Miracle-dz/UniFAR-FTUs huggingface dataset:
Economic evaluation of a minimal psychological intervention in chronically ill elderly patients with minor or mild to moderate depression: A randomized trial (the DELTA-study)

Objectives: Depression is associated with high healthcare utilization and related costs. Effective treatments might reduce the economic burden. The objective of this study was to establish the cost-utility of a minimal psychological intervention (MPI) aimed at reducing depression and improving quality of life in elderly persons with diabetes or chronic obstructive pulmonary disease and co-occurring minor, mild, or moderate depression. Methods: Trial-based cost-utility analysis was used to compare the MPI with usual care. Annual costs and quality-adjusted life-years (QALYs) based on the Euroqol (EQ5D) and on depression-free days were calculated. Results: Annual costs and effects were not significantly different for the MPI group and care as usual. Bootstrap analysis indicated a dominant intervention, with a probability of 63 percent that the MPI is less costly and more effective than usual care. Conclusions: The cost-effectiveness analysis does not support dissemination of the MPI in its current form. The economic evaluation study showed limited probability that MPI is cost-effective over usual care. Further adjustments to the MPI are needed to make the intervention suitable for dissemination in regular care. Trial registration: isrctn.org, identifier: ISRCTN92331982.
Functional analysis of the murine Pax8 promoter reveals autoregulation and the presence of a novel thyroid-specific DNA-binding activity.

BACKGROUND Organogenesis of the thyroid gland requires the Pax8 protein. Absence or reduction of Pax8 results in congenital hypothyroidism in animal models and humans, respectively. This study aims at elucidating the regulatory mechanism leading to the expression of Pax8 in thyroid cells. METHODS The murine Pax8 gene promoter was functionally dissected by mutagenesis and transfection in the thyroid cell line FRTL-5. Nuclear factors important for thyroid-specific gene expression were identified by DNA-binding assays. RESULTS We show that Pax8 binds to and controls the expression of its own promoter. Furthermore, we identify a novel, thyroid-specific, DNA-binding activity (denominated nTTF [for novel Thyroid Transcription Factor]) that recognizes a specific region of the Pax8 promoter. CONCLUSIONS The Pax8 promoter appears to be autoregulated, a feature that might be responsible for the haploinsufficiency displayed by this gene.
Blood Cells. A Practical Guide

Blood Cells enables both the haematologist and laboratory scientist to identify blood cell features, from the most common to the more obscure. * Provides essential information on methods of collection, blood film preparation and staining, together with the principles of manual and automated blood counts * Completely revised and updated, incorporating much newly published information: now includes advice on further tests when a specific diagnosis is suspected * Four hundred high quality photographs to aid with blood cell identification * Highlights the purpose and clinical relevance of haematology laboratory tests throughout
ENDPOINTS FOR RELATIVE EFFECTIVENESS ASSESSMENT (REA) OF PHARMACEUTICALS

Objectives: Clinical endpoints are defined as valid measures of clinical benefit or harm due to treatment, that describe the impact of treatment on how a patient feels, functions, and survives. The choice of endpoints and the manner in which they are reported have a major impact on the relative effectiveness assessment (REA) of pharmaceuticals. The aim of this article is to describe the guideline development process and the key findings that set a framework for appropriate use of endpoints in REAs in Europe. Methods: A multi-health technology assessment (HTA)-agency collaborative process in EUnetHTA JA1 was used to scope, draft, and finalize methodological guidelines for REA in Europe. Results: Patient-relevant clinical endpoints can be broadly categorized into: mortality, morbidity and health-related quality of life. A clinical endpoint is a main symptom or sign of a disease that is clinically relevant, valid, reproducible and responsive to change. Preference is for long-term or final endpoints whenever possible. Surrogate endpoints may be used when there is compelling evidence of a clear and consistent correlation of treatment effects on the surrogate and final outcome of interest. Conclusions: The relevance and hierarchy of the different types of clinical endpoints depend on the research question, disease, and the treatment investigated. Not only the primary endpoint, but also other relevant endpoints are assessed in comparison to adequate comparator(s). This simultaneous assessment of all relevant endpoints is a hallmark of REA.
A new mutation in the promoter region of the PAX8 gene causes true congenital hypothyroidism with thyroid hypoplasia in a girl with Down's syndrome.

