Trans 10, cis 12-conjugated linoleic acid reduced reproductive ability by disrupting the estrus cycle in female mice.

As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating lipid metabolism, and stimulating energy expenditure. However, the t10c12-CLA products are mostly mixtures, making it difficult to obtain accurate results. Studies are needed to investigate the effects of pure t10c12-CLA on animals and humans. In this study, we used the biallelic transgenic (tg) mice, which could produce t10c12-CLA itself, to investigate the effects of pure t10c12-CLA on female reproductive ability. The results showed that the body and relative ovary weights had no significant difference between tg and wild-type (wt) littermates at ages 3 or 10 weeks. While the fecundity test found that tg mice had a significantly longer first litter time (32.0 ± 4.70 days vs. 21.3 ± 2.31 days, P<0.05), and a significantly lower number of litters (4.75 ± 2.75 vs. 6.67 ± 0.57, P<0.05) when compared with wt mice during continuous mating within seven months. Hormone profiles showed that serum estradiol levels did not change in tg mice; however, significantly (P<0.05) decreased progesterone and increased prostaglandin E2 levels were observed in tg mice compared with those of wt mice. Hematoxylin-eosin staining showed no pathological characteristics in tg ovaries, except for the increased atresia follicles (P<0.05). Moreover, the tg mice had a significantly more extended diestrus period than the wt mice (48.4 ± 6.38% vs. 39.6 ± 3.81%, P<0.05). In summary, t10c12-CLA could affect serum progesterone and prostaglandin E2 levels, lead to a disordered estrus cycle, and impact the reproductive performance of female mice. This study provided theoretical and biosafety recommendations for applying t10c12-CLA in female mammals.

Influence of thoracolumbar kyphosis on postoperative spinal alignment in patients with Lenke type 5C adolescent idiopathic scoliosis.

PURPOSE: This study aimed to examine the changes in thoracolumbar kyphosis (TLK) following correction surgery in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and to evaluate its influence on postoperative spinal alignment and clinical outcomes. METHODS: Sixty-six patients with Lenke type 5C AIS were included and followed up for a minimum of 5 years after surgery. First, the patients were divided into two groups according to the preoperative TLK angle (Study 1; Kyphosis and Lordosis group). The patients were further classified into two groups according to the presence or absence of postoperative changes in TLK (Study 2; Changed and Maintained groups). Finally, the outcome variables were compared between these groups and analyzed for spinal alignment and clinical outcomes. RESULTS: In Study 1, patients demonstrated a significant kyphotic change in the Lordosis group and a significant lordotic change in the Kyphosis group postoperatively. No statistically significant differences were found between the two groups when comparing the pre- and postoperative coronal and sagittal alignment. In Study 2, there were no statistically significant differences between the Changed and the Maintained groups in each spinal alignment pre- and postoperatively. Each domain of the Scoliosis Research Society 22-item questionnaire remained unchanged at 5 years postoperation. CONCLUSION: In many patients with Lenke type 5C AIS, TLK changed significantly and approached 0° after surgery. However, the magnitude of the preoperative TLK and the presence or absence of improvement did not affect postoperative spinal alignment. Furthermore, the patients had satisfactory clinical outcomes irrespective of TLK modification. LEVEL OF EVIDENCE: III.

Ktrans Calculation Using Reference Method Corrected Native T10 for Breast Cancer Diagnosis.

