. Descriptive statistics were calculated to describe the participants in terms of their characteristics, practice setting, compensation and IP competencies. 2,030 APIC members (response rate 13%) participated in the study. Results indicated that the demographic characteristics of IPs remained the same between the 2015 and 2020 surveys. Similar to 2015 data, slightly less than half of respondents are currently certified and plan to recertify. Less than 50% of IPs reported feeling adequately satisfied with their overall compensation. IPs reported spending the largest proportion of their time on surveillance and epidemiologic investigations and the least amount of time on employee and occupational health, cleaning and sterilization and education/research. As the healthcare industry continues to evolve, public health emergencies persist, and regulatory requirements expand, the results of the APIC MegaSurvey can inform future educational initiatives, the development of programs and ongoing hiring and retention strategies for this critical profession.


Trends in educational and income inequalities in cardiovascular morbidity in middle age in Northern Sweden 1993-2010.
Aims: Research is scarce regarding studies on income and educational inequality trends in cardiovascular disease in Sweden. The aim of this study was to assess trends in educational and income inequalities in first hospitalizations due to cardiovascular disease (CVD) from 1993 to 2010 among middle-aged women and men in Northern Sweden. Methods: The study comprised repeated cross-sectional register data from year 1993-2010 of all individuals aged 38-62 years enrolled in the Västerbotten Intervention Programme (VIP). Data included highest educational level, total earned income and first-time hospitalization for CVD from national registers. The relative and slope indices of inequality (RII and SII, respectively) were used to estimate educational and income inequalities in CVD for six subsamples for women and men, and interaction analyses were used to estimate trends across time periods. Results: Educational RII and SII were stable in women, while they decreased in men. Income inequalities in CVD developed differently compared with educational inequalities, with RII and SII for both men and women increasing during the study period, the most marked for RII in women rising from 1.52 in the 1990s to 2.62 in the late 2000s. Conclusions: The trend of widening income inequalities over 18 years in the middle-aged in Northern Sweden, in the face of stable or even decreasing educational inequalities, is worrisome from a public health perspective, especially as Swedish authorities monitor socioeconomical inequalities exclusively by education. The results show that certain social inequalities in CVD rise and persist even within a traditionally egalitarian welfare regime.


Global crop forecasting.
Many foreign countries are as dependent on imports of food as the United States is on imports of oil. As the world's largest exporter of food, the United States needs reliable information on fluctuating foreign crop production. But available information is often inadequate and at best untimely. It is gathered by the foreign governments' often outmoded systems and its release may be delayed out of economic self-interest. Recently three U.S. government agencies put together a crop inventory system using satellite remote sensing and worldwide weather reporting and tested it in the Large Area Crop Inventory Experiment (LACIE). A 1977 real-time forecast of U.S.S.R. wheat production indicates that the approach works and may be expandable to other areas and other crops.


Positional shunt assist for slit ventricle syndrome.
Hydrocephalus is one of the most common pathologies in pediatric neurosurgery. One of the causes of recurring events of headaches among shunted children is "slit ventricle syndrome" (SVS). Several potential treatments have been proposed, yet SVS often represents a treatment challenge. The goal of the current series is to present our experience with adding a positional shunt-assist (SA) (Miethke, Aesculap) for the treatment of SVS. Clinical data was retrospectively collected from all consecutive children with SVS that were treated with SA (Miethke, Aesculap) at our center. Surgical and clinical outcomes as expressed by hospital visits, or need for additional surgery, were evaluated. Nine cases were included. Hydrocephalus etiology included IVH (6), postinfectious (1), and congenital syndromes (2). Average age at first shunt was 4 months. Primary shunt type was differential-pressure-valve in all. Average age at SVS onset was 4 years. Average age at SA placement was 5.5 years. There were no perioperative complications besides a single stich abscess. A 6-month follow-up period after SA was compared to a 6-month period prior to the SA: average hospital visits decreased from 2.4 to 0.6 per patient (p < 0.0002). 4/9 patients needed an LP or shunt revision before the SA surgery, while no procedure was indicated during the immediate 6-month follow-up. At the last follow-up, there was a significant reduction in the rate of ER visits compared to prior to surgery; however, the number of neurosurgical procedures did not significantly differ. Using a SA for SVS was associated with a short-term improvement of symptoms in the majority of cases, reduction in hospital visits, and reduced need for SVS-related procedures.