BACKGROUND Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described. OBJECTIVE We studied a girl with DS and CH who had a mutation in the promoter sequence of the PAX8 gene. RESULTS A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of >150 mU/L and a free thyroxine (fT4) of 15.1 pmol/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the PAX8 gene revealed a new heterozygous maternally inherited mutation (-3C>T) close to the transcription initiation site. Electromobility shift assay studies of the wild type and the mutant PAX8 sequence incubated with nuclear extracts from PCCL3 cells exhibited that the sequence at position -3 is not involved in specific protein binding. However, the mutant PAX8 promoter showed a significantly reduced transcriptional activation of a luciferase reporter gene in vitro tested in HEK, PCCL3, as well as in HeLa cells, indicating that this mutation is very likely to lead to reduced PAX8 expression. CONCLUSIONS The persistent CH in this patient with DS is likely to be attributable to the diminished PAX8 expression due to a new heterozygous mutation in the PAX8 promoter sequence. Our case shows that true CH may occur in DS, as in the general population. Furthermore, it is possible that the trisomy 21 itself may have resulted in a more severe phenotypic expression of the PAX8 mutation in the child than the mother.
The Use of Low Transmission Lenses for Patients with Pigmentary Degeneration of the Retina

The use of low transmission lenses in a small sample of retinitis pigmentosa patients is reported. Patients were provided with dark brown plastic goggles which were found to meet the theoretical requirements of the Adrian lens, yet were readily available at modest cost. Subjective reports of improvement in visual function were obtained in most cases and suggest that all retinitis pigmentosa patients should be offered the opportunity to try low transmission filters in spectacle mounted form.
Fertilization in vitro with spermatozoa from different mice increased variation in the developmental potential of embryos compared to artificial parthenogenetic activation

Although successful embryo development is dependent upon genetic and epigenetic contributions from both the male and female, the male potential to adversely affect embryo development has been scarcely studied. It is unclear whether the sperm variation among different males would affect the outcome of oocyte evaluation by embryo development following fertilization. In the present study, variation in the developmental potential of mouse embryos was first compared between in vitro fertilization with epididymal spermatozoa from different males and Sr2+ parthenogenetic activation using oocytes of different qualities, and then the effect of male on fertilization and embryo development was examined using randomly chosen oocytes and spermatozoa from cauda epididymidis, vas deferens or electro‐ejaculates. Rates of fertilization and blastocyst formation were significantly higher with spermatozoa from cauda epididymidis or vas deferens than with ejaculated spermatozoa. Rates of embryonic development differed significantly between different males, but not between different ejaculates of the same male. Analysis of standard errors of means and coefficients of variance indicated that as long as multiple males were involved, the variation in oocyte fertilization/activation and blastocyst formation was always higher after fertilization than after Sr2+ parthenogenetic activation whether spermatozoa were collected from epididymidis, vas deferens or ejaculates and regardless of oocyte qualities. It is concluded that (1) epididymal mouse spermatozoa fertilize more oocytes than ejaculated spermatozoa under identical experimental conditions; (2) like farm animals, the mice also show a remarkable male effect on the developmental potential of in vitro produced embryos although they are supposed to be less genetically diverse; (3) parthenogenetic activation is recommended for assessment of oocyte quality to exclude the effect of male. Mol. Reprod. Dev. 76: 239–245, 2009. © 2008 Wiley‐Liss, Inc.
Flaxseed Improves Lipid Profile without Altering Biomarkers of Bone Metabolism in Postmenopausal Women