Purpose: The objective of the study is to use multiple tube phantoms to generate correction factor at different spatial locations for each breast coil cuff to correct the native T10 value in the corresponding spatial location of the breast lesion. The corrected T10 value was used to compute Ktrans and analyze its diagnostic accuracy in the classification of target condition, i.e., breast tumors into malignant and benign. Materials and Methods: Both in vitro phantom study (external reference) and patient's studies were acquired on simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) Biograph molecular magnetic resonance (mMR) system using 4 channel mMR breast coil. The spatial correction factors derived using multiple tube phantom were used for a retrospective analysis of dynamic contrast-enhanced (DCE) MRI data of 39 patients with a mean age of 50 years (31-77 years) having 51 enhancing breast lesions. Results: Corrected and non-corrected receiver operating characteristic (ROC) curve analysis revealed a mean Ktrans value of 0.64 min-1 and 0.60 min-1, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy for non-corrected data were 86.21%, 81.82%, 86.20%, 81.81%, and 84.31%, respectively, and for corrected data were 93.10%, 86.36%, 90%, 90.47%, and 90.20% respectively. The area under curve (AUC) of corrected data was improved to 0.959 (95% confidence interval [CI] 0.862-0.994) from 0.824 (95% CI 0.694-0.918) of non-corrected data, and for NPV, it was improved to 90.47% from 81.81%, respectively. Conclusion: T10 values were normalized using multiple tube phantom which was used for computation of Ktrans. We found significant improvement in the diagnostic accuracy of corrected Ktrans values that results in better characterization of breast lesions.

Regulation and Functionality of a Holin/Endolysin Pair Involved in Killing of Galleria mellonella and Caenorhabditis elegans by Yersinia enterocolitica.

The insecticidal toxin complex (Tc) proteins are produced by several insect-associated bacteria, including Yersinia enterocolitica strain W22703, which oscillates between two distinct pathogenicity phases in invertebrates and humans. The mechanism by which this high-molecular-weight toxin is released into the extracellular surrounding, however, has not been deciphered. In this study, we investigated the regulation and functionality of a phage-related holin/endolysin (HE) cassette located within the insecticidal pathogenicity island Tc-PAIYe of W22703. Using the Galleria mellonella infection model and luciferase reporter fusions, we revealed that quorum sensing contributes to the insecticidal activity of W22703 upon influencing the transcription of tcaR2, which encodes an activator of the tc and HE genes. In contrast, a lack of the Yersinia modulator, YmoA, stimulated HE gene transcription, and mutant W22703 ΔymoA exhibited a stronger toxicity toward insect larvae than did W22703. A luciferase reporter fusion demonstrated transcriptional activation of the HE cassette in vivo, and a significantly larger extracellular amount of subunit TcaA was found in W22703 ΔymoA relative to its ΔHE mutant. Using competitive growth assays, we demonstrated that at least in vitro, the TcaA release upon HE activity is not mediated by cell lysis of a significant part of the population. Oral infection of Caenorhabditis elegans with a HE deletion mutant attenuated the nematocidal activity of the wild type, similar to the case with a mutant lacking a Tc subunit. We conclude that the dual holin/endolysin cassette of yersiniae is a novel example of a phage-related function adapted for the release of a bacterial toxin. IMPORTANCE Members of the genus Yersinia cause gastroenteritis in humans but also exhibit toxicity toward invertebrates. A virulence factor required for this environmental life cycle stage is the multisubunit toxin complex (Tc), which is distinct from the insecticidal toxin of Bacillus thuringiensis and has the potential to be used in pest control. The mechanism by which this high-molecular-weight Tc is secreted from bacterial cells has not been uncovered. Here, we show that a highly conserved phage-related holin/endolysin pair, which is encoded by the genes holY and elyY located between the Tc subunit genes, is essential for the insecticidal activity of Y. enterocolitica and that its activation increases the amount of Tc subunits in the supernatant. Thus, the dual holY-elyY cassette of Y. enterocolitica constitutes a new example for a type 10 secretion system to release bacterial toxins.

An ensemble multi-stream classifier for infant needs detection.