Hydroxycinnamic acids used as external acceptors of electrons: an energetic advantage for strictly heterofermentative lactic acid bacteria.
The metabolism of hydroxycinnamic acids by strictly heterofermentative lactic acid bacteria (19 strains) was investigated as a potential alternative energy route. Lactobacillus curvatus PE5 was the most tolerant to hydroxycinnamic acids, followed by strains of Weissella spp., Lactobacillus brevis, Lactobacillus fermentum, and Leuconostoc mesenteroides, for which the MIC values were the same. The highest sensitivity was found for Lactobacillus rossiae strains. During growth in MRS broth, lactic acid bacteria reduced caffeic, p-coumaric, and ferulic acids into dihydrocaffeic, phloretic, and dihydroferulic acids, respectively, or decarboxylated hydroxycinnamic acids into the corresponding vinyl derivatives and then reduced the latter compounds to ethyl compounds. Reductase activities mainly emerged, and the activities of selected strains were further investigated in chemically defined basal medium (CDM) under anaerobic conditions. The end products of carbon metabolism were quantified, as were the levels of intracellular ATP and the NAD(+)/NADH ratio. Electron and carbon balances and theoretical ATP/glucose yields were also estimated. When CDM was supplemented with hydroxycinnamic acids, the synthesis of ethanol decreased and the concentration of acetic acid increased. The levels of these metabolites reflected on the alcohol dehydrogenase and acetate kinase activities. Overall, some biochemical traits distinguished the common metabolism of strictly heterofermentative strains: main reductase activity toward hydroxycinnamic acids, a shift from alcohol dehydrogenase to acetate kinase activities, an increase in the NAD(+)/NADH ratio, and the accumulation of supplementary intracellular ATP. Taken together, the above-described metabolic responses suggest that strictly heterofermentative lactic acid bacteria mainly use hydroxycinnamic acids as external acceptors of electrons.


Sensory palmar stimulation in the diagnosis of carpal tunnel syndrome.
The measurement of motor and sensory latencies of the median and ulnar nerves using conventional techniques in able-bodied subjects and patients with a history compatible with carpal tunnel syndrome (CTS) is described. The results obtained by conventional techniques are compared with measurement of median nerve sensory latency obtained by palmar stimulation and the difference of median-ulnar nerve distal sensory latencies. It is concluded that the use of measurement of median palmar sensory latency under the flexor retinaculum adds to the sensitivity of the nerve conduction studies in the diagnosis of CTS. It is suggested that, in patients with suspected CTS in whom conventional nerve conduction studies are normal, other techniques such as the measurement of palmar sensory latency, difference between median and ulnar nerve distal sensory latency and examination of all the digits should be carried out.


Fecundity of Chub Mackerel (Scomber japonicus Houttuyn, 1782) in the Aegean Sea.
This study was carried out in April - June 2014 to determine absolute fecundity (F) of the chub mackerel (Scomber japonicus Houttuyn, 1782) in Saros Bay (Aegean Sea, Turkey). The relations between the absolute fecundity and total length, total weight and age of the chub mackerel females were estimated as F=0.0318TL4.81, F=1573.9TW- 42858 and F=109607A-136129, respectively. This study aims to contribute to the reproductive biology of S. japonicus by reporting the first findings about the absolute fecundity of the species for the Aegean Sea.


Relationships between sensorimotor impairments and reaching deficits in acute hemiparesis.
To determine the relationships between sensorimotor impairments and upper extremity reaching performance during the acute phase of stroke and to determine which, if any, measures of sensorimotor impairment can predict variance in reaching performance during this phase. Sensorimotor impairments of upper extremity (UE) strength, active range of motion, isolated movement control, light touch sensation, joint position sense, spasticity, and shoulder pain were evaluated in a group of 46 individuals with acute hemiparesis (mean time since insult = 9.2 days). Subjects performed a reaching task to a target placed on their affected side. Three-dimensional kinematic analyses were used to assess reaching speed, accuracy, and efficiency. Forward stepwise multiple linear regression analyses were used to determine which impairment was the best predictor of variance in reaching performance. Measures of UE strength predicted the largest proportion of variance in the speed, accuracy, and efficiency of forward reaching. Isolated movement control, somatosensory deficits, and elbow spasticity predicted smaller amounts of variance in reaching performance. The authors' data show that deficits in strength appear to be the most influential sensorimotor impairment associated with limited reaching performance in subjects with acute hemiparesis.


Economic Burden of Mosquito-Borne Diseases in Low- and Middle-Income Countries: Protocol for a Systematic Review.
Globally, among all the vector-borne diseases, mosquito-borne diseases are responsible for a substantial number of cases and deaths and amount to an economic cost of US $12 billion per year. However, there is a dearth of systematic research conducted on the economic burden of mosquito-borne diseases. To address the lack of comprehensive information on this topic, a systematic review will be conducted to synthesize evidence for informing targeted policies and strategies addressing this growing burden and for better financial protection of households. The systematic review aims to review the economic burden of mosquito-borne diseases in low- and middle-income countries (LMICs). The review estimates the total cost, which is the compilation of both the direct costs and indirect costs. Additionally, it reports cost estimates per disease, country, and patient. The review outcome will also discuss the impact of the economic burden in terms of out-of-pocket expenditure, catastrophic health expenditure, impoverishment, and gross domestic product impact due to mosquito-borne diseases in LMICs. Systematic searches will be conducted in PubMed (MEDLINE), Ovid Embase, Scopus, the cumulative index of nursing and allied health literacy, and Cochrane CENTRAL. Additionally, websites of the World Bank, World Health Organization, and Asian Development Bank as well as grey literature (eg, Malaria No More and the Ministry of Health websites) will be searched to gather comprehensive information on the topic and identify studies published in the English language. The titles and abstracts will be independently screened by 2 reviewers, followed by a full-text review against the inclusion criteria. Disagreements will be resolved through discussion with a third author. The methodological reporting quality of the studies will be evaluated using the Larg and Moss checklist, Cochrane risk-of-bias tool for randomized trials, and the Consensus on Health Economic Criteria. Data will be extracted using a standardized data extraction form. The protocol was registered in PROSPERO (CRD42023427111) prior to the initiation of the search strategy. The review is currently ongoing and will synthesize information from the identified studies through a process involving structured screening, data extraction, and critical appraisal in the form of tables and a narrative summary of studies reporting the economic burden incurred due to mosquito-borne diseases in LMICs. This review seeks to report the economic burden of mosquito-borne diseases. It will act as evidence for policymakers to prioritize their decisions regarding containing the prevalence of mosquito-borne diseases and the means to lowering the incidence of diseases spread by mosquitoes. PROSPERO CRD42023427111; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=427111. PRR1-10.2196/50985.


