Enhancing follicular growth as a prerequisite for GnRH treatment of true anestrum in buffalo.
A total of 140 true anestrous buffalo were divided on the basis of receiving short-term (20 days) nutritional supplementation (N, n=80) or not (WN, n=60). The animals in N group were subdivided into NQ (n=40) where the quantity of the offered diet was increased by 20% and NF (n=40) where the offered diet was supplemented by 3% of dry protected fat. Buffaloes in either NQ or NF were equally allotted on the following treatment regimens: Insulin/GnRH (NQi or NFi, n=10 for each); rbST/GnRH (NQr or NFr, n=10 for each); GnRH alone treated (NQG or NFG, n=10 for each) and saline-treated control (NQc or NFc, n=10 for each). Insulin-treated subgroups (NQi or NFi) received s/c injection of insulin at a dose of 0.25 I.U./kg on Days 21, 22 and 23 while rbST-treated subgroups (NQr or NFr) received single IM injection of rbST (500 mg Sometribove) on Day 21. GnRH was injected at a dose of 0.020 mg buserelin (5 ml Receptal(®)) on Day 24 in all subgroups except NQCand NFC where Day 1 was the first day of the short-term nutritional improvement. Buffalo in the WN (n=60) were equally allotted on the same treatment regimens applied in the first group insulin/GnRH (WNi, n=15), rbST/GnRH (WNr, n=15); GnRH alone treated (WNG, n=15) and saline-treated control (WNC, n=15). Ultrasonic scanning of ovaries was conducted on Day 24 to measure largest follicle diameter (LFD). The results showed increases (P<0.05) in the LFD following nutritional supplementation with insulin or rbST. The recorded EIRs for GnRH pre-treated with nutritional improvement - metabolic hormones combinations (9/10 and 8/10 for NQi and NFi or 8/10 for NQr) were greater (P<0.05) than those pre-treated with either metabolic hormone alone (7/15 for WNi and/or WNr) or nutritional improvement alone (6/10 for NQG and/or NFG) and control as well. The greatest CR was recorded in the NQi group. It could be concluded that pre-GnRH nutritional improvement plus administration of insulin or rbST increases LFD in true anestrous buffalo having LFD<8.5 mm thereby increasing their fertility response to GnRH in terms of EIRs and CRs.


Comparing the acceptor promiscuity of a Rosa hybrida glucosyltransferase RhGT1 and an engineered microbial glucosyltransferase OleD(PSA) toward a small flavonoid library.
Glycosylation is a widespread modification of plant secondary metabolites, and catalyzed by a superfamily of enzymes called UDP-glycosyltransferases (UGTs). UGTs are often involved in late biosynthetic steps and show broad substrate specificity or regioselectivity. In this study, the acceptor promiscuity of a Rosa hybrid UGT RhGT1 and an evolved microbial UGT OleD(PSA) toward a small flavonoid library was probed and compared. Interestingly, RhGT1 showed comparable acceptor promiscuity in comparison with OleD(PSA), though the acceptor binding pocket of the latter is much more open and large. This clearly indicates that stabilization of the acceptor position by suitable hydrophobic interactions is important for the specificity or regioselectivity determination as well as overall fit of the acceptor into a 'big enough' binding pocket. This also poses a challenge for structure-based UGT engineering to alter the glucosylation pattern of flavonoids.


Calmodulin inhibits the epidermal growth factor receptor tyrosine kinase.
We demonstrate in this report that the epidermal growth factor (EGF) receptor from rat liver can be isolated by calmodulin affinity chromatography by binding in the presence of Ca2+ and elution with a Ca(2+)-chelating agent. The bulk of the EGF receptor is not eluted by a NaCl gradient in the presence of Ca2+. We ascertained the identity of the isolated receptor by immunoblot and immunoprecipitation using a polyclonal antibody against an EGF receptor from human origin. The purified receptor is autophosphorylated in tyrosine residues in an EGF-stimulated manner, and EGF-dependent phosphorylation of serine residues was also detected. Both the EGF and the transforming growth factor-alpha stimulate the tyrosine-directed protein kinase activity of the isolated receptor with similar affinities. Furthermore, we demonstrate that calmodulin inhibits the EGF-dependent tyrosine-directed protein kinase activity associated to the receptor in a concentration-dependent manner. This inhibition is partially Ca2+ dependent and is not displaced by increasing the concentration of EGF up to an EGF/calmodulin ratio of 10 (mol/mol). In addition, calmodulin was phosphorylated in an EGF-stimulated manner in the presence of a basic protein (histone) as cofactor and in the absence, but not in the presence, of Ca2+.


Androgenic correlates of genetic variation in the gene encoding 5alpha-reductase type 1.
Androgens determine male secondary sexual characteristics and influence a variety of metabolic pathways. Circulating levels of androgens are highly heritable; however, the genes involved are largely unknown. The 5alpha-reductase enzymes types 1 and 2 responsible for converting testosterone to the more potent androgen dihydrotestosterone are encoded by the SRD5A1 and SRD5A2 genes, respectively. We performed indirect genetic association studies of SRD5A1 and SRD5A2 and the dihydrotestosterone/testosterone ratio that reflects the activity of 5alpha-reductase in 57 males with type 2 diabetes. We found evidence of significant association between a single nucleotide polymorphism in SRD5A1 and the dihydrotestosterone/testosterone ratio (median 0.10, interquartile range 0.08 vs. median 0.06, interquartile range 0.04, P = 0.009). The polymorphism was not associated with any diabetic phenotypes. These results suggest that functional genetic variants might exist in or around SRD5A1 that affect the activity of the 5alpha-reductase enzyme type 1 and influence androgen levels.


High Resolution Computed Tomography of Temporal Bone: The Predictive Value in Atticoantral Disease.
To evaluate predictive value of high resolution computed tomography in atticoantral disease. We conducted a prospective observational study in 49 patients suffering from atticoantral disease at tertiary referral institute. Preoperatively, all the patients underwent unenhanced high resolution computed tomography (HRCT) of temporal bone parallel to orbitomeatal line by using multislice scanner. We evaluated presence of soft tissue attenuation, ossicular erosion, facial canal erosion, dural exposure, erosion of semicircular canal, labyrinthine fistula, erosion of scutum and tegmen tympani in CT scan. HRCT is recommended in atticoantral disease with complications. This study demonstrates the predictive value of HRCT of temporal bone as a diagnostic modality in atticoantral disease. HRCT shows 100% sensitivity (Sn) of soft tissue density detected in middle ear, aditus and attic. Specificity (Sp) was more for eustechian tube area and sinus tympani. Ossicular erosions of malleus (Sn = 90.9%, Sp = 75%), incus (Sn = 93.2%, Sp = 80%), stapes (Sn = 78.8%, Sp = 68.8%) were detected. Erosion of scutum (Sn = 94.1%, Sp = 80%), tegmen (Sn = 66.7%, Sp = 100%), sinus plate (Sn = 100%, Sp = 97.9%), facial nerve canal (Sn = 75%, Sp = 100%), semicircular canal fistula (Sn = 80%, Sp = 97.7%) and cochlear promontory fistula (Sn = 50%, Sp = 97.9%) were evaluated. HRCT temporal bone helps to evaluate disease extent and involvement of surrounding structures. Hence it helps in deciding surgical approach and also prevents impending complications.


Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft.
Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally verified their selective inhibitory activity. Three inhibitors exhibited low-micromolar IC50 values. Molecular dynamics simulations revealed a common binding mode for these inhibitors, involving association to the TDP2 DNA-binding cleft. MM-PBSA per-residue energy decomposition identified important interactions of the compounds with specific TDP2 residues. These interactions could provide new avenues for synthetic optimization of these scaffolds.


Comparing Heterotopic Ossification in Two Cervical Disc Prostheses.
Retrospective analysis using data from randomized clinical trials. To compare the occurrence of heterotopic ossification (HO) between two cervical disc prostheses. Clinical outcome and range of motion (ROM) were also evaluated. Cervical arthroplasty was reported to be able to maintain the segmental ROM. However, controversy exists since the difference of the occurrence of HO concerning cervical prosthesis is still huge. Patients who underwent anterior cervical discectomy with arthroplasty for a cervical radiculopathy due to a herniated disc from the The Netherlands Cervical Kinematics (NECK) trial (activC; metal endplates with a polyethylene inlay and a keel for primary stability) and the PROCON trial (Bryan; metal-on-polymer with titanium coated endplates without a keel) were analyzed for HO at 12 and 24 months postoperatively. HO was scored according to the McAfee-Mehren classification. Segmental ROM was defined by a custom developed image analysis tool, and global cervical ROM was measured by Cobb's angle. Clinical outcome was evaluated by means of the neck disability index (NDI) as well as physical-component summary (PCS) and mental-component summary (MCS). At 2-year follow-up, the occurrence of HO was 68% in patients treated with the activC prosthesis (severe HO 55%), which was comparable with 85% (P = 0.12) in patients with the Bryan disc (severe HO 44%; P = 0.43). The HO progression was similar between groups. Clinically, the patients had comparable NDI, PCS, and MCS at 2-year follow-up, and comparable improvement of clinical outcomes. The global ROM in the Bryan group (56.4 ± 10.8°) was significantly higher than in the activC group (49.5 ± 14.0, P = 0.044) at 2-year follow-up. In comparison of two cervical disc prostheses the development of HO is independent on their architecture. Although global ROM was higher in the Bryan prosthesis group, this difference was not deemed clinically important, particularly because the clinical condition of patients with and without severe HO was comparable. 2.


Redox-Active Metal-Organic Composites for Highly Selective Oxygen Separation Applications.
A redox-active metal-organic composite material shows improved and selective O2 adsorption over N2 with respect to individual components (MIL-101 and ferrocene). The O2 sensitivity of the composite material arises due to the formation of maghemite nanoparticles with the pore of the metal-organic framework material.


Anaerobiospirillum succiniciproducens sepsis in an autopsy patient: A troublesome diagnostic workup.
Anaerobiospirillum succiniciproducens is an uncommon yet potentially lethal gram-negative bacterium typically affecting patients with comorbidities. We report a case of A. succiniciproducens infection in an autopsy patient who had hepatitis C and type 2 diabetes and describe the difficulties in the laboratory identification of this pathogen.