The risk of cardiovascular disease and osteoporosis drastically increases at the onset of menopause. Phytoestrogens have been suggested to inhibit bone loss and protect the cardiovascular system, in part by improving lipid profiles. The purpose of the present study was to examine the effects of flaxseed, a rich source of the phytoestrogens called lignans, on lipid metabolism and biomarkers of bone turnover in postmenopausal women. Postmenopausal women who were not on hormone replacement therapy were assigned to one of two treatment groups in a double-blind randomized study. Women were asked to consume 40 g of either ground flaxseed or wheat-based comparative control regimen daily for 3 months. In addition, all subjects received 1,000 mg calcium and 400 IU vitamin D daily. Flaxseed supplementation lowered (P < 0.05) both serum total cholesterol and non-high-density lipoprotein cholesterol by 6%, whereas the comparative control regimen had no such effect. Flaxseed regimen reduced serum levels of both low-density- and high-density-lipoprotein cholesterol by 4.7% and triglyceride by 12.8%, albeit not statistically significant. Serum apolipoprotein A-1 and apolipoprotein B concentrations were significantly (P < 0.005) reduced by 6 and 7.5%, respectively, by the flaxseed regimen. Markers of bone formation and resorption were not affected by either of the treatments. The findings of this study indicate that flaxseed supplementation improves lipid profiles but has no effect on biomarkers of bone metabolism in postmenopausal women.
American cutaneous leishmaniasis: In situ immune response of patients with recent and late lesions

TNF‐α, IFN‐γ, IL‐10, IL‐17, CD68 and CD57 were evaluated in biopsies of patients with American cutaneous leishmaniasis living in Sorocaba, Brazil. The analyses were performed considering the time of lesions from 23 patients with recent lesions (Group I) and 19 patients with late lesions (Group II). All patients were infected with Leishmania (Viannia) braziliensis. Immunostaining cells for CD68, CD57, TNF‐ α, IFN‐γ, IL‐10 and IL‐17 were performed by immunohistochemistry. Except for CD68 and IL‐17, the distribution of in situ for CD57, IL‐10, TNF‐α and IFN‐γ showed that patients with recent lesions expressed higher levels than those with late lesions. The comparison of cytokine expression/group showed that IL‐10 was significantly higher than IL‐17 and IFN‐γ (similar data were shown in IL‐17 compared with TNF‐α), suggesting an immunological balance between inflammatory‐anti‐inflammatory agents. This balance was similar for two groups of patients. In conclusion, these data suggested that (i) patients from Group I had recent lesions (in the beginning of chronic phase) compared to those from Group II and (ii) the modulation of inflammatory response in patients with recent American cutaneous leishmaniasis was correlated with IL‐10 expression in skin lesions preventing the development of mucosal forms. The parasite treatment also prevented the evolution of severe forms.
Metalogic machines: a retrospective rationale for the Japanese Fifth Generation

Abstract The oft quoted inadequacy of von Neumann architectures for AI applications has regularly been used to justify the design of special purpose parallel machines. In particular, the von Neumann computational model has been criticized as being unsuitable for parallelism because of the memory access bottleneck. For the design of a new machine both top-down and bottom-up methodologies have drawbacks. The middle-out strategy, working both up and down from an intrinsically concurrent high-level programming language as a means of both representing and processing knowledge provides an attractive way of providing a symbiosis between software and hardware. The longest established and most well-founded symbolic method for the representation and manipulation of knowledge is logic. A notable result of the last decade, work on mechanical theorem proving was that a subset of predicate logic, Horn Clauses, can form the foundation of a computational model. The execution model of Prolog, the first popular language based on Horn Clauses, was designed for efficient evaluation on von Neumann architectures. An alternative computational model, more suitable for expressing reactive systems but retaining Prolog's affinity for metaprogramming, has given rise to a new class of languages, concurrent logic languages. One among many of these languages, FGHC (flat Guarded Horn Clauses), was developed by the Japanese as the kernel of their Fifth Generation initiative. A background familiarity with Prolog would be helpful in understanding this article.
Can curcumin provide an ideal contraceptive?