Trocarless laparoscopic pyloromyotomy with conventional instruments: Our experience.
The incidence of hypertrophic pyloric stenosis is approximately 1-3 per 1,000 live births. Hypertrophic pyloric stenosis is seen more often in males, with a male-to female ratio of 4:1. Laparoscopic pyloromyotomy is becoming increasingly popular as the standard treatment for hypertrophic pyloric stenosis. We describe our initial experience with laparoscopic pyloromyotomy in 16 infants using conventional laparoscopic instruments. Laparoscopic pyloromyotomy was performed through 5-mm umbilical port with 5mm 30 endoscope. Two 3-mm working instruments were inserted directly into the abdomen via separate lateral incisions. All patients were prospectively evaluated. The procedure was performed in 16 infants with a mean age of 36 days and mean weight of 3.1 kg. All procedures, except two, were completed laparoscopically with standard instruments. Average operating time was 28 mins, and average postoperative length of stay was 2.8 days. There were no major intraoperative and postoperative complications. Laparoscopic pyloromyotomy can be safely performed by using standard conventional laparoscopic trocarless instruments.


Oliveros virus: a novel arenavirus from Argentina.
During the past few decades several newly recognized rodent-borne arenaviruses have been shown to be associated with severe hemorrhagic fever cases in South America. Changes in ecology and farming practices throughout the region have increased the concern over the potential public health threat posed by such emerging virus diseases. Oliveros (OLV) virus is a recently discovered arenavirus of the rodent Bolomys obscurus in Argentina. Genetic analysis of the small genomic RNA segment, which encodes the nucleocapsid protein and the envelope glycoproteins, shows that Oliveros is a novel, phylogenetically distinct member of the Arenaviridae family which differs in nucleotide sequence from the previously characterized members by approximately 35% or more. Despite this level of diversity, OLV virus possesses the same ambisense genome structure and many overall RNA and protein features in common with other arenaviruses. These data represent an important first step in the development of specific immunological and PCR diagnostic reagents to allow assessment of the prevalence and disease potential of this virus.


Isotope-coded protein label based quantitative proteomic analysis reveals significant up-regulation of apolipoprotein A1 and ovotransferrin in the myopic chick vitreous.
This study used isotope-coded protein label (ICPL) quantitative proteomics and bioinformatics analysis to examine changes in vitreous protein content and associated pathways during lens-induced eye growth. First, the vitreous protein profile of normal 7-day old chicks was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry. A total of 341 unique proteins were identified. Next, myopia and hyperopia were induced in the same chick by attaching -10D lenses to the right eye and +10D lenses to the left eye, for 3 and 7 days. Protein expression in lens-induced ametropic eyes was analyzed using the ICPL approach coupled to LCMS. Four proteins (cystatin, apolipoprotein A1, ovotransferrin, and purpurin) were significantly up-regulated in the vitreous after 3 days of wearing -10D lenses relative to +10D lens contralateral eyes. The differences in protein expression were less pronounced after 7 days when the eyes approached full compensation. In a different group of chicks, western blot confirmed the up-regulation of apolipoprotein A1 and ovotransferrin in the myopic vitreous relative to both contralateral lens-free eyes and hyperopic eyes in separate animals wearing +10D lenses. Bioinformatics analysis suggested oxidative stress and lipid metabolism as pathways involved in compensated ocular elongation.


Pulmonary endothelial cell activation during experimental acute kidney injury.
Acute kidney injury (AKI) leads to increased lung microvascular permeability, leukocyte infiltration, and upregulation of soluble inflammatory proteins in rodents. Most work investigating connections between AKI and pulmonary dysfunction, however, has focused on characterizing whole lung tissue changes associated with AKI. Studies at the cellular level are essential to understanding the molecular basis of lung changes during AKI. Given that the pulmonary microvascular barrier is functionally abnormal during AKI, we hypothesized that AKI induces a specific proinflammatory and proapoptotic lung endothelial cell (EC) response. Four and 24 h after kidney ischemia/reperfusion injury or bilateral nephrectomy, murine pulmonary ECs were isolated via tissue digestion followed by magnetic bead sorting. Purified lung ECs were analyzed for changes in mRNA expression using real-time SuperArray polymerase chain reaction analysis of genes related to EC function. In parallel experiments, confluent rat pulmonary microvascular ECs were treated with AKI or control serum to evaluate functional cellular alterations. Immunocytochemistry and FACS analysis of Annexin V/propidium iodide staining were used to evaluate cytoskeletal changes and promotion of apoptosis. Isolated murine pulmonary ECs exhibited significant changes in the expression of gene products related to inflammation, vascular reactivity, and programmed cell death. Further experiments using an in vitro rat pulmonary microvascular EC system revealed that AKI serum induced functional cellular changes related to apoptosis, including structural actin alterations and phosphatidylserine translocation. Analysis and segregation of both upregulated and downregulated genes into functional roles suggest that these transcriptional events likely participate in the transition to an activated proinflammatory and proapoptotic EC phenotype during AKI. Further mechanistic analysis of EC-specific events in the lung during AKI might reveal potential novel therapeutic targets for the deleterious kidney-lung crosstalk in the critically ill patient.