In this paper, we propose a novel multi-stream video classifier for infant needs detection. The proposed system is an ensemble-based system that combines several machine learning to improve the overall result of the state-of-the-art algorithms. It is a multi-stream in the sense that it combines the output predictions of both audio and images of infants from every single classifier employed in the system for a unified result. This produces better performance and results compared to the previous other research techniques, which relied on only one of these modalities. For training and testing the proposed system, from the Dunstan Baby Language video collection, we built three separate datasets for videos, images, and sounds encompassing the five primary infant needs that require predicting. These are: hunger, have wind, uncomfortable (require diaper change), wants to burp or tired, with a total of 3348 samples. We used four different ensemble algorithms for the best reachable performance. The proposed algorithm improves the overall accuracies of each single classifier from a low of 51% to a high of 99%. The proposed method also improves the accuracy of the classification process by about 9% compared to the state-of-the-art approaches, which was 90%.

Predicting and explaining absenteeism risk in hospital patients before and during COVID-19.

In order to address one of the most challenging problems in hospital management - patients' absenteeism without prior notice - this study analyses the risk factors associated with this event. To this end, through real data from a hospital located in the North of Portugal, a prediction model previously validated in the literature is used to infer absenteeism risk factors, and an explainable model is proposed, based on a modified CART algorithm. The latter intends to generate a human-interpretable explanation for patient absenteeism, and its implementation is described in detail. Furthermore, given the significant impact, the COVID-19 pandemic had on hospital management, a comparison between patients' profiles upon absenteeism before and during the COVID-19 pandemic situation is performed. Results obtained differ between hospital specialities and time periods meaning that patient profiles on absenteeism change during pandemic periods and within specialities.

Chromosome Translocation t(10;19)(q26;q13) in a CIC-sarcoma.

BACKGROUND/AIM: CIC-sarcomas are characterized by rearrangements of the capicua transcriptional repressor (CIC) gene on chromosome subband 19q13.2, generating chimeras in which CIC is the 5'-end partner. Most reported CIC-sarcomas have been detected using PCR amplifications together with Sanger sequencing, high throughput sequencing, and fluorescence in situ hybridization (FISH). Only a few CIC-rearranged tumors have been characterized cytogenetically. Here, we describe the cytogenetic and molecular genetic features of a CIC-sarcoma carrying a t(10;19)(q26;q13), a chromosomal rearrangement not previously detected in such neoplasms. MATERIALS AND METHODS: A round cell sarcoma removed from the right thigh of a 57-year-old man was investigated by G-banding cytogenetics, FISH, PCR and Sanger sequencing. RESULTS: The tumor cells had three cytogenetically related clones with the translocations t(9;18)(q22;q21) and t(10;19)(q26;q13) common to all of them. FISH with a BAC probe containing the CIC gene hybridized to the normal chromosome 19, to der(10)t(10;19), and to der(19)t(10;19). PCR using tumor cDNA as template together with Sanger sequencing detected two CIC::DUX4 fusion transcripts which both had a stop TAG codon immediately after the fusion point. Both transcripts are predicted to encode truncated CIC polypeptides lacking the carboxy terminal part of the native protein. This missing part is crucial for CIC's DNA binding capacity and interaction with other proteins. CONCLUSION: In addition to demonstrating that CIC rearrangement in sarcomas can occur via the microscopically visible translocation t(10;19)(q26;q13), the findings in the present case provide evidence that the missing part in CIC-truncated proteins has important functions whose loss may be important in tumorigenesis.

Trans-10, cis-12 conjugated linoleic acid- and caloric restriction-mediated upregulation of CNDP2 expression in white adipose tissue in rodents, with implications in feeding and obesity.

