Quantitative evaluation of spermatogenesis by fluorescent histochemistry.
Identifying the types of spermatogenic cells that compose seminiferous tubules, as well as qualitative confirmation of the presence or absence of disorders, has been regarded as crucial in spermatogenesis. Sperm count and fertilizing capacity, both of which depend on the quality as well as quantity of spermatogenesis, are factors critical to fertilization. However, the quantitative assessment of spermatogenesis is not commonly practiced. Spermatogenesis has species-specific stages; when the specific stage in the seminiferous tubules is precisely determined, the types of spermatogenic cells in each stage can be spontaneously identified. Thereafter, a unique marker is used to classify the cells observed in each stage. Quantitative assessment of spermatogenesis has the potential to detect inapparent spermatogenesis disorders or numerically indicate the degree of the disorder. To this end, a histochemical approach using unique markers is indispensable for the quantitative assessment of spermatogenesis. Future developments in techniques to measure cell populations using computer software will further facilitate the establishment of quantitative assessment of spermatogenesis as a standard analysis method that can contribute significantly to advance our understanding of spermatogenesis.


Vesicouterine fistula presenting with cyclical haematuria mimicking bladder endometriosis: A case report.
Vesicouterine fistula (VUF) is an abnormal communication between the bladder and uterus, occurring 1-4% of all urogenital fistulas. Diagnosis is still a challenge because symptoms may appear late or fistula may be missed even after repeated examination. A 37-year old woman who has two children born through caesarean section complained of the absence of menstruation for the past three years. At the same time point, she experienced cyclic haematuria and amenorrhea. The diagnosis was made through ultrasonography, cystoscopy and hysteroscopy. She was then managed with laparoscopic bladder fistula repair continued with total laparoscopic hysterectomy. The VUF can present as an undesirable consequence of caesarean section.


[Anal sphincter injury during operative vaginal delivery using spatulas. What are the risk factors?].
To assess risk factors for anal sphincter injury during operative vaginal delivery using spatulas. A monocentric retrospective study of all assisted vaginal deliveries using Thierry and Teissier's spatulas between January 1st, 2008 and December 31st, 2009 in a teaching level III maternity. We studied risk factors such as primiparity, gestational age, maternal age, previous perineal laceration, level and type of presentation, type of expulsion, unsuccessful extraction and successive use of tools, episiotomy, type of anaesthesia and birth weight. There were 346 perineal tears (60.5%); among them, 175 (31%) were type 1, 131 (23%) type 2, 35 (6.1%) type 3 and five (0.9%) type 4. There were 235 episiotomy (41.1%). There was no statistically significant difference between all the supposed risk factors and the severe perineal tears. There are no relationship between third and fourth degree perineal lesions during spatula's delivery and supposed risk factors of anal sphincter injury. Only statistical tendances between first vaginal delivery and anal sphincter injury and between occipitosacral delivery and anal sphincter injury were found. We need further randomized studies comparing assisted births using spatulas, forceps and vacuum extractors to better assess perineal tears risk factors.


The effects of exercise and feeding on the activity of lipoprotein lipase in nine different adipose depots of guinea pigs.
1. The activity of lipoprotein lipase (LPL) was measured in whole adipose tissue from 9 identified adipose depots of sedentary, fasting adult guinea pigs and following 30 min of exercise or voluntary ingestion of chow, and in adipocyte and stromal-vascular fractions from exercised specimens. 2. In sedentary, fasting specimens, LPL activity was up to 4 times higher in the small intermuscular depots than in the perirenal and epididymal depot (Table 1). 3. LPL activity increased significantly after feeding only in the large superficial depot, groin, and in the perirenal depot. LPL activity decreased after exercise only in the 2 intermuscular depots and in small anterior superficial depots. These effects of exercise were consistently greater in males than in females (Table 3). 4. Following exercise, there was up to twice as much LPL in the adipocytes as in the stromal-vascular fraction of the intermuscular depots, about 50% more in adipocytes from the minor superficial depots and about equal quantities in the 2 fractions of the intra-abdominal and groin depots (Table 2). 5. The data demonstrate the physiological inhomogeneity of both superficial and internal adipose depots, and are consistent with the hypothesis that LPL originating from adipose tissue may enter the circulation.


Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.
The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity.


[Therapeutic relevance of HRCT findings from a pneumological viewpoint].
The high-resolution computed tomography (HRCT) technique is an essential component in diagnosing interstitial lung disease (ILD) as it provides important and specialized information and a much greater accuracy than chest X-rays. It contributes to a narrowing down of the differential diagnoses and is also important for planning further invasive investigations, e.g. bronchoscopy, bronchoalveolar lavage, transbronchial lung biopsy and surgical lung biopsy, if needed. An accurate diagnosis of ILD is based on a multidisciplinary discussion involving pulmonologists, radiologists and pathologists experienced in the diagnosis of ILD.The therapy approaches of five different entities of ILD are shown as examples. In hypersensitivity pneumonitis the mainstay of treatment is complete avoidance of exposure to the provoking antigen. In cryptogenic organizing pneumonia most patients recover with corticosteroid therapy with prednisolone over a period of 6 months to 1 year. In cases of sarcoidosis therapy depends on organ involvement and functional impairment but there is no durable benefit to routine treatment of patients with acute pulmonary sarcoidosis, even among those with stage II or III chest radiographs. In general, patients with severe or progressive disease will require treatment.In idiopathic pulmonary fibrosis (IPF) a confident radiological diagnosis of definitive usual interstitial pneumonia (UIP) obviates the need for surgical lung biopsy. Other etiologies of a HRCT pattern of UIP, such as domestic and occupational environmental exposure, connective tissue disease and drug toxicity must be ruled out. In IPF antifibrotic therapy with pirfenidone (approval since 2011) or the triple tyrosine kinase inhibitor nintendanib (pending approval in 2015) can reduce disease progression but therapy with acetylcysteine alone or in combination with prednisolone and azathioprine failed to meet efficacy endpoints. In the management of scleroderma associated ILD rapid semiquantitative evaluation of the extent of the disease on HRCT > 20% is useful for identifying patients who require treatment.


The epidemiology of antibiotic resistance in Campylobacter.
Antibiotic resistance, particularly with the fluoroquinolones and macrolide antibiotics, has now emerged globally with thermophilic campylobacters, including Campylobacter jejuni and C. coli, giving rise to concerns about how these organisms have acquired such resistance characteristics, as well as consequences for human and animal treatment. This review examines (i) the clinical epidemiology of antibiotic resistance in human and animal thermophilic campylobacters, (ii) an update on resistance rates globally, (iii) surveillance of antimicrobial resistance in campylobacters originating from animals, particularly poultry, (iv) the role of the environment in the acquisition and transmission of antibiotic-resistant campylobacters, as well as (v) issues of biocide resistance in campylobacters.


Modeling Microdebrider-Mediated Ophthalmic Damage: A Word of Caution in Endoscopic Sinus Surgery.
The microdebrider has become nearly universal in the treatment of sinonasal pathology; however, recent case reports have demonstrated the potential for major ophthalmic complications. The goal of this study was twofold: 1) determine the anatomical proximity of ophthalmic structures to the paranasal sinuses, and 2) assess the timeframe at which ophthalmic injury may occur with the use of a microdebrider during FESS utilizing a cadaveric model. Computed tomography scans from 50 patients were accessed retrospectively. The distances between the lamina papyracea (LP) and orbital structures were determined at varying depths. Seven cadavers (14 sides) were studied using three microdebrider systems operated by otolaryngology residents. Following removal of a window of LP, the time from activation of the microdebrider on the periorbita until transection of the medial rectus (MR), optic nerve (ON), and to aspiration of the globe were measured. The mean distance between the LP and MR at the level of the anterior aspect of the anterior ethmoid and basal lamella were 3.59 ±1.2mm and 1.5 ±0.8mm, respectively. The mean distance between the LP and ON at the level of the basal lamella was 8.1 ±2.1mm. Mean transection times for the MR and ON were 13.4 ± 7.3 seconds and 37.3 ± 9.2 seconds, respectively, with minimum times of 4 seconds and 26 seconds. The proximity of orbital structures to the paranasal sinuses and the rapidity of ophthalmic damage following violation of the periorbita reaffirms the need for cautious use of the microdebrider during FESS.


Gut-type glucagon immunoreactivity in nerves of the rat brain.
Nerve fibers reacting with antisera demonstrating gut-type glucagon were numerous in certain areas of hypothalamus and thalamus but absent from neocortex and hippocampus. They did not react with glucagon antisera specific for pancreatic type glucagon. Immunoreactive cell bodies were not observed.


IL-7δ5 protein is expressed in human tissues and induces expression of the oxidized low density lipoprotein receptor 1 (OLR1) in CD14+ monocytes.
The 6-exon-spanning 'canonical' Interleukin-7 (IL-7c) is a non-redundant cytokine in human T-cell homeostasis that undergoes extensive alternative pre-mRNA splicing. The IL-7 gene variant lacking, exon 5 (IL-7δ5), exhibits agonistic effects as compared to IL-7c. We studied in this report for the first time the protein expression of IL-7δ5 variant in tissues and its role in monocyte activation. We visualized the expression of IL-7δ5 protein by immunohistochemistry in both healthy and malignant (human) tissues and investigated the impact of IL-7δ5 stimulation on CD14+ monocytes using gene expression analysis and flow cytometry. IL-7δ5 is largely expressed by human epithelial cells, yet also by stromal cells in malignant lesions. Gene expression analysis in CD14+ monocytes, induced by the 6-exon spanning IL-7 or IL-7δ5 showed similar changes resulting in a pro-inflammatory phenotype and increased expression of genes involved in lipid metabolism. IL7δ5 was superior in inducing upregulation of the oxidised low density lipoprotein receptor (OLR), measured by flow cytometry, in CD14+ cells. IL-7δ5, produced from non-transformed and transformed cells, may contribute to chronic inflammatory responses and development of 'foamy' cells by increased OLR1 expression that mediates increased oxLDL uptake.


