Miracle-dz/UniFAR-FTUs huggingface dataset:
Transforaminal Lumbar Interbody Fusion Versus Anterior Lumbar Interbody Fusion as an Adjunct to Posterior Instrumented Correction of Degenerative Lumbar Scoliosis: Three Year Clinical and Radiographic Outcomes

Study Design. Prospective, nonrandomized consecutive single surgeon series. Objective. To compare the clinical and radiographic outcomes in degenerative lumbar scoliosis (DLS) patients treated with posterior instrumented correction and fusion with additional anterior lumbar interbody fusion (ALIF) versus transforaminal lumbar interbody fusion (TLIF) to help define whether anterior surgery should be routinely required in treating DLS. Summary of Background Data. The benefits of interbody support in promoting postoperative stability and arthrodesis are well established. Whether the interbody fusion is better performed from an anterior or posterior approach has not been studied for patients undergoing surgical correction for DLS. Methods. Forty consecutive patients with DLS, stenosis, and olisthesis underwent posterior instrumented reduction/arthrodesis at average 7 levels (range: 4–9 levels). Additional ALIF was performed in 20 patients, TLIF in the other 20. Follow-up averaged 38 months (24–68 months). Oswestry Disability Index (ODI), visual analog pain scores (VAS) were evaluated preoperative, 1 and 2 years postoperative. Radiograph measurements included the scoliosis, T12 to S1 lordosis, coronal and sagittal balance, and pelvic incidence. CT evaluation of the fusion integrity was performed after 1 year. Results. The ALIF group complications included 4 nonunions, 5 adjacent level fractures, 5 adjacent degeneration, 3 infections, and 1 footdrop. Revision surgery was performed in 8 of 20. Medical complications included 2 nonfatal pulmonary embolus, 1 ileus requiring colostomy, and 1 stroke. TLIF group complications included 3 adjacent segment degeneration, 2 adjacent fractures, 2 nonunions, and 1 infection and transient footdrop. Two of 20 required revision surgery. VAS and ODI improvements for both groups showed significant improvement frompreoperative (P < 0.0019) but were not different. Deformity correction was also similar (70%) between ALIF and TLIF groups. Conclusion. With current deformity correction techniques, both ALIF and TLIF are effective in DLS surgery. Anterior surgery is not routinely required to treat all cases of DLS.
Transcriptional regulation of multidrug resistance‐1 gene by interleukin‐2 in lymphocytes

P‐glycoprotein, encoded by the multidrug resistance (MDR)‐1 gene, expels various drugs from cells resulting in drug resistance. However, its functional relevance to lymphocytes and the regulatory mechanism remain unclear. Although MDR‐1 is known to be induced by various cytotoxic stimuli, it is poorly understood whether the activation stimuli such as cytokines induce MDR‐1 transcription. We investigated the transcriptional regulation of MDR‐1 in lymphocytes by activation stimuli, particularly by interleukin (IL)‐2. IL‐2 induced translocation of YB‐1, a specific transcriptional factor for MDR‐1, from the cytoplasm into nucleus of lymphocytes in a dose‐dependent manner and resulted in the sequential events; transcription of MDR‐1, expression of P‐glycoprotein on the cell surface, and excretion of the intracellular dexamethasone added in vitro. Transfection of YB‐1 anti‐sense oligonucleotides inhibited P‐glycoprotein expression induced by IL‐2. Cyclosporin A, a competitive inhibitor of P‐glycoprotein, recovered intracellular dexamethasone levels in lymphocytes. We provide the first evidence that IL‐2, a representative lymphocyte‐activation stimulus, induces YB‐1 activation followed by P‐glycoprotein expression in lymphocytes. Our findings imply that lymphocytes activation by IL‐2 in vivo, in the context of the pathogenesis of autoimmune diseases, results in P‐glycoprotein‐mediated multidrug resistance, and that P‐glycoprotein could be an important target for the treatment of refractory autoimmune diseases.
Use of Genotype MTBDR Assay for Molecular Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis Clinical Strains Isolated in Italy