Lentiviral transduction of human postnatal skeletal (stromal, mesenchymal) stem cells: in vivo transplantation and gene silencing.
Systems for gene transfer and silencing in human skeletal stem cells (hSSCs, also stromal or mesenchymal stem cells) are important for addressing critical issues in basic hSSC and skeletal biology and for developing gene therapy strategies for treatment of skeletal diseases. Whereas recent studies have shown the efficacy of lentiviral transduction for gene transfer in hSSCs in vitro, no study has yet proven that lentivector-transduced hSSCs retain their distinctive organogenic potential in vivo, as probed by in vivo transplantation assays. Therefore, in addition to analyzing the in vitro growth and differentiation properties of hSSCs transduced with advanced-generation lentivectors, we ectopically transplanted LV-eGFP-transduced hSSCs (along with an osteoconductive carrier) in the subcutaneous tissue of immunocompromised mice. eGFP-transduced cells formed heterotopic ossicles, generating osteoblasts, osteocytes, and stromal cells in vivo, which still expressed GFP at 2 months after transplantation. eGFP-expressing cells could be recovered from the ossicles 8 weeks posttransplantation and reestablished in culture as viable and proliferating cells. Further, we investigated the possibility of silencing individual genes in hSSCs using lentivectors encoding short hairpin precursors of RNA interfering sequences under the control of the Pol-III-dependent H1 promoter. Significant long-term silencing of both lamin A/C and GFP (an endogenous gene and a transgene, respectively) was obtained with lentivectors encoding shRNAs. These data provide the basis for analysis of the effect of gene knockdown during the organogenesis of bone in the in vivo transplantation system and for further studies on the silencing of alleles carrying dominant, disease-causing mutations.


Cloning and regulation of a mRNA specifically expressed in the preadipose state.
A cDNA library of Ob1771 preadipocytes was constructed, and a cDNA clone designated pOb24 was isolated by differential screening. The pOb24 mRNA, 6 kilobases in length, rose sharply in early differentiating Ob1771 and 3T3-F442A cells and decreased thereafter. In mouse adipose tissue, it was present at a high level in stromal-vascular cells (containing adipose precursor cells) and at a low level in mature adipocytes. Thus, pOb24 mRNA appears to be both in vitro and in vivo an unique marker of the preadipose state, i.e. of cell commitment during adipose cell differentiation. In contrast to glycerol-3-phosphate dehydrogenase mRNA, the emergence of pOb24 mRNA in Ob1771 cells required neither growth hormone or triiodothyronine as obligatory hormones nor insulin as a modulating hormone. Comparative studies of the expression of pOb24 and dihydrofolate reductase genes during the cell cycle suggest that arrest at the G1/S boundary was critical for the entry into the preadipose state. Tumor necrosis factor and transforming growth factor-beta were able to induce a large decrease of pOb24 mRNA level in growth-arrested Ob1771 cells. This decrease was shown to be only confined to early differentiating, glycerol-3-phosphate dehydrogenase negative cells as no decrease of pOb24 mRNA level was observed in glycerol-3-phosphate dehydrogenase positive cells. This result suggests that signals generated by tumor necrosis factor and transforming growth factor-beta have no effect on a commitment-related gene in late differentiated cells.


Association between SIRT6 Methylation and Human Longevity in a Chinese Population.
Sirtuin 6 gene (SIRT6) is a longevity gene that is involved in a variety of metabolic pathways, but the relationship between SIRT6 methylation and longevity has not been clarified. We conducted a case-control study on 129 residents with a family history of longevity (1 of parents, themselves, or siblings aged ≥90 years) and 86 individuals without a family history of exceptional longevity to identify the association. DNA pyrosequencing was performed to analyze the methylation status of SIRT6 promoter CpG sites. qRT-PCR and ELISA were used to estimate the SIRT6 messenger RNA (mRNA) levels and protein content. Six CpG sites (P1-P6) were identified as methylation variable positions in the SIRT6 promoter region. At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (p < 0.001 and p = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of SIRT6 decreased in the control group (p < 0.0001 and p = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (rs = -0.173, p = 0.011) and P5 sites (rs = -0.207, p = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (rs = 0.136, p = 0.046) but showed no significant correlation with the methylation rate at the P2 site. The low level of SIRT6 methylation may be a potential protective factor of Chinese longevity.


Studies on the Q-branch spectral lines of high-lying rovibrational transitions of diatomic system.
An analytical formula is suggested to predict the accurate Q-branch spectral lines of rovibrational transitions for diatomic systems by taking multiple spectral differences, and is applied to study the high-lying Q-branch emission spectra of the (0, 0) band of the ⁴Γ₅/₂-⁴Φ₃/₂ and ⁴Γ₇/₂ -⁴Φ₅/₂ systems of TiF molecule using fifteen known accurate experimental transition data. The results show that not only the known experimental transition lines are accurately reproduced, but also the correct values of the unknown spectral lines are predicted.


Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells.
During initiation of antiviral and antitumor T cell-mediated immune responses, dendritic cells (DCs) cross-present exogenous antigens on major histocompatibility complex (MHC) class I molecules. Cross-presentation relies on the unusual "leakiness" of endocytic compartments in DCs, whereby internalized proteins escape into the cytosol for proteasome-mediated generation of MHC I-binding peptides. Given that type 1 conventional DCs excel at cross-presentation, we searched for cell type-specific effectors of endocytic escape. We devised an assay suitable for genetic screening and identified a pore-forming protein, perforin-2 (Mpeg1), as a dedicated effector exclusive to cross-presenting cells. Perforin-2 was recruited to antigen-containing compartments, where it underwent maturation, releasing its pore-forming domain. Mpeg1-/- mice failed to efficiently prime CD8+ T cells to cell-associated antigens, revealing an important role for perforin-2 in cytosolic entry of antigens during cross-presentation.


Sleep and wake disorders in shift workers. Part II: Prevention and treatment strategies.
The present review deals with preventive and treatment strategies for sleep and wake disorders, and the other problems of shift workers. Management must take into account the direction, speed and other parameters of the rotation schedule. Good sleep-wake hygiene may alleviate the problems. Further, additional napping may compensate - at least partially - for sleep deprivation and fatigue. Hypnotics must be avoided as much as possible. Finally, new techniques for manipulation of circadian rhythms are discussed: light, melatonin and benzodiazepines.


NMR Investigation of Protein-Carbohydrate Interactions: The Recognition of Glycans by Galectins Engineered with Fluorotryptophan Residues.
Fluorine (19 F) incorporation into glycan-binding proteins (lectins) has been achieved and exploited to monitor the binding to carbohydrate ligands by nuclear magnetic resonance (NMR) spectroscopy. Galectins are a family of lectins that bind carbohydrates, generally with weak affinities, through a combination of intermolecular interactions including a key CH-π stacking involving a conserved tryptophan residue. Herein, Galectin-3 (Gal3) and Galectin-8 (Gal8) with one and two carbohydrate recognition domains (CRDs), respectively, were selected. Gal3 contains one Trp, whereas Gal8 contains three, one at each binding site and a third one not involved in sugar binding; these were substituted by the corresponding F-Trp analogues. The presence of fluorine did not significantly modify the affinity for glycan binding, which was in slow exchange on the 19 F NMR chemical-shift timescale, even for weak ligands, and allowed binding events taking place at two different binding sites within the same lectin to be individualized.


Client education experiences and expectations of women at the first level of maternal and child care in Kaduna state, Nigeria.
to explore the client education experiences of women at first level maternal and child health-care facilities in Kaduna State Nigeria. The lack of access to appropriate information to assist women in making decisions about their health and utilize available services is recognized as a major contributory factor to the unabated high maternal and child mortality rates in Nigeria. a qualitative descriptive study was conducted. Nine focus group discussions were held with 65 women across the three senatorial zones of Kaduna State, Nigeria. Participants were recruited using maximum variation sampling technique. Audio recordings of the discussions were transcribed and the content analysed. The themes were determined by a priory approach and findings compared across groups through manually developed data matrices. midwives were the major source of useful health information to the women who wished the midwives could cover more issues. The information provided by the midwives was skewed towards children and postnatal care, and some midwives ignored, or considered some of the women's questions interrupting. The harshness of midwives in emphasizing the need for prompt care, to women who came late to register or deliver, kept some women away. Women who never delivered in the facilities were not aware that the 'nurses' at the clinics were midwives, and desired to know more about midwifery in the facilities being tired of traditional birth attendants. the desire of women for more information and to know the 'midwife' suggests a gap between what the women expected and what they were provided. it is important to expand the scope of client education to include critical pregnancy and labour related issues and friendly midwifery practices in the facility.


A novel dinuclear iridium(III) complex as a G-quadruplex-selective probe for the luminescent switch-on detection of transcription factor HIF-1α.
A novel dinuclear Ir(III) complex 5 was discovered to be specific to G-quadruplex DNA, and was utilized in a label-free G-quadruplex-based detection platform for transcription factor activity. The principle of this assay was demonstrated by using HIF-1α as a model protein. Moreover, this HIF-1α detection assay exhibited potential use for biological sample analysis.


A wireform surgical drape-retractor.
I devised a malleable plastic-coated wireform drape-retractor that increases patient comfort during surgery by keeping drapes off the nose and mouth. It is small and does not interfere with the surgeon's hand movements.


Selenium concentration in the blood and wool and glutathione peroxidase activity in the blood of three breeds of sheep.
The activity of the enzyme glutathione peroxidase (GSH-Px) in whole blood and the selenium concentrations in whole blood and wool were measured in samples taken from 15 Scottish Blackface, 16 Welsh Mountain and 16 Finnish landrace sheep. Blood selenium sheep had almost twice the GSH-Px activity and blood selenium concentration of the other two breeds (P less than 0.001). Wool selenium concentrations of the three breeds were not significantly different. Blood selenium concentration and GSH-Px activity were highly correlated (r = 0.8, P less than 0.01) but wool selenium concentration was not significantly correlated with either of these measurements.