Certain dietary supplements such as trans-10, cis-12 conjugated linoleic acid (t10-c12 CLA), and diets including caloric-restricted diets can promote weight loss in certain animal models and humans. A very recent study showed that exercise induces the biosynthesis of N-lactoyl-phenylalanine (Lac-Phe), a circulating signaling metabolite that suppresses feeding and obesity selectively in mice fed with a high-fat diet, and that cytosolic nonspecific dipeptidase 2 (CNDP2) catalyzes the synthesis of Lac-Phe from lactate (Lac) and phenylalanine (Phe). In this in silico study, we found that two anti-obesity strategies, namely treatment with t10-c12 CLA and caloric restriction, increase CNDP2 expression in adipose tissue in mice and rats, respectively. We showed that the effect of t10-c12 CLA on CNDP2 expression might be isomer-specific. We hypothesized that these t10-c12 CLA treatment- or caloric-restricted diet-mediated increases in CNDP2 expression might contribute to their anti-obesity effects, possibly due to increased Lac-Phe levels and ultimately due to Lac-Phe-mediated decreases in daily food consumption, reduced body weight and fat mass. A better understanding of the regulation of CNDP2 expression in diverse tissues in mammals might be of high importance in the treatment of obesity, considering its role in the synthesis of Lac-Phe, a metabolite that decreases body weight and fat mass selectively in mice fed with a high-fat diet. Further research is needed to find out how these two strategies lead to the upregulation of CNDP2 expression and whether this increased expression of CNDP2 might translate to reduced body weight and fat mass through higher Lac-Phe levels.

Cervical sagittal alignment is influenced by changes in thoracic and lumbar sagittal alignments after correction surgery in patients with lenke type 6 adolescent idiopathic scoliosis.

Background: Few studies have examined the changes in cervical sagittal alignment (CSA) and its relationship with other sagittal alignments in AIS patients with major thoracolumbar/lumbar (TL/L) curve who underwent correction surgery. This study investigated the radiographical changes in CSA after correction surgery in patients with Lenke type 6 adolescent idiopathic scoliosis (AIS) and assess any possible factors affecting postoperative CSA. Methods: Forty-four patients with Lenke type 6 AIS (3 males and 41 females, mean age at surgery of 15.6 ± 2.8 years) who could be followed up for 3 years after correction surgery were included in this study. Variations of outcome variables were analyzed in various spinal sagittal parameters using radiographic outcomes. Univariate correlation analyses were used to evaluate possible factors influencing the postoperative CSA. The Scoliosis Research Society (SRS)-22 questionnaires and the Oswestry Disability Index (ODI) were used for clinical evaluation, and the changes between pre- and 3-year post-operation were compared. Results: The Cobb angle of the major and minor curve was significantly improved after correction surgery. Furthermore, CSA, such as C2-7 angle and T1 slope, changed significantly postoperatively. The magnitude of coronal curve correction did not affect CSA postoperatively, while the postoperative TK, T10-L2 kyphosis and LL were significantly correlated with the postoperative C2-7 angle, respectively. None of the patients in this study complained of neck or low back pain during the period up 3 years after the operation. Comparing each domain of SRS-22 or ODI score, these were unchanged between pre-, 1-year, and 3-year post-operation, with no statistically significant differences. Conclusions: CSA changed significantly after correction surgery, and cervical kyphosis indicated a tendency to decrease in Lenke type 6 AIS patients, which was associated with an improvement in thoracic and lumbar sagittal alignment, not correction for coronal deformity.

Effects of in ovo feeding of t10,c12-conjugated linoleic acid on hepatic lipid metabolism and subcutaneous adipose tissue deposition in newly hatched broiler chicks.