ABSTRACT Mycobacterium tuberculosis is one of the leading causes of death worldwide, and multidrug-resistant tuberculosis (MDR-TB) is associated with a high case fatality rate. Rapid identification of resistant strains is crucial for the early administration of appropriate therapy, for prevention of development of further resistance, and to curtail the spread of MDR strains. The Genotype MTBDR (Hain Lifescience, Nehren, Germany) is a reverse hybridization line probe assay designed for the rapid detection of rpoB and katG gene mutations in clinical isolates. The ability of this technique to correctly identify resistant and MDR-TB strains was tested on 206 isolates from the Italian drug resistance surveillance system. This panel included the majority of MDR strains isolated in Italy in the past 3 years. The results of the test were compared to conventional drug susceptibility test performed on isolated strains and verified by sequencing the regions of interest of the bacterial genome. The rate of concordance between the results of the MTBDR and those obtained with “in vitro” sensitivity was 91.5% (130 of 142) for rifampin and 67.1% (116 of 173) for isoniazid. We also applied this test directly to a panel of 36 clinical specimens collected from patients with active TB. The MTBDR correctly identified the two cases of MDR-TB included in the panel. These results show that the MTBDR test is useful in the detection and management of tuberculosis when MDR disease is suspected.
Urinary uronate and sulfated glycosaminoglycan levels: markers for interstitial cystitis severity.

PURPOSE Urologists frequently rely on symptom and problem indexes to monitor patients with interstitial cystitis (IC). Uronic acid is a component of most glycosaminoglycans (GAGs), which is a protective bladder urothelium coating. We evaluated whether urinary uronate and sulfated GAG levels correlate with IC severity and we characterized urinary GAG species. MATERIALS AND METHODS Urine samples, and a completed O'Leary-Sant IC symptom and problem index questionnaire were obtained from 37 patients with IC and 14 normal individuals. Patients with IC were in group 1-1 or 2 indexes less than 50% the maximum score or group 2-each index 50% or greater the maximum score. All patients fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria except glomerulations. Urinary uronate was fractionated using cetyltrimethylammonium bromide (CETAB). Uronate and sulfated GAG levels in urine, CETAB precipitates and CETAB supernatants were measured by the Bitter and Muir, and Farndale assays, respectively, and normalized to creatinine in microg/mg creatinine. GAG species were analyzed by agarose gel electrophoresis. RESULTS Mean urinary uronate levels were increased in group 2 compared with normal and group 1 values regardless of glomerulations and treatment (1,614 +/- 904.6 vs 612.4 +/- 327.2 and 593.8 +/- 422.1 microg/mg creatinine, respectively, p <0.001). A small portion of urinary uronate was CETAB precipitable, representing macromolecular GAGs. Uronate levels in CETAB precipitates and CETAB supernatants were approximately 2.8-fold increased in group 2 (8.0 +/- 5.07 and 1,393 +/- 671.9 microg/mg creatinine, respectively) compared with normal and group 1 values (p <0.001), and they contained fast and slow moving GAG species. Uronate and sulfated GAG had 80% and 88% sensitivity, and 92.3% and 69.2% specificity, respectively, to detect IC severity. CONCLUSIONS The majority of urinary GAGs likely exist as small oligosaccharides. Urinary uronate and sulfated GAG levels are increased in patients with IC who have severe disease. They may become useful markers for monitoring IC.
Effects of elevated ecdysteroid on tissue expression of three guanylyl cyclases in the tropical land crab Gecarcinus lateralis: possible roles of neuropeptide signaling in the molting gland