The population explosion, unintended pregnancies, sexually transmitted diseases, and cancer (cervical and breast) continue to cause major public health issues worldwide. Curcumin, diferuloyl methane, the yellow pigment component of the curry spice turmeric (Curcuma longa), has immense biological effects and has recently drawn considerable attention. Curcumin has antibacterial, antiviral, antiinflammatory, and anticancer properties. It has shown a lack of toxicity in animals and human clinical trials. Yet, its effect on reproduction has not been examined. The present study was conducted to examine if curcumin affects sperm function in vitro and fertility in vivo. Sperm (human and murine) were collected and incubated with curcumin to examine the effect on motility, capacitation/acrosome reaction, and in vitro fertilization. The effect on in vivo fertility using the mouse model was also examined. Incubation of sperm with curcumin caused a concentration‐dependent decrease in sperm forward motility, capacitation/acrosome reaction, and murine fertilization in vitro. At higher concentrations, there was a complete block of sperm motility and function within 5–15 min. Administration of curcumin, especially intravaginally, caused a significant (P < 0.001) reduction in fertility. The antifertility effect of curcumin was reversible. This is the first study to report the inhibitory effect of curcumin on sperm function, fertilization, and fertility. The findings suggest that curcumin may constitute a double‐edged sword to block conception, infection, and cancer, thus providing an ideal contraceptive. Mol. Reprod. Dev. 78:116–123, 2011. © 2010 Wiley‐Liss, Inc.
Protein tyrosine kinase signaling during oocyte maturation and fertilization

The oocyte is a highly specialized cell capable of accumulating and storing energy supplies as well as maternal transcripts and pre‐positioned signal transduction components needed for zygotic development, undergoing meiosis under control of paracrine signals from the follicle, fusing with a single sperm during fertilization, and zygotic development. The oocyte accomplishes this diverse series of events by establishing an array of signal transduction pathway components that include a select collection of protein tyrosine kinases (PTKs) that are expressed at levels significantly higher than most other cell types. This array of PTKs includes cytosolic kinases such as SRC‐family PTKs (FYN and YES), and FAK kinases, as well as FER. These kinases typically exhibit distinct patterns of localization and in some cases are translocated from one subcellular compartment to another during meiosis. Significant differences exist in the extent to which PTK‐mediated pathways are used by oocytes from species that fertilize externally versus internally. The PTK activation profiles as well as calcium signaling pattern seems to correlate with the extent to which a rapid block to polyspermy is required by the biology of each species. Suppression of each of the SRC‐family PTKs as well as FER kinase results in failure of meiotic maturation or zygote development, indicating that these PTKs are important for oocyte quality and developmental potential. Future studies will hopefully reveal the extent to which these factors impact clinical assisted reproductive techniques in domestic animals and humans. Mol. Reprod. Dev. 78:831–845, 2011. © 2011 Wiley Periodicals, Inc.
Immortalization of swine umbilical vein endothelial cells (SUVECs) with the simian virus 40 large‐T antigen

Implementation of the swine umbilical vein endothelial cells (SUVECs) model in vitro can be instrumental in determining the biology of endothelial cells. We have generated an immortalized endothelial cell line, G‐1410, using Simian virus 40 T‐antigen (SV40 T‐ag) primarily to overcome the short life span before the onset of senescence and high variability among enzymatically isolated cells of primary cultures. Fast proliferating cells were selected from cultures and, after a fifth passage, examined for the presence of the SV40 T‐ag by PCR and immunocytochemistry. Phase contrast and transmission electron microscopy revealed that G‐1410 cells did not differ morphologically from SUVECs. The G‐1410 cells exhibited positive staining for vascular endothelial (VE)‐cadherin and von Willebrand factor (vWF), and formed capillary‐like tube structures on Matrigel. Despite the strong oncogenic signal provided by SV40 T‐ag, these transformed G‐1410 cells have remained karyotypically normal and non‐tumorigenic. G‐1410 cells also responded to stimulation with VEGF, FGF‐2, and newborn calf serum. Moreover, G‐1410 cells showed elevated expression of VEGF120, VEGF164 (VEGF‐A), and FGF‐2 at both mRNA and protein levels. In conclusion, based on the cytological and functional evaluation of the newly obtained immortalized cell line, it can be concluded that G‐1410 cells provide a useful tool for studying the effects of VEGF and FGF systems, and other signal transduction pathways related to angiogenesis. Mol. Reprod. Dev. 78:597–610, 2011. © 2011 Wiley‐Liss, Inc.
Mouse versus rat: Profound differences in meiotic regulation at the level of the isolated oocyte