Central monoamines in free-ranging lizards: differences associated with social roles and territoriality.
During the breeding season different social classes of field-active lizards, Sceloporus jarrovi, exhibit regionally specific changes in central monoaminergic activation. Changes in serotonergic content and turnover between lizards from different social classes are seen in forebrain structures (telencephalon and diencephalon) and reflect events associated with reproductive behaviors, stress and aggression. Males without territories (satellite males) exhibit higher forebrain serotonin (5-HT) system activation compared to territorial males and adult females. This serotonergic activation includes increased 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio, suggesting increased release and catabolism. Satellite males also exhibit higher 5-HIAA/5-HT ratios (serotonergic turnover) compared to territorial males following agonistic interactions. Territorial males, immediately following aggressive defense of territories against intruder males, exhibit increased 5-hydroxytryptophan (5-HTP) levels, higher 5-HIAA levels and 5-HIAA/5-HT ratio, higher epinephrine levels, greater MHPG/NE, more DOPAC and larger DOPAC/DA ratio compared to territorial males that did not have an aggressive encounter. These differences suggest activation of 5-HT, norepinephrine (NE), and dopamine (DA) systems by the synthesis and release of more 5-HT and the release of more NE and DA during aggressive defense of territory. The highest activity of serotonergic system is exhibited by satellite males compared to territorial males, perhaps reflecting stress in subordinate animals from social and ecological sources.


Evaluation of the stiffnesses of the Achilles tendon and soleus from the apparent stiffness of the triceps surae.
The triceps surae plays an important role in the performance of many sports. Although the apparent average mechanical properties of the triceps surae may be a satisfactory parameter for estimating the training level of an athlete, a knowledge of the mechanical properties of the individual constituents of the triceps surae (in particular the Achilles tendon and soleus) permits a more detailed and in-depth control of the effects of training from more physically based parameters. The objective of this work is therefore the estimation of the individual viscoelastic properties (stiffness and viscosity) of soleus and Achilles tendon from the apparent properties of the triceps surae obtained by free vibration techniques. Different procedures have been developed and discussed, showing a high degree of robustness in the predictions. The results obtained for a non-oriented set of subjects present a high level of variability, depending on the training conditions and anthropometric features, although the corresponding average values compare well with data previously reported in the literature, particularly those associated with the tendon stiffness.


Volume regulation and plasma membrane injury in aerobic, anaerobic, and ischemic myocardium in vitro. Effects of osmotic cell swelling on plasma membrane integrity.
The relationship between cell swelling and plasma membrane disruption has been evaluated in thin myocardial slices incubated in oxygenated or anoxic Krebs-Ringer phosphate media. Electron microscopy and measurements of inulin-diffusible space were used to monitor plasma membrane integrity. Inulin is excluded from the intracellular space of intact cells; therefore, an increase in tissue inulin content is an excellent marker of loss of plasma membrane integrity. Cell volume was increased during exposure of aerobic slices to hypotonic media, but the inulin-diffusible space was not increased and electron micrographs showed no detectable plasma membrane alterations. Likewise, during prolonged anoxic isotonic incubation, no evidence of plasma membrane damage was observed. Incubation in anoxic hypotonic media for 60 minutes resulted in a larger increase in cell volume than under aerobic conditions, but plasma membrane integrity was maintained. Extended anoxic hypotonic incubation (300 minutes) produced no further change in tissue water, but the inulin-diffusible space was increased and electron micrographs revealed breaks in the plasma membranes primarily in association with large subsarcolemmal blebs. Likewise, myocardial slices incubated in isotonic anoxic media for 240 minutes and hypotonic anoxic media for 60 minutes had an increased inulin-diffusible space and the ultrastructural appearance was similar. This ultrastructural appearance is indistinguishable from that observed in myocytes lethally injured by ischemia. Measurements of tissue osmolarity during total ischemia showed that osmotically induced cell swelling could occur in ischemic myocardium prior to the onset of plasma membrane disruption. Our results indicate that cell swelling per se is incapable of rupturing plasma membranes; however, after prolonged periods of energy deficiency, the plasma membrane or its cytoskeletal scaffold become injured, which allows the membrane to rupture if the cell is swollen, as might occur during ischemia or reperfusion.