The purpose of this study was to investigate whether in ovo feeding of t10,c12-conjugated linoleic acid (CLA) could regulate hepatic lipid metabolism and decrease lipid accumulation in newly hatched chicks. Three hundred and sixty fertilely specific pathogen-free hatching eggs were selected and randomly divided into 6 groups. On embryonic day 11 of incubation (E11), 0, 1.5, 3.0, 4.5, 6.0, or 7.5 mg t10,c12-CLA were injected into the eggs. The results indicated that in ovo feeding of t10,c12-CLA significantly decreased the subcutaneous adipose tissue (SAT) mass and the relative SAT weight of newly hatched chicks in linear and quadratic manners (P < 0.05). In liver, the levels of triglycerides were reduced linearly and quadratically and total cholesterol were reduced quadratically as the dose of t10,c12-CLA increased (P < 0.05). Meanwhile, the hepatic carnitine palmitoyltransferase-1a (CPT1a) content and polyunsaturated fatty acid proportion were increased quadratically in t10,c12-CLA groups (P < 0.05), accompanied by the decrease of malondialdehyde level and the increase of glutathione peroxidase and total antioxidant capacity activities (P < 0.05). In addition, in ovo feeding of t10,c12-CLA decreased the mRNA expression levels of fatty acid synthase, acetyl-CoA carboxylase 1 in linear and quadratic manners (P < 0.05), and decreased the mRNA expression of adipose triacylglyceride lipase and stearoyl-CoA desaturase significantly in liver (P < 0.05), accompanied by upregulating the mRNA expression of CPT1a quadratically and AMP-activated protein kinase α linearly and quadratically (P < 0.05). In SAT, the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) and sterol regulatory element-binding protein-1c were decreased linearly and quadratically (P < 0.05), and the expression of PPARα and CPT1a genes were increased linearly and quadratically as the dose of t10,c12-CLA increased (P < 0.05). In conclusion, our findings demonstrate that in ovo feeding of t10,c12-CLA alleviates lipid accumulation in newly hatched chicks by suppressing fatty acid synthesis and stimulating lipolysis in the liver and inhibiting adipocyte differentiation in subcutaneous adipose tissue.

Adult Acute Myeloid Leukemia with the KMT2A-Mixed Lineage Leukemia T10 Fusion: An Analysis of 10 Cases Showed Common Features and Frequent Mutations in the RAS Signaling Pathway.

Mixed lineage leukemia (MLL) T10 is a relatively rare partner for the KMT2A lysine (K)-specific methyltransferase 2A gene. The common features and coexisting mutations of acute myeloid leukemia (AML) patients with KMT2A-MLLT10 remain unknown. In this study, 10 adult AML patients with KMT2A-MLLT10 fusions were picked up from 496 AML patients by using RT-polymerase chain reaction (PCR) and/or fluorescence in situ hybridization, and then screened for mutations in the 49 genes panel with next-generation sequencing and PCR, followed by direct Sanger sequencing. Of the 10 unique individuals identified, 6 were male and 4 were female (M:F ratio, 1.5:1) with ages ranging from 19 to 52 years (median 39.5 years). Most (90%, 9/10) patients with KMT2A-MLLT10 were accompanied by additional mutations. Twelve mutated genes were detected, averaging 2.1 mutations per patient (range, 0-4). The most frequently mutated gene was NRAS (n = 5). Clinical and laboratory data pointed to common features: French American British-M5 subtype (n = 7), a high rate of relapse, and biomarkers CD33 (n = 10), CD117 (n = 9), CD13 (n = 8), and CD64 (n = 8). Overall, most patients harbored at least one mutation. A high incidence of mutations affecting the RAS signaling pathway or RAS regulating components was found in 50% (5/10) patients. The overall survival is about 12.0 months. Allogeneic-hematopoietic stem cell transplantation trends to improve survival in selected patients.

Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies: Implications in interpretation of cell uptake studies.

Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles, with their tunable structural features and capability of loading a wide range of drugs and reporter probes, are emerging as versatile injectable nanopharmaceuticals. Secondary emulsifiers, such as Pluronic block copolymers, are commonly used for colloidal stabilization of LLC nanoparticles, but their inclusion often compromises the biological safety (e.g., poor hemocompatibility and enhanced cytotoxicity) of the formulation. Here, we introduce a library of colloidally stable, structurally tunable, and pH-responsive lamellar and non-lamellar liquid crystalline nanoparticles from binary mixtures of a phospholipid (phosphatidylglycerol) and three types of omega-3 fatty acids (ω-3 PUFAs), prepared in the absence of a secondary emulsifier and organic solvents. We study formulation size distribution, morphological heterogeneity, and the arrangement of their internal self-assembled architectures by nanoparticle tracking analysis, synchrotron small-angle X-ray scattering, and cryo-transmission electron microscopy. The results show the influence of type and concentration of ω-3 PUFAs in nanoparticle structural transitions spanning from a lamellar (Lα) phase to inverse discontinuous (micellar) cubic Fd3m and hexagonal phase (H2) phases, respectively. We further report on cell-culture medium-dependent dynamic fluctuations in nanoparticle size, number and morphology, and simultaneously monitor uptake kinetics in two human cell lines. We discuss the role of these multiparametric biophysical transformations on nanoparticle-cell interaction kinetics and internalization mechanisms. Collectively, our findings contribute to the understanding of fundamental steps that are imperative for improved engineering of LLC nanoparticles with necessary attributes for pharmaceutical development.

trans 10, cis 12, but Not cis 9, trans 11 Conjugated Linoleic Acid Isomer Enhances Exercise Endurance by Increasing Oxidative Skeletal Muscle Fiber Type via Toll-like Receptor 4 Signaling in Mice.

Conjugated linoleic acid (CLA) has been implicated in regulating muscle fiber. However, which isomer elicits this effect and the underlying mechanisms remain unclear. Here, male C57BL6/J mice and C2C12 cells were treated with two CLA isomers, and the exercise endurance, skeletal muscle fiber type, and involvement of Toll-like receptor 4 (TLR4) signaling were assessed. The results demonstrated that dietary t10, c12, but not c9, t11-CLA isomer enhanced exercise endurance of mice (from 115.88 ± 11.21 to 130.00 ± 15.84 min, P < 0.05) and promoted the formation of oxidative muscle fiber type of gastrocnemius muscle (from 0.15 ± 0.04 to 0.24 ± 0.05, P < 0.05). Consistently, t10, c12-CLA isomer increased the mRNA expression of oxidative muscle fiber type in C2C12 myotubes (from 1.00 ± 0.08 to 2.65 ± 1.77, P < 0.05). In addition, t10, c12-CLA isomer increased TLR4 signaling expression in skeletal muscle and C2C12 myotubes. More importantly, knockdown of TLR4 eliminated the t10, c12-CLA isomer-induced enhancement of exercise endurance in mice and elevation of oxidative muscle fiber type in C2C12 myotubes and gastrocnemius muscle. Together, these findings showed that t10, c12, but not c9, t11-CLA isomer enhances exercise endurance by increasing oxidative skeletal muscle fiber type via TLR4 signaling.

The Danger of Walking with Socks: Evidence from Kinematic Analysis in People with Progressive Multiple Sclerosis.

Multiple sclerosis (MS) is characterized by gait impairments and severely impacts the quality of life. Technological advances in biomechanics offer objective assessments of gait disabilities in clinical settings. Here we employed wearable sensors to measure electromyography (EMG) and body acceleration during walking and to quantify the altered gait pattern between people with progressive MS (PwPMS) and healthy controls (HCs). Forty consecutive patients attending our department as in-patients were examined together with fifteen healthy controls. All subjects performed the timed 10 min walking test (T10MW) using a wearable accelerator and 8 electrodes attached to bilateral thighs and legs so that body acceleration and EMG activity were recorded. The T10MWs were recorded under three conditions: standard (wearing shoes), reduced grip (wearing socks) and increased cognitive load (backward-counting dual-task). PwPMS showed worse kinematics of gait and increased muscle coactivation than controls at both the thigh and leg levels. Both reduced grip and increased cognitive load caused a reduction in the cadence and velocity of the T10MW, which were correlated with one another. A higher coactivation index at the thigh level of the more affected side was positively correlated with the time of the T10MW (r = 0.5, p < 0.01), Expanded Disability Status Scale (EDSS) (r = 0.4, p < 0.05), and negatively correlated with the cadence (r = -0.6, p < 0.001). Our results suggest that excessive coactivation at the thigh level is the major determinant of the gait performance as the disease progresses. Moreover, demanding walking conditions do not influence gait in controls but deteriorate walking performances in PwPMS, thus those conditions should be prevented during hospital examinations as well as in homecare environments.