Cumulus cell‐enclosed oocytes (CEO), denuded oocytes (DO), or dissected follicles were obtained 44–48 hr after priming immature mice (20–23 days old) with 5 IU or immature rats (25–27 days old) with 12.5 IU of equine chorionic gonadotropin, and exposed to a variety of culture conditions. Mouse oocytes were more effectively maintained in meiotic arrest by hypoxanthine, dbcAMP, IBMX, milrinone, and 8‐Br‐cGMP. Atrial natriuretic peptide, a guanylate cyclase activator, suppressed maturation in CEO from both species, but mycophenolic acid reversed IBMX‐maintained meiotic arrest in mouse CEO with little activity in rat CEO. IBMX‐arrested mouse, but not rat, CEO were induced to undergo germinal vesicle breakdown (GVB) by follicle‐stimulating hormone (FSH) and amphiregulin, while human chorionic gonadotropin (hCG) was ineffective in both species. Nevertheless, FSH and amphiregulin stimulated cumulus expansion in both species. FSH and hCG were both effective inducers of GVB in cultured mouse and rat follicles while amphiregulin was stimulatory only in mouse follicles. Changing the culture medium or altering macromolecular supplementation had no effect on FSH‐induced maturation in rat CEO. The AMP‐activated protein kinase (AMPK) activator, AICAR, was a potent stimulator of maturation in mouse CEO and DO, but only marginally stimulatory in rat CEO and ineffective in rat DO. The AMPK inhibitor, compound C, blocked meiotic induction more effectively in hCG‐treated mouse follicles and heat‐treated mouse CEO. Both agents produced contrasting results on polar body formation in cultured CEO in the two species. Active AMPK was detected in germinal vesicles of immature mouse, but not rat, oocytes prior to hCG‐induced maturation in vivo; it colocalized with chromatin after GVB in rat and mouse oocytes, but did not appear at the spindle poles in rat oocytes as it did in mouse oocytes. Finally, cultured mouse and rat CEO displayed disparate maturation responses to energy substrate manipulation. These data highlight significant differences in meiotic regulation between the two species, and demonstrate a greater potential in mice for control at the level of the cumulus CEO. Mol. Reprod. Dev. 78:778–794, 2011. © 2011 Wiley Periodicals, Inc.
Mesobuthus eupeus scorpionism in Sanliurfa region of Turkey

The epidemiology and clinical findings of scorpion stings in Sanliurfa region of Turkey, from May to September 2003, were evaluated in this study. Mesobuthus eupeus (M. eupeus) plays a role on 25.8% of the scorpionism cases. This study also showed that intoxications caused by M. eupeus in the southeast of Anatolia region were seen in hot months of the summer, especially on July. Females and people above 15 years old were mostly affected and stung on extremities. Intense pain in the affected area was observed in 98.7% cases, hyperemia in 88.8%, swelling in 54.6%, burning in 19.7%, while numbness and itching were seen less frequently. In our study, the six most frequently observed symptoms were local pain, hyperemia, swelling, burning, dry mouth, thirst, sweating, and hypotension. In this study involving 152 M. eupeus toxicity cases, patients showed local and systemic clinical effects but no death was seen. Autonomic system and local effects characterized by severe pain, hyperemia and edema were dominantly seen in toxicity cases.