Puppets facilitate attention to social cues in children with ASD.
Diminished visual attention to faces of social partners represents one of the early characteristics of autism spectrum disorder (ASD). Here we examine if the introduction of puppets as social partners alters attention to speakers' faces in young children with ASD and typically developing (TD) controls. Children with ASD (N = 37; Mage = 49.44 months) and TD (N = 27; Mage = 40.66 months) viewed a video depicting a puppet and a human engaged in a conversation. Dwell time on these faces was analyzed as a function of group and speaker's identity. Unlike TD controls, the ASD group exhibited limited visual attention to and chance-level visual preference for the human speaker. However, attention to and preference for the puppet speaker's face was greater than chance and comparable across the two groups. While there was a strong association between low human speaker preference and high autism severity, no association with autism severity was found for puppet speaker preference. Unlike humans, expressive and verbal puppets attracted the attention of children with ASD at levels comparable to that of TD controls. Considering that puppets can engage in reciprocal interactions and deliver simplified, salient social-communicative cues, they may facilitate therapeutic efforts in children with ASD. LAY SUMMARY: While studies have shown support for therapeutic uses of robots with children with autism, other similar agents such as puppets remain to be explored. When shown a video of a conversation between a puppet and a person, young children with ASD paid as much attention to the puppet's face as typically-developing (TD) children. Since puppets can engage in back-and-forth interactions and model social interactions and communication, they may play a promising role in therapeutic efforts for young children with ASD.


[Effect of recombinant super-compound interferon (rSIFN-co) on human breast cancer cells in vitro].
To study the anti-cancer activities of recombinant super-compound interferon (rSIFN-co) against human breast cancer cells, its cooperative anti-tumor effect with chemotherapy and the possible mechanism of these effects. The rSIFN-co, infergen, epirubicin were applied separately or combined in cultured human breast cancer cells MCF-7 and adriamycin-resistant strains of MCF-7/ADR cells. MTT assays and flow cytometry were applied to determine the growth inhibition and cell apoptosis index (AI) of MCF-7 and MCF-7/ ADR after different treatment. Immunohistochemical was used to detect the expression of P53, Bcl-2, CerbB-2 in treated MCF-7 and MCF-7/ADR cells. The rSIFN-co demonstrated a efficiency of inhibiting the cell proliferation, induce apoptosis of both MCF-7 cells and MCF-7/ADR cells, which was stronger than that of infergen in the same concentration; rSIFN-co combined with epirubicin has a synergistic action in inhibiting cell proliferation, inducing apoptosis of both type of breast cancer cells; rSIFN-co can also decrease the expression level of P53 and CerbB-2, increase the expression of Bcl-2 in both cell lines. In vitro conditions, rSIFN-co can inhibit cell growth of human breast cancer cell MCF-7 and MCF-7/ADR, which may attribute to influence the proliferation-associated factor expression, and induce apoptosis of cancer cells.


Immunohistochemical localization of the insulinlike growth factor binding protein-1 in female reproductive tissues by monoclonal antibodies.
Human insulinlike growth factor binding protein-1 (hlGFBP-1) is a secretory protein that modulates the receptor-binding and biological actions of the insulinlike growth factor I (IGF-I). Human endometrium expresses the mRNA for IGFBP-1, and this protein is secreted by the secretory phase and pregnancy endometrium as well as by ovarian granulosa cells in vitro. In this study, we examined the cellular localization of IGFBP-1 in female reproductive tissues by using a purified monoclonal antibody Mab 6303 with an immunoperoxidase technique. Proliferative- and early secretory-phase endometrium as well as all extrauterine tissues except decidualized cells at the implantation site on the ovaries of ovarian pregnancies were negative for IGFBP-1. In midsecretory-phase endometrium, focal staining was first observed in the cytoplasm of glandular epithelial cells, with weaker staining in the stromal cells. In late secretoryphase endometrium, strong immunostaining was observed in predecidualized stromal cells, with weak focal staining remaining in some of the glandular epithelial cells. In early pregnancy, intense staining was detected in the cytoplasm of decidualized stromal cells of zona compacta in each sample, whereas the nondecidualized stromal cells remained unstained. Strong to medium staining was detected simultaneously in the glandular epithelial cells in 70% of the early pregnancy specimens. In term pregnancy, IGFBP-1 was localized in decidual cells of placental bed and decidua parietalis. Immunolocalization of IGFBP-1 to both endometrial epithelial and stromal cells, although only stromal cells express the gene of IGFBP-1 [14], supports the hypothesis of paracrine actions between these cells. The localization of IGFBP-1 to decidualized cells at the extrauterine implantation sites implies its association with decidual differentiation.


Policy-Driven, Multimodal Deep Learning for Predicting Visual Fields from the Optic Disc and OCT Imaging.
To develop and validate a deep learning (DL) system for predicting each point on visual fields (VFs) from disc and OCT imaging and derive a structure-function mapping. Retrospective, cross-sectional database study. A total of 6437 patients undergoing routine care for glaucoma in 3 clinical sites in the United Kingdom. OCT and infrared reflectance (IR) optic disc imaging were paired with the closest VF within 7 days. EfficientNet B2 was used to train 2 single-modality DL models to predict each of the 52 sensitivity points on the 24-2 VF pattern. A policy DL model was designed and trained to fuse the 2 model predictions. Pointwise mean absolute error (PMAE). A total of 5078 imaging scans to VF pairs were used as a held-out test set to measure the final performance. The improvement in PMAE with the policy model was 0.485 (0.438, 0.533) decibels (dB) compared with the IR image of the disc alone and 0.060 (0.047, 0.073) dB with to the OCT alone. The improvement with the policy fusion model was statistically significant (P < 0.0001). Occlusion masking shows that the DL models learned the correct structure-function mapping in a data-driven, feature agnostic fashion. The multimodal, policy DL model performed the best; it provided explainable maps of its confidence in fusing data from single modalities and provides a pathway for probing the structure-function relationship in glaucoma.


Epidemiology of sepsis in cancer patients in Victoria, Australia: a population-based study using linked data.
To determine the clinical characteristics, outcomes and longitudinal trends of sepsis occurring in cancer patients. Retrospective study using statewide Victorian Cancer Registry data linked to various administrative datasets. Among 215,763 incident cancer patients, incidence of sepsis within one year of cancer diagnosis was estimated at 6.4%. The incidence of sepsis was higher in men, younger patients, patients diagnosed with haematological malignancies and those with de novo metastatic disease. Of the 13,316 patients with a first admission with sepsis, 55% had one or more organ failures, 29% required care within an intensive care unit and 13% required mechanical ventilation. Treatments associated with the highest sepsis incidence were stem cell/bone marrow transplant (33%), major surgery (4.4%), chemotherapy (1.1%) and radical radiotherapy (0.6%). The incidence of sepsis with organ failure increased between 2008 and 2015, while 90-day mortality decreased. Sepsis in patients with cancer has high mortality and occurs most frequently in the first year after cancer diagnosis. Implications for public health: The number of cancer patients diagnosed with sepsis is expected to increase, causing a substantial burden on patients and the healthcare system.


Gastric distention exacerbates ischemia in a rodent model of partial gastric devascularization.
Occult ischemia of the mobilized gastric fundus is an important etiologic factor for esophagogastric anastomotic leaks after esophagectomy. Postoperative gastric distention is another possible predisposing factor for anastomotic leakage. We hypothesized that gastric distention could worsen gastric ischemia. To test this hypothesis, gastric tissue perfusion was studied in 20 Sprague-Dawley rats. Baseline serosal gastric tissue perfusion was measured by laser-Doppler flowmetry at a point 10 mm distal to the gastroesophageal junction. Perfusion was measured after left gastric artery occlusion, gastric distention to 20 cm water pressure, and combined left gastric artery occlusion and gastric distention. Gastric tissue perfusion (in tissue perfusion units, TPU) was 64.2 +/- 9.1 TPU at baseline measurement, 18.6 +/- 4.3 TPU after left gastric artery occlusion, 22.0 +/- 4.1 TPU after gastric distention, and 7.8 +/- 1.8 TPU after combined left gastric artery occlusion and gastric distention. Distention (P < 0.0001) and arterial occlusion (P < 0.0001) both reduced gastric tissue perfusion; of the two, arterial occlusion produced the greatest reduction in perfusion (P < 0.021). The combination of distention and arterial occlusion caused greater reduction in gastric perfusion than either factor alone (P < 0.0001). In this model, gastric distention exacerbated the ischemia produced by partial gastric devascularization. In clinical esophageal surgery, postoperative gastric distention may similarly potentiate the ischemic effects of gastric transposition for esophageal reconstruction.


Cross-phenotype association analysis of gastric cancer: in-silico functional annotation based on the disease-gene network.
A gene or variant has pleiotropic effects, and genetic variant identification across multiple phenotypes can provide a comprehensive understanding of biological pathways shared among different diseases or phenotypes. Discovery of genetic loci associated with multiple diseases can simultaneously support general interventions. Several meta-analyses have shown genetic associations with gastric cancer (GC); however, no study has identified associations with other phenotypes using this approach. Here, we applied disease network analysis and gene-based analysis (GBA) to examine genetic variants linked to GC and simultaneously associated with other phenotypes. We conducted a single-nucleotide polymorphism (SNP) level meta-analysis and GBA through a systematic genome-wide association study (GWAS) linked to GC, to integrate published results for the SNP variants and group them into major GC-associated genes. We then performed disease network and expression quantitative trait loci (eQTL) analyses to evaluate cross-phenotype associations and expression levels of GC-related genes. Seven genes (MTX1, GBAP1, MUC1, TRIM46, THBS3, PSCA, and ABO) were associated with GC as well as blood urea nitrogen (BUN), glomerular filtration rate (GFR), and uric acid (UA). In addition, 17 SNPs regulated the expression of genes located on 1q22, 24 SNPs regulated the expression of PSCA on 8q24.3, and rs7849820 regulated the expression of ABO on 9q34.2. Furthermore, rs1057941 and rs2294008 had the highest posterior causal probabilities of being a causal candidate SNP in 1q22, and 8q24.3, respectively. These findings identified seven GC-associated genes exhibiting a cross-association with GFR, BUN, and UA.


Klebsiella pneumoniae in endodontic therapy. Report of a case.
A 48-year-old man underwent endodontic treatment of the lower left central incisor. In the course of treatment two acute exacerbations occurred. Penicillin therapy was initiated at the time of the first exacerbation. It was ineffective, and a culture of the purulent exudate was taken at the time of the second acute response. The causative organism was Klebsiella pneumoniae, which was found to be sensitive to tetracyclines. After tetracycline therapy, endodontic therapy was completed. Healing has been uneventful.