SUMMARY Two eyestalk (ES) neuropeptides, molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), increase intracellular cGMP levels in target tissues. Both MIH and CHH inhibit ecdysteroid secretion by the molting gland or Y-organ (YO), but apparently through different guanylyl cyclase (GC)-dependent pathways. MIH signaling may be mediated by nitric oxide synthase (NOS) and NO-sensitive GC. CHH binds to a membrane receptor GC. As molting affects neuropeptide signaling, the effects of ecdysteroid on the expression of the land crab Gecarcinus lateralis β subunit of a NO-sensitive GC (Gl-GC-Iβ), a membrane receptor GC (Gl-GC-II) and a NO-insensitive soluble GC (Gl-GC-III) were determined. Gl-GC-Iβ isoforms differing in the absence or presence of an N-terminal 32-amino acid sequence and Gl-GC-III were expressed at higher mRNA levels in ES ganglia, gill, hepatopancreas, ovary and testis, and at lower levels in YO, heart and skeletal muscle. Three Gl-GC-II isoforms, which vary in the length of insertions (+18, +9 and +0 amino acids) within the N-terminal ligand-binding domain, differed in tissue distribution. Gl-GC-II(+18) was expressed highly in striated muscle (skeletal and cardiac muscles); Gl-GC-II(+9) was expressed in all tissues examined (ES ganglia, YO, gill, hepatopancreas, striated muscles and gonads); and Gl-GC-II(+0) was expressed in most tissues and was the dominant isoform in ES and thoracic ganglia. ES ablation, which increased hemolymph ecdysteroid, increased Gl-GC-II(+18) mRNA level in claw muscle. Using real-time RT-PCR, ES ablation increased Gl-GC-Iβ, Gl-GC-III and ecdysone receptor mRNA levels in the YOs ∼ten-, ∼four- and∼ twofold, respectively, whereas Gl-GC-II mRNA level was unchanged. A single injection of 20-hydroxyecdysone into intact animals transiently lowered Gl-GC-Iβ in hepatopancreas, testis and skeletal muscle, and certain Gl-GC-II isoforms in some of the tissues. These data suggest that YO and other tissues can modulate responses to neuropeptides by altering GC expression.
Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo

Background:It has been suggested that mutations of R77A and R80A in the HIV-1 viral protein R (Vpr) impair its proapoptotic activity and that a naturally occurring R77Q variation is associated with non-progressive HIV-1 infection. Rationale:To assess the effect of Vpr R77Q, R77A and R80A mutations on the efficiency of CCR5(R5)- and CXCR4(X4)-tropic HIV-1 replication and cytopathicity in human lymphoid tissue (HLT). Methods:Vpr mutants of the X4-tropic HIV-1 NL4-3 clone and an R5-tropic derivative were generated by PCR mutagenesis. Virus stocks established by transfection of 293T cells were used to infect macrophages and ex vivo HLT. HIV-1 replication was assessed by measuring p24 core antigen in the culture supernatants and CD4 T-cell depletion and apoptosis were measured by flow cytometric analysis. Results:The R5-tropic HIV-1 Vpr mutants replicated with slightly (R77A, R77Q) to moderately (R80A) reduced efficiency in ex vivo-infected HLT and macrophages. In comparison, the changes in Vpr had negligible effects on replication of the X4-tropic forms in lymphatic tissues. Mutation of R77Q and R80A reduced apoptosis of HIV-1-infected cells in ex vivo-infected HLT independently of the viral coreceptor tropism. However, only the R5-tropic HIV-1 Vpr mutants caused markedly less CD4 T-cell depletion than wild-type HIV-1 at the end of ex vivo HLT culture. Conclusions:The observation that Vpr R77Q reduces the cytopathicity of R5-tropic HIV-1 in lymphoid tissues supports a role in non-progressive HIV-1 infection but the attenuating effects might be dependent on the viral subtype and coreceptor tropism.
Five-year study on the autumn food habits of the Asiatic black bear in relation to nut production

We studied the autumn food habits of the Asiatic black bear (Ursus thibetanus) from 1993 to 1997, based on 202 fecal samples in the Chichibu Mountains, central Japan. Nuts occupied the highest proportions of autumn foods (59.9–85.8% important values). Although the proportion of nuts of Quercus crispula, Fagus crenata and Fagus japonica varied greatly between the years, acorns of Q. crispula were most prevalent in four of the five years. We also determined the relative nut production of these three species by counting the number of nuts or cupules on the ground. Black bears consumed the nuts according to their relative availabilities. Nuts of Q. crispula appeared to be the most important food because: (i) these nuts were eaten in the highest proportion in four of the five study years; and (ii) even in poor years the bears consumed acorns of Q. crispula, whereas nuts of Fagus spp. were not consumed. We discuss the significance of alternative foods for black bears in relation to food tree diversity in the forest and the necessity for long-term studies examining the food habits of Asiatic black bears.
Augmentation strategies for treatment‐resistant depression: a literature review