Mg2+ Is a Missing Link in Plant Cell Ca2+ Signalling and Homeostasis-A Study on Vicia faba Guard Cells.
Hyperpolarization-activated calcium channels (HACCs) are found in the plasma membrane and tonoplast of many plant cell types, where they have an important role in Ca2+-dependent signalling. The unusual gating properties of HACCs in plants, i.e., activation by membrane hyperpolarization rather than depolarization, dictates that HACCs are normally open in the physiological hyperpolarized resting membrane potential state (the so-called pump or P-state); thus, if not regulated, they would continuously leak Ca2+ into cells. HACCs are permeable to Ca2+, Ba2+, and Mg2+; activated by H2O2 and the plant hormone abscisic acid (ABA); and their activity in guard cells is greatly reduced by increasing amounts of free cytosolic Ca2+ ([Ca2+]Cyt), and hence closes during [Ca2+]Cyt surges. Here, we demonstrate that the presence of the commonly used Mg-ATP inside the guard cell greatly reduces HACC activity, especially at voltages ≤ -200 mV, and that Mg2+ causes this block. Therefore, we firstly conclude that physiological cytosolic Mg2+ levels affect HACC gating and that channel opening requires either high negative voltages (≥ -200 mV) or displacement of Mg2+ away from the immediate vicinity of the channel. Secondly, based on structural comparisons with a Mg2+-sensitive animal inward-rectifying K+ channel, we propose that the likely candidate HACCs described here are cyclic nucleotide gated channels (CNGCs), many of which also contain a conserved diacidic Mg2+ binding motif within their pores. This conclusion is consistent with the electrophysiological data. Finally, we propose that Mg2+, much like in animal cells, is an important component in Ca2+ signalling and homeostasis in plants.


Flexural strength and crystalline stability of a monolithic translucent zirconia subjected to grinding, polishing and thermal challenges.
The objective of this study is to investigate the magnitude of structural degradation of a monolithic translucent zirconia caused by clinically relevant grinding and polishing procedures, when associated or not with low temperature degradation (LTD), induced by accelerated hydrothermal aging using autoclave or thermocycling Ninety disks (Ø12 × 1 mm) were prepared from dental zirconia for monolithic restorations (Vipi Block Zirconn Translucent, Vipi). The specimens were divided into 3 groups (n = 30) according to surface treatment: As Sintered (untreated), Grind (diamond bur), Grind + Polish (diamond bur + polish); and then subdivided according to aging method (n = 10): Baseline (no aging), Autoclave (134°C, 2.2 kgf/cm2 pressure for 5 h), and Thermocycling (200,000 cycles, 5°C and 55°C, for 15 s each). Roughness, biaxial flexural strength and percentage of monoclinic phase were evaluated. Regarding surface treatment, the Grind group presented higher roughness and greater flexural strength compared to As Sintered group, while Grind + Polish showed intermediate roughness and flexural strength similar to Grind group. Aging had little effect on roughness, but yielded a significant reduction in flexural strength. Tetragonal to monoclinic phase transformation was observed in all groups, caused by both mechanical stresses (grinding and polishing) and LTD, which was similarly induced by the traditional autoclave method, as well as the thermocycling method The use of diamond burs to grind zirconia surface may result in deleterious effects on the surface quality of monolithic zirconia restorations, yet has a potential toughening effect by phase transformation. However, when zirconia is exposed to LTD, regardless of the surface treatment, degradation of the surface quality and strength are observed.


Self-calibrating dual-sensing electrochemical sensors for accurate detection of carbon dioxide in blood.
A paper-based electrochemical dual-function biosensor capable of determining pH and TCO2 was synthesized for the first time using an iridium oxide pH electrode and an all-solid-state ion electrode (ASIE). In the study, to obtain highly reliable results, the biosensor was equipped with a real-time pH correction function before TCO2 measurements. Compared to traditional liquid-filling carbon dioxide detection sensors, the utilization of ferrocene endows our novel sensor with abundant positive sites, and thus greatly improves its performance. Conversely, the introduction of MXene with conductivity close to that of metals reduces electrode resistance, which is beneficial for accelerating the electrochemical reaction of the sensor and reducing LOD. After optimization, the detection range of TCO2 is 0.095 nM-0.66 M, with a detection limit of as low as 0.023 nM. In addition, the sensor was used in real serum sample-spiked recovery experiments and comparison experiments with existing clinical blood gas analyzers, which confirmed the effectiveness of its clinical application. This study provides a method for the rational design of paper-based electrochemical biosensors and a new approach for the clinical detection of blood carbon dioxide.


CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice.
In addition to androgenic properties mediated via androgen receptors, dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate pathway. These estrogenic functions of DHT are mediated by its metabolite 5α-androstane-3β, 17β-diol (3β-diol) binding to estrogen receptor β (ERβ). CYP7B1 enzyme converts 3β-diol to inactive 6α- or 7α-triols and plays an important role as a regulator of estrogenic functions mediated by 3β-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene (CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior. Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were assessed for their behavioral phenotype, anxiety-related behavioral measures, and hypothalamic pituitary adrenal axis reactivity. No significant effects of genotype were evident in anxiety-like behaviors in open field (OFA), light-dark (L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO and WT littermates. T also attenuated the corticosterone response to EPM in both genotypes. In GDX animals, T was able to reinstate male-specific reproductive behaviors (latencies and number of mounts, intromission, and ejaculations) in the WT but not in the CYP7B1KO mice. The male reproductive behavior defect in CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role for the CYP7B1 enzyme in the regulation of male reproductive behaviors.