Marriage, mortgage, motherhood: what longitudinal studies can tell us about gender, drug 'careers' and the normalisation of adult 'recreational' drug use.
Through a consideration of quantitative and qualitative data obtained from young women aged 18-28 in the later years of the North West England Longitudinal Study, this paper explores how women's drug careers develop, progressing the authors' normalisation thesis of 'recreational' drug use from adolescence into adulthood. Longitudinal studies are here compared with repeated cross-sectional surveys more usually favoured and funded by governments. The authors argue that firstly, in relation to methodology, longitudinal studies provide a unique opportunity to elucidate how drug careers develop across the life course and to chart the various impacts of life events and transitions on these careers and vice versa. Secondly, through this exploration of gender differences in drug careers and life transitions, we develop an age and gender-sensitive understanding of how recreational drug use fits into women's adult lives. The paper concludes that the challenge for policy makers is how to address adult women's 'normalised' recreational drug use, in the face of a regime focused on educational provision aimed at adolescent prevention; public health information designed for teenagers; and treatment resources focused on predominantly male and non parenting problem drug users, and the links between addiction and acquisitive crime.


Canine pulmonary angiotensin-converting enzyme. Physicochemical, catalytic and immunological properties.
Antiontensin-converting enzyme (peptidyldipeptide hydrolase, EC 18.104.22.168) has been solubilized from canine pulmonary particles and purified to apparent homogeneity. A value of approx. 140000 was estimated for the molecular weight of the native and the reduced, denatured forms of the enzyme. No free NH2-terminal residue was detected by the dansylation procedure. Carbohydrate accounted for 17% of the weight of the enzyme, and the major residues were galactose, mannose and N-acetylglucosamine with smaller amounts of sialic acid and fucose. Removal of sialic acid residues with neuraminidase did not alter enzymatic activity. The enzyme contained one molar equivalent of zinc. Addition of this metal reversed stimulation and inhibition of activity observed in the presence of Co2+ and Mn2+, respectively. Immunologic homology of pure dog and rabbit enzymes was demonstrable with goat antisera. Fab fragments and intact IgG antibodies displayed similar inhibition dose vs. response curves with homologous enzyme, whereas the fragments were poor inhibitors of heterologous activity compared to the holoantibodies. The canine glycoprotein was much less active than the rabbit preparation in catalyzing hydrolysis of Hip-His-Leu. In contrast, the two enzymes exhibited comparable kinetic parameters with angiotensin I as substrate.


Serum metabolomics study of the association between dairy intake and the anti-müllerian hormone annual decline rate.
Dairy intake has been implicated in later ovarian aging but mechanism underlying the association is unknown. This study aimed to investigate (1) associations between dairy intake and metabolites previously shown related to anti-müllerian hormone (AMH) decline rate; (2) mediating roles of these metabolites in the prospective association of total dairy consumption with odds of AMH fast decline rate. The participants comprised 186 reproductive-aged women randomly selected from the Tehran Lipid and Glucose Study. AMH was measured at baseline (1999-2001) and the 5th follow-up (2014-2017), and dietary data was collected at the second follow-up (2005-2008) using a food frequency questionnaire. Untargeted metabolomics was performed by gas chromatography-mass spectrometry using fasting-serum samples of the second follow-up. We analyzed dairy intake in association with the eight metabolites linked to the higher odds of AMH fast decline rate using linear regression with the Benjamini-Hochberg false discovery correction. Mediatory roles of the metabolites were assessed by bootstrapping. Mean age and BMI of the participants at metabolomics assessment were 44.7 ± 5.87 years and 28.8 ± 4.88 kg/m2, respectively. Phosphate, branched-chain amino acids (BCAAs), and proline decreased significantly from the first to the third tertile of total dairy intake. Total dairy as a continuous variable inversely associated with phosphate (beta = -0.166; p value = 0.018), valine (beta = -0.176; p value = 0.016), leucine (beta = -0.226; p value = 0.002), proline (beta = -0.219; p value = 0.003), and urea (beta = -0.156; p = 0.035) after accounting for all potential covariates and correction for multiplicity (q-value < 0.1). Fermented dairy showed similar results, but milk did not associate with any of the metabolites. Simple mediation showed significant indirect effects for phosphate, proline, and BCAAs but not urea. Entering the sum of phosphate, proline, and BCAAs as a mediator, the metabolites' total indirect effects were significant [β = -0.12 (95% CIs - 0.26, - 0.04)]. In contrast, the direct association of total dairy intake with the fast decline in AMH was non-significant [β = -0.28 (95% CIs - 0.67, 0.10)]. Total dairy was inversely associated with AMH decline rate-related metabolites. Inverse association of dairy intakes with the odds of AMH fast decline rate was indirectly mediated by lower phosphate, proline, and BCAAs.


Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection.
Viral mutations at Gag residue 242 and relevant viral polymorphisms were analyzed in a cohort of 42 individuals with primary HIV-1 subtype C infection using single-genome amplification/sequencing. In HLA-B*57/5801-negative subjects infected with 242N escape variant, reversion to Asn appeared at median (IQR) 103 days (97-213 days) post-seroconversion (p/s) and became dominant at 193 days (170-215 days) p/s. In subjects expressing HLA-B*57/5801 and infected with the wild-type virus, the T242N escape appeared at 203 days (196-231) p/s, reached dominance at 277 days (265-315 days) p/s, and became complete at 323 days (289-373 days) p/s. HLA-B*57/5801-negative subjects infected with 242N escape variant did not show reduced viral load or increased CD4 count. The study highlights the differential selection of T242N escape by HLA-B*57 and B*5801 and suggests that the presence of HLA-B*57/5801-mediated immune pressure is able to control replication of the wild-type virus encoding Thr at Gag residue 242 but fails to suppress the T242N escape variant.


Evaluation of carotid wall thickness and vertebro-basilar system insufficiency in patients with obese polycystic ovary syndrome.
To investigate the risk of cardiovascular disease by measuring carotid intima-media thickness (CIMT) and to evaluate the diameters and blood flow volume of vertebral arteries using Doppler ultrasound and the possible contribution of hyperandrogenemia that exists in these patients. We prospectively studied 64 Caucasian women aged 18-35 years (31 with polycystic ovary syndrome [PCOS] and 33 healthy controls). Patients were classified according to body mass index into obese (BMI > 27 kg/m(2) ). All subjects were examined with ultrasound to measure CIMT and blood flow volume and diameters of vertebral arteries. A significant difference between the two groups in CIMT (0.51 ± 0.08 vs 0.39 ± 0.02 mm, P < 0.001) and diameters of vertebral arteries (right, 3.03 ± 0.37 vs 3.44 ± 0.68 mm and left, 2.94 ± 0.34 vs 3.33 ± 0.63 mm, P < 0.05) were found, respectively. Right-left and total flow volumes of the vertebral arteries (VA) were significantly lower in the PCOS group than in the control group (P ≤ 0.001). Compared to the control group, diameters of right and left VA decreased (P < 0.05). The results of this study suggest that hyperandrogenemia in obese PCOS patients affects carotid and vertebro-basilar system arteries wall thickness. Pre-atherosclerotic vascular impairment with androgen excess should determine early examination of vertebro-basilar system with ultrasound. All patients with PCOS must be routinely examined using color Doppler ultrasound to measure CIMT carotid and vertebro-basilar arteries, and diameters and blood flow volume of vertebral arteries.


Heterogeneity of risk for melanoma and pancreatic and digestive malignancies: a melanoma case-control study.
Data addressing the interfamilial heterogeneity of melanoma are limited. In the current study, the authors assessed melanoma risk according to family history of melanoma and other melanoma-associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies. The authors obtained patient histories of malignancy in first-degree relatives as part of a clinic-based case-control study. The case group included 737 newly diagnosed patients with invasive melanoma, and the control group included 1021 outpatients from clinics at the same medical centers. To assess heterogeneity of risk among families affected by melanoma, a nonparametric method was used to detect extrabinomial variation. In addition, selected patients with melanoma (n=133) were tested for germline mutations in CDKN2A. The adjusted odds ratio associated with a family history of melanoma was 1.7 (95% confidence interval, 1.1-2.7). Family histories of pancreatic, gastrointestinal, brain, breast, or lymphoproliferative disease did not increase the risk of melanoma significantly. Among case families, significant evidence of familial heterogeneity was found for melanomas, but not for pancreatic or gastrointestinal malignancies. Two mutations in CDKN2A previously associated with melanoma risk were identified among the 133 patients tested in the case group; mutation detection did not differ between families with low and high heterogeneity scores. Familial heterogeneity testing in the study population did not improve the selection of high-risk families for genetic study. Even in a large case-control study, few families that had multiple members with melanoma were identified, and family members with pancreatic malignancies were rare.


On the in vivo origin of human nasal mesenchymal stem cell cultures.
Mesenchymal stem cells (MSCs), classically expanded in culture from bone marrow, are of broad interest to the regenerative medicine community. Human nasal turbinate mesenchymal-like stem cell cultures have also been described, defined by an in vitro phenotype similar to bone marrow MSCs. Nonetheless, the identity in vivo of the cells that give rise to nasal MSC-like cultures remains unclear, and these cells are often suggested to be related to olfactory lineages. Here, we sought to define the in vivo phenotype of human nasal MSC-like cells. Human turbinate tissue samples were used for RNA and immunohistochemical analysis. We also analyzed a recently published single cell RNA-sequencing dataset from adult human olfactory and respiratory mucosa samples from our lab, to focus on cell populations expressing MSC markers. Immunochemistry was performed to stain turbinate sections and nasal MSC cultures for selected markers. While there is no single MSC-specific gene, we identified a human nasal mucosal cell population in vivo that uniquely expressed transcripts characteristic of typical MSC cultures, including ENG (CD105), NES, and CD34, and lacked expression of other transcripts associated with surface epithelia. The expression of transcription factors such as SOX17, EBF1, and FOXP1 suggests cells in the MSC-like cluster maintain an ability to direct cell fate, consistent with the behavior of nasal MSC-like cells in vitro. SOX17 was found to be uniformly expressed by nasal MSC cultures, consistent with the in vivo data. Immunohistochemistry of human nasal tissue samples indicated that ENG, CD34, and SOX17 expression localized selectively to cells surrounding blood vessels in the lamina propria. Our findings provide evidence that the in vivo origin of nasal MSC-like cultures is likely a vascular or pericyte population, rather than cells related to the olfactory neuronal lineage. NA.