Background: The large majority of depressed patients fail to remit on the first antidepressant prescribed. These patients with residual symptoms have higher relapse rates and poorer outcomes than those who remit. Treatment‐resistant depression (TRD) is a therapeutic challenge for the clinician. Augmentation pharmacotherapy refers to the addition of drugs that are not standard antidepressants in order to enhance the effect of a classical antidepressant drug. The aim of this paper was to review the available evidence on the various augmenting agents that have been tested for efficacy in TRD.
Relationship between body mass index and the risk of ovarian cancer in the Japanese population: Findings from the Japanese Collaborate Cohort (JACC) study

Aim: The incidence of ovarian cancer in Japan has increased since the 1970s. The many studies that have assessed the relationship between body mass index (BMI) and the risk of ovarian cancer have produced contradictory results. Here we investigated this relation using data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk, which was initiated in 1988.
Syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (Carney complex): breast imaging findings.

PURPOSE To study the imaging appearances of breast lesions in female patients with Carney complex. MATERIALS AND METHODS Seven patients with Carney complex underwent mammography (n = 5), ultrasound (US) (n = 6), or magnetic resonance (MR) imaging (n = 6) in a prospective study. Previous breast images in three patients were reviewed. Mammograms in two additional patients were retrospectively reviewed. Thus, nine patients aged 16-61 were included in this study. RESULTS Mammograms showed well-defined, iso- or hypodense masses; most were not calcified. Two lesions contained calcifications; both were biopsy-proved ductal adenomas. US demonstrated solid, hypoechoic, well-circumscribed masses in six patients and complex cystic masses (myxoid fibroadenomas) in one patient. MR imaging with a fat-suppressed, fast spin-echo, T2-weighted sequence demonstrated high-signal-intensity lesions (n = 5). Fat-suppressed, spoiled gradient-recalled-echo MR images demonstrated hypointense lesions with variable contrast material enhancement (n = 5). Five of seven patients in the prospective review had multiple breast lesions on at least one study. Mammograms and US scans were negative in three patients each. Chest and breast MR images were negative in only one patient. CONCLUSION Female patients with Carney complex often have multiple breast masses with variable imaging appearances that probably represent myxoid fibroadenomas or ductal adenomas. MR imaging showed the most lesions. These lesions all demonstrate benign characteristics and should not prompt multiple biopsies.
Growth Factor-Induced Cell Motility in Tumor Invasion

Tumor progression to the invasive and metastatic states dramatically enhances the morbidity and mortality of cancer. Rational therapeutic interventions will only be possible when we understand the molecular mechanisms governing the cell behavior underlying this transformation. For invasion, a subpopulation of tumor cells must recognize the extracellular matrix barrier, modify the barrier, migrate through the barrier, and then proliferate in the adjacent but ectopic locale. Prevention of any one of these steps would prevent invasion, but determining the most sensitively dysregulated step should provide the most promising therapeutic index. In many invasive tumors, upregulation of active motility is stimulated by growth factor receptor signaling, the EGF receptor being the most frequently implicated. Two key downstream molecular switches, PLC n and m-calpain, are required for growth factor-induced motility but not basal, matrix-stimulated motility. Inhibition of either of these enzymes blocks in vitro and in vivo invasion of prostate, breast, and bladder carcinomas and glioblastomas. These represent novel and potentially selective targets for drug development. Future advances in the imaging of tumors in animals and ex vivo organ culture systems should provide additional new targets.
Measurement of protein turnover in normal man using the end-product method with oral [15N]glycine: comparison of single-dose and intermittent-dose regimens