Conjugated Linoleic Acid and Its Beneficial Effects in Obesity, Cardiovascular Disease, and Cancer.

Conjugated linoleic acid (CLA) is a dietary polyunsaturated fatty acid found in animal fats suchas red meat and dairy products [1].[...].

Can L5 Be Trusted During Proximal Extension of Fusion? A Case Series and a Review of the Literature.

BACKGROUND: Debate on whether to stop fusion at L5 or to extend fusion to S1 in a long spinal construct has been a controversial topic in spine surgery. Fewer data are available to support whether to include a prior solid fusion at L4-L5 or to extend to S1 during a proximal extension of fusion to T10. The purpose of this review is to report and discuss 2 cases of L5 vertebra fracture after proximal extension of solid L4-L5 fusion to T10 and to provide a guideline to surgeons based on the available literature. METHODS: Case report and literature review. RESULTS: Literature review identified multiple publications with levels of evidence from level 2 to level 4. Advanced L5-S1 degeneration with long-segment fusion to L5 is reported to be greater than 60% with a new rate of symptom development approaching 20%-25%. There is no prior literature specific to L5 fracture development after thoracic lumbar fusion with the lowest instrumented level at a fused L4-L5 segment. Reoperation rate is not consistently affected by the lowest instrumented vertebral level L5 versus sacrum/ilium. CONCLUSIONS: Literature review is inconclusive as to the need to include the lumbosacral junction when performing a proximal extension of fusion from L5 to the thoracic spine, especially during a revision adult deformity surgery. Stress of the long lever arm of a long-segment thoracolumbar fusion above a prior solid L4-L5 fusion could cause the L5 vertebra to split in the coronal plane, resulting in vertebral body fracture even with a mildly degenerated disc at L5-S1 prior to surgery. LEVEL OF EVIDENCE: 4.

MLLT10 rearranged acute leukemia: Incidence, prognosis, and possible therapeutic strategies.

Rearrangements of the MLLT10 gene occur in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), most commonly T-lineage ALL (T-ALL), in patients of all ages. MLLT10 rearranged (MLLT10r) acute leukemia presents a complex diagnostic and therapeutic challenge due to frequent presentation of immature or mixed phenotype, and a lack of consensus regarding optimal therapy. Cases of MLLT10r AML or T-ALL bearing immature phenotype are at high risk of poor outcome, but the underlying molecular mechanisms and sensitivity to targeted therapies remain poorly characterized. This review addresses the incidence and prognostic significance of MLLT10r in acute leukemia, and how the aberrant gene expression profile of this disease can inform potential targeted therapeutic strategies. Understanding the underlying genomics of MLLT10r acute leukemia, both clinically and molecularly, will improve prognostic stratification and accelerate the development of targeted therapeutic strategies, to improve patient outcomes.

A novel translocation t(10;17)(p13;q11.2) harboring two cryptic deletions identified by array-CGH and characterized by SUZ12 overexpression in a patient with chronic thrombocytosis.