Scar overlapping suture for treating chronic tendinous mallet finger in children.
To evaluate the effect of scar overlapping suture for treating chronic tendinous mallet finger deformity in children. Six patients younger than 18 years were investigated retrospectively. The active extensor lags of the distal interphalangeal joint (DIPJ) were all more than 40°, and the passive ranges of DIPJ motion were normal. They were all treated surgically by scar overlapping suture technique, featuring careful overlapping suture of the extensor scar and temporary transarticular Kirschner wire fixation of the DIPJ. Average follow-up was 3.1 years (ranging from 2 to 5 years). All patients made significant improvement in DIPJ activity. Three patients achieved full active DIPJ extension, whereas one patient had a 10° extensor lag and two patients had 5° extensor lags. All patients achieved normal active flexion ranges and full passive motion ranges of DIPJ compared with their uninjured side. There was no bone dysplasia, pain, or deformity recurrence. Scar overlapping suture for treating chronic tendinous mallet finger in children is safe and effective. According to the Crawford criteria, all patients were graded as excellent.


Preliminary evaluation of the anaerobic biodegradability of three biobased materials used for the production of disposable plastics.
Biodegradable plastics have been introduced to the market to substitute "traditional", non-biodegradable, petro-based plastics to alleviate plastic pollution. Biochemical methane potential tests were carried out on compostable bags made of MaterBi®, biodegradable bottle wine corks and cellulosic plates to examine the anaerobic biodegradability of those materials. The impact of four factors: type of pretreatment (predigestion, mechanical, alkaline, predigestion and alkaline), digestion duration, type of inoculum and temperature were statistically evaluated through regression modeling. Anaerobic tests on compostable and polyethylene bags (control) were carried out in mesophilic (35 °C) and thermophilic (55 °C) conditions, while tests on bottle wine corks and cellulosic plates were carried out in mesophilic conditions only. After 15 days of digestion, a dry mass reduction of 22.8 ± 6.2 % and 27.6 ± 14.0 % for mesophilic and thermophilic tests respectively was recorded for MaterBi®. Chemical pretreatment with NaOH led to a mass reduction of 78.2 ± 7.2 % and was the only statistically significant factor to affect both methane yields and dry mass loss. A higher digestion temperature led to an increased mass loss without a concurrent increase in methane production. The cellulosic plates were completely degraded (99.9 ± 0.03 % mass reduction), while the wine bottle corks weight did not change.


Performance of the Abbott RealTime and Roche Cobas TaqMan hepatitis C virus (HCV) assays for quantification of HCV genotypes.
We evaluated the Abbott RealTime (ART) and Roche Cobas TaqMan Hepatitis C virus (HCV) viral load assays for quantification of HCV genotypes in patient specimens. The ART HCV assay was a more sensitive and precise tool for accurate HCV viral load quantification across the HCV genotypes tested, especially genotype 1b.


Mixed-Valent Mn16-Containing Heteropolyanions: Tuning of Oxidation State and Associated Physicochemical Properties.
The two 16-manganese-containing, Keggin-based 36-tungsto-4-silicates [Mn(III)10Mn(II)6O6(OH)6(PO4)4(A-α-SiW9O34)4](28-) (1) and [Mn(III)4Mn(II)12(OH)12(PO4)4(A-α-SiW9O34)4](28-) (2) have been prepared by reaction of the trilacunary Keggin precursor [A-α-SiW9O34](10-) with either Mn(OOCCH3)3·2H2O (for 1) or MnCl2·4H2O (for 2), in aqueous phosphate solution at pH 9. Polyanions 1 and 2 comprise mixed-valent, cationic {Mn(III)10Mn(II)6O6(OH)6}(24+) and {Mn(III)4Mn(II)12(OH)12}(24+) cores, respectively, encapsulated by four phosphate groups and four {SiW9} units in a tetrahedral fashion. Both polyanions were structurally and compositionally characterized by single-crystal XRD, IR, thermogravimetric analysis, and X-ray absorption spectroscopy. Furthermore, studies were performed probing the magnetic, electrochemical, oxidation catalytic, and Li-ion battery performance of 1 and 2.


Gestational and Lactational Iron Deficiency Anemia Impairs Myelination and the Neurovascular Unit in Infant Rats.
Iron deficiency anemia is a prevalent health problem among pregnant women and infants, particularly in the developing countries that causes brain development deficits and poor cognitive outcomes. Since tissue iron depletion may impair myelination and trigger cellular hypoxic signaling affecting blood vessels, we studied myelination and the neurovascular unit (NVU) in infant rats born to mothers fed with an iron deficient (ID) or control diet from embryonic day 5 till weaning. Blood samples and brains of rat pups at postnatal day (PND) 14 and 30 were analyzed. PND 14 ID rats had severe microcytic hypochromic anemia that was almost reversed at PND 30 although hypomyelination and astrocyte immature phenotype in the corpus callosum were significant at that age. In CA1 hippocampal region, PND 14 and PND 30 ID rats showed significant reduced expression of the receptor β of the platelet-derived growth factor localized in pericytes and associated to aquaporin 4 (AQP4) immunopositive capillaries. Shorter AQP4 + capillaries and reduced AQP4 expression were also evidenced in PND 14 and PND 30 ID rats. In addition, pericyte membrane permeability through large-pore channels was transiently increased in ID rats at PND 14 but not at PND 30, while the blood-brain barrier permeability was not affected. Remarkably, transient increased pericyte permeability found in PND 14 ID rats was not directly related to iron depletion, suggesting the involvement of other iron deficiency anemia-induced mechanisms. In summary, severe ID during gestation and lactation produces persistent hypomyelination and significantly affects hippocampal pericytes and astrocytes in the NVU which may trigger impaired neurovascular function.


Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations.
Costello syndrome (OMIM# 218040) is a distinctive rare multisystem disorder comprising a characteristic coarse facial appearance, intellectual disabilities, and tumor predisposition. Although the diagnosis can be suspected clinically, confirmation requires identification of a heterozygous mutation in the proto-oncogene HRAS. In contrast to somatic oncogenic mutations in neoplasia, the Costello syndrome changes are typically introduced in the paternal germline. The predicted amino acid substitutions allow for constitutive or prolonged activation of the HRAS protein, resulting in dysregulation of the Ras/mitogen activated protein kinase pathway. Dysregulation of this signaling pathway is the disease mechanism shared among Costello syndrome and other rasopathies, including neurofibromatosis type 1, Noonan syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. The Ras/mitogen activated protein kinase pathway governs cell proliferation and differentiation, and its dysregulation affects cardiac and brain development, accounting for the significant overlap in physical and developmental differences and common medical problems among rasopathies. Unlike the genetically heterogeneous Noonan syndrome and cardio-facio-cutaneous syndrome, Costello syndrome is caused by HRAS mutations only. Patients, clinicians, and researchers may benefit from a multidisciplinary "rasopathy clinic," which serves patients with more common conditions such as Noonan syndrome and neurofibromatosis and those affected by rare conditions such as Costello syndrome.


Alar reconstruction with subcutaneous pedicled nasolabial flap: difficulties, considerations, and conclusions for this procedure.
The subcutaneous pedicled nasolabial flap is a useful material for alar reconstruction. This article describes the difficulties and considerations in this procedure and discusses the procedural problems involved, drawing conclusions from them. Case 1: a folded flap was used with a conchal cartilage strut sandwich. Case 2: only a folded flap was used. Case 3: the flap was used to cover the outer surface of the ala, and a mucoperiosteal graft from the hard palate was used for the ala lining. The cartilage strut was not sufficient to support the shape of the ala in case 1. Harvesting a sufficiently wide flap is thought to be important. However, a folded flap had some drawbacks, with the formation of a thick alar rim. The combination of a flap for the outer surface and a mucoperiosteal graft as a lining is thought to be an excellent option for alar reconstruction.


Investigation of Heme Oxygenase 2 Enzyme Protein Expression in Keratoconus and Normal Human Corneal Epithelium: An Immunohistochemical Study.
To compare heme oxygenase 2 (HO-2) enzyme levels detected by immunohistochemical staining methods in the cornea epithelium obtained from keratoconus patients and normal subjects. The keratoconus group included 69 eyes of 69 patients with keratoconus scheduled for cross-linking surgery. The control group included 52 eyes of 52 patients with refractive error scheduled for photorefractive keratectomy surgery. After a detailed ophthalmologic examination, corneal topographic maps of each patient were generated, and then the patients underwent surgery. The corneal epithelium was collected mechanically during the surgery, fixed with formalin, embedded in paraffin blocks, and sectioned by microtomes. HO-2 antibodies were applied to the samples for immunohistochemical evaluation. The intensity of the staining was identified as negative, weak, moderate or strong. The keratoconus group was classified as early (average keratometry (AvrK) ≤ 47 D), moderate (AvrK 47-55 D) and advanced keratoconus (AvrK ≥ 55 D). Finally, intergroup and intragroup comparison analyses were made statistically. In the keratoconus group, 20 (29%) (14 weak and 6 moderate staining) of the 69 corneal epithelial specimens were identified with HO-2 expression. In the control group, 40 (76.9%) (16 moderate and 24 strong staining) of the 52 corneal epithelial specimens were identified with HO-2 expression. HO-2 expression in the corneal epithelial specimens was significantly less in the keratoconus group than in the control group (p < 0.001). There was no substantial difference among the keratoconus subgroups in terms of staining with the HO-2 antibody (p = 0.797). The HO-2 enzyme staining using immunohistochemical methods was at lower amounts in the keratoconic corneal epithelial cells as compared with normal corneal epithelial cells. The HO-2 enzyme may play a role in the etiopathogenesis of keratoconus.


Evolution of the basal metabolic rate after Roux-en-Y gastric bypass: a systematic review and meta-analysis.
Patients who undergo Roux-en-Y gastric bypass (RYGB) exhibit a reduction in total basal metabolic rate (BMR) after surgery, which seems to be intimately related to the amount of postoperative weight loss. The objective was to perform a systematic review and meta-analysis of the literature to determine and evaluate BMR changes after RYGB. The search was performed in certified databases, and the strategy was structured according to the PRISMA ScR. The quality evaluation of the articles included in this review was assessed with two different bias risk tools (ROBINS-I and NIH) according to each study design. Two meta-analyses were elaborated based on the results. 163 articles were selected (from 2016 to 2020), and 9 articles met the inclusion criteria. All of the selected studies evaluated only adult patients, mostly women. Postoperative BMR diminished in all of the included studies after surgery compared to preoperative values. The follow-up periods were 6, 12, 24 and 36 months. Eight articles were used for the meta-analysis after the quality assessment, a total of 434 participants. Compared to baseline values, mean postoperative reductions of 356.66 kcal/d after 6 months (p < 0.001) and 432.89 kcal/d (p < 0.001) after 1 year were observed. The BMR decreases during the first years after Roux-en-Y gastric bypass, especially during the first year postsurgery.