The ‘single-dose end-product’ approach for the measurement of protein turnover is the only method suited for application to free-living individuals and for field studies. However, the method has never been widely accepted because the results obtained appear to vary from one situation to another. There is the need for a formal comparison of the different approaches that have been used and the assumptions on which they are based in order to be able to understand the extent to which the variation in the results obtained is real or might be attributed to methodological differences. The present study used the ‘prime/intermittent-dose end-product’ approach over 18 h as a reference with which to compare the ‘single-dose end-product’ approach, with urine being collected for periods of 9 to 48 h. N flux was derived in a total of thirteen normal men using oral [15N]glycine and measurement of I5N enrichment in urinary NH3 or urea, with isotope being given either as prime/intermittent doses or a single dose in separate studies. The pattern of results was similar to those reported in the literature. In all studies the rates of N flux derived from urea were higher than those derived from NH3, under equivalent conditions, by about 25–30%. The single-dose approach, with urine collection over 9 h, gave results which were consistently higher than the prime/intermittent-dose approach. The extent of the difference was influenced by the duration of time over which the cumulative excretion of isotope in urine was determined, and with NH3 as the end-product the most consistent estimates of N flux could be obtained with a urine collection of at least 12 h and no greater than 24 h. With urea as the end-product, correction for the label retained in the body pool at 9 h gave similar results for N flux to those derived from the total excretion of label in urea over 24 h. The derivation of values for protein synthesis and protein degradation from measures of flux requires care to ensure that the time periods over which N intake and excretion are measured accord with those for which the measurement of flux apply. It is concluded that measurements of protein turnover similar to those obtained with the prime/intermittent-dose approach can be obtained with the single-dose approach in the fed state during the daytime, either from the excretion of label in urinary NH3 over a period of 12 h or with the excretion of label in urinary urea over a period of 24 h. The suitability of the method for use in the fasted state or at night time remains to be determined.
CD105/Ki67 Coexpression Correlates With Tumor Progression and Poor Prognosis in Epithelial Ovarian Cancer

Aim To analyze the expression patterns of CD105 and Ki67 in human epithelial ovarian cancer (EOC) and to evaluate the clinical significance of these two markers in the progression and prognosis in EOC. Materials and Methods The CD105 and Ki67 protein expression patterns in paraffin-embedded specimens gathered from 166 patients with EOC were detected by immunohistochemistry analysis. The association of CD105 and Ki67 protein expression with the prognosis in EOC was subsequently assessed. Results The CD105 and Ki67 proteins were positively expressed in 101/166 (60.8%) and 129/166 (77.7%) of EOC patients, respectively. The CD105+ tumors are more likely to have higher tumor grade (P = 0.02). Patients with positive Ki67 staining are more likely to be at the advanced stage of the disease (P = 0.008). Marker CD105 was positively correlated with Ki67 (r = 0.66, P = 0.01). In addition, Ki67 (hazards ratio [HR], 4.8; confidence interval [CI], 1.2–16.6; P = 0.008) and CD105 (HR, 4.1; CI, 1.0–15.2; P = 0.01) were both independent prognostic factors for poor overall survival in EOC patients. Furthermore, combined CD105/Ki67 expression was significantly related to unfavorable overall survival (HR, 16.6; CI, 1.2–128.9; P < 0.001). Conclusions Our results suggest that the CD105 and Ki67 expressions might be involved in the progression of EOC and patient prognosis. A combined detection of CD105/Ki67 coexpression may benefit us in predicting the prognosis in EOC.
Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila

Significance We report the identification and characterization of a family of proteins encoded by insect DNA viruses and present in the venom of parasitic wasps. These molecules are homologous to the product of the uncharacterized Drosophila gene diedel (die). We show that Diedel is an immunomodulatory cytokine, which down-regulates the evolutionarily conserved immune deficiency (IMD) pathway of host defense in flies. The importance of this factor is highlighted by the fact that die mutant flies, which express high levels of IMD-regulated immunity genes, have reduced viability. Our work provides the first characterization of virokines in insects to our knowledge, and reveals that besides RNA interference and apoptosis, two well-characterized antiviral responses, insect viruses can also suppress a major signaling pathway of the innate immune response. Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.