Porous zirconia/hydroxyapatite scaffolds for bone reconstruction.
Highly porous apatite-based bioceramic scaffolds have been widely investigated as three-dimensional (3D) templates for cell adhesion, proliferation, and differentiation promoting the bone regeneration. Their fragility, however, limits their clinical application especially for a large bone defect. To address the hypothesis that using a ZrO(2)/hydroxyapatite (HAp) composite might improve both the mechanical properties and cellular compatibility of the porous material, we fabricated ZrO(2)/HAp composite scaffolds with different ZrO(2)/HAp ratios, and evaluated their characteristics. In addition, porous ZrO(2)/HAp scaffolds containing bone marrow derived stromal cells (BMSCs) were implanted into critical-size bone defects for 6 weeks in order to evaluate the bone tissue reconstruction with this material. The porosity of a ZrO(2)/HAp scaffold can be adjusted from 72% to 91%, and the compressive strength of the scaffold increased from 2.5 to 13.8MPa when the ZrO(2) content increased from 50 to 100wt%. The cell adhesion and proliferation in the ZrO(2)/HAp scaffold was greatly improved when compared to the scaffold made with ZrO(2) alone. Moreover, in vivo study showed that a BMSCs-loaded ZrO(2)/HAp scaffold provided a suitable 3D environment for BMSC survival and enhanced bone regeneration around the implanted material. We thus showed that a porous ZrO(2)/HAp composite scaffold has excellent mechanical properties, and cellular/tissue compatibility, and would be a promising substrate to achieve both bone reconstruction and regeneration needed in the treatment of large bone defects.


Can knees kneel? Kneeling ability after total, unicompartmental and patellofemoral knee arthroplasty.
This study investigates patients' perception of kneeling ability before and at 1 and 2 years after total, unicompartmental knee replacement (UKR) and patellofemoral knee replacement (PFR), for osteoarthritis. Kneeling is an important function of the knee joint required for many daily activities and inability to kneel after knee surgery is a frequent cause of dissatisfaction. Data were prospectively collected on 253 knees. A kneeling score was obtained by analysis of the relevant section of the Oxford knee score. Scores were obtained pre-operatively and at 1 and 2 years post-operatively. Absolute values and change following surgery were recorded. Correlations with pain and other knee functions were also made. Kneeling ability prior to surgery was poor in all 3 groups (80% found it extremely difficult or impossible to kneel) and improved in all groups after surgery (20% had little or no difficulty to kneel at 2 years). Kneeling ability was best in UKR and worst in PFR. These results suggest that kneeling ability in osteoarthritic patients is poor but improves with knee arthroplasty surgery, however the majority of patients will still have difficulty in kneeling.


Engineered cells as glioblastoma therapeutics.
In spite of significant recent advances in our understanding of the genetics and cell biology of glioblastoma, to date, this has not led to improved treatments for this cancer. In addition to small molecule, antibody, and engineered virus approaches, engineered cells are also being explored as glioblastoma therapeutics. This includes CAR-T cells, CAR-NK cells, as well as engineered neural stem cells and mesenchymal stem cells. Here we review the state of this field, starting with clinical trial studies. These have established the feasibility and safety of engineered cell therapies for glioblastoma and show some evidence for activity. Next, we review the preclinical literature and compare the strengths and weaknesses of various starting cell types for engineered cell therapies. Finally, we discuss future directions for this nascent but promising modality for glioblastoma therapy.


Prenatal diagnosis of rare cloacal exstrophy: A case report.
Cloacal Exstrophy (CE) is a rare congenital birth defect. A correct prenatal diagnosis of CE is rarely made, even when congenital abnormalities are suspected on prenatal ultrasound examination. We report a case of CE with an abdominal defect about 5.31 cm in diameter seen below the umbilicus covered by a membrane. It was difficult to identify the left kidney, the bladder, the genital, and the anal dimple in the early third trimester ultrasound. The diagnosis of CE was then confirmed postnatally. Omphalocele and persistent bladder nonvisualization despite normal amniotic fluid volume detected by prenatal ultrasound can be suggestive for CE. Accurate prenatal diagnosis of CE is important to carry out multidisciplinary management and prenatal counseling to parents.


Haplotype-based genomic analysis reveals novel association of CNTNAP5 genic region with primary angle closure glaucoma.
Primary angle closure glaucoma (PACG) is one of the major causes of blindness worldwide. The underlying genetic aetiology is complex in nature and molecular mechanism remains elusive. Here, we identify genomic alterations using haplotype-based genome-wide association study in 148 PACG and 92 anatomically predisposed non-glaucomatous individuals. Logistic regression was performed on each common haplotype (within blocks of 3-8 SNPs) across the genotype and a total of 59 SNPs were found below genome wide suggestive threshold (p <1e-05). We found majority of these SNPs (n = 13) are located in CNTNAP5 genic region. The prioritized rs780010 of CNTNAP5 is also significantly associated with Cup to Disc ratio, which is a clinical parameter directly correlated with glaucomatous neurodegeneration. We further validated rs780010, present in all the significant haplotype blocks with p-value = 2.131e-06 (discovery phase), in a separate replication cohort (PACG, n = 50; control, n = 39) and observed significant association (p = 0.012, per G allele OR = 2.3079; 95 % CI: 1.23-4.33). Bioinformatics analyses also suggested neuronal expression of CNTNAP5 with active chromatin structure. KEGG pathway analysis indicates towards pathways related to apoptosis and neurodegeneration. Overall, these results not only indicate a strong genetic association of CNTNAP5 locus with PACG but also suggest its potential involvement in glaucomatous neurodegeneration.


Long non-coding RNA LINC01003 suppresses the development of multiple myeloma by targeting miR-33a-5p/PIM1 axis.
Numerous long non-coding RNAs (lncRNAs) are reported to affect the progression of multiple myeloma (MM). This study is aimed to explore the role and downstream mechanism of lncRNA LINC01003 in MM. Xenograft tumor assay was used to assess the function of LINC01003 in MM in vivo. The mRNA expression levels of LINC01003, miR-33a-5p, and PIM1 were determined by quantitative real-time polymerase chain reaction. Cell viability was examined by MTT assay. Relative protein levels of apoptosis-related factors (Bcl-2 and Bax) and proviral integration site of the Moloney leukemia virus kinase 1 (PIM1) were detected via western blot. Adhesion-related proteins were measured by Enzyme-linked immunosorbent assay was used to determine the levels of adhesion-related proteins. Besides, the target relation among LINC01003, miR-33a-5p and PIM1 was tested via dual-luciferase reporter assay. Low expression of LINC01003 was observed in MM cell lines and peripheral blood samples of MM patients. Both LINC01003 up-regulation and miR-33a-5p down-regulation repressed cell viability and adhesion, and promoted apoptosis of MM cells. Moreover, LINC01003 suppressed the growth of xenograft tumor in mice. We then identified miR-33a-5p as a downstream target of LINC01003, and confirmed that PIM1 was a direct target gene of miR-33a-5p. Both high expression of miR-33a-5p and low expression of PIM1 reversed the suppressive effects of LINC01003 overexpression on cell adhesion and viability, and the promoting effect on apoptosis in MM cells. LINC01003 functioned as a sponge of miR-33a-5p to inhibit the development MM by regulating PIM1 expression.


Acute respiratory response to individual particle exposure (PM1.0, PM2.5 and PM10) in the elderly with and without chronic respiratory diseases.
Limited data were on the acute respiratory responses in the elderly in response to personal exposure of particulate matter (PM). In order to evaluate the changes of airway inflammation and pulmonary functions in the elderly in response to individual exposure of particles (PM1.0, PM2.5 and PM10), we analyzed 43 elderly subjects with either asthma, chronic obstructive pulmonary disease (COPD) or Asthma COPD Overlap (ACO) and 40 age-matched subjects without asthma nor COPD in an urban community in Shanghai, China. Data were collected at the baseline and in 6 follow-ups from August 2016 to December 2018, once every 3 months except for the last twice with a 6-month interval. In each follow-up, pulmonary functions, fractional exhaled nitric oxide (FeNO), 7-day continuous personal exposure to airborne particles were measured. Multivariate linear mixed effect regression models were applied to investigate the quantitative changes of pulmonary functions and FeNO in two respective groups. The results showed that on average 4.7 follow-up visits were completed in each participant. In subjects with CRDs, an inter-quartile range (IQR) increase of personal exposure to PM1.0, PM2.5 and PM10 was significantly associated with an average increase of FeNO(Lag1) of 6.7 ppb (95%CI 1.2, 9.9 ppb), 6.2 ppb (95%CI 1.5, 12.0 ppb) and 5.6 ppb (95%CI 1.5, 11.0 ppb), respectively, and an average decrease of FEV1(Lag2) of -3.6 L (95%CI -6.0, -1.1 L), -3.6 L (95%CI -6.4, -0.8 L) and -3.2 L (95%CI -5.8, -0.6 L), respectively, in the single-pollutant model. These associations remained consistent in the two-pollutant models adjusting for gaseous air pollutants. Stratified analysis showed that subjects with lower BMI, females and non-allergies were more sensitive to particle exposure. No robust significant effects were observed in the subjects without CRDs. Our study provided data on the susceptibility of the elderly with CRDs to particle exposure of PM1.0 and PM2.5, and the modification effects by BMI, gender and history of allergies.


Astrocyte responses to nanomaterials: Functional changes, pathological changes and potential applications.
Astrocytes are responsible for regulating and optimizing the functional environment of neurons in the brain and can reduce the adverse impacts of external factors by protecting neurons. However, excessive astrocyte activation upon stimulation may alter their initial protective effect and actually lead to aggravation of injury. Similar to the dual effects of astrocytes in the response to injury within the central nervous system (CNS), nanomaterials (NMs) can have either toxic or beneficial effects on astrocytes, serving to promote injury or inhibit tumors. As the important physiological functions of astrocytes have been gradually revealed, the effects of NMs on astrocytes and the underlying mechanisms have become a new frontier in nanomedicine and neuroscience. This review summarizes the in vitro and in vivo findings regarding the effects of various NMs on astrocytes, focusing on functional alterations and pathological processes in astrocytes, as well as the possible underlying mechanisms. We also emphasize the importance of co-culture models in studying the interaction between NMs and cells of the CNS. Finally, we discuss NMs that have shown promise for application in astrocyte-related diseases and propose some challenges and suggestions for further investigations, with the aim of providing guidance for the widespread application of NMs in the CNS.