Pseudothrombophlebitis in a patient with Behçet's syndrome: Doppler ultrasound and magnetic resonance imaging findings.
A 33-year-old man with a known diagnosis of Behçet's syndrome (BS), presented with pseudothrombophlebitis resulting from acute rupture of a popliteal cyst. Doppler ultrasound and magnetic resonance imaging findings are explained. Differentiation of rupture of a Baker's cyst from true thrombophlebitis, especially in patients with BS, who are potentially susceptible to thrombotic events, is extremely important.


Glucose, the key substrate in the microbiological changes occurring in meat and certain meat products.
The literature dealing with the role of glucose in the microbiological changes of meat and certain meat products is reviewed. Discussion is centered on two aspects. First, glucose plays a part in the selection of the dominant spoilage organisms, Pseudomonas fragi, Ps. lundensis, and Ps. fluorescens, on red meat stored aerobically under chill (2-7 degrees C) conditions. It is concluded that the pseudomonads flourish because they convert glucose to the less commonly used substrate, gluconate. The latter serves as an extracellular energy store. With its depletion, the pseudomonads utilize amino acids, thereby producing the characteristic off-odors of spoiled meat. Storage of meat in a modified atmosphere (viz., 20% CO2:80% O2) selects Gram-positive flora (lactobacilli and Brochothrix thermosphacta) which impart a "cheesy odor" through acid production from glucose and volatile fatty acids from amino acids. The first mentioned organisms produce the same off-odors in "acid" meat (pH 5.5) from which oxygen is excluded. So too does the less acid-tolerant Br. thermosphacta in less acid meat (pH greater than 5.8), especially if trace amounts of O2 are present. Such meat may be colonized by Shewanella putrefaciens also, with green discoloration resulting from the release of H2S from amino acids. The addition of glucose and NO2- to, and the exclusion of oxygen from, comminuted meat selects a flora dominated by Lactobacillus spp. and staphylococci such as Staphylococcus carnosus. Second, sulfite, the preservative of British-style sausages, has a sparing action on glucose. As a consequence of its curtailed breakdown there is only a meager acid drift with storage even though a fermentative flora of lactobacilli and Br. thermosphacta is selected. Yeasts also contribute to the microbial association in sausages; members of four of the six commonly occurring genera bind sulfite through acetaldehyde production. Glucose appears to be essential for acetaldehyde synthesis. The role of glucose in spoilage and the conditions which select particular groups of spoilage organisms are considered in the context of chemical probes and/or instrumental methods for routine assessment of the "freshness" of meat and meat products.


Necessity of routinely performing foraminoplasty during percutaneous endoscopic transforaminal discectomy (PETD) for lumbar disc herniation.
To assess the role of foraminoplasty during percutaneous endoscopic transforaminal discectomy (PETD) and compared the 2-year clinical results of patients underwent PETD w/o foraminoplasty. A total of 412 patients, who underwent PETD at L3-S1 by the same surgical group, were enrolled in this study. The MRI was used to determine the height (H1) and width (W1) of the intervertebral foramen of L3-S1, the distance between the exiting nerve root and the upper edge of the lower vertebral pedicle (H2), and the distance (W2) between the point with 3 mm to the ventral side of the intervertebral space and superior articular process. The intervertebral foramen widths in the flexion (W3) and extension positions (W4) were also measured. A VAS of low back pain (LBP) and leg pain, ODI and JOA scores of LBP were used to assess the clinical results. Intraoperative verification showed that 347 cases (group A) did not need foraminoplasty, while the other 65 patients (group B) needed foraminoplasty, including 31 at L4-5 and 34 at L5-S1. The H1 and H2 of L3-S1 were reduced gradually without significant difference between two groups. The W1, W2, W3 and W4 were higher in group A (p < 0.05). The W3 was higher than W4 in both groups (p < 0.05). At 2-year follow-up, there was no significant difference of ODI and JOA score between two groups (p > 0.05). The VAS score of LBP was better in group A (p < 0.05). Most of PETD procedure at L3-S1 levels could reach the therapeutic target without foraminoplasty. Due to anatomic characteristics of L5-S1, the foraminoplasty rate was much higher at L5-S1.


Nasal Bone Osteotomies with Nonpowered Tools.
Controlling the shape of the nasal bones has long been a frustrating problem. Conventional osteotomies are associated with bleeding, loss of reduction, inability to achieve the desired alignment, improperly placed osteotomy sites, and spicule formation. A nonpowered osteotomy method empirically provided the safest and most controlled technique to achieve the desired anatomic result. The nasal bones should be thought of as 2 thin nasal plates that can be released from their medial and lateral attachments to become mobile units that can affect the dorsal width and bony base independently. There is a learning curve to osteotomies.


Clinical analysis of EV-Fingerprint to predict grade group 3 and above prostate cancer and avoid prostate biopsy.
There is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen-specific risk calculators. We determined the accuracy of the blood-based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies. This study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study. The EV machine learning analysis platform was used to generate predictive EV models from microflow data. Logistic regression was then used to analyze the combined EV models and patient clinical data and generate the patients' risk score for GG ≥3 prostate cancer. The EV-Fingerprint test was evaluated using the area under the curve (AUC) in discrimination of GG ≥3 from GG ≤2 and benign disease on initial biopsy. EV-Fingerprint identified GG ≥3 cancer patients with high accuracy (0.81 AUC) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cutoff, 95% of men with GG ≥3 would have been recommended a biopsy while avoiding 144 unnecessary biopsies (35%) and missing four GG ≥3 cancers (5%). Conversely, a 5% cutoff would have avoided 31 unnecessary biopsies (7%), missing no GG ≥3 cancers (0%). EV-Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies.


Twelve-year clinico-therapeutic experience in pemphigus: a retrospective study of 54 cases.
Pemphigus, a common immunobullous disease of skin and mucous membranes affecting both sexes of all ages, was almost fatal before the advent of corticosteroids. Better strategies to avoid their side-effects and recent introduction of adjuvant therapy has further improved its prognosis. As the treatment remains need-based and patient-specific, different regimens and strategies have evolved, each with its own merits and demerits. This retrospective hospital-based study was carried out to understand the clinico-therapeutic aspects of pemphigus in our clinic. Medical records of all new patients admitted to our hospital with the diagnosis of pemphigus from 1990 to 2002 were analyzed. The diagnosis was mainly clinical and confirmed by positive Tzanck's test and histopathology. All patients were assessed clinically on a severity score of 1+ to 4+. These patients had received treatment with dexamethasone-cyclophosphamide pulse (DCP) therapy, oral mini-pulse (OMP) with betamethasone, or intramuscular triamcinolone acetonide alone or with azathioprine, dapsone or cyclophosphamide. They were followed up for clinical remission and side-effects of therapy. There were a total of 54 new patients comprising 53.7% females and 46.3% males, and 12.9% of these were < 18 years of age. Pemphigus vulgaris was the commonest clinical type seen in 81.48% and mucosal involvement was seen in 63.63% of cases. The severity of mucosal lesions was not proportionate to that of cutaneous lesions. Associated diseases seen were seropositive rheumatoid arthritis, hypertension, diabetes mellitus and hyperthyroidism in one case each. Dexamethasone-cyclophosphamide pulse therapy was given to 75% of the pemphigus vulgaris patients while those having less severe disease were treated with other regimens. In general, clinical remission was seen after 2-16 (mean 6.5) DCP doses. Two patients have been in complete remission for the last 5 and 7 years of completion of DCP therapy, respectively. Addition of other adjuvants to corticosteroids was also helpful. However, azathioprine 50 mg/day was not as effective as cyclophosphamide 50 mg/day. Menstrual irregularities, amenorrhoea, azoospermia, rise in blood pressure and glycosuria were the major side-effects seen during DCP pulse therapy. Drop out rate was unacceptably high with all modes of treatment, although with DCP therapy it appears to be partly owing to early disease control. There was no mortality in this series. Pemphigus vulgaris is the commonest clinical type. Mucosal surfaces other than the oral cavity are uncommonly involved, it may herald the onset of disease and takes longer to heal. Dexamethasone-cyclophosphamide pulse therapy seems to have a definite advantage over treatment with steroids alone, especially in terms of better control of disease activity, near absence of steroid side-effects and significantly reduced hospital stay. However, ways and means to reduce gonadal toxicity of adjuvants need to be explored as DCP therapy is likely to stay as a treatment of choice.


The benefits of varicocele repair for achieving pregnancy in male infertility: A systematic review and meta-analysis.
Varicocele is one of the most common treatable causes of male infertility. However, the decision to perform varicocelectomy before starting a fertility program remains controversial. This study aimed to thoroughly review and analyze the benefit of varicocele repair and its impact on the success rate of a fertility program. A systematic literature search was performed using MEDLINE, Cochrane Library, and Wiley Library. The primary outcome was the pregnancy rate, and the secondary outcomes were live birth rate and surgical sperm retrieval success rate. Outcomes were compared between men who underwent treatment for a varicocele and those that did not. The pooled analysis data are presented as odds ratios with 95% confidence intervals. A total of 31 articles were included in the meta-analysis. The pregnancy rate was significantly higher in the treated group (odds ratio = 1.82; 95% confidence interval: 1.37-2.41; P < 0.0001) along with the live birth rate (odds ratio = 2.80; 95% confidence interval: 1.67-4.72; P = 0.0001). The further subgroup analysis revealed a higher pregnancy rate in treated men with azoospermia, subnormal semen parameters, and normozoospermia (P = 0.04, P = 0.0005, and P = 0.002, respectively), while the live birth rate was only significantly higher in the treated men with subnormal semen parameters and normozoospermia (P = 0.001 and P < 0.0001). Treated varicocele also led to a higher sperm retrieval rate in azoospermic patients (odds ratio = 1.69; 95% confidence interval: 1.16-2.45; P = 0.006). Varicocele repair increased the pregnancy and live birth rates regardless the semen analysis result, along with the sperm retrieval success rate in azoospermic men. Thus, varicocele repair may be beneficial prior to joining a fertility program.