Thyrotrophin and prolactin release in prolonged critical illness: dynamics of spontaneous secretion and effects of growth hormone-secretagogues.
Infusion of GH secretagogues appears to be a novel endocrine approach to reverse the catabolic state of critical illness, through amplification of the endogenously blunted GH secretion associated with a substantial IGF-I rise. Here we report the dynamic characteristics of spontaneous nightly TSH and PRL secretion during prolonged critical illness, together with the concomitant effects exerted by the administration of GH-secretagogues, GH-releasing hormone (GHRH) and GH-releasing peptide-2 (GHRP-2) in particular, on night-time TSH and PRL secretion. Twenty-six critically ill adults (mean +/- SEM age: 63 +/- 2 years) were studied during two consecutive nights (2100-0600 h). According to a weighed randomization, they received 1 of 4 combinations of infusions, within a randomized, cross-over design for each combination: placebo (one night) and GHRH (the next night) (n = 4); placebo and GHRP-2 (n = 10); GHRH and GHRP-2 (n = 6); GHRP-2 and GHRH + GHRP-2 (n = 6). Peptide infusions (duration 21 hours) were started after a bolus of 1 microgram/kg at 0900 h and infused (1 microgram/kg/h) until 0600 h. Serum concentrations of TSH and PRL were determined by IRMA every 20 minutes and T4, T3 and rT3 by RIA at 2100 h and 0600 h in each study night. Hormone secretion was quantified using deconvolution analysis. During prolonged critical illness, mean night-time serum concentrations of TSH (1.25 +/- 0.42 mlU/l) and PRL (9.4 +/- 0.9 micrograms/l) were low-normal. However, the proportion of TSH and PRL that was released in a pulsatile fashion was low (32 +/- 6% and 16 +/- 2.6%) and no nocturnal TSH or PRL surges were observed. The serum levels of T3 (0.64 +/- 0.06 nmol/l) were low and were positively related to the number of TSH bursts (R2 = 0.32; P = 0.03) and to the log of pulsatile TSH production (R2 = 0.34; P = 0.03). GHRP-2 infusion further reduced the proportion of TSH released in a pulsatile fashion to half that during placebo infusion (P = 0.02), without altering mean TSH levels. GHRH infusion increased mean TSH levels and pulsatile TSH production, 2-fold compared to placebo (P = 0.03) and 3-fold compared to GHRP-2 (P = 0.008). The addition of GHRP-2 to GHRH infusion abolished the stimulatory effect of GHRH on pulsatile TSH secretion. GHRP-2 infusion induced a small increase in mean PRL levels (21%; P = 0.02) and basal PRL secretion rate (49%; P = 0.02) compared to placebo, as did GHRH and GHRH + GHRP-2. The characterization of the specific pattern of anterior pituitary function during prolonged critical illness is herewith extended to the dynamics of TSH and PRL secretion: mean serum levels are low-normal, no noctumal surge is observed and the pulsatile fractions of TSH and PRL release are reduced, as was shown previously for GH. Low circulating thyroid hormone levels appear positively correlated with the reduced pulsatile TSH secretion, suggesting that they have, at least in part, a neuroendocrine origin. Finally, the opposite effects of different GH-secretagogues on TSH secretion further delineate particular linkages between the somatotrophic and thyrotrophic axes during critical illness.


Choice for the removal of bloody cerebrospinal fluid in postcoiling aneurysmal subarachnoid hemorrhage: external ventricular drainage or lumbar drainage?
External ventricular drainage (EVD) and lumbar drainage (LD) are the most widely used procedures for continued bloody cerebrospinal fluid drainage. Each has his own advantages and disadvantages. Here, we compared complications and clinical outcomes in patients with World Federation of Neurosurgical Societies (WFNS) grade III aneurysmal subarachnoid hemorrhage (aSAH) who underwent coil placement followed by EVD or LD. In this prospective, controlled study, all patients with aSAH classified as WFNS grade III who underwent coil placement at our institution were divided randomly into 2 groups: the EVD group and the LD group. The ratios of intracerebral hemorrhage, vasospasm, infection, duration of catheter placement, hydrocephalus, and Glasgow outcome scale (GOS) after 2 months of onset were analyzed between the 2 groups. A total of 148 patients (mean age 56.8 years) were enrolled in this study. Seventy-six patients were assigned to the EVD group, and 72 patients were assigned to the LD group. The average time interval from stroke onset to surgery was 35.1 h. Compared with the EVD group, the LD group had a lower incidence of intracerebral hemorrhage, slightly higher rates of infection and hydrocephalus, and similar vasospasm and chronic hydrocephalus rates, durations of catheter placement, and GOS scores at 2 months after onset. In order to improve the clinical outcomes of patients with aSAH, we suggest that LD is better than EVD for patients with WFNS grade III aSAH who underwent coil placement.