Multiple requirements for glycogen synthesis by hepatocytes isolated from fasted rats.
Glycogen synthesis from various combinations of substrates by hepatocytes isolated from rats fasted 24 h was studied. As reported by Katz et al. (Katz, J., Golden, S., and Wals, P. A. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 3433-3437), appreciable rates of glycogen synthesis occurred only in the presence of gluconeogenic precursors and one of several amino acids, which includes L-glutamine. L-Leucine had negligible effects on glycogen synthesis from 20 mM dihydroxyacetone and/or 15 mM glucose when L-glutamine was not added to the medium. In the presence of 10 mM L-glutamine, L-leucine greatly increased glycogen synthesis from these substrates. alpha-Ketoisocaproate was ineffective, as was oleate. NH4Cl depressed glycogen synthesis from 10 mM glucose plus 20 mM dihydroxyacetone in the absence of added L-glutamine and enhanced that in its presence, but these effects were weak compared to those of L-leucine. The amino acid analogues L-norvaline and L-norleucine exerted effects that were similar to those exerted by L-leucine. Under all conditions studied, cycloheximide and puromycin inhibited net glycogen synthesis. Cycloheximide did not stimulate gluconeogenesis from dihydroxyacetone, or phosphorylase in hepatocytes from starved rats, or glycogenolysis in hepatocytes from fed rats. Puromycin, however, stimulated glycogenolysis in hepatocytes from fed rats. Glycogen synthesis from 20 mM dihydroxyacetone proceeds with a pronounced initial lag phase that can be shortened by incubation of cells with glutamine plus leucine before addition of dihydroxyacetone. Concurrent measurements of glycogen synthesis, glycogen synthase, and gluconeogenesis under different conditions reveal that in addition to protein synthesis, activation of glycogen synthase, which must occur to allow glycogen synthesis in hepatocytes, requires a second component which can be satisfied by addition of dihydroxyacetone or fructose to the cells.


Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus.
Postprandial hyperglycemia is associated with increased cardiovascular mortality; therefore, lowering postprandial hyperglycemia seems crucial in type 2 diabetes mellitus. We assessed the effect of 2 different postprandial glucose-lowering agents, the alpha-glucosidase inhibitor miglitol and the meglitinide analogue mitiglinide, on metabolic profile and atherosclerosis-related markers. Glucose levels, insulin levels, lipid profile, serum adiponectin, pulse wave velocity (PWV), and urinary albumin excretion rate (AER) were assessed before and after 3 months in 28 patients with type 2 diabetes mellitus randomly allocated to either miglitol 150 mg/d or mitiglinide 30 mg/d. Both agents improved postprandial glucose levels but exhibited different patterns of insulin levels. Body mass index (BMI) tended to decrease with miglitol (P = .06), and homeostasis model assessment of insulin resistance and AER significantly decreased (P < .05 and P < .001, respectively) with miglitol; these changes were not obtained with mitiglinide. Pulse wave velocity did not change. The 3-month changes in 1,5-anhydroglucitol levels were significantly more with miglitol than with mitiglinide (P = .007). Adiponectin levels were significantly increased only with miglitol (P < .01), and the 3-month changes were significantly more with miglitol than with mitiglinide (P = .048). The significant increase in adiponectin by miglitol was inversely correlated with the ratio of the 60-minute change in blood glucose at 3 months divided by the change at baseline (r = -0.59, P = .020), which was independent of the effect of age, sex, changes in hemoglobin A(1c) and BMI, and the baseline concentration of adiponectin. The present comparative study indicated favorable effects of miglitol on BMI, homeostasis model assessment of insulin resistance, adiponectin, and AER, which are markers related to insulin resistance and atherosclerosis. Future studies are needed to elucidate the long-term effect.


Preliminary Structural Data Revealed That the SARS-CoV-2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity.
The evolution of new SARS-CoV-2 variants around the globe has made the COVID-19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor-binding motif (RBM) of the receptor-binding domain (RBD) spike glycoprotein, i. e. L452R-E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R-E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic-stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural-dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS-CoV-2 variants.


Functional and morphologic imaging of coronary atherosclerosis in living mice using high-resolution color Doppler echocardiography and ultrasound biomicroscopy.
This study aimed to establish non-invasive methods of assessing coronary artery morphology in normal and atherosclerotic mice in vivo. Coronary flow velocity reserve (CFVR) has been shown to correlate with coronary minimal lumen diameter (MLD) in patients with coronary artery stenosis. In mice, there are no existing non-invasive imaging techniques allowing quantitative measurement of the coronary artery morphology and function. Systemic hemodynamic effects of adenosine were studied in seven C57BL/6 mice. In 17 C57BL/6 mice, CFVR was measured in the mid left coronary artery (LCA) using either hypoxia- or adenosine-induced coronary hyperemia. Further, in another 10 atherosclerotic low-density lipoprotein receptor (LDLR)-/- mice, the hypoxia-induced CFVR was performed and proximal LCA MLD was measured using ultrasound biomicroscopy (UBM). Histologic sections of the LCA were collected. The adenosine dose of 160 microg/kg/min induced maximal coronary hyperemia without any systemic hemodynamic effects. Adenosine and hypoxia-induced CFVR values averaged at 2.0 +/- 0.1 and 1.9 +/- 0.3, respectively, in C57BL/6 mice (p = NS). In LDLR-/- mice, CFVR and MLD ranged between 1.4 to 2.9 microm and 190 to 370 microm, respectively. Histology revealed proximal lumen-narrowing plaques in the LCA. Significant correlation was found between hypoxia-induced CFVR and the MLD (p < 0.005, R2 = 0.8707). The CDE and UBM technique can be used to measure atherosclerosis-related lumen narrowing of the LCA in living mice. These non-invasive techniques may provide us with novel tools for following up disease status in mouse coronary arteries in a quantitative manner.


Human plasminogen-derived N-acetyl-Arg-Leu-Tyr-Glu antagonizes VEGFR-2 to prevent blood-retinal barrier breakdown in diabetic mice.
Targeting the vascular endothelial growth factor (VEGF)/its receptor-2 (VEGFR-2) system has become a mainstay of treatment for many human diseases, including retinal diseases. We examined the therapeutic effect of recently developed N-acetylated Arg-Leu-Tyr-Glu (Ac-RLYE), a human plasminogen kringle-5 domain-derived VEGFR-2 antagonists, on the pathogenesis of diabetic retinopathy. Ac-RLYE inhibited VEGF-A-mediated VEGFR-2 activation and endothelial nitric oxide synthase (eNOS)-derived NO production in the retinas of diabetic mice. In addition, Ac-RLYE prevented the disruption of adherens and tight junctions and vascular leakage by inhibiting S-nitrosylation of β-catenin and tyrosine nitration of p190RhoGAP in the retinal vasculature of diabetic mice. Peptide treatment preserved the pericyte coverage of retinal capillaries by upregulating angiopoietin-2. These results suggest that Ac-RLYE potentially prevents blood-retinal barrier breakdown and vascular leakage by antagonizing VEGFR-2; Ac-RLYE can be used as a potential therapeutic drug for the treatment of diabetic retinopathy.


[Determination of the localization of the kcpA gene on the chromosome of E. coli O124. I. Use of the type F' plasmids of varying length].
The loss of virulence was observed in some of the transconjugates of E. coli O124 in the process of the transfer of the plasmids differing in length: F' 200 PS, F'x 573 and F'x 363, carrying the genes of the chromosome area lac--pur E. The genetic determinants contributing to the ability of E. coli O124 to produce keratoconjunctivitis seem to be localized near the lactose marker, and not near E as in Sh. flexneri. In E. coli O124 these genetic determinants are probably localized on both sides of the lactose operon.


Development and validation of a new PCR optimization method by combining experimental design and artificial neural network.
Polymerase chain reaction (PCR) is one of the most powerful techniques in a variety of clinical and biological research fields. In this paper, a chemometrics approach, combining experimental design (ED) and artificial neural network (ANN), was proposed for optimization of PCR amplification of lycopene cyclase gene carRA in Blakeslea Trispora. Five-level star design was carried out to obtain experimental information and provide data source for ANN modeling. Nine variables were used as inputs in ANN, including the added amount of template, primer, dNTP, polymerase and magnesium ion, the temperature of denaturating, annealing and extension, and the number of cycles. The output variable was the efficiency (yield) of the PCR. Based on the developed model, the effects of each parameter on PCR efficiency were predicted and the most suitable operation condition for present system was determined. At last, the validation experiment was performed under the optimized condition, and the expectant results were produced. The results obtained in this paper showed that the combination of ANN and ED provided a satisfactory optimization model with good descriptive and predictive abilities, indicating that the method of combining ANN and ED can be a useful tool in PCR optimization and other biological applications.


Interaction of C3 nephritic factor (NEF) with erythrocyte membranes complement-independent binding to sheep and patients' erythrocytes.
Complement-independent binding of C3 nephritic factor (NEF) to sheep erythrocytes was observed in heat-inactivated sera from patients having this autoantibody. The binding was observed after neuraminidase treatment of erythrocytes but not following trypsin treatment. Purified IgG from patients' sera was able to bind to ShE membranes. Binding to rat and rabbit erythrocytes was also observed but not to human group O+ erythrocytes. By Western blot NEF ab recognizes a 26 kD protein on the sheep erythrocytes and a 21 kD protein on human erythrocytes. NEF activity decreased at these positions when blotted nitrocellulose was incubated with NEF antibody. This autoantibody binds human erythrocytes membranes from patients but not from 55 normal blood donors. IgG from a pool from 10 different controls did not bind membrane E from the patients. The amino acid analysis of the 21 kD protein of the patients showed differences in basic residues (Arg and Lys) when compared with the 21 kD protein obtained from controls. N-terminal sequence analysis indicated that it is blocked in both proteins.