Aβ(1-42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease.
Increasing evidence has suggested that formation and propagation of misfolded aggregates of 42-residue human amyloid β (Aβ(1-42)), rather than of the more abundant Aβ(1-40), provokes the Alzheimer's disease cascade. However, structural details of misfolded Aβ(1-42) have remained elusive. Here we present the atomic model of an Aβ(1-42) amyloid fibril, from solid-state NMR (ssNMR) data. It displays triple parallel-β-sheet segments that differ from reported structures of Aβ(1-40) fibrils. Remarkably, Aβ(1-40) is incompatible with the triple-β-motif, because seeding with Aβ(1-42) fibrils does not promote conversion of monomeric Aβ(1-40) into fibrils via cross-replication. ssNMR experiments suggest that C-terminal Ala42, absent in Aβ(1-40), forms a salt bridge with Lys28 to create a self-recognition molecular switch that excludes Aβ(1-40). The results provide insight into the Aβ(1-42)-selective self-replicating amyloid-propagation machinery in early-stage Alzheimer's disease.


A systems approach to child abuse: management and treatment issues.
In the systems approach certain patterns of family interaction are seen as fitting with physical abuse towards children in the family. If these interactions are blocked or changed using specific family therapy interventions, the risk of further abuse will be significantly reduced. Identifying typical patterns of interaction that fit with abuse is a useful first step in planning the management of physically abusing families. A full systemic formulation of the presenting problem will address numerous systems and sub-systems simultaneously, notably the family-professional system, the family within the extended family/friendship system, and the nuclear family. Interventions may have to be directed on a variety of these levels. The Marlborough Family Service has assessed and treated over 100 child-abusing families. A family day unit is used as the setting, and a multifamily group as the principle medium of treatment. Within the day unit real life stress situations are recreated around everyday issues, enabling families to find new and nonviolent solutions to the problems of daily life. In the cases seen, approximately one-third have resulted in a recommendation of permanent alternative family care for the children. In those families reunited, the re-injury rate has been found to be extremely low.


Sentiments analysis of fMRI using automatically generated stimuli labels under naturalistic paradigm.
Our emotions and sentiments are influenced by naturalistic stimuli such as the movies we watch and the songs we listen to, accompanied by changes in our brain activation. Comprehension of these brain-activation dynamics can assist in identification of any associated neurological condition such as stress and depression, leading towards making informed decision about suitable stimuli. A large number of open-access functional magnetic resonance imaging (fMRI) datasets collected under naturalistic conditions can be used for classification/prediction studies. However, these datasets do not provide emotion/sentiment labels, which limits their use in supervised learning studies. Manual labeling by subjects can generate these labels, however, this method is subjective and biased. In this study, we are proposing another approach of generating automatic labels from the naturalistic stimulus itself. We are using sentiment analyzers (VADER, TextBlob, and Flair) from natural language processing to generate labels using movie subtitles. Subtitles generated labels are used as the class labels for positive, negative, and neutral sentiments for classification of brain fMRI images. Support vector machine, random forest, decision tree, and deep neural network classifiers are used. We are getting reasonably good classification accuracy (42-84%) for imbalanced data, which is increased (55-99%) for balanced data.


Congenital rectovestibular fistula associated with rectal atresia: A rare occurrence.
We report a rare variety of anorectal malformation, rectal atresia associated with rectovestibular fistula. The case was successfully treated by posterior sagittal repair. The fistula was mobilized and the continuity of the rectum was established by circumferential anastomosis.


Machinery for protein sorting and assembly in the mitochondrial outer membrane.
Mitochondria contain translocases for the transport of precursor proteins across their outer and inner membranes. It has been assumed that the translocases also mediate the sorting of proteins to their submitochondrial destination. Here we show that the mitochondrial outer membrane contains a separate sorting and assembly machinery (SAM) that operates after the translocase of the outer membrane (TOM). Mas37 forms a constituent of the SAM complex. The central role of the SAM complex in the sorting and assembly pathway of outer membrane proteins explains the various pleiotropic functions that have been ascribed to Mas37 (refs 4, 11-15). These results suggest that the TOM complex, which can transport all kinds of mitochondrial precursor proteins, is not sufficient for the correct integration of outer membrane proteins with a complicated topology, and instead transfers precursor proteins to the SAM complex.


Enrolling older persons in cancer trials: the effect of sociodemographic, protocol, and recruitment center characteristics.
To determine the effect of patient, protocol, geographic, and institutional factors on enrollment of older persons onto cancer trials. We conducted a cross-sectional analysis of patients enrolled onto National Cancer Institute-sponsored lung, breast, colorectal, and prostate cancer trials during 1996 to 2002. We used a cross-classified logistic multilevel model to examine the associations between patient, hospital, county, and protocol characteristics, and the likelihood of participants being elderly (>or= 65 years old). The final study sample consisted of 36,167 patients enrolled onto 33 trials. After accounting for cancer type, only 6% of the variation in elderly enrollment onto cancer trials was at the protocol level. In contrast, more than 55% of the variation in elderly enrollment was attributable to patient level variation. In multivariate analysis, nonwhite patients were significantly less likely to be elderly than whites (odds ratio [OR] for blacks, 0.51; 95% CI, 0.44 to 0.58; and OR for Hispanics, 0.49; 95% CI, 0.40 to 0.59 v whites). Participants living less than 7 miles from their recruitment center were significantly more likely to be elderly (OR, 1.31; 95% CI, 1.24 to 1.38). Among the 910 recruitment centers, the median adjusted proportion of patients who were elderly was 24.9% (interquartile range, 24.0% to 26.9%). There were a significantly higher number of outlier centers (<or= 20.8% or >or= 29.3% elderly) than would be expected by a normal distribution (68 observed v six expected; P < .0001). Race and proximity to trial enrollment centers were significantly related to age of trial participants after adjusting for protocol factors. Additional work should explore why some recruitment centers were outliers regarding enrollment of older persons.


[Evaluation of the accumulation of dry substance and active componentsevaluation of the accumulation of dry substance and active components of Radix Aconiti Lateralis Praeparata].
To study the accumulation rules of dry substance and active components in the Radix Aconiti Lateralis Praeparata for providing the basic evidences to collection time. The Roots were collected periodically and their fresh weight and dry weight were measured. The contents of total alkaloids and three diester aconitum alkaloids aconitine, hypaconitine and mesaconitine were determined by titration and HPLC respectively. During the stage of root inflation, the content of total alkaloids was at a certain level, while the content of diester aconitum alkaloids were increased gradually. The total amount of alkaloid and diester aconitom alkaloids were increased rapidly from the last third of April to the middle third of June, and then maintained at relative constant levels and were decreased from the first third of July. It is more preferable to collect the Radix Aconiti Lateralis Praeparata during the period from the last third of June to first third of July.


Complete nucleotide sequence of the hemagglutinin-neuraminidase (HN) mRNA of mumps virus and comparison of paramyxovirus HN proteins.
The complete nucleotide sequence of the hemagglutinin-neuraminidase protein (HN) mRNA of the virulent SBL-1 strain of mumps virus has been determined. The mRNA contains 1887 nucleotides excluding the poly(A). The protein encoded by the mRNA has 582 amino acids and a membrane anchorage domain near the amino terminus. The calculated molecular mass (64 kDa) of the protein is in good agreement with that of the unglycosylated HN protein (63 kDa) identified in tunicamycin treated mumps virus infected cells (Herrler and Compans, 1983). The predicted sequence has nine potential N-glycosylation sites out of which two contain a cysteine residue and one has a proline residue as the variable amino acid X in the glycosylation site (Asn-X-Ser or Asn-X-Thr) and therefore, may not be utilized. One potential glycosylation site is in the cytoplasmic region which may not also be glycosylated. Comparison of the mumps HN protein sequence with the HN protein sequences of Sendai virus, simian-virus 5 (SV5), parainfluenza virus type 3 and Newcastle disease virus (NDV) shows two major homology regions, one region near the middle of the protein and the other in the second half of the molecule. In terms of percentage amino acid homology, the HN proteins of mumps virus, SV5 and NDV are closely related to each other but distinct from Sendai virus and parainfluenza virus type 3 HN proteins.


Pd-Cu nanoalloy for dual stimuli-responsive chemo-photothermal therapy against pathogenic biofilm bacteria.
Photothermal therapy (PTT) is a promising strategy for antimicrobial therapy. However, the application of PTT to treat bacterial infections remains a challenge as the high temperature required for bacterial elimination can partly damage healthy tissues. Selecting the appropriate treatment temperature is therefore a key factor for PTT. In this work, we designed a near-infrared/pH dual stimuli-responsive activated procedural antibacterial system based on zeolitic imidazolate framework-8 (ZIF-8), which was bottom-up synthesized and utilized to encapsulate both Pd-Cu nanoalloy (PC) and the antibiotic amoxicillin (AMO). This procedural antibacterial therapy comprises chemotherapy (CT) and PTT. The former disrupts the bacterial cell wall by releasing AMO in an acidic environment, which depends on the sensitive response of ZIF-8 to pH value change. With the progression in time, the AMO release rate decreased gradually. The latter can then significantly stimulate drug release and further complete the antibacterial effect. This impactful attack consisted of two waves that constitute the procedural therapy for bacterial infection. Accordingly, the treatment temperature required for antibacterial therapy can be significantly lowered under this mode of treatment. This antibacterial system has a significant therapeutic effect on planktonic bacteria (G+/G-) and their biofilms and also has good biocompatibility; thus, it provides a promising strategy to develop an effective and safe treatment against bacterial infections. STATEMENT OF SIGNIFICANCE: We have developed a near infrared/pH dual stimuli-responsive activated procedural antibacterial system that combines enhanced antibiotic delivery with photothermal therapy and has highly efficient antimicrobial activity. The antibacterial effect of this therapy was based on two mechanisms of action: chemotherapy, in which the bacterial cell wall was first destroyed, followed by photothermal therapy. After exposure to irradiation with an 808 nm laser, the inhibition rates were 99.8% and 99.1% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the clearance rates for their established biofilms were 75.3% and 74.8%, respectively. Thus, this procedural antibacterial therapy has shown great potentiality for use in the photothermal therapy of bacterial infectious diseases, including biofilm elimination.