Left ventricular unloading alters receptor tyrosine kinase expression in the failing human heart.
Experimental and clinical data suggest that the loss of membrane receptor tyrosine kinase (RTK) activity in cardiac myocytes results in increased frequency of apoptotic cell death and progression of heart failure. The goal of our study was to examine the expression characteristics of RTKs in ventricular myocardium obtained from patients before and after mechanical unloading. We extracted RNA from paired formalin-fixed, paraffin-embedded left ventricular tissue blocks obtained at the time of left ventricular assist device (LVAD) implantation and explantation from a cohort of 36 patients (median age 51 years). The duration of LVAD support ranged from 1 to 314 days (median 95 days), 17 patients had ischemic and 19 non-ischemic cardiomyopathy at the time of LVAD implantation. Using real-time reverse transcription-polymerase chain reaction (RT-PCR) we quantitated transcripts for atrial natriuretic factor (ANF) and tumor necrosis factor-alpha (TNF-alpha), markers of heart failure, and the RTKs Her2/neu, Her4 and gp130, regulators of cardiac cell survival. In patients undergoing mechanical unloading, ANF and TNF-alpha mRNA levels were independently suppressed. Her2/neu, along with Her4 was upregulated, mostly in cases of ischemic cardiomyopathy, whereas gp130 levels decreased. Post-LVAD transcript levels of Her2 correlated tightly with gp130 in patients with non-pathologic entry values of gp130. Duration of treatment and age were also determining factors in the change of expression of these genes. Real-time quantitative (Q)-RT-PCR can be used to quantitate gene expression in archival myocardial tissue blocks. Mechanical unloading leads to a re-adjustment of RTK transcript levels, but not their reverting to control values in heart failure patients.


Isomerase Pin1 stimulates dephosphorylation of tau protein at cyclin-dependent kinase (Cdk5)-dependent Alzheimer phosphorylation sites.
Neurodegenerative diseases associated with the pathological aggregation of microtubule-associated protein Tau are classified as tauopathies. Alzheimer disease, the most common tauopathy, is characterized by neurofibrillary tangles that are mainly composed of abnormally phosphorylated Tau. Similar hyperphosphorylated Tau lesions are found in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) that is induced by mutations within the tau gene. To further understand the etiology of tauopathies, it will be important to elucidate the mechanism underlying Tau hyperphosphorylation. Tau phosphorylation occurs mainly at proline-directed Ser/Thr sites, which are targeted by protein kinases such as GSK3β and Cdk5. We reported previously that dephosphorylation of Tau at Cdk5-mediated sites was enhanced by Pin1, a peptidyl-prolyl isomerase that stimulates dephosphorylation at proline-directed sites by protein phosphatase 2A. Pin1 deficiency is suggested to cause Tau hyperphosphorylation in Alzheimer disease. Up to the present, Pin1 binding was only shown for two Tau phosphorylation sites (Thr-212 and Thr-231) despite the presence of many more hyperphosphorylated sites. Here, we analyzed the interaction of Pin1 with Tau phosphorylated by Cdk5-p25 using a GST pulldown assay and Biacore approach. We found that Pin1 binds and stimulates dephosphorylation of Tau at all Cdk5-mediated sites (Ser-202, Thr-205, Ser-235, and Ser-404). Furthermore, FTDP-17 mutant Tau (P301L or R406W) showed slightly weaker Pin1 binding than non-mutated Tau, suggesting that FTDP-17 mutations induce hyperphosphorylation by reducing the interaction between Pin1 and Tau. Together, these results indicate that Pin1 is generally involved in the regulation of Tau hyperphosphorylation and hence the etiology of tauopathies.


Morphology of ovarian changes during the reproductive cycle of the house lizard, Hemidactylus flaviviridis.
Ovarian changes during the reproductive cycle of the oviparous wall lizard (Hemidactylus flaviviridis Rüppel) are described and discussed. It ovulates from mid-March to mid-May with a peak in April. Two eggs, one from each ovary, are ovulated at a time. After the breeding season is over, the ovaries are reduced in size. From June to third week of February they contain small pre-vitellogenic fillicles which start increasing in size with the approach of March when yolk deposition occurs rapidly. The histological details of developing the pre-ovulatory follicles are described. Follicle cell nuclei are taken into the ooplasm of pre-vitellogenic follicles; they are finally absorbed before yolk deposition starts. Pre-ovulatory follicles show highly vascularized thecae and invaginations of the follicular epithelium. Follicular atresia generally occurs in follicles with polymorphic granulosae, in post-ovulatory ovaries. Their granulosa cells give rist to phagocytes which, after removing the ooplasmic contents, degenerate, while the theca interna cells are hypertrophied to form the interstitial gland cells in the walls of degenerated follicles. After ovulation, the granulosa cells hypertrophy to form luteal cell mass filling the follicular cavity. Fibroblasts which appear to arise from the thecal layer, invade the luteal cell mass and form septa. Blood vessels occur in the luteal cell mass. The possible physiological significance of corpora lutea in the wall lizard is discussed.