Comparative transcriptomic analysis indicates genes associated with local and systemic resistance to Colletotrichum graminicola in maize.
The hemibiotrophic fungus Colletotrichum graminicola may cause severe damage to maize, affecting normal development of the plant and decreasing grain yield. In this context, understanding plant defense pathways at the inoculation site and systemically in uninoculated tissues can help in the development of genetic engineering of resistance against this pathogen. Previous work has discussed the molecular basis of maize - C. graminicola interaction. However, many genes involved in defense have not yet been exploited for lack of annotation in public databases. Here, changes in global gene expression were studied in root, male and female inflorescences of maize under local and systemic fungal infection treatments, respectively. RNA-Seq with qPCR was used to indicate genes involved in plant defense. We found that systemic acquired resistance induction in female inflorescences mainly involves accumulation of salicylic acid (SA)-inducible defense genes (ZmNAC, ZmHSF, ZmWRKY, ZmbZIP and PR1) and potential genes involved in chromatin modification. Furthermore, transcripts involved in jasmonic acid (JA) and ethylene (ET) signaling pathways were also accumulated and may participate in plant immunity. Moreover, several genes were functionally re-annotated based on domain signature, indicating novel candidates to be tested in strategies involving gene knockout and overexpression in plants.


Immobilization of glucose oxidase into polyaniline nanofiber matrix for biofuel cell applications.
Glucose oxidase (GOx) was immobilized into the porous matrix of polyaniline nanofibers in a three-step process, consisting of enzyme adsorption, precipitation, and crosslinking (EAPC). EAPC was highly active and stable when compared to the control samples of enzyme adsorption (EA) and enzyme adsorption and crosslinking (EAC) with no step of enzyme precipitation. The GOx activity of EAPC was 9.6 and 4.2 times higher than those of EA and EAC, respectively. Under rigorous shaking at room temperature for 56 days, the relative activities of EA, EAC and EAPC, defined as the percentage of residual activity to the initial activity, were 22%, 19% and 91%, respectively. When incubated at 50°C under shaking for 4h, EAPC showed a negligible decrease of GOx activity while the relative activities of EA and EAC were 45% and 48%, respectively. To demonstrate the feasible application of EAPC in biofuel cells, the enzyme anodes were prepared and used for home-built air-breathing biofuel cells. The maximum power densities of biofuel cells with EA and EAPC anodes were 57 and 292 μW/cm(2), respectively. After thermal treatment at 60°C for 4h, the maximum power density of EA and EAPC anodes were 32 and 315 μW/cm(2), representing 56% and 108% of initially obtained maximum power densities, respectively. Because the lower power densities and short lifetime of biofuel cells are serious problems against their practical applications, the present results with EAPC anode has opened up a new potential for the realization of practical biofuel cell applications.


Elevated troponin level is not synonymous with myocardial infarction.
Elevated troponin I in the absence of angiographically visible coronary lesions is seen in up to 10-15% of those undergoing angiography for suspected coronary artery disease. This study aims to elucidate the etiology of elevated cardiac troponin I in patients with normal coronary arteries on angiography. We identified 1551 (8.6%) patients with normal coronary arteries from our catheterization database of 17,950 patients from Jan 2000 to Jun 2004. Elevated troponin I levels were found in 217 (14%) of 1551 patients with normal coronary arteries. Of these 217 patients, 73 surgical patients were excluded, and the remaining 144 patients formed the study population. The study population was compared with age and gender matched patients with myocardial infarction and coronary artery disease (Group II). The patients with elevated cardiac troponin I (cTnI) with normal coronary arteries had significantly lower prevalence of atherosclerotic risk factors and significantly higher left ventricular ejection fractions. The cTnI in patients with normal coronary arteries was elevated due to a number of causes including tachycardia, myocarditis, pericarditis, severe aortic stenosis, gastrointestinal bleeding, sepsis, left ventricular hypertrophy, severe congestive heart failure, cerebrovascular accident, electrical trauma, myocardial contusion, hypertensive emergency, myocardial bridging, pulmonary embolism, diabetic ketoacidosis, chronic obstructive pulmonary disease exacerbation and coronary spasm. Cardiac troponin I could be elevated in a number of conditions, apart from acute myocardial infarction, and could reflect myonecrosis. Acute myocardial infarction is a clinical diagnosis as the laboratory is an aide to, not a replacement for, informed decision making.


An ELISA for the detection of rhinovirus specific antibody in serum and nasal secretion.
An enzyme-linked immunosorbent assay (ELISA) which detects rhinovirus specific antibody in human sera and nasal secretions, has been developed. This sandwich ELISA utilizes a rabbit antirhinovirus hyperimmune serum as the capture antibody and was found to be very sensitive, detecting rhinovirus specific antibody in the serum at dilutions of 1:10(6) and 1:10(3.5) for IgG and IgA immunoglobulins, respectively. Thus, this new assay is 10(2)-10(4) times more sensitive than our standard neutralization test. Furthermore, this increase in sensitivity has enabled us to reliably detect rhinovirus specific immunoglobulins in unconcentrated nasal washings, which are thought to be particularly important for protection against rhinovirus reinfection. A preliminary study of the immune response in human volunteers challenged with rhinovirus using this new ELISA system is presented and further applications and potential of the method are also discussed.


Dietary changes in an acceptance-based weight loss pilot intervention study.
To evaluate pre-post changes in dietary intake and the possible role of emotional eating (EE) as a mediator of dietary changes in a novel behavioral weight loss intervention (Live FREE). Secondary analysis of an open label pilot study. Thirty-nine adults with overweight/obesity and EE. Live FREE is a 16-week group-based program in which participants learn emotional regulation skills from Dialectical Behavior Therapy followed by traditional behavioral weight loss techniques. Dietary intake and EE were measured at baseline and post-treatment with the Automated Self-Administered 24-Hour Dietary Assessment Tool and the depression subscale of the revised Emotional Eating Scale. Paired sample t-tests and mediation for repeated measures designs. Consumption of calories (t(33) = 5.31, p < .001), saturated fat (t(33) = 5.25, p < .001), and added sugar (t(33) = 4.44, p < .001) decreased from pre-post-treatment. EE change mediated the effect of the intervention on change in saturated fat intake pre-post-treatment, B = 6.16, BootSE = 2.47, 95 % CI (1.53 to 11.37), but did not mediate change in caloric or added sugar intake. Participants reported improvement in caloric, saturated fat, and added sugar intake. Improvement in EE may be closely related to decreasing saturated fat consumption. (200).


Water reclamation and intersectoral water transfer between agriculture and cities--a FAO economic wastewater study.
Cost-benefit studies on replacing conventional agricultural water resources with reclaimed water in favour of cities are still rare. Some results of a study under auspices of the Food and Agriculture Organisation (FAO) are presented. By means of an illustrative example at Lobregat River basin in Spain, it could be proved that reclaimed water reuse and intersectoral water transfer can result in economic and environmental benefits at the watershed level. The agricultural community faces cost savings in water pumping and fertilising, increases in yields and incomes; the municipality benefits from additional water resources released by farmers. Farmers should be encouraged to participate by implementing adequate economic incentives. Charging farmers with the full cost of water reclamation may discourage farmers from joining water exchange projects. Particularly in regions with water scarcity, investments in reclaimed water reuse and water exchange arrangements usually pay back and are profitable in the long term.


Winery wastewater treatment by combination of Cryptococcus laurentii and Fenton's reagent.
Winery wastewaters (WW) have high levels of organic matter, resulting in high COD and BOD and suspended solids. This paper studies the combination of biological and chemical processes in WW treatment. Among 10 yeast isolates, Filobasidium sp. (AGG 577) and Cryptococcus laurentii (AGG 726) were selected due to their superior performance in COD removal. During WW degradation, COD and total polyphenols (TPP) content removal of 89-90% for Filobasidium sp. and 90-93% for C. laurentii were obtained. However, despite similar degradation efficiency for both yeasts, COD kinetics and pH evolution during treatment reveals that C. laurentii presents a faster response than Filobasidium sp. The toxicity (inhibition of Vibrio fischeri luminescence) of C. laurentii treated WW decreases to an inhibition value below 2.5%. However, treated WW exceeds the legal limits, making necessary an additional treatment. In this case, the selection of Fenton's reagent as a chemical final polish step process is a good compromise between efficiency and lower practical complexity. The best results for both COD and TPP removal were obtained with H2O2 initial concentration of 39.2mM and a H2O2:Fe(2+) molar ratio of 15:1. The combined C. laurentii - Fenton's reagent treatment of WW achieved a total reduction of 98% and 96%, for COD and TPP, respectively.


A machine learning model of response to hypomethylating agents in myelodysplastic syndromes.
Hypomethylating agents (HMA) prolong survival and improve cytopenias in individuals with higher-risk myelodysplastic syndrome (MDS). Only 30-40% of patients, however, respond to HMAs, and responses may not occur for more than 6 months after HMA initiation. We developed a model to more rapidly assess HMA response by analyzing early changes in patients' blood counts. Three institutions' data were used to develop a model that assessed patients' response to therapy 90 days after the initiation using serial blood counts. The model was developed with a training cohort of 424 patients from 2 institutions and validated on an independent cohort of 90 patients. The final model achieved an area under the receiver operating characteristic curve (AUROC) of 0.79 in the train/test group and 0.84 in the validation group. The model provides cohort-wide and individual-level explanations for model predictions, and model certainty can be interrogated to gauge the reliability of a given prediction.


One-step production of lactate from cellulose as the sole carbon source without any other organic nutrient by recombinant cellulolytic Bacillus subtilis.
Although intensive efforts have been made to create recombinant cellulolytic microorganisms, real recombinant cellulose-utilizing microorganisms that can produce sufficient secretory active cellulase, hydrolyze cellulose, and utilize released soluble sugars for supporting both cell growth and cellulase synthesis without any other organic nutrient (e.g., yeast extract, peptone, amino acids), are not available. Here we demonstrated that over-expression of Bacillus subtilis endoglucanase BsCel5 enabled B. subtilis to grow on solid cellulosic materials as the sole carbon source for the first time. Furthermore, two-round directed evolution was conducted to increase specific activity of BsCel5 on regenerated amorphous cellulose (RAC) and enhance its expression/secretion level in B. subtilis. To increase lactate yield, the alpha-acetolactate synthase gene (alsS) in the 2,3-butanediol pathway was knocked out. In the chemically defined minimal M9/RAC medium, B. subtilis XZ7(pBscel5-MT2C) strain (ΔalsS), which expressed a BsCel5 mutant MT2C, was able to hydrolyze RAC with cellulose digestibility of 74% and produced about 3.1g/L lactate with a yield of 60% of the theoretical maximum. When 0.1% (w/v) yeast extract was added in the M9/RAC medium, cellulose digestibility and lactate yield were enhanced to 92% and 63% of the theoretical maximum, respectively. The recombinant industrially safe cellulolytic B. subtilis would be a promising consolidated bioprocessing platform for low-cost production of biocommodities from cellulosic materials.