Usefulness of PCR for diagnosis of imported malaria in Poland.
The aim of the present study was to use the polymerase chain reaction (PCR) to detect and identify Plasmodium spp. in diagnostic specimens, especially in those from patients diagnosed by microscopy as having possible mixed infections, and in those demonstrating low parasitemia or those that were parasite-negative. For most of the specimens, the PCR results were in accordance with microscopic findings, and in 16.2% of the cases with low parasitemia PCR enhanced the results by identifying the parasite species. This method detected one additional case of Plasmodium falciparum malaria among the patients with fever of unknown origin. The sensitivity of PCR for detecting Plasmodium DNA was found to correspond to 1.35-0.38 and 0.12 for Plasmodium falciparum and Plasmodium vivax parasites per microliter of blood, respectively. Follow-up examinations demonstrated that most of the patients became negative for Plasmodium DNA from 1 to 4 days after the disappearance of parasitemia, as determined by examination of blood films. In conclusion, PCR performed by the reference laboratory significantly enhanced the microscopic diagnosis of malaria and proved very helpful in cases of low parasitemia and in cases of mixed infection.


[Hemoperitoneum during the course of gallbladder perforation].
A case is presented of haemoperitoneum due to gall bladder perforation during calculosis with cholecystitis. There was no history of earlier abdominal trauma nor haemobilia. Cholecystectomy was performed. The postoperative course was uncomplicated. Cure was achieved.


Cytochrome P450 epoxygenase CYP2J2 and the risk of coronary artery disease.
Cytochrome P450 (CYP) enzyme 2J2, an epoxygenase predominantly expressed in the heart, metabolizes arachidonic acid to biologically active eicosanoids. One of the CYP2J2 products, 11,12-epoxyeicosatrienoic acid, has several vasoprotective effects. A frequent promoter polymorphism of CYP2J2 decreases gene expression and is associated with coronary artery disease. This association supports the vascular protective role of CYP-derived eicosanoids in cardiovascular disease.


A configuration of cortical coupling differentiating good from poor readers.
Thirty-one children, aged 8-5 to 10-11 years, were divided into three groups according to reading levels (poor, borderline, and good), and EEGs were recorded during conditions of rest, light flash, click, and flash/click. The hypothesis that cortical coupling patterns in the left angular gyrus differentiate good and poor readers was supported.


Recognition of p63 by the E3 ligase ITCH: Effect of an ectodermal dysplasia mutant.
The E3 ubiquitin ligase Itch mediates the degradation of the p63 protein. Itch contains four WW domains which are pivotal for the substrate recognition process. Indeed, this domain is implicated in several signalling complexes crucially involved in human diseases including Muscular Dystrophy, Alzheimer's Disease and Huntington Disease. WW domains are highly compact protein-protein binding modules that interact with short proline-rich sequences. The four WW domains present in Itch belong to the Group I type, which binds polypeptides with a PY motif characterized by a PP xY consensus sequence, where x can be any residue. Accordingly, the Itch-p63 interaction results from a direct binding of Itch-WW2 domain with the PY motif of p63. Here, we report a structural analysis of the Itch-p63 interaction by fluorescence, CD and NMR spectroscopy. Indeed, we studied the in vitro interaction between Itch-WW2 domain and p63(534-551), an 18-mer peptide encompassing a fragment of the p63 protein including the PY motif. In addition, we evaluated the conformation and the interaction with Itch-WW2 of a site specific mutant of p63, I549T, that has been reported in both Hay-Wells syndrome and Rapp-Hodgkin syndrome. Based on our results, we propose an extended PP xY motif for the Itch recognition motif (P-P-P-Y-x(4)-[ST]-[ILV]), which includes these C-terminal residues to the PP xY motif.


Demyelination precedes oligodendrocyte loss in canine distemper virus-induced encephalitis.
Canine distemper virus (CDV), a negative-stranded RNA morbillivirus, causes a persistent infection within the central nervous system resulting in a progressive, multifocal demyelinating disease. Demyelination is thought to be caused by a selective alteration of the myelin-producing oligodendrocytes. Metabolic impairment and morphological changes of the oligodendrocytes after CDV infection have previously been observed in vitro as well as in vivo. Until now it has been suggested that the oligodendrocytes completely disappear from CDV-induced demyelinating lesions. However, ultrastructural analysis in brain tissue sections and immunohistochemical examination of oligodendrocytes in dog brain cell cultures contradicted these observations. In this study oligodendrocytes from different categories of CDV-induced lesions were examined by in situ hybridization for proteolipid protein mRNA and--as a new tool employed on canine brain tissue sections--by immunohistochemistry using a monoclonal antibody against 2',3'-cyclic nucleotide 3'-phosphodiesterase, a myelin-specific enzyme. A down-regulation in the myelin gene transcription was detected already before demyelination occurred. However, a decrease in the number of oligodendrocytes was not observed until demyelination became evident. Although there was further depletion of oligodendrocytes in plaques with progressive demyelination, we demonstrated for the first time that these cells were still present in a significant amount even in chronic, completely demyelinated distemper lesions.


Immediate effect of photobiomodulation therapy on Achilles tendon morphology and mechanical properties: an exploratory study.
Evaluate the immediate (within 4 hours) effects of laser-induced photobiomodulation (PBM) therapy on Achilles tendon morphology and mechanical properties in healthy and pathologic tendons. Twenty people with healthy Achilles tendons and twelve people with Achilles tendinopathy participated. One Achilles tendon received PBM treatment following an established protocol and the contralateral side received a placebo treatment. Achilles tendon morphology and mechanical properties were evaluated bilaterally with ultrasound imaging and continuous shear wave elastography immediately before treatment, immediately after treatment, then 2- and 4-hours after treatment. There were no immediate effects of PBM on tendon morphology or mechanical properties when comparing the PBM-treated side and placebo-treated side within each cohort. Additionally, the effects of PBM did not differ between healthy and pathologic Achilles tendons. When treated with a laser-induced PBM treatment, healthy and pathologic Achilles tendons do not have immediate (within 4 hours) changes in tendon morphology or mechanical properties. These findings suggest that PBM therapy can be administered before other clinical treatments or high-load activities.


Robust inactivation of Plasmodium falciparum in red blood cell concentrates using amustaline and glutathione pathogen reduction.
Plasmodium falciparum is the parasite responsible for most malaria cases globally. The risk of transfusion-transmitted malaria (TTM) is mitigated by donor deferrals and blood screening strategies, which adversely impact blood availability. Previous studies showed robust inactivation of P. falciparum using nucleic acid-targeting pathogen reduction technologies (PRT) for the treatment of plasma and platelet components or whole blood (WB). The efficacy of the amustaline-glutathione (GSH) PRT to inactivate P. falciparum is here evaluated in red blood cells (RBC), as well the impact of PRT on parasite loads, stages, and strains. RBC units resuspended in AS-1 or AS-5 additive solutions were spiked with ring stage-infected RBC and treated with the amustaline-GSH PRT. Parasite loads and viability were measured in samples at the time of contamination, and after treatment, using serial 10-fold dilutions of the samples in RBC cultures maintained for up to 4 weeks. P. falciparum viability assays allow for the detection of very low levels of parasite. Initial parasite titer was >5.2 log10 /ml in AS-1/5 RBC. No infectious parasites were detected in amustaline-GSH-treated samples after 4 weeks of culture. Amustaline-GSH inactivated high parasite loads regardless of parasite stages and strains. Amustaline readily penetrates the parasite, irreversibly blocks development, and leads to parasite death and expulsion from RBC. Amustaline-GSH PRT demonstrated robust efficacy to inactivate malaria parasites in RBC concentrates. This study completes the portfolio of studies demonstrating the efficacy of nucleic acid-targeting PRTs to mitigate TTM risks as previously reported for platelet concentrates, plasma, and WB.


Maternal interpregnancy weight change and premature birth: Findings from an English population-based cohort study.
The relationship between maternal weight change between pregnancies and premature birth is unclear. This study aimed to investigate whether interpregnancy weight change between first and second, or second and third pregnancy is associated with premature birth. Routinely collected data from 2003 to 2018 from one English maternity centre was used to produce two cohorts. The primary cohort (n = 14,961 women) consisted of first and second live-birth pregnancies. The secondary cohort (n = 5,108 women) consisted of second and third live-birth pregnancies. Logistic regression models were used to examine associations between interpregnancy BMI change and premature births adjusted for confounders. Subgroup analyses were carried out, stratifying by initial pregnancy BMI groups and analysing spontaneous and indicated premature births separately. In the primary cohort, 3.4% (n = 514) of births were premature compared to 4.2% (n = 212) in the secondary cohort, with fewer indicated than spontaneous premature births in both cohorts. Weight loss (>3kg/m2) was associated with increased odds of premature birth (adjusted odds ratio (aOR):3.50, 95% CI: 1.78-6.88), and spontaneous premature birth (aOR: 3.34, 95%CI: 1.60-6.98), in women who were normal weight (BMI 18.5-25kg/m2) at first pregnancy. Weight gain >1kg/m2 was not associated with premature birth regardless of starting BMI. Losing >3kg/m2 was associated with increased odds of premature birth (aOR: 2.01, 95%CI: 1.05-3.87), when analysing the whole sample, but not when restricting the analysis to women who were overweight or obese at second pregnancy. Normal-weight women who lose significant weight (>3kg/m2) between their first and second live pregnancies have greater odds of premature birth compared to normal-weight women who remain weight stable in the interpregnancy period. There was no evidence of association between weight change in women who were overweight or obese at the start of their first pregnancy and premature birth.


Assessment of heavy metal accumulation in freshwater fish of Dongting Lake, China: Effects of feeding habits, habitat preferences and body size.
We measured the concentrations of Cr, Fe, Ni, Cu, Zn, Cd, Pb and Hg, and the stable isotope ratios (δ13C and δ15N) in 87 fish samples within 12 economic fish species collected from the Dongting Lake, the second largest freshwater lake in China. With few exceptions in concentration of Cr, most of fish species showed lower concentrations of the 8 metals than legislation thresholds. Piscivorous fishes had significantly higher values of δ15N (possessing higher trophic level) and metal concentrations than planktivorous and herbivorous fishes. Moreover, demersal fishes showed higher concentrations of Cu, Zn, Cd and Pb than pelagic and benthopelagic fishes. We found positive correlations between concentrations of Fe, Pb and Hg and δ15N ratio, confirming the biomagnification of the three metals through trophic transfer. In contrast, fishes showed clear growth dilution effect for Ni, Zn, Cu, Pb and Hg, indicated by the negative correlations between their concentrations and fish weight or length. Multiple regression analysis demonstrated that growth dilution and biomagnification effects simultaneously governed the metal concentrations in fish muscle, and the two effects' importance varied among different metals. The human health risk assessment indicated that all 8 metals gave target hazard quotient (THQ) values < 1.0, i.e., the estimated daily intake (EDI) of metals did not exceed the oral reference dose (RfD), indicating a safe consumption of these fish species for consumer. Our study provides comprehensive approaches to better understand the determining processes and potential risk of heavy metals in freshwater lake fishes.