No specific translocation is associated with myeloproliferative neoplasms (MPNs). However, an interstitial deletion involving subband 17q11.2 which includes the NF1 gene, although rare, is a recurrent aberration in several myeloid disorders including MPNs. For the first time, we report an acquired novel translocation involving 10p13 and 17q11.2 in a 62-year-old Caucasian female which was referred for investigation of chronic and persistent unexplained thrombocytosis. The patient had no history of hematological sequelae and genomic testing for JAK2, CALR, and MPL mutations were negative. She was subsequently diagnosed with a triple negative essential thrombocythemia. Array-CGH analysis noted that the translocation harbored two cryptic deletions, one of which involved 17q11.2 encompassing the NF1 gene. One of the junction breakpoints involved the SUZ12 gene. Immunohistochemical assessment of the marrow trephine showed increased megakaryocytic expression of the SUZ12 protein, as well as EZH2 and Ki67; biochemical abnormalities suggestive of excess megakaryocytic hyperplasia. This novel translocation may affect the expression of SUZ12 and its downstream targets, and may represent a unique pathogenomic etiology which drives chronic thrombocytosis in essential thrombocythemia.

A single amino acid substitution in the FAD-binding domain causes the inactivation of Propionibacterium Acnes isomerase.

We previously demonstrated the efficient production of trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) in Lactococcus lactis by ectopically expressing a Propionibacterium acnes isomerase (pai) gene and also mentioned that a recombinant strain was unable to accumulate t10c12-CLA product, despite the normal transcription. Here, the molecular analysis indicated that this mutated strain harbors a pai gene with a single-nucleotide mutation converting GC50A to GTA, leading to a corresponding change of Alanine residue into Valine. The expression of the reverse mutation resulted in the recovery for enzyme activity. Site-directed mutagenesis indicated that the codon usage of Val17 was not responsible for the enzyme inactivation in the Ala17Val mutation. Western blot analysis revealed that the recombinant PAI protein was not detectable in the His tag-marked Ala17Val mutant. It is, therefore, reasonable to assume that Ala17 residue is critical for PAI functionality.Abbreviations: pai: propionibacterium acnes isomerase; CLA: conjugated linoleic acid; t10c12-CLA: trans 10, cis 12-CLA; LA: linoleic acid (18:2n-6); FAD: flavin adenine dinucleotide.

Regulation of Stearoyl-Coenzyme A Desaturase 1 by trans-10, cis-12 Conjugated Linoleic Acid via SREBP1 in Primary Goat Mammary Epithelial Cells.

trans-10, cis-12 Conjugated linoleic acid (t10c12-CLA) is a biohydrogenation intermediate in the rumen that inhibits mammary fatty acid de novo synthesis in lactating dairy goats. However, the underlying molecular pathways in milk-lipid metabolism affected by t10c12-CLA are not completely understood. The present study investigated the lipid-regulation mechanisms in goat mammary epithelial cells (GMECs) in response to t10c12-CLA. Gene-expression analysis indicated sterol-regulatory-element-binding transcription factor1 ( SREBF1) and its putative target gene stearoyl-CoA desaturase ( SCD1) were down-regulated (fold changes of 0.33 ± 0.04, P < 0.05, and 0.19 ± 0.01, P < 0.01, respectively). Concentrations of cellular palmitoleic acid (C16:1) and oleic acid (C18:1) were decreased (1.12 ± 0.05 vs 1.69 ± 0.11% and 15.70 ± 0.44 vs 24.97 ± 0.82%, respectively, P < 0.01), whereas those of linoleic acid (C18:2) were increased (5.00 ± 0.14 vs 3.81 ± 0.25%, P < 0.05); the desaturation indices of C16 and C18 were decreased in response to t10c12-CLA treatment (6.90 ± 0.05 vs 8.00 ± 0.30% and 61.41 ± 0.65 vs 67.73 ± 1.33%, respectively, P < 0.05). A luciferase-activity assay indicated that deletion of the sterol-response-element (SRE) site and the nuclear-factor (NF-Y) site in the SCD1-promoter region (-511/+65 bp) suppressed the regulatory effect of t10c12-CLA. Overexpression of SREBF1 partly counteracted the inhibitory effect of t10c12-CLA on de novo fatty acid synthesis. Overall, t10c12-CLA causes an inhibition of fatty acid synthesis and desaturation and regulates SCD1 expression by affecting the binding of SREBP1 protein to the SRE and NF-Y sites.