Loss of imprinting of the insulin-like growth factor 2 and the H19 gene in testicular seminomas detected by real-time PCR approach.
IGF2 and H19 are imprinted genes in normal human tissue, but many studies have observed a loss of imprinting (LOI) of these genes in tumors as an epigenetic alteration of the DNA, that leads to a biallelic expression predisposing cells to carcinogenesis and tumor growth. The aim of this study was to test the reliability of LightCycler-assisted Real-time PCR in detecting LOI of IGF2 and H19 in 39 patients with testicular germ cell tumors by comparing these results with the analysis generated by the golden standard restriction fragment length polymorphism (RFLP). With LightCycler-assisted Real-time PCR for IGF2 44% and for H19 49% of the patients were found to be heterozygous. This was consistent with the results obtained by RFLP, but surprisingly RFLP failed in more than 7% of the patients. In detecting LOI (for IGF2 in 41% and for H19 in 68% of the informative patients) the approach by RFLP was superior, since the results derived from LightCycler-assisted Real-time PCR showed reliable results in 76 and 10% of the samples concerning IGF2 and H19, respectively. Again, no discrepancy between the results obtained by the two methods occurred. In sum, LightCycler-assisted Real-time PCR is a sufficiently working approach for the rapid and reliable detection of heterozygosity of IGF2 or H19 gene and identification of LOI of IGF2 and thus may be helpful in conducting large epidemiological studies. However, for the identification of LOI of the H19 gene in this cohort it possesses only restrictive use.


Sinus augmentation for dental implants: the use of alloplastic materials.
The ability to augment the sinus floor has dramatically expanded the scope of implant dentistry. Clinical and scientific studies abound as to the efficacy of this procedure. The debate still ensues as to the best material to use for this augmentation, with autogenous bone, freeze-dried bone, xenografts, and alloplasts all being advocated. This article will substantiate through scientific and clinical studies, how the use of allplastic materials in sinus augmentation techniques can greatly reduce the morbidity and the expense of the procedure while predictably producing bone that has been shown to support dental implants in function for extended periods of time.


[Pathological modifications of the P wave due to probable primary changes in intra-atrial conduction].
Two cases of variable changes in ECG P oscillation not due, as is usually the case, to familiar cardiac or respiratory conditions suggested a review of the literature on the subject. It is concluded that these anomalies are the result of changes in the intra-atrial conduction of the stimulus through preferential ways or to aberrant atrial conduction. These are situations of no little practical interest because they may be precursors of major rhythm disturbances such as atrial flutter or atrial fibrillation.


Conventional x-ray in early arthritis.
This article reviews radiographic data from six cohorts of patients with early inflammatory arthritis. Of the patients, 8% to 15% had erosive disease at the first encounter with the rheumatologist. Classic scoring methods were applied to quantify damage, but baseline damage was low in early inflammatory arthritis. Yearly progression in damage score was assessed only in patients with high suspicion of rheumatoid arthritis at baseline or who had a final diagnosis of rheumatoid arthritis at follow-up and varied between 0.5% and 1.7% of the maximal damage of the scoring method per year. The large number of patients with zero values for erosions and lower progression rates will influence sample sizes in clinical trials in early inflammatory arthritis when including radiographic change as an outcome.


Ten-Eleven Translocation 1 Promotes Malignant Progression of Cholangiocarcinoma With Wild-Type Isocitrate Dehydrogenase 1.
Cholangiocarcinoma (CCA) is a highly lethal disease without effective therapeutic approaches. The whole-genome sequencing data indicate that about 20% of patients with CCA have isocitrate dehydrogenase 1 (IDH1) mutations, which have been suggested to target 2-oxoglutarate (OG)-dependent dioxygenases in promoting CCA carcinogenesis. However, the clinical study indicates that patients with CCA and mutant IDH1 have better prognosis than those with wild-type IDH1, further complicating the roles of 2-OG-dependent enzymes. This study aimed to clarify if ten-eleven translocation 1 (TET1), which is one of the 2-OG-dependent enzymes functioning in regulating 5-hydroxymethylcytosine (5hmC) formation, is involved in CCA progression. By analyzing The Cancer Genome Atlas (TCGA) data set, TET1 mRNA was found to be substantially up-regulated in patients with CCA when compared with noncancerous bile ducts. Additionally, TET1 protein expression was significantly elevated in human CCA tumors. CCA cells were challenged with α-ketoglutarate (α-KG) and dimethyl-α-KG (DM-α-KG), which are cosubstrates for TET1 dioxygenase. The treatments with α-KG and DM-α-KG promoted 5hmC formation and malignancy of CCA cells. Molecular and pharmacological approaches were used to inhibit TET1 activity, and these treatments substantially suppressed 5hmC and CCA carcinogenesis. Mechanistically, it was found that knockdown of TET1 may suppress CCA progression by targeting cell growth and apoptosis through epigenetic regulation. Consistently, targeting TET1 significantly inhibited CCA malignant progression in a liver orthotopic xenograft model by targeting cell growth and apoptosis. Our data suggest that expression of TET1 is highly associated with CCA carcinogenesis. It will be important to evaluate TET1 expression in CCA tumors before application of the IDH1 mutation inhibitor because the inhibitor suppresses 2-hydroxyglutarate expression, which may result in activation of TET, potentially leading to CCA malignancy.


Influence of Long-term Dialysis on the Outcome of Kidney Transplantation: A Single-Center Study.
We investigated clinical outcomes of patients in Japan with a history of long-term dialysis treatment. We conducted 1171 kidney transplantations between 2000 and 2015. Sixty of the patients had undergone dialysis therapy for >20 years before the transplantation. We compared graft and patient survivals between the recipients with >20 years of dialysis (long dialysis group [LGD]) and those with <20 years (control group [CG]) in a case-control study, in which sex and age of both donors and recipients, ABO compatibility, and calendar year of transplantation were matched. Average age of LDG was 52.8 ± 8.9 years, and that of CG was 54.2 ± 12.6 (P > .05). Durations of dialysis were 25.4 ± 1.57 vs 5.8 ± 5.8 years, respectively (P < .05). The graft survival rates were 91.6%, 89.9%, and 81.8% at 3, 5, and 10 years in LDG vs 90.71%, 84.8%, and 78.3% in CG, respectively (P > .05). The patient survival rates were 96.6%, 93.2%, and 88.6% in LDG vs 94.5%, 91.0%, and 83.9%, respectively (P > .05). There was no significant difference in mean estimated glomerular filtration rates for post-transplant 10 years between them. LDG showed satisfying clinical outcomes comparable to those of CG both in graft and patient survivals and renal function.


Identification and expression analysis of MicroRNAs in chicken spleen in a corticosterone-induced stress model.
For investigating the effects of stress on the immune response of chickens, we established a corticosterone (CORT)-induced stress model by exogenous intake of CORT. Control group was fed with a basal diet and the stress model group was fed with a 30 mg/Kg CORT-treated diet in ad libitum conditions for 7 days. Then, we used RNA-seq technology to identify the expression pattern of miRNAs, target genes, and relevant pathways in chicken spleen. Results showed that 71 differentially expressed miRNAs (DEMs) were determined, 9 of which were significantly differentially expressed miRNAs (SDEMs), and 241 target genes of DEMs were predicted. GO annotation and KEGG pathway analysis were carried out to understand the role of the DEMs. Out of 287 significantly enriched GO terms, 37 were stress- or immune-related, such as response to light stimulus, detection of oxidative stress, and immune response in mucosal-associated lymphoid tissue. Out of 85 KEGG pathways, 8 were related to stress or immunity, such as cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, and RLR signaling pathway. We then constructed the interaction networks between target genes from immune-related pathways and their DEMs. The analysis results suggested that some DEMs (gga-miR-17 family, gga-miR-15/16 family, gga-miR-2954 and gga-miR-34b-5p) and target genes (SIKE1, CX3CL1, IL11Ra, PIGR, and CDKN1A) were core miRNAs and genes. This study revealed the dynamic miRNA transcriptome, target genes and related pathways in chicken spleen under CORT-induced stress model, which provided a basis for studying the molecular mechanism of stress affecting immune function.


White matter lesion load is associated with lower within- and greater between- network connectivity across older age.
White matter hyperintensities (WMH) are among the most prominent structural changes observed in older adulthood. These changes coincide with functional changes to the intrinsic network organization of the aging brain. Yet little is known about how WMH are associated with changes to the whole-brain functional connectome in normal aging. We used a lesion prediction algorithm to quantify WMH as well as resting-state multiecho functional magnetic resonance imaging to characterize resting-state functional connectivity in a cross-sectional sample of healthy older adults (N = 105, 60-83 years of age). In a multivariate analysis, we found that higher lesion load was associated with a global pattern of network dedifferentiation, marked by lower within- and greater between- network connectivity. Network specific changes included greater visual network integration and greater posterior-anterior connectivity. The relationship between WMH and resting-state functional connectivity was negatively associated with fluid IQ as well as Blood Oxygen Level Dependent signal dimensionality. Reduced functional network segregation is a widely observed pattern of age-related change. Our findings show that these functional changes are associated with the accumulation of WMH in older adulthood.


Povidone-Iodine-Based Solutions for Decolonization of Nasal Staphylococcus aureus: A Randomized, Prospective, Placebo-Controlled Study.
Nasal Staphylococcus aureus decolonization reduces the risk of surgical site infections after orthopedic procedures. Povidone-iodine (PI)-based solutions have shown promising results in bacteria decolonization. The unique physiology of the nose may pose challenges for the bioactivity profiles of PI solutions. This study compared the antibacterial efficacy of an off-the-shelf PI product with a specifically manufactured PI-based skin and nasal antiseptic (SNA). This randomized, placebo-controlled study was conducted at a single institution between April 2014 and July 2015. Four hundred and twenty-nine patients undergoing primary or revision total joint arthroplasty, femoroacetabular osteoplasty, pelvic osteotomy, or total shoulder arthroplasty were included. 10% off-the-shelf PI, 5% PI-based SNA, or saline (placebo) were used for nasal decolonization. Baseline cultures were taken immediately preoperatively, followed by treatment of both nares twice for 2 minutes with 4 applicators. Reculturing of the right nostril occurred at 4 hours and the left at 24 hours. Ninety-five of the 429 patients (22.1%) had a positive culture result for S. aureus; 13 (3.03%) were methicillin-resistant S. aureus. Of these 95, 29 were treated with off-the-shelf PI, 34 with SNA, and 32 with saline swabs. At 4 hours post-treatment, S. aureus culture was positive in 52% off-the-shelf PI patients, 21% SNA patients, and 59% saline patients. After 24 hours posttreatment, S. aureus culture was positive in 72% off-the-shelf PI patients, 59% SNA patients, and 69% saline group. SNA was significantly more effective at decolonizing S. aureus over the 4-hour time interval (P = .003); no significant difference was observed over the 24-hour time interval between the 3 groups. A single application of PI-based SNA before surgery may be effective in eliminating nasal S. aureus in over two-thirds of patients. Off-the-shelf PI swabs were not as effective at 4 hours as the specifically manufactured product for S. aureus decolonization.