[Biophysics of the DNA molecule: a new trend].
Briefly discussed are experiments with single molecules, representing a novel trend in the biophysical study of DNA. The techniques of optical and magnetic tweezers whereby external force can be applied to individual DNA molecules were used to assess the structural transitions of the DNA double helix under such conditions. Discussed are the latest data on the dependence of the rate of complementary chain synthesis by DNA polymerase on the stretching of the template.


The free radical-generating function of a familial amyotrophic lateral sclerosis-associated D90A Cu,Zn-superoxide dismutase mutant.
The free radical-generating functions of the D90A Cu,Zn-superoxide dismutase (SOD) associated with Swedish familial amyotrophic lateral sclerosis (FALS) patients are investigated. The results show that both the wild-type and mutant enzymes have identical dismutase activity, while the free radical-generating activity of the D90A mutant is enhanced relative to that of the wild-type enzyme. The studies suggest that the active channel of the D90A mutant is larger than that of the wild-type enzyme. A higher free radical-generating activity of the mutant enzyme led to the release of copper ions from the damaged protein. The generation of strand breaks in plasmid DNA was enhanced more effectively by the D90A mutant Cu,Zn-SOD than by the wild-type enzyme. The results suggest that the pathology of FALS may be attributed to oxidative damage caused by the gain-of-function of FALS Cu,Zn-SOD mutant.


Ketorolac tromethamine LS 0.4% versus nepafenac 0.1% in patients having cataract surgery. Prospective randomized double-masked clinical trial.
To compare the clinical, subjective, and objective outcomes of the use of 2 topical nonsteroidal antiinflammatory drugs--ketorolac tromethamine LS 0.4% (Acular) and nepafenac 0.1% (Nevanac)--in patients having cataract surgery. Single-center private practice, Las Vegas, Nevada, USA. One hundred eighty-three patients (193 eyes) with visually significant cataract were recruited for the study. Consenting patients were randomized to a standard regimen of Acular, gatifloxacin 0.3% (Zymar), and prednisolone acetate 1% (Pred Forte) (ketorolac group) or Nevanac, moxifloxacin hydrochloride 0.5% (Vigamox), and prednisolone acetate (Econopred) (nepafenac group). Analysis included subjective complaints (burning, itching, foreign-body sensation, pain level after surgery) and objective findings (visual function, degree of inflammation in the anterior segment, complications). The ketorolac group consisted of 94 patients (100 eyes) and the nepafenac group, 89 patients (93 eyes). The between-group differences in visual outcomes and anterior chamber inflammation were not statistically significant (mean P = .33). There was a higher incidence of posterior capsule opacification in the nepafenac group (P = 0.019). Patient satisfaction, patient compliance, and postoperative pain control were statistically significantly better in the ketorolac group (P = .022, P = .023, and P = .025, respectively). Ketorolac tromethamine was statistically significantly better than nepafenac in terms of patient satisfaction, compliance, and postoperative pain control.


A CFD-based Kriging surrogate modeling approach for predicting device-specific hemolysis power law coefficients in blood-contacting medical devices.
Most stress-based hemolysis models used in computational fluid dynamics (CFD) are based on an empirical power law correlation between hemolysis generation and the flow-induced stress and exposure time. Empirical model coefficients are typically determined by fitting global hemolysis measurements in simplified blood shearing devices under uniform shear conditions and with well-defined exposure times. CFD simulations using these idealized global empirical coefficients are then performed to predict hemolysis in a medical device with complex hemodynamics. The applicability, however, of this traditional approach of using idealized coefficients for a real device with varying exposure times and non-uniform shear is currently unknown. In this study, we propose a new approach for determining device- and species-specific hemolysis power law coefficients (C, a, and b). The approach consists of calculating multiple hemolysis solutions using different sets of coefficients to map the hemolysis response field in three-dimensional (C, a, b) parameter space. The resultant response field is then compared with experimental data in the same device to determine the coefficients that when incorporated into the locally defined power law model yield correct global hemolysis predictions. We first develop the generalized approach by deriving analytical solutions for simple uniform and non-uniform shear flows (planar Couette flow and circular Poiseuille flow, respectively) that allow us to continuously map the hemolysis solution in (C, a, b) parameter space. We then extend our approach to more practical cases relevant to blood-contacting medical devices by replacing the requirement for an analytical solution in our generalized approach with CFD and Kriging surrogate modeling. Finally, we apply our verified CFD-based Kriging surrogate modeling approach to predict the device- and species-specific power law coefficients for developing laminar flow in a small capillary tube. We show that the resultant coefficients are much different than traditional idealized coefficients obtained from simplified uniform shear experiments and that using such idealized coefficients yields a highly inaccurate prediction of hemolysis that is in error by more than 2000% compared to experiments. Our approach and surrogate modeling framework may be applied to more complex medical devices and readily extended to determine empirical coefficients for other continuum-based models of hemolysis and other forms of flow-induced blood damage (e.g., platelet activation and thrombosis).


Morphophysiological analyses of Neochloris oleoabundans (Chlorophyta) grown mixotrophically in a carbon-rich waste product.
Neochloris oleoabundans is considered one of the most promising oil-rich microalgae because of its ability to store lipids under nitrogen starvation. However, high biomass densities, required for applications on medium to large scale, are not reached in this condition of growth. As previous studies on other microalgae have shown that mixotrophy allows to obtain higher biomass in comparison to autotrophic cultures, we performed morphophysiological analyses in order to test the mixotrophic growth capability of N. oleoabundans. A carbon-rich manure derived from the apple vinegar production (AWP) was added to the medium. Cells were also cultivated under nutrient starvation (tap water), to observe the expected lipids accumulation, and combining AWP to water, to test the potential of this waste in a low-cost culture system. The results highlighted that AWP in the medium allowed to obtain the highest final cell density. Moreover, starch granules were stored inside chloroplast at the beginning of the experiment. The presence of AWP did not induce variations on light harvesting complex II (LHCII)-photosystem II (PSII) assembly, even if an interesting promotion of pigment synthesis in cells was observed. On the other hand, in starved cells, chloroplast degeneration, pigment content decrease, altered LHCII-PSII assembly and accumulation of high amount of lipid globules were observed, irrespective of the presence of AWP. The results suggest that mixotrophy promotes growth in N. oleoabundans and open up the possibility of using waste products from agri-food industries for this purpose. After growth, cells could be transferred under nutrient starvation to induce lipid accumulation.


First and second generation DESs reduce diabetes adverse effect on mortality and re-intervention in multivessel coronary disease: 9-Year analysis.
Diabetes portends an increased risk of adverse early and late outcomes in patients undergoing PCI. In this study, we aimed to investigate if the adverse effect of diabetes mellitus (DM) on early and late PCI outcomes is reduced with drug-eluting (DES) compared to bare-metal (BMS) stents. We reviewed the Mount Sinai Beth Israel Hospital first PCI experience for multivessel coronary artery disease (CAD, 1998-2009). Patients were excluded if they had single-vessel CAD, emergency, no stent, prior bypass graft or myocardial infarction <24h. Diabetes-effect was derived from 9-year all-cause mortality and re-intervention risk-adjusted hazard ratios [AHR (95% confidence intervals)] for DES (N=2679; 48% three-vessel; 39% DM) and BMS (N=2651; 40% three-vessel; 33% DM) and then stratified based on stent (DES/BMS) and vessel disease (two/three). Diabetes-effect on mortality was lower for DES (AHRDM/NoDM=1.41 [1.14-1.74]) versus BMS (AHRDM/NoDM=1.71 [1.50-2.01]), but this was predominantly driven by two-vessel patients. This diabetes effect was similar for first (DES1: AHRDM/NoDM=1.43 [1.14-1.79]) and second (DES2: AHRDM/NoDM=1.53 [0.77-3.07]) generation DES. Re-intervention comparisons were similarly increased by diabetes in all sub-cohorts. Our analysis of a large real-world PCI series indicates that diabetes is associated with worse 9-year mortality irrespective of stent type, albeit this is mitigated to varying degrees with DES, particularly in DES2 and in case of 2-vessel disease. A complementary stent-effect analysis confirmed DES-to-BMS and DES2-to-DES1 superiority in both diabetics and non-diabetics.


Prevalence of health services utilization in Brazil: a systematic review and meta-analysis.
to analyze the prevalence of use of health services in Brazil. systematic review and meta-analysis of population-based cross-sectional studies; MEDLINE, EMBASE, other sources, and microdata of surveys were searched; two researchers selected the studies, extracted the data and assessed methodological quality to include in the meta-analysis. from 1,979 retrieved references, 27 studies were included; the prevalence of medical visits in the previous year was 71% (confidence interval of 95% [95%CI] = 69; 73%; I2=99%); the proportion of women in each study (p=0.001; R2=25%) and the recall period (p>0.001; R2= 72%) contributed to the heterogeneity; prevalence of dental consultation was 37% (95%CI = 32; 42%; I2=100%), and of hospitalization, 10% (95%CI = 9; 11%; I2=98%), in the last year. more than half of the population had at least one medical visit, about one-third had a dental consultation and a tenth was hospitalized in the previous year.


Mannosylated engineered trichosanthin-legumain protein vaccine hydrogel for breast cancer immunotherapy.
The development of cancer vaccines based on tumor-associated antigens is hurdled by lack of an efficient adjuvant and insufficient efficacy. To improve the efficacy of vaccines, a genetically-engineered method was employed in this work to achieve the codelivery of antigen and adjuvant to enhance immune responses. Trichosanthin is a plant-derived protein that possesses cancer immune stimulation function. A genetically engineered protein vaccine composed of trichosanthin (adjuvant) and legumain domain (a peptidic antigen) was constructed, which was further chemically modified with mannose for targeting dendritic cells (DCs). The method is facile and ready for scaling up for massive production. Such a "two-in-one" vaccine is advantageous for codelivery for augmenting the immune responses. The vaccine inhibited the tumors by triggering a robust cytotoxic T lymphocyte response in the orthotopic-breast-tumor mice. Furthermore, the vaccine was loaded into the temperature-sensitive hydrogel based on Pluronic F127 for implanting use in the post-surgical site. The sustained-released vaccine from the hydrogel inhibited not only the tumor recurrence but also the lung metastases of breast cancer. These findings demonstrated that it was a safe and effective vaccination for breast cancer immunotherapy in a prophylactical and therapeutical manner for remodeling the tumor immune microenvironment and arresting tumor growth.