The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor: A Meta-analysis of 25 RCTs.
To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) patients with wild-type (WT) EGFR tumors, we performed an indirect meta-analysis to assess the treatment effects of EGFR-TKIs in such patients. We searched for randomized controlled trials in Medline, Embase, the Cochrane controlled trials register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Effect measures used were hazard ratios (HR) for progression-free survival (PFS) and overall survival. Out of 2134 retrieved articles, 25 randomized controlled trials including more than 4467 patients were identified. This pooled analysis showed the inferior efficacy of TKI over chemotherapy among patients with WT EGFR NSCLC in terms of PFS (HR, 1.37; 95% confidence interval [CI]: 1.10, 1.72; P=0.006). When used as first-line treatment, TKIs have also fared worse than chemotherapy when compared with standard platinum doublet regimens in patients with WT EGFR in terms of PFS (HR, 2.15; 95% CI: 1.68, 2.76; P<0.001). And, the same inferior trend was found with TKIs in those trials of second-line/third-line treatment in terms of PFS (HR, 1.35; 95% CI: 1.13, 1.61; P<0.001). However, according to the pooled results, EGFR-TKIs still produced a reduction of 19% in the risk of progression over placebo in such WT EGFR patients ineligible for further chemotherapy (HR, 0.81; 95% CI: 0.68, 0.97; P=0.02). Furthermore, addition of EGFR-TKI to chemotherapy resulted in an improvement of PFS over chemotherapy alone (HR, 0.83; 95% CI: 0.71, 0.96; P=0.01). Among patients with advanced NSCLC harboring WT EGFR, EGFR-TKIs were inferior to standard chemotherapy both for first-line treatment and for second-line/third-line treatment, but still superior to placebo in patients unfit for further chemotherapy. And, addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such patients.


Dexamethasone Implant Migration through an Iris Coloboma.
Ozurdex® 0.7 mg (dexamethasone 0.7 mg implant, Allergan, Dublin, Ireland), an intravitreal biodegradable implant, is indicated for cystoid macular edema due to various causes. One of its known and uncommon complications is implant migration to the anterior chamber, causing corneal edema that, in some cases, is irreversible. Reported risk factors for device migration are open or defective lens capsule and prior history of vitrectomy. We present a case of dexamethasone implant migration through a congenital iris coloboma in a pseudophakic patient with an intact lens capsule. The patient is a 56-year-old pseudophakic man with a history of congenital iris coloboma, myopia, retinal tears, and a branch retinal vein occlusion with subsequent cystoid macular edema resistant to anti-VEGF medications but responsive to corticosteroids. He presented with sudden painless decreased vision in his left eye, 8 weeks following dexamethasone implant (Ozurdex) injection to the same eye. Upon presentation, he was diagnosed with corneal edema caused by anterior chamber migration of the implant. He was referred for immediate surgical intervention to extract the implant, with a resolution of the corneal edema within 2 weeks postoperatively. To conclude, this is the first case that reports Ozurdex implant migration through an iris coloboma in the setting of an intact posterior capsule. In addition, we describe a novel surgical approach for implant removal from the anterior chamber that is simple and efficient.


Report of an autopsy case of colon cancer with amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.


Diversity in midwifery care: working toward social justice.
As midwifery moved from lay practice to a regulated health-care profession in Ontario toward the end of the twentieth century, it brought with it many of its social movement goals and aspirations. Among these was the desire to attend to diversity and equity in the provision of birthing care. Drawing on interviews with currently practicing Ontario midwives, this paper focuses on midwives' conceptualizations of diversity and explores their everyday work to support and strengthen diversity among those using and those providing midwifery care. We argue that midwifery's recent relocation within state structured health care means neither that the social change projects of midwifery are complete nor that midwifery has abandoned its movement-based commitment to social change. Responses to social diversity in health care range from efforts to simply improve access to care to analyses of the role of social justice in recognizing the needs of diverse populations. The social justice aspiration to "create a better world" continues to animate the work of midwives postregulation. This paper explores the legacy of midwifery as a social movement, addressing the connections between diversity, social justice and midwifery care.


Comparing CST Lesion Metrics as Biomarkers for Recovery of Motor and Proprioceptive Impairments After Stroke.
Background. Corticospinal tract (CST) damage is considered a biomarker for stroke recovery. Several methods have been used to define CST damage and examine its relationship to motor performance, but which method is most useful remains unclear. Proprioceptive impairment also affects stroke recovery and may be related to CST damage. Methods. Robotic assessment quantified upper-limb motor and proprioceptive performance at 2 weeks and 6 months poststroke (n = 149). Three previously-established CST lesion metrics were calculated using clinical neuroimaging. Diffusion magnetic resonance imaging quantified CST microstructure in a subset of participants (n = 21). Statistical region of interest (sROI) analysis identified lesion locations associated with motor and proprioceptive deficits. Results. CST lesion metrics were moderately correlated with motor scores at 2 weeks and 6 months poststroke. CST fractional anisotropy (FA) was correlated with motor scores at 1 month poststroke, but not at 6 months. The FA ratio of the posterior limb of the internal capsule was not correlated with motor performance. CST lesion metrics were moderately correlated with proprioceptive scores at 2 weeks and 6 months poststroke. sROI analysis confirmed that CST damage was associated with motor and proprioceptive deficits and additionally found that putamen, internal capsule, and corticopontocerebellar tract lesions were associated with poor motor performance. Conclusions. Across all methods used to quantify CST damage, correlations with motor or proprioceptive performance were moderate at best. Future research is needed to identify complementary or alternative biomarkers to address the complexity and heterogeneity of stroke recovery.