Biological mesh repair of a strangulated perineal hernia following abdominoperineal resection.
Perineal hernia is a recognized but uncommon complication following proctectomy. Emergency presentations of this hernia are very rare and are not well described in the literature. We present the case of an 81-year-old lady who presented with small bowel obstruction with strangulation secondary to a perineal hernia 2 years after abdominoperineal resection for carcinoma of the rectum. At laparotomy, a small bowel resection was required and a biological mesh was used to repair the perineal defect.


Temporal distribution of emergency room visits in patients with migraine and other headaches.
Background: Headache is a leading reason for presentation to the emergency department (ED) with migraine being the most frequently headache. To ensure the adequate staffing of healthcare providers during peak times of headache visits, we analyzed the temporal distribution of emergency department visits in patients presenting with headache and/or migraine.Research design and methods: The authors conducted an ecological study, including all consecutive visits to the ED for headache. Patients were classified according to the IHS Classification. We analyzed circadian, circaseptan and circannual patterns for number of visits, comparing migraine patients with other headache patients.Results: There were 2132 ED visits for headache, including primary headache in 1367 (64.1%) cases; migraine in 963 (45.2%); secondary headache in 404 (18.9%); and unspecified headache in 366 (17.1%). The circadian pattern showed peaks around 11:00-13:00 and 17:00-19:00, with visits during the night shift 45% less frequent (p < 0.001). The circaseptan pattern showed a peak on Monday-Tuesday and a low point on Sunday (p < 0.007). The circannual pattern peaked in March and decreased in June.Conclusions: ED visits for headache showed specific circadian, circaseptan and circannual variations. No differences were found in these patterns when comparing migraine patients to other headache patients.


Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl-JAK/STAT Signaling Pathways.
This study evaluates the anticancer effects of dehydrocostus lactone, a plant-derived sesquiterpene lactone, on human chronic myeloid leukemia cells. Dehydrocostus lactone significantly inhibits cell proliferation by inducing cells to undergo cell cycle arrest, apoptosis, and differentiation. Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK1) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells. Dehydrocostus lactone also induces apoptosis by increasing the generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential (MMP), and modulating the protein levels of Bcl-2 family members. We also found that dehydrocostus lactone significantly inhibits the phosphorylation expression of Bcr/Abl, STAT5, JAK2, and STAT3 and downstream molecules including p-CrkL, Mcl-1, Bcl-XL, and Bcl-2 proteins in K562 cells. At a low concentration, dehydrocostus lactone significantly increased CD11b and CD14 expression on the surface of K562 cells, and induced cells to differentiate into monocytes or mature macrophages. Taken together, this study provides new insight into the molecular mechanisms of dehydrocostus lactone actions that may contribute to the chemoprevention of chronic myeloid leukemia. J. Cell. Biochem. 118: 3381-3390, 2017. © 2017 Wiley Periodicals, Inc.


Steroids in Stroke with Special Reference to Progesterone.
Both sex and steroid hormones are important to consider in human ischemic stroke and its experimental models. Stroke initiates a cascade of changes that lead to neural cell death, but also activates endogenous protective processes that counter the deleterious consequences of ischemia. Steroids may be part of these cerebroprotective processes. One option to provide cerebroprotection is to reinforce these intrinsic protective mechanisms. In the current review, we first summarize studies describing sex differences and the influence of steroid hormones in stroke. We then present and discuss our recent results concerning differential changes in endogenous steroid levels in the brains of male and female mice and the importance of progesterone receptors (PR) during the early phase after stroke. In the third part, we give an overview of experimental studies, including ours, that provide evidence for the pleiotropic beneficial effects of progesterone and its promising cerebroprotective potential in stroke. We also highlight the key role of PR signaling as well as potential additional mechanisms by which progesterone may provide cerebroprotection.


Editorial for Special Issue on "Regulation and Effect of Taurine on Metabolism".
Taurine (2-aminoethanesulfonic acid) is well known to be abundantly contained in almost all the tissues and cells of various mammals, fish, and shellfish [...].


A data-driven group emergency decision-making method based on interval-valued intuitionistic hesitant fuzzy sets and its application in COVID-19 pandemic.
The outbreak of Corona Virus Disease 2019 (COVID-19) makes people more concerned about the validity and timeliness of emergency decision making. When an emergency occurs, it is difficult for decision makers (DMs) to give accurate assessment information in the early stage due to the urgency of time, the incompleteness of information, and the limitations of DMs' cognition and knowledge. Hence, we use interval-valued intuitionistic hesitant fuzzy sets rather than exact numbers to better characterize the fuzziness and uncertainty of emergencies. In addition, the Internet has become a major platform for the public to express their opinions or concerns, so we can collect the user-generated content on social media to help DMs determine appropriate emergency decision-making criteria which are the premise and basis of scientific decisions. However, there is likely to be some correlation between the obtained criteria. To this end, we first extend the Bonferroni mean (BM) operator to the interval-valued intuitionistic hesitant fuzzy environment, and propose three interval-valued intuitionistic hesitant fuzzy BM operators to capture the interrelation of fuzzy input variables, including an interval-valued intuitionistic hesitant fuzzy BM operator, a simplified interval-valued intuitionistic hesitant fuzzy BM operator, and a simplified interval-valued intuitionistic hesitant fuzzy weighted BM (SIVIHFWBM) operator. Then, a new group emergency decision-making method based on the SIVIHFWBM operator and social media data is proposed, and the specific steps of ranking all emergency plans are put forward. Moreover, our method is applied to evaluate emergency plans for the prevention and control of COVID-19. Finally, the effectiveness and feasibility of the method are verified by the sensitivity analysis, validity test, and comparative analysis.


Effect of training community health workers and their interventions on cardiovascular disease risk factors among adults in Morogoro, Tanzania: study protocol for a cluster randomized controlled trial.
Cardiovascular diseases (CVDs) increasingly contribute to morbidity and mortality in Tanzania. Public knowledge about CVD risk factors is important for the primary prevention of CVDs and can be improved through community-based interventions delivered by community health workers (CHWs). However, evidence of the utility of CHWs in improving knowledge and CVD risk factors profile is lacking in Tanzania. This study aims at assessing the effect of training CHWs and their CVD-specific interventions for reduction of hypertension and other CVD risk factors among adults in Morogoro, Tanzania. This study will use a mixed-methods design with both quantitative and qualitative approaches. A baseline quantitative survey will be conducted to assess knowledge, prevalence, and determinants of CVD risk factors in a random sample of 2950 adults aged 25-64 years. A cluster randomized controlled design with pre-test will be used to assess the effects of CVD-specific interventions delivered by CHWs on reduction of blood pressure and proportion of other CVD risk factors among 516 adults with raised blood pressure from 12 randomly selected villages in Morogoro, Tanzania. Focus group discussion (FGDs) will be conducted at the end of the intervention to assess perceived quality and acceptability of CVD-specific interventions delivered by CHWs. The intervention will consist of a five-day CVD-specific training to CHWs from villages randomized to the intervention. Trained CHWs will then provide home health education and healthy lifestyle promotion for prevention of CVD risk factors, counseling about hypertension screening for early identification, and referral and linkage of individuals with elevated blood pressure to health facilities. Since intensity of the intervention is key to reinforce behavior change, CHWs will visit the participants every month for the first six months, then bi-monthly thereafter up to 12 months. Except for referral of participants with raised blood pressure identified during the baseline survey, control villages will not receive any interventions delivered by CHWs. At the end of the intervention period, an end-line survey will be conducted in both intervention and control villages to evaluate changes in knowledge, blood pressure, and proportion of other CVD risk factors. The results of this study are likely to have positive policy implications for the prevention of CVD risk factors through the use of CHWs in the provision of CVD-specific interventions, especially now that the Tanzanian government is considering implementing and scaling up a nation-wide multitask CHW cadre. PACTR Registry, PACTR201801002959401 . Registered on 10 January 2018.


Evaluation of the safety and efficacy of a novel product for the removal of impacted human cerumen.
This open-label study evaluated the safety and efficacy of a novel product for the removal of impacted cerumen in adult patients. This was a prospective, single-center, single-arm, self-controlled clinical trial conducted in a community general practice setting. The novel product contains glycolic acid in an otologically-acceptable buffer containing sodium bicarbonate and glycerin and other buffering agents. The product was instilled into the ear canal prior to irrigation with warm water. Severity of cerumen impaction was graded using a 5-point scale. Improvement in tympanic membrane visualization was assessed after instillation and irrigation. A majority (83%, 25/30) of ears showed improvement with one application: with 53% (16/30) totally dissolved and gained 100% TM visualization. Total dissolution was observed in 80% (24/30) of the study ears per the intent-to-treat analysis and 86% (24/28) if irrigation instructions were followed. Most of the ears/participants that had cerumen blockage symptoms experienced significant improvement with the application. Feelings of fullness disappeared in 92% (11/12) of the affected ears; ears itching, 91% (10/11); water trapping or cracking, 78%, and decreased hearing disappeared in 71% (10/14). All (100%, 18) of the participants who completed the application satisfaction assessment were satisfied with the application process in terms of time needed and the overall rinse procedure. Only one mild adverse event (ear pruritis) occurred that was related to application. The tested cerumen removal product was effective and safe for removing moderate to severe blockage in patients with impacted cerumen. Procedure satisfaction for the product was high. This trial is registered on http://www.clinicaltrials.gov/. The registration number is NCT02829294. The trial was retrospectively registered on July 8, 2016.