Decoding ceRNA regulatory network and autophagy-related genes in benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is a common disease among aging males. We obtained BPH transcriptional signatures by high-throughput RNA sequencing analysis. Accordingly, we determined the differentially expressed RNAs (DERNAs) between BPH tissues and normal prostate tissues. WebGestalt and R package (clusterprofiler) was used to enrichment analysis. Clinical correlations were analyzed using Spearman's coefficient. TargetScan, ENCORI, miRNet, and miRDB databases were used to predict targets' relationships in ceRNA networks. Immunofluorescence staining and qRT-PCR analyses were performed to validate the findings. Microarray analysis of the datasets showed 369 DElncRNAs, 122 DEpseudogenes, 6 DEmiRNAs and 1358 DEmRNAs. DEmRNAs were particularly enriched in the autophagy-related pathways. Following the screening of DEmRNAs and autophagy-related genes (ARGs), 50 DEARGs were selected. MCODE analysis on Cytoscape was performed for the 50 DEARGs, and 3 hub genes (ATF4, XBP1, and PPP1R15A) were obtained. Spearman's correlation analysis showed that the mRNA expression of XBP1 correlated positively with age, total score, and storage score, but negatively with the maximum flow rate. Subsequently, the pseudogene/lncRNA- hsa-miR-222-3p-XBP1 pathway was identified. Our findings elucidate that the pseudogene/lncRNA-hsa-miR-222-3p-XBP1 pathway may play a regulatory role in the occurrence of BPH through autophagy.


Mitigating the Risk of Infectious Diseases Among Rural Drug Users in Western North Carolina: Results of the Southern Appalachia Test, Link, Care (SA-TLC) Health Care Provider Survey.
To characterize how health care providers in western North Carolina (NC) manage patients with substance use disorders and to inform strategies for preventing injection drug use (IDU)-associated outbreaks of bloodborne infectious diseases. We collected data on practice characteristics, provider sociodemographics, and attitudes and beliefs about hepatitis C virus (HCV), human immunodeficiency virus (HIV), opioid use, and IDU via online survey. Providers in 8 counties of western NC were invited to participate by email. Results were analyzed using descriptive and bivariate statistics. Of 84 respondents participating between 30 July and 3 December 2018, 81% were practicing clinicians and 46% served a county identified as being vulnerable to IDU-associated outbreaks of HCV or HIV. A substantial proportion was unsure about injecting behaviors among patients. Scores reflected comfort working with opioid users, though this varied by medical specialty. One-quarter of respondents "never" discussed harm reduction or HCV treatment with patients known to inject drugs; 22% "never" discussed HIV screening with injectors; and 1 in 3 referred at-risk patients out for HCV or HIV testing rather than ordering a test themselves. Scores indicated low levels of stigma toward persons living with HCV or HIV. Respondents identified HIV treatment, HCV treatment, and liver disease management as training needs. Our findings provide insights to inform health infrastructure improvement, with the goal of preventing HCV or HIV outbreaks in southern Appalachia. Rural health care workers are willing to receive additional training if it can improve care for patients affected by substance use disorders.


Global processes in stereopsis: some comments on Ramachandran and Nelson (1976).
The use of the term 'global in the context of stereopsis is discussed. It is concluded that different meanings of this term need to be kept carefully distinguished at all times. The discussion centres around a series of demonstrations introduced by Ramachandran and Nelson, and interpretations are offered for these demonstrations in terms of spatial-frequency-tuned stereopsis channels.


Molecular memories in the regulation of seasonal flowering: from competence to cessation.
Plants commit to flowering based on endogenous and exogenous information that they can remember across mitotic cell divisions. Here, we review how signal perception and epigenetic memory converge at key integrator genes, and we show how variation in their regulatory circuits supports the diversity of plant lifestyles.


Tympanoplasty Before Tympanoplasty: Alea Jacta Erat!
Tympanoplasty is the most common ear surgery performed throughout the world. As its basic principles remain the same since its introduction, many publications usually explain, in the introduction, that tympanoplasty has been a successful technique since the 1950s. The aim of this historical notice is to go back to the origin of the word tympanoplasty, and its final introduction as a specific defined surgical concept. Historical study based solely on original publications in different languages. The term tympanoplasty was first used by Hirch in 1912 for an operation for chronic adhesive catarrh of the middle ear. It was revived by Wullstein in 1952. One Polish, Miodonski, and three German otologists played an important role in the development of the actual concept and definition of tympanoplasty: Moritz, Zöllner and Wullstein, the two latter being recognized as worldwide dispensers of the technique. The history of the term tympanoplasty can be divided into two periods: the first being 1912 to 1913 with its first use for an operation to treat chronic adhesive catarrh of the middle ear, and the second 1952 to 1955, with its revival and definitive implementation in the surgery of the ear based on the concept of protection of the round window and construction of an effective sound-transmitter system through the oval window. Nevertheless, the concept of tympanoplasty was already established in 1950 but not surgically definitively implemented: alea jacta erat-the die was cast!


Heterogeneity in the effect of marked weight loss on metabolic function in women with obesity.
BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.


Occupational burnout and chronic work disability: an eight-year cohort study on pensioning among Finnish forest industry workers.
The objective was to explore if burnout, a syndrome from chronic work stress, predicts work disability during eight years among industrial employees. We investigated whether burnout would predict disability in initially healthy employees and all subgroups by the most common causes for disability. Of the participants in a company-wide survey (n=9705, 63%) performed in 1996, 8371 employees were identified and 7810 provided full information. The impact of burnout and its sub-dimensions, assessed with the Maslach Burnout Inventory-General Survey, on being granted register-based new disability pension till 2004 was analysed with Cox hazard regression and multinomial regression. The analyses were adjusted for socio-demographic factors, registered medication use, and self-reported chronic illness at baseline. The hazard ratio (HR) for new disability pension was 3.8 (95% confidence interval CI 2.7-5.4) with severe burnout. The risk of severe burnout and severe exhaustion for work disability attenuated but remained significant after adjustments. The association between severe burnout and work disability was significant also in the subpopulation of employees without registered medication at baseline but not among employees healthy by self-report. Crude associations between burnout and all categories of cause-specific disability were significant. The exhaustion dimension predicted work disability due to mental and miscellaneous disorders after adjustments. A non-random one-branch sample was used. The final sample covered 50% of eligible employees. In industrial work, burnout-related chronic work disability is general in nature. Burnout predicts work disability among healthy employees when health is assessed with registered use of medication but not when it is determined by self-report.


Spinal cord.
We first present a brief historic review of developments in the understanding of spinal cord clinical neuroanatomy and neurophysiology over the past 200 years. We then discuss the technical aspects that apply to the examination of the human spinal cord giving details on the interrelations between the spinal cord and the overlying structures, including the meninges and vertebrae. The subsequent discussion focuses on diseases of the spinal cord. Diseases that affect the spinal cord are vascular disease, diseases of spinal column, trauma, developmental abnormalities, central nervous system degenerative disease, inflammatory disease, metabolic and nutritional myelopathies, and tumors. We summarize our knowledge regarding general reactions of spinal cord tissue to disease, in particular Wallerian degeneration of descending/ascending tracts and axonal reaction. Two categories of disease will be covered in depth: vascular disease of the spinal cord, including a review of normal vascular anatomy, and diseases of the vertebral column that can affect the cord secondarily.


Utility of insects for studying human pathogens and evaluating new antimicrobial agents.
Insect models, such as Galleria mellonella and Drosophila melanogaster have significant ethical, logistical, and economic advantages over mammalian models for the studies of infectious diseases. Using these models, various pathogenic microbes have been studied and many novel virulence genes have been identified. Notably, because insects are susceptible to a wide variety of human pathogens and have immune responses similar to those of mammals, they offer the opportunity to understand innate immune responses against human pathogens better. It is important to note that insect pathosystems have also offered a simple strategy to evaluate the efficacy and toxicity of many antimicrobial agents. Overall, insect models provide a rapid, inexpensive, and reliable way as complementary hosts to conventional vertebrate animal models to study pathogenesis and antimicrobial agents.


The Effect of Preoperative Combined with Intravenous Lidocaine and Ketamine vs. Intravenous Ketamine on Pediatric Patients Undergoing Upper Gastrointestinal Endoscopy.
Ketamine is widely used in pediatric sedation. New studies have recommended combination therapy to reduce the side effects of ketamine. This study investigated the effect of adding intravenous (IV) lidocaine to ketamine on hemodynamic parameters, endoscopist satisfaction, and recovery time of children undergoing gastrointestinal endoscopy. This triple-blind, randomized, controlled clinical trial was conducted in Isfahan, Iran (2021). One hundred twenty children between the ages of 1 and 6 were enrolled. Patients were divided into 2 groups. The intervention group received 1.0 mg/kg of IV lidocaine and 1.0 mg/kg of IV ketamine, and the placebo group received 1.0 mg/kg of IV ketamine and placebo 2 minutes before entering the endoscopic room. Patients in both groups were sedated with 1.0 mg/kg of propofol, 0.1 mg/kg of midazolam, and 2.0 ug/kg of fentanyl for the procedure. The pulse rate, mean arterial pressure (MAP), respiratory rate, and oxygen saturation were recorded 1 minute before injection and every 5 minutes afterward. The mean (SD) ages of the intervention and control groups were 3.4 (1.5) and 3.4 (1.7), respectively. The mean difference in hemodynamic parameters between the 2 groups was insignificant during the investigation (P > 0.05). Furthermore, no significant differences were found regarding endoscopist satisfaction scores and length of recovery room stay (P > 0.05). Adding low-dose IV lidocaine to ketamine for pediatric sedation does not significantly affect the hemodynamic status, endoscopist satisfaction, and